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

Malignant bowel obstruction (MBO) is common in advanced ovarian cancer (AOC). Treatment options are limited as majority of cases present with widespread, multilevel peritoneal dissemination and platinum-resistant disease. The benefit of Parenteral Nutrition (PN) in MBO is debated, given the limited overall survival (OS) of this patient group. Aim: to identify which clinical features correlate with improved survival in AOC and MBO, to support clinical decision-making.

Methods

Retrospective review of patients admitted with MBO between April 2019 and October 2021 to a single tertiary cancer centre. Those with AOC established on PN with the aim to discharge home on PN were included. Univariate analysis for survival after commencing PN was performed using log-rank test.

Results

103 patients with MBO were identified with 33 patients excluded (PN not initiated, 15; PN withdrawn: covid service constraint, 5, acute medical event, 13). 70 patients were successfully established on PN and 49 discharged on PN; 16 patients clinically deteriorated; 5 returned to enteral diet. Median OS of patients that did not receive PN was 19 days, PN stopped due to general deterioration 39 days and 100 days (range 18-807) for those established on PN (p<0.0001). Clinical features associated with improved OS: no prior systemic therapy (p=0.0067), platinum sensitivity (p=0.043), ECOG performance status (PS) 1 vs 2-3 (p=0.004), falling modified Glasgow Prognostic Score (mGPS) during admission (p=0.0027). In the treatment naïve group, chemotherapy resolved MBO in 6/9 cases. In the pre-treated group, 60% of patients received subsequent chemotherapy (median duration 8 weeks), with early cessation due to toxicity and no clinical benefit. Only 1 patient achieved resolution of MBO on chemotherapy.

Conclusions

PN may improve survival of patients with AOC in MBO. ECOG PS, platinum sensitivity and mGPS trend may be useful to select patients for PN. In those presenting with MBO at AOC diagnosis, PN can enable safe delivery of chemotherapy, which usually will resolve MBO. In pre-treated patients, PN is a life-long commitment and chemotherapy is largely ineffective in resolving MBO. Further research should focus on quality of life in patients receiving PN.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Cervical cancer is one of the leading causes of death by neoplasia in the world. In Brazil, it is the 3rd cause of women's death by neoplasia. Since its implantation, 20 years ago, the federal program to prevent cervical cancer frequently had logistic and technical difficulties, especially in remote areas. Morbimortality studies are necessary to evaluate the evolution of the prevention program.

Methods

The present study evaluated cervical cancer hospitalizations in the state of Sergipe between 2008 and 2015. The data was extracted from a public database containing information about the unified public health system. The variables age, city of residence and type of hospitalization (clinical or surgical) were analyzed. Changes in hospitalization rates after the introduction of Papanicolaou test as a priority in primary care were considered through a temporal analysis using Joinpoint regression software. For this purpose, it was devised a linear logarithmic model that includes points and calculate the difference from a statistically significant value using a Monte-Carlo permutation test. The Average Annual Percent Change (AAPC), Annual Percent Change (APC) and temporal tendencies in hospitalization frequencies were calculated.

Results

873 hospitalizations were analyzed, the median age was 46 years. Surgical hospitalizations correspond to 67%.The temporal analysis showed a yearly decrease in hospitalizations of about 10%, both for the population living in the capital and in other cities of the state. When the hospitalizations in the whole state were divided by age subgroups, there was a statistically significant reduction in the subgroups 40 to 59 years and 60 years or more.

