Henri Azaïs

Impact of lymph node staging on survival in presumed early-stage ovarian cancer: a multicentric retrospective study

This study aimed to assess the impact of comprehensive staging on survival outcomes in this population. Patients who underwent surgery for epithelial ovarian cancer in one of the 14 Francogyn cancer centers between 2000 and 2020 were included in the study. The primary analysis evaluated the impact of lymphadenectomy on overall survival and recurrence-free survival. Lymph node count was analyzed as a continuous variable, and its association with survival, considered as a continuous outcome was assessed using linear regression (secondary analysis). Survival was compared using the log-rank test, and multivariate analysis was performed using a Cox model. A total of 467 patients with presumed early-stage epithelial ovarian cancer were included, of which 198 underwent complete lymphadenectomy and 266 did not. No significant association was found between lymph node staging and survival in the primary analysis, possibly due to limited statistical power and a selection bias, as patients without lymphadenectomy had more favorable disease profiles (p=0.600 and p=0.700, respectively). Complete lymphadenectomy was associated with a significantly higher risk of complications (34.5% vs. 14%, p<0.001). In secondary analysis, the number of para-aortic lymph nodes harvested was identified as an independent predictor of both overall survival and recurrence-free survival (p=0.007 and p=0.002, respectively). Histological characteristics and adjuvant chemotherapy also showed a significant correlation with improved survival outcomes. Extensive para-aortic lymphadenectomy in early-stage epithelial ovarian cancer is associated with better overall and recurrence-free survival but comes with an increased risk of complications.

Clinical value of circulating tumor DNA for patients with epithelial ovarian cancer

Despite progress in recent years, epithelial ovarian cancer remains a pathology with a poor prognosis, primarily because of late and invasive diagnosis. Conventional follow-up relies on imaging, CA125, and predictive tools such as KELIM-CA125 and the chemotherapy response score. However, these methods are non-specific and result in delays before obtaining results. Recently, many research teams have focused on liquid biopsies, which provide direct access to tumor material in biological fluids. This review examines the clinical potential of circulating tumor DNA (ctDNA) in epithelial ovarian cancer. A systematic search of the PubMed database was conducted. Inclusion criteria were studies published in English, original research articles, reviews, or meta-analyses focused on ctDNA and ovarian cancer. Exclusion criteria included non-peer-reviewed sources, articles with insufficient data, and studies not directly related to the topic. In epithelial ovarian cancer, ctDNA allows quantitative evaluation of tumor burden and qualitative analysis by detecting specific tumor DNA variations, such as epigenetic modifications or genetic mutations. Furthermore, its half-life is less than 2 hours, enabling dynamic monitoring of tumor evolution. This capability could facilitate earlier diagnosis, better screening, and more effective therapeutic follow-up. The qualitative approach also has the potential to predict chemoresistance. Technologies used to detect ctDNA in blood include quantitative polymerase chain reaction, digital polymerase chain reaction, and next-generation sequencing, which allow quantification and identification of DNA molecule modifications. CtDNA is a promising biomarker for epithelial ovarian cancer and could address several challenges in its management. However, further research is needed to establish its role in routine clinical practice, particularly, to identify a detection method that is highly sensitive, specific, and generalizable to a wide patient population.

Robotic Sentinel Lymph Node Dissection for Presumed Early-Stage Epithelial Ovarian Cancer Stadification by Transperitoneal and Retroperitoneal Approaches

