Background

Retinoblastoma is a rare intraocular malignancy, occurring in approximately one out of every 18,000 live births in the global population. Due to its scarcity, there is not enough data in the literature regarding the best treatment modality of retinoblastoma, especially eye sparing types. The aim of this study is to evaluate the survival outcome of different treatment strategies and the risk of multiple primary malignancies of retinoblastoma.

Methods

Data of 1490 patients were extracted from a national cancer database diagnosed with retinoblastoma from 2000 to 2020. We subdivided the patients according to the treatment modality into four groups: chemotherapy, transpupillary thermotherapy, enucleation and combined enucleation and chemotherapy. MP-SIR session was used to calculate the Standardized incidence Ratio (SIR) as Observed/Expected (O/E) with significant results if P>0.05 and Excess Absolute Risk (EAR) per 10,000.

Results

Both transpupillary thermotherapy and enucleation had improved relative survival compared to primary chemotherapy and adjuvant chemotherapy after enucleation (100%, 98.8%, 96.0% and 95.4% respectively; P=0.01). Performing COX-regression model for age, race, gender, laterality and stage showed race (HR=1.514, 95% CI: 1.999-1.146; P=0.003) and stage (HR=0.195, 95% CI: 0.471-0.081; P<0.001) were significantly associated with survival outcome while gender (HR=0.788, 95% CI: 1.321x-0.470; P=0.365), age (HR=0.947, 95% CI: 1.407-0.638; P=0.789) and laterality (HR=0.943, 95% CI: 1.319-0.674; P=0.732) had no statistical significance. However, a second primary ocular malignancy was observed in 30 cases along ten years after diagnosis with EAR of 31.26 and (O/E) = 14.69, 95% CI:25.13-7.82; P< 0.05).

Conclusions

The results of this study showed promising survival outcomes of transpupillary thermotherapy for treatment of retinoblastoma, which can discourage both enucleation and chemotherapy. It was also shown that stage and race had increased risk of incidence. A second ocular malignancy had increased incidence with previous history with retinoblastoma. Finally, more studies should evaluate the efficacy of transpupillary thermotherapy treatment.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Gliomas are brain tumors the most common being glioblastoma (GBM). GBM treatment is not curative and even patients who respond to initial treatment will recur. Systemic inflammatory markers are related to tumor growth and tumor recurrence. High neutrophil/lymphocyte ratio (NLR), monocyte/lymphocyte ratio (MLR), platelet/lymphocyte ratio (PLR), prognostic nutritional index (PNI), systemic immune-inflammation index (SII) and systemic inflammatory response index (SIRI) are established prognostic factors in some solid tumors. This study aims to evaluate the correlation of these markers with the prognosis of patients with GBM.

Methods

The clinical data of patients from four centers with GBM diagnosed from Jan 2018 to Jan 2022 were analyzed retrospectively. ROC curves were used to determine cut-offs for NLR, PLR, MLR, SIRI and Sil in each phase of treatment. Kaplan-Meier curves were implemented for variables that were close to the 70% AUC criterion. Significance was considered for p<0.05.

Results

A total of 184 patients were included in the analysis, most were females and <65 years old at diagnosis. Most patients were treated with STUP as 1st line. Prevalence of therapy with corticosteroids increased along treatment phases. Median OS was 15 months, median of PFS after 1st-line and 2nd-line treatment was 6 months. PNI (p < 0.001), MLR (p=0.002) and Sil (p=0.005) were significantly lower after 1^st-line or 2^nd-line treatments when compared with the phase before treatment. After implementing ROC curves none of the parameters filled the 70% AUC criterion. However, after examining the results, SIRI after 1^st-line treatment and NLR after 2^nd-line treatment for OS were the parameters that were most close to that criterion. Hence, we established as cut-offs, SIRI after 1^st-line treatment ≥ 1292.86 and NLR after 2^nd-line treatment ≥ 2.58. Kaplan-Meier survival function results show that patients above the established criteria of SIRI and NLR have low OS, p=0.009 and p=0.002, respectively.

Conclusions

Post-treatment the ratios NLR and SIRI were associated with worse OS. Steroids did not influence the results. The retrospective study design limits the interpretation. A longer follow-up time and a larger sample size are needed to support these findings.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Glioblastoma is the most common and aggressive type of primary brain tumor. The prognosis for patients diagnosed with GBM is unfortunately very poor, with a median overall survival of only 14 months and very limited options for treatment. Several studies have detected a mutation in the isocitrate dehydrogenase 1 (IDH1) gene as a molecular marker associated with improved survival in patients with glioblastoma, but the evidence is inconsistent and inconclusive. We conducted this meta-analysis to investigate the link between IDH1 mutation and overall survival in glioblastoma patients.

Methods

A thorough literature search of databases (PubMed, Scopus, Cochrane, Embase, and Web of Science databases) yielded five studies involving 541 glioblastoma cases that reported overall survival by IDH1 mutation status. The meta-analysis was conducted using Cochrane review manager V 5.4.

Results

Our meta-analysis encompassed five studies, involving a total of 541 patients (480 with IDH1 wild type and 61 with mutant type). Among these, three studies focused on patients with recurrent glioblastoma (GBM), while two studies involved newly diagnosed GBM cases. The treatment modalities varied, with one study employing alkylating agents, two studies utilizing tyrosine kinase inhibitors, one study combining immunotherapy with alkylating agents, and one study not specifying the treatment. The pooled hazard ratio (HR) was 2.37 (95% CI 1.81–3.12; p < 0.001; I2=0%), indicating a significant association between IDH1 mutation and prolonged overall survival in glioblastoma patients, irrespective of the therapeutic intervention. For recurrent GBM, the pooled HR was 2.28 (95% CI 1.72–3.03; p < 0.001; I2=0%). Additionally, in the context of newly diagnosed GBM, the pooled HR was 3.06 (95% CI 0.48–19.63; p < 0.001; I²=39%).

Conclusions

This study clearly demonstrates that IDH1 mutation in patients with glioblastoma is a favorable prognostic factor for overall survival, regardless of the treatment modality or disease stage. The findings suggest that IDH1 mutation status should be considered in the clinical management and stratification of glioblastoma patients.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Ewing Sarcoma (ES) tumors are malignant tumors mainly affecting pediatric patients. Extra-osseous primary sites are infrequent, being central nervous system (CNS)-ES extremely rare. Diverse differential histological diagnoses for these “small blue round cell” tumors matched to their rareness make diagnosis an arduous challenge.

Methods

Our single-center retrospective study included patients with cranial CNS-ES and defining molecular features between 10/2007-11/2023. We analyzed clinical presentation, radiologic and histologic features, and median survival.

Results

Medical records from twenty-four patients were analyzed. The median age was 22 years (range 2-65); 15 adults (>18). Most patients were male (2:1). Headache was the most frequent symptom (35%), followed by seizures, unilateral numbness/weakness, cerebellar syndrome and visual impairments. Findings in brain Magnetic Resonance Imaging; 11 supratentorial lesions, 7 infratentorial and 6 showed diffuse meningeal infiltration. Histopathology showed in most cases conventional diffuse pattern with small round blue cells (n=12). Confirmatory (11;22) translocation was achieved in all cases: 22 confirmed by Protein-Chain-Reaction analysis and 2 by Fluorescence in situ hybridization for EWSR1 gene rearrangement. One case was confirmed by deoxyribonucleic acid (DNA) methylation profiling. Median overall survival (OS) was 78 months (0-140). 21 patients had an OS exceeding 12 months, while 3 patients suffered rapid progression and died within the year of diagnosis. No significant relations were found between treatment and survival.

Conclusions

Primary CNS-ES is an orphan pathology and its clinical course and treatment options are barely known. In our experience, it is a heterogeneous group in clinical onset, imaging and histopatological findings, treatment response and outcome. Advances in diagnosis technologies such as DNA methylation profiling with subtypes clustering will probably favour further understanding and guide treatment tayloring.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Despite the favorable outcomes of chemoradiation (CRT) in locoregional squamous-cell carcinoma of the anus (SCCA), treatment of advanced disease remains a challenge due to the high rate of patients ineligible for radical CRT or failing to achieve complete response (CR) after CRT. The aim of this report is to evaluate the safety and outcomes of Carboplatin-Paclitaxel (CP) regimen used as induction chemotherapy (iCTx) to maximize the chance of achieving CR following CRT.

Methods

From Feb 2020 to May 2023, 16 consecutive pts with locally advanced SCCA not qualifying for primary CRT due to extensive involvement in pelvis, with stage IIIA (n=2), IIIC (n=11) and stage IV disease with pelvic metastases (n=3), with a median age of 62 years (range 37-73 years), received CP iCTx at National Institute of Oncology in Warsaw, Poland.

Results

All 16 pts received CP iCTx as planned, with a median treatment time of 39 days (range 15-127 days). After a median follow-up of 324 days (range 157-1134 days), 25% (n=4) incidence of grade 2 non-hematological toxicities occurred (n=1 diarrhea, n=1 urinary tract infection, n=1 fatigue and n=1 hypersensitivity to Paclitaxel). There were no grade 3-5 non-hematological toxicities. Grade 2 neutropenia occurred in 5 pts (31%) and 3 pts (19%) experienced grade 2 thrombocytopenia. There was a 12% (n=2) incidence of grade 3 neutropenia and 6% (n=1) incidence of grade 3 thrombocytopenia. One patient experienced grade 4 neutropenia. 14 pts (88%) reported a clinical response following iCTx with a 81% (n=13) incidence of improvement in pain control and 38% (n=6) incidence of reduction in tumor bleeding. After iCTx, 3 pts were ultimately disqualified from CRT due to progressive disease (n=2) and lack of response (n=1) and received palliative RT. The remaining 13 patients (81%) were qualified for CRT. 6 pts (38%) achieved long-term clinical CR. 2 pts (12%) achieved PR or CR with follow-up period too short to assess final response. 4 pts (25%) experienced treatment failure due to local recurrence (n=2) and distant metastases (n=2). One patient did not complete CRT due to urosepsis.

Conclusions

CP iCTx has an acceptable toxicity profile and is a viable option for patients with advanced SCCA to maximize the chance of achieving CR.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Verrucous carcinoma (VC) is an extremely rare variant of squamous cell carcinoma. There are only 50 cases reported in the literature and limited to few case reports. It is slowly progressive, well-differentiated and grows as a cauliflower-like mass. So surgery is the most widely used treatment strategy. However, due to its scarcity, there are no available data about the other treatment modalities. So this study aims to evaluate different management approaches and the clinicopathological features of gastrointestinal VC for better understanding of this rare subtype.

Methods

We obtained the data from a national cancer database for patients diagnosed with gastrointestinal verrucous carcinoma from 2000-2020. We subdivided the patients according to their treatment strategy into three groups: surgery with no systemic therapy, medical therapy (chemotherapy/radiotherapy) and adjuvant chemo(radio)therapy following the surgery. We used SPSS version 23 for data analysis. Survival analysis was done using Kaplan-Meier and Log-Rank test.

Results

Out of 215 patients, 74.9% were males. The mean age was 54.9 (SD=15.6). The majority had anaorecatal VC (77.6%) and osoephageal VC (14.4%). VC had 3-year and 5-year relative survival of 80.2% and 74.0%. About 53% were treated surgically with no systemic therapy, 29.3% received adjuvant therapy and 8.8% were treated medically with 5-year relative survival of 81.9%, 73.9% and 51.8% respectively; P=0.03. Performing COX-regression model, annorectal VC was associated with significant improved survival (HR=0.79, P=0.007, 95%CI: 0.107-5.78) while age (HR=1.03, P>0.00, 95%CI: 1.016-1.05) and race (HR=1.054, P=0.025, 95%CI: 1.007- 1.104) were significantly associated with worst survival outcome.

Conclusions

Gastrointestinal VC has good survival outcome and more common in males. Surgery has improved survival outcome compared adjuvant therapy and has survival benefit about 30% compared to medical treatment. These results highlight surgical excision as the best strategy and encourage to avoid chemo(radio)therapy in VC management for better quality of life after VC management and less serious systemic side effects.

Legal entity responsible for the study

The author.

Funding

Has not received any funding.

Disclosure

The author has declared no conflicts of interest.

Background

Developing lymphoma as a second primary malignancy (SPM) after colorectal cancer is a very rare event reported in the literature, with an incidence of 0.5%. Very few studies reported an association of lymphoma with pre- and post-operative radiotherapy in colorectal cancer management. The potential risk of SPM, including lymphomas, is debatable in cancer management. So the aim of this study is to assess the risk of lymphoma as an SPM in colorectal cancer across different age groups.

Methods

Data were extracted using the Surveillance Epidemiology and End Result (SEER) database. We used an MP-SIR session with multiple outcome analysis to assess the risk of second primary lymphoma in colorectal cancer patients. SIR was calculated as observed/expected (O/E), and excess absolute risk (EAR) is per 10,000. Results were considered significant at P<0.05 with a 95% confidence interval (CI). We use the WHO age classification (0–24 young, 25–63 middle age, and older than 64 years).

Results

The risk of lymphoma as an SPM in colorectal cancer patients had an O/E of 0.93 (P<0.05, 95%CI: 0.89-0.97, EAR=-0.52) while in the 2–11 months interval the O/E was 1.19 (P<0.05,95%CI: 1.07-1.33, EAR=1.28). The risk of Nodal non-Hodgkin lymphoma had an overall O/E of 0.93 (P<0.05, 95%CI: 0.88-0.98, EAR=-0.34) while in the 2-11 months interval the O/E was 1.27 (P<0.05, EAR=1.140). The risk of lymphoma in the young age had an O/E 0.00 (95%CI: 0.00-4.14, P<0.05, EAR= -0.70) while the middle age had an overall O/E of 0.90 (P<0.05, 95%CI: 0.83-0.97, EAR=-0.47) with slight increased risk in the 2-11 months interval (O/E=1.12, P<0.05,). The risk of extranodal Hodgkin lymphoma had an O/E of 0.00 (P<0.05, EAR= -0.01). In the old age, the EAR was -0.57 for developing lymphoma (O/E=0.95, P<0.05) while in the 2–11 months interval had an O/E of 1.22 (P<0.05).

Conclusions

The results of this study show colorectal cancer patients have an increased risk of developing SPM lymphoma, especially in the 2–11-month interval. As early discovery will raise the chance of a successful outcome, we advise all middle-aged and older individuals with colorectal cancer to undergo routine follow-up starting from the time of diagnosis.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Testicular cancer (TC) is highly curable cancer commonly diagnosed at a younger age [1]. A high cure rate may come at a cost of late side effects potentially having a negative impact on social, economic and sexual wellbeing [2]. We conducted this study to determine the prevalence and severity of this effect on TC survivors in Ireland. 1. Kusler, K.A. and J.N. Poynter, International testicular cancer incidence rates Cancer Epidemiology, 2018. 56; 2. Kerns, S.L., et al., Relationship of Cisplatin-Related Adverse Health Outcomes With Disability and Unemployment Among Testicular Cancer Survivors. JNCI Cancer Spectr, 2020. 4(4).

Methods

Patients attending the testicular survivorship clinic at Tallaght University Hospital Dublin were requested to fill out a survey questionnaire to determine the severity of the impact of testicular cancer on fertility, socioeconomic and sexual health using a five point Likert scale.

Results

A total of 83 patients completed our survey questionnaire. Respondents reported that TC had a major impact on personal financial goals with 42% stating a minor to very significant impact. Career choices and job stability remained intact for almost 70% patients but performance at work was affected in 41% participants. One third of patients reported minor to very significant effect on their relationship with their partner. Around 30% of patients reported minor to very significant effect on erectile function and ejaculation. Satisfaction with sexual activity was affected in 39% patients. TC affected the libido in almost half of the patients while 20% reported an effect on their ability to find a new partner. Among participants 34% had children after TC and 17% reported seeking medical assistance for conception.

Table: 11P

Conclusions

A significant number of young TC survivors are enduring the negative sequelae of TC on their social, financial and sexual health. More studies are needed to identify at risk population and also more supports are required to cater their needs.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Primitive Retroperitoneal Germinal Cell Tumors (pR-GCT) corresponds to the clinical case of retroperitoneal ascertained GCT without evidence of primary testicular tumor and accounts for up to 40 % of extragonadal GCTs. An occult primary testicular tumor is often missed at diagnosis. Treatment modalities and outcomes have not been specifically addressed, preventing robust recommendations. We performed an international call to assess prognosis of treatment outcomes of these pts.

Methods

Clinical, pathological and treatment data pts with pR-GCT between April 1988 and January 2022 were retrospectively collected across four referral centers. Kaplan Meier methods, univariable and multivariable Cox regression models (MCRMs) were used.

Results

Ninety-nine pts (median age 37 years - IQR: 29-45) were collected. Ninety-three (94%) had histological diagnosis by biopsy or primary retroperitoneal lymph-node dissection: 60 (62.5%) had non-seminomatous (pR-NSGCTs) and 33 (34.4%) had seminomatous (pR-SGCTs). IGCCCG prognostic allocation was possible in 91 pts: 34 (35.8%) were good, 23 (24.2%) intermediate and 34 (35.8%) poor-risk, respectively. All pts underwent cisplatin-based chemotherapy, usually BEP (94.9%). After chemotherapy, 25 (25.3%) pts underwent orchiectomy: viable tumor was present in 8 (32%), burn-out lesions in 6 (24%) and no lesion in 11 (44%). After a median FUP of 45 m (IQR:15-90), the 5-yrs OS was 58%, being 85% in case of pR-SGCT and 46% in case of pR-NSGCT. According to IGCCCG classification 5-yrs OS was 83.3% for good, 57% for intermediate, 42% for poor-risk pts, respectively. No difference in term of OS (60% vs 56%, p-value 0.81) was observed between patient who had or not radical orchiectomy. At MCRMs only IGCCCG poor risk category (HR 3.2, CI: 1.18-8.84, p-value 0.02) was independent predictor of a worse OS.

Conclusions

Eventually, a significant proportion of patients with pR-GCT had a misclassified primary testicular tumor. 5 years-OS according to IGCCCG-classification is worse than expected. The role of a surgical exploration of the suspected primary tumor remains controversial and the existence of a real category of p-RGCT cannot be excluded.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Platinum-based chemotherapy has shown benefits in the first-line (1-L) setting in patients (pts) with metastatic penile squamous cell carcinoma (pSCC). Nevertheless, immune checkpoint inhibitors (ICI) have reported adequate tumor response with more acceptable safety. Among ICI, cemiplimab (C) received approval for advanced cutaneous SCC (cSCC) and for advanced cervical cancer. pSCC may develop on chronic Human Papilloma Virus (HPV) infection, similarly to cervical SCC. Because of similarities between cervical and penile SCC, C might represent a valid option for patients with metastatic SCC developed from cutis of penis. In light of these evidence, we have designed a retrospective study to evaluate 1-L CEMiplimab in metastatic PENile SCC (CemPen).

Methods

CemPen is a retrospective, observational, monocentric study involving pts with metastatic pSCC treated with 1-L C between April 2021 and December 2023 at Careggi University Hospital. We assessed objective response rate (ORR) at 12 weeks according to iRECIST, median progression free survival (PFS), overall survival (OS), clinical benefit rate (CBR), and safety profile according to CTCAE v 5.0.

Results

Eighteen penile SCC pts were enrolled. Median age was 70 years. With a median follow up of 14 months (mo), 9 pts (50%) had discontinued C. The 12-week ORR was 11% (2 partial response [PR]), 22% of pts had stable disease (SD), with a CBR of 33%. Notably, the PR were reported in 2 metastatic HPV-negative pSCC and they are still ongoing. At the time of analysis, 9 pts (50%) had PD, the median PFS was 6.4 mo (95% CI [2.7; NR]). Moreover, 8 pts had died (all in PD), the median OS was 12.3 mo (95% CI [7.3; NR]). Overall, one patient, after two years of treatment, experienced grade 3 immune-related cutaneous rash, successfully treated with methylprednisolone 2 mg/Kg i.v. Due to his durable partial response, Cemiplimab was permanently discontinued, without progression.

Conclusions

We report the largest known data of Cemiplimab in 1-L treatment of advanced pSCC. Data of CBR and safety are encouraging and support the use of C in this setting. Prospective studies are needed. The value of HPV status as predictive factor will be investigated.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Struma ovarii, a rare form of teratoma with mature thyroid tissue, accounts for 2-5% of ovarian teratomas, with less than 5% exhibiting malignant transformation. Understanding the clinicopathological characteristics and prognostic factors in malignant struma ovarii (MSO) is crucial for informed clinical decision-making.

Methods

Data were obtained from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2020. Patients who met any of the following criteria were excluded: diagnosis not confirmed by histology, not first tumor, and unknown data. Chi-square tests were used to compare clinicopathological features, while survival rates and prognostic factors were identified using the Kaplan-Meier estimator, log-rank tests, and Cox proportional hazard regression.

Results

In total, 329 patients were included. Most patients were 45 years or older (52.9%), and 42.9% had a tumor size of 40 mm or greater, with an average tumor size of 40.2 mm. years, with the predominant race being white (n=247). Most of the patients were in the localized stage (80.9%). Primary surgical resection was performed in 94.2% of the patients (n=310), 5.2% had undergone chemotherapy, and 13.4% were administered radiotherapy. After multivariate adjustment, older age, chemotherapy, and advanced stage of the primary tumor were found to be significant prognostic factors for adverse overall survival. In contrast, Asian ethnicity and surgery were good prognostic factors for overall survival.

Conclusions

Our study showed that surgical intervention alone can enhance overall survival rates in individuals with MSO. These findings offer significant information on MSO treatment and its prognostic factors for future clinical decisions. Additional research is necessary to confirm these results and explore any possible confounding variables that may have influenced the outcomes.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Granulosa cell tumors are uncommon ovarian cancers. Most patients have an early diagnosis, and they have a good prognosis generally. The only prognostic factor that has been proven to be positively correlated with survival is the stage at diagnosis. In this study, we sought to examine the clinical and pathological features of women treated at a single center after being diagnosed with malignant ovarian granulosa cell tumors.

Methods

Patients who had treatment or follow-up for the ten-year period (2012–2023) at Ege University Hospital after being diagnosed with an ovarian granulosa cell tumor were the subjects of a retrospective study. Information on the patient's age upon diagnosis, menopausal status, parity number, surgical procedure used, application complaint, tumor stage, recurrence status, disease-free survival (DFS), and overall survival (OS) was gathered. The location, size, mitotic index, inhibin A, and estrogen receptor level were among the pathological aspects of the tumor.

Results

A total of 56 patients were included in the study. 32% of the patients were between the ages of 46-55 at the time of diagnosis. Abdominal distension was the most common complaints, accounting for 37.5% of cases. A primary surgical staging procedure was performed in 92.8% of the patients. The tumor was 55% located in the left ovary. 71% of the patients were stage 1A at the time of diagnosis. Three patients had concurrent endometrial adenocarcinoma. 30.3% of the 17 patients had adjuvant therapy. With a rate of 41.1%, carboplatin+paclitaxel was the most often chosen regimen. It was shown that 9 individuals (16%) had recurrences. Three of these patients were in stage 3C, while six of them were in stage 1. Of the patients who experienced recurrence, 44.4% had peritoneal implants, 22.2% had visceral organ metastases, and 33.3% had local recurrence. Relapses occurred on average after 63 months. The patients' 5-year OS was 88.37%, and their 2-year OS was 98.18%.

Conclusions

These tumors have a decent prognosis but need to be followed up on for a long time. Survival and recurrence are mostly correlated with the tumor's early stages. Recurrence is also linked to the size of the tumor and the existence of residual tumor. To investigate how additional factors affect the result, more research is required.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Gynaecologic carcinosarcomas (GCS) are rare cancers with poor prognosis. From 2003 onwards, GCS are no longer considered sarcomas but epithelial carcinomas, thus shifting the chemotherapy used in their multidisciplinary management. We aim to analyse the chemotherapy regimens used in GCS at our institution and patient’s outcomes.

Methods

Retrospective analysis of 57 GCS patients (pts) treated in HCSC from 1995-2003 and 2003-2022.

Results

Median age at diagnosis: 65 years (range 30-90); ECOG 0 63%. Primary disease: uterus 80.7%, ovary 17.5% or vaginal stump 1.8%. FIGO 2018 staging at diagnosis: I 40.4%, II 14%, III 22.8% and IV 22.8%. Carboplatin (C) and paclitaxel (T) were used initially in 50% of pts (57% adjuvant, 14.2% neoadjuvant and 19% fist line), from 2003, and as a retreatment (monotherapy, CT, or in combination with epirubicin, pegylated liposomal doxorubicin, bevacizumab, gemcitabine or ifosfamide) 10 times. Other drugs used as first strategy were anthracyclines, ifosfamide, cisplatin, cyclophosphamide, gemcitabine, docetaxel and in following lines dacarbazine, etoposide, bevacizumab, methotrexate, trabectedin, megestrol, niraparib and dostarlimab (Table). 11 pts relapsed after a complete response: local 45.5%, lymph node 18.1%, peritoneal 36.4%, visceral 18.2%, lung 10%. After a median follow-up of 20,67 months, median overall survival (mOS) 25.23 months (95% CI, 9-41.5 months) and median progression free survival (mPFS) 16.03 months (95% IC, 7-25 months). Pts treated from 2003 have better mOS than those treated before 2003 (40.5 vs. 9.7 months, p 0.034).

Table: 17P

Intention of initial chemotherapy treatment in the two cohorts regarding FIGO 2018 staging and outcomes

Conclusions

We have used different chemotherapy regimens in GCS, more liberal use of adjuvant therapy, being CT the main regimen from 2003 onwards concurring with mOS improvement.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Gynaecological cancers (GC) encompass malignancies affecting the female reproductive system, and dealing with acquired chemoresistance poses a significant challenge in their treatment. The study focuses on the therapeutic potential of deubiquitinating enzymes (DUBs), specifically ubiquitin-specific proteases (USPs), in addressing acquired chemoresistance and metastasis in GC.

