Background

Cervical cancer is the 4th most common cancer in women in the world, and the 9th overall. External beam radiotherapy (EBRT) with concurrent cisplatin followed by brachytherapy forms the standard of care for advanced cervical carcinoma. High dose-rate (HDR) intracavitary brachytherapy (ICBT) for cervical cancer is now well established because of its numerous advantages. This study aimed to assess and compare the local control and toxicities between HDR ICBT with 7.5 Gy per fraction in three fractions (Control Arm) and 9 Gy per fraction in two fractions (Study Arm) after EBRT in treatment of carcinoma cervix.

Methods

A total of 180 patients meeting the inclusion criteria were included in the study and randomly assigned to the 2 arms of 90 patients each. Arm A received HDR ICBT with a dose of 7.5 Gy per fraction, 1 fraction per week for 3 fractions and Arm B received HDR brachytherapy 9 Gy per fraction , 1 fraction per week for 2 fractions. Patients were evaluated monthly for assessment of local control and toxicities. Statistical evaluation was done with mean, percentage and frequency using Chi Square, and Student T test.

Results

A total of 180 patients were analysed with 90 patients in each arm. All patients had received EBRT with a dose of 50 Gy in 25 fractions. 91% of the patients received concurrent chemotherapy to a mean of 4 cycles. Complete response was seen in 80 patients (89%) in arm A and in 87 patients (96.7%) in arm B. 4 patients in arm A and 2 patients in arm B has local recurrence. Grade 2 and above proctitis was seen in 3.3 % of the patients in arm A and in 6.6 % of the patients arm B. 1 patient in arm A and 1 patient in arm B had grade 1 hematuria.

Conclusions

This study, with 9 Gy in 2 fractions showed a better local control of the tumour till 6 months when compared to 7.5 Gy in 3 fractions. Although there was no statistical significance, our study also suggested that the rate of rectal toxicities was slightly higher in the 9 Gy arm when compared with 7.5 Gy arm, which could be managed medically. The study also highlighted the need for completion of total treatment of EBRT and brachytherapy within 60 days to reduce recurrence rates.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Recent studies have indicated that N6-methyladenosine (m6A) methylation modification and regulators play a critical role in human cancers. However, the possible functions of m6A and its regulators on cervical cancer (CC) tumorigenesis are still unclear. This study explored the function and mechanism of METTL3 (methyltransferase-like 3) and its downstream target oncogenes in CC.

Methods

First, we investigated the expression of m6A regulator gene (METTL3) mRNA and proteins by qRT-PCR and western blot assays in cervical cancer cell lines. In addition, we performed a series of functional studies to investigate the oncogenic role of METTL3 and its downstream target oncogenes in CC cells. m6A-methylated RNA immunoprecipitation sequencing (MeRIP-seq) was used to screen the target genes of METTL3. m6A level of mRNA was measured by an m6A-RNA methylation quantification kit.

Results

The level of m6A RNA methylation was significantly increased in CC cells. METTL3 is a major catalytic enzyme involved in the abundant m6A RNA modification and plays an important role in carcinogenesis. We observed that METTL3 expression was frequently up-regulated in CC cell lines. Functional studies with METTL3 knockdown in CC cells dramatically inhibited cellular proliferation, migratory potential and colony formation abilities. Mechanistically, MeRIP-seq illustrated that Yin-Yang 1 (YY1) as a target of METTL3. Recent studies reported that YY1 is highly expressed in different types of cancer, whereby it is associated with cell proliferation, metastasis, survival, metabolic reprogramming, and poor patient survival. The TCGA data analysis revealed that YY1 mRNA and protein were highly expressed cervical cancer tissues. In addition, Pearson correlation analysis showed that highly expressed METTL3 was positively correlated with YY1 expression. Thus, the METTL3/m6A/YY1 axis promotes cervical carcinogenesis.

