Background

Desmoid tumors (aggressive fibromatosis) can negatively affect patients’ lives and overall quality of life due to the associated symptoms and complications. This analysis describes patient-reported symptom severity and impact of desmoid tumors on participants’ lives.

Methods

This is an analysis of the global, survey-based Desmoid Tumor Research Foundation (DTRF) Natural History Study using data collected from Sept 2017 to Aug 2023. Participants and/or their caregivers reported a desmoid tumor diagnosis, symptoms, and the impact on their lives. Symptom severity and impact were evaluated using a desmoid tumor-specific measure: the GOunder/DTRF Desmoid Symptom Scale (GODDESS© DTSS) and Impact Scale (GODDESS DTIS), where higher scores indicate worse symptoms or more severe impact (Qual Life Res 2023;32:2861). Mean scores for participants with a current tumor versus those without were compared using Analysis of Variance (ANOVA); other comparisons were descriptive.

Results

367 participants completed the GODDESS surveys (median age, 39 years). Participants reported a high symptom burden, with an overall total symptom mean score of 4.1 out of 10. Item scores for pain, fatigue, and impaired mobility were significantly higher (worse) in participants with a current tumor versus those without (Table). Desmoid tumors had a negative impact on the participants’ reported physical, sleep, and emotional domain scores (Table). Participants with abdominal wall desmoid tumors reported numerically higher (worse) symptom scores for pain, fatigue, and emotional items versus participants with intra-abdominal, extra-abdominal, and/or other tumor locations.

Table: 148P

GODDESS DTSS and DTIS domain scores

Conclusions

The pain and impaired physical functioning and emotional well-being reported by participants can have a negative impact on their lives. Effective care of patients with desmoid tumors depends on understanding the real-world burden and impact of these tumors.

Editorial acknowledgement

Writing and editing support was provided by Rebekka Harding-Smith and Jessica Warren of IQVIA with funding from SpringWorks Therapeutics, Inc.

Legal entity responsible for the study

Desmoid Tumor Research Foundation.

Funding

SpringWorks Therapeutics.

Disclosure

K.A. Mercier: Financial Interests, Institutional, Research Grant: SpringWorks Therapeutics, Inc.; Non-Financial Interests, Personal, Principal Investigator: Desmoid Tumor Research Foundation. L. Hernandez: Financial Interests, Institutional, Research Grant: SpringWorks Therapeutics, Inc.; Non-Financial Interests, Personal, Other, Executive Director: Desmoid Tumor Research Foundation. A. Lucas: Financial Interests, Institutional, Research Grant: SpringWorks Therapeutics, Inc.; Non-Financial Interests, Personal, Other, Staff Associate: Desmoid Tumor Research Foundation. T. Bell, B. Tumminello, S. Zhou: Financial Interests, Personal, Full or part-time Employment: SpringWorks Therapeutics, Inc..

Background

Patients with desmoid tumors (aggressive fibromatosis) have several treatment options, and individual experiences are vast and varied. This analysis describes the treatment landscape for patients with desmoid tumors after diagnosis.

Methods

This is a descriptive analysis of the global, survey-based Desmoid Tumor Research Foundation (DTRF) Natural History Study using data collected from Sept 2017 to Aug 2023. Participants and/or their caregivers reported desmoid tumor diagnosis and treatment. The N values vary for these analyses due to incomplete data.

Results

Of the 383 participants who completed the treatment survey (median age, 39 years), 58% (223/383) reported having a current tumor. Among the 43% (163/383) of participants who received surgery to treat desmoid tumors, 63% (103/163) reported subsequent continued tumor growth or recurrence. Among those who responded to surgical questions, 43% (50/115) reported receiving surgery both before and after a confirmed diagnosis. Surgery was reported as the 1^st-line treatment for 59% (74/126) of participants who received multiple lines of treatment. 76% (281/369) of participants received systemic therapy after diagnosis, including NSAIDS (40%), tyrosine kinase inhibitors (32%), chemotherapeutics (31%), and hormone antagonists (17%) (Table). Participants reported continued tumor growth whether they received prior treatment (43%; 92/216) or not (54%; 70/129).

Table: 149P

Systemic therapies (any line; N = 281)

Conclusions

Surgery was the most prevalent 1^st-line therapy for participants with multiple treatments, with a high rate of recurrence after surgery. No trends were reportedfor use of systemic treatments. With the FDA approval of nirogacestat for the treatment of desmoid tumors, clear guidelines for sequencing surgery and systemic therapies are needed for optimum patient care.