Methods

The study utilized the TCGA database to assess the impact of (USPs), specifically USP37 and USP14, on the prognosis of GCs. Expression analysis at RNA and protein levels was conducted in various GC cell lines. Proliferation and metastasis assays were performed to evaluate the effect of depleting USP37 and USP14 on survival and metastasis in GC cells under replication stress. A 3D in-vitro culture platform was developed to study the impact of USP37 downregulation on cellular proliferation and metastasis, with a comparison to 2D culture. Proteomics analysis identified interacting proteins regulating proliferation and metastasis. To investigate the role of DUBs in chemoresistance, chemoresistant (CR) cell lines were generated and characterized.

Results

Analysis of the TCGA database revealed elevated USP37 and USP14 expression associated with poor Overall Survival (OS) and Disease-free Survival (DFS) in GC. Increased expression of USP37 and USP14 was observed in GC cell lines, and their inhibition reduced proliferation and hindered metastasis. The 3D culture system proved effective in mimicking in-vivo conditions. Target exploration of USP37 revealed associations with EMT markers. Proteomics analysis identified proteins associated with replication, DNA damage, cell cycle, and metastasis. Cisplatin-resistant GC cell lines displayed altered cell cycle distribution and increased proliferation. Comparative interactome analysis revealed altered protein sets associated with USP37 and USP14 in CR and CS GC cells.

Conclusions

The research presents evidence that supports the participation of DUBs in GC, emphasizing changes in the oncogenic network. It underscores the sensitivity of the 3D culture system in assessing the oncogenic potential of DUBs, and elucidates the roles of these DUBs in chemoresistant cell lines.

Legal entity responsible for the study

All India Institute of Medical Sciences, New Delhi.

Funding

The Indian Council of Medical Research (ICMR), New Delhi, All India Institute Of Medical Sciences, New Delhi.

Disclosure

All authors have declared no conflicts of interest.

Background

Non-epithelial rare germ cell tumors (GCT) and sex cord stromal tumors (SCST) are mainly associated with long survival. The treatment includes surgery, frequently combined with chemotherapy (CT). The French Rare Malignant Gynecological Tumors (TMRG)/GINECO case-control VIVROVAIRE Rare tumors study already reported the QOL among survivors, treated with surgery +CT, compared to age-matched healthy women (HW). Looking to the different clinical profile of pts, we intend to describe the long-term fatigue according to subtype of cancers (SCST, GCT).

Methods

Non-epithelial ovarian cancer survivors (nEOCS), cancer-free ≥2 years after treatment, were identified from the TMRG Network. HW were issued from the ‘Seintinelles’ research platform. Primary endpoint was chronic fatigue (MFI) compared between patients (SCST/GCT) versus HW. A minimal 5% difference for the score between groups was considered as clinically relevant.

Results

97 SCST and 120 GCT were included. Patients' characteristics are detailed in the table. SCST patients were older than GCT and mostly FIGO stage I. Median delay from the end of treatment was 6 yrs. In univariate analysis, among SCST treated with CT, levels of general fatigue were significantly higher compared with HW (MFI general fatigue median score 27.0 [IQR: 21.0-31.0] vs 23.0 [17.3-27.8], p= 0.02). Among GCT treated with CT, fatigue was not different from HW (MFI general fatigue median score 24.0 [20.0-29.0] vs 23.0 [18.0-30.0], p= 0.592). After adjustment on age, schooling, BMI, insomnia and physical activity (IPAQ), fatigue remained significantly higher for all SCST, compared with all HW (beta= 1.67; p = 0.026); but not for SCST compared with age-matched HW (p=0.098).

Table: 19P

Patients’ characteristics and levels of fatigue

Conclusions

SCST patients (older pts compared to GCT) have long-term fatigue more than 6yrs after the end of treatments, which was not observed for GCT patients. This long-term fatigue need to be integrated in the follow-up care plan of nEOCS.

Clinical trial identification

NCT03418844.

Legal entity responsible for the study

The authors.

Funding

ARC Foundation for Cancer Research and the IMAGYN association.

Disclosure

C. Dubot: Financial Interests, Institutional, Invited Speaker: MSD, Amgen; Non-Financial Interests, Personal, Principal Investigator: AstraZeneca; MSD; GSK. I.L. Ray-Coquard: Financial Interests, Institutional, Research Grant: MSD, Roche, BMS; Financial Interests, Personal, Invited Speaker: Agenus, Advaxis, BMS, PharmaMar, Genmab, Pfizer, AstraZeneca, Merck; Financial Interests, Personal, Advisory Board: AbbVie, Agenus, Advaxis, BMS, PharmaMar, Genmab, Pfizer, AstraZeneca, Roche/Genentech, GSK, MSD, Deciphera, Mersena, Merck Sereno, Novartis, Amgen, Tesaro and Clovis; Springworks, Adaptimmune, Immunogen, Seagen, Novocure, Daiichi Sankyo, Travel support fro. P. Pautier: Financial Interests, Personal, Advisory Board, 2015, 2022: PharmaMar; Financial Interests, Institutional, Advisory Board, 2020: Roche, Clovis; Financial Interests, Institutional, Advisory Board, 2021: AstraZeneca; Financial Interests, Personal, Advisory Board, 2019-2020: AstraZeneca; Financial Interests, Institutional, Advisory Board: GSK; Financial Interests, Personal, Advisory Board, 2018-2019: Roche; Financial Interests, Institutional, Expert Testimony, 2022: MSD; Financial Interests, Personal and Institutional, Research Grant: PharmaMar; Financial Interests, Personal, Research Grant: Onxeo. F. Selle: Financial Interests, Personal, Invited Speaker: AstraZeneca, MSD, GSK/Tesaro, Eisai; Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, GSK/Tesaro. T. De La Motte Rouge: Financial Interests, Personal, Advisory Board: Pfizer, AstraZeneca, GSK, Clovis Oncology, Roche, MSD, Mylan, Tesaro, Gilead, Sanofi, Seagen; Financial Interests, Personal, Invited Speaker: Novartis, MSD; Financial Interests, Institutional, Research Grant: Novartis, Pfizer, MSD, Seagen; Financial Interests, Institutional, Invited Speaker: Roche, AstraZeneca, GSK, MSD, Pfizer, Netris Pharma; Non-Financial Interests, Personal, Advisory Role: French National Cancer Institute, Unicancer; Non-Financial Interests, Personal, Principal Investigator: Arcagy, Unicancer; Non-Financial Interests, Personal, Other, Co-Principal Investigator: Unicancer; Non-Financial Interests, Personal, Other, partnership using a Natera solution for a clinical trial funded by academic grant: Natera. J. Alexandre: Financial Interests, Personal, Advisory Board: Eisai, MSD, GSK, Janssen, Pfizer; Financial Interests, Personal, Invited Speaker: Eisai, MSD, AstraZeneca, GSK, Novartis; Financial Interests, Institutional, Research Grant: Janssen, GSK, MSD; Financial Interests, Institutional, Invited Speaker: MSD, Eisai, Agenus, GSK, Immunogen, Incyte. P. Augereau: Financial Interests, Personal, Invited Speaker: AstraZeneca, Daiichi Sankyo, Novartis, MSD, GSK. J.E. Kurtz: Financial Interests, Personal, Advisory Board: AstraZeneca, Eisai, GSK, MSD, Roche, PharmaMar; Financial Interests, Personal, Invited Speaker: Chugai, Clovis, Dragonfly, Tesaro; Financial Interests, Personal, Principal Investigator: Mersana. F. Joly Lobbedez: Financial Interests, Personal, Invited Speaker: Amgen, Eisai, Janssen; Financial Interests, Personal, Advisory Board: AstraZeneca, Astellas, Bayer, GSK, Ipsen, MSD, Novartis, Pfizer, Seagen; Financial Interests, Institutional, Invited Speaker: Viatris; Other, Personal, Research Grant: BMS. All other authors have declared no conflicts of interest.

Background

Neuroendocrine carcinoma of the cervix (NECC) is a rare variant of cervical cancer with biologically aggressive in nature. This study aimed to report the clinicopathological characteristics, treatment patterns, survival and factors affecting survival of NECC patients treated at National Cancer Institute, Malaysia.

Methods

This is a retrospective study of NECC patients registered at our centre between 2013 and 2023. Kaplan-Meier and Cox regression methods were used for statistical analyses.

Results

A total of 32 patients were included. 62.5% patients were < 45 years old (range, 25 - 77). Most patients were multiparous (81.3%), with 90.6% presented with vaginal bleeding. 62.5% had advanced disease upon diagnosis with majority had tumour > 4 cm (65.6%) and nodal negative (53.1%). On histopathologic review, all tumours were high grade with 75% tumours were classified as small cell, 21.9% were large cell, and 3.1% was mixed small and large cell. Out of 32 histopathological specimens, 26 proceeded for immunohistochemistry profile where all were tested positive for at least a single neuroendocrine marker and 84.6% were expressed for at least 2 neuroendocrine markers. Synaptophysin was tested positive in 95.8%, chromogranin in 79.2% and CD56 in 100% of tumours. In term of treatments, 53.1% and 21.9% received surgical based primary treatment and radiotherapy based primary treatment respectively. The most used chemotherapy regime as neoadjuvant, adjuvant or first-line palliative chemotherapy were Etoposide/platinum (n = 14) and Paclitaxel/carboplatin (n = 1). Folinic acid/fluorouracil/oxaliplatin (n = 1) and single agent irinotecan (n = 2) were also reported in subsequent line of palliative setting. After a median follow-up of 10.8 months (range, 0.8 - 98.9), the median overall survival for early stage and advanced stage were 30.2 and 8.0 months respectively. The 1-year and 2-year survival rates were 75% and 25% respectively for early stage, while 20% and 5% respectively for advanced stage. On multivariate analysis, advanced stage at diagnosis was predictive of poor survival.

Conclusions

NECC is a rare variant of cervical cancer that present in the advanced stage and portend poor prognosis.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Head and neck sarcomas are rare however, they tend to be aggressive and carry poor prognosis. We have limited data regarding their trends due to this scarcity which in turn lead to poorly developed screening and treatment guidelines. So, we aim to analyze age-adjusted trends of head and neck sarcoma.

Methods

We extracted the data of 9044 from the Surveillance, Epidemiological, and End Results (SEER) database diagnosed from 2000-2020. We analyzed Age-Adjusted Trends and Age-adjusted incidence rates. Rates are per 100,000 and age-adjusted to the 2000 US Std Population (19 age groups - Census P25-1130) standard; Confidence intervals are 95% for rates (Tiwari mod) and trends. Percent changes were calculated using 1 year for each end point; APCs were calculated using weighted least squares method.

Results

The overall incidence rate is 30%. The age-adjusted trend analysis showed a Percent change (PC) of 18.9 and an annual percent change (APC) of 1.3 (95%CI: 0.8 to 1.8). With stratification by sex, males showed higher PC and APC; PC:24.6, APC:1.4 (95%CI: 0.9 to 2.0) compared to females; PC:3.2, APC:0.6 (95%CI: -0.1 to 1.4). We also analyzed age-adjusted trends based on age groups; 0-19, 20-39, 40-59, and 60+. They showed PCs of -7.1, -3.2, -14.0, 46.7 respectively and APCs of 0 (95%CI: -1.1 to 1.2), 0.4 (95%CI -0.5 to 1.4), 0.4 (95%CI -0.7 to 1.5), and 1.9 (95%CI 1.3 to 2.5) respectively.

Conclusions

Head and neck sarcomas showed an overall high incidence rate. It also demonstrated a rising incidence rate throughout the years. Both Males and females showed an increase with more predominance by males. Only age group 60+ had a rising incidence rate, while the rest of age groups had a declining incidence rate. The poor prognosis combined with high incidence rate of head and neck sarcoma warrants the need to develop screening guidelines to combat this rise. We recommend more focus on males and aged 60+ as they showed the most increase.

Legal entity responsible for the study

The author.

Funding

Has not received any funding.

Disclosure

The author has declared no conflicts of interest.

Background

Adenoid Cystic Carcinoma (ACC) is a rare malignancy characterized by high incidence of relapse, with a poor long-term prognosis. The pharmacological approach is based on the combination of the chemotherapy drugs (cisplatin and doxorubicin); however, the response rate is low and not long-lasting. Alternative approaches for second-line therapies in case of disease progression are still lacking. In this study, the cytotoxic effects of both standard chemotherapy and targeted therapy drugs were evaluated, both in vitro and in vivo.

Methods

Cisplatin and doxorubicin as well as lenvatinib, vorinostat, everolimus, palbociclib and olaparib were tested alone or combined. The human ACC (hTERT) cell line, derived from a primary untreated ACC was used as experimental cell model. Cell viability was assessed by MTT assay, the cell proliferation was evaluated by cell counts. For in vivo evaluation, Danio rerio embryos were xenografted with ACC cells and exposed to the drugs for 3 days. The effect was evaluated by measuring the tumor areas.

Results

Cisplatin and doxorubicin reduced ACC cell viability and proliferation (over 90% efficacy). Vorinostat, olaparib, palbociclib and everolimus reduced the cell viability and proliferation, although with lower efficacy, except for vorinostat. Lenvatinib was scarcely effective and then excluded from subsequent evaluations. In the in vivo models, the drugs tested significantly reduced the tumor area. In the combination experiments, vorinostat + cisplatin or doxorubicin induced synergistic cytotoxic effects in ACC cells compare to single treatments. The combination of olaparib + cisplatin or doxorubicin resulted in an increased potency.

Conclusions

Vorinostat and olaparib significantly increased the standard chemotherapy cytotoxic effects, suggesting new interesting therapeutic options for ACC. These results on ACC, together with other high grade salivary gland cancers cell models, are now explored in depth as preclinical aim of the project granted by FRRB (ID3438215 - In depth analysis of salivary gland cancers: from cell lines and genomic evaluation towards clinical trials in locally advanced and recurrent/metastatic disease – INDAGA).

Legal entity responsible for the study

The authors.

Funding

University of Brescia (Local grant).

Disclosure

A. Berruti: Financial Interests, Personal, Invited Speaker: HRA; Financial Interests, Personal, Advisory Board: HRA; Financial Interests, Personal, Research Grant: Janssen, Sanofi, Novartis. P. Bossi: Financial Interests, Personal, Advisory Board: Merck, Sanofi-Regeneron, Sun Pharma, Angelini, Nestlé; Financial Interests, Institutional, Invited Speaker: MSD, GSK; Financial Interests, Personal, Invited Speaker: Merus, Pfizer, Elevar. All other authors have declared no conflicts of interest.

Background

Sinonasal neuroendocrine tumors are a rare histological subtype of sinonasal carcinomas. Most of these tumors are diagnosed as an advanced disease and, due to their rarity, there is no optimal treatment sequence that has been established. The aim of the present work is to review our institutional experience with sinonasal undifferentiated carcinomas (SNUC) and esthesioneuroblastomas (ENB) as well as to analyze the different therapeutic strategies and their impact in terms of survival and disease control.

Methods

This is a retrospective observational study, in which epidemiological data were collected and analyzed, as well as those related to the disease and its initial management in localized or locally advanced disease, in patients diagnosed with SNUC or ENB from 2009 until the present, at The Miguel Servet Hospital. The Kaplan Meier method was used to estimate disease-free survival (DFS) and overall survival (OS).

Results

We identified 15 patients with sinonasal neuroendocrine tumor; 73.3% were SNUC and 26.7% ENB. The median age at diagnosis was 61 years. Most cases were diagnosed as a locally advanced disease. Regarding initial management, 12 patients received induction chemotherapy (IC), and 3 underwent primary surgery. In all cases they received subsequent chemo-radiotherapy (CRT). With a median follow-up of 44 months, 26.7% of patients had relapsed, and only one patient had died. The 5-year DFS was 60.6%, while the 5-year OS was 83.3%. No significant differences were observed in DFS or OS according to the therapeutic strategy. We did observe a lower DFS in N+ patients in comparison to N0 patients (29 months vs 156 months, p=0.002), with a risk of relapse 10 times higher in N+ patients than in N0 patients (p=0.001).

Conclusions

It seems to be no difference in terms of survival and disease control between IC and primary surgery, followed in both cases by CRT. Nodal involvement could be considered a risk factor for relapse. However, in order to compare therapeutic alternatives and analyze prognostic factors we would require a larger sample size and a prospective study design.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Head and neck soft tissue sarcoma carries poor prognosis. They are also known for their high recurrence rate however, the possibility of a second primary is still unclear. So, we aim to assess the risk of developing a second primary cancer in the head and neck region to highlight the association with head and neck soft tissue sarcoma and for better quality of life.

Methods

We extracted the data of 5935 patients from Surveillance, Epidemiology, and End Results (SEER) database diagnosed from 2000-2019. Using MP-SIR seer session, the standardized incident ratio (SIR) was assessed as Observed/Expected (O/E) ratio and Excess Absolute Risk (EAR) is per 10000. Confidence intervals are 95% and P value is significant P<0.05.

Results

The overall 5-year relative survival of head and neck soft tissue sarcoma was 66.9%. It had an overall EAR of 30.67 and O/E of 37.4 (P<0.05, 95%CI: 29.5-46.8). The nasal cavity was the most site to have a risk for a second primary cancer with EAR of 19.4, and O/E= 444.2 (P<0.05, 95%CI: 326.4-590.7). The larynx had the second highest risk of a second primary tumor with EAR=10.4 and O/E= 28.3 (P<0.05, 95%CI: 18.5-41.5). The gum of the mouth demonstrated the third highest risk with EAR= 6.5 and O/E= 16.1 (P<0.05, 95%CI: 6.9-31.8). Salivary glands had an EAR of 6.1 and O/E of 57.0 (P<0.05, 95%CI: 31.9-94.0). Nasopharynx had an EAR=4.1 and O/E= 83.48 (P<0.05, 95%CI: 40.03-153.52).

Conclusions

These results show a 30-fold increase in the risk of developing a second primary cancer in the head and neck region. Nasal cavity had the highest fold risk increase by 19 folds followed by larynx by 10 folds. The gum and salivary glands both had around 6-fold rise in the risk of a second primary tumor. Nasopharynx showed the least risk by 4 folds. We recommend follow up screening of the nasal cavity and the larynx as most sites at risk of a second primary especially cancers at these sites only manifest at later stages making it hard to treat.

Legal entity responsible for the study

The author.

Funding

Has not received any funding.

Disclosure

The author has declared no conflicts of interest.

Background

The S1609 DART trial is designed to assess the clinical relevance of combination dual ipilimumab and nivolumab in rare tumors. We focused on immune profiling 2 cohorts comprised of subtypes of neuroendocrine carcinomas; cohort 23 (nonpancreatic neuroendocrine (NET) and cohort 52 (pan high-grade neuroendocrine).

Methods

FFPE tissue collected at baseline and PBMCs and plasma collected at baseline and cycle 2 week 9 (C2W9) were utilized. Samples were subjected to multi-omics analyses including IHC, multiplex immunofluorescence (mIF), gene expression profiling, WES, TCR sequencing, CyTOF and Olink. Known viral TCRs were removed in silico from analysis. Hierarchical clustering based on an interacting distance of 25μm and minimum neighborhood size of 10 cells was used to identify neighborhoods of interacting cells in the TME from mIF. Biomarker data was dichotomized by median and Cox Proportional Hazard regression model used for multivariate survival analysis. For continuous biomarker data, we use Spearman’s rank correlation, Mann-Whitney U test, or Kruskal-Wallis test. We dichotomized biomarker data and used Chi-Square test for response analysis. Benjamini & Hochbert method was used for multiple-testing adjustment of p-values.

Results

Immune cells clustered in the tumor regions of responding patients and in the stroma of non-responding patients. Gene expression profiling showed a B cell signature correlated with superior response (p=0.0037) and longer progression-free survival (PFS, p=0.0067) and a tertiary lymphoid signature (TLS) associated with better response (p=0.05). Lymphoid aggregates were confirmed using H&E and correlated with B cell and TLS gene signatures. Response was associated with a decrease in IL8, an increase in IFNg, and expansion of CD4⁺ T cell memory subsets and activation by C2W9 in peripheral blood. TCRseq revealed high richness and density correlation with improved PFS (p=0.00011) at C2W9 but not at baseline.

Conclusions

With limited sample size fully acknowledged, multiomics analysis of NET cohorts revealed B cell/TLS signatures in tumor, diverse/dense T cells and expansion of CD4+ memory T cells in peripheral blood associate with improved outcome to ipi/nivo treatment.

Clinical trial identification

NCT02834013; Ethics Approval: The study was approved by the NCI Adult Central Institutional Review Board, approval number 02834013.

Legal entity responsible for the study

University of Texas MD Anderson Cancer Center.

Funding

Scientific and financial support for the CIMAC-CIDC Network is provided through the National Cancer Institute (NCI) Cooperative Agreements U24CA224319 (to the Icahn School of Medicine at Mount Sinai CIMAC), U24CA224285 (to the MD Anderson Cancer Center CIMAC), U24CA224309 (to the Stanford University CIMAC), and U24CA224316 (to the CIDC at Dana-Farber Cancer Institute) as well as funding through U10CA180888, U10CA180819; and in part by Bristol-Myers Squibb Company.

Disclosure

C. Haymaker: Financial Interests, Personal, Advisory Board: Regeneron; Financial Interests, Personal, Other, Consulting: Avenge; Financial Interests, Personal, Other, Stock options as a member of the Scientific Advisory Board: Briacell; Financial Interests, Institutional, Research Grant: Iovance, Dragonfly, BTG, Sanofi, Avenge, KSQ; Non-Financial Interests, Personal, Advisory Role, Co-Chair of SAB: Mesothelioma Applied Research Foundation. S. Gnjatic: Financial Interests, Institutional, Research Grant: Regeneron Pharmaceuticals, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Genentech, EMD Serono, Pfizer, Takeda. J. Zhang: Financial Interests, Personal, Advisory Role: Merck, Johnson and Johnson, Novartis, AstraZeneca, GenePlus, Innovent, Catalyst, Henlius, Summit, Hengrui; Financial Interests, Institutional, Research Grant: Merck, Johnson and Johnson, Novartis, AstraZeneca, GenePlus, Innovent, Catalyst, Henlius, Summit, Hengrui. All other authors have declared no conflicts of interest.

Background

NETS is a rare subtype cancer with a poor prognosis. Etoposide plus platinum-based chemotherapy, the most frequently used first-line treatment for NETS, results in poor survival (median overall survival [OS] 11 to 19 months). Camrelizumab combined with apatinib mesylate had improved outcomes across tumor types; little is known about the efficacy in NETS.

Methods

Patients were eligible if they were aged 18 through 75 years; had histologically or cytologically confirmed high-grade NETS with TNM clinical stage IIIB-IV; had received no previous systemic therapy; Camrelizumab (200mg, every 21 days) and apatinib mesylate (250mg, everyday) were given until disease progression, Etoposide (100mg/m², d1-3) and cisplatin(25mg/m², d1-3) were given for up to 6 cycles. The primary endpoint was progression free survival (PFS) defined by the RECIST 1.1 guideline.

Results

12 patients were enrolled from July 19, 2021 to May 24, 2023. The median age was 61 years (range, 58-68). 7 patients were males (58.3%) and 5 females (41.7%). The Eastern Cooperative Oncology Group performance status score was 0 in 8 patients (66.7%) and 1 in 4 patients (33.3%). The tumors were primarily located in the mediastinum for 4 patients (33.33%), skin for 2 patients (16.7%), and in the parotid gland, lung, descending colon, nasal cavity, stomach's cardia, and ureter, with one patient (8.3%) in each location. All patients showed a Ki-67 index of over 55%. 11 underwent efficacy evaluation, including 9 partial response, 1 stable disease, and 1 progression disease. The objective response rate was 81.8%, and the disease control rate was 90.9%. At data cutoff, 8 of 12 patients experienced disease progression, with a median PFS of 10.7 months. The median OS has not yet been reached. Adverse events occurred in 10 (83.3%) patients, the most grade 1-2. Only one patient (8.3%) experienced grade 4 thrombocytopenia.

Conclusions

Camrelizumab combined with apatinib mesylate and chemotherapy achieved high response rate and longer median progression free survival in the treatment of newly diagnosed advanced high-grade NETS, with good safety.

Clinical trial identification

ChiCTR2300076887.

Legal entity responsible for the study

Jiangsu Hengrui Pharmaceutical Co., Ltd.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Neuroendocrine tumors (NETs) display relatively slow growth and heterogeneous treatment responses. Recent advances in systemic and locoregional therapies have shown efficacy in delaying progression. Imaging, while crucial for follow-up, faces challenges with conventional evaluation criteria (RECIST), criticized for variability in target lesion selection and measurements. AI-enabled automated segmentations may provide a time-efficient, accurate, and reproducible method for treatment response monitoring.

Methods

Two AI segmentation models were trained to delineate liver metastases in NET patients, following an iterative training-radiologist correction scheme: a portal venous phase (PVP) model (trained on 65 scans) and an arterial phase (AP) model (trained on 36 scans). AP model was trained in three different settings. The training dataset was from a previously published study. External validation involved testing the final models on an independent dataset with follow-up data from three exemplary patients with long follow-ups. The evaluation utilized the Dice Correlation Coefficient Score (DSC) quantifying the overlap between predicted and ground truth, coefficient of determination (r2).

Results

PVP model DSCs were 66%, 77%, and 93% for each patient, respectively. Correlation between AI volume and radiologist volume was high per lesion (r2=0.93), and total tumor burden (r2=0.79). The three settings used for the AP models showed similar results in terms of median DSC (87%, 88%, 91%). Both PVP and AP models exhibited variability in DSC due to lesion density and enhancement differences and heterogeneity, with PVP excelling in identifying the hypodense lesions and AP performing better in hyperdense lesions. Differences were observed between RECIST and AI-volume trends in a preliminary comparison.