Conclusions

Taken together, our findings demonstrated the oncogenic role of METTL3 in cervical cancer by regulating YY1 expression in an m6A-dependent manner and provide a new insight into the pathogenesis of CC. Hence, METTL3/m6A/YY1 axis represents a potential target for CC therapy.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

IL-8 gene polymorphisms are involved in the carcinogenesis of many malignant neoplasms, but their role in the development of cervical cancer (CC) has not been fully elucidated. The aim of the study was to evaluate the relationship between the presence of IL-8 gene polymorphism (845 T/C) and the development of severe cervical intraepithelial neoplasia (CIN) and cervical cancer.

Methods

The study included 21 patients with CIN III and stage Ia FIGO cervical cancer and 20 healthy women (control). The study was conducted in accordance with the requirements of the USU Ethics Commission (No. 9 dated September 15, 2016). We determined the level of IL-8 (CJSC Vector-Best-Volga, Russia) using ELISA in neutrophil lysate and serum. For the analysis of SNP IL-8 845 T/C (rs2227532), the samples were genotyped by PCR with restriction enzyme analysis using Vsp I endonuclease (SibEnzyme, Russia). The digested PCR products were separated by electrophoresis in 1.5% agarose gel. Statistical processing was carried out using Statistica 13 (StatSoft).

Results

We found that the -845C* allele was more common in the group with cervical lesions (76.2%) than in the control group (10%) (chi-square=18.223, p=0.001). The risk of developing CIN increased in the presence of the -845C* allele (OR=28.8, 95% CI 4.892-169.546, p=0.038). The level of IL-8 in neutrophils in CIN (p=0.015) was lower than that in the control. At the same time, the level of IL-8 in neutrophils and serum in CIN is not associated with the frequency of occurrence of the -845T* and -845C alleles.

Conclusions

The presence of IL-8 gene polymorphism (845 T/C) is associated with CIN.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Currently, there is a paucity of data evaluating post-treatment human papillomavirus (HPV) clearance in patients who receive definitive chemoradiotherapy (CRT) for the treatment of locally advanced cervical cancer and its correlation with oncological outcomes.

Methods

We included patients with histopathologically-confirmed locally advanced cervical cancer who were amenable to definitive CRT and brachytherapy. The subjects underwent a pretreatment liquid-based cytology to perform mRNA-based testing for HPV infection. We repeated the HPV testing 6 weeks after the patients completed their treatment. Response to treatment was evaluated with clinical examination, cervical cytology, and a contrasted pelvic MRI.

Results

Over a 6-month period, 23 patients were included in our study. The mean age at diagnosis was 65 years. Regarding clinical stage (CS), 13% of cases were classified as CS IIA1 non-bulky disease, whereas 87% were classified as CS IB2 to IVB disease. HPV infection was reported in 87% of cases, from which 34% presented more than one HPV genotype. The most prevalent HPV genotype was 16 (48%), followed by 72 (13%) and 18 (9%). Sixteen patients completed the treatment protocol and underwent evaluation for clinical response and post-treatment HPV testing. A complete response (CR) was documented in 81% of cases. Of the sixteen evaluable patients, 13 were initially positive for HPV infection; viral clearance was documented in 8 cases (62%). From all patients who achieved HPV clearance, we documented CR in 54% of cases, whereas only 31% of patients who did not achieve HPV clearance presented a CR. After analysis, we did not find a statistically significant correlation between HPV clearance and CR. HPV clearance was neither correlated with the CS at diagnosis.

Conclusions

Despite the high rate of post-treatment HPV clearance reported among our patients with locally advanced cervical cancer, we found no correlation with achieving a CR. The role of HPV clearance in this setting needs to be further evaluated to determine its value in clinical response and other oncological outcomes like disease-free interval or overall survival.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Advanced/recurrent cervical cancer has limited therapeutic options, with a median progression-free survival after the failure of systemic treatments ranging between 3.5 and 4.5 months. Here, we reported our preliminary experience in the use of BYL719 (alpelisib) in advanced/recurrent cervical cancer after failure of at least 2 lines of treatment.

Methods

This is a prospective trial testing the role of alpelisib in PIK3CA mutated patients. The Fondazione IRCCS Istituto Nazionale dei Tumori di Milano (Italy) approved this prospective investigation (IRB number 20205720).