Conclusions

A consistent reduction in cervical cancer hospitalizations was observed in the state of Sergipe in the analyzed time period. This suggests an improvement after 20 years of the cervical cancer prevention program. Better access to diagnostic methods and appropriate treatment allow for more effective interventions, with fewer hospitalizations. There is, however, a long way to go, especially with regard to expanding health care for the population across the state, also aiming at reducing mortality 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

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

There is an urgent need for new treatments for platinum-resistant recurrent ovarian cancer (PROC). Addition of bevacizumab (bev) to non-platinum-based chemotherapy (chemo) significantly improved PFS in patients (pts) with PROC but did not show a clear OS benefit. Thus far, the combination of paclitaxel + bev has shown the most promise in PROC, although the proportion of pts eligible for bev is limited by treatment-related toxicities. Combination of the anti-PD-1 antibody pembrolizumab (pembro) with weekly paclitaxel showed antitumor activity and manageable toxicity in pts with PROC in a single-arm, phase II study. ENGOT-ov65/KEYNOTE-B96 (NCT05116189) compares the efficacy and safety of pembro + standard of care chemo (weekly paclitaxel) ± bev vs placebo (pbo) + weekly paclitaxel ± bev in pts with PROC.

Trial design

In this randomized, pbo-controlled, double-blind, phase III study, eligible pts are aged ≥18 y with histologically confirmed epithelial ovarian, fallopian tube, or primary peritoneal carcinoma with 1-2 prior lines of systemic therapy, including ≥1 prior platinum-based therapy with ≥4 cycles in first line. Pts must have platinum-resistant disease (radiographic evidence of PD ≤6 mo after last platinum-based therapy dose), be eligible for paclitaxel (± bev per investigator discretion), have ECOG PS ≤1, radiographically evaluable disease per RECIST v1.1, and have a tumor sample for central evaluation of PD-L1 status. ∼616 pts will be randomized 1:1 to pembro 400 mg IV or pbo Q6W for up to 18 cycles (∼2 y) + paclitaxel 80 mg/m² on days 1, 8, and 15 of each Q3W cycle (± bev 10 mg/kg Q2W per investigator discretion) until PD or unacceptable toxicity. Randomization is stratified by planned bev use (yes vs no), region (US vs Europe vs rest of world), and PD-L1 status (combined positive score [CPS] <1 vs CPS 1-<10 vs CPS ≥10). Primary endpoint is PFS per RECIST v1.1 by investigator review in pts with tumor PD-L1 CPS ≥1 and in all pts. Secondary endpoints are OS in pts with tumor PD-L1 CPS ≥1 and in all pts, PFS per RECIST v1.1 by blinded independent central review in pts with tumor PD-L1 CPS ≥1 and in all pts, safety, and pt-reported outcomes. Enrollment is ongoing.

Clinical trial identification

NCT05116189.