Conclusions

This pilot study shows promising preliminary results for the creation of response criteria based on AI-quantified volumetry in NET tumors, with the algorithm being able to reproduce the results of experienced radiologists. Future outlook includes extension of the study cohort and formal comparison with RECIST 1.1.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Chemotherapy is considered the primary treatment for stage IV pancreatic neuroendocrine carcinoma (pNEC). However, the optimal management of metastatic pNEC as defined by the updated WHO classification (2022) has not been adequately explored. This study analyzed the clinical features and prognostic factors of metastatic pNEC and assessed the efficacy of surgery and chemotherapy in these patients based on the latest classification.

Methods

Data of stage IV pNEC patients diagnosed between 2004-2020 were extracted from the Surveillance, Epidemiology and End Results database. Cox regression was performed to identify prognostic factors with SPSS-29. Demographic, oncological and clinicopathological data were compared between groups with Chi-square test. Propensity score matching (PSM) was used to ensure comparability between groups. K-M plots were used to estimate overall survival (OS) and cause-specific survival (CSS).

Results

267 patients were eligible for this study, including 16 (6.0%) patients who underwent palliative primary tumor resection. Primary tumor in pancreatic tail, surgery and chemotherapy were identified as independent protective factors by Cox regression (p=0.017, p<0.01, p<0.001, respectively). Patients who underwent surgery exhibited both a median OS and CSS of 26 months, compared to 7 months and 8 months for those who did not, respectively (p=0.002 for both OS and CSS). After PSM, surgery continued to be significantly associated with improved survival (p=0.016 for OS, p=0.007 for CSS). According to subgroup analysis without surgery, OS and CSS did not significantly differ between the chemotherapy and nonchemotherapy groups of large cell NEC (LCNEC) patients (p=0.276 for OS, p=0.208 for CSS). Conversely, chemotherapy significantly improved prognosis in small cell NEC (SCNEC) patients before (p<0.001 for both OS and CSS) and after PSM (p<0.001 for both OS and CSS).

Conclusions

This study identified primary tumor in pancreatic tail, surgery and chemotherapy as protective factors for stage IV pNEC. Palliative primary tumor resection was associated with improved prognosis in selected patients. Further studies are required to confirm the effect of chemotherapy in LCNEC patients.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are uncommon cancers globally. The data on their clinical presentation, site of tumour and its grading, from India is scarce.

Methods

We retrospectively collected anonymised patient data from our electronic health records from 1^st May 2011 to 1^st Oct 2023. The information was initially collected in an excel sheet and then analysed for various parameters.

Results

We saw 418 patients with Neuroendocrine Neoplasms in our data set. Out of those, more than 81% (n=339) were GEP-NENs with male preponderance (Females=138). The median age of presentation for GEP-NENs was 60 years (Range: 12-90). Most common primary site of tumour was small intestine (37%, n=123) with maximum incidence in Pancreas (n=80) followed by Duodenum (n=72). Least common site was Esophagus/Gastroesophageal junction (n=5). With respect to tumour grading (WHO), we found G1 (125) G2 as most common (n=83) and G3 the least (n=50), information for 39% of tumours was not available, mostly because of inadequate tissue sample or incomplete review due to lack of follow up by the patients. Only 10 patients (3%) presented with carcinoid syndrome and most common symptom was diarrhoea (n=9). DOTA PET scan was done in about 44% (n=143) patients as initial imaging tool for staging. Half of the patients with GEP-NENs presented to our clinic with metastasis to various sites with liver being most common organ. About 19% patients had upfront Echocardiography to see for any carcinoid heart but only 1 patient was found to have hypertrophy of the right ventricle.

Conclusions

GEP-NENs are most common NENs observed. Small intestine is the most common site for GEP-NENs and it matches with the published global data. Carcinoid syndrome can be the presenting complaint, but we had less incidence.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

According to the latest WHO classification, within high-grade NEN, the distinction between neuroendocrine tumor (NET) G3 and carcinoma (NEC) G3 is clinically and prognostically meaningful. Platinum-based chemotherapy remains the recommended first-line treatment in metastasized NEC patients, but there is no established standard for NET G3.

Methods

Retrospective analysis of high-grade NEN treated in our hospital with platinum since August 2014, after pathology review and re-classification in NET G3 or NEC G3. We analyzed demographic features, platinum response and survival. We used IBM SPSS Statistics v.25.

Results

A total of 26 patients (69.2% male, 30.8% female) were included. About primary location of the tumour, 38.5% were pancreatic, 19.2% gastrointestinal, 3.2% bronchial, 11.5% other locations and 26.9% unknown. After pathology review, 23.1% were NET G3 and 76.9% NEC G3. Furthermore, 61.5% had Ki67 > 50%, and 65.4% > 20 mitosis/10HPF. 92.3% received platinum as first line of treatment (53.8% with carboplatin and 46.2% with cisplatin). In whole group, we observed a median progression-free survival (PFS) of 5.8 months, median overall survival (OS) of 10.7 months, a response rate (RR) of 50%, and disease control rate (DCR) of 65.4%. When we analyzed by pathological subtypes, in NET G3 we got 4.6 months of PFS, 26.8 months of OS, 16.7% of RR and 50% of DCR. On the other hand, in NEC G3 we found 5.9 months of PFS, 9.8 months of OS, 65% of RR and 75% of DCR. However, the differences in PFS and OS were not statistically significant (p value 0.527 and 0.198 respectively). 50% patients received a second line of treatment, in most cases irinotecan-based chemotherapy or re-challenge with platinum, with a median PFS of 4.1 months, RR of 15.4% (all with platinum re-challenge) and DCR of 38.5%. At the moment of the analysis, 80.8% of patients were passed away.

Conclusions

Although platinum-based chemotherapy is a good option for first line in all NEN G3, it seems to be more effective in NEC than in NET G3, with more RR and DCR (even though the differences in survival are not statistically significant). Although the benefit of the second lines is very debatable, if considered we should prioritize the rechallenge if possible.

Legal entity responsible for the study

P. Santos Fernandez.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Whether environmental pollution may influence adrenocortical carcinoma (ACC) development remains largely unknown. The aim of this study was to evaluate the impact of exposition to environmental pollutants on ACC presentation and prognosis in Italy.

Methods

A retrospective analysis was done on 500 patients affected by ACC, who were diagnosed in 12 reference centers in Italy from 1990 to 2018 and followed-up for a median of 37.5 months (interquartile range, IQR, 11-83). Patients were stratified according to: i) residence in Sites of National Interest (SIN) which are areas with contaminated soil and water, classified as dangerous by the Italian Ministry of Environment and in need of remediation; ii) residence in areas with different degrees of urbanisation, considered as index of exposure to air pollution.

Results

At diagnosis, 50 (10%) patients were resident in SIN (Res-SIN) and 450 (90%) patients were not (Not-SIN). The two groups had similar characteristics in terms of age, ENSAT stage, tumor size, Weiss score and Ki67%. However, incidental diagnosis of ACC was more frequent in Not-SIN patients (40.0% vs 19.6%; p=0.011). Res-SIN patients showed shorter recurrence-free survival (RFS) (21 months vs 41 months; p=0.027). In multivariate analysis, residence in SIN was an independent negative prognostic factor for RFS (HR 1.82, 95%CI 1.10-3.03; p=0.021). Overall survival (OS) showed a similar pattern although the difference between the 2 groups was not significantly different. At diagnosis, 205 (41%) patients were resident in “cities” (> 50% of population in urban centers, with density >1,500 inhabitants/km² and population >50,000), 230 (46%) in “towns/suburbs” (>50% in urban clusters with density >300 inhabitants/km² and population >5,000), and 65 (13%) in “rural areas” (> 50% of population not meeting the previous criteria). No statistically significant differences were observed among the 3 groups in terms of clinical presentation, RFS and OS.

Conclusions

The different clinical presentation and worse outcome of ACC in patients living in areas with contaminated soil and water suggest that environmental pollutants in these matrices may have a role in conditioning the behavior of this rare tumor. Conversely, air pollution does not seem to influence the ACC disease course.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Adrenocortical carcinomas (ACC) are often associated with cortisol and/or androgen hypersecretion. Metirapone and osilodrostat are used for syndrome control despite they induce androgen levels increase. Abiraterone acetate (AA) is an irreversible inhibitor of 17α-hydroxylase/C17, 20-lyase (CYP17) that blocks the adrenal synthesis of cortisol and androgens. The aim of this study was to assess the efficacy of AA in ACC patients with Cushing’s syndrome.

Methods

ABACUS (NCT 03145285) is a phase II trial aiming to assess the activity of AA in normalizing 24-h urinary free cortisol (UFC) excretion within 1 month from treatment start in two cohorts of patients (I: pretreated patients; II: mitotane-naïve patients). Secondary endpoints were to assess: the activity of AA in attaining 50% reduction of 24-h UFC excretion; AA safety.

Results

15 ACC patients, 7 in cohort I and 8 in cohort II, were treated with AA. In 8 patients, multiple steroid secretion was found. Overall, median 24-h UFC (measured by gas-mass spectrometry) was 368 μg/24h (121-7422) at baseline and 94 μg/24h (20-1793) at end of treatment (p=0.01). A normalization of 24-h UFC was obtained in 8 patients (53%), 57% in cohort I and 50% in cohort II. Androgen were also significantly reduced by AA treatment in patients with multiple secretion. In cohort I, a >50% decrease in 24-h UFC was seen in 7 patients (100%) with a median time to effect of 22 days (14-163). After AA, 6 patients received a further line of chemotherapy with a median OS of 5.4 months (0.9-23.2). In cohort II, a >50% decrease in 24-h UFC was seen in 6 patients (75%) with a median time to effect of 16 days (9-29). After AA, 6 patients received at least one line of chemotherapy and 1 patient underwent abdominal surgery, the median OS was 5.8 months (0.9-76). At the end of AA treatment all patients experienced syndrome relapse. AA was well tolerated. Only 1 patient developed a drug-related toxicity (G2 transaminitis), reversible with AA interruption.

Conclusions

The results of this proof-of-concept study show that AA is a promising drug to control both cortisol and androgen excess sustained by ACC. Short duration of the study does not allow us to obtain information on long term drug efficacy.

Clinical trial identification

NCT 03145285.

Legal entity responsible for the study

ASST Spedali Civili of Brescia.

Funding

Janssen.

Disclosure

S. Grisanti: Financial Interests, Personal, Advisory Board: Roche, Takeda, Novartis; Financial Interests, Personal, Invited Speaker: AstraZeneca, Bristol Myers Squibb; Financial Interests, Institutional, Funding: Roche, AstraZeneca. M. Terzolo: Financial Interests, Personal, Invited Speaker: HRA. A. Berruti: Financial Interests, Personal, Advisory Role: HRA; Financial Interests, Personal, Invited Speaker: HRA; Financial Interests, Institutional, Research Grant: Janssen, Sanofi, Novartis. All other authors have declared no conflicts of interest.

Background

Adrenocortical carcinoma (ACC) is a rare and aggressive tumor with a dismal prognosis. The pharmacotherapy of ACC is based on mitotane with/without etoposide, doxorubicin, and cisplatin. The limited efficacy and the toxicity of this treatment require new drug strategies. Progesterone (Pg) is a lipophilic hormone involved in both physiological and pathological processes. Trabectedin (T) is an alkylating drug with a complex mechanism of action. We have already reported Pg and T cytotoxicity in ACC cells, involving the Wnt/β-catenin pathway. Here, we investigated their effect on ACC cells invasiveness and metastatization.

Methods

Cell lines of primary (NCI-H295R) and metastatic (MUC-1 and TVBF-7) ACC were used to study the in vivo efficacy of Pg and T, by establishing tumor xenografts in Danio rerio embryos. The tumor mass areas were evaluated as well as metastasis-positive embryos. The in vitro invasiveness was evaluated in transwell assay. MMP2 (metalloprotease 2) secretion and activity were evaluated by western-blot and by zymography in cell culture-conditioned media.

Results

Xenograft experiments demonstrated Pg- and T-related reduction of tumor area in each ACC cell mode. Metastasis-derived cells proved to be able to metastasize in different regions of the embryos. Metastasis formation was reduced after Pg and T (Table). These results were confirmed in vitro, where Pg and T reduced the invasiveness of ACC cells across the matrix, which was greater at baseline for the metastatic models compared to primary-derived one. In metastatic models, protein analysis demonstrated a reduction of MMP2 secretion and activity in the culture medium after Pg and T exposure.

Table: 36P

Percentage of xenografted zebrafish embryos with metastasis

Conclusions

Our results indicate the ability of Pg and T to interfere with invasive and metastasis processes, with an involvement of MMP2. Furthermore, these results support those previously published and reinforce the promising role of Pg and T in ACC.

Legal entity responsible for the study

The authors.

Funding

Fondazione AIRC per la ricerca sul cancro (IG 23009; P.I. Prof. Alfredo Berruti - IG 27233 P.I. Prof. Sandra Sigala) University of Brescia (local grants) Trabectedin was kindly given by PharmaMar S.A. (Madrid, Spain).

Disclosure

A. Berruti: Financial Interests, Personal, Invited Speaker: HRA; Financial Interests, Personal, Advisory Board: HRA; Financial Interests, Personal, Research Grant: Janssen, Sanofi, Novartis. All other authors have declared no conflicts of interest.

Background

Mitotane is the cornerstone of both adjuvant and metastatic treatment of adrenocortical carcinoma (ACC). The side effects of this drug include those related to its estrogenic mimetic action, which has not been well studied.

Methods

We conducted a retrospective study to assess the rate of menometrorrhagia, endometrial thickness, and ovarian cysts among female ACC patients (F-ACC), as well as gynecomastia among male ACC patients (M-ACC patients) who had been taking mitotane for at least 6 months. Secondary objectives were to examine the correlation between these toxicities and possible clinical factors.

Results

35 F-ACC and 25 M-ACC patients were enrolled; of these, 22 (36.7%) F-ACC and 7 (11.7%) M-ACC patients developed mitotane-related estrogenic effects, respectively. Among F-ACCs, 10 (28.6%) had menometrorrhagia, 8 (22.9%) endometrial thickening, and 13 (37.1%) ovarian cysts. Serum levels of testosterone (p 0.006) and DHEAS (p 0.002) had an inverse correlation with these side effects, but there was no correlation with mitotane plasma concentration, duration of mitotane therapy (p 1.0) and serum levels of LH (p 0.5), FSH (p 1.0), estradiol (p 0.587), cortisol (p 0.234), ACTH (p 0.139), 17-OH progesterone (p 0.381). M-ACC patients developing gynecomastia had higher mitotane concentrations (median: 17 mg/l vs 10 mg/l, p 0.005). Whereas there was no statistically significant correlation between this side effect and serum values of estradiol (p 0.643), testosterone (p 0.222), cortisol (p 1.0), ACTH (p 0.71), 17-OH progesterone (p 0.857) and DHEAS (p 0.143).

Conclusions

Women with ACC are particularly susceptible to estrogen-mimetic side effects of mitotane, which are inversely correlated with androgen levels. Serum mitotane levels can affect men's gynecomastia.

Legal entity responsible for the study

A. Berruti.

Funding

Has not received any funding.

Disclosure

S. Grisanti: Financial Interests, Personal, Advisory Board: Roche, Takeda, Novartis; Financial Interests, Personal, Invited Speaker: AstraZeneca, Bristol Myers Squibb; Financial Interests, Institutional, Funding: Roche, AstraZeneca. A. Berruti: Financial Interests, Personal, Advisory Board: HRA; Financial Interests, Personal, Invited Speaker: HRA; Financial Interests, Personal, Research Grant: Janssen, Sanofi, Novartis. All other authors have declared no conflicts of interest.

Background

Adrenocortical carcinoma (ACC) patients have a high chance of developing venous thromboembolism (VTE) due to numerous risk factors that include malignancy, hormonal excess, surgery, and immobility. The incidence of VTE in these patients is unclear.

Methods

In this multicentre retrospective study, we evaluated ACC patients (pts) treated in 6 Referral Centres from January 2005 to September 2023. The study aimed to assess the prevalence of VTE in ACC pts, describe their characteristics and identify potential prognostic factors.

Results

Out of 1597 ACC pts, 124 (8%) presented at least one VTE, of whom 45 (36%) developed pulmonary embolism, 52 (42%) deep venous thrombosis and 27 (22%) both. Among pro-thrombotic risk factors, 28 (23%) patients were current or former smokers, 36 (29%) had a central venous catheter, 10 (8%) presented familiar history or genetic predisposition. Thirty-four (27%) pts presented intra vena cava or renal vein tumor thrombus at ACC diagnosis. The majority of patients underwent adrenalectomy (86%), of whom 17 (14%) did not attained a complete resection. The median age at first VTE appearance was 54 years, thirty-one (25%) patients had cortisol overproduction at VTE diagnosis and 109 (88%) presented with III or IV ENSAT stage ACC. One-hundred eighteen (95%) pts developed VTE after at least 3 months since ACC diagnosis. Nine (7%) pts required urgent medication and 57 (46%) needed lifelong anti-coagulant treatment. Median OS was 45 months, at multivariate analysis the presence of tumor thrombus (HR 1.78, CI: 1.05-3.04, p=0.032) and surgery on primary ACC (HR 0.067, CI: 0.02-0.16, p ≤ 0.001) confirmed their prognostic role.

Conclusions

ACC patients are at moderate risk of developing VTE, which requires proper management. The presence of thrombosis at initial diagnosis has a negative impact on prognosis.

Legal entity responsible for the study

A. Berruti.

Funding

Has not received any funding.

Disclosure

M. Fassnacht: Financial Interests, Institutional, Invited Speaker, Clinical trial on adrenocortical carcinoma and malignant pheochromocytoma: Enterome Bioscience; Financial Interests, Institutional, Invited Speaker, Clinical trial in Cushing's syndrome: HRA Pharma, Corcept; Non-Financial Interests, Personal, Leadership Role: European Network for the Study of Adrenal Tumor; Non-Financial Interests, Personal, Member of Board of Directors: European Society of Endocrinology; Non-Financial Interests, Personal, Member: European Network for the Study of Adrenal Tumors; Other, Personal, Other, Data safety board for a clinical trail (compensation is paid to the Institution): Bayer Pharma. A. Berruti: Financial Interests, Personal, Advisory Board: HRA; Financial Interests, Personal, Invited Speaker: HRA; Financial Interests, Personal, Research Grant: Jansen, Sanofi, Novartis. All other authors have declared no conflicts of interest.

Background

Rare cancers constitute a heterogeneous group of diseases that, although individually with a low incidence, correspond to 20-25% of new cases of malignancies as a group. Despite this fact, rare cancers – including sarcomas – are often overlooked in National Cancer Control Plans (NCCPs), National Non-communicable Chronic Disease Plans (NCDs), and National Rare Diseases Plans (NRDPs).

Methods

We performed a qualitative review of NCCPs, NCDs, and NRDPs from South American countries, gathered from each ministry of health or equivalent website, and the International Cancer Control Partnership (ICCP) portal. Following an initial assessment of whether rare cancers were mentioned in the documents, we proceeded with an in-depth analysis to provide a descriptive review of how rare cancers and sarcoma were addressed.

Results

We reviewed documents from 12 countries within South America – 7 NCCPs, 9 CNDs, 4 NRDPs. Two countries had no documents to be reviewed. Rare cancers are rarely addressed specifically in any of the documents reviewed. For 5/10 countries with documents reviewed, rare cancers were not mentioned specifically in any of the documents analyzed. The document that provided a more in-depth assessment of rare cancers was NCCP from Argentina, which describes a project for telemedicine for rare cancers and, specifically, a pilot project for sarcomas to improve diagnostics, access to multidisciplinary discussion, and appropriate care. Table: 41P

Conclusions

The limited inclusion of rare cancers in the majority of NCCPs/NCDs/NRDPs from South America suggests a lack of awareness and understanding regarding their unique aspects. It is key to enhance the national policy frameworks that tackle the challenges faced by patients diagnosed with rare cancers – including sarcomas – positioning NCCPs as essential strategic documents in this effort.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

R. Carmagnani Pestana: Financial Interests, Personal, Advisory Board: Bayer, Servier, Astellas; Financial Interests, Personal, Invited Speaker: Bayer, Servier, Pfizer, Amgen, BMS, Merck, Knight therapeutics; Financial Interests, Institutional, Invited Speaker: Servier; Non-Financial Interests, Personal, Leadership Role: LACOG, SBOC. B.B. Lopes David: Financial Interests, Personal, Invited Speaker, Participation in the scientific program of the Americas Oncologia International Symposium (08/2019). Air ticket and Accommodation: COI Institute/Americas Oncologia; Financial Interests, Personal, Invited Speaker, Satellite symposium at the Brazilian Congress of Orthopedics: Deciphera; Financial Interests, Personal, Other, Scholarship. Project Manager - SELNET Consortium: Istituto Nazionale dei Tumori; Financial Interests, Personal, Other, Senior Medical Advisor in Sarcomas for Latin America: Orphan DC; Financial Interests, Institutional, Other, Project Manager, Scholarship. Observational study for Quality Assessment of Sarcoma as a model to improve diagnosis and clinical care of rare tumors through a European and Latin American multidisciplinary Network (SELNET) HORIZON 2020-SC1-BHC-2018-2020/H2020-SC1-2018-Single-Stage-RTD: Istituto Nazionale dei Tumori; Non-Financial Interests, Personal, Member, Promotion of training and research, continuing education, health policies, professional defense, national and international relations: SBOC - Brazilian Society of Clinical Oncology; Non-Financial Interests, Personal, Member, Member-FellowStructured educational pathway that spans careers from medical student through to taking on leadership responsibilities. ESO has offered young oncologists an expanding array of educational opportunities, from oncology basics to specialist courses and fellowships, delivered face to face or online: ESCO - College of the European School of Oncology. C. Mello: Financial Interests, Personal, Advisory Role: Boehringer Ingelheim, Servier, Addium; Financial Interests, Personal, Invited Speaker: Servier, Addium. M.L. Gonzalez Donna: Financial Interests, Personal, Research Grant: ASCO-Pfizer. R. Ramella Munhoz: Financial Interests, Personal, Invited Speaker: BMS, MSD, Sanofi, Novartis, Merck Serono; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Invited Speaker, Invited speaker: Pfizer; Financial Interests, Institutional, Invited Speaker: Roche, Novartis, Bayer, Agenus, Pfizer. M. Zapata: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Bayer, Biotoscana, BMS, Boehringer Ingelheim, Eli Lilly, Janssen, MSD, Merck-Serono, Novartis, Roche, Sanofi. C.L. Martins: Financial Interests, Personal, Invited Speaker: MSD, AstraZeneca; Financial Interests, Personal, Advisory Board: MSD, AstraZeneca. M.R. Chacon: Financial Interests, Personal, Invited Speaker: Novartis, BMS, Elea, MSD. All other authors have declared no conflicts of interest.

Background

Alongside the scarcity of treatment options and the aggressive biology of liver sarcoma (LS), patients with this type of tumor often present with giant tumor size after months of unsuccessful diagnostic and treatment workup in low-volume centers. Awareness about LS among health care professionals of general hospitals could be raised with recognition and making emphasis on factors leading to delay in referral of patients with LS to tertiary care center

Methods

Data on diagnostic and treatment work-up before and after referral to the specialized center of 11 adult patients with primary hepatic and metastatic LS were analyzed.

Results

The median time interval between the first hospital visit and referral to the specialized center was 2.8 months (1.5-5 months). In 4 cases, the diagnosis before referral was liver abscess, in 4 cases – unknown type of tumor, in 1 case – liver hemangioma, in 1 case – liver pleomorphic sarcoma, in 1 case – liver tuberculoma. In almost half of the cases, invasive procedures were performed before referral, including percutaneous draining (n=4), surgical exploration complicated with tumor rupture (n=1), and tumor cytology (n=1), and in the remaining cases (n=5) only imaging before referral was performed. The median tumor size in the greatest dimension was 16 cm. All patients underwent surgical treatment at our center indicated by complications of the giant tumor size with or without tumor rupture. According to the histologic report, there were 4 cases of undifferentiated embryonal liver sarcoma, 2 cases of liver metastases of uterine leiomyosarcoma, 2 cases of liver angiosarcoma, 1 case of primary liver leiomyosarcoma, 1 case of liver metastases of gastrointestinal stromal tumor of small intestine and 1 case of liver PEComa.

Conclusions

Lack of awareness about liver sarcoma among general healthcare professionals is an established issue. However, another concern on the performance of invasive diagnostic and treatment procedures in non-specialized centers should be raised. The latter imposes patients to a tremendous pathway before true diagnosis will be established, substantially worsening oncological, as well as, surgical prognosis.

Legal entity responsible for the study

M. Bilych.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Several studies have highlighted the need to improve management of rare cancers, such as neuroendocrine tumors (NETs). To do this best, it is essential to involve and inform patients. This survey aimed to explore patient awareness regarding diagnosis and management of their rare neuroendocrine cancer.

Methods

An anonymous survey was conducted from April to September 2023, recruiting patients with NETs in about 30 clinics in Italy. We collected sociodemographics and diagnostic characteristics and data on patient’s awareness and knowledge about their cancer.