Editorial acknowledgement

Writing and editing support was provided by Rebekka Harding-Smith and Jessica Warren of IQVIA with funding from SpringWorks Therapeutics, Inc.

Legal entity responsible for the study

Desmoid Tumor Research Foundation.

Funding

SpringWorks Therapeutics, Inc.

Disclosure

K.A. Mercier: Financial Interests, Institutional, Research Grant: SpringWorks Therapeutics, Inc.; Non-Financial Interests, Personal, Principal Investigator: Desmoid Tumor Research Foundation. L. Hernandez: Financial Interests, Institutional, Research Grant: SpringWorks Therapeutics, Inc.; Non-Financial Interests, Personal, Other, Executive Director: Desmoid Tumor Research Foundation. A. Lucas: Financial Interests, Institutional, Research Grant: SpringWorks Therapeutics, Inc.; Non-Financial Interests, Personal, Other, Staff Associate: Desmoid Tumor Research Foundation. T. Bell, A.B. Oton, S. Zhou: Financial Interests, Personal, Full or part-time Employment: SpringWorks Therapeutics, Inc..

Background

Desmoid tumours (DT) are benign, although locally aggressive, monoclonal fibroblastic proliferations; despite their indolent pathology, their behaviour can be unpredictable and some cases can be very symptomatic. In those unresectable and symptomatic cases, sorafenib has shown some meaningful clinical activity compared to placebo in a phase III trial.

Methods

Retrospective cohort analysis of 19 patients with symptomatic DT treated with sorafenib as 1^st-line treatment (2020-2023) until progression and/or unacceptable toxicity. Analysis of radiological response according to RECIST v1.1, toxicity rates according to CTCAE v5.0 and clinical response defined as radiological response and/or symptomatic improvement in pain after 4 months of treatment.

Results

19 patients, 62.5% female. Median age 37 years (range 18-80 years). Familiar adenomatous polyposis in 31.3%. Retroperitoneal in 25%, limbs in 18.8%, abdominal wall in 50%, head and neck region 6.3%, 50% de novo disease. All patients symptomatic and deemed unresectable without undue morbility. Overall response rate of 43.8% (37.5% partial response and 6.3% complete response), stable disease in 49.1%; only 1 progression (5.3%). 75% reported toxicity, 68.75% grade 1-2 and 18.75% grade 3. The most frequent toxicity seen was fatigue (50%) and palmo-plantar erythrodisestesia (31.25%). 2 patients required dose reduction and 1 patient treatment interruption due to toxicity. Clinical benefit was seen in 77.8% of patients, in most cases secondary to an improved analgesic control. 68.75% of patients reported clinical improvement in pain after four months of treatment, with less analgesic requirements or even suspension of all painkillers. No patients needed third-step opioid treatment after sorafenib introduction.

Conclusions

In our series, sorafenib is a useful and cost-effective treatment for patients with symptomatic DT. Most patients had a radiological response and symptomatic progression was very uncommon. Clinical benefit was seen in a higher percentage of patients compared to the radiological benefit; RECIST criteria may not be the best way to evaluate these responses. We observed a lower grade 3-4 toxicity rate compared to the pivotal phase III, which was easily manageable.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Mesothelioma in tunica vaginalis testis (MTVT) is extremely rare and less than 300 cases have been reported worldwide, the vast majority being case reports. We present characteristics and treatment outcome in a consecutive cohort from a national treatment program in Denmark (population 5.8 million).

Methods

The oncological treatment of MTVT is centralized to one national center due to the rarity of this disease, and diagnosis is verified by the Dept of Pathology at the center. Patients (pts) are followed for totally five years, then through the Centralized Person Register in Denmark until death. No pts are lost to follow-up. Previously we reported results on fewer pts, while this is an enlarged cohort with updated results on treatment, recurrence, and survival.

