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Hyperthermic Intraperitoneal Chemotherapy (HIPEC) at the Time of Primary Curative Surgery in Patients with Colorectal Cancer at High Risk for Metachronous Peritoneal Metastases

  • Gastrointestinal Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

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.

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Disclosures

Dario Baratti, Shigeki Kusamura, Domenico Iusco, Silvia Gimondi, Filippo Pietrantonio, Massimo Milione, Marcello Guaglio, Serena Bonomi, Antonio Grassi, Salvatore Virzì, Ermanno Leo, and Marcello Deraco have no conflicts of interest or financial disclosures to declare.

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    Authors and Affiliations

    1. Peritoneal Malignancy Program, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy

      Dario Baratti MD, Shigeki Kusamura PhD & Marcello Deraco MD

    2. General Surgery Unit, Bentivoglio Hospital, AUSL Bologna, Bentivoglio, Bologna, Italy

      Domenico Iusco PhD, Serena Bonomi MD, Antonio Grassi MD & Salvatore Virzì MD

    3. Department of Haematology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy

      Silvia Gimondi PhD

    4. Department of Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy

      Filippo Pietrantonio MD

    5. Department of Pathology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy

      Massimo Milione MD

    6. Colorectal Cancer Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy

      Marcello Guaglio MD & Ermanno Leo MD

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    1. Dario Baratti MD
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    Correspondence to Dario Baratti MD.

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    Marcello Deraco, Ermanno Leo, and Salvatore Virzì contributed equally to this paper.

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    Baratti, D., Kusamura, S., Iusco, D. et al. Hyperthermic Intraperitoneal Chemotherapy (HIPEC) at the Time of Primary Curative Surgery in Patients with Colorectal Cancer at High Risk for Metachronous Peritoneal Metastases. Ann Surg Oncol 24, 167–175 (2017). https://doi.org/10.1245/s10434-016-5488-5

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    • DOI: https://doi.org/10.1245/s10434-016-5488-5

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