Results

We collected 435 reports. Patients were 45% females and 55% males. Median age was 65 years (21-90). Primary tumors sites were small intestine 29%, pancreatic 24%, lung 10%, other (e.g. MEN, Merkel cell carcinoma, paraganglioma) and non- specified 31%. 33% were followed at a general hospital, 34% at a university hospital and 25% at a clinical research hospital. 85% of patients know they have a rare cancer. Actually 22% of these do not know the real meaning of rare, so only 65% of patients have a full awareness of the meaning of rare cancer. 88% for patients were informed by a specialist about their rarity, only 12% by general clinicians, 9% by internet. 78% of patients know about the presence of a multidisciplinary team in their hospital, both in southern and northern Italy, and 36% were informed about their doctor’s consultation with a reference center about disease management. 43% of patients were enrolled in clinical trials, 57% at a clinical research hospital, 44% at a university hospital, 35% at a general hospital. Almost one in two patients is driving for health tourism, 29% outside their region, especially patients from the south of Italy and regardless of the clinic they are followed in. Patients are not informed about new radioligand therapy (70%), however, 72% are not worried about radioactivity. 77% of patients admit they do not know of advocacy group for patients. Less of 10% consult associations for information about their cancer, compared to 44% and 21% who consult the internet and information materials from their physician, respectively.

Conclusions

There is still work to be done to increase patient awareness and to improve their treatment path.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Desmoid tumors (DT) are rare tumors and can cause significant morbidity and psychosocial harm. Their rarity amplifies challenges, particularly in middle-income countries. To understand these difficulties, the DT patient organization of Brazil (DB) conducted a qualitative study on the challenges faced by Brazilian DT patients (pts).

Methods

From Oct/2022 to Nov/2023, an online questionnaire was made available to pts who joined DB. It gathered data on gender, age at diagnosis, primary site, and prior treatments, as well as personal challenges including pain, travel for treatment, and healthcare trust. Volunteers then openly described their greatest challenges and perspectives. All comments underwent review and were classified based on recurring themes.

Results

A total of 279 pts completed the form. 86% (240) were female, and 14% (39) were male. Age at diagnosis was 30-49 years in 53% (148), 18-29 in 28% (78), 0-17 in 11.5% (32) and 50-69 in 7.5% (21). DT primary site was extra abdominal in 88.5% (247), while 11.5% (32) were intra-abdominal. Surgery was performed in 60.9% (170) of pts. Of these, 58.2% (99) reported a chronic decline in their quality of life as a result, and 59.4% (101) reported recurrence. 46.2% (129) of the pts reported pain, and 22.2% (62) reported insecurity with their healthcare team. 43% (120) of them reported needing to travel for treatment. Of the 243 (87%) pts who answered the two open-ended questions, the most cited challenges were lack of DT information in 32.1% (78) of comments, lack of a specialist team in 23.8% (58), psychological distress in 22.2% (54). The primary perspectives shared by 99 pts were: appreciation for the existence of a patient advocacy organization in 23.7% (24), and desire for further information and support in 20.7% (21).

Conclusions

Lack of information and access to specialists were the major challenges faced by DT pts in Brazil, while their main perspective was gratitude for having a patient advocacy organization and desire for further information and support. Considering the findings, DB has identified its focus for the next 5 years as promoting DT information and facilitating access to specialists.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

There is limited knowledge of the early signs and symptoms of sarcoma that people present with when consulting their general practitioner (GP). However, gaining a deeper understanding of this pre-diagnostic trajectory holds the potential to create referral guidelines and interventions. Our aim was to investigate the pattern of GP visits within the 12 months leading up to individuals’ sarcoma diagnosis and comparing it to a control group without cancer.

Methods

Individuals newly diagnosed with a sarcoma in 2010-2020 were identified through the Netherlands Cancer Registry and linked to Nivel Primary Care Database, covering approximately 10% of the Dutch population. Sarcoma cases were age and gender matched to cancer-free controls (2:1 or 1:1 ratio). Consultations at the GP and the symptoms patients presented with were extracted for the 12 months preceding the diagnosis.

Results

A total of 787 individuals with soft-tissue sarcoma (STS) and 188 individuals with bone sarcoma (BS) were identified. No differences were observed between STS cases and controls up to 8 months before diagnosis, and for BS cases and controls, this pattern persisted up to 7 months before diagnosis. A noticeable increase in the mean monthly number of GP consultations was evident from 4 months to the last month before STS diagnosis, while for BS cases, this increase was already apparent in the 5 months preceding the diagnosis. Most prevalent health conditions for which STS cases contacted the GP were nonspecific and included musculoskeletal neoplasm (26.6%), uncomplicated hypertension (15.6%) and cystitis/other urinary infections (12.2%). Musculoskeletal neoplasm (42.8%), knee symptoms/complaints (9.7%) and shoulder symptoms/complaints (9.7%) were the most frequently recorded heath conditions for BS cases.

Conclusions

An increase in GP consultations was observed before the diagnosis of sarcoma. STS cases predominantly manifested with nonspecific symptoms, whereas BS cases presented with more clinically apparent symptoms. A better understanding of the pre-diagnostic trajectory could aid GPs in early identification of sarcoma patients, potentially leading to the development of strategies to minimize diagnostic delays and improve patient outcomes.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Czech Republic is a center European country with about 10.5 million inhabitants. The aim of analysis was to collect information on epidemiology, treatment and outcomes of sarcoma patients. The Czech National Cancer Registry (CNCR) has been in operation since 1977, when it was instituted as a national database covering 100% of cancer diagnoses and the entire Czech population. The registration of malignant neoplasms is stipulated by the legislation and it is obligatory. The CNCR is a part of the National Health Information System and is administered by the Institute of Health Information and Statistics of the Czech Republic. Out of about 190 hospitals in total is the fully specialized oncology care provided in 15 Complex Oncology Care Centres (COCC).

Methods

There were analyzed data from the CNCR of sarcoma patients diagnosed and treated between 2005-2021. Data of 8 884 soft tissue (STS) and 1 380 bone sarcoma (BS) patients are available. The primary end-point was the overall survival (OS) and the contribution of treatment centralization.

Results

The average incidence in the last 5-year period (2017-2021) was 640 new STS and 87 BS per year (0.85% of all malignancy). The median age was 64 years in STS and 48 years in BS. The incidence has been increasing for the last two decades to 6 per 100 thousand in year. In the last 15 years, the prognosis hasńt changed (except of gastrointestinal stromal sarcoma and BS). 5year OS in STS was 60.1% during 2005-2009, 61.4% during 2010-2015 and 62.6% during 2016-2021, in BS 46.9%, 57.5% and 56.2% respectively. The treatment results depend on early and correct therapy in experiences centres. During 2012-2016, 147 first-contact hospitals and 223 other health centres have participated in the diagnostics and primary treatment. Only 70% of patients were referred to specialized COCC. During 2017-2021 has been a slight reduction in the number of workplaces, but, still 79.5% of patients only were refered to the COCC.

Conclusions

According to the database of CNCR of the Czech Republic, patients have been surgicaly treated in more than 100 various hospitals. One fifth of these patients have never reached specialized treatment in COCC. The centralization of treatment is the only way to improve the prognosis of these patients.

Legal entity responsible for the study

The authors.

Funding

Supported by MH CZ - DRO (MMCI, 00209805) and by Ministry of Health of the Czech Republic grant NV18-07-00073.

Disclosure

All authors have declared no conflicts of interest.

Background

Delay of diagnosis is common in patients with sarcoma, however, the factors that impact the delay remain incompletely understood.

Methods

We included patients with newly diagnosed sarcoma who were referred to Stanford sarcoma clinic from August 2022 to December 2023 for establishing care, and excluded patients who were referred for second opinion, or transferred care, or after completing surgery, radiation or both.

Results

Among total of 150 eligible patients (37% had Medicare/Medicaid and 63% had private insurance), approximately 40% of patients did not have a visit with their primary care provider within five weeks after the onset of symptoms (pain, palpable mass, etc.) (median 5 weeks). Among patients who were 18 to 30 years old, more than 40% of patients did not have an imaging study performed within five weeks after their first visit with primary care provider (median 2 weeks), this percentage dropped to 25% for the patients who were 30-50 years old (median 1 week), and less than 20% among patients who were older than 50 years (median 1 week). Among 79 patients who had high-grade sarcoma, more than 40% of patients with high-grade sarcoma did not have a visit with their primary care provider within five weeks after the onset of symptoms (pain, palpable mass, etc.) (median 5 weeks), and approximately 20% of the patients did not have their first imaging study performed within five weeks after their visit (median 2 weeks). For all patients, approximately 95% of patients were seen in the sarcoma clinic within five weeks after the referral to sarcoma clinic was initiated. There was no significant difference between insurance type or sex.

Conclusions

Significant percentage of patients with newly diagnosed sarcoma, including those with high-grade sarcoma, did not have an imaging study performed within five weeks after the initial visit with primary care physician, especially the AYA patients who were 18-30 years old.

Legal entity responsible for the study

Stanford University.

Funding

Stanford University.

Disclosure

M. Pan: Financial Interests, Personal, Advisory Board: Aadi Bioscience, Boehringer Ingelheim. All other authors have declared no conflicts of interest.

Background

Extremity soft tissue sarcomas are rare neoplasms. Because these tumors are usually pseudo-capsulated, many practices are initially thought to be benign and are excised without a proper preoperative imaging, biopsy, or planning by an unwary surgeon. These excisions have termed “Whoops! Procedure” indicating the surprise and distress that the surgeon experiences, after the pathologist reports a malignant neoplasm in a postoperative specimen. We aimed at studying the oncological outcomes of patients undergoing unplanned (whoops) excision for soft-tissue sarcomas (STS) at a tertiary cancer institute.

Methods

This was a retrospective analysis of patients of STS of trunk and extremity from 2017 to 2021. we compared patients who had undergone ‘whoops’ surgery with or without re-surgery versus patients had undergone wide local excision WLE for the oncological outcomes, including overall survival (OS) and disease-free survival (DFS).

Results

After excluding patients with gross residual (R2) and incomplete medical data, Sixty-nine patients were included with median age of 44, patients were divided into two groups: group 1 included 44(63.7%) who underwent whoops surgery and group 2 included 25 (36.3%) underwent WLE. The median follow-up period was 39.6 months. Group 1 were more likely to have smaller tumors (T1-2) 31 patients (70.4%) vs 9 patients (36%) in group 2. Considering margin; R0 was achieved in 4 patients (9.5%) and R1 in 38 patients (90.5%) in group 1 vs R0 in 17 patients (68%) and R1 in 8 patients (32%) in group 2. There were 9 (20.5%) local recurrences in group 1 and 3 (12%) in group 2 (P=0.411). There was no difference in DFS and OS in both groups. The median DFS in group 1 was 21.3 months vs 32.3 months in group 2 (p=0.414), the median OS was 42 months in group 1 vs 38.5 months in group 2 (p=0.974). There was no significant difference in local recurrence in the whoops group between patients who underwent re-excision or not. Also there was no difference in median DFS in re-resection group which was 7.7 months vs 27.5 months in patients who had not undergone re-resection (p=0.06).

Conclusions

Although local recurrence is much more common in the whoops surgery group, re-resection does not seem to affect DFS or OS.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

The management of bone sarcoma has too many challenges in the management of patients with Bone Sarcoma in the region. This study was undertaken to underscore these difficulties and pave the way for improvements in patient management. Identifying and addressing these challenges will contribute to enhancing the overall quality of care for individuals with Bone Sarcoma specially with recent inauguration of the University Hospital of Tangier. Aim of study:To identify and address the shortcomings in the management of bone sarcomas, thereby improving the quality of care.

Methods

This is a retrospective study that included patients diagnosed with STS at the Medical Oncology Department of the university hospital in Tangier between December 2019 and November 2023. Data were collected from medical records using a pre-established sheet form. Statistical analysis was conducted using SPSS.

Results

The study included 44 patients, with a median age of 26 years and 61% being males. Most patients had no personal medical history. The femur was the most common localization (32%). Ewing sarcoma accounted for 47.7%, while osteosarcoma comprised 52.3% (conventional osteosarcoma in 45% of the cases). Immunohistochemistry was performed in 52% of patients, molecular biology in 26% of patients with Ewing sarcoma (It was requested but not done), and histopathological review in only 28%. Staging procedures included MRI and chest CT for almost all patients, bone scintigraphy for 22%, and bone marrow biopsy for 9%. At diagnosis, 70.5% of patients had a local or locally advanced stage, and 29.5% were metastatic. Multidisciplinary team reviews occurred in 13.6% at diagnosis and 27.3% during management. Surgery was performed in 36.4%, exclusively at the university hospital, while radiotherapy was administered in 29.5% (57% palliative). Chemotherapy was given to 100% of metastatic patients and 65% of locally staged patients. The median survival was 36 months.

Conclusions

This study highlights challenges, especially regarding the anatomopathology diagnosis, the review process and molecular biology. There are also challenges related to the availability of extension assessments. In the hope that with the efforts made by the team of the department, we will achieve better results in the future.

Legal entity responsible for the study

M. Amzerin.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Ripretinib is a switch-control tyrosine kinase inhibitor approved in the US and EU for patients (pts) with gastrointestinal stromal tumor (GIST) who received prior treatment with 3 or more kinase inhibitors, including imatinib. Sunitinib is approved for advanced GIST after imatinib failure. In an exploratory analysis of baseline circulating tumor DNA (ctDNA) from the INTRIGUE trial, pts with primary mutations in KIT exon 11 and secondary mutations exclusively in KIT exons 17/18 (KIT exon 11 + 17/18) received clinical benefit from ripretinib but not sunitinib (Heinrich MC, et al. Nat Med. 2024). Here, we present final overall survival (OS) and updated safety in pts with KIT exon 11 + 17/18 mutations from INTRIGUE.

Methods

INTRIGUE (NCT03673501) is an open-label, phase 3 study of adults with advanced GIST who had disease progression on or intolerance to imatinib. Randomization was 1:1 to ripretinib 150 mg once daily (QD) or sunitinib 50 mg QD (4 wks on/2 wks off). Final OS analysis was prespecified to occur with ≥200 and ≥145 events in the all-patient intention-to-treat (ITT) and KIT exon 11 ITT populations, respectively. Baseline peripheral whole blood was analyzed by Guardant360, a 74-gene ctDNA next-generation sequencing–based assay. Data cutoff was March 15, 2023.

Results

Of 453 pts, ctDNA was analyzed in an exploratory analysis for 362; 52 had mutations exclusively in KIT exon 11 + 17/18 (ripretinib, n = 27; sunitinib, n = 25). Pts with KIT exon 11 + 17/18 mutations had better OS with ripretinib vs sunitinib (median, not reached vs 17.5 months; HR, 0.37; 95% CI, 0.17 to 0.80; nominal P = 0.0091). Fewer of these pts had grade 3/4 drug-related treatment-emergent adverse events and serious adverse events with ripretinib vs sunitinib (33% vs 50% and 3.7% vs 13%, respectively). Median treatment duration in these pts for ripretinib vs sunitinib was 15.6 vs 3.0 months.

Conclusions

In this updated exploratory analysis from INTRIGUE, OS was longer for ripretinib vs sunitinib for pts with KIT exon 11 + 17/18 mutations identified by baseline ctDNA. The safety profile was consistent and more favorable for ripretinib vs sunitinib in these pts.

Clinical trial identification

NCT03673501.

Editorial acknowledgement

Medical writing and editorial support were provided by Steven Walker, PhD, of AlphaBioCom, a Red Nucleus company, and were funded by Deciphera Pharmaceuticals, LLC.

Legal entity responsible for the study

Deciphera Pharmaceuticals, LLC and the INTRIGUE study investigators.

Funding

Deciphera Pharmaceuticals, LLC.

Disclosure

J-Y. Blay: Financial Interests, Institutional, Invited Speaker: MSD, MSD, PharmaMar; Financial Interests, Institutional, Advisory Board: Bayer, GSK, Roche; Financial Interests, Personal, Advisory Board: Deciphera; Financial Interests, Personal, Other, member of the supervisory board. No remunerations in 2021 and 2022: Innate pharma; Financial Interests, Personal, Member of Board of Directors: Transgene; Financial Interests, Institutional, Funding: MSD, BMS, Deciphera; Financial Interests, Institutional, Research Grant: AstraZeneca, Roche, Bayer, GSK, Novartis, OSE pharma. R.L. Jones: Financial Interests, Personal, Expert Testimony, I worked as a consultant: Adaptimmune, Bayer, Boehringer Ingelheim, Blueprint, Clinigen, Eisai, Epizyme, Daiichi Sankyo, Deciphera, Immunedesign, Lilly, Springworks, Tracon, Upto Date, PharmaMar; Financial Interests, Personal, Advisory Board, I worked as a consultant.: Athenex, Astex, Immunicum, Karma Oncology, Merck, Mundipharma, Synox; Financial Interests, Institutional, Research Grant, Research grant for a clinical trial: MSD. H. Gelderblom: Financial Interests, Institutional, Invited Speaker: Daiichi Sankyo, Deciphera, Novartis, Boehringer Ingelheim, AmMax Bio, Debiopharm, Cytovation, Abbisko. S. George: Financial Interests, Personal, Stocks/Shares, Stock/other ownership interests: Abott Laboratories; Non-Financial Interests, Personal, Other, Honoraria: CStone Pharmaceuticals; Financial Interests, Personal, Advisory Role, Consulting or advisory role: Blueprint Medicines, Deciphera Pharmaceuticals, LLC, Lilly, UpToDate, Research to Practice, MORE Health, Daiichi Sankyo, KayoThera, Immunicum; Financial Interests, Institutional, Funding, Research funding: Blueprint Medicines, Deciphera Pharmaceuticals, LLC, Daiichi Sankyo RD Novare, Merck; Financial Interests, Institutional, Funding, Research: Eisai, SpringWorks Therapeutics, TRACON Pharma, Theseus Pharmaceuticals, NewBay, IDRX; Financial Interests, Personal, Funding, Research: BioAtla; Financial Interests, Personal, Royalties, Patients/Royalties/Intellectual property: UptoDate; Other, Personal, Other: WCG. P. Schöffski: Financial Interests, Personal, Other, Honoraria: Blueprint Medicines; Financial Interests, Personal, Advisory Role, Consulting or advisory role: Deciphera Pharmaceuticals, LLC, Ellipses Pharma, Blueprint Medicines, Transgene, Exelixis, Boehringer Ingelheim, Studiecentrum voor Kernenergie (SCK CEN), SQZ Biotechnology, Adcendo, PharmaMar, Merck, Medpace; Financial Interests, Institutional, Funding, Research funding: CoBioRes NV, Eisai, G1 Therapeutics, PharmaMar, Genmab, Merck, Sartar Therapeutics, ONA Therapeutics. M. von Mehren: Financial Interests, Personal, Advisory Role, Consulting or advisory role: Deciphera Pharmaceuticals, LLC, GSK; Financial Interests, Institutional, Funding, Research funding: Novartis, Deciphera, LLC, Gradalis, Genmab, ASCO, Solaris Health; Financial Interests, Personal, Royalties, Patents/Royalties/other intellectual property: Cell line; Other, Personal, Other, Other relationship: NCCN. J.R. Zalcberg: Non-Financial Interests, Personal, Leadership Role: ICON Group; Financial Interests, Personal, Stocks/Shares, Stock/other ownership interests: Biomarin, Opthea, Amarin Corporation, Concert Pharmaceuticals, Frequency Therapeutics, Gilead Sciences, Madrigal Pharmaceuticals, UniQure, Zogenix, Orphazyme, Moderna Therapeutics, Twist Bioscience, Novavax; Financial Interests, Personal, Other, Honoraria: Specialised Therapeutics, Merck Serono, Targovax, Halozyme, Gilead Sciences, Deciphera Pharmaceuticals, LLC; Financial Interests, Personal, Advisory Role, Consulting or advisory role: Merck Serono, Targovax, Merck Sharp & Dohme, Halozyme, Lipotek, Specialised Therapeutics, Center for Emerging & Neglected Diseases (CEND), Deciphera Pharmaceuticals, LLC, Revolution Medicine, FivePHusion, Genor BioPharma, 1Globe Health Institute, Novotech; Financial Interests, Institutional, Funding, Research funding: Merck Serono, Bristol Myers Squibb, AstraZeneca, Pfizer, IQVIA, Mylan, Ipsen, Eisai, Medtronic, MSD Oncology; Financial Interests, Personal, Funding, Funding for travel/accommodations/expenses: Merck Serono, AstraZeneca, Merck Sharp & Dohme, Deciphera Pharmaceuticals, LLC, Sanofi. Y. Kang: Financial Interests, Personal, Advisory Board: ALX Oncology, Zymeworks, Amgen, Novartis, Macrogenics, Daehwa, Blueprint, Surface Oncology, BMS, Merck, Roche, Liscure. A.R. Abdul Razak: Financial Interests, Personal, Advisory Role, Consulting or advisory role: Adaptimmune, Bayer, GSK, Medison, Inhibrx; Financial Interests, Personal, Funding, Research funding: Deciphera Pharmaceuticals, LLC, Karyopharm Therapeutics, Pfizer, Roche/Genentech, Bristol Myers Squibb, MedImmune, Amgen, GSK, Blueprint Medicines, Merck, AbbVie, Adaptimmune, Iterion Therapeutics, Neoleukin Therapeutics, Daiichi Sankyo, Symphogen, Rain Therapeutics; Non-Financial Interests, Personal, Expert Testimony: Medison. J.C. Trent: Financial Interests, Personal, Advisory Role, Consulting or advisory role: Blueprint Medicines, Deciphera Pharmaceuticals, LLC, Daiichi Sankyo, Epizyme, Agios, C4 Therapeutics, Bayer, AADI Bioscience, LLC, Foghorn Therapeutics, Boehringer Ingelheim, Cogent Medicine, Servier. S. Attia: Financial Interests, Institutional, Funding, Research funding: AB Science, TRACON Pharma, Bayer, Novartis, Lilly, Immune Design, Karyopharm Therapeutics, Epizyme, Blueprint Medicines, Genmab, CBA Pharma, Desmoid Tumor Research Foundation, Merck, Philogen, Gradalis, Deciphera Pharmaceuticals, LLC, Takeda, Incyte, SpringWorks Therapeutics, Adaptimmune, Advenchen Laboratories, Bavarian Nordic, BTG, PTC Therapeutics, GSK, FORMA Therapeutics, Ayala Pharmaceuticals, Trillium Therapeutics, Boehringer Ingelheim, Salarius Pharmaceuticals, Theseus Pharmaceuticals, Monopar Therapeutics, C4 Therapeutics, InhibRx, Noxopharm, Rain Therapeutics. A. Le Cesne: Financial Interests, Personal, Other, Honoraria: Bayer, PharmaMar, Deciphera Pharmaceuticals, LLC. E. Davis: Financial Interests, Personal, Stocks/Shares, Stock ownership: Deciphera Pharmaceuticals, LLC; Financial Interests, Personal, Full or part-time Employment: Deciphera Pharmaceuticals, LLC. K. Sprott: Financial Interests, Personal, Full or part-time Employment: Deciphera Pharmaceuticals, LLC; Financial Interests, Personal, Full or part-time Employment, For immediate family member not self: Stablix; Financial Interests, Personal, Stocks/Shares, Stock and other ownership: Deciphera Pharmaceuticals, LLC; Financial Interests, Personal, Stocks/Shares, Stock and other ownership for immediate family member: Stablix. P. Cox: Financial Interests, Personal, Full or part-time Employment: Deciphera Pharmaceuticals, LLC; Financial Interests, Personal, Stocks/Shares, Stock and other ownership interests: Deciphera Pharmaceuticals, LLC. M.L. Sherman: Financial Interests, Personal, Full or part-time Employment: Deciphera Pharmaceuticals, LLC; Financial Interests, Personal, Member of Board of Directors: Pieris Pharmaceuticals; Financial Interests, Personal, Leadership Role: Deciphera Pharmaceuticals, LLC, Pieris Pharmaceuticals; Financial Interests, Personal, Stocks/Shares: Deciphera Pharmaceuticals, LLC, Pieris Pharmaceuticals; Financial Interests, Personal, Royalties, Patents/royalties/other intellectual property: Acceleron Pharma. R. Ruiz-Soto: Financial Interests, Personal, Full or part-time Employment: Deciphera Pharmaceuticals, LLC; Financial Interests, Personal, Stocks/Shares: Deciphera Pharmaceuticals, LLC, ImmunoGen; Financial Interests, Personal, Royalties, Patents/royalties/other intellectual property; Transferred the rights to Deciphera Pharmaceuticals, LLC, has not received [and will not receive] any royalties: Deciphera Pharmaceuticals, LLC; Financial Interests, Personal, Royalties, Patents/royalties/other intellectual property; Transferred the rights to ImmunoGen, LLC, has not received [and will not receive] any royalties: ImmunoGen. M. Heinrich: Financial Interests, Personal, Other, Honoraria: Novartis; Financial Interests, Personal, Advisory Role, Consulting or advisory role: Blueprint Medicines, Novartis, Theseus Pharmaceuticals, Deciphera Pharmaceuticals, LLC; Financial Interests, Institutional, Royalties, Patents/royalties/other intellectual property licensed to Novartis: Novartis; Financial Interests, Personal, Research Grant, Partial salary from a research grant from the Jonathan DavidFoundation, a VA Merit Review Grant (I01BX005358): Jonathan David Foundation; Financial Interests, Personal, Research Grant, Partial salary from a research grant from an NCI R21 grant (R21CA263400): NCI. S. Bauer: Financial Interests, Personal, Other, Honoraria: Bayer, GSK, Novartis, Pfizer, PharmaMar, Deciphera Pharmaceuticals, LLC; Financial Interests, Personal, Advisory Role, Consulting or advisory role: ADC Therapeutics, Adcendo, Bayer, Blueprint Medicines, Boehringer Ingelheim, Daiichi Sankyo, Exelixis, GSK, Janssen-Cilag, Lilly, Mundipharma, Deciphera Pharmaceuticals, LLC, Nanobiotix; Financial Interests, Personal, Funding, Research funding: Blueprint Medicines, Novartis; Financial Interests, Institutional, Funding, Research funding: Incyte; Financial Interests, Personal, Funding, Funding for travel/accommodations/expenses: PharmaMar.