Results

This cohort is constituted of 10 consecutive pts diagnosed 2016 through 2023, with updates on January 2024. Annual incidence was 1.4 pts out of 5.8 million Inhabitants, i.e. 0.02 cases/100,000. Median age was 73 years (range 26-86 years), and 6 pts (60%) had had previous cancers [male breast cancer, neuroendocrine large intestine, prostate, squamous cell skin, and basocellular skin (2 cases), respectively]. Only 20% reported prior asbestos exposure. Nine pts had epithelioid subtype while one had biphasic with 40% sarcomatoid component. Ki67 index ranged from 5% to 60%. All received primary scrotal surgery with only three having R0 resection (no microscopic residual disease). Repeated surgery was possible in three cases, resulting in R0 resection, while radiotherapy with curative intention was used in two cases. One pt had advanced disease. Seven received adjuvant chemotherapy (platinum + pemetrexed). Four (40%) had disease recurrence, and two (20%) have died. Median PFS is 23 months (range 3+ - 75+ months), and median OS 47 months. Genomic evaluation is ongoing.

Conclusions

MTVT is extremely rare with an incidence of 0.02 cases/100,000. 70% of pts did not achieve initial R0 resection, but use of re-surgery, radiotherapy with curative intent, and adjuvant chemotherapy led to median OS of 47 months. Thus, prognosis may be somewhat better than for pleural and peritoneal mesothelioma. The rarity of MTVT argues for centralization of treatment.

Legal entity responsible for the study

J.B. Sørensen.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

A variety of recurrent chromosomal translocations have been characterized from rare cancer patient tumors, which result in fusion oncogenes that play essential roles in disease pathogenesis. For instance, the t(11:22)(q24:q212) translocation in Ewing’s sarcoma fuses the transcriptional regulatory domains of EWSR1 to the DNA binding domain of the FLI1 gene, causing aberrant FLI1 activation and expression. However, the roles of many fusion oncogenes in rare cancers are unknown, including why specific fusions recur in certain diseases arising from different tissues. We postulate that the tissue-specificity of rare cancer fusion oncogene incidence is driven by a mix of positive selection in permissive tissues and stress-induced negative selection in non-permissive tissues.

Methods

We performed a combination of computational and fusion gene overexpression studies.

Results

Meta-analysis of fusion gene partnerships found in rare cancers suggests that diseases arising from the same tissue tend to select fusions from overlapping gene sets. Overexpressing EWSR1-CREB1 in a 'non-permissive' tissue (mammary epithelial cells) led to apoptosis, whereas 'native' fusions found in breast cancers could be stably expressed without causing cellular stress. To further investigate this phenomenon, we titrated the expression level of 4 fusion oncogenes using a doxycycline inducible promoter in healthy cell lines derived from different tissues and conducted bulk mRNA sequencing across a range of fusion doses. We then compared our in vitro data to tumors containing each fusion to analyze differences in transcriptomic landscapes. We found that EWSR1-CREB1 induced an inflammatory response (such as upregulation of IL6) and reduced cell cycle gene expression in a dose-dependent manner in mammary epithelial cells. Tumors containing EWSR1-CREB1 revealed partially similar gene expression profiles, including upregulation of inflammatory signaling.

Conclusions

However, how these profiles may lead to tumorigenesis in soft tissues but not mammary tissues is unknown. Further analyses of fusion oncogene effects across tissues will reveal key insights to the role fusions play in rare cancer disease pathogenesis, and their restriction to certain cell types during tumorigenesis.

Legal entity responsible for the study

The authors.

Funding

UMass Chan Medical School.

Disclosure

All authors have declared no conflicts of interest.

Background

Giant cell tumor (GCT) is an intermediate, locally aggressive primary bone tumor. In addition to local therapy, new drugs for the treatment of this disease have become available. Denosumab, which was originally used to treat osteoporosis and the solid tumor metastases to bone, eventually began to be used to treat giant cell bone tumors. In treatment of GCT, denosumab was used as the only remedy in patients with inoperable tumors, and was also used before surgery to reduce the size of the tumor and to preserve the joint. To evaluate the effectiveness of denosumab, while using in the preoperative period of GCT treatment.

Methods

A study was conducted of 49 patients with GCT of tubular limb bones who received denosumab before surgery, and 60 patients (retrospectively evaluated, without using denosumab in our hospital from 2015 to 2019). Propensity scores were compared in a 1:1 ratio between the groups receiving denosumab and the control group to minimize possible selection bias; recurrence rates, limb function, and surgical impairment were compared between the two groups.