Results

From April 2020 to September 2020, 17 consecutive patients with recurrent cervical cancer had next-generation sequencing (NGS). Patients harboring PIK3CA mutation were included in the study. Overall, six patients were included in the study. All patients had been treated with at least 2 previous lines of systemic treatment: 3 patients received >2 prior lines of treatment in the recurrent or metastatic setting; 60% had received prior bevacizumab in combination with chemotherapy. All patients started alpelisib at the daily dosage of 300 mg. Investigator-assessed confirmed objective response rate (ORR) was 33%. The disease control rate (DCR) was 100%. According to RECIST 1.1, two patients had a partial response (PR), and four patients had stable disease (SD). No complete response was observed. The mean duration of response (DOR) was 11.5 (SD 3.75) months; five patients had PR lasting for >9 months. One patient stopped the treatment at 0.82 months due to the onset of a grade 2 adverse event (AE) (skin rash). Grade 3 treatment-related AEs included: lymphoedema (n=1, 20%) and rash (n=1, 20%). No treatment-related grade 4-5 AEs occurred.

Conclusions

Alpelisb seems associated with promising anti-tumor activity in cervical cancer patients harboring PIK3CA mutation. Further prospective trials are needed to assess the safety and effectiveness of alpelisib in PIK3CA-mutated pre-treated cervical cancer.

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 prognosis of locally-advanced unresectable or metastatic (LA/M) cervical and uterine cancer remains poor, with HER2 alterations occurring in 0.5-21% of cervical cancers and 2-80% of uterine cancers, respectively. Tucatinib (TUC), a highly selective HER2 directed TKI, is approved in combination with trastuzumab (Tras) and capecitabine in multiple regions for HER2+ metastatic breast cancer and is being investigated in other HER2+ cancers, including LA/M cervical and uterine cancer. SGNTUC-019 (NCT04579380) is an open-label, international phase II basket study evaluating TUC and Tras in adult patients (pts) with LA/M HER2+ or HER2-mutated solid tumors.

Trial design

SGNTUC-019 will evaluate TUC and Tras in pts with previously treated, LA/M solid tumors that display HER2 overexpression/amplification or activating mutations, including HER2+ cervical and uterine cancer cohorts. Pts will receive TUC 300 mg PO BID and Tras 8 mg/kg IV on Cycle 1 Day 1 and 6 mg/kg q21 days from Cycle 2 Day 1. HER2+ cervical and uterine cancer cohorts will enroll 12 pts each with potential for expansion up to 30 pts. Pts with HER2-mutated cervical, uterine, and other gynecologic cancers may enroll in a pooled cohort of 30 pts with HER2-mutated solid tumor types. Eligible pts must have progressed on or after their last systemic therapy, with prior platinum-based chemotherapy ± bevacizumab required in pts with metastatic cervical cancer. Pts must have ECOG PS ≤1, adequate organ function, and have not received HER2-directed therapy; pts with uterine serous carcinoma may have received prior Tras. HER2 alterations can be demonstrated by HER2 overexpression/amplification in tumor tissue by prior IHC/ISH, or by HER2 amplification/mutation in a prior or on-study NGS assay of ctDNA or prior tissue NGS assay. The primary endpoint is confirmed ORR per investigator. DCR, DOR, PFS, OS, safety, and PK are secondary endpoints. Disease assessments per RECIST 1.1 will occur q6 weeks for 24 weeks, then q12 weeks. QoL will be evaluated q2 cycles using EQ-5D-5L. Enrollment is now open in Europe, the US, and Asia Pacific.

Clinical trial identification

NCT04579380.

Legal entity responsible for the study

Seagen Inc., Bothell, WA, USA in collaboration with Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Ind., Kenilworth, NJ, USA.

Funding

Seagen Inc., Bothell, WA, USA in collaboration with Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Ind., Kenilworth, NJ, USA.