Background

KIT/PDGFR wild-type (KPWT) gastrointestinal stromal tumors (GIST) constitute a minority of all metastatic GIST cases. Most studies to date involve case reports or small series, and treatment approaches vary widely among teams. Additional research is needed to define the optimal management of metastatic KPWT GIST patients. This retrospective study aimed to assess the outcomes of KPWT GIST patients treated with Tyrosine Kinase Inhibitors (TKI) at our institution.

Methods

We conducted a retrospective study at the Centre Léon Bérard (CLB). The NetSarc national sarcoma database was queried for KPWT GIST patients at CLB. Data were extracted from individual patient files and reviewed by an expert sarcoma pathologist. Whole exome-RNAseq was performed with FFPE material in the absence of known neurofibromatosis type 1 (NF1) or SDH-deficiency.

Results

A total of 78 KPWT GIST patients were identified. Four molecular groups could be formed, NF1-associated GIST (N=29), SDHB-deficient GIST (N=13), other rare alterations (N=7 with 3 BRAF V600E mutation, 1 NTRK3 rearrangement, 1 TSC1 variant, 1 FLNA mutation, and 1 FGFR2 mutation), and wild-type GIST (N=29). SDHB-deficient GIST patients were significantly younger (p-value = 0.0006), and NF1-associated GIST were more likely to be primarily located in the small intestine (p-value < 0.0001). Median PFS with imatinib was 9.5 months (with a noteworthy PFS of 199 months in a wild-type GIST), and 10 months with sunitinib. Regorafenib was significantly less effective with a median PFS of 3 months (p-value = 0.01). Pazopanib showed the highest median PFS of 30 months (with a notable PFS of 116 months in an SDHB-deficient GIST). Overall survival was of 190 months for NF1-patients, 246 months for SDHB-patients, 45.7 months with other molecular alterations, and 185 months for wild-type GIST (p-value = 0.5).

Conclusions

This retrospective series is one of the largest describing clinical characteristics and treatment response of KPWT GIST, a rare disease. Imatinib and sunitinib demonstrated good responses, while regorafenib showed no efficacy. Long responders were reported with multi-targeted TKI, warranting further investigation through prospective trials to validate those results.

Legal entity responsible for the study

M. Dupont.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Previous studies have shown that the majority of drugs used in sarcomas have not demonstrated substantial clinical benefit according to validated international scales. European Society for Medical Oncology-Magnitude of Clinical Benefit Scale version 1.1 (ESMO-MCBS) and American Society for Medical Oncology (ASCO) Value Framework (AVF) are the most important scales. Little is known about the clinical benefits of guideline-recommended cancer drugs in GIST in routine practice. Here, we evaluate the clinical benefit of drugs recommended by NCCN in advanced GIST.

Methods

We reviewed publications between January 2002 and March 2023 that support recommendations of NCCN guideline version 1.2023 for GIST. We collected data regarding trial characteristics, efficacy, toxicity and quality of life (QoL). ESMO-MCBS and AVF were applied. Substantial clinical benefit was defined as a grade 4 or 5 (in a scale from 1 to 5) for ESMO-MCBS and a net health benefit (NHB) score ≥45 for AVF.

Results

We identified 16 recommended drugs or combinations in the GIST NCCN guidelines, 13 of them based on trials that included only GIST patients: 3 phase III randomized trials and 10 single arm trials (8 phase II and 2 phase I). Efficacy and toxicity data were reported in all trials but quality of life (QoL) was reported just in 2 (15,4%). ESMO-MCBS could be applied in all 13 trials. Nevertheless, AVF could only be applied in 3 (the 3 phase III trials). Only imatinib met the ESMO-MCBS substantial benefit threshold (4 points, one of them due to phase 4 experience). Ripretinib met the AVF threshold.

Table: 64P

Clinical benefit of drugs recommended by NCCN in advanced GIST

Conclusions

ESMO-MCBS could be applied in all trials supporting drugs used in advanced GIST but AVF just in a minority of them. Clinical benefit was only achieved by imatinib according to ESMO-MCBS and by ripretinib according to AVF. QoL should be analysed in future studies to determine real benefit according to these scales.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

STS has a therapeutic challenge with limited preoperative treatment options. SUR, a kinase inhibitor targeting VEGFR 1, 2, 3, FGFR 1, and CSF-1R, has shown synergistic effects in combination with immunotherapy in previous studies. Furthermore, radiotherapy is reported to potentiate immunotherapy efficacy in "cold" tumors by inducing immunogenic death and remodeling the tumor microenvironment. This study aims to assess the combined preoperative efficacy and safety of RT, SUR, and SIN for STS.

Methods

In this Ph Ib/II trial, up to 52 patients (pts) were planned to be enrolled. Pts underwent treatment with RT, SUR (250 mg, po, qd, every 21 days as a cycle), and SIN (200 mg, i.v., d1, q3w) for 6 cycles before surgery. Primary endpoint was objective response rate (ORR) according to RECIST 1.1 with secondary endpoints including the rate of pathological complete response (pCR) and near pCR (defined as < 10% viable tumor cells), progression free survival (PFS), overall survival (OS) and safety. The Ph Ib (3+3 design) assessed SUR's recommended phase 2 dose (RP2D), while Ph II focused on efficacy and safety.

Results

As of Dec., 2023, 7 unresectable STS (1 trunk STS and 6 limbs STS) pts were enrolled. The median age was 57 years (range 21-71). 6/7 (86%) was histological grade 3. Among the 7 pts, 6 (86%) pts underwent previous surgery and 5 (71%) pts received prior chemotherapy. One DLT (grade 3 increased bilirubin) was observed in 6 pts receiving SUR (250 mg, qd) in combination with SIN (200 mg, d1,q3w), and then the RP2D was confirmed. The most common TRAEs were increased blood bilirubin in 3/7 pts (43%) and diarrhea in 1/7 pts (14%). For the 6 evaluable pts, 3 achieved partial response and 2 had stable disease with an ORR of 50% (3/6) and a DCR of 83% (5/6). 5 pts underwent surgery with a 100% (5/5) rate of R0 resection, and all achieved limb preservation with no serious wound complications. The rate of pCR and near pCR reached 40% (2/5) with 1 pCR and 1 near pCR. Median PFS and OS had not yet reached.

Conclusions

The combination of radiotherapy, SUR, and SIN showed a potential efficacy and tolerable toxicity in high-risk localized limbs and trunk STS. The trial is still ongoing.

Clinical trial identification

NCT05839275.

Legal entity responsible for the study

The authors.

Funding

Chinese Society of Clinical Oncology (grant number: Y-Young2020-0477) for Yan Wang and Science and Technology Commission of Shanghai Municipality (grant number: 21Y21900200) for Zhen Zhang.

Disclosure

All authors have declared no conflicts of interest.

Background

Extremity STS poses a considerable challenge due to its propensity for local recurrence despite advancements in treatment modalities. The nomogram construction involved comprehensive analysis of clinicopathological variables, treatment regimens, and patient outcomes, aiming to offer a reliable and personalized predictive tool. Through rigorous statistical modeling, this nomogram integrates pertinent prognostic factors, enabling clinicians to estimate an individual's risk of local recurrence with enhanced precision. Implementation of this nomogram holds significant promise in guiding clinical decision-making, facilitating tailored surveillance strategies, and ultimately improving patient care by enabling proactive interventions to mitigate the risk of local recurrence in extremity soft tissue sarcoma.

Methods

A retrospective review of our prospective sarcoma database identified 1000 patients with primary, nonmetastatic soft tissue sarcomas (STS) who underwent surgery with radiotherapy and/or chemotherapy exclusively between June 1993 and December 2021. Clinicopathologic factors such as age, sex, grade, depth, size, site, margin status, and adjuvant treatments were assessed for their prognostic significance in relation to local recurrence rates. Variables exhibiting significance in univariate analysis at the 0.05 level were incorporated into a multivariate competing risk regression model. Subsequently, a nomogram predicting the 5-year LR risk was developed based on the outcomes of the multivariate analysis.

Results

A total of 1000 patients were included. In a median follow-up of 37 months, 30.5% (305) of patients developed recurrence. Of these, there were 11.5% LR and 19% SR. The nomogram encompassed factors like age (≤50 vs >50), site (extremity vs non extremity), margin status (negative vs positive), depth (superficial vs deep), and adjuvant radiation (yes vs no).

Conclusions

The established nomogram tailored for extremity STS, incorporating age, site, margin status, tumour depth, and adjuvant radiation, effectively forecasts 5-year risk of local recurrence following completion of treatment of soft tissue sarcoma.

Legal entity responsible for the study

AIIMS, New Delhi, India.

Funding

Has not received any funding.

Disclosure

The author has declared no conflicts of interest.

Background

The standard treatment for large, intermediate-, and high-grade extremity soft tissue sarcoma (ESTS) involves wide excision and radiotherapy. However, for those with unfavorable characteristics, the risk of distant recurrence and mortality can exceed 50%. Unfortunately, there is a lack of universally accepted data able to clarify which treatments are more effective to prevent recurrence and improve survival for high-risk group. The definition of 'high risk' is subject to debate, but tools like the SARCULATOR may assist in refining this definition.The study aims to assess the impact of perioperative chemotherapy (CTX) on patients with high-risk ESTS.

Methods

28 adult patients with high-risk ESTS (SARCULATOR OS<60%) were enrolled in the study. Data were extracted from a prospectively maintained database, augmented by a retrospective review of medical records from those who underwent neoadjuvant chemotherapy (NCT) and resection. The response to treatment was assessed using EORTC–STBSG.

Results

All 28 patients received NCT. The median age was 42 years, with 65.5% being male, and 79.3% presented with stage III disease. The most common histological subtypes were synovial sarcoma (37.9%) and liposarcoma (31%). Over a median follow-up of 17 months, the most frequently used NCT regimen was Doxorubicin/ifosfamide (69%), with the dosage intensity for 44.8% being Q4W. Concurrent radiotherapy was administered to 24 patients, 23 patients (79.3%) completed treatment, 17.2% developed Grade 3 neutropenia, and 34.5% developed Grade 2 anemia. Five patients experienced disease progression during NCT, but 20 of the 28 patients achieved limb preservation. A poorer response was observed in synovial sarcoma with a p-value of 0.034 according to EORTC–STBSG criteria.

Conclusions

NCT is a feasible and viable treatment option. It has been less effective for synovial sarcoma, highlighting the need for further research to improve outcomes in this subgroup. Side effects from NCT were not associated with an increased mortality rate.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

G.C. Alamilla Garcia: Non-Financial Interests, Personal, Other: AstraZeneca, MSD. All other authors have declared no conflicts of interest.

Background

Elderly patients (pts) with soft tissue sarcoma (STS) are underrepresented in clinical trials and evidence-based management guidelines in this population remain scarce. The objective of this study is to describe the characteristics of pts over 70 years(y) with STS and compare them with the younger population. Moreover, we analyze the variables that impact overall survival (OS) and treatment tolerance.

Methods

Is a single-center retrospective study of a cohort of pts aged ≥18y from the Hospital G. U. Gregorio Marañón database with STS diagnosis between 2012 and 2023. Demographic data, histological subtype, and extent of disease at diagnosis were analyzed.

Results

Out of 1375 pts identified for this analysis, 23.3% (320) were ≥70 y and 76.7% (1055) were <70y. The most frequent histological subtypes were liposarcoma (LPS) (29.7% 93/313) and undifferentiated pleomorphic sarcoma (UPS) (23.3% 73/313) in elderly pts (>70y), LPS (26.4% 272/1030) and leiomyosarcoma (LMS) 11.9% 123/1030) in younger pts. Synovial sarcoma was more common in younger pts (4.9% vs 0.9%). UPS was more common in older pts (23.3% vs 9.8%). LPS and LMS were similar in both groups. Elderly pts had a higher proportion of grade 3 tumors (41% 90/219 vs 33% 199/602), higher proportion of larger tumors (>=5cm) (71.9% 197/274 vs 64.5% 575/892), and higher proportion of advanced disease (aSTS) at diagnosis (47% 146/312 vs 41% 423/1037). Treatment received by pts aged <70y was compared with treatment received by elderly pts. No significant differences were seen in surgical or radiotherapy interventions, but younger pts received more chemotherapy in localized disease (younger: 17% 104/613; elderly 6,6% 11/166) and metastatic settings (younger 71.4% 302/423; elderly 48.6% 71/146). Median OS in aSTS pts <70y was 16.2 months (95%CI, 14.2-18.3) while OS in elderly pts was 8.9 months (95% CI, 7.1-10.7) p <0.0001. OS in localized pts was not calculated because of missing data.

Conclusions

Elderly pts (≥70y) in our cohort present with more advanced and aggressive disease and receive less chemotherapy treatment. Elderly pts with aSTS have worse OS than younger pts. Further studies are needed to help assess which variables determine these results and therefore influence treatment decisions.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

As life expectancy increases, the number of elderly patients with soft-tissue sarcoma (STS), for whom aggressive surgery may not be indicated due to poor general condition, is expected to increase. The purpose of this study is to evaluate the prognosis of >70 years old patients with STS who did not undergo surgery and reasons for non-surgical management.

Methods

>70 years old patients with STS and treated without surgery between 2013 and 2023 at our institution were included. Age, sex, follow-up period, tumor size, histopathological diagnosis, tumor location, tumor depth, performance status (PS), and reason for non-surgical management were reviewed. In addition, sarcoma-specific survival (SSS) was calculated.

Results

Out of 94 patients with STS, of whom each medical chart was reviewed, 11 patients did not undergo surgery. The median age was 84 years (range 72–95). Patients consisted of 6 male and 5 female. The median follow-up period was 5.1 months (range 1.1–34.2). Tumor size was over 10 cm in all patients. All patients were diagnosed by histopathological examination as follows: 2 patients of liposarcoma, 1 patient of each undifferentiated pleomorphic sarcoma (UPS), Ewing sarcoma, leiomyosarcoma. 6 patients were diagnosed as STS, of which specific type could not be confirmed. The tumors were located in the lower extremities in 5 patients and the trunk in 6 patients. The depth of the tumors was as follows: deeper than the superficial fascia in 10 patients and shallower than the superficial fascia in 1 patient. The PS was as follows: 0 in 1 patient, 1 in 6 patients, 2 in 2 patients, 3 in 1 patient, 4 in 1 patient. Two patients rejected indicated surgeries. In other 9 patients, surgeries were not indicated due to the following reasons: 7 patients had distant metastases, 1 patient was in poor general condition, 1 patient was considered inoperable because the tumor was located deep in the axilla. The 1-year SSS was 20%.

Conclusions

Even in >70 years old elderly patients with STS, the most primary reason for non-surgical management was the presence of metastases, although neither age nor poor general condition.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Multidisciplinary treatment including neo-adjuvant/adjuvant chemotherapy, radical surgery, and radiation is challenging for super elderly patients (aged > 80 years old) with soft-tissue sarcoma because due to deterioration of physiological function/tolerance for chemotherapy and medical complications. The purpose of the present study was to clarify clinical outcomes of elderly patients aged > 80 years old with soft-tissue sarcoma (STS) who underwent surgery without neo-adjuvant nor adjuvant chemotherapy.

Methods

Twenty-three consecutive patients aged ≥ 80 years, who underwent surgical resections of STS between January 2013 and December 2022, were included. As prognostic factors, depth of the tumor, maximum diameter of the tumor, Geriatric Nutrition Index (GNRI) for geriatric status, High-sensitivity modified Glasgow Score (HS-mGSP) for inflammatory status, local recurrence, and distant metastasis were evaluated.

Results

The median age was 84 (range 80–91) years. The median follow-up period was 49 (range 6–119) months. Histological diagnoses were as follows: myxofibrosarcoma in 8 patients, undifferentiated pleomorphic sarcoma in 7 patients, dedifferentiated liposarcoma in 4 patients, leiomyosarcoma in 3 patients, and synovial sarcoma in 1 patient. The locations of the primary tumor were superficial in 13 patients and deep layer in 10 patients, respectively. All patients underwent surgical resections. R0 margins were achieved in all patients. The 1-, 2-, and 5-year disease-specific survival rates were 95.7%, 91.1%, and 85.%, (median 58 months). Univariate analysis showed local recurrence and distant metastasis may affect disease-specific survival (p < 0.05, respectively). GNRI and Hs-mGPS were not influenced on disease-specific survival. Multivariate logistic regression analysis showed that distant metastasis was independent risk factor for the disease-specific survival (p < 0.05).

Conclusions

In the current study, we observed a comparable survival rate, despite no neo-adjuvant or adjuvant chemotherapies performed. Tumor resections with adequate margins might, at least in part, have contributed to the decent survival ratio regardless of histological grade.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Leiomyosarcoma (LMS) comprises up to 10-20% of soft tissue sarcomas. LMS arises from the smooth muscle cells or from the precursor mesenchymal stem cells that would eventually differentiate into smooth muscle cells present in the muscular wall of the veins. Venous thromboembolism (VTE) is a leading cause of death in patients with cancer. Nevertheless, its prevalence, characteristics, the role of the predictive scores and the association with survival in LMS has not yet been evaluated.

Methods

This retrospective study included 101 patients with LMS treated at a single national reference center for Sarcoma in Barcelona between January 2012 and December 2020. The main objective was to describe the frequency of VTE and its clinical characteristics as well as the accuracy of Khorana and ONKOTEV scores to predict VTE in LMS. Additionally, we evaluated the development of VTE and its association with overall survival (OS).

Results

Median age of the evaluated population was 60.3 years and 60.4% of the patients were women. LMS was grade 3 in 56.5% of the patients. The majority of LMS were located in the lower extremities (31.7%) followed by uterus (24.8%) and retroperitoneum (18%). Tumor size was > 5cm in 76% of the patients and 40.6% had metastases at diagnosis (lungs 63% and liver 19%). VTE diagnosis was more frequent in the metastatic setting than in localized disease (31% vs 18% p = 0.021). Inferior extremities deep vein thrombosis represented 51.6% of VTE events, and in 60.2% of cases LMS was originated also in the lower extremities. Pulmonary embolism represented 25.8% of VTE events, and the most frequent primary LMS locations were retroperitoneum and uterus (53.2% and 30%, respectively). ONKOTEV score achieved better predictive capacity for VTE compared to Khorana (AUC 0.69 vs 0.59) in ROC curves. OS was decreased by the presence of VTE in metastatic patients (39 vs 30 months, HR 0.74, p = 0.053).

Conclusions

VTE is a frequent phenomenon in LMS, particularly in the metastatic disease, with similar incidence to those reported in pancreatic adenocarcinoma. ONKOTEV score showed greater predictive capacity than Khorana score for VTE risk in LMS patients. Our findings suggest a detrimental impact of VTE in OS.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Leiomyosarcoma (LMS) is the second largest group of soft tissue sarcomas and often has an aggressive tumor biology. While evidence supports different biological behavior between uterine (ULMS) and non-uterine leiomyosarcomas (NULMS), the data on clinical outcome for NULMS depending on tumor localization (ie. visceral, retroperitoneal and pelvic) is scarce. This study aimed to analyze the association between tumor localization and oncological outcomes in NULMS.

Methods

Pts with LMS located in the abdomen and pelvis diagnosed between 2005 and 2022 were identified in the institutional sarcoma database at the Norwegian Radium Hospital. Non-operated, ULMS or pts with missing data were excluded. Included pts were divided into 3 subgroups based on primary tumor localisation: visceral, retroperitoneal and pelvic.

Results

A total of 123 pts (73 women) with a median age 62 years were included in the study. There were 48 pts in the retroperitoneal, 35 pts in the visceral and 40 pts in the pelvic subgroup. Median tumor size was 8 (1-32) cm. Retroperitoneal tumors were significantly larger than visceral, median 10.0 cm vs. 5.5 cm; P=0.048. 52 pts had French malignancy grade III. No significant differences in malignancy grade between the subgroups were observed. A free microscopic margin (R0) was achieved in 79 (66%) pts. The R0 rate was lower in the retroperitoneal and pelvic subgroups than for visceral tumors, 46% and 71% vs. 82% respectively; P=0.048. The median follow-up time was 23 (1-135) months. Fifty (47%) pts had disease recurrence; 16 (32%) local recurrences and 34 (68%) pts distant metastases. The median time to recurrence was 8 (3-54) months. The entire cohort's 5- and 10-year OS was 70% and 34%. For pts with retroperitoneal tumors, 5- and 10-year OS was 52% and 24% vs. 61% and 41% in the pelvic and 70% vs. 63% in the visceral subgroup; P=0.018. 5- and 10-year DFS was 30% and 10% for patients with retroperitoneal tumors, 49% and 32% for patients with pelvic tumors and 46% and 36% in the visceral subgroup; P=0.167. The median time from relapse to death was 21 (1-88) months.

Conclusions

Pts with visceral LMS had better oncological outcomes compared to pts with retroperitoneal tumors. Recurrence rates were high and long-term outcome after disease relapse was dismal.

Legal entity responsible for the study

Oslo University Hospital.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Leiomyosarcomas (LMS) belong to the group of soft tissue sarcomas (STS) and are one of the most common subtypes, along with liposarcoma (LPS). In the initial stages the gold standard treatment is based on surgery, while the role of chemotherapy (CT) is reserved for advanced stages, although its use has also been studied in the adjuvant and neoadjuvant context, with not enough evidence to support its use in these context. First-line treatment include doxorubicin in monotherapy or in association with other active agents such as gemcitabine, dacarbazine and trabectedin. Other molecules can be used for further lines such as hormone treatment, pazopanib and others.

Methods

We conducted a retrospective, longitudinal and observational study. We reviewed a total of 50 patients with LMS who have received treatment with CT either in the context of adjuvant or metastatic disease. The data was analyzed using the free statistics software Jamovi, using non-parametrical tests for variable associations and frequency measurements for descriptive analysis.

Results

Regarding adjuvant treatment, a total of 26 cases were analyzed, and the relapse rate was 57.6%. Not affected surgical margins was the only factor associated with better OS (50 vs 23 months, p value= 0.005) and RFS (12 vs 3, p value= 0.039). Of the 34 patients with metastatic disease analyzed. Main findings of different regimens and agents of RR, median OF and median PFS are shown in the table. Table: 75P

Conclusions

The only factor that was associated with better RFS and OS in patients who received adjuvant treatment with CT was the presence of free surgical margins. First-line treatment with CT in patients with metastatic disease with regimens based on doxorubicin showed more activity compared with others such as gemcitabine, trabectedin, but no statistically significant differences were found. We consider that any of these three agents can be used for patients with metastatic disease.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Leiomyosarcomas are one of the most common types of sarcomas, with an estimated incidence between 10 and 20% of all sarcomas. Unfortunately, despite optimal locoregional treatments, leiomyosarcoma may relapse. At the European level through EORTC, efforts were made to assess different regimens in combination with doxorubicin for the treatment of metastatic unresectable leiomyosarcoma.

Methods

A total of 71 patients treated between 2010-2023 were retrospectively selected, all of whom had provided consent for the use of their data. To obtain a more homogeneous sample, only those patients treated in the first line with anthracyclines in monotherapy or in combination, and gemcitabine and docetaxel were selected from the initially identified group.

Results

A total of 71 patients were retrospectively reviewed, comprising 62 women and 9 men. Age at diagnosis was 53 years (range: 26-86 years). The most common location uterine in 46%. 52,11% (37 patients) exhibited metastatic onset. 64% had pulmonary involvement, predominantly followed by peritoneal localization. Survival in patients with non-metastatic onset, was 58 months (range: 51-64 months), compared to 24 months for metastatic onset (range: 13-34 months), p-value of 0.003. PFSl in different treatment lines: Doxorubicin (D): 8 months, Doxorubicin + dacarbazine(D+DTIC): 12 months, Doxorubicin+trabectedin(D+tra): 9 months, Epirubicin + ifosfamide (Epi+Ifo): 7 month, gemcitabine + docetaxel (Gem+Doc): 7 months and Doxorubicin + olaratumab (D+olara): 7 months, p=0,07. Overall survival (OS) D: 47 months, D+DTIC: 74 months, D+tra 42 month, Epi+Ifo: 30 months, Gem+Doc: 37 months and D+olara: 34 months.

Conclusions

Limitation of retrospective assessment. Slight increase in progression-free survival comparing with the literature. Epi+Ifo should not be a standard option in leiomyosarcoma, as literature data show a low response and limited disease control. However, in our historical series, it was a chosen line in 7 patients. OS, the combination of D+DTIC stands out, doubling overall survival compared to historical data. 86% reach second lines. Assessing PFS2 in treatment, a notable survival of 9 months with tra stands out, surpassing the average and comparing with the trabectedin second-line study showing a PFS of 4.2 months.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Orbital rhabdomyosarcoma, more commonly known as RMS, is a malignant tumour that plagues the tissue surrounding the orbit. Relative to mesenchymal malignancies and tumours in general, it is quite rare. we analyzed data obtained from the SEER database to evaluate various therapeutic options on the survival outcomes for patients with RMS.

Methods

We examined data from 217 patients diagnosed with orbital rhabdomyosarcoma between 1975 to 2020, sourced from the SEER database. Cox proportional hazards model assessed the relationships between the therapeutic procedure and survival outcomes.

Results

The results of the therapeutic procedures analysis (n=217, 44.2% females). The gender distribution showed 70% of patients were aged 9 years or younger. Tumor size varied, with 20.3% >3cm. Regarding the stage of cancer, 45.6% had an unknown stage, while 38.2% were localized. For therapeutic procedures, surgery, chemotherapy and RT were performed in 54.4%, 89.9%, 82.9% of cases, respectively. The histological types varied, with 73.3% classified as embryonal rhabdomyosarcoma. The ethnic distribution showed that 58.1% of patients were non-Hispanic White. Univariate analyses using a Cox proportional hazard model demonstrated significant associations with survival outcomes. Patients aged over 9 years demonstrated a significantly increased hazard, with an HR of 2.555 (95% CI: 1.302-5.015, p=0.006) compared to those aged 9 years or younger. Tumor size, stage and racial factors were all associated with varying hazards. For therapeutic procedures, surgery, chemotherapy and RT showed varied HRs 0.533 (95% CI: 0.269-1.056), 0.807 (95% CI: 0.308-2.118), 0.497 (95% CI: 0.238-1.040). Notably, the combined therapy of RT and surgery showed a trend towards a lower hazard compared to radiotherapy alone (HR=0.498, 95% CI: 0.221-1.123, p=0.093).