Results

The recurrence rate after 3 years in the denosumab group and the control group was 12.2% and 23.3%, respectively. In the denosumab group, 100% (n=49) of patients underwent surgical treatment. In 44 patients treated with denosumab, the indices of limb joint preservation were 89.8% and 36.6% in 22 control patients. Postoperative MSTS scores were higher in patients in the denosumab group than in the control group.

Conclusions

Preoperative treatment with denosumab reduced the risk of local recurrence of GCT. Preoperative treatment with denosumab is indicated for patients with advanced GCT to facilitate surgical treatment and preserve the joint. Denosumab remains a highly effective treatment for patients with GCT of bone.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Giant cell bone tumors (GCT) are primary locally aggressive neoplasms that occasionally manifest with distant metastasis. Denosumab, a fully humanized monoclonal antibody against the RANK ligand, is indicated for its effectiveness in the treatment of unresectable or metastatic GCT.

Methods

An observational, descriptive, cross-sectional, and retrospective study was conducted at the Instituto Nacional de Enfermedades Neoplásicas de Lima, Peru evaluating patients diagnosed between 2018 and 2022 who received neoadjuvant denosumab treatment.

Results

In this study of 34 patients with an average age of 30.5 years, predominantly females (55.9%), the average time from symptom onset to diagnosis was 7 months. Common symptoms included pain (91.2%), swelling (64.7%), and fractures (14.7%). The most frequent tumor locations were the femur, fibula, sacrum, and tibia, each accounting for 11.8%. No metastases were observed at onset. Soft tissue involvement occurred in 50% of patients, joint involvement in 17.2%, fractures in 13.1%, and adjacent bone involvement in 17.2%. Radiologically, 8.8% had type II disease, 88.3% had type III by the Campanacci classification, and 2.9% were undetermined. By Enneking classification, 2.9% had type I, 88.2% had type III, and 8.9% were undetermined. Regarding neoadjuvant Denosumab treatment, 35.35% experienced adverse effects, mostly grade 1, including bone pain, hypocalcemia, and anemia. Surgical intervention was undergone by 58.8%, with 81% opting for conservative surgeries. Only 20.6% received radiotherapy. Follow-up studies showed 96.6% with no progression, 97.1% remained alive, and 2.9% resulted in death.

Conclusions

This is the first study in Peru that provides a detailed perspective on neoadjuvant Denosumab treatment in patients with GCT. Treatment with denosumab has allowed conservative surgeries to be performed in the majority of previously inoperable patients. These findings support the feasibility and effectiveness of the neoadjuvant approach with Denosumab, with a low incidence of significant adverse effects.

Legal entity responsible for the study

Instituto Nacional de Enfermedades Neoplásicas de Lima, Peru.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Recurrent respiratory papillomatosis (RRP) is a benign neoplasm of the respiratory system caused by the human papilloma virus. A prospective, multi-center, single-arm, multi-cohort, phase 2 trial was conducted to investigate the efficacy and safety of angiogenesis inhibition with bevacizumab or programmed death 1 blockade with sintilimab in patients with aggressive RRP. Herein, we report results of the pediatric cohort treated with bevacizumab.

Methods

Eligible patients were aged 18 years old or younger and diagnosed with RRP. Patients with an aggressive course had lung involvement or underwent frequent surgeries (≥ 4 times in the previous 12 months). All patients received systemic bevacizumab treatment for up to 6 months (investigator’s choice of 5mg/Kg on day1, 14 days per cycle; or 7.5mg/Kg on day1, 21 days per cycle). The primary endpoint was the change in the number of surgeries per 12 patient-months before and after bevacizumab treatment. Secondary endpoints included objective response rate and adverse events (AEs).

Results

A total of 20 patients were treated. The median age was 5 years old (range 2-10), with 70% of patients being male. Three patients (15%) had undergone tracheotomy, and eight patients (40%) had pulmonary papilloma. The median number of surgeries one year before treatment was 4.5 (range 0-12). Twelve patients (60%) had at least 12 months of follow-up data available. Using each patient's surgical history as their own control, we observed a significant reduction in the number of surgeries required after bevacizumab treatment (p＜0.001). However, papilloma recurrence/progression occurred within a median duration of 4.9 months (range 1.2-10.8) after discontinuation of bevacizumab. Subsequent response was observed in all patients when bevacizumab treatment was resumed. According to RECIST 1.1 criteria, all evaluable lesions showed an objective response. The most common treatment-related AEs of any grade were lip cyanosis (15%) and hand-foot syndrome (10%). No ≥ grade 3 AEs or treatment-related death occurred.

