Role of Hyperthermic Intraperitoneal Chemotherapy Combined with Cytoreductive Surgery as Consolidation Therapy for Advanced Epithelial Ovarian Cancer.

BACKGROUND: Patients with advanced epithelial ovarian cancer who undergo incomplete surgery followed by six cycles of chemotherapy could benefit from second-look or consolidation cytoreductive surgery (CCRS). The primary goal of this study was to evaluate the overall survival (OS) in patients undergoing complete CCRS and the factors affecting survival. The secondary goal was to study the benefit of hyperthermic intraperitoneal chemotherapy (HIPEC) in these patients. METHODS: This was a retrospective analysis of 173 patients with CCRS with (n = 118) or without (n = 55) HIPEC treated at 12 French centers. Only patients having a completeness of cytoreduction (CC) 0/1 resection and a minimum of 5 years of follow-up were included. HIPEC was performed systematically for all patients except those treated at the four centers that did not perform HIPEC. RESULTS: The median Peritoneal Cancer Index was 6 (range 0-33). Closed HIPEC was performed in 59 (34.1%) patients and open HIPEC was performed in 56 (32.3%) patients. Grade 3-4 complications occurred in 64 (36.9%) patients. The median OS was 35.67 months (95% confidence interval [CI] 29.8-46.1) and was significantly longer for CCRS + HIPEC (31.4 months without HIPEC and 42.5 months with HIPEC; p = 0.022). On multivariate analysis, closed HIPEC (hazard ratio [HR] 0.46, 95% CI 0.29-0.73; p < 0.001) resulted in a longer OS, and age > 65 years (HR 2.17, 95% CI 1.14-4.11; p = 0.018) and bowel resection (HR 1.98, 95% CI 1.27-3.08; p = 0.020) led to a shorter OS. On multivariate logistic regression analysis, closed HIPEC (odds ratio 0.18; p = 0.001) was associated with a lower risk of dying at 5 years. CONCLUSIONS: CCRS was performed with an acceptable morbidity and resulted in good overall survival. The role of HIPEC in addition to CCRS should be evaluated in prospective, randomized studies and the closed technique prospectively compared with the open technique.

Multicystic peritoneal mesothelioma treated with cytoreductive surgery followed or not by hyperthermic intraperitoneal chemotherapy: results from a large multicentric cohort.

BACKGROUND: Multicystic peritoneal mesothelioma (MCPM) is a rare, slowly growing, condition prone to recur after surgery. The role of hyperthermic intraperitoneal chemotherapy (HIPEC) added to complete cytoreductive surgery (CRS) remains controversial and difficult to assess. As patients are mostly reproductive age women, surgical approach, and fertility considerations are important aspects of the management. This observational retrospective review aimed to accurate treatment strategy reflections. METHODS: The RENAPE database (French expert centers network) was analyzed over a 1999-2019 period. MCPM patients treated with CRS were included. A special focus on HIPEC, mini-invasive approach, and fertility considerations was performed. RESULTS: Overall 60 patients (50 women) were included with a median PCI of 10 (4-14) allowing 97% of complete surgery, followed by HIPEC in 82% of patients. A quarter of patients had a laparoscopic approach. Twelve patients (20%) recurred with a 3-year recurrence free survival of 84.2% (95% confidence interval 74.7-95.0). The hazard of recurrence was numerically reduced among patients receiving HIPEC, however, not statistically significant (hazard ratio 0.41, 0.12-1.42, p = 0.200). A severe post-operative adverse event occurred in 22% of patients with five patients submitted to a subsequent reoperation. Among four patients with a childbearing desire, three were successful (two had a laparoscopic-CRS-HIPEC and one a conventional CRS without HIPEC). CONCLUSION: MCPM patients treatment should aim at a complete CRS. The intraoperative treatment options as laparoscopic approach, fertility function sparing and HIPEC should be discussed in expert centers to propose the most appropriate strategy.

Cytoreductive Surgery With or Without Hyperthermic Intraperitoneal Chemotherapy for Gastric Cancer With Peritoneal Metastases (CYTO-CHIP study): A Propensity Score Analysis.

