Homologous recombination deficiency (HRD) testing on cell-free tumor DNA from peritoneal fluid.

BACKGROUND: Knowing the homologous recombination deficiency (HRD) status in advanced epithelial ovarian cancer (EOC) is vital for patient management. HRD is determined by BRCA1/BRCA2 pathogenic variants or genomic instability. However, tumor DNA analysis is inconclusive in 15-19% of cases. Peritoneal fluid, available in > 95% of advanced EOC cases, could serve as an alternative source of cell-free tumor DNA (cftDNA) for HRD testing. Limited data show the feasibility of cancer panel gene testing on ascites cfDNA but no study, to date, has investigated HRD testing. METHODS: We collected ascites/peritoneal washings from 53 EOC patients (19 from retrospective cohort and 34 from prospective cohort) and performed a Cancer Gene Panel (CGP) using NGS for TP53/HR genes and shallow Whole Genome Sequencing (sWGS) for genomic instability on cfDNA. RESULTS: cfDNA was detectable in 49 out of 53 patients (92.5%), including those with limited peritoneal fluid. Median cfDNA was 3700 ng/ml, with a turnaround time of 21 days. TP53 pathogenic variants were detected in 86% (42/49) of patients, all with HGSOC. BRCA1 and BRCA2 pathogenic variants were found in 14% (7/49) and 10% (5/49) of cases, respectively. Peritoneal cftDNA showed high sensitivity (97%), specificity (83%), and concordance (95%) with tumor-based TP53 variant detection. NGS CGP on cftDNA identified BRCA2 pathogenic variants in one case where tumor-based testing failed. sWGS on cftDNA provided informative results even when tumor-based genomic instability testing failed. CONCLUSION: Profiling cftDNA from peritoneal fluid is feasible, providing a significant amount of tumor DNA. This fast and reliable approach enables HRD testing, including BRCA1/2 mutations and genomic instability assessment. HRD testing on cfDNA from peritoneal fluid should be offered to all primary laparoscopy patients.

Late cervical and vaginal clear cell adenocarcinoma in women exposed in utero to diethylstilbestrol: Evaluation and screening.

OBJECTIVES: We aimed to evaluate the risk of cervical and vaginal clear cell adenocarcinoma (CCA) in women, aged 50 years or more, exposed in utero to diethylstilbestrol (DES) and contribute to a reevaluation of the recommendations for cervical and vaginal cancer and pre-cancer screening for these women. METHODS: We carried out a retrospective review for patients received in a cancer institute. Two cohorts were consecutively studied, the first from 1970 to 2003 and the second from 2004 to 2021, and then linked. RESULTS: During the first period, we observed 61 CCA cases, with a mean age at diagnosis of 23 years (7-42), 36 (59%) following DES exposure in utero. During the second period, we found 27 cases, with one case of DES exposure (4%) for a women diagnosed at the age of 40 years. The mean age of the second cohort was 38 years (14-79). For the seven women aged 50 years or more at the time of CCA diagnosis, DES exposure was excluded for five and considered unlikely for the other two. CONCLUSION: In total, 88 cases of cervical or vaginal CCA were observed over a period of 51 years in a cancer center. The 37 cases associated with DES exposure represented approximatively one third of the CCA related to DES expected in France. DES exposure was improbable for the seven cases of CCA for women aged 50 years or more. These results do not support the hypothesis of late cervical or vaginal CCA in women exposed to DES in utero and indicate the need for larger multicentric studies. For the present, we propose specific screening for women exposed to DES in utero in terms of : 1) methods: association of cytology and hrHPV testing, with cervical and vaginal sampling, 2) timing : annual, or without exceeding a three-year interval, continuing after 65 years of age and after hysterectomy.

Induction or spontaneous labor for pregnant patients on anticoagulants?

OBJECTIVE: There are two approaches to peripartum management for pregnant patients undergoing anticoagulation treatments: spontaneous labor or scheduling an induction. A long interval without anticoagulation is a thrombosis risk factor, while a short interval leads to risks of delivery without epidural analgesia or post partum hemorrhage. Our objective was to evaluate the impact of planned induction versus spontaneous labor on obtaining neuraxial analgesia. MATERIALS AND METHODS: A retrospective single-center study was conducted from 2012 to 2020 including all patients on preventive or curative low molecular-weight heparin at the time of delivery, excluding planned cesarean sections. The rates of neuraxial analgesia were compared between two groups: spontaneous labor and induction, as well as the intervals without anticoagulants. RESULTS: 127 patients were included. In the spontaneous labor group, 78% (44/56) received neuraxial analgesia versus 88% (37/42) in the induction group (p = 0.29). For curative dose treatment, the rate of neuraxial analgesia was 45,5% in the spontaneous group versus 78,6% (p = 0.12). The median time without anticoagulation was 34 h [26-46] in the spontaneous labor group and 43 h [34-54] in the induction group (p = 0.01), without an increased incidence of thrombosis. The rate of postpartum hemorrhage did not differ between the two groups. CONCLUSION: Planned induction tended to increase the rate of neuraxial analgesia, without reaching significance, and most women in spontaneous labor accessed analgesia. Peripartum management should be a shared decision with the patient considering the obstetrical and thrombosis risk context for each patient.