Legal entity responsible for the study

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Funding

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Disclosure

N. Colombo: Financial Interests, Personal, Full or part-time Employment, Employment of Immediate Family Member: Sarepta Therapeutics; Financial Interests, Personal, Advisory Role: Roche/Genentech, AstraZeneca, Clovis Oncology, Pfizer, MSD Oncology, Tesaro, GlaxoSmithKline, Immunogen, Mersana, Eisai, Advaxis, Nuvation Bio, Advaxis; Financial Interests, Personal, Other, Honoraria: Roche/Genentech, AstraZeneca, Tesaro, GlaxoSmithKline, MSD Oncology, Clovis Oncology, Pfizer, Amgen, Immunogen, Novartis, Pfizer, Mersana, Eisai, Advaxis, Nuvation Bio. R.L. Coleman: Financial Interests, Personal, Full or part-time Employment: US Oncology; Financial Interests, Personal, Advisory Role: Clovis Oncology, Genentech/Roche, AstraZeneca/MedImmune, Genmab, Tesaro, OncoMed, Sotio, Oncolytics, AbbVie/Stemcentrx, Immunogen, AbbVie, Agenus, Novocure, Merck, OncXerna Therapeutics, Alkermes, Gradalis, Regeneron; Financial Interests, Personal, Leadership Role: Onxeo; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Merck, AstraZeneca/MedImmune, Array BioPharma, Clovis Oncology, Roche/Genentech, Research to Practice, GOG Foundation, Sotio, Vaniam Group; Financial Interests, Personal, Stocks/Shares: McKesson; Financial Interests, Personal, Ownership Interest: McKesson; Financial Interests, Personal, Research Grant: AstraZeneca/MedImmune, Esperance Pharmaceuticals, Array Biopharma, Clovis Oncology, Johnson & Johnson, Merck, Roche/Genentech, Abbott/AbbVie; Financial Interests, Institutional, Research Grant: Immunogen, Mirati Therapeutics, Amgen, Pfizer, Lilly, Regeneron. F. Kose: Financial Interests, Personal, Advisory Role: Roche, AstraZeneca, MSD/Merck, GlaxoSmithKline, Novartis, Pfizer, Takeda, Deva, Nobel, Astellas, Janssen; Financial Interests, Institutional, Other, Honoraria: Roche, AstraZeneca, MSD/Merck, GlaxoSmithKline, Novartis, Pfizer, Takeda, Deva, Nobel, Astellas, Janssen; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Roche, AstraZeneca, MSD/Merck, GlaxoSmithKline, Novartis, Pfizer, Takeda, Deva, Nobel, Astellas, Janssen. R. Wenham: Financial Interests, Personal, Advisory Role: Mersana, Merck, Tesaro, Clovis Oncology, Genentech, Regeneron, AbbVie, AstraZeneca, GlaxoSmithKline, Seattle Genetics/Astellas, Legend Biotech; Financial Interests, Personal, Speaker’s Bureau: Tesaro, Clovis Oncology, Genentech; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: TapImmune Inc; Financial Interests, Personal, Stocks/Shares: Ovation Diagnostics; Financial Interests, Personal, Ownership Interest: Ovation Diagnostics; Financial Interests, Personal, Other, Honoraria: Tesaro, Seattle Genetics; Financial Interests, Institutional, Research Grant: Merck, Prescient Therapeutics, Anixa Biosciences. Other Relationship: AstraZeneca, GlaxoSmithKline/Tesaro; Other, Personal, Other: AstraZeneca, GlaxoSmithKline/Tesaro. A. Sebastianelli: Financial Interests, Personal, Advisory Role: AstraZeneca, Merck, GlaxoSmithKline; Financial Interests, Personal, Other, Honoraria: AstraZeneca, Merck, GlaxoSmithKline. K. Hasegawa: Financial Interests, Personal, Advisory Role: MSD K.K., Kaken Pharmaceutical, Eisai, Takeda; Financial Interests, Personal, Other, Honoraria: MSD K.K., Daiichi Sankyo, Chugai Pharma, AstraZeneca, Eisai, Kyowa Kirin, Takeda, Genmab; Financial Interests, Personal, Research Grant: Ono Pharmaceutical, Daiichi Sankyo, Merck, Takeda, Eisai. E. Zsiros: Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Other, Honoraria: Survivornet, AstraZeneca, TeneoBio; Financial Interests, Personal, Research Grant: Merck. T. De La Motte Rouge: Financial Interests, Personal, Other, Honoraria: AstraZeneca, MSD/Merck, Clovis Oncology, Tesaro, GlaxoSmithKline, Pfizer, Gilead Sciences, Eisai, French National Cancer Institute (INCa); Financial Interests, Personal, Advisory Role: AstraZeneca, MSD/Merck, Clovis Oncology, Tesaro, GlaxoSmithKline, Pfizer, Gilead