Disclosure

D. O'Malley: Financial Interests, Personal and Institutional, Research Grant, Consultancy: AbbVie; Financial Interests, Personal and Institutional, Research Grant, Consultancy: Agenus; Financial Interests, Personal, Other, Consultancy: Ambry; Financial Interests, Personal, Other, Consultancy: Arquer; Financial Interests, Personal and Institutional, Research Grant, Consultancy: AstraZeneca; Financial Interests, Personal, Other, Consultancy: Celsion; Financial Interests, Personal and Institutional, Research Grant, Consultancy: Clovis; Financial Interests, Personal, Other, Consultancy: Corcept; Financial Interests, Personal and Institutional, Research Grant, Consultancy: Eisai; Financial Interests, Personal, Other, Consultancy: Elevar; Financial Interests, Personal and Institutional, Research Grant, Consultancy: Genentech/Roche; Financial Interests, Personal and Institutional, Research Grant, Consultancy: GOG Fnd; Financial Interests, Personal and Institutional, Research Grant, Consultancy: Immunogen; Financial Interests, Personal and Institutional, Research Grant: Inc. Research; Financial Interests, Personal and Institutional, Research Grant: InVentiv Health; Financial Interests, Personal and Institutional, Research Grant, Consultancy: Iovance; Financial Interests, Personal and Institutional, Research Grant, Consultancy: Janssen; Financial Interests, Personal and Institutional, Research Grant, Consultancy: Johnson & Johnson; Financial Interests, Personal, Other, Consultancy: Merck; Financial Interests, Personal and Institutional, Research Grant, Consultancy: Mersana; Financial Interests, Personal, Other, Consultancy: Myriad; Financial Interests, Personal, Other, Consultancy: Novartis Novocure; Financial Interests, Personal, Other, Consultancy: Regeneron; Financial Interests, Personal, Other, Consultancy: Roche; Financial Interests, Personal, Other, Consultancy: Rubis; Financial Interests, Personal, Other, Consultancy: SDPOnc; Financial Interests, Personal, Other, Consultancy: Seagen Inc.; Financial Interests, Personal, Research Grant, Consultancy: Amgen; Financial Interests, Personal, Other, Consultancy: Inxmed; Financial Interests, Personal and Institutional, Research Grant: Ajinomoto; Financial Interests, Personal and Institutional, Research Grant: Array; Financial Interests, Personal and Institutional, Research Grant: BMS; Financial Interests, Personal and Institutional, Research Grant: Cerulean; Financial Interests, Personal and Institutional, Research Grant: EMD Serono; Financial Interests, Personal and Institutional, Research Grant: Ergomed; Financial Interests, Personal and Institutional, Research Grant: GenMab; Financial Interests, Personal and Institutional, Research Grant: Ludwig Cancer Research; Financial Interests, Personal and Institutional, Research Grant: Merck; Financial Interests, Personal and Institutional, Research Grant: New Mexico CCA; Financial Interests, Personal and Institutional, Research Grant: Novocure; Financial Interests, Personal and Institutional, Research Grant: PRA Int'l; Financial Interests, Personal and Institutional, Research Grant: Regeneron; Financial Interests, Personal and Institutional, Research Grant: SDPOnc; Financial Interests, Personal and Institutional, Research Grant: Seagen Inc.; Financial Interests, Personal and Institutional, Research Grant: Serono; Financial Interests, Personal and Institutional, Research Grant: Stemcentrx; Financial Interests, Personal and Institutional, Research Grant: Tarveda; Financial Interests, Personal and Institutional, Research Grant: Tesaro/GSK; Financial Interests, Personal and Institutional, Research Grant: Tracon Pharma; Financial Interests, Personal and Institutional, Research Grant: VentiRx; Financial Interests, Personal and Institutional, Research Grant: Yale University; Financial Interests, Personal, Invited Speaker: Sorrento; Financial Interests, Personal, Other, Consultancy: Takeda; Financial Interests, Personal, Other, Consultancy: Tesaro/GSK; Financial Interests, Personal, Other, Consultancy: Toray. F.J. Jin: Financial Interests, Personal, Full or part-time Employment: Merck; Financial Interests, Personal, Ownership Interest: Merck; Financial Interests, Personal, Other, Travel Expenses: Merck. J.D. Ramos: Financial Interests, Personal, Full or part-time Employment: Seagen Inc.; Financial Interests, Personal, Ownership Interest: Seagen Inc. Q. Tan: Financial Interests, Personal, Full or part-time Employment: Seagen Inc.; Financial Interests, Personal, Ownership Interest: Seagen Inc.; Financial Interests, Personal, Other, Travel Expenses: Seagen Inc. B.J. Monk: Financial Interests, Personal, Other, Consultant: Agenus; Financial Interests, Personal, Other, Consultant: Akeso Bio; Financial Interests, Personal, Other, Consultant: Amgen; Financial Interests, Personal, Other, Consultant: Aravive; Financial Interests, Personal, Other, Speaker/Consultant: AstraZeneca; Financial Interests, Personal, Other, Consultant: Bayer; Financial Interests, Personal, Other, Speaker/Consultant: Clovis; Financial Interests, Personal, Other, Speaker/Consultant: Eisai; Financial Interests, Personal, Other, Consultant: Elevar; Financial Interests, Personal, Other, Consultant: EMD Merck; Financial Interests, Personal, Other, Consultant: Genmab/Seagen; Financial Interests, Personal, Other, Consultant: GOG Foundation; Financial Interests, Personal, Other, Consultant: Gradalis; Financial Interests, Personal, Other, Consultant: ImmunoGen; Financial Interests, Personal, Other, Consultant: Karyopharm; Financial Interests, Personal, Other, Consultant: Iovance; Financial Interests, Personal, Other, Consultant: Macrogenics; Financial Interests, Personal, Other, Speaker/Consultant: Merck; Financial Interests, Personal, Other, Consultant: Mersana; Financial Interests, Personal, Other, Honorarium: Novartis; Financial Interests, Personal, Other, Consultant: Novocure; Financial Interests, Personal, Other, Consultant: Myriad; Financial Interests, Personal, Other, Consultant: OncoC4; Financial Interests, Personal, Other, Consultant: Pieris; Financial Interests, Personal, Other, Consultant: Pfizer; Financial Interests, Personal, Other, Consultant: Puma; Financial Interests, Personal, Other, Consultant: Regeneron; Financial Interests, Personal, Other, Speaker/Consultant: Roche/Genentech; Financial Interests, Personal, Other, Consultant: Sorrento; Financial Interests, Personal, Other, Speaker/Consultant: Tesaro/GSK; Financial Interests, Personal, Other, Consultant & Investigator: US Oncology Research; Financial Interests, Personal, Other, Consultant: VBL.

