title: Hyperthermic Intraperitoneal Chemotherapy (HIPEC) at the Time of Primary Curative Surgery in Patients with Colorectal Cancer at High Risk for Metachronous Peritoneal Metastases.
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).
  
  
  CONCLUSIONS
  Adjuvant HIPEC may benefit CRC patients at high-risk for peritoneal failure. These results warrant confirmation in phase III trials.
authors: Peritoneal Malignancy Program, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy. dario.baratti@istitutotumouri.mi.it.
authors: Dario
authors: D
authors: Baratti
authors: Peritoneal Malignancy Program, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors: Shigeki
authors: S
authors: Kusamura
authors: General Surgery Unit, Bentivoglio Hospital, AUSL Bologna, Bentivoglio, Bologna, Italy.
authors: Domenico
authors: D
authors: Iusco
authors: Department of Haematology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors: Silvia
authors: S
authors: Gimondi
authors: Department of Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors: Filippo
authors: F
authors: Pietrantonio
authors: Department of Pathology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors: Massimo
authors: M
authors: Milione
authors: Colorectal Cancer Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors: Marcello
authors: M
authors: Guaglio
authors: General Surgery Unit, Bentivoglio Hospital, AUSL Bologna, Bentivoglio, Bologna, Italy.
authors: Serena
authors: S
authors: Bonomi
authors: General Surgery Unit, Bentivoglio Hospital, AUSL Bologna, Bentivoglio, Bologna, Italy.
authors: Antonio
authors: A
authors: Grassi
authors: General Surgery Unit, Bentivoglio Hospital, AUSL Bologna, Bentivoglio, Bologna, Italy.
authors: Salvatore
authors: S
authors: Virzì
authors: Colorectal Cancer Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors: Ermanno
authors: E
authors: Leo
authors: Peritoneal Malignancy Program, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors: Marcello
authors: M
authors: Deraco
mesh_terms: D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology* / Q000601:surgery*; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods; D007558:Italy; D008297:Male; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000556:secondary*; D010534:Peritoneal Neoplasms / Q000556:secondary*; D011446:Prospective Studies; D012307:Risk Factors