Sciences, Eisai, French National Cancer Institute (INCa); Financial Interests, Institutional, Research Grant: Pfizer, Novartis, Seagen; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: AstraZeneca, MSD/Merck, Clovis Oncology, Tesaro, GlaxoSmithKline, Pfizer, Gilead Sciences, French National Cancer Institute (INCa). M. Bidzinski: Financial Interests, Personal, Other, Honoraria: AstraZeneca, MSD/Merck, GlaxoSmithKline, Johnson & Johnson, Olympus. I. McNeish: Financial Interests, Personal, Advisory Role: Clovis Oncology, AstraZeneca, Carrick Therapeutics, Roche, BeiGene, Scancell Ltd., GlaxoSmithKline, Epsila; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: AstraZeneca; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Institutional, Research Grant: AstraZeneca. J. Sehouli: Financial Interests, Personal, Advisory Role: AstraZeneca, Clovis Oncology, PharmaMar, Merck, Pfizer, Tesaro, MSD Oncology, Lilly, Novocure, Johnson & Johnson, Roche, Ingress Health, Riemser, Sobi, GlaxoSmithKline, Novartis; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: AstraZeneca, Clovis Oncology, PharmaMar, Roche Pharma AG, Tesaro, MSD Oncology, Olympus; Financial Interests, Personal, Other, Honoraria: AstraZeneca, Eisai, Clovis Oncology, Olympus Medical Systems, Johnson & Johnson, PharmaMar, Pfizer, Teva, Tesaro, MSD Oncology, GlaxoSmithKline, Bayer; Financial Interests, Institutional, Research Grant: AstraZeneca, Clovis Oncology, Merck, Bayer, PharmaMar, Pfizer, Tesaro, MSD Oncology, Roche. J. Korach: Financial Interests, Institutional, Research Grant: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. P.R. Debruyne: Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Janssen; Financial Interests, Personal, Stocks/Shares: Alkermes, Biocartis Group NV; Financial Interests, Personal, Ownership Interest: Alkermes, Biocartis Group NV; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb, Merck/Pfizer, MSD, Roche, Bayer. J. Kim: Financial Interests, Personal, Advisory Board: Takeda Korea, GSK Korea, Boryung, Vifor Pharma, MSD Korea; Financial Interests, Personal, Invited Speaker: CMIC, AstraZeneca, Janssen; Financial Interests, Personal, Expert Testimony: LG Pharma. A.C. De Melo: Financial Interests, Personal, Speaker’s Bureau: BMS Brazil, MSD Oncology; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: MSD Oncology; Financial Interests, Personal, Other, Honoraria: MSD Oncology, Novartis, BMS Brazil; Financial Interests, Institutional, Research Grant: Roche, MSD Oncology, BMS Brazil, Novartis, Clovis Oncology, AstraZeneca. X. Peng: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. A.M. Bogusz: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc., Kenilworth, NJ, USA; Financial Interests, Personal, Ownership Interest: Merck & Co., Inc., Kenilworth, NJ, USA. K. Yamada: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc., Kenilworth, NJ, USA; Financial Interests, Personal, Ownership Interest: Merck & Co., Inc., Kenilworth, NJ, USA. B.J. Monk: Financial Interests, Personal, Advisory Role: Agenus, Akeso Biopharma, Amgen, Aravive, AstraZeneca, Clovis Oncology, Eisai, Genmab/Seattle Genetics, GOG Foundation, ImmunoGen, Iovance Biotherapeutics, Merck, Mersana, Myriad Pharmaceuticals, Pfizer, Puma Biotechnology, Regeneron, Roche/Genentech, Tesa; Financial Interests, Personal, Leadership Role: US Oncology; Financial Interests, Personal, Speaker’s Bureau: Roche/Genentech, AstraZeneca, Clovis Oncology, Eisai, Tesaro/GlaxoSmithKline, Merck; Financial Interests, Personal, Other, Honoraria: Agenus, Akeso Biopharma, Amgen, Aravive, AstraZeneca, Clovis Oncology, Eisai, Genmab/Seattle Genetics, ImmunoGen, Iovance Biotherapeutics, Merck, Mersana, Pfizer, Puma Biotechnology, Regeneron, Roche/Genentech, Tesaro/GlaxoSmithKline, Vascular Biogenics; Financial Interests, Institutional, Research Grant: Novartis, Amgen, Genentech, Lilly, Janssen, Array BioPharma, Tesaro, Morphotek, Pfizer, Advaxis, AstraZeneca, Immunogen, Regeneron, Nucana. All other authors have declared no conflicts of interest.