Background

The new ESGO-ESTRO-ESP 2020 risk classification system (molecular classification unknown) has allocated fewer patients to the high-risk group compared to the previous risk stratification system in 2016. The study aims to clinically validate the new system in predicting the outcome compared to the previous one.

Methods

We retrospectively analyzed the data of 684 patients treated between 2009 and 2013 for carcinoma endometrium in a tertiary care oncology center. The three years overall survival (OS) and disease-free survival (DFS) estimates were generated independently using the Kaplan Meier method for the new and previous classification system. Akaike information criterion and concordance index was calculated between both staging systems to identify better predictive model.

Results

After re-classification, 43% of patients in the high-risk group based on the 2016 system are shifted to the high-intermediate group and 93% of patients migrated from the high-intermediate to intermediate-risk group (Table). The 3-year OS for low risk, intermediate risk, high intermediate risk, high risk, and advanced patients according to the 2016 risk stratification system was 98.3%,95.7%,98%,90.1%, and 64.2% respectively and was 98.3%, 96.6%,92.9%,88.9% and 61.3% respectively according to the 2020 system. The 3-year DFS was 97.9%,79.3%,88.9%,77.3% and 57.2% according to the 2016 system and 97.9%,83%,85.3%,72.2% and 53.8% respectively with the 2020 system. The survival rate decreased from low to advanced risk groups and the newer high-risk group has a lower survival rate than the previous one. The Akaike Information Criterion was lower (0.685 versus 0.702) and Concordance Index values were better (1566.661 versus1545.505) for ESGO 2020 system for DFS, indicating that the newer edition gives a better predictive model Table: 22P

ESGO 2016 and ESGO-2020 cross-tabulation

Conclusions

The new 2020 risk stratification appears better predictive of survival events.

