Prognostic value of BRCA1 promoter methylation for patients with epithelial ovarian cancer.

OBJECTIVE: BRCA1 promoter methylation (BRCA1pm) is suspected to alter prognosis of patients with epithelial ovarian cancer (EOC). We aimed to evaluate the prognostic impact of this epigenetic modification. METHODS: We conducted a retrospective, monocentric study from 11/2006 to 08/2018. Patients with EOC and available status concerning somatic BRCA1/2 mutation and BRCA1pm were included. Three groups were defined: patients without BRCA1/2 mutation or BRCA1pm, patients with BRCA1/2 mutation and patients with BRCA1pm. BRCA1/2 mutations were analyzed in current care settings by next-generation sequencing (NGS). BRCA1pm analysis was assessed and quantified from bisulfite converted DNAs using fluorescent methylation specific polymerase chain reaction (PCR) and fragment analysis. All patients signed a consent form and the study was authorized by a Personal Protection Committee. Descriptive statistics were used to describe groups. Multivariate analysis was performed using the logistic regression model and including the variables that could be known at the time of diagnosis and that were significant at univariate analysis. Survival was compared between the groups. Kaplan-Mayer curves were used to express the differences in survival that were compared using log rank tests. RESULTS: 145 patients were included: 95 (65.5 %) patients without BRCA1/2 mutation or BRCA1pm, 32 (22.1 %) patients with BRCA1/2 mutation, 18 (12.4 %) patients with BRCA1pm. Median survival was decreased in patients with BRCA1pm. Comparison of survival revealed a significant difference in overall survival (p = 0.0078) with a worse prognosis for patients with a BRCA1pm. CONCLUSION: BRCA1pm in patients with EOC is an independent factor associated with a decreased overall survival. SYNOPSIS: BRCA1 promotor methylation in patients with epithelial ovarian cancer is an independent factor associated with a decreased overall survival.

Peritoneal Tumour DNA in Peritoneal Fluid: Emerging Tool for Peritoneal Metastasis Detection.

The prognostic significance of positive peritoneal cytology still varied between cancer types and geographical origin. However, because of the lack of sensitivity of this biomarker, conventional cytology is not routinely performed in every country. Here, we wanted to test a new biomarker, peritoneal tumour DNA, using NGS technique, in order to compare it with the historical one, in patients having peritoneal metastases of gastrointestinal or ovarian cancer.

First external validity study of the Fagotti score in ovarian cancer.

Epithelial ovarian cancer is mostly discovered at the stage of peritoneal carcinosis. Complete cytoreductive surgery improves overall survival. The Fagotti score is a predictive score of resectability based on peritoneal laparoscopic exploratory. Our aim was to study the inter-observer concordance in an external validation of the Fagotti score. An observational, prospective, multicenter study was conducted using the Francogyn research network. The primary outcome was inter-observer concordance of the Fagotti score. 15 patients in which an ovarian mass was discovered were included. For each patient, the first exploratory laparoscopy before any treatment/chemotherapy was recorded. This bank of 15 videos was subject to blind review accompanied by a Fagotti score rating by 11 gynecological surgeons specializing in oncology. A total of 165 blind reviews were performed. Inter-observer concordance was very good for the Fagotti score with an intraclass correlation coefficient (ICC) of 0.83 [95% CI 0.71; 0.93]. Inter-observer concordance for the adjusted Fagotti score, which accounts for unexplorable areas with extensive carcinomatosis, resulted in an ICC of 0.64 [95% CI 0.46; 0.82]. According to the reviewers, the three least explorable parameters were mesentery involvement, stomach infiltration and liver damage. The ICC of the explorable Fagotti score, i.e. score with deletion of the parameters most often unexplored by laparoscopy, was 0.86 [0.75-0.94]. This study confirms the reproducibility of the Fagotti score during first assessment laparoscopies in cases of advanced ovarian cancer. The explorable Fagotti score has an equivalent or better inter-observer concordance than the Fagotti score.

Variability of treatment of locally advanced cervical cancer: How French multidisciplinary teams follow European guidelines?

INTRODUCTION: Cervical cancer is a global public health concern. Despite ESGO recommendations and FIGO classification changes, management of locally advanced cervical cancer (LACC) remains debated in France. Our study aimed to review LACC treatment practices and assess adherence to ESGO recommendations among different practitioners. METHODS: From February 2021 to August 2022, we conducted a survey among gynecologic oncology surgeons, radiation oncologists, and medical oncologists practicing in France and managing LACC (FIGO stages IB3-IVA) according to the 2018 FIGO classification. We analyzed responses against the 2018 ESGO recommendations as a "gold standard." RESULTS: Among 115 respondents (56% radiation oncologists, 30% surgeons, 13% medical oncologists), 48.6% of gynecologic surgeons didn't perform para-aortic lymphadenectomy (PAL) with significant radiologic pelvic involvement. PAL, when indicated by PET-CT, was more common in university hospitals (66.7% of surgeons). Surgeons in university hospitals also followed ESGO recommendations more closely. Overall, compliance with all ESGO recommendations was low: 5.7% of surgeons, 21.5% of radiation oncologists, and 60% of medical oncologists. Prophylactic para-aortic irradiation, per ESGO, was more frequent in comprehensive cancer centers (52% of radiation oncologists). CONCLUSION: Adherence to ESGO recommendations for LACC treatment appears low in France, particularly in surgery, with limited PAL in cases of lymph node negativity on PET-CT. However, these recommendations are more often followed by surgeons in university hospitals and radiation oncologists in cancer centers. Adherence to these recommendations may impact patient survival and warrants evaluation of care quality, justifying the organization of LACC management in expert centers.

What is the most pertinent definition of malnutrition in epithelial ovarian cancer to assess morbidity and mortality?

INTRODUCTION: Malnutrition is common in ovarian cancer and is a major cause of morbidity and mortality. We aimed to define the most pertinent way to assess malnutrition in patients with epithelial ovarian cancer (EOC) in order to study its impact on morbidity (intra and post-operative complications) and survival (OS, overall survival and RFS, recurrence-free survival). METHODS: We retrospectively included all patients with EOC from 2003 to 2020. Nutritional status was assessed using the weight loss at diagnosis (more or <5%), albuminemia, the Nutritional Risk Index (NRI), and the Malnutrition Universal Screening Tool (MUST). RESULTS: Six hundred and fifteen patients were included. Among them, 34% declared having lost >5% of their usual weight, 58% had an albuminemia <35 g/L, 86% presented an abnormal NRI and 29% an abnormal MUST score. After univariate analysis, weight loss>5% appeared to be significantly associated with RFS. An abnormal NRI or MUST score were significantly associated with a decrease in OS in univariate analysis. None of the markers of malnutrition studied were correlated with morbidity. CONCLUSION: We were not able to reach a consensus concerning the most accurate definition to define malnutrition and predict morbidity and mortality in EOC. However, this modifiable prognosis factor must be systematically assessed and managed accordingly.