Salvage lymphadenectomy in recurrent ovarian cancer patients: Analysis of clinical outcome and BRCA1/2 gene mutational status.

OBJECTIVE: This study is aimed to analyze the clinical outcome of recurrent ovarian cancer patients bearing isolated lymph-node recurrence (ILNR) who underwent salvage lymphadenectomy (SL). The prognostic role of clinicopathological variables and the mutational status of BRCA1/2 have also been investigated. METHODS: This retrospective, single-institutional study included women with platinum-sensitive lymph node recurrence underwent to SL between June 2008 and June 2018. Univariate and multivariate analysis was performed to evaluate the impact of clinical parameters, and BRCA1/2 mutational status on post salvage lymphadenectomy progression-free survival (PSL-PFS). RESULTS: As of June 2019, the median follow-up after SL was 30 months, and the relapse has been documented in 48 (56.5%) patients. In the whole series, the median PSL-PFS was 21 months, and the 3-year PSL-PFS was 36.7%. The median PSL-PFS, according to patients with ILNR (N = 71) versus patients with lymph-nodes and other sites of disease (N = 14), was 27 months versus 12 months, respectively. Univariate analysis of variables conditioning PSL-PFS showed that platinum-free interval (PFI) ≥12 months, normal Ca125 serum levels, and number of metastatic lymph-nodes ≤3 played a statistically significant favorable role. In multivariate analysis, PFI duration ≥12 months and the number of metastatic lymph nodes ≤3 were shown to keep their favorable, independent prognostic value on PSL-PFS. CONCLUSIONS: In the context of SL, the patients with long PFI and low metastatic lymph node numbers at ILNR diagnosis have the best outcome. The BRCA mutational status seems not associated with clinical variables and PSL-PFS, differently from other sites of disease in ROC patients.

Long-Term Survival for Platinum-Sensitive Recurrent Ovarian Cancer Patients Treated with Secondary Cytoreductive Surgery Plus Hyperthermic Intraperitoneal Chemotherapy (HIPEC).

BACKGROUND: To analyze the 5- and 7-year survival outcomes for women with platinum-sensitive recurrent epithelial ovarian cancer (REOC) who underwent secondary cytoreductive surgery (SCS) plus platinum-based hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: From the electronic databases of the Department of Obstetrics and Gynecology at the Catholic University of the Sacred Heart of Rome and of the S. Orsola Hospital, University of Bologna, a consecutive series of REOC patients were selected using the following inclusion criteria: primary platinum-free interval (PFI-1) of 6 months or longer, completeness of secondary cytoreduction score (CC) of 1 or lower, minimum follow-up period of 48 months, Eastern Cooperative Group (ECOG) performance status at recurrence of 1 or less, and platinum-based HIPEC. Progression-free survival (PFS) and post-relapse survival (PRS) were calculated as the time between SCS + HIPEC and secondary recurrence or death, respectively. RESULTS: The final study population included 70 women with platinum-sensitive REOC. The median follow-up time was 73 months (range 48-128 months), and the median PFI-1 was 19 months (range 6-100 months). At the time of recurrence, the median peritoneal cancer index was 7 (range 1-21), and a CC score of 0 was achieved for 62 patients (88.6 %). As the HIPEC drug, we used oxaliplatin in 17 cases (38.6 %) and cisplatin in 43 cases (61.4 %). No postoperative deaths were observed, and the complication rate for grades 3 and 4 disease was 8.6 %. The median PFS duration was 27 months (range 5-104 months), and the 5- and 7-year PRS rates were respectively 52.8 and 44.7 %, (median PRS 63 months). CONCLUSIONS: The current study demonstrated favorable 5- and 7-year PRS rates for platinum-sensitive REOC patients undergoing SCS + HIPEC, which encourages the inclusion of patients in randomized clinical trials for definitive conclusions to be drawn.

Minimally invasive secondary cytoreduction plus HIPEC for recurrent ovarian cancer: a case series.

OBJECTIVE: To analyze the feasibility of laparoscopic/robotic secondary cytoreductive surgery and hyperthermic intraperitoneal intra-operative chemotherapy (SCS+HIPEC) in a retrospective series of isolated platinum sensitive recurrent ovarian cancer. METHODS: We retrospectively evaluated a consecutive series of ovarian cancer patients with isolated platinum sensitive relapse. Isolated relapse was defined as the presence of a single nodule, in a single anatomic site. In all cases the presence of isolated relapse was assessed at pre-operative FDG-PET/CT scan, and confirmed with staging laparoscopy performed immediately before SCS+HIPEC. RESULTS: 84 women with platinum sensitive relapse received SCS+HIPEC during a 4-year period. Among them, 10 cases (11.9%) showed isolated relapse and were treated with laparoscopic/robotic SCS+HIPEC. In all cases complete debulking was achieved. In HIPEC treatment, 9 women received cisplatin at 75 mg/m(2), and the remaining patient oxaliplatin 460 mg/m(2). In 7 patients SCS was performed through the laparoscopic route, and in 3 cases with a robotic approach. The median operative time from skin incision to the end of cytoreductive surgery was 122 min (95-140), estimated blood loss was 50 cm(3) (50-100), and the median length of hospital stay was 4 days (3-7). The interval from surgery to adjuvant chemotherapy was 21 days (19-32). No grade 3/4 surgical, metabolic, or hematologic complications occurred. In all cases post-operative FDG-PET/CT scan was negative, and after a median time of 10 months (6-37) from SCS+HIPEC no secondary recurrence was observed. CONCLUSIONS: Minimally invasive SCS+HIPEC can be safely performed in selected ovarian cancer patients with platinum sensitive isolated relapse.

Long-term analysis of clinical outcome and complications in locally advanced cervical cancer patients administered concomitant chemoradiation followed by radical surgery.

OBJECTIVE: Preoperative chemoradiation (CT/RT) has been shown to achieve encouraging results in terms of clinical outcome in locally advanced cervical cancer (LACC). The study aims at analyzing the long-term results of this multimodal approach in a single institution series of 184 cases. METHODS: Patients underwent whole pelvic irradiation combined with cisplatin and 5-fluorouracil. After evaluation of clinical response, patients were triaged to surgery. Surgical morbidity was classified according to Chassagne grading system. Univariate and multivariate analyses were used to assess the prognostic and predictive role of clinicopathological parameters. RESULTS: Clinical response was observed in 96.1% of cases. A total of 174 cases were submitted to radical surgery: 124 patients (71.3%) showed complete/microscopic pathological response. In multivariate analysis, clinical response, stage of disease, and histotype predicted response to CT/RT. With a median follow-up of 58 months, recurrence and death of disease were observed in 42 and 40 patients, respectively. The 5-year DFS was 75.5%, while the 5-year OS was 77.4%. Patients with no residual disease showed a significant longer DFS than patients with microscopic (p value = 0.0128), and macroscopic (p value = 0.0001) residual tumor after treatment. In multivariate analysis, residual tumor and stage of disease were the two most relevant prognostic factors for DFS and OS. As far as long-term toxicity is concerned, 8 out of 22 complications were grade 3/4. CONCLUSION: Preoperative CT/RT is worth further investigation in LACC patients, providing encouraging survival outcomes and a favourable long-term toxicity profile.

Secondary cytoreduction plus oxaliplatin-based HIPEC in platinum-sensitive recurrent ovarian cancer patients: a pilot study.

OBJECTIVES: To assess feasibility, complications and efficacy of secondary surgical cytoreduction (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in a selected group of platinum-sensitive recurrent ovarian cancer patients. METHODS: Recurrent ovarian cancer patients with a platinum-free interval of at least 6 months were prospectively enrolled. After complete CRS they were submitted to intraperitoneal perfusion of oxaplatinum (460 mg/m(2)) heated to 41.5 degrees C for 30 min. Then they received systemic chemotherapy with taxotere 75 mg/m(2) and oxaliplatin 100 mg/m(2) for 6 cycles. Patients were followed up routinely until recurrence or death. RESULTS: Twenty-five recurrent ovarian cancer patients were valuable for the study. The median Platinum Free Interval (PFI) was 25 months (range 7-67). The majority of the patients (76%) had diffuse carcinosis. Nobody had ascites. An optimal residual disease was obtained in all patients. The median duration of CRS+HIPEC was 312 min (range 138-619). Median intensive care unit (ICU) stay was 2 days (1-6), median hospital stay was 13 days (7-30). Post-operative major complications were observed in 7 patients (28%). Post-operative mortality was 0%. With a median follow-up time of 18 months (range 3-38), 24 patients (96%) are alive, but seven women (28%) have relapsed. CONCLUSIONS: Adequate pre-operative selection can improve feasibility of CRS and HIPEC. Morbidity rate is comparable to aggressive cytoreduction without HIPEC. Although associated with some post-operative morbidity, long-term results are encouraging, waiting for larger series and longer follow-up data.

Preoperative concomitant chemoradiotherapy in locally advanced cervical cancer: safety, outcome, and prognostic measures.

OBJECTIVES: To evaluate the morbidity, and the therapeutic value of surgery after chemoradiation in a large series of locally advanced cervical cancers (LACC). The prognostic role of different clinico-pathological factors has been also evaluated. METHODS: Between October 1997 and October 2006, 161 LACC patients were treated at both the Gynecologic Oncology Units of the Catholic University of Rome and Campobasso. Radiotherapy was administered to the whole pelvic region in combination with cisplatin and 5-fluorouracil. Radical surgery was performed 5-6 weeks after the end of the treatment. RESULTS: A clinical complete/partial response was observed in 153 patients and radical surgery was performed in 152 cases. The overall rate of surgical complications was 33% with 15 (10%) patients experiencing severe toxicities. At pathological examination 111 of 152 patients (73%) showed absent/microscopic residual disease. With a median follow-up of 28 months, the 5-year disease free-survival (DFS) was 83% and the 5-year overall survival (OS) 90%. Advanced FIGO (Federation Internationale de Gynecolgie et d'Obstetrique) stage, pathological response and lymph node involvement were found significantly associated with clinical outcome. CONCLUSIONS: We confirmed in a larger series the safety and efficacy of this multimodal approach in the treatment of LACC. The pathological assessment of response can allow not only a tailored surgery in selected patients, but also the identification of patients with higher risk of recurrence to be submitted to adjuvant therapies.