Epithelial ovarian cancer (EOC) is a significant global health concern. Early detection remains rare, with only 20% of cases identified at an early stage, highlighting the critical need for effective staging interventions [1]. Traditional extensive lymphadenectomy, associated with considerable morbidity, has led to the exploration of selective sentinel lymph node biopsy (SLNB), which is still under study [1-4]. SLNB, enhanced by robotic technology, is demonstrated through two clinical case studies studies that show how robotic systems are used to meticulously identify and map sentinel nodes, focusing on procedural specifics and fluorescence-guided node identification. The article synthesizes insights from recent studies [1-4], emphasizing the integration of robotic technology with SLNB to enhance surgical precision, improve recovery, and reduce morbidity. We examine SLNB through retroperitoneal and transperitoneal approaches, highlighting technical aspects and the benefits of robotic assistance over conventional laparoscopy, such as improved precision and ergonomics. A recent analysis and meta-analysis [1] showed a high pooled detection rate, though the evidence quality is low. Recently, the MELISA [3] and SELLY [2] studies were published, with MELISA showing higher detection, sensitivity, and specificity rates than SELLY. Sentinel lymph nodes vary in location, requiring meticulous exploration [1]. The retroperitoneal approach might offer an advantage for para-aortic dissection, particularly in obese patients, however, in sentinel lymph node biopsy, the need for extensive dissection could potentially limit its use [5]. Key technique aspects include injection zones and using combined tracers [2]. Limitations include variable detection rates, lack of standardized protocols, accessibility to robotic technology, and the need for advanced surgical skills [1]. SLNB, particularly with robotic assistance, shows promise for improving accuracy and reducing morbidity in epithelial ovarian cancer. However, its use remains limited to clinical trials. Future studies should focus on developing standardized protocols to achieve consistent results and provide sufficient evidence for its integration into routine clinical practice.

Prognostic impact of para-aortic surgical staging in stage IIIC1 cervical cancer according to the FIGO 2018 classification

To assess overall survival in stage IIIC1 cervical cancer patients (International Federation of Gynecology and Obstetrics 2018 classification) comparing those with and without para-aortic surgical staging, and, secondarily, to evaluate disease-free survival. This multi-center retrospective study used the FRANCOGYN cohort, covering 12 French institutions and including 2410 patients diagnosed from January 1996 to December 2023. Inclusion criteria were: patients with stage IIIC1 cervical cancer and pelvic lymph node involvement identified by positron emission tomography-computed tomography, histology, or magnetic resonance imaging. Exclusion criteria were: neuroendocrine carcinomas, unavailable imaging, lymph nodes less than 10 mm in diameter on magnetic resonance imaging, and therapeutic management not following practice guidelines. The Kaplan-Meier method was used to estimate survival distribution. A Cox proportional hazards model was used to account for the influence of multiple variables. Out of 279 patients, 189 (67.7%) underwent para-aortic surgical staging, while 90 (32.3%) did not. The mean age was 51.5 ± 12.3 years, and most patients had squamous cell carcinoma (81.7%). Patients who underwent surgical staging were younger, had lower body mass index, and had smaller primary tumor size. The mean follow-up was 38.8 months (IQR, 14.6-56.8). Positive para-aortic lymph nodes were found in 39 patients (20.9%). There was no significant survival improvement with para-aortic staging for overall survival (HR 0.70, 95% CI 0.36 to 1.37) or disease-free survival (HR 0.81, 95% CI 0.49 to 1.33). Perioperative complications occurred in 14.8% of cases (3.7% intraoperative and 11.1% post-operative). The most frequent post-operative complication was lymphocele, while ventilatory complications with hypercapnia were the most common intraoperative events. Our study found no significant survival benefit for para-aortic surgical staging compared to radiologic staging in patients with stage IIIC1 cervical cancer. These results challenge the principle of surgical staging in this patient population.

Folate Receptor Targeted Photodynamic Therapy: A Novel Way to Stimulate Anti-Tumor Immune Response in Intraperitoneal Ovarian Cancer

