Dario Baratti1, Shigeki Kusamura2, Domenico Iusco3, Silvia Gimondi4, Filippo Pietrantonio5, Massimo Milione6, Marcello Guaglio7, Serena Bonomi3, Antonio Grassi3, Salvatore Virzì3, Ermanno Leo7, Marcello Deraco2. 1. Peritoneal Malignancy Program, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy. dario.baratti@istitutotumouri.mi.it. 2. Peritoneal Malignancy Program, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy. 3. General Surgery Unit, Bentivoglio Hospital, AUSL Bologna, Bentivoglio, Bologna, Italy. 4. Department of Haematology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy. 5. Department of Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy. 6. Department of Pathology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy. 7. Colorectal Cancer Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
Abstract
BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) are maximally effective in early-stage colorectal cancer peritoneal metastases (CRC-PM); however, the use of HIPEC to treat subclinical-stage PM remains controversial. This prospective two-center study assessed adjuvant HIPEC in CRC patients at high risk for metachronous PM ( www.clinicaltrials.gov NCT02575859). METHODS: During 2006-2012, a total of 22 patients without systemic metastases were prospectively enrolled to receive HIPEC simultaneously with curative surgery, plus adjuvant systemic chemotherapy (oxaliplatin/irinotecan-containing ± biologics), based on primary tumor-associated criteria: resected synchronous ovarian (n = 2) or minimal peritoneal (n = 6) metastases, primaries directly invading other organs (n = 4) or penetrating the visceral peritoneum (n = 10). A control group retrospectively included 44 matched (1:2) patients undergoing standard treatments and no HIPEC during the same period. The cumulative PM incidence was calculated in a competing-risks framework. RESULTS: Patient characteristics were comparable for all groups. Median follow-up was 65.2 months [95 % confidence interval (CI) 50.9-79.5] in the HIPEC group and 34.5 months (95 % CI 21.1-47.9) in the control group. The 5-year cumulative PM incidence was 9.3 % in the HIPEC group and 42.5 % in the control group (p = 0.004). Kaplan-Meier estimated 5-year overall survival (OS) was 81.3 % in the HIPEC group versus 70.0 % in the control group (p = 0.047). No operative death occurred. Grade 3-4 [National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4] morbidity rates were 18.2 % in the HIPEC group and 25 % in controls (p = 0.75). At multivariate analysis, HIPEC correlated to lower PM cumulative incidence [hazard ratio (HR) 0.04, 95 % CI 0.01-0.31; p = 0.002], and better OS (HR 0.25, 95 % CI 0.07-0.89; p = 0.039) and progression-free survival (HR 0.31, 95 % CI 0.11-0.85; p = 0.028). CONCLUSION: Adjuvant HIPEC may benefit CRC patients at high-risk for peritoneal failure. These results warrant confirmation in phase III trials.
BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) are maximally effective in early-stage colorectal cancer peritoneal metastases (CRC-PM); however, the use of HIPEC to treat subclinical-stage PM remains controversial. This prospective two-center study assessed adjuvant HIPEC in CRC patients at high risk for metachronous PM ( www.clinicaltrials.gov NCT02575859). METHODS: During 2006-2012, a total of 22 patients without systemic metastases were prospectively enrolled to receive HIPEC simultaneously with curative surgery, plus adjuvant systemic chemotherapy (oxaliplatin/irinotecan-containing ± biologics), based on primary tumor-associated criteria: resected synchronous ovarian (n = 2) or minimal peritoneal (n = 6) metastases, primaries directly invading other organs (n = 4) or penetrating the visceral peritoneum (n = 10). A control group retrospectively included 44 matched (1:2) patients undergoing standard treatments and no HIPEC during the same period. The cumulative PM incidence was calculated in a competing-risks framework. RESULTS:Patient characteristics were comparable for all groups. Median follow-up was 65.2 months [95 % confidence interval (CI) 50.9-79.5] in the HIPEC group and 34.5 months (95 % CI 21.1-47.9) in the control group. The 5-year cumulative PM incidence was 9.3 % in the HIPEC group and 42.5 % in the control group (p = 0.004). Kaplan-Meier estimated 5-year overall survival (OS) was 81.3 % in the HIPEC group versus 70.0 % in the control group (p = 0.047). No operative death occurred. Grade 3-4 [National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4] morbidity rates were 18.2 % in the HIPEC group and 25 % in controls (p = 0.75). At multivariate analysis, HIPEC correlated to lower PM cumulative incidence [hazard ratio (HR) 0.04, 95 % CI 0.01-0.31; p = 0.002], and better OS (HR 0.25, 95 % CI 0.07-0.89; p = 0.039) and progression-free survival (HR 0.31, 95 % CI 0.11-0.85; p = 0.028). CONCLUSION: Adjuvant HIPEC may benefit CRC patients at high-risk for peritoneal failure. These results warrant confirmation in phase III trials.
Authors: Ángel Serrano Del Moral; Estíbalitz Pérez Viejo; Israel Manzanedo Romero; Fernando Pereira Pérez Journal: Ann Med Surg (Lond) Date: 2021-01-24
Authors: Charlotte E L Klaver; Roos Stam; Didi A M Sloothaak; Johannes Crezee; Willem A Bemelman; Cornelis J A Punt; Pieter J Tanis Journal: Oncotarget Date: 2017-04-17