Legal entity responsible for the study

Institutional Review Board, Regional Cancer Centre, Thiruvananthapuram.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Prognosis in advanced or recurrent endometrial cancer (aEC) is poor (5-year overall survival [OS] 15%-17%). Paclitaxel plus carboplatin (PC) is standard of care (SOC) first-line (1L) chemotherapy (CT), and no 2L SOC is established. We conducted a systematic literature review to assess the real-world effectiveness and safety of CTs in aEC.

Methods

MEDLINE, Embase, and the Cochrane Library and five relevant conference databases (2018-2020) were searched (January 2000-July 2020) for aEC studies that met prespecified inclusion/exclusion criteria. Uterine cancer was included to capture all relevant evidence. Key outcomes included OS, progression-free survival (PFS), and adverse events (AEs).

Results

84 publications met the criteria, and most assessed outcomes in (neo)adjuvant settings. Totals of five and six studies reported OS or PFS in 1L and ≥2L, respectively. Studies were from the US (n=6), Asia (n=2), Europe (n=2), and South America (n=1), and sample sizes ranged from 20 to 3197. CTs in 1L studies included PC (n=2), taxane-based CT (n=1), platinum-based CT (n=1), or any CT (n=1); ≥2L CTs included PC (n=3), doxorubicin (n=2), or any platinum-based CT (n=1) Median OS (mOS) was reported in four of five 1L studies: 11 to 28.5 months with CT not specified, 16.9 months with taxane-based CT, and 12.5 months with PC. A median PFS (mPFS) of 5.1 months was reported in one study. All six ≥2L studies reported mOS and mPFS. Of the four studies that investigated platinum-based therapies, two provided results split by treatment-free interval (TFI). One study reported mOS as 13 months for patients with treatment-free intervals (TFI) ≥ 6 months from prior systemic therapy and 5.5 months for those with TFI < 6 months. AEs (from 3 studies) were nausea (18.9%), palmar-plantar erythrodysesthesias (16.4%), and muscle weakness (12.3%) for doxorubicin, neurotoxicity (0%-10.6%) and hypersensitivity reaction (0%-2.4%) for PC, and neutropenia (16%) for carboplatin plus epirubicin.

Conclusions

The limited evidence found low OS and PFS for aEC following CT in both 1L and ≥2L settings, further emphasizing the high unmet need for new treatment options in this aggressive indication.

Legal entity responsible for the study

Eisai Inc.

Funding

Eisai Inc.

Disclosure

All authors have declared no conflicts of interest.

Background

The use of somatic tumor mutational profiling is growing. We envision that somatic alterations of the MMR genes can inform on the MMR-D phenotype in endometrial cancer.

Methods

We analyzed the whole-exome sequence data of 570 patients with endometrial cancer from two previously reported studies (Nature. 2013;497(7447):67–73 and Clin Cancer Res. 2018;24(23):5939–47). Another 148 patients not previously reported were included. We used the Benjamini-Hochberg procedure (q-value) for multiple hypothesis testing.