Photodynamic therapy (PDT) has shown improvements in cancer treatment and in the induction of a proper anti-tumor immune response. However, current photosensitizers (PS) lack tumor specificity, resulting in reduced efficacy and side effects in patients with intraperitoneal ovarian cancer (OC). In order to target peritoneal metastases of OC, which overexpress folate receptor (FRα) in 80% of cases, we proposed a targeted PDT using a PS coupled with folic acid. Herein, we applied this targeted PDT in an in vivo mouse model of peritoneal ovarian carcinomatosis. The efficacy of the treatment was evaluated in mice without and with human peripheral blood mononuclear cell (PBMC) reconstitution. When mice were reconstituted, using a fractionized PDT protocol led to a significantly higher decrease in the tumor growth than that obtained in the non-reconstituted mice (p = 0.0469). Simultaneously, an immune response was reflected by an increase in NK cells, and both CD4+ and CD8+ T cells were activated. A promotion in cytokines IFNγ and TNFα and an inhibition in cytokines TGFβ, IL-8, and IL-10 was also noticed. Our work showed that a fractionized FRα-targeted PDT protocol is effective for the treatment of OC and goes beyond local induction of tumor cell death, with the promotion of a subsequent anti-tumor response.

Anti-NMDA receptor encephalitis associated with ovarian tumor: the gynecologist point of view

Anti-NMDA receptor antibody (anti-NMDAr) encephalitis, although still a rare condition, is well known to neurologists as it is the leading cause of non-infectious acute encephalitis in young women. However, this is less well known to gynecologists, who may have a decisive role in etiological management. Indeed, in 30-60% of cases in women of childbearing age, it is associated with the presence of an ovarian teratoma, whose removal is crucial in the resolution of symptomatology. Primary objective of our work was to present a review in a very schematic and practical way for gynecologists, about the data on anti-NMDAr encephalitis in terms of epidemiology, clinical symptomatology, treatment and prognosis. The second objective was to propose a decision tree for gynecologists to guide them, in collaboration with neurologists and anesthesiologists, after the diagnosis of NMDAr encephalitis associated with an ovarian mass. We conducted an exhaustive review of existing data using PubMed and The Cochrane Library. Then, we illustrated this topic by presenting two typical cases from our experience. Anti-NMDA antibody encephalitis association with an ovarian teratoma is common, especially in women of reproductive age. Complementary examinations in search of an ovarian teratoma must therefore be systematic to envisage a possible surgical excision that may improve patient prognosis. Anti-NMDA antibody encephalitis should not be ignored by gynecologists whose role in management is central.

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

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. 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." 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). 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.

First external validity study of the Fagotti score in ovarian cancer

Abstract 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.

Patent Blue SLN in Early Ovarian Cancer Prospective Study (FIGO I-II) Evaluating Patent Blue SLN Mapping. Injection Into IP/UO Ligaments in Situ. Goals: Assess Feasibility and Accuracy vs Standard Lymphadenectomy to Minimize Surgical Morbidity

the standard of care in case of early ovarian cancer (stage I or II) is a complete surgery. This surgery includes : hysterectomy (remove of the uterus), bilateral salpingo-oophorectomy (remove of the adnexa), omentectomy (remove of the epiploon), bilateral pelvic lymphadenectomy (remove of pelvic lymph nodes) and para-aortic lymphadenectomy (remove of para-aortic lymph nodes). This procedure is diagnostic, curative and prognostic surgery. In fact, it allows us provider care giver to stratify the stage of the cancer, hence we give the appropriate adjuvant therapy. However, this surgery, especially the extended lymphadenectomy, is associated with some risks: lymphocele, vessel injury, blood loss, morbidity, long recovery period ... In order to reduce these risks, we propose a sentinel lymph node biopsy. This intervention allows us to detect first lymph node relay whether pelvic or para-aortic. In our study, we chose the patent blue dye as a tracer. This tracer is widely used in oncologic surgery (for example in breast cancer) and approved but not in ovarian cancer yet. During surgery for early stage ovarian cancer, we will inject the patent blue dye on both side of the ovarian tumor. Then, we will check for first colorful lymph node, in both pelvic and para-aortic regions. We will send these dissected lymph node to pathology for analysis. Finally, we will continue the procedure as the standard of care. Our objective is to compare the results between the sentinel lymph node and the complete lymphadenectomy and to study the technique of sentinel lymph node biopsy using the blue patent dye as tracer.