Conclusions

Most patients were classified of embryonal rhabdomyosarcoma. Tumor size, stage and racial factors associated with better survival outcomes. There is no treatment of choice for orbital rhabdomyosarcoma in terms of survival. However, RT is a reasonable alternative treatment to surgery. The results require further validation by future prospective studies.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Kaposi sarcoma (KS), associated with human herpesvirus 8 and often linked to HIV, poses therapeutic challenges, and may require cytotoxic chemotherapy in aggressive disease. While liposomal doxorubicin is commonly recommended as the preferred first-line chemotherapy, limited data compare its efficacy against paclitaxel. This study aimed to assess the effectiveness and safety of these agents in the first-line treatment of KS.

Methods

A single-center retrospective study in Brazil included 106 KS patients, 54 required systemic therapy and were included in the analysis. Treatment regimens comprised liposomal doxorubicin (50.9%), paclitaxel (35.8%), and other regimens (13.2%). Objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) served as endpoints. ORR was compared using Fisher’s exact test and time-to-event endpoints were estimated using the Kaplan-Meier method with Cox regression providing hazard ratios (HR) and 95% confidence intervals.

Results

Liposomal doxorubicin exhibited a higher ORR (74%) than paclitaxel (52.6%), though not statistically significant (p=0.2). Median PFS was not reached, with 5-year PFS at 64.4% for doxorubicin and 77% for paclitaxel (HR 0.63, p=0.51). Median OS was not reached, with 5-year OS at 70.6% for doxorubicin and 84% for paclitaxel (HR 0.44, p=0.31). Discontinuations due to toxicity were higher in the paclitaxel group (17.6%) compared to doxorubicin (7.4%). Among HIV-associated KS cases (40 patients), most initiated antiretroviral therapy < 3 months before chemotherapy, 40.5% had CD4 > 200, and 68.4% had a positive HIV viral load.

Conclusions

The proportion of KS patients requiring systemic treatment was low. Both liposomal doxorubicin and paclitaxel demonstrated a high ORR, favorable PFS, and OS. No statistically significant differences emerged between the two drugs, despite a numerically higher ORR with liposomal doxorubicin. This study suggests effective disease control with both agents in first-line treatment of KS. However, considering the retrospective nature and the relatively small sample size, caution is warranted in interpreting the findings.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Head and neck soft tissue sarcomas are rare, accounting for about 1% of head and neck malignancies and 5% of sarcomas. These tumours may arise from the musculofascial or the visceral compartment. The most frequently histological subtypes undifferentiated pleomorphic sarcoma, fibrosarcoma, leiomyosarcoma and neurogenic sarcoma. Outcomes have historically been worse in this group, due to anatomic constraints leading to difficulty in completely excising tumours, with high rates of local recurrence.

Methods

A retrospective analysis of the head and neck STS managed in the department of Surgical Oncology DRBRAIRCH, AIIMS, New Delhi from 1995-2020 was performed from the database. We aim to analyse head and neck STS database and describe clinicopathological characteristics, treatment and outcomes.

Results

A total of 77 head and neck soft tissue sarcoma cases were operated from 1995-2020 out of which 49(63.6%) were male and 28(36.4%) were female. The mean age was 39 years. Majority (93.5%) patients presented with swelling with average duration of 7 weeks followed by pain (24.6%) with average duration of 2 weeks. 21(27.2%) were treatment naïve patients and 56(72.7%) patients had received treatment in the form of surgery, CT or RT before reporting to our centre. WLE was done in 67(87%) cases, R2 resection was done in 8(10.3%) cases and 1 patient turned out to be inoperable. Reconstruction was required in 44(57%) cases and in majority of cases local flaps (32) were used. The most frequent histological type was DFSP (27%) followed by neurogenic tumour (15%), leiomyosarcoma (8%) and rhabdomyosarcoma (8%). Margins was involved in 15(19.4%) patients. No lymph nodal metastasis was not detected in any cases. Adjuvant RT was given in 44(57%) cases and adjuvant CT in 18(23%) cases. Recurrence was detected in 23(29.8%) patients out of which 15(11.5%) were locoregional recurrence and 8(10.3%) were systemic recurrence.

Conclusions

Head and neck soft tissue sarcomas are rare tumours with multiple histological subtypes with distinct clinicopathological behaviour and literature on the management protocols is scarce. In our experience standard management should include wide excision with aim of clear margin and adjuvant chemotherapy and radiotherapy in high grade and close margin/positive margin.

Legal entity responsible for the study

The author.

Funding

Has not received any funding.

Disclosure

The author has declared no conflicts of interest.

Background

Limited progress has been made in the treatment of advanced soft tissue sarcoma (STS) in the last 20 years, and chemotherapy (chth) remains the backbone of therapy in metastatic settings. Considering the rarity of each STS subtype and the heterogeneity of responses to available treatment regimens, real-world data constitutes a valuable source of evidence. In this study, we aimed to describe the pattern of care and outcomes for patients with advanced synovial sarcoma.

Methods

This is a retrospective analysis of patients with advanced or metastatic sarcoma treated with systemic therapies (+/- local therapy). Patient and tumor characteristics were collected from electronic records at MSCNRIO in Warsaw, Poland.

Results

Between 1 January 2000 to 31 December 2021 134 patients (49.3% females) were included. The median age was 41.6 years (16-90). The majority, 88.1%, underwent curative surgery for the primary disease, and 84.7% of them received perioperative chth. Distant metastases were present at diagnosis in 44 patients (32.8%). The median time from diagnosis to systemic therapy was 18.3 months. Median number of lines was 3 (1-8). Median PFS and OS in 1^st line were 7.8 (95%CI 7.0-8.6) and 22.3 (95%CI 19.9-24.7) months, respectively. The most common chth in 1st line was high-dose ifosfamide in 65.7%, followed by doxorubicin-based regimens in 29.9%, but no differences in PFS were observed between both regimens (8.7 vs 7.0 months, p=0.735) in the overall population. 52.2% of patients underwent surgery in 1^st line, which resulted in improved PFS (19.9 vs. 4.2 months, p<0.001). Among patients without local therapy, ifosfamide-based chth was more effective than doxorubicin (6.0 vs. 2.9 months, p=0.012). Median PFS in 2nd and 3rd lines were 3.5 and 3.0 months, respectively. In further lines, pazopanib was the most active drug, with a median PFS of 5.1 months. Disease control as best response was achieved in 65.7% of patients in 1^st line and 34.6% in 2^nd line.

Conclusions

Our study confirmed observations from previous studies about the role of local therapy and the activity of ifosfamide-based chth in patients with advanced synovial sarcoma. The activity of systemic therapy in 2^nd and next lines is very limited, with some activity of pazopanib and rechallenge with ifosfamide.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

P. Sobczuk: Financial Interests, Personal, Other, Travel grant: Novartis; Financial Interests, Personal, Other, Travel Grant: MSD, BMS; Financial Interests, Personal, Invited Speaker: Swixx BioPharma, BMS, Gilead; Financial Interests, Personal, Advisory Board: Sandoz; Financial Interests, Personal, Stocks/Shares: CelonPharma; Non-Financial Interests, Institutional, Product Samples: Immutep; Non-Financial Interests, Personal, Leadership Role, Board Member, Chair of Young Oncologists Section: Polish Society of Clinical Oncology. K. Kozak: Financial Interests, Personal, Invited Speaker: Bristol Myers Squib, MSD, Novartis, Pierre Fabre, Sanofi. P. Teterycz: Financial Interests, Personal, Other, travel grant: Bristol Myers Squibb, MSD, Novartis, Roche. P. Rogala: Financial Interests, Personal, Other, travel grant: BMS, MSD, Novartis, Pierre Fabre, Roche; Financial Interests, Personal, Invited Speaker: BMS, MSD, Novartis, Roche; Financial Interests, Personal, Advisory Board: Pierre Fabre. T. Switaj: Financial Interests, Personal, Invited Speaker: BMS, MSD, Novartis, Roche, Pierre Fabre; Financial Interests, Personal, Other, travel grant: MSD. H.M. Kosela Paterczyk: Financial Interests, Personal, Invited Speaker: BMS, MSD, Novartis, Pierre Fabre, Roche; Financial Interests, Personal, Other, travel grant: PharmaMar. P. Rutkowski: Financial Interests, Personal, Invited Speaker, honoraria for lectures: MSD, BMS, Pierre Fabre; Financial Interests, Personal, Advisory Board: MSD, BMS, Pierre Fabre, Merck, Sanofi, Blueprint Medicines, Philogen; Financial Interests, Personal, Invited Speaker: Merck, Sanofi, Novartis, AstraZeneca; Financial Interests, Institutional, Research Grant, research grant for ISS: Pfizer; Financial Interests, Institutional, Funding, research grant for institution: BMS; Non-Financial Interests, Personal, Member of Board of Directors: Polish Society of Surgical Oncology; Non-Financial Interests, Personal, Member of Board of Directors, President: Polish Oncological Society. All other authors have declared no conflicts of interest.

Background

Malignant peripheral sheath tumor (MPNST) is a rare malignant soft tissue tumor with complex morphological appearance. Some cases are associated with type I neurofibromatosis (NF1). It has a wide range of involved location in the body and with aggressive clinical outcome. We tried to summarize the clinical and pathological characteristics of MPNST cases in our center, to improve our understanding.

Methods

This is a retrospective study enrolled 134 cases of MPNST at Cancer Hospital of the Chinese Academy of Medical Sciences from April 2017 to December 2022, including 99 consultative cases. We summarized the clinical-morphological characteristics.

Results

There were 64 males and 70 females enrolled in the study, with an average age of 44.3 years (range 4-83 years), including 6 patients with neurofibromatosis type I. A total number of 14 patients experienced tumor recurrence or metastasis. The above tumors are distributed in 150 affected areas, with the majority occurring in the trunk (46 cases), followed by the limbs (34 cases), the head and neck (33 cases), internal organs (22 cases), and the female reproductive system (6 cases). The thighs, neck, and back were the three most common affected areas, all with dense distribution of somatic nerves. There were 16 cases involved the skull. The classic MPNST with typical focal necrosis, inflammatory cell infiltration, and mitosis count >20/10HPF are the main subtypes, followed with 10 cases of low-grade and epithelioid MPNST. Among them, 7 cases showed rhabdomyoma differentiation (malignant salamander tumor). The immunophenotype exhibits various expression level of neurogenic markers (S100 and SOX10), negative or weakly positive for epithelial markers. The Ki67 index shows a high proliferative activity of over 30% in most cases. The deficiency of H3K27me3 was found in 23 out of 34 test cases (67.6%).

Conclusions

MPNST is a rare sarcoma always affected middle-aged and elderly patients., with various morphological appearance. The expression of immunohistochemical markers S100 and SOX10, as well as the loss of H3K27me3 expression is of great diagnostic value. MPNST shows frequent incidence of recurrence and metastasis. It is urgent to explore effective targeted and new therapies to improve prognosis.

Legal entity responsible for the study

The author.

Funding

Department of Pathology, National Cancer Center.

Disclosure

The author has declared no conflicts of interest.

Background

Alveolar soft part sarcoma (ASPS) is a rare, indolent soft tissue sarcoma, with a high predilection for systemic dissemination. This study aims at elucidating the patterns of clinical presentation of ASPS and their treatment outcomes, with emphasis on the efficacy of anti-angiogenesis agents, and the challenges faced in managing these rare tumours in low and middle-income countries (LMICs).

Methods

This was a retrospective cohort that included patients with advanced ASPS treated at our institute between 2016-2023. Clinicopathological data was obtained from case records, and analysed to assess outcomes.

Results

The study included 30 patients (17 males, 13 females) with a median age of 28 (3-72) years (Table). The median time from the onset of symptoms to final diagnosis was 9 (5-15) months. 7 patients presented with localized disease, and 23 with upfront metastatic disease. The most common site of primary was the extremities (73%), and the most common sites of metastasis included the lungs (82%) and bones (21%). Brain metastasis was seen in 6 patients at baseline (26%). 90% of patients with metastatic disease received a tyrosine kinase inhibitor (TKI) in the first-line setting with a median PFS of 12 months. The median OS in this subset was 36 months. 5 patients with advanced disease received immune-checkpoint inhibitors (ICI) (2-atezolizumab, 3 -nivolumab); the 2 patients on atezolizumab continue to be progression free at 12 and 8 months respectively. Patients with brain metastasis were seen to have markedly poor outcomes (median OS 9.4 months vs 56 months).

Table: 83P

Baseline characteristics of the patients

Conclusions

The use of anti-angiogenic agents has significantly improved survival in patients with advanced ASPS in LMICs. Delays in diagnosis and restricted access to immune checkpoint inhibitors represent significant challenges in further improving outcomes. This study represents the largest cohort of patients with advanced ASPS from this region.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

The clinical profiles of recurrent retroperitoneal liposarcoma (RLS) need to be explored. The recurrence patterns of RLS are controversial and ambiguous.

Methods

A total of 138 patients with recurrent RLS were finally recruited in the study. The analysis of overall survival (OS) and recurrence-free survival (RFS) was performed by Kaplan‒Meier analysis. The nomogram model was built to predict the survival status of patients. Univariate and multivariate analysis were performed for the selection of independent prognostic factors that were correlated with OS or RFS.

Results

Among patients, the 1-, 3-, and 5-year OS rates were 70.7%, 35.9% and 30.9%, respectively. The 1-, 3- and 5-year RFS rates of the 55 patients who underwent R0 resection were 76.1%, 50.8% and 34.4%, respectively. The multivariate analysis revealed that resection method, tumor size, status of pathological differentiation, pathological subtypes and recurrence pattern were independent risk factors for OS or RFS. Patients with distant recurrence (DR) pattern usually had multifocal tumors (90.5% vs. 74.7%, P < 0.05); they were prone to experience changes of pathological differentiation (69.9% vs. 33.3%, P < 0.05) and had a better prognosis than those with local recurrence (LR) pattern. R0 resection and combined organ resection favored the survival of patients with DR pattern in some cases.

Conclusions

Patients with DR pattern had a better prognosis, and they may benefit more from aggressive combined resection than those with LR. Classifying the recurrence patterns of RLS provides guidance for individualized clinical management of recurrent RLS.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Solitary fibrous tumour (SFT) is an uncommon soft-tissue sarcoma that can appear in any location, most commonly in the pleural surfaces. The presence of anomalous fusion genes between NAB2 and STAT6, with a high nuclear expression of STAT6 is characteristic. Although indolent, there is a small risk of long-term relapses and dedifferentiation to more aggressive disease.

Methods

Retrospective review of 56 patients diagnosed with SFT (2000-2023); clinical and pathological basal data, primary treatment, local and systemic relapses, treatment used for advanced disease and long-term overall survival (OS).

Results

56 patients (pts), 60% female. Median age 55 years (13-78). Location: 38% pleura, 15% lung, 11% lower limbs, 6% orbit, 6% subcutaneous; other < 5%. 5 patients (9%) with metastasis at diagnosis, all high-grade. Primary treatment: surgery in 83% (R0 resection 89%), watchful waiting (WW) in 11%. 1 pt with adjuvant radiotherapy. 4 pts treated with surgery (7%) had a local relapse; median time to relapse was 78 months (19-204). 3 of the 4 pts treated with WW (5%) had a local relapse, median time to relapse of 78 months (70-108). All 8 pts were rescued surgically. 3 systemic relapses (3%), again in high-grade tumours. 1st systemic treatment in 8 pts: anthracycline-based CT in 2 pts (3%, partial response in both), immunotherapy-antiangiogenic therapy in 2 pts (3%, stable disease in both) and pazopanib in 5 pts (9%, 1 partial response, 2 stable diseases 2 progressions). 4 pts with 2nd line CT and 2 pts with 3rd line CT. Disease control were poor with rapid progression. Median follow-up of 70 months (6-204), median OS 167 months (6-204 months); 86% remain free of disease, 9% alive with active disease and 5% deaths due to progression.

Conclusions

SFT is a heterogenous disease that can appear in any anatomical location and in a wide age range. Most patients can be treated surgically with good long-term results and salvage surgery is feasible in most cases of local relapse, with no need of adjuvant therapy. Unfortunately, distant metastases, although infrequent, are more difficult to treat. Targeted therapy such as pazopanib and immunotherapy show promising results. It is hoped that knowledge on the molecular drivers in SFT could show us potential targets for future therapies.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

DFSP is a rare uncommon disease with scarce literature, especially in developing countries. In India, expert diagnosis by a sarcoma pathologist is available, but mainly in tertiary care centres (molecular testing is not available).

Methods

Based on expert histopathology, we analysed the database of patients with DFSP who presented to the sarcoma clinic from January 2016 to December 2023. We have included all cases of locally advanced or metastatic DFSP. The dose of imatinib depended on the physician’s discretion, clinical response and the patient's tolerance.

Results

A total of 38 patients, with a median age of 36 years (range: 19-76 years) with male preponderance 25 patients (65%). All cases were diagnosed based on histopathology alone, by experts at a tertiary-level hospital. The most common primary site is the trunk and the metastatic site is the lung. The time from baseline diagnosis to development of metastasis is 23 months with a standard deviation of 43 months. Our patients had undergone a median of two surgeries (range: 0-4 surgeries) and 14 cases (36%) had received radiotherapy Among the 21 DFSP cases, 2 has complete response (CR), 5 has partial response (PR), 6 has stable disease (SD) with imatinib 400mg and 8 pts experienced disease progression (PD) while on imatinib. Thus, the overall disease control achieved with imatinib is 62% (13/21). The median PFS post imatinib treatment was 8 months (95% CI, 1-72 months). The overall median OS was 84 months (range: 21 - 168). Eight cases who had progressive disease on imatinib, two were lost to follow and 6 were tried with increased doses of imatinib (600mg or 800 mg doses) for later progression and were treated with dacarbazine, pazopanib, sorafenib, cabozantinib and doxorubicin.

Table: 86P

Conclusions

In the absence of translocation studies, diagnosis based on expert histopathology may help in targeted therapy-based treatment. The fibrosarcomatous variant has a worse prognosis, and further research is a must in this subset.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Myoepithelial tumors (MT) constitute a group of ultra-rare soft tissue sarcomas (STS) with unique characteristics. Initial approach is based on optimal surgery but some may exhibit local or distant relapse. There is lack of recommendations regarding the therapeutic approach in this subset of pts. The paper aims to assess the clinical features and outcomes among pts diagnosed with MT.

Methods

We have performed a retrospective analysis of all pts diagnosed with MT (myoepithelioma (ME) or myoepithelial carcinoma (MC)) at Gustave Roussy from January 2000 until December 2023. Clinical and survival data in addition to response to therapy were gathered from electronic records.

Results

11 pts with MT (4 MC and 7 ME) were included. There were 6 men (54.5%) with a median age of 50.5 yrs (3-71). The most common site of disease were: the upper arm (45.4%) followed by the lower arm (36.4%). All pts had initial localized disease except one with synchronous metastatic MC. The initial approach included surgery in 9 pts followed by adjuvant RT in two pts. One underwent an isolated limb perfusion while no adjuvant chemotherapy were given. After a median DFS of 13.31 mo., 5 pts exhibited a local relapse of whom 3 had metastatic relapse (MR) while 2 pts had prolonged disease remission after local therapy. 3 pts had MR (2 MC and 1 ME), all presenting with lung mets, after almost 4 years of remission. Systemic therapy was administered to 4 pts but no tumor response were recorded across all lines. Pazopanib was most commonly used with 1 stable disease (SD) out of 3 (treated in 2^nd or 3^rd line). Chemotherapy also showed limited efficacy (1 SD with Paclitaxel and Cisplatine, 1 PD (progressive disease) with oral vinorelbine, 1 PD with oral metronomic cyclophosphamide (met.C). 2 pts were enrolled in clinical trials: 1 had SD with Tazemetostat while another had PD after a combination of a Notch inhibitor and CDK4-6 inhibitor. One pt. had SD with hormone therapy (letrozole) and met.C.

Conclusions

MT represent a subgroup of STS with a distinct pattern of disease evolution. This analysis showed a chemo-resistant nature with low sensitivity to commonly used agents in STS. Multicentric data collection with molecular analysis in search of targetable alterations are eagerly needed in this rare entity.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Epithelioid sarcoma (ES) is a rare sarcoma subtype characterized by the loss of expression of INI1 (SMARCB1). Conventional chemotherapy and tazemetostat have moderate activity in ES. There have been anecdotal reports of responses to checkpoint inhibitors in epithelioid sarcoma (Pecora et al., 2020) (Blay et al., 2020).

Methods

A retrospective search of a prospective database was used to identify ES patients treated with checkpoint inhibitor therapy at the Royal Marsden between April 2021 and December 2023. Patients received combination ipilimumab (1mg/kg) and nivolumab (3mg/kg) every 3 weeks for 4 cycles followed by nivolumab 240 mg every 2 weeks through a compassionate access program. Progression free survival (PFS) was estimated from Cycle 1, Day 1 to disease progression or death and duration of response (DOR) from the date of first response to disease progression or death.

Results

Six patients were treated, 1 female and 5 males with a median age of 41 years. Ipilimumab/nivolumab was administered as 2^nd-line therapy in 4 patients and 4^th and 5^th line respectively for the other 2 patients. Five patients were previously treated with tazemetostat and 3 had prior treatment with doxorubicin. Four patients had stable disease and 2 partial response as best response by RECIST. Four patients have developed progressive disease and 3 patients have died. The median PFS were 6.63 (95% CI, 2-11.27) months and the median DOR 4.1 (95% CI, 1.23-6.97) months respectively. Three patients are still on treatment, one of them has developed oligoprogression in the brain. Three patients developed G2 hypothyroidism, one G2 transaminitis and one G3 transaminitis. The patient with G2 transaminitis, discontinued treatment after developing G2 colitis. One patient developed G3 hypoadrenalinism. Three patients had more than one immunotherapy-related toxicities. There were no treatment related deaths.

Conclusions

Ipilimumab plus nivolumab is safe with encouraging efficacy in patients with epithelioid sarcoma. Further investigation is warranted, ideally in the context of a prospective clinical trial.

Clinical trial identification

not applicable

Editorial acknowledgement

not applicable

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

As immunotherapy continues to play an increasingly prominent role in the standard care for various cancers, its effectiveness in unselected sarcomas has been disappointing, with objective response rates (ORR) ranging from 10-15%. However, some outlying responders were reported, suggesting a critical challenge in refining patient selection. This involves the identification of reliable response predictors.

Methods

The IMPRESARC study, a retrospective and multicenter cohort analysis, included all patients treated with immune checkpoint inhibitors (ICI) for advanced sarcomas across six different centers in France from October 2015 to December 2023 (Centre Léon Bérard, Institut Curie, Institut Gustave Roussy, IUCT Oncopôle, Institut de Cancérologie de l’Ouest). Our aim was to identify clinical and biological factors associated with responses to ICI.

Results

A total of 272 patients were included, displaying an ORR of 17%, a disease control rate of 49% (according to RECIST 1.1), a median progression-free survival (PFS) of 2.7 months, and a median overall survival of 13.5 months. Remarkably, 32% of patients were still alive at 24 months, and 27% at 36 months, with 15% experiencing a response duration exceeding 12 months. Factors independently associated with PFS included dNLR, WHO performance status, histologic subtype, and associated treatment. Alveolar soft part sarcoma correlated with better PFS, while dedifferentiated liposarcoma (ddLPS) was linked to worse PFS. Concomitant chemotherapy was associated with a decline in PFS. Molecular biology data, available for only about a third of the patients, were not included in the multivariate analysis. In this subset of patients, RB1 alterations were associated with worse PFS in univariate analysis, while tumor mutational burden did not seem prognostic in terms of PFS.

Conclusions

This large cohort reports a promising signal of activity for the use of ICI in ASPS, contrasting with poor prognostic factors such as ddLPS histology, concomitant chemotherapy, high WHO performance status and dNLR scores. These response predictors should be considered to refine therapeutic approaches, but further investigations are needed to identify reliable biomarkers.

Legal entity responsible for the study

M. Brahmi.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Following the advancement of immunotherapy (IO) in other cancers, there is heightened interest in exploring its role in soft tissue sarcoma (STS). Immune checkpoint inhibitors (ICIs) have been investigated either as monotherapy or in combinations in small phase 2 clinical trials including various STS histotypes. Their results were modest, with the exception of alveolar soft part sarcoma (ASPS). We aimed to assess the real-world clinical outcomes and safety of ICIs in Greek STS patients.

Methods

Medical records from STS patients treated with off-label ICIs (as monotherapy or in combinations) from 2020 to 2023 at 8 centers within the Hellenic Group of Sarcoma and Rare Cancers were retrospectively reviewed. End-points were progression-free survival (PFS), overall survival (OS) and safety.