PURPOSE: Gastric cancer (GC) with peritoneal metastases (PMs) is a poor prognostic evolution. Cytoreductive surgery (CRS) yields promising results, but the impact of hyperthermic intraperitoneal chemotherapy (HIPEC) remains controversial. Here we aimed to compare outcomes between CRS-HIPEC versus CRS alone (CRSa) among patients with PMs from GC. PATIENTS AND METHODS: From prospective databases, we identified 277 patients with PMs from GC who were treated with complete CRS with curative intent (no residual nodules > 2.5 mm) at 19 French centers from 1989 to 2014. Of these patients, 180 underwent CRS-HIPEC and 97 CRSa. Tumor burden was assessed using the peritoneal cancer index. A Cox proportional hazards regression model with inverse probability of treatment weighting (IPTW) based on propensity score was used to assess the effect of HIPEC and account for confounding factors. RESULTS: After IPTW adjustment, the groups were similar, except that median peritoneal cancer index remained higher in the CRS-HIPEC group (6 v 2; P = .003). CRS-HIPEC improved overall survival (OS) in both crude and IPTW models. Upon IPTW analysis, in CRS-HIPEC and CRSa groups, median OS was 18.8 versus 12.1 months, 3- and 5-year OS rates were 26.21% and 19.87% versus 10.82% and 6.43% (adjusted hazard ratio, 0.60; 95% CI, 0.42 to 0.86; P = .005), and 3- and 5-year recurrence-free survival rates were 20.40% and 17.05% versus 5.87% and 3.76% (P = .001), respectively; the groups did not differ regarding 90-day mortality (7.4% v 10.1%, respectively; P = .820) or major complication rate (53.7% v 55.3%, respectively; P = .496). CONCLUSION: Compared with CRSa, CRS-HIPEC improved OS and recurrence-free survival, without additional morbidity or mortality. When complete CRS is possible, CRS-HIPEC may be considered a valuable therapy for strictly selected patients with limited PMs from GC.

Iterative cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastases: A multi-institutional experience.

BACKGROUND AND OBJECTIVES: The aims of this multi-institutional study were to assess the feasibility of iterative cytoreductive surgery (iCRS)/hyperthermic intraperitoneal chemotherapy, iCRS in colorectal peritoneal carcinomatosis (CRPC), evaluate survival, recurrence, morbidity and mortality outcomes, and identify prognostic factors for overall survival. METHODS: Patients with CRPC that underwent an iCRS, with or without intraperitoneal chemotherapy, from June 1993 to July 2016 at 13 institutions were retrospectively analyzed from prospectively maintained databases. RESULTS: The study comprised of 231 patients, including 126 females (54.5%) with a mean age at iCRS of 51.3 years. The iterative high-grade (3/4) morbidity and mortality rates were 23.4% and 1.7%, respectively. The median recurrence-free survival was 15.0 and 10.1 months after initial and iCRS, respectively. The median and 5-year survivals were 49.1 months and 43% and 26.4 months and 26% from the initial and iCRS, respectively. Independent negative predictors of survival from the initial CRS included peritoneal carcinomatosis index (PCI) > 20 ( P = 0.02) and lymph node positivity ( P = 0.04), and from iCRS, PCI > 10 ( P = 0.03 for PCI 11-20; P < 0.001 for PCI > 20), high-grade complications ( P = 0.012), and incomplete cytoreduction ( P < 0.001). CONCLUSION: iCRS can provide long-term survival benefits to highly selected colorectal peritoneal carcinomatosis patients with comparable mortality and morbidity rates to the initial CRS procedure. Careful patient selection is necessary to improve overall outcomes.

Peritoneal Carcinomatosis of Rare Ovarian Origin Treated by Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: A Multi-Institutional Cohort from PSOGI and BIG-RENAPE.

PURPOSE: Ovarian cancer is the most common deadly cancer of gynecologic origin. Patients often are diagnosed at advanced stage with peritoneal metastasis. There are many rare histologies of ovarian cancer; some have outcomes worse than serous ovarian cancer. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) can be considered for patients with recurrence. This study was designed to assess the impact of CRS and HIPEC on survival of patient with peritoneal metastasis from rare ovarian malignancy. METHODS: A prospective, multicentric, international database was retrospectively searched to identify all patients with rare ovarian tumor (mucinous, clear cells, endometrioid, small cell hypercalcemic, and other) and peritoneal metastasis who underwent CRS and HIPEC through the Peritoneal Surface Oncology Group International (PSOGI) and BIG-RENAPE working group. The postoperative complications, long-term results, and principal prognostic factors were analyzed. RESULTS: The analysis included 210 patients with a median follow-up of 43.5 months. Median overall survival (OS) was 69.3 months, and the 5-year OS was 57.7%. For mucinous tumors, median OS and DFS were not reached at 5 years. For granulosa tumors, median overall survival was not reached at 5 years, and median DFS was 34.6 months. Teratoma or germinal tumor showed median overall survival and DFS that were not reached at 5 years. Differences in OS were not statistically significant between histologies (p = 0.383), whereas differences in DFS were (p < 0.001). CONCLUSIONS: CRS and HIPEC may increases long-term survival in selected patients with peritoneal metastasis from rare ovarian tumors especially in mucinous, granulosa, or teratoma histological subtypes.

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Carcinomatosis in the Elderly: A Case-Controlled, Multicenter Study.

OBJECTIVE: This study was designed to identify factors associated with morbidity and mortality in patients older than 70 years who underwent cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis (PC). BACKGROUND: Major surgery is associated with higher morbidity and mortality in elderly patients. For PC, CRS and HIPEC is the only current potential curative therapy, but the risks inherent to this patient population have called its benefits into question. METHODS: We retrospectively analyzed a multi-center database from 1989 to 2015. All patients who underwent CRS and HIPEC for PC were selected and patients older than 70 years were matched 1:4 with a younger cohort according to cancer origin, peritoneal cancer index (PCI), and completeness of cytoreduction. Major morbidity and mortality were analyzed. RESULTS: Of 2328 patients, 188 patients older than aged 70 years were matched with 704 younger patients. Patients older than aged 70 years demonstrated a higher American Society of Anesthesiologist score (≥ASA III 10.8 vs. 6.6 %, p = 0.008). There was no difference in overall 90-day morbidity (≥70: 45.7 % vs. <70: 44.5 %; p = 0.171); however, patients older than 70 years had significantly more cardiovascular complications (13.8 vs. 9.2 %, p = 0.044). Differences between the older and younger cohorts failed to reach significance for 90-day mortality (5.4 and 2.7 %, respectively; p = 0.052), and failure-to-rescue (11.6 and 6.1 %, respectively; p = 0.078). In multivariate analysis, PCI > 7 (95 % CI 1.051-5.798, p = 0.038) and HIPEC duration (95 % CI 1.106-6.235, p = 0.028) were independent factors associated with morbidity in elderly patients. CONCLUSIONS: CRS and HIPEC appear feasible for selected patients older than aged 70 years, albeit with a higher risk of medical complications associated with increased mortality.

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for First Relapse of Ovarian Cancer.

BACKGROUND: To assess impact of surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients treated for a first relapse of ovarian cancer (FROC). PATIENTS AND METHODS: Patients with a FROC treated with second-line chemotherapy, surgery and HIPEC were retrospectively included from 13 Institutions. Studied parameters were interval free between the end of initial treatment and the first relapse, second-line chemotherapy, peritoneal cancer index and completeness of surgery, HIPEC, mortality and morbidity, pathological results and survival. RESULTS: From 2001 to 2010, 314 patients were included. The main strategy was secondary chemotherapy followed by surgery and HIPEC (269/314-85.6%). Mortality and morbidity rates were respectively 1% and 30.9%. Median follow-up was 50 months, 5-year overall survival was 38.0%, with no difference between platinum-sensitive or -resistant patients and 5-year disease-free survival was 14%. CONCLUSION: HIPEC allows encouraging survival in the treatment of FROC, better in case of complete surgery, with acceptable mortality and morbidity rates.