Morbidity, mortality, and oncological outcomes of 401 consecutive cytoreductive procedures with hyperthermic intraperitoneal chemotherapy (HIPEC)

Our plain-English summary of Morbidity, mortality, and oncological outcomes of 401 consecutive cytoreductive procedures with hyperthermic intraperitoneal chemotherapy (HIPEