CHRONO: randomized trial of the CHROnology of surgery after Neoadjuvant chemotherapy for Ovarian cancer.

BACKGROUND: In patients treated for advanced ovarian cancer not suitable for complete primary surgery, interval surgery after three courses of neoadjuvant chemotherapy has been considered standard management since the EORTC randomized trial published in 2010. An alternative approach with delayed surgery after six courses of neoadjuvant chemotherapy was reported in retrospective series. PRIMARY OBJECTIVES: To assess the efficacy on progression free survival of interval cytoreduction surgery after three cycles of neoadjuvant chemotherapy compared with delayed surgery after six cycles of neoadjuvant chemotherapy. STUDY HYPOTHESIS: In women with ovarian cancer not suitable for primary surgical cytoreduction, surgery after six cycles of neoadjuvant chemotherapy will prove better disease-free survival than cytoreductive surgery after only three cycles. TRIAL DESIGN: CHRONO is a multicenter, randomized phase III trial. After three courses of neoadjuvant chemotherapy, eligible patients will be randomized (1:1) to either completion surgery followed by an additional five cycles of chemotherapy (control arm) or an additional three cycles of neoadjuvant chemotherapy followed by completion surgery and then two additional cycles of chemotherapy (experimental arm). Patients in both groups will receive eight total cycles of chemotherapy. MAJOR INCLUSION/EXCLUSION CRITERIA: The main inclusion criteria are histologically confirmed epithelial high-grade serous or endometrioid ovarian cancer, documented FIGO stage IIIB-IVA unsuitable for complete primary surgery but considered resectable after three courses of neoadjuvant chemotherapy. The main exclusion criteria are mucinous, clear cell, carcinosarcoma, or low-grade serous histologies. PRIMARY ENDPOINT: The primary endpoint is progression-free survival. SAMPLE SIZE: 210 eligible patients ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: The estimated date for completing accrual will be Q2 2023. The estimated date for presentation of the first results is Q3 2028. TRIAL REGISTRATION NUMBER: NCT03579394.

Laparoscopic management of advanced epithelial ovarian cancer after neoadjuvant chemotherapy: a phase II prospective multicenter non-randomized trial (the CILOVE study).

OBJECTIVE: The aim of this study was to explore the feasibility and safety of the laparoscopic approach after neoadjuvant chemotherapy among selected chemosensitive patients with advanced ovarian cancer. METHODS: The CILOVE study was a phase II prospective non-randomized multicenter study. It aimed to enroll 47 women with unresectable disease at the time of initial diagnosis (International Federation of Gynecology and Obstetrics (FIGO) stage IV and/or diffuse extensive carcinomatosis for advanced FIGO stage IIIC or patients unfit to withstand radical primary surgery), in response to chemotherapy and fit to undergo laparoscopy. RESULTS: Among the 48 patients enrolled in the trial, 44 (92%) patients underwent exploratory staging laparoscopy and, as a result, 41 patients were eligible for cytoreductive surgery. Among them, 32 were intended to be managed by laparoscopy and nine patients were managed by laparotomy. The conversion rate to laparotomy was 9.4% (3/32) and the reasons were multiple surgical adhesions (n=1), miliary carcinomatosis and adhesion to the intraperitoneal mesh (n=1), and poor laparoscopic evaluation of transverse colon involvement (n=1). All except one patient had optimal cytoreduction (97% complete cytoreduction, 3% incomplete cytoreduction (residual tumor <2.5 mm)). The median operative time was 267 min (range 146-415) and the median estimated blood loss was 150 mL (range 0-500). Two patients had intra-operative complications: one diaphragm rupture that was repaired during laparoscopy and one bradycardia. Six patients experienced early post-operative complications (<1 month), but there were no grade 3 and 4 complications (3 infections, 1 lymphoedema, 2 hemorrhage). After cytoreductive laparoscopy, the percentage of patients without progression at 12 months was 87.5%. CONCLUSIONS: Interval ovarian cytoreduction by a laparoscopic approach is safe and feasible for patients with a favorable response to chemotherapy. With the widespread use of neoadjuvant chemotherapy in the management of advanced ovarian cancer, a minimally invasive approach may be a potential option.

Management of desmoid tumours: A nationwide survey of labelled reference centre networks in France.

PURPOSE: The optimal management of rare tumours (i.e. from accurate diagnosis to management in reference centres) is a public health challenge. In 2009, the French National Cancer Institute (INCa) identified and financially supported the two expert networks for pathological and clinical diagnosis and management of soft tissue tumours. METHODS: The activities of both networks were prospectively collected using a nationwide database (rreps.org). Data describing the diagnosis management of 863 successive cases of desmoids tumours (DT) were prospectively collected from 2010 to 2013 and analysed. RESULTS: The number of confirmed DT constantly improved from January 2010 to December 2013 (from 173 to 273 cases per year); the expected incidence ranged from 132 to 330 cases/year. The rate of cases diagnosed with core-needle biopsies and CTNNB1 mutational status analysis increased from 30.6 to 40.7% and from 87.8 to 94.1%, respectively. The mean delay for pathological diagnosis confirmation constantly decreased from 107 to 47 d. Among the 846 adult patients, 414 (48.9%) patients were treated by reference centres. The rate of patients managed by reference centres constantly increased with time from 36.9 to 49.5% since 2010. The median management time of the referral centres constantly decreased from 440 to 67 d. CONCLUSION: The two expert networks worked synergistically and improved diagnosis modalities of rare desmoid tumours at a national level. The impact of management by expert networks on the outcome will be prospectively analysed in the future.