1st Evidence-based Italian consensus conference on cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal carcinosis from ovarian cancer.

Ovarian cancer (OC) remains relatively rare, although it is among the top 4 causes of cancer death for women younger than 50. The aggressive nature of the disease and its often late diagnosis with peritoneal involvement have an impact on prognosis. The current scientific literature presents ambiguous or uncertain indications for management of peritoneal carcinosis (PC) from OC, both owing to the lack of sufficient scientific data and their heterogeneity or lack of consistency. Therefore, the Italian Society of Surgical Oncology (SICO), the Italian Society of Obstetrics and Gynaecology, the Italian Association of Hospital Obstetricians and Gynaecologists, and the Italian Association of Medical Oncology conducted a multidisciplinary consensus conference (CC) on management of advanced OC presenting with PC during the SICO annual meeting in Naples, Italy, on September 10-11, 2015. An expert committee developed questions on diagnosis and staging work-up, indications, and procedural aspects for peritonectomy, systemic chemotherapy, and hyperthermic intraperitoneal chemotherapy for PC from OC. These questions were provided to 6 invited speakers who answered with an evidence-based report. Each report was submitted to a jury panel, representative of Italian experts in the fields of surgical oncology, gynecology, and medical oncology. The jury panel revised the reports before and after the open discussion during the CC. This article is the final document containing the clinical evidence reports and statements, revised and approved by all the authors before submission.

Cytoreduction (Peritonectomy Procedures) Combined with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Advanced Ovarian Cancer: Retrospective Italian Multicenter Observational Study of 511 Cases.

PURPOSE: The aim of this study was to help with the process of selecting patients with advanced ovarian cancer to undergo cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) by analyzing outcome data at distinct clinical time points reflecting the natural history of the disease. METHODS: In a retrospective Italian multicenter study investigating patients with advanced ovarian cancer who underwent CRS plus HIPEC between 1998 and 2014, we analyzed data for consecutive patients at eight treatment time points: primary debulking surgery (PDS); interval debulking surgery after partial response, after no response, and after a pathologic complete response to neoadjuvant chemotherapy; first recurrence with a progression-free interval >12, <12 months, or >12 months in patients who underwent further chemotherapy before CRS and HIPEC; and patients who underwent two or more CRS procedures and chemotherapy lines before CRS and HIPEC. RESULTS: The 511 enrolled patients underwent 3373 procedures; 72.6% achieved complete cytoreduction, with an overall major morbidity of 17.4%. At a median follow-up of 53.8 months, overall survival (OS) was 54.2 months (95% confidence interval [CI] 44-58.4) and progression-free (PFS) survival was 16.6 months (95% CI 14.7-19.1). Outcome analysis in patients in whom CRS plus HIPEC was used for primary advanced cancer or recurrent ovarian cancer showed significant differences in OS and PFS according to the time points analyzed. Multivariate analysis identified completeness of CRS, Peritoneal Cancer Index, and the times when patients underwent CRS plus HIPEC as independent prognostic factors. CONCLUSIONS: This selective information on survival should help in interpreting the findings from ongoing randomized studies focusing on CRS plus HIPEC in patients with advanced ovarian cancer.

Hyperthermic intraperitoneal chemotherapy with cisplatin and paclitaxel in advanced ovarian cancer: a multicenter prospective observational study.

OBJECTIVE: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been recently reported with favorable oncological outcomes as treatment of advanced epithelial ovarian cancer (EOC). The aim of this study was to demonstrate the feasibility of CRS+HIPEC with cisplatin and paclitaxel for the treatment of advanced EOC. METHODS: This is a prospective observational study of 54 patients, from April 2007 to October 2013, with primary or recurrent peritoneal carcinomatosis due to EOC. The mean age was 54.51±9.34. Thirty patients (59%) had primary EOC, and 24 patients (41%) had recurrent disease. RESULTS: Mean peritoneal cancer index was 10.11 (range, 0 to 28), complete cytoreduction (CC0) was achieved for 47 patients (87%), CC1 for seven patients (13%). Patients with suboptimal cytoreduction (CC2 and CC3) were not included in the study. The mean stay in intensive care unit was 4.73±5.51 days and the mean hospitalization time was 24.0±10.03 days. We did not observe any intraoperative death. Seven patients (13%) required additional operations. Three patients (5.6%) died within 30 days from the procedure. Severe complications were seen in 19 patients (35.2%). During the follow-up period, disease recurred in 33 patients (61.1%); the median disease-free survival time was 12.46 months and the median overall survival time was 32.91 months. CONCLUSION: CRS+HIPEC with cisplatin and paclitaxel for advanced EOC is feasible with acceptable morbidity and mortality. Additional follow-up and further studies are needed to determine the effects of HIPEC on long term survival.