Background

Cervical cancer is the fourth most common cancers among women worldwide. Although the cure rates in early-stage disease are good, 30% to 40% of patients in advanced-stage disease ultimately develop locoregional or distal recurrence or both. The prognosis of recurrent cervical carcinoma is very poor, and treatment of such patients remains a challenge. Because of the limited success and significant toxicity with cytotoxic chemotherapy drugs in such subset of patients, interest has grown in EGFR targeted therapeutics. This prospective study defines the role of gefitinib in recurrent or metastatic cervical carcinoma.

Methods

The eligible criteria were patients with locoregional recurrence or distant metastasis, not suitable for curative surgery or re-irradiation or for active chemotherapy due to low performance score, patients who developed progression of disease during the salvage chemotherapy; and patients who developed severe toxicity during the course of chemotherapy and therefore could not continue it. Eligible patients were treated with gefitinib at a dose of 250 mg/d orally. It was continued until disease progression or till development of intolerable adverse effects.

Results

A total of 30 patients were enrolled. Median age was 55 years and median disease-free interval was 15 months. Median duration of gefitinib therapy was 6 months. 4 patients had complete response, 8 patient had partial response, 8 patients had stable disease, and 10 patients had progressive disease. None of the patient had severe drug related toxicity.

Conclusions

Gefitinib is tolerated and effective in recurrent or metastatic cervical carcinoma. Further studies are warranted to identify patients who are more likely to benefit from gefitinib.

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.

Background

Poly (ADP-ribose) polymerase (PARP) inhibitors alone and in combination with Bevacizumab have shown significant clinical benefit as maintenance therapy in women with newly diagnosed ovarian cancer (OC) regardless BRCA mutational status and in homologous-recombination deficiency (HRD)-positive patients, respectively. However, despite the remarkable improvements in the therapeutic algorithm of ovarian cancer disease over the years, several open questions remain: a) what is the best treatment in HRD-positive patients? b) what is the added value of bevacizumab in HRD positive tumors with respect to PARPi alone? c) what is the preferred treatment in HRD-negative tumors: PARPi or bevacizumab? MITO 25.1 aims to evaluate the best first line treatment regimen in the different molecular subgroups, HRD-positive and HRD-negative OC, evaluated with Foundation Medicine LOH test.

Trial design

MITO 25.1 is a multicenter, randomized open-label, phase II study in which patients with high-grade serous or endometrioid advanced OC will be randomized in a 1:1 ratio according to a molecular driven treatment to receive: HRD-negative patients · ARM A: Carboplatin AUC 5 + Paclitaxel 175 mg/m2 q 21 + Bev 15 mg/kg for 5 cycles (starting from cycle 2) followed by Bev 15 mg/kg q 21 for 16 cycles · ARM B: Carboplatin AUC 5 + Paclitaxel 175 mg/m2 q 21 for 6 cycles followed by Rucaparib 600 mg BID q 28 for 24 cycles as maintenance HRD-positive patients · ARM B: Carboplatin AUC 5 + Paclitaxel 175 mg/m2 q 21 for 6 cycles followed by Rucaparib 600 mg BID q 28 for 24 cycles as maintenance · ARM C: Carboplatin AUC 5+ Paclitaxel 175 mg/m2 q 21 + Bev 15 mg/kg for 5 cycles (starting from cycle 2) followed by Bev 15 mg/kg q 21 days for 16 cycles + Rucaparib 500 mg part BID q 28 for 24 cycles as maintenance The primary endpoint will be PFS. The secondary endpoints will be overall survival (OS), PFS2, adverse events according to CTCAE 5.0 and patient-reported outcome. Patients recruiting started in March 2021. To date, 136 of the 290 patients planned have been enrolled.

Clinical trial identification

NCT03462212.

Legal entity responsible for the study

D. Lorusso.

Funding

Clovis Oncology.

Disclosure

G. Scambia: Financial Interests, Personal, Other: MSD; Financial Interests, Personal, Invited Speaker: Clovis Oncology. V. Salutari: Financial Interests, Personal, Other: GSK; Financial Interests, Personal, Other: PharmaMar; Financial Interests, Personal, Other: Clovis-Oncology; Financial Interests, Personal, Other: MSD; Financial Interests, Personal, Other: AstraZeneca. S. Pignata: Financial Interests, Personal, Other: MSD; Financial Interests, Personal, Other: AstraZeneca; Financial Interests, Personal, Other: Clovis-Oncology; Financial Interests, Personal, Other: Roche; Financial Interests, Personal, Other: Pfizer. D. Lorusso: Financial Interests, Personal, Other: GSK; Financial Interests, Personal, Other: MSD; Financial Interests, Personal, Other: AstraZeneca; Financial Interests, Personal, Other: MSD; Financial Interests, Personal, Other: Genmab; Other, Institutional, Member of the Board of Directors: GCIG. All other authors have declared no conflicts of interest.

Background

Presently, the treatment of localized adenocarcinoma cervix patients is the same as squamous cell carcinoma. This study analyzes the long-term survival outcome and pattern of failure of adenocarcinoma patients treated at our institute.

Methods

All ladies diagnosed and treated with localized adenocarcinoma cervix at our institute between 2012 and 2018 were included. These patients were followed up till January 2022. The stages of all patients at the time of diagnosis were restaged according to FIGO 2018. The patient, treatment, and follow-up details were collected from the electronic filing system. Lost-to-follow-up patients were contacted through telephone. The statistical analysis was done using SPSS 23.0.

Results

Adenocarcinoma constituted 7.8% (66 out of 847 patients) of the entire cervical cancer patients detected during the study period – 44% of patients presented with either stage I or II. There were no patients with stage IVa. The median age was 53.5 years (66.7 % were 55 years or less). 69.7% of adenocarcinoma were HPV-associated. The treatment modalities undergone by these patients include radical concurrent chemoradiation and brachytherapy (36.4%), surgery alone (30.3%), surgery followed by adjuvant radiation in (15.2%), and surgery followed by concurrent chemoradiation in (18.2%). All the patients who underwent radiotherapy used the intensity-modulated radiotherapy technique for external beam radiotherapy and image-based adaptive brachytherapy. A few patients (16.7%) received neoadjuvant chemotherapy (NACT) before undergoing curative treatments. The median follow-up period was 54 months. The 10-year overall survival (OS) was 62.2% (84.2% in stage I, 56% in stage II, and 53.1% in stage III). The OS of those who received NACT was 72.7 percent versus 59.9% who did not receive it. Most of the patients who recurred had distant metastasis (64.3%), and the median disease-free interval of those who had distant metastasis was 7 months (2 - 30).

Conclusions

Further molecular studies should be done to better understand this distinctly different subset of cervical cancer patients to tailor the treatment modalities.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Ovarian cancer (OC) is the most common cause of gynecologic cancer mortality worldwide. Next generation sequencing (NGS) provides molecular biomarkers which can potentially predict oncological outcomes. We performed a retrospective study to examine progonostic biomarkes for ovarian cancer patients treated in our institution.

Methods

We retrospectively evaluated demographic and clinical information of OC patients referred for NGS molecular testing between 2011-2020 at the Tel-Aviv Medical Center. Cox models were used to analyze the clinical impact of molecular biomarkers including LOH and TMB by assessing overall survival (OS) and progression free survival (PFS).

Results

Of 1026 consecutive patients reviewed, 946 were included in the analysis: 108 (11.4%) were referred to NGS and 838 (88.6%) served as control. Patient baseline parameters were similar between the groups. High loss of heterozygosity (LOH) was associated with longer mOS (99.0 vs. 48.2 months, p=0.004). Sixty-six patients had information on TMB status: 75.8% (50/66) had low TMB status (<5) and 24.2% (16/66) had intermediate TMB status (5-15). None had a high TMB status. Analysis of TMB using the Breslow test showed that patients with TMB ≥4 had a statistically significant longer OS compared with patients with TMB<4 (92.8 months [95%CI, 47.1-138.6] vs. 52.77 months [95% CI, 26.4-79.2], p=0.026).