Conclusions

Systemic bevacizumab is a safe and effective alternative to frequent surgical treatment in pediatric patients with aggressive RRP.

Clinical trial identification

ChiCTR2200059627.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Sensitivity of Next-Generation Sequencing (NGS) methods to tissue sample quantity and quality is insufficiently reported in rare tumors. We conducted a retrospective study to estimate the NGS failure rate due to insufficient quantity or quality of material in rare tumors and to identify its predictors.

Methods

Patients with sarcomas, rare carcinomas, and rare melanomas who underwent NGS at SQCCCRC between January 2022 and October 2023 were eligible. Clinicopathological and NGS-related data were extracted from clinical charts and quantitatively described. We constructed a univariable logistic regression models with the outcome variable Insufficient quantity or quality of material, and the following explanatory variables: Assay [whole exome sequencing (WES) vs. targeted panel], Sampling method (surgery vs. biopsy), Source tissue (bone vs. soft tissue), and Storage time.

Results

We identified 102 NGS reports from 86 patients with sarcomas (73.3%), rare carcinomas (16.3%), and rare melanomas (10.5%). The median age was 40 years, interquartile range (IQR) = 23-61 years. Samples were obtained by biopsy (51%) and surgery (48%) from soft tissue (92.1%) or bone (7.9%) lesions. The median storage time was 2.5 months (IQR = 1.3 - 4.6). Targeted sequencing and WES were used in 39.2% and 60.8% of reports, respectively. Material quantity or quality was insufficient in 14.7% of tests and 4.7% of patients. Repeated testing was successful in 7 out of 8 patients. WES was significantly associated with higher probability of NGS failure due to low quantity or quality of material as compared to targeted panel (OR = 11.4, 95% confidence interval = 1.4 - 90.4, p = 0.022). No other variable significantly predicted NGS failure.

Conclusions

Our results suggest that the overall, the NGS failure rate due to sample quantity or quality issues is low. WES demands significantly higher sample quantity and quality compared to targeted panels. Retesting can often overcome quantity or quality issues.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Myeloid sarcoma (MS) is a rare hematological malignancy with a reported incidence of 2.5-9.1%. In most cases, MS arises with Acute Myeloid Leukemia (AML) and only very few cases reported as a first primary MS. It is unclear if MS should be considered as a manifestation of hematological malignancy, or an independent malignancy. So this study aims to evaluate the clinicopathological features of myeloid sarcoma and assess the risk of developing multiple primary tumors to add an updated evidence to the literature and understand MS behavior for better management.

Methods

Data of patients diagnosed with primary MS between 2000 and 2020 were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. We used MP-SIR session with multiple outcome analysis to calculate the standardized incidence ratio (SIR), as observed/expected (O/E) and was considered significant if P<0.05, Excess Absolute Risk (EAR) per 10,000, and 95% confidence interval (CI). SPSS version 23 was used for data analysis.

Results

Out of 411 patients with primary MS, the mean age was 50 (SD=22.64). Subcutaneous primary MS was the most common (30%) followed by lymph nodes and gastrointestinal MS (17% and 10.5%). About 94 patients developed second primary malignancies with overall O/E of 7.93 (P<0.05, 95%CI: 0.0971%-0.0641%, EAR=533.2). About 60 patients (14%) with primary MS had high risk for developing developed Acute Non-Lymphocytic Leukemia (ANLL) (O/E=520.91 P<0.05, 95% CI=3.97%-6.7%, EAR=388.69) with increased risk in the interval 0-11 months (O/E=1697.27, P<0.05, 95%CI: 22.76-12.33, EAR=1488.97). About 13.3% of patients with primary MS developed AML with EAR of 356.31 (O/E=530.84, P<0.05%, 95%CI: 6.9-3.99) and 6 patients developed Non-Hodgkin Lymphoma (NHL) (O/E=11.77, P<0.05, 95%CI: 0.246-0.0432, EAR=35.63).

Conclusions

MS is a very rare malignancy. This study showed difference in behavior of MS and first primary MS, with different presentation sites. Primary MS showed a significant risk of developing ANLL within the 0-11 months interval, most commonly AML, as well as a significant risk of developing NHL. This highlights the importance of screening for hematological malignancies once MS is diagnosed for early detection and better management.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.