Results

In total, 25 patients with metastatic STS were identified (median age 62 years, range 23-85). Patients had received 0-6 (median 2) prior treatment lines for advanced disease. Biomarkers related to IO were available for 12 patients: PDL1 expression in immune cells was positive (low) in 2/8, tumor mutational burden (TMB) was high in 2/9 and microsatellite instability (MSI) was high in 1/11 tested tumors. Nine patients exhibited partial response as best response (36% response rate), with the following histotypes: 2 leiomyosarcomas, 2 undifferentiated pleomorphic sarcomas, 1 ASPS, 1 myxofibrosarcoma, 1 dedifferentiated liposarcoma, 1 pleomorphic dermal sarcoma and 1 malignant granular cell tumor. Among the responders, only two expressed a biomarker of IO (one high TMB and another one MSI-high). Median PFS was 4.5 months (0.9-30.6) and median OS 9 months (1.7-34). Four patients experienced prolonged PFS (>12 months). IO regimens were well tolerated, with mainly grade 1-2 adverse events (colitis, anorexia, thyroid disorders, fatigue, skin toxicity), none of which led to treatment discontinuation.

Conclusions

With the limitation of a small sample size and a retrospective study design, this analysis shows that ICIs benefit a subset of STS patients. Prospective studies are needed to identify the optimal patient population. A histology-driven approach, coupled with the establishment of novel IO biomarkers, is warranted.

Legal entity responsible for the study

Hellenic Group of Sarcoma and Rare Cancers.

Funding

Has not received any funding.

Disclosure

S. Kokkali-Zervos: Financial Interests, Institutional, Invited Speaker: AstraZeneca. A. Kyriazoglou: Financial Interests, Institutional, Advisory Board: MSD, BMS, Roche. All other authors have declared no conflicts of interest.

Background

Soft tissue (STS) and bone sarcomas are a heterogeneous group of diseases, with over 150 subtypes, proving a major challenge in enrollment in prospective studies. The overall survival for metastatic sarcoma is dismal around 15%. In the era of immunotherapeutic strategies and next generation sequencing (NGS), much research is ongoing to identify optimal treatments. Our single center, retrospective analyze, aims to evaluate the efficacy of immune checkpoint inhibitors (ICIs) treated patients with advanced or metastatic sarcoma.

Methods

Patients with advanced or metastatic sarcomas, ECOG 0-2, treated between February 2020 and December 2023 at Sarcoma Center of University Hospital of Lausanne were analyzed retrospectively. Patients had been prescribed off-label ICIs in monotherapy or in combination with TKIs or chemotherapy.

Results

Fifteen patients with soft tissue (STS, N = 15) and two bone sarcoma (N = 2), received IV nivolumab 3 mg/kg every 2 weeks, pembrolizumab 200 mg every 3 weeks or ipilimumab 1mg/kg every 6 weeks in monotherapy or in combination with TKIs or chemotherapy. Median age was 55 (33–79), female: male ratio was 7:10. All patients underwent NGS. Four patients had variable PD-1 expression, none had high microsatellite instability, two patients expressed high tumor mutation burden (TMB). One patient with metastatic angiosarcoma received double ICIs (nivolumab plus ipilimumab), two patients received ICI and chemotherapy, five patients received TKIs and nine patients received monotherapy. Clinical benefit (response + stability) was observed in 58% of the evaluable patients, with six partial responses (three ongoing treatment) and four patients with stable disease; 7 patients had progression of disease. Grade 3–4 toxicity occurred in one patient (colitis).

Conclusions

We describe a cohort of 17 sarcoma patients treated with ICIs with or without TKIs or chemotherapy. We found clinical benefit within 58% of the treated patients. For most sarcomas the right combination of immune checkpoint inhibition is yet to be found. The need of prospective phase II/III randomized studies of ICIs alone or in combination, as well as real world data collection, are needed to better understand the real value of ICIs approach in sarcoma patients.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

We described and compared the immune microenvironment in uterine (UL) and non-uterine (NUL) leiomyosarcomas, and evaluated the clinical impact in a group of patients enrolled in a randomised phase III trial comparing doxorubicin to doxorubicin+trabectedin as first-line therapy in advanced/metastatic tumors.

Methods

The study group contained 53 UL and 63 NUL. By multiplex immunochemistry, we assessed the percentage of CD3+, CD20+, CD68+ and CD57+ cells in immune cells, in stroma and tumor. TILMs (lymphocytes + macrophages) was defined as the percentage of stromal area occupied by immune cells. P53expressionwas evaluated semi-quantitatively, from 1 to 3.

Results

In both subgroups, CD68 labeled 80% of immune-cells found in contact with tumor-cells. In the stroma, CD3+ cells were more frequent (45% in NUL, 30% in UL). CD20 and CD57 stained > 5% of all immune-cells. When comparing the subgroups, high-CD3 (>27,5%) was encountered more frequently in NUL than UL (p : 0,0369). Conversely, high-CD68 (>65%) was observed mostly in UL. Patients with high CD57 appeared to have a better prognosis in term of progression-free survival. Additionally, the therapy effect seemed to be more important in patients with low-P53 (>>30%). however, for all markers, there were no statistically significant associations with the outcomes/therapy response, regardless of group or type of treatment.

Conclusions

Several differences have been identified between UL and NUL, with regard to the tumour-infiltrating immune cells. It seems that CD3 is more expressed in NUL. High CD57 values appeared to correlate with a better progression-free survival, but further investigation is needed to confirm these data. However, there is no suggestion that immune microenvironment or TILMS can be prognostic factors or predictive markers of response to therapy, be it doxorubcin alone or doxorubicin+trabectedin.

Editorial acknowledgement

no

Legal entity responsible for the study

The author.

Funding

Has not received any funding.

Disclosure

The author has declared no conflicts of interest.

Background

The study aims to evaluate the predictive factors of disease relapse in patients with soft tissue sarcoma, focusing on systemic and intratumoral immune status and molecular features, to guide optimal therapeutic planning and prevent disease relapse in patients affected by WDL, DDL, MFS, and UPS.

Methods

The study involved patients with localized WDL, DDL, MFS, or UPS who underwent surgery from 2010 to 2020. FFPE samples of the surgical specimen were collected from 71 patients to perform an RNAseq, among these 47 samples with more than 4M reeds were selected to perform a CIBERSORT analysis to assess tumour-infiltrating immune cells. A differential gene expression analysis was performed comparing G1 VS G2, G2 VS G3, G1 VS G3, Relapse VS No Relapse, Local relapse VS Distant metastasis.

Results

106 patients were included in this single-centre retrospective study, including 31WDL, 30 DDL, 21 MFS, 24 UPS. Patients had better RFS and OS when SSI < 991 (P = 0,0001; P < 0,0001) NLR < 2,5 (P = 0,0006; P =0,0001), PLR < 190 (P = 0,0003; P < 0,0001), LMR ≥2,4 (P = 0,0067; P = 0,0011). Interestingly, patients with naive B-cell fraction (nBC) >3.13% of the total tumor-infiltrating immune cell population had worse RFS (P =0.0181). Furthermore, patients with activated dendritic cells (aDC) >1.02% had better RFS (P = 0.022). Event if not statistically significant, patients with higher histological grading seem to have a higher level of intratumoral monocytes and M2 macrophages. 3 main patient groups have been identified based on the intratumoral immune cell cluster analysis: Cluster A: patient with no disease's relapse and with an higher level of memory B cells and plasma cells; Cluster B: patient with disease's relapse and the highest number of M2 macrophages; Cluster C: high grade patients but with late relapse (>30 months) and the highest level of monocyte (C1) or with just a local relapse and high levels of aDC (C2). The differential expression analysis has revealed five genes (SLC17A8, OR5M8, TIMM8BP2, SLC5A8, and HIST1H4K) that are overexpressed in patients with higher grading and disease recurrence.

Conclusions

The findings of our study, if validated in larger series, may define new biomarkers useful to assess STS's patients risk assessment.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

LAG3 is an inhibitory receptor expressed by T cells related to inhibition of IFNg production and mitochondrial biogenesis in naive CD4 T cells. Combined expression with other immune checkpoints (ICs) like TIM3 and PD1 is associated with exhausted T cells. It is unknown if tumor-infiltrating lymphocytes (TIL) metabolism reprogramming is related to the presence of ICs impacting their anti-tumoral ability.

Methods

TIL expansion was performed using the TIL 3.0 methodology from 62 surgically resected liposarcoma (LPS) tumors. Flow cytometry phenotypic analysis included CD73, PD1, Tim3, CTLA4, LAG3, OX40, ICOS and 41BB. Cytotoxicity by IFNγ secretion and CD107a degranulation, reactive oxygen species (ROS) and mitochondrial membrane potential (ΔΨm) was measured on the expanded TIL.

Results

TIL expansion success was 54.8% (n=34/62 expanded). The median proportion of T cell populations post expansion was 2.68% CD4+, 80.7% CD8+ and 11.45% CD4-CD8- (DN) comprised mainly of γδ T cells. LAG3 was the highest expressed checkpoint receptor across the TIL subtypes (median 5.28% of CD4+, 3.37% of CD8+ and 15.7% of DN). Likewise, TIM3, OX40, and PD-1 were differentially expressed (median TIM3 1.23% CD4+, 2.73% CD8+, 7.3% DN; OX40 9.4% CD4+, 0.43% CD8+, 0.3% DN; PD-1 9.2% CD4+, 2.8% CD8+, 2.28% DN). Higher metabolic fitness by ROS and ΔΨm correlated with increased IFNγ and CD107a degranulation. We identified three distinctive clusters driven by LAG3 expression and metabolic signature. 1) High LAG3, cytotoxicity, and metabolic fitness, 2) Low cytotoxic-metabolic fitness and low LAG3 and 3) absence of LAG3 and high cytotoxic-metabolic fitness. The data suggest clusters 1 and 2 describe two different patterns; one more activated that might be associated with the presence of LAG3, and the other is dysfunctional by the lack of cytotoxic and metabolic response. Meanwhile, the third cluster suggests a naive bystander T-cell population with a high degranulation and metabolic profile.

Conclusions

We describe a potential relationship between metabolic profiles and LAG3 expression. This data underscores the importance of metabolic fitness driving cytotoxic function and deepens our understanding of potentially important biomarkers in adoptive T cell therapy.

Clinical trial identification

Research samples were collected using the IRB-approved protocol LAB08-0151.

Legal entity responsible for the study

University of Texas MD Anderson Cancer Center.

Funding

Sarcoma-Oma Foundation.

Disclosure

C. Haymaker: Financial Interests, Personal, Advisory Board: Regeneron; Financial Interests, Personal, Other, Consulting: Avenge; Financial Interests, Personal, Other, Stock options as a member of the Scientific Advisory Board: Briacell; Financial Interests, Institutional, Research Grant: Iovance, Dragonfly, BTG, Sanofi, Avenge, KSQ; Non-Financial Interests, Personal, Advisory Role, Co-Chair of SAB: Mesothelioma Applied Research Foundation. All other authors have declared no conflicts of interest.

Background

The tumor microenvironment plays an important role in tumor behavior and the effectiveness of the therapy. However, in soft tissue sarcoma (STS), the impact of the tumor microenvironment has not been practically studied. The aim of the research was to study the effect of the immune microenvironment on the clinical course and prognosis of soft tissue sarcomas.

Methods

Retrospective research was conducted on 168 soft tissue sarcoma patients who received care at the Republican specialized Scientific and practical Medical Center of Oncology and Radiology of Uzbekistan. Tumor-infiltrating lymphocytes and lymphocyte subpopulations were investigated by immunohistochemical analyses of CD3, CD4, CD8, CD20, CD68.

Results

The most common type of cells in the immune microenvironment were macrophages of CD68+ and CD3+ T cells. A multivariate analysis using the Fine & Gray risk regression model with death as a competing event revealed a significant positive correlation between CD68 expression and the risk of local recurrence (p=0.014) regardless of age, resection margins and the presence of B cells. Moreover, the abundance of macrophages was significantly higher in patients older than middle age (p=0.002), while the number of B cells was significantly lower (p=0.013) in elderly patients. As for histological subtypes with a high total number of tumor-infiltrating lymphocytes in general and macrophages in particular, these cells were more often observed in undifferentiated pleomorphic sarcoma and myxofibrosarcoma.

Conclusions

The study confirms the high level of CD68 macrophages in soft tissue sarcomas and its adverse effect on the prognosis for local recurrence.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Immunotherapy has surfaced as a new treatment approach for certain soft tissue sarcomas with tertiary lymphoid structures (TLS). These ectopic lymphoid aggregates promote an immune response in the tumor microenvironment. Assessing TLS as a predictive biomarker at scale on patient specimens remains challenging. Even though tissue microarrays (TMAs) could facilitate this assessment, it is not clear if small TMA cores can represent associated TLS responses.

Methods

We used multiplex immunohistochemistry to identify key components of TLS such as B cells, T cells, and dendritic cells on a single slide. Staining panels (CD20/CD79a, CD3, CD208, and PNAd) were applied to 80 cases on both TMAs and their corresponding full-faced sections from epithelioid sarcoma and dedifferentiated/well-differentiated liposarcoma arrays, as the training set. Additionally, 68 cases from the malignant peripheral nerve sheath tumor array were used as the validation set. TMAs were digitally scored for the number of immune cells, and cognate full-faced sections were visually evaluated for the presence of TLS.

Results

We observed that the Combined Immune Marker (defined as the presence of more than 24% CD3, or 0.51% CD20, or 0.14% CD208 cells on TMA cores) is a highly specific marker (100%) with moderate sensitivity (61%) to predict the existence of TLS on full-faced sections. Validation data indicate that the Combined Immune Marker remains highly specific (80%) but shows reduced sensitivity (27%) in detecting TLS.

Conclusions

The Combined Immune Marker assessed on TMAs is a highly specific marker to detect the traces of TLS on full-faced sections. Therefore, despite the small area sampled, TMAs may be utilized to assess the clinical value of TLS on large datasets; particularly to validate the predictive capacity of TLS for immunotherapy benefit in sarcomas.

Legal entity responsible for the study

The authors.

Funding

Terry Fox Research Institute, grant number 1082- BC Cancer Foundation, Rising Star Award to Elahe Shenasa.

Disclosure

All authors have declared no conflicts of interest.

Background

Chondrosarcoma, or malignant cartilage tumor, is the second most common bone cancer after osteosarcoma. Chemo- and radio-resistant due to its poor vascularization and the chondrogenic nature of its extracellular matrix (ECM), its management relies mainly on surgery, underlining the limited therapeutic arsenal. In addition to its unique appearance, this tumor is characterized by a microenvironment rich in immune cells such as lymphocytes and tumor-associated macrophages (TAMs). TAMs are the most common cell population in these tumors, and can represent more than 50% of tumor mass. Most of these cells, known as M2-like TAMs since they display the characteristics of M2 macrophages, have pro-tumoral properties and participate in various processes such as invasion and chemoresistance. Due to the rarity of this pathology, few data are available on cancer cell/TAM interactions, highlighting the need to develop models to study these interactions and evaluate therapeutic strategies involving the macrophagic component such as mifamurtide, an immunostimulator. In this context, UMR 1240 Inserm/UCA IMoST, drawing on its expertise in chondrosarcoma, has developed an innovative cocultured tumoroid model between grade 3 chondrosarcoma cells (CH2879) and immortalized human monocytes (THP-1).

Methods

This new in vitro model was characterized and compared to the in vivo xenograft model and then used to assess treatment effect. After demonstrating the ability of cancer cells to recruit monocytes, tumoroid microenvironment was characterized.

Results

Interestingly, as the in vivo preclinical model, the tumoroid is characterized by the presence of M2-like TAMs in the periphery, correlating with increased accumulation of MMP-9 and COX-2 (enzymes involved in ECM remodeling and invasion). In addition, the cocultured tumoroid showed chemoresistance to doxorubicin with IC50 two times higher compared to the monoculture model. Finally, Mifamurtide treatment is currently being evaluated, suggesting a potential effect.

Conclusions

Taken together, these results point to the development of a relevant preclinical model mimicking cell/matrix and cell/cell interactions that can be used to evaluate new treatments, with the aim of improving the management of this orphan pathology.

Legal entity responsible for the study

UMR 1240 INSERM UCA.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Angiosarcoma is a relatively rare neoplasm of the breast (less than 0.05% of all malignant mammary tumours). Tumours can arise : i) de novo; secondary to a long standing lymphoedema ; iii) secondary to radiation therapy. In the last few years, the importance of studies about tumour microenvironment (TME) has been steadily growing, especially in order to identify potential responders to immune checkpoint inhibitors (ICIs) even in angiosarcoma. The aim of this study was to evaluate some TME features in angiosarcoma of the breast and to correlate such features with clinicopathological and follow up data.

Methods

The retrospective study was performed on tissue samples with medical records available at The Istituto Nazionale Tumori ‘G. Pascale’, Naples, Italy. Immunohistochemical parameters evaluated encompassed lymphoid cell markers (CD3+, CD8+, GrzB+, FoxP3+, CD103+) and immune checkpoint receptors (PD-L1, VISTA, TIM3, OX40). Fluorescence in situ hybridization was used to assess c-myc amplification. The immunohistochemical expression of the mismatch repair proteins was also investigated and, in ‘indeterminate’ cases, followed by automated RT-qPCR examination for microsatellite instability (IdyllaTM platform). Overall survival (OS) was estimated by Kaplan-Meier method and compared with Log-rank test.

Results

Nine cases of primary (pAS) and nine cases of secondary angiosarcoma (sAS) were retrieved. Comparison of mean tumor-infiltrating lymphocytes (TILs) and immune checkpoint receptor (ICrs) densities between pAS and sAS showed a statistically significant difference only in GrzB+ cells, which were more represented in pAS (p=0.042). Furthermore, we simultaneously quantified the number of stained T cells by multiple immunofluorescence to verify the balance between cytotoxic (CT) and immunosuppressive (IS) activity in the TME. In about 50% of cases, we found colocalisation of CD8+ and FOXP3+ cells. Although not significant, a higher degree of immunosuppression was observed in SAS cases (p = 0.266).

Conclusions

Our prelimary data suggest that sAS discloses an immunosuppressive environment; therefore, compared to pAS, sAS might be a better candidate to immunotherapy.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

MAOB is one of the rarest types of breast tumors which represents less than 0.2% of all breast tumors and is associated with a poor prognosis. Mastectomy or BCs are the best therapeutic techniques in patients with MAOB, but there is a debate about the need for postoperative RT. We aimed to study the effectiveness of postoperative RT for MAOB over a long period.

Methods

Patients with MAOB, who underwent a mastectomy and BCS, were identified through the SEER database from 2000 to 2020. Descriptive analyses were conducted to evaluate the clinical characteristics of patients with MAOB.Cancer-specific survival (CSS) was predestined using the Kaplan Meier and compared using the log rank test. Univariate and multivariate Cox proportional hazards regressions were performed to evaluate the prognostic power of factors on CSS.

Results

A total of 542 women with MAOB were included in this study. Most women 82.8% underwent mastectomy, while 17.2% underwent BCS. postoperative RT was performed in 102 women 18.8%, with 27,29.0% in the BCS group and 75,16.7% in the mastectomy group. Postoperative RT was more likely to be performed in women with adverse risk factors, including larger tumor size in the mastectomy group and higher tumor grade in both groups. lymph node metastasis was unwillingly found in MAOB, only 11 patients had positive lymph node metastasis, and among them, 9 patients underwent mastectomy, and 2 patient underwent BCs. Additionally, lymph node involvement increased the chance of postoperative RT in the mastectomy group. In both groups, the need for postoperative RT decreased as the tumor became more invasive. However, this pattern was less obvious in the BCS group. In multivariate analysis, there weren’t any significant prognostic factors impact on CSS in mastectomy group, postoperative RT (P=0.656). In BCS group, age, tumor size and lymph node metastasis were significant predictive factors on CSS, meantime postoperative RT had no effect on (CSS) (P=0.152).

Conclusions

MAOB patients with more inverse prognostic factors were received postoperativeRT, and CSS was not statistically varied from the non-postoperative RT group, independent of surgical type mastectomy or BCs.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Cardiac hemangiosarcomas originate from blood vessel-forming cells and are described as aggressive malignant tumors. However, with limited data on the safety and efficacy of different therapeutic modalities an optimal treatment strategy remains unclear. We conducted a comprehensive analysis on the effect of various therapeutic procedures on the survival outcomes of cardiac hemangiosarcoma patients.

Methods

In a retrospective cohort analysis, we examined data from 196 patients diagnosed with cardiac hemangiosarcoma between 2000 to 2020, sourced from the SEER database. Cox proportional hazards model assessed the relationships between these factors and survival outcomes.

Results

The study included 196 patients (47.7 females) with cardiac hemangiosarcoma. Among the subjects, 55.6% were less than 50 years old, while 44.4% were aged 50 or older. The grade distribution was as follows: 2.6% for Grade 2, 18.9% for Grade 3, 19.9% for Grade 4, while 58.7% were of unknown grade. Most patients were in distant stage, 41.3%. Treatment modalities among the participants were diverse: 53.6% underwent surgery, 20.4% received radiation therapy, and 61.7% were treated with chemotherapy. By the study's conclusion, 89.3% of the patients had deceased, while 10.7% were still living. Tumor size distribution revealed 4.6% with a size less than 3cm, 38.8% with a size equal to or greater than 3cm, and 56.6% with unknown tumor size. Univariate and multivariate analyses using a Cox Proportional Hazard Model demonstrated significant associations with survival outcomes for surgery (HR=0.614, 95% CI [0.454-0.831], P=0.002; HR=0.562, 95% CI [0.414-0.764], P=<0.001), chemotherapy (HR=0.529, 95% CI [0.386-0.725], P=<0.001; HR=0.49, 95% CI [0.356-0.676], =P=<0.001), and in significant in radiation (HR=0.786, 95% CI [0.545-1.132], P=0.196; HR=0.754, 95% CI [0.523-1.089], P=0.132).

Conclusions

Our findings revealed that surgery and chemotherapy were significantly associated with improved overall survival, while radiation therapy had no significant effect on patients with cardiac hemangiosarcoma. The results require further validation by future prospective studies and exploration in the optimal sequence each therapeutic modality.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

The treatment of primary malignant phyllodes tumors of the breast (B-MPT) consists of wide local excision with negative margins (≥1 cm). However, because of their rarity, prognostic factors, optimal type of surgery and adjuvant treatments are still a matter of debate.

Methods

We conducted a single-center, retrospective study on the clinical outcomes and prognostic factors in patients with primary B-MPT, who underwent breast surgery from January 2000 to December 2021. The primary endpoint was the cumulative incidence of any recurrence. Secondary endpoints were the cumulative incidence of distant and local recurrences.

Results

131 patients were included. All received surgery, 5 underwent adjuvant chemotherapy and 15 radiation therapy. After a median follow-up of 6.4 years, the cumulative incidences at 5-years of any, local and distant recurrences were of 26% (95% Confidence Interval [CI], 4-34%), 16% (95%CI, 10-24%) and 10% (95%CI, 5-16%), respectively. Tumor size ≥5 cm was associated with higher distant recurrences (p=0.05). Among small tumors (<5 cm), distant recurrences were higher in those with heterologous differentiation and/or multifocal disease (p=0.06). Evolution from and/or previous history of fibroadenomas, benign or borderline phyllodes tumors of the breast were associated with lower distant recurrences (p=0.014). Type of breast surgery (mastectomy vs. lumpectomy/excision) was not found to be significantly associated with distant (p=0.32) or local (p=0.17) recurrence, even after controlling local recurrence incidence for negative pathologic prognostic factors (p=0.17).

Table: 101P

Conclusions

The natural history of B-MPT can be burdened by local and distant recurrences. Pathologic prognostic factors (i.e., tumor size, heterologous differentiation, multifocal disease, previous history of fibroepithelial tumors) more than the type of wide breast surgery (mastectomy vs. lumpectomy) seem to represent the most significant prognostic factors for recurrences.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

G. Curigliano: Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, Daiichi Sankyo, Novartis, Pfizer, Pfizer; Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Daiichi Sankyo, Lilly, Pfizer, Veracyte, BMS, Merck, Exact Sciences, Celcuity; Financial Interests, Personal, Advisory Board, Advisory Board: Menarini, Gilead; Financial Interests, Personal, Other, Advisory Board: Ellipsis; Financial Interests, Institutional, Research Grant, Investigator Initiated Trial: Merck; Financial Interests, Institutional, Funding, Phase I studies: BMS, Novartis, AstraZeneca, Daiichi Sankyo, Roche, Blueprint Medicine, Kymab, Astellas, Sanofi, Philogen; Financial Interests, Institutional, Invited Speaker, Phase I clinical basket trial: Relay Therapeutics; Non-Financial Interests, Personal, Officer, Italian National Health Council as Advisor for Ministry of Health: Consiglio Superiore di Sanità; Non-Financial Interests, Personal, Advisory Role, Member of the Scientific Council. Patient advocacy association: Europa Donna; Non-Financial Interests, Personal, Advisory Role, Cancer Research Foundation: Fondazione Beretta; Non-Financial Interests, Personal, Member of Board of Directors, No compensation for this role. This a public national company for cancer prevention: Lega Italiana Lotta ai Tumori; Non-Financial Interests, Personal, Officer, Member of the Advisory Council: EUSOMA; Non-Financial Interests, Personal, Officer, ESMO Clinical Practice Guidelines Chair: ESMO; Non-Financial Interests, Personal, Member of Board of Directors, Chair of Clinical Practice Guidelines Committee: ESMO. All other authors have declared no conflicts of interest.

Background

Imaging is crucial in monitoring treatment effects in soft tissue sarcoma (STS), where tumor size and intensity are key factors. Standard evaluation criteria, RECIST and Choi, have been criticized for inconsistencies and limited correlation with patient outcomes. While more accurate in predicting response, Choi criteria are labor intensive for radiologists, necessitating improved evaluation methods.

Methods

We analyzed Spearman correlations between tumor diameter, intensity and volume. Cohen’s kappa was used to measure agreement between RECIST, Choi and segmentation-based criteria (using RECIST cut-offs for volume and Choi cut-offs for intensity). Wilcoxon tests compared pre-/post-radiotherapy measurements. Correlations with pathology (% necrosis, fibrosis, viable tumor) were computed when available. We trained an AI model to segment STS in MRI and benchmarked against radiologist segmentations using a modified dice coefficient, assigning a value of 1 for correctly identifying tumor absence.