Results

A total of 706 pts were eligible for final analysis. Pts with somatic alterations in at least one of the MMR genes (MMR alt) were 16% (112/706) of pts. MMR alt group were diagnosed at an earlier median age than the non-MMR alt group (60 vs. 64 years, p = 0.005). No significant difference among pts of different races (p=0.24). The pts with MMR alt had a superior 5-year overall survival compared to the non-MMR alt pts (93.6% vs. 72.1%, Log-rank p=0.002). Pts with MMR alt were significantly enriched with mutations in cancer-related genes, such as PTEN and PIK3CA (q<0.0001). Meanwhile, TP53 mutations were enriched in the non-MMR alt group (q<0.0001). Pts with MMR alt had significantly higher MSI-high and POLE-hypermutated phenotype tumors compared to pts with non-MMR alt (52.04% vs. 23.72% and 43.88% vs. 1.47%, p< 0.001, respectively). Pts with MMR alt showed a higher MMR-D phenotype as detected by IHC compared to non-MMR alt pts (71.43% vs. 8%, p <0.001). In pts with available transcriptomic data from non-MMR alt (419 pts) and MMR alt (98 pts) subgroups, the expression of the mRNA transcripts of MSH6 was significantly higher in the non-MMR alt compared to the MMR alt group (Log ratio =0.24, q= 0.028), suggesting decreased expression in the MMR alt group. Moreover, PD-L1 expression was negatively correlated with PMS2 expression (Spearman’s R=-0.28, p<0.001).

Conclusions

Somatic MMR gene alterations delineated a subgroup of pts with endometrial cancer that had better survival, younger age, and highly mutated genomic profile. There is a significant association between somatic MMR alterations and standard MSI testing, suggesting the potential use of somatic tumor testing to identify MMR-D phenotype in tissue or liquid biopsies.

Legal entity responsible for the study

K. Shohdy.

Funding

European School of Oncology (ESO).

Disclosure

All authors have declared no conflicts of interest.

Background

The COVID-19 outbreak has correlated with the disruption of screening activities and diagnostic assessments. Endometrial cancer is one of the most common gynecological malignancies and it is often detected at an early stage because it frequently produces symptoms. Here, we aim to investigate the impact of the COVID-19 outbreak on patterns of presentation and treatment of endometrial cancer.

Methods

This is a retrospective study involving 54 centers in Italy. We evaluated patterns of presentation and treatment of endometrial cancer patients before (period 1: March 1, 2019, to February 29, 2020) and during (period 2: April 1, 2020, to March 31, 2021) the COVID-19 outbreak.

Results

Charts of 5,164 endometrial cancer patients were retrieved from 54 Italian centers over the whole study period. Overall, 2,718 and 2,446 women with endometrial cancer received treatment in periods 1 and 2, respectively. The prevalence of patients aged > 65 years was similar between the two study periods (1,400 (51.5%) in period 1 vs. 1,248 (51.0%); p=0.726). Similarly, the prevalence of elderly patients (i.e. aged >85 years) was comparable between groups (189 (6.9%) vs. 180 (7.4%); p=0.572). Considering data on the histological characterization, the prevalence of endometrioid FIGO grade 1, 2, and 3 was consistent over the study period (p=0.855). However, the prevalence of non-endometrioid endometrial cancer was lower in period 1 than in period 2 (15.6% vs. 17.9%; p=0.032). Surgery was the mainstay of treatment before and during the COVID-19 pandemic. Overall, 2,539 and 2,286 women received surgery in period 1 and 2, respectively (93.4% vs. 93.5%; p=0.948). Primary conservative attempts was performed in 72 (2.7%) and 56 (2.3%) patients in period 1 and 2, respectively (p=0.406). Overall, 1,280 (50.4%) and 1,021 (44.7%) patients had no adjuvant therapy in period 1 and 2, respectively (p<0.001). Adjuvant therapy use has increased during the COVID-19 pandemic (p<0.001).

Conclusions

Our data suggest that the COVID-19 pandemic had a significant impact on the characteristics and patterns of care of endometrial cancer patients. These findings highlight the need to implement healthcare services during the pandemic.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Uterine sarcomas (US) are rare tumors, representing less than 3% of gynecologic malignancies and between 3% and 7% of uterine malignancies. US are characterized by being aggressive with a high rate of local and metastatic recurrence. Their management is not well codified. The aim of our study was to investigate the epidemiological, clinical, therapeutic, and prognostic characteristics of US.

Methods

This was a monocentric, descriptive, retrospective study that included patients with US treated in Salah Azaiez Tunisian oncological institute between 2000 and 2020.

