Cyril Touboul

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.

Isolated lymph node recurrence in epithelial ovarian cancer: Recurrence with better prognosis?

The aim of this study was to compare overall survival (OS) between women with isolated lymph node recurrence (ILNR) and those with isolated peritoneal localization of recurrence (ICR), in patients managed for epithelial ovarian cancer. Data from 1508 patients with ovarian cancer were collected retrospectively from1 January 2000 to 31 December 2016, from the FRANCOGYN database, pooling data from 11 centres specialized in ovary treatment. Median overall survival was determined using the Kaplan-Meier method. Univariate and multivariate analyses were performed to define prognostic factors of overall survival. Patients included had a first recurrence defined as ILNR or ICR during their follow up. 79 patients (5.2 %) presented with ILNR, and 247 (16.4 %) patients had isolated carcinomatosis recurrence. Complete lymphadenectomy was performed more frequently in the ILNR group vs. the ICR group (67.1 % vs. 53.4 %, p = 0.004) and the number of pelvic lymph nodes involved was higher (2.4 vs. 1.1, p = 0.008). The number of involved pelvic LN was an independent predictor of ILNR (OR = 1.231, 95 % CI [1.074-1.412], p = 0.0024). The 3-year and 5-year OS rates in the ILNR group were 85.2 % and 53.7 % respectively, compared to 68.1 % and 46.8 % in patients with ICR. There was no significant difference in terms of OS after initial diagnosis (p = 0.18). 3- year and 5-year OS rates after diagnosis of recurrence were 62.6 % and 15.6 % in the ILNR group, and 44 % and 15.7 % in patients with ICR (p = 0.21). ILNR does not seem to be associated with a better prognosis in terms of OS.

Impact of neoadjuvant chemotherapy cycles on survival of patients with advanced ovarian cancer: A French national multicenter study (FRANCOGYN)

The purpose of this study was to compare two groups of patients presenting advanced ovarian carcinoma benefiting from neoadjuvant chemotherapy (NAC) followed by cytoreductive surgery: after 3-4 cycles (group 1) or ≥ 5 cycles (group 2), regarding overall survival (OS) and progression-free survival (PFS), complications related to surgery as well as the extent of cytoreduction were assessed. We conducted a retrospective, multicenter cohort study in nine referral centers of France, reviewing the charts of all patients who underwent NAC between January 2000 and June 2017. We performed an OS analysis using multivariate Cox regression models adjusted for potential confounders. We also analyzed PFS and surgery-related morbidity. Of 501 patients included, 236 (47.1 %) benefited from ≤ 4 NAC cycles and 265 (52.9 %) from ≥ 5 NAC cycles. Characteristics data were similar in both groups. The rate of achievement of complete surgery was similar in both groups (p = 0.28). Surgical morbidity and postoperative complications showed no significant differences between both groups. The median OS was 54.2 months, 64 months for group 1 and 49.2 months for group 2. The 5-year survival rate was 45.6 % and 27.6 %. This difference was not statistically significant [HR 1.81 (0.89-3.71), p = 0.09]. Five-year PFS was 19.7 % and 11.7 % respectively (p = 0.31). In a large series of advanced ovarian cancer, patients receiving late IDS (≥ 5 NAC cycles) seem to show a poorer prognosis than patients operated on earlier. The survival appears to be mainly determined by optimal resection and response to chemotherapy.

Akt-Activated Endothelium Increases Cancer Cell Proliferation and Resistance to Treatment in Ovarian Cancer Cell Organoids

Ovarian cancer (OC) is a heterogeneous disease characterized by its late diagnosis (FIGO stages III and IV) and the importance of abdominal metastases often observed at diagnosis. Detached ovarian cancer cells (OCCs) float in ascites and form multicellular spheroids. Here, we developed endothelial cell (EC)-based 3D spheroids to better represent in vivo conditions. When co-cultured in 3D conditions, ECs and OCCs formed organized tumor angiospheres with a core of ECs surrounded by proliferating OCCs. We established that Akt and Notch3/Jagged1 pathways played a role in angiosphere formation and peritoneum invasion. In patients’ ascites we found angiosphere-like structures and demonstrated in patients’ specimens that tumoral EC displayed Akt activation, which supports the importance of Akt activation in ECs in OC. Additionally, we demonstrated the importance of FGF2, Pentraxin 3 (PTX3), PD-ECGF and TIMP-1 in angiosphere organization. Finally, we confirmed the role of Notch3/Jagged1 in OCC–EC crosstalk relating to OCC proliferation and during peritoneal invasion. Our results support the use of multicellular spheroids to better model tumoral and stromal interaction. Such models could help decipher the complex pathways playing critical roles in metastasis spread and predict tumor response to chemotherapy or anti-angiogenic treatment.

Comparison of survival outcomes between laparoscopic and abdominal radical hysterectomy for early-stage cervical cancer: A French multicentric study

A recent randomized controlled trial has reconsidered the use of laparoscopy for treating patients with early-stage cervical cancer with radical hysterectomy (RH). We aimed to evaluate if surgical approach had an impact on surgical and oncological outcomes in these patients in a French setting. Data of 1706 patients with cervical cancer treated between 1996 and 2017 were extracted from maintained databases of 9 French University hospitals. Patients, with FIGO stage IA2 to IIB tumors, treated by radical hysterectomy were selected for further analysis. A propensity score matching was used with a ratio of 2:1 in favor of laparoscopic approach was used. The Kaplan Meier method was used to estimate the survival distribution. 34 patients treated with laparotomy were matched with 61 patients treated by minimally invasive surgery (MIS). There was no difference regarding overall survival (91 % vs 81 %, p > 0.05) or disease-free survival (82 % vs 78 %, p > 0.05). There was no difference regarding surgical outcomes with no excess of postoperative complication in patients with MIS. Hospital stay was significantly longer in patients operated on laparotomy. In our study, there was no evidence of a difference in survival between minimally invasive surgery and laparotomy in patients treated with radical hysterectomy for early-stage cervical cancer.