Short-term outcome of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: preliminary analysis of a multicentre study.

AIM: To assess the incidence of morbidity and mortality of Cytoreductive Surgery plus Hyperthermic Intraperitoneal Chemotherapy. PATIENTS AND METHODS: A retrospective multicentric study was performed. Six hundred and eighty-three patients were recorded. Predictors of morbidity and mortality were evaluated with univariate and multivariate analysis. RESULTS: In univariate analysis, older age, Eastern Cooperative Oncology Group score, a greater value of Peritoneal Cancer Index (PCI) and sub-optimal cytoreduction were correlated with higher mortality, while older age, presence of ascites, ovarian origin of carcinomatosis, closed technique, a greater value of PCI, longer operative time and sub-optimal cytoreduction were predictors of higher morbidity. In multivariate analysis, older age and a greater value of PCI were correlated with higher mortality; older age, ovarian origin of tumor, presence of ascites, closed technique and longer operative time were predictors of higher morbidity. CONCLUSION: Careful patient selection has to be performed to improve clinical outcomes.

Evaluation of extensive cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with advanced epithelial ovarian cancer.

OBJECTIVE: Although standard treatment for advanced epithelial ovarian cancer (EOC) consists of surgical debulking and intravenous platinum- and taxane-based chemotherapy, favorable oncological outcomes have been recently reported with the use of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The aim of the study was to analyze feasibility and results of CRS and HIPEC in patients with advanced EOC. MATERIALS/METHODS: This is an open, prospective phase 2 study including patients with primary or recurrent peritoneal carcinomatosis due to EOC. Thirty-nine patients with a mean (SD) age of 57.3 (9.7) years (range, 34-74 years) were included between September 2005 and December 2009. Thirty patients (77%) had recurrent EOC and 9 (23%) had primary EOC. RESULTS: For HIPEC, cisplatin and paclitaxel were used for 11 patients (28%), cisplatin and doxorubicin for 26 patients (66%), paclitaxel and doxorubicin for 1 patient (3%), and doxorubicin alone for 1 patient (3%). The median intra-abdominal outflow temperature was 41.5°C. The mean peritoneal cancer index (PCI) was 11.1 (range, 1-28); and according to the intraoperative tumor extent, the tumor volume was classified as low (PCI <15) or high (PCI ≥15) in 27 patients (69%) and 12 patients (31%), respectively. Microscopically complete cytoreduction was achieved for 35 patients (90%), macroscopic cytoreduction was achieved for 3 patients (7%), and a gross tumor debulking was performed for 1 patient (3%). Mean hospital stay was 23.8 days. Postoperative complications occurred in 7 patients (18%), and reoperations in 3 patients (8%). There was one postoperative death. Recurrence was seen in 23 patients (59%) with a mean recurrence time of 14.4 months (range, 1-49 months). CONCLUSIONS: Hyperthermic intraperitoneal chemotherapy after extensive CRS for advanced EOC is feasible with acceptable morbidity and mortality. Complete cytoreduction may improve survival in highly selected patients. Additional follow-up and further studies are needed to determine the effects of HIPEC on survival.

Local α-tocopherol for acute and short-term vaginal toxicity prevention in patients treated with radiotherapy for gynecologic tumors.

INTRODUCTION: Data in literature about the use of adjuvant treatment to reduce acute adverse effects of radiotherapy on the pelvis are scant, with the exception of a few reports on the topical use of estrogen, which promotes proliferation of epithelium. MATERIALS AND METHODS: In this prospective trial, α-tocopherol acetate was topically administered to patients affected by endometrial and cervical cancer and undergoing radiation treatment to avoid acute vaginal complications. RESULTS: Vaginal application of α-tocopherol reduced vaginal toxicity and pain, although vaginal secretion was not significantly different in the 2 groups studied. The histological scoring system showed a significant reduction of inflammation, no difference in fibrosis, and an increase of acanthosis. CONCLUSIONS: The use of α-tocopherol as adjuvant treatment to reduce the acute adverse effects of radiotherapy on the vagina should be considered.