Results

The study included 103 patients. The average age was 50 years. Menometrorrhagia was the main circumstance of discovery (n=70). In 73.8% of cases, the diagnosis was postoperative. Histological confirmation was done on hysterectomy specimen in 82 patients. The most frequent histological type was leiomyosarcoma in 72.8% of cases. Stage I was the most represented (41.7%). Ninety-seven patients underwent surgery, 87 of them had a total hysterectomy associated with bilateral salpingo-oophorectomy and lymph node dissection. Adjuvant chemotherapy was indicated in 16.5% of cases. Adjuvant pelvic radiotherapy was performed in 35 patients. Thirty-one patients received first-line chemotherapy. The protocol used was the combination of doxorubicin and ifosfamide in 82.3% of cases. Two patients received palliative endocrine therapy after progression to first line. After a median follow-up of 56 months, the overall survival at 2 and 5 years, all stages combined, was 56% and 40%, respectively. For metastatic stages, the overall survival was 36% and 25% at 2 and 3 years, respectively. In multivariate analysis, no prognostic factors were identified. Progression-free survival at 3 and 5 years was 82% and 72%, respectively. In multivariate analysis, only the circumstance of discovery was a prognostic factor impacting progression-free survival (p=0.042).

Conclusions

US is a particular neoplasm. Prospective randomized studies are needed to better codify its management.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

No residual disease after debulking surgery is the most critical independent prognostic factor for advanced ovarian cancer (AOC). There is an unmet clinical need for selecting primary or interval debulking surgery in AOC patients using existing prediction models such as CA-125, CT, PET-CT, or laparoscopy.

Methods

In this multiphase cohort study, 348 pre-treatment plasma and postsurgical tissue consecutive samples, and 272 patients were collected from four clinical centers. Circulating sEVs miRNAs profile associated with residual disease was revealed by RNA sequencing in AOC patients. MiRNAs expression was measured via TaqMan quantitative real-time PCR. The prediction model was established via the least absolute shrinkage and selection operator (LASSO), and logistic regression analysis based on the discovery-validation set. Plasma and tissue sEVs were captured by the magnetic bead sorting system (MACS) using cell-type-specific proteins as markers (EpCAM, FAP, CD45, CD235a, CD31).

Results

After analyzing a comprehensive plasma sEVs miRNAs profile in AOC, we identified and optimized a risk prediction model consisting of plasma sEVs-derived 4-miRNA (miR-320a-3p, miR-378a-3p, miR-1307-3p, let-7d-3p) and CA-125 (AUC:0.903; sensitivity:0.897; specificity:0.910; PPV:0.926; NPV:0.871). The quantitative evaluation of Net Reclassification Improvement (NRI) and Integrated Discrimination Improvement (IDI) suggested that the additional predictive power of the combined model was significantly improved contrasted with CA-125 or 4-miRNA alone (model vs CA-125, NRI=0.471, P<0.001; IDI=0.538, P<0.001; model vs 4-miRNA panel, NRI=0.122, P=0.001; IDI=0.185, P=0.003). Tumor cells-derived sEVs captured on EpCAM+ magnetic beads were the major vehicles affecting circulating sEVs 4-miRNA expressions. Moreover, the model index scores were significant differences between AOC and other confusable diseases (e.g., advanced colorectal cancer).

Conclusions

A reliable and stable model of circulating tumor-derived sEVs 4-miRNA plus CA-125 was established for preoperatively anticipating the high-risk AOC patients of residual disease to optimize clinical therapy.

Legal entity responsible for the study

J. Tang.

Funding

This work was supported by Grants from the General Project of Natural Science Foundation of Hunan Province (No. 2020JJ4051); Promotion Project of Health Suitability Program in Health Department of Hunan Province (No. WZ2020-15); Science and Technology Innovation Program of Hunan Province (No. 2020SK51101); Hunan Cancer Hospital Climbing Fund (No. ZX2020004); Capacity Building Project of Central Subsidy Medical and Health Institutions (No. 20201127-1001); Key Specialty Construction Project in Hunan Province (No. 20210826-1004); General Project in Health Department of Hunan Province (No. 202205015388).

Disclosure

The author has declared no conflicts of interest.