Results

High diameter vs. volume (ρ = 0.94), but weak volume vs. intensity (ρ = -0.26) and diameter vs. intensity (ρ = -0.28) correlations were seen in 270 scans (142 patients), median volume 110 cm³ (IQR: 30 - 414). RECIST-Choi, Choi-segmentation and segmentation-RECIST agreements in 178 follow-ups (144 patients) were 0.38, 0.55 and 0.32. In 121 neoadjuvant radiotherapy patients significant post-radiotherapy changes were observed in tumor intensity (p<0.001), but not in volume (p = 0.40) or diameter (p = 0.16). Pathology (available in 107 patients) showed significant correlations for volume vs. necrosis (ρ = 0.44), volume vs. fibrosis (ρ = -0.44), diameter vs. necrosis (ρ = 0.40), diameter vs. fibrosis (ρ = -0.26), intensity vs. fibrosis (ρ = -0.24) and intensity vs. viable tumor (ρ = 0.26), suggesting larger tumors show increased necrosis and decreased fibrosis while higher intensity indicates more viable tumor. The AI model scored 0.86 dice in an initial 24 patient test set and 0.62 in a new clinical 47 patient set.

Conclusions

Low agreement in STS radiologic response criteria, likely due to complementary information provided by size and intensity data, underscores the need for new methods. Our preliminary segmentation results show promise but require further refinement.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Liposarcoma (LPS), a rare and aggressive soft tissue cancer, lacks effective treatment options. Traditional drug discovery methods have been largely ineffective against LPS. Our study represents a paradigm shift in cancer treatment discovery, employing advanced AI algorithms to identify novel druggable targets and predict compounds with polypharmacological potential for LPS therapy.

Methods

Utilizing Kantify's proprietary AI-based drug discovery platform, Zeptomics, we embarked on a twofold approach: first, identifying novel targets shared across LPS subtypes based on published drug screening data, and second, conducting an in-silico screen of approximately 10,000 drugs and natural compounds that haven't previously been considered for LPS. This approach prioritized compounds predicted to modulate simultaneously multiple novel predicted targets, addressing cancer cell compensation mechanisms. We validated these findings through in-vitro screenings of nine leading compounds on dedifferentiated and myxoid LPS cell lines, coupled with CRISPR-Cas9 depletion of the identified targets.

Results

Over the course of just three months, we ran the in-silico screening, followed by in-vitro validation. The validation resulted in an unprecedented hit rate (∼77%) with seven compounds demonstrating significant efficacy in reducing LPS cell viability, with IC50 ranging from 1.5uM to nM scales. This method's efficiency far exceeds traditional drug repurposing rates. Among the effective compounds, two are oncology drugs, three are prescription medications with minimal side effects, one is a natural compound, and one is a veterinary drug. Furthermore, the CRISPR-Cas9 gene depletion substantiated the importance of seven novel targets for LPS survival.

Conclusions

This study not only unveils novel targets for LPS treatment but also exemplifies the power of AI in predicting multi-targeted therapeutic compounds. This groundbreaking approach, transcending traditional drug discovery methods, holds immense potential for broadening cancer treatment strategies and is poised to make a significant impact in oncological drug development and repurposing approaches.

Legal entity responsible for the study

The authors.

Funding

Kantify.

Disclosure

N. Subramanian, S. Martin: Financial Interests, Personal and Institutional, Ownership Interest, financial interest in Kantify (either through employment, board seats, or stock ownership): Kantify. N. Maignan, D. Papazian, J. Dawe, M. Georges, C. Hudson Queiroz de Souza, R. Ravinder: Financial Interests, Personal and Institutional, Full or part-time Employment, financial interest in Kantify (either through employment, board seats, or stock ownership): Kantify. All other authors have declared no conflicts of interest.

Background

There is an urgent clinical need to develop new combination therapies for patients with refractory high grade soft tissue sarcomas, particularly fibrosarcoma. These aggressive tumors, with overall survival rates less than 30%, respond poorly to conventional therapies. Standard systemic care for these tumors includes doxorubicin (DXR). A Tyr peptide analogue (TPA), developed in our laboratory, specifically targets cancer stem cells (CSC).

Methods

For the primary tumor growth model, half a million luciferase-labeled human fibrosarcoma HT1080 cells were xenografted in the quadriceps of 25-gram Nu/Nu male mice. Tumor growth was monitored by IVIS imaging. For the metastatic model, one million luciferase-labeled HT1080 cells were injected intravenously and survival assessed per UM IACUC protocol 19-079. DXR was delivered intravenously once at 15mg/kg while TPA at 0.025 mg/hour using Alzet osmotic minipumps transplanted subcutaneously. qRT-PCR, immunoblot, cell toxicity assays, tissue culture.

Results

Our results show that TPA specifically targets and significantly inhibits cancer stem cell growth, cell maintenance by drastically reducing expression of the polycomb group protein enhancer of zester (EZH2) and its downstream targets ALDH1A1, a well-characterized cancer stem cell marker, along with embryonic transcription factor Nanog. In addition, TPA and DXR used in combination for the treatment of relapsed DXR-treated fibrosarcoma led to a seven-fold decrease in primary tumor growth. In an experimental metastatic model, there was more than two-fold decrease in tumor growth with 100% survival observed at 58 days for the same combo group. Tyr peptide also efficiently inhibited other connective tissue malignancies tested in vitro- other types of sarcoma and acute lymphocytic leukemia.

Conclusions

Treatment-refractory cancer, which is associated with drug resistance, is thought to stem from cellular heterogeneity and driven by a small population of CSCs. Our studies showed that TPA, which targets CSC, expands the therapeutic efficacy of DXR both in vitro and in vivo, leading to decreased tumor burden and increased survival.

Legal entity responsible for the study

The authors.

Funding

Miami Center of Orthopedic and Research.

Disclosure

K. Galoian: Other, Institutional, Proprietary Information, MiamiPCT in TYr Peptide with university of: University of Miami, Miller School of Medicine, Department of Orthopedics. All other authors have declared no conflicts of interest.

Background

LX-101, a next-generation, targeted therapy directed to the insulin-like growth factor 1 receptor (IGF-1R), consists of a proprietary optimized IGF-1 variant coupled to a cytotoxic methotrexate payload. LX-101 was previously evaluated in phase 1 trials of adult patients with advanced, pretreated cancers, where it was well-tolerated and demonstrated single agent activity. Maximum tolerated dose and dose limiting toxicity were not reached, allowing for additional dose escalation and schedule optimization. Several aggressive cancers of unmet need have genetic alterations affecting the IGF-1R pathway and/or high IGF-1R expression which correlates with poor outcomes, including Ewing’s sarcoma (ES), rhabdomyosarcoma (RMS), and others. Prior attempts at inhibiting the IGF-1R with non-payload bearing approaches produced a range of clinical outcomes, including some partial and complete responses. None were ultimately approved in an oncology setting, potentially due to suboptimal potency that allowed for redundant signaling pathways and other escape mechanisms. Here, we investigated the anti-tumor activity of LX-101 against sarcomas and other rare IGF-related cancer cell lines in vitro.

Methods

Cell lines were incubated with LX-101 (∼1.6 - 2500nM). Viability was assessed by CellTiter-Glo after 4 days. IC₅₀s were calculated using GraphPad PRISM software.

Results

All ES cell lines tested were sensitive to LX-101, including EWSR1-FLI1+ (RD-ES, IC₅₀ = 10 nM; A-673, IC₅₀ = 14 nM; SK-ES-1, IC₅₀ = 29 nM) and EWSR1-ERG+ (CADO-ES1, IC₅₀ = 14 nM) cell lines. LX-101 was active against PAX3-FOXO1+ alveolar RMS (SJCRH30, IC₅₀ = 23 nM) and osteosarcoma (143B, IC₅₀ = 6 nM; HOS, IC₅₀ = 7 nM; U2OS, IC₅₀ = 32 nM). LX-101 was also potent against adrenocortical carcinoma cell line SW-13 (IC₅₀ = 9 nM).

Conclusions

These results demonstrate that LX-101 has potent preclinical anti-tumor activity against sarcoma and other rare cancer cells with well-established ties to the IGF-1R pathway, including those with different oncogenic gene fusions. These data support the clinical development of LX-101 in IGF-1R-related sarcomas and other rare cancers. Clinical trials are planned.

Legal entity responsible for the study

Lirum Therapeutics, Inc.

Funding

Lirum Therapeutics, Inc.

Disclosure

M. Hoberman: Financial Interests, Personal, Full or part-time Employment: Lirum Therapeutics; Financial Interests, Personal, Stocks/Shares: Lirum Therapeutics.

Background

MAP (methotrexate, Adriamycin and cisplatin) neoadjuvant chemotherapy is the osteosarcoma standard of care. To date, there are no biomarkers to predict pathological response to treatment which is a major prognostic factor. Additionally, no biomarkers exist to predict toxicity derived from the treatment that may lead to treatment delays or serious complications. The aim of this study, embedded in the GEIS33 protocol, was to evaluate the role of germline single nucleotide polymorphisms (SNPs) as predictive biomarkers for toxicity and response in localised osteosarcoma patients treated with MAP.

Methods

Peripheral blood DNA was extracted from 69 patients enrolled in the GEIS33 protocol that evaluated the value of P-glycoprotein as a stratification factor for localised osteosarcoma. A total of 13 polymorphisms in 8 genes involved in DNA repair and drug metabolism pathways were selected using HapMap and literature review. Genotyping was performed by real-time PCR using TagMan probes.

Results

Of the 69 patients treated with 2 cycles of neoadjuvant MAP, 26 (37.7%) patients achieved a good pathological response (>90%). P-glycoprotein expression was positive in 35 patients but did not correlate with pathological response.In the multivariate analysis including 66 evaluable patients, two SNPs (ERCC2/XPD rs1799793 and ABCC2 rs2273697) correlated with the probability of achieving good pathological response. Toxicity was evaluated in 43-56 patients depending on the tested parameter. In the multivariate analysis, ABCC1 rs1128503 and ABCC3 rs4793665 were associated with methotrexate hepatotoxicity grade 3-4. ABCC1 rs1045642 was associated with the risk of grade 3-4 thrombopenia and ABCC2 rs3740066 with the risk of neutropenia grade 3-4.

Conclusions

SNPs in the DNA single nucleotide repair and drug metabolisms pathways may serve as predictive biomarkers of response. Additionally, these polymorphisms may help tailor MAP neoadjuvant treatment to prevent toxicity and treatment delays.

Legal entity responsible for the study

Grupo Español de Investigación en Sarcomas GEIS.

Funding

Grupo Español de Investigación en Sarcomas GEIS.

Disclosure

A. Sebio Garcia: Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: PharmaMar; Financial Interests, Personal, Expert Testimony: PharmaMar, Deciphera, GSK; Financial Interests, Personal, Training: Boston Scientific; Non-Financial Interests, Personal, Other, Board of Directors member: GEIS. J. Martin-Broto: Financial Interests, Personal, Expert Testimony, Honoraria: Lilly, PharmaMar, Eisai, Bayer, Roche, Boehringer Ingelheim, Amgen; Financial Interests, Personal, Invited Speaker: PharmaMar; Financial Interests, Personal, Advisory Board, Speaker: Tecnofarma, Asofarma; Financial Interests, Institutional, Invited Speaker: PharmaMar, Eisai, Novartis, IMMIX Biopharma, Lixte, Karyopharm, Bayer, Celgene, Pfizer, BMS, Blueprint, Deciphera, NEKTAR, FORMA, Amgen, Daiichi Sankyo, Lilly, AROG, Adaptimmune, GSK, Ran Therapeutics, INHIBRX, Ayala Pharmaceuticals, Philogen, Cebiotex, PTC Therapeutics, Inc. and SpringWorks therapeutics. F.J. Bautista Sirvent: Non-Financial Interests, Personal, Principal Investigator: Sanofi; Financial Interests, Personal, Advisory Board: Bayer, Roche, Amgen, Eisai, EusaPharma; Financial Interests, Personal, Invited Speaker: Roche. J. Martinez-Garcia: Financial Interests, Personal, Advisory Board: AstraZeneca, Clovis, GSK-Thesaro, PharmaMar; Financial Interests, Institutional, Research Grant: Roche, GSK; Other, Personal, Other, Travel/accommodation/expenses for oncology meeting: PharmaMar, GSK-Thesaro, Pfizer. J. Martinez Trufero: Financial Interests, Personal, Advisory Board, Advisory Board meeting: PharmaMar, Eisai; Financial Interests, Personal, Invited Speaker: Roche, Eisai, Merck, Medicamenta, MSD, Ipsen; Financial Interests, Personal, Advisory Board, Advisory Board Meeting: GSK, Deciphera, Boehringer Ingelheim, Eisai; Financial Interests, Personal, Other, Meeting travel expenses: Roche, PharmaMar; Financial Interests, Institutional, Invited Speaker, Clinical trial: RAIN Therapeutics, Blueprint, Lilly, Kariopharm Therapeutics, Syneos Health, Boehringer Ingelheim, Ayala Pharmaceuticals, SynOx Therapeutics; Non-Financial Interests, Personal, Member of Board of Directors, Spanish group of Sarcoma Research: GEIS Group; Non-Financial Interests, Personal, Member of Board of Directors, Spanish Group of Head and Neck cancer Research: TTCC Group. C.M. Valverde Morales: Financial Interests, Personal, Advisory Board: PharmaMar, Bayer, GSK, Mundipharma, Lilly, Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Institutional, Invited Speaker, Clinical Trial: Adaptimmune, Karyopharm, Lilly, Foghorn Therapeutics, Ayala therapeutics, Inhibrx; Financial Interests, Institutional, Invited Speaker, Clinical Proyect: Bayer; Non-Financial Interests, Personal, Member of Board of Directors, President 2018-ongoing: GEIS- Spanish Sarcoma Group for Research. M.A. Vaz Salgado: Financial Interests, Personal, Advisory Board: Novocure; Financial Interests, Personal and Institutional, Invited Speaker: Pfizer. R.M. Alvarez: Financial Interests, Personal, Invited Speaker: PharmaMar; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, Novartis, Roche; Financial Interests, Personal, Other, conference registration: MSD Oncology; Financial Interests, Institutional, Invited Speaker: Roche; Financial Interests, Personal and Institutional, Invited Speaker: Janssen Oncology, Rain Therapeutics, Boehringer Ingelheim, Cebiotex, Novartis. All other authors have declared no conflicts of interest.

Background

Methionine (MET) addiction is a fundamental and general hallmark of cancer cells, including osteosarcoma cells, which is termed the Hoffman effect, due to overuse of exogenous MET for highly increased transmethylation reactions. The beta catenin/cyclin-D1 pathway is associated with tumor progression, including osteosarcoma. In the present study, we targeted MET addiction with the combination of methioninase (rMETase), and the MET analogue, ethionine (ETH), to eradicate osteosarcoma cells and down regulate beta catenin/cyclin-D1 pathway.

Methods

The efficacy of rMETase, ETH, or the combination of both rMETase and ETH on cell viability was compared with the WST-8 assay in 143B osteosarcoma cells and Hs27 normal human foreskin fibroblasts. The expression of beta catenin and cyclin-D1 was determined with Western immunoblotting and compared in 143B cells treated with/without rMETase, ETH, or the combination of both rMETase and ETH.

Results

143B cells were more sensitive toboth rMETase and ETH than Hs 27 cells, with the following IC₅₀: rMETase (143B: 0.2 U/ml, Hs27: 1.17 U/ml); ETH (143B: 0.29 mg/ml, Hs27: 0.82 mg/ml). 143B cells were synergistically eradicated by the combination of rMETase and ETH (p<0.001). In contrast, Hs27 fibroblasts were relatively resistant to the combination. The expression of both beta catenin and cyclin-D1 was significantly down-regulated by the combination of rMETase and ETH in 143B cells (p<0.001, p=0.04, respectively).

Conclusions

In the present study, the synergistic combination efficacy of rMETase and ETH on osteosarcoma cells was shown, in contrast to normal fibroblasts, which were relatively resistant. The combination of rMETase and ETH down regulated the expression of both beta catenin and cyclin-D1 in osteosarcoma cells, which may be epigenetically dysregulated via suppression of transmethylation reactions by the combination therapy. The present results indicate the combination of rMETase and ETH can be a potential future clinical strategy.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Pts with advanced or metastatic osteosarcoma may have a promising anti-tumor response to tyrosine kinase inhibitors (TKIs). This study aims to evaluate the efficacy and safety of FRU-based therapy for pts with advanced or metastatic osteosarcoma.

Methods

Pts with pathologically confirmed advanced or metastatic osteosarcoma were eligible. One group received FRU, while the other group received a combination of FRU with chemotherapy, bio-targeted therapy, or immune checkpoint inhibitors (ICIs). On day 1– 21 of a 28-day cycle, pts received a once-daily oral dosage of 5 mg FRU for adults or 4mg FRU for pts < 18 years old. Safety and efficacy of FRU based therapy were reviewed retrospectively.

Results

From 2021/10 to 2023/05, this retrospective study involved 26 pts, with a median follow-up duration of 7.5 months (mon). Among them, 6 were in the FRU monotherapy group and the other 20 in the combination therapy group. The median age of the participants was 25.8 years, (range: 8-63). A majority of 92.3% were diagnosed at stage IV, all of whom experienced lung metastasis. 84.6% having an ECOG performance status of 0-1 and 15.4% scoring 2. 80.8% had not received prior targeted therapy, and 42.3% treated as a second-line treatment or above (2L＋). The overall response rate was 11.5%, with a disease control rate of 96.2%. The median progression-free survival was 10.0 mon (95% CI: 5.9 mon–NA) overall, extending to 14.3 mon (95% CI: 5.9 mon–NA) with combination therapy, and 10 mon (95% CI: 1.3 mon-NA) with FRU monotherapy. Overall Survival data are still immature (not presented). 11 pts underwent surgery, with 10 (91%) achieving R0 resection and 1 (9%) having R1 resection, despite both were being initially deemed unresectable before the FRU-based therapy. In the combination therapy group, the most common grade 3 (G3) or higher adverse events (AEs) included leukopenia (40.0%), thrombocytopenia (15.0%), pneumothorax (5.0%), and anemia (5.0%). Conversely, pts in the monotherapy group experienced no G3 or higher AEs, with no severe AEs reported.

Conclusions

This real-world study revealed that FRU-based therapy is effective and safe for pts with advanced or metastatic osteosarcoma, including as a tumor conversion therapy.

Legal entity responsible for the study

The authors.

Funding

This study was funded by the Shanghai Pujiang Program (grant number 21PJD050); the National Natural Science Foundation of China (grant numbers 82272835); the Retrospective Clinical Study of the Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (grant numbers ynhg202110).

Disclosure

All authors have declared no conflicts of interest.

Background

We have observed that osteosarcoma often localizes and causes severe cortical bone destruction in the metaphysis, and it can extend intramedullary but does not invade the cortical bone structure in the diaphysis. In these cases, resecting a large bone segment or total bone replacement poses challenges and may yield less acceptable outcomes. To address this complexity, our approach involves using a combination of bone recycling with liquid nitrogen and megaprosthesis for reconstruction. We use nitrogen liquid to treat cancer cells in bone segments that are structurally intact, but where there is suspicion of malignant lesions in the root canal due to the spread of the primary tumor or skip lesions. This technique helps preserve the joint far from the tumor, avoiding radical surgery. Additionally, taking advantage of this graft increases the length of the root canal tunnel, facilitating the implantation of artificial materials.

Methods

This retrospective study included ten patients diagnosed with conventional osteosarcoma who underwent tumor resection and reconstruction using bone recycling with liquid nitrogen and megaprosthesis from 2022 to 2023.

Results

The average follow-up period was 14 months. The average duration for graft union was 5.75 months (range 4-7), and none of the patients required additional bone grafting. No local recurrence, metastasis, or wound infection was detected. Furthermore, there were no complications related to prosthetic or osteosynthesis autograft fractures, non-union, or aseptic loosening. The average MSTS score was 89% (range 86-92).

Conclusions

The surgical method combining artificial prosthesis and autografts treated with liquid nitrogen is an effective advancement in limb-sparing surgery for patients with large-sized bone cancer tumors that invade almost the total bone. It has shown significant benefits, including improved postoperative limb function, reduced treatment costs, and a lower complication rate and it could be a good alternative for total bone replacement or reconstruction with MGP or APC.

Legal entity responsible for the study

S.Q. Nguyen Tran Quang.

Funding

Has not received any funding.

Disclosure

The author has declared no conflicts of interest.

Background

Our research aimed to investigate the potential correlations between the extent of tumor necrosis and various factors, such as histopathological types, preoperative chemotherapy regimens, and other factors, in high-grade osteosarcoma patients treated at our institution.

Methods

We retrospectively reviewed 79 patients with stage IIB high-grade osteosarcoma treated in our institution from 2021 to 2023. Patient and treatment factors such as age, gender, tumor site, histological type, tumor size, tumor necrosis rate, chemotherapy regimens and cycles were recorded.

Results

Our 79 patients included 52 males and 27 females, ranging in age from 8 to 33 years (median, 15 years). The tumor necrosis rate ranged from 5 to 100% (median 85%). The tumor necrosis rate was greater than 90% in 21 patients, 70–90% in 30 patients, and less than 70% in 22 patients. Tumor necrosis rates were not significantly different when patients were grouped by age, gender, tumor site, tumor size, pathological type, or preoperative chemotherapy regimens.

Conclusions

In our study, no correlation was observed between the degree of tumor necrosis and both preoperative treatment regimens and histological types among osteosarcoma patients. Our findings underscore the importance of conducting future research with larger sample sizes to provide a more comprehensive understanding of these intricate relationships within the context of bone cancer pathology.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Primary bone sarcomas of the pelvis represent the most challenging problem in limb-saving surgery. Chondrosarcoma is the most common type, followed by osteosarcoma and Ewing's sarcoma.

Methods

We propose to study a group of patients with primary bone sarcoma of the pelvis treated with limb salvage surgery and analyze overall survival, local recurrence rates and functional outcomes. A retrospective review was performed, and all patients diagnosed with pelvic primary bone sarcomas at a specialized oncology centre in the Republic of Uzbekistan between 2017 and 2022 were analyzed. Patients treated with limb salvage surgery and with a minimum of 12-month follow-up for patients alive were included. The overall survival and the local recurrence rate were calculated for the assessment of oncological results. The associations with gender, age, histological grade, type of surgery, margins chemotherapy response and use of navigation were examined.

Results

Thirty-two patients were included in the study. The mean age was 37 years (range 16-58), and mean follow-up was 34 months (range 6-129). Among the tumor lesions on the first place patients with chondrosarcoma - 18 (56,25%), Ewing's sarcoma - 2 (6,25%), osteosarcoma - 8 (25%), GCT - in 4 (12,5%). Four (12.5%) tumors were histologically classified as high-grade sarcomas, four (12.5 %) as low-grade sarcomas and three (75 %) as dedifferentiated sarcomas. Cancer-specific overall survival was 37.5 % for 5 years and 31 % for 10 years. Local recurrence rate was 30 %. High-grade tumors and chemotherapy necrosis below 90 % were negative prognosis factor. Postoperative complication rate was 34.5 % (n:11), being deep infection the most prevalent (n:3). Reconstruction of the pelvis after an oncology resection for primary pelvic sarcomas increased the incidence of complication significantly (p < 0.001).

Conclusions

Patients with low grade pelvic sarcomas have a good prognosis after pelvic resection, but those with high grade sarcomas continue to have a poor prognosis. Independent prognostic factors are few; an adequate surgical margin is critical to prevent local recurrence, and the surgical stage is related to the risk of distant metastasis.

Legal entity responsible for the study

Oncology and Medical Radiology, Tashkent State Dental Institute, Tashkent, Uzbekistan.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Conventional osteogenic sarcoma is an aggressive bone tumour. High dose methotrexate-based regimen remains the cornerstone of management in osteosarcoma. However, the administration of High Dose MTX in osteosarcoma is a therapeutic challenge specially when facility for therapeutic drug monitoring is not available. Due to the practical difficulties with HD MTX, OGS 12 protocol, (a non-HD MTX) based 3 drug regimen was developed by Tata Memorial Hospital (TMH). Here, we are presenting a multicentric study on our treatment experience with OGS 12 protocol amongnon-metastatic conventional osteosarcoma of extremities.

Methods

We were treating all patients presenting with non-metastatic conventional osteosarcoma of extremity patient uniformly with OGS-12 protocol over last 2 years. A total of 22 patients were treated over 2 years on OGS-12 protocol. The Initial four cycle of chemotherapy were neo-adjuvant therapy. After resection, histopathology reports were collected and 4 cycles of adjuvant chemotherapy were given. Patients were followed up for end of treatment response with imaging and treatment related complications.

Results

A total of 22 patients were studied over 2-year duration. The median age of presentation was 16 years with range (8-27). Out of them 17(72.7%) were male patients and 5(22.7%) were female patients. At the end of neo-adjuvant chemotherapy, 17 patients underwent local limb salvage procedures whereas 5 patients underwent amputation. On histopathologic evaluation, specimen was tumour free among 41.66% and necrosis >90% was reported in 25% cases. Some patient underwent intra-corporal RT where chemotherapy response could not be assessed. Chemotherapy was well tolerated with some episodes of neutropenia’s without fever. There were no chemotherapy toxicity related deaths in the entire cohort.

Conclusions

In the real-world scenario, OGS-12 protocol appear feasible and well tolerated. However, in our experience, the pathological response was inferior to the original OGS-12 study from TMH. In scenarios, where High dose methotrexate feasibility is a challenge; the OGS-12 holds some promise. However, a future refinement in multidisciplinary treatment approach in tertiary care Institutes India is warranted.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.