Search

Refinements of brachytherapy techniques have led to better local control of locally advanced cervical cancer (LACC), especially with the development of image-guided adaptive brachytherapy (IGABT). Data on the efficacy of brachytherapy in cervical cancer spreading to adjacent organs are scarce. We report the experience of our institution in the treatment of these advanced tumors with IGABT.Medical records of patients treated for a LACC spreading to the bladder and/or rectum between 2006 and 2020 at Gustave Roussy Institute were analyzed. Dosimetric parameters were collected and converted into 2 Gy per fraction equivalent doses, including the minimal dose received by 90% of the high-risk target volume (DA total of 81 patients were identified. All patients received pelvic+/- para-aortic radiotherapy, 45 Gy in 25 fractions +/- boost to gross lymph nodes. Concomitant platinum-based chemotherapy was administered in 93.8% of cases. The median DAdvances in brachytherapy modalities improved local control and survival while reducing toxicities. Enhancing local control through dose escalation and combined intracavitary/interstitial brachytherapy techniques is a major factor in patients cure probability, together with systemic intensification to better control distant events.

Kinase inhibitors (KI) and antibodies targeting the VEGF pathway are approved in a broad spectrum of cancers and associated with an increased risk of bleeding and thromboembolic events (TE). The use of direct oral anticoagulants (DOACs) apixaban and rivaroxaban is increasing in cancer patients, but limited data are available for patients receiving anti-VEGF agents.To assess safety of DOAC with concomitant anti-VEGF agents, a retrospective chart review of all patients receiving concomitantly DOAC and anti-VEGF agents was performed from 2013 to 2020 in our center. Data on demographics, safety, and time on treatment were collected. Main outcome was safety (bleeding and thromboembolic events).Of 92 patients (median age 66 years (IQR: 59-72)), 40 were treated with KI and 52 with bevacizumab. The most frequent primary tumor sites were colon/rectum (24%), kidney (21%), ovary (13%), lung (11%), soft tissue sarcoma (10%), and thyroid (9%); 2% had brain metastases. Apixaban 5 mg bid (n = 41) or rivaroxaban 20 mg daily (n = 51) were given for TE (65%), atrial fibrillation (32%), or other indications (3%). The median duration of concomitant treatment was 4.8 months (95%CI: 0.7-50.0) with bevacizumab and 11.7 months (95%CI: 0.1-53.8) with KI. Grade ≥ 3 bleeding events occurred in 5 patients (5%): 4 patients receiving bevacizumab (one grade 5 upper digestive tract bleeding and three grade 3 rectal or vaginal hemorrhages) and 1 patient under cabozantinib for kidney cancer with endobronchial metastasis (grade 3 hemoptysis). Grade ≥ 3 TE occurred in 8 patients (9%): 7 patients receiving bevacizumab (including one grade 5 pulmonary embolism), and one patient receiving sunitinib (grade 3 pulmonary embolism). Median time-to-event (bleeding or thrombotic event) was not reached (NR) (95%CI: 76.9-NR) for KI and 86.9 months (95%CI: 42.9-148.0) for bevacizumab. CONCLUSIONS AND RELEVANCE: In our experience, the use of DOAC was safe in selected patients treated with KI, but unclear with bevacizumab. More data are needed to endorse guidelines in this specific group of patients.

Background: Knowledge regarding the homologous recombination deficiency (HRD) status at diagnosis is essential to manage patients (pts) with advanced epithelial ovarian cancer (EOC). HRD is defined by either a BRCA1 or BRCA2 mutation, or genomic instability (GI). These genomic tests are performed on FFPE tumor samples and unfortunately non-contributive in 12-18% of cases. Advanced OC frequently presents with ascites which could provide an alternative source of Cell-free tumor DNA (cftDNA). Methods: We collected data from 53 patients undergoing primary (N=35) or interval (N=12) laparoscopy for suspected/confirmed EOC, or abdominal paracentesis at relapse (N=6). cftDNA was extracted from 20ml of ascites, or 20ml of peritoneal washings if no ascites was present. Intraperitoneal cfDNA was subjected to next generation sequencing (NGS) to confirm tumoral origin and to identify BRCA1/2 mutations, and GI was assessed by measuring large scale genomic alterations on shallow Whole Genome Sequencing (sWGS). Matching FFPE tumor samples underwent NGS and GI testing. Results: A total of 53 patient were included. Overall, intraperitoneal cfDNA was detectable in more than 90% (48/53) pts, and in 100% (35/35) of pts at diagnosis. Even among patients without visible ascites, peritoneal washings yielded cfDNA in 40% of cases (3/7). DNA quality (presence of mononucleosomal pics around 160bp and low contamination with high molecular DNA greater than 700bp) and quantity (median concentration: 3700 ng/ml; range 109 - 65 000 ng/ml) was excellent and median turn-around testing time was 21 days. Ascitic cfDNA was confirmed as tumoral in 98% of cases, largely due to detection of TP53 mutations (85,5%, 41/48), other variants in cftDNA included. Seven (15%) and 6 (12,5%) patients had BRCA1 and BRCA2 mutations, respectively. For 36 pts, NGS results on matching tumor tissue were available, and among those 97% (35/36) had concordant mutations detected in ascitic cftDNA and tumor tissue DNA. In 5 pts for whom tumor tissue-based NGS was non-contributive, NGS on cftDNA from ascites was informative and uncovered a BRCA2 mutation in one pt. We then performed GI testing on 18 cftDNA samples using sWGS and 100% of samples yielded contributive GI test results. Of these 18 pts, 42% (7/18) has failed GI testing on matching tumor sample. Conclusion: Genomic profiling on cftDNA from ascites is feasible, yields high quality and quantity tumor derived cfDNA. Importantly this approach has a fast testing turn-around time and only requires 20ml of ascites so that the majority of pts with advanced OC would be eligible to this approach. This cftDNA is suitable for HRD testing combining both BRCA mutation analysis and GI testing and should be done in every patient at primary laparoscopy Citation Format: Cyril Roussel-Simonin, Felix Blanc-Durand, Etienne Roueau, Audrey Le Formal, Laure Chardin, Elisa Yaniz, Sebastien Gouy, Amandine Maulard, Stéphanie Cherrier, Claire Sanson, Lea Mauny, Sophie Coterret, Francois Zaccarini, Roseline Tang, Alexandra Leary. Homologous recombination deficiency (HRD) testing on cell-free tumor DNA in ascites of patients with newly diagnosed advanced epithelial ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3368.