Conclusions

We identified LOH and TMB ≥4 as strong prognostic biomarkers among OC patients. Prospective studies evaluating larger cohorts are necessary to generate a more extensive evaluation of additional prognostic and predictive biomarkers.

Legal entity responsible for the study

The authors.

Funding

Roche Israel.

Disclosure

All authors have declared no conflicts of interest.

Background

While traditional pelvic exenterations (PE) represent a potentially curative treatment for recurrent tumours localized centrally in the pelvis, new surgical techniques have been developed recently to enable a complete resection even in tumours invading into the pelvic side wall. Extended pelvic exenterations (EPE) include resection of internal, external, or common iliac vessels, pelvic side-wall muscles, large pelvic nerves, or pelvic bones. EPE are currently performed only in a few institutions and data on treatment morbidity are not available. The aim of the study was to compare health-related quality of life (QoL) and oncological outcome after PE and EPE.

Methods

Data from 72 patients with cervical (36), vulvar (19), endometrial (14) and low-grade ovarian (5) cancer who underwent PE (42) or EPE (32) for persistent (20%) or recurrent (80%) disease between 2014 to 2019 at a single tertiary centre were analysed. Quality of life was evaluated in surviving patients using EORTC QLQ-C30, EORTC CX-24, and QOLPEX questionnaire developed specifically for patients after extensive pelvic procedures.

Results

Median overall and disease-specific survival reached in the whole cohort 45 and 49 months, without significant differences between PE and EPE groups (P >0.999). We did not observe any difference in post-surgical complication types or frequency between the groups. Thirty-one survivors participated in the QoL assessment (20 PE, 11 EPE) and no significant differences were found in global health status (P=0.951) or in any of the functional scales. The groups were not differing in therapy satisfaction (P=0.502), and both expressed similar willingness to potentially undergo treatment again (P=0.317) (Table). Table: 47P

EORTC QLQ 30, EORTC QLQ-CX24 – Main results

Conclusions

EPE are associated with similar post-treatment QoL and survival as traditional PE. These procedures represent potentially curative treatment option for patients with persistent or recurrent pelvic cancer invading into pelvic wall structures without further compromising QoL.

Legal entity responsible for the study

The authors.

Funding

Charles University in Prague (UNCE 204065 and PROGRES Q28/LF1).

Disclosure

All authors have declared no conflicts of interest.

Background

To evaluate the impact of the Laparoscopic Approach to Cervical Cancer (LACC) trial on patterns of care and surgery-related morbidity in early-stage cervical cancer.

Methods

This is a retrospective, multi-institutional study evaluating 90-day surgery-related outcomes of patients undergoing treatment for early-stage cervical cancer before (period I: 01/01/2016-06/01/2018) and after (period II: 01/01/2019-06/01/2021) the publication of the results of the LACC trial.

Results

Charts of 1,295 patients were evaluated: 581 (44.9%) and 714 (55.1%) before and after the publication of the LACC trial, respectively. After the publication of the LACC trial the number of patients treated with minimally-invasive radical hysterectomy decreased from 64.9% to 30.4% (p<0.001). Overall, 90-day complications occurred in 110 (18.9%) and 119 (16.6%) patients in the period I and period II, respectively (p=0.795). Similarly, the number of severe (grade 3 or worse) complications did not differ between the two periods (38 (6.5%) vs. 37 (5.1%); p=0.297). Overall and severe 90-day complications were consistent between periods even evaluating stage IA (p=0.471), IB1 (p=0.929), and IB2 (p=0.074), separately.

Conclusions

The present investigation highlighted that in referral centers the shift from minimally invasive to open radical hysterectomy does not influence 90-day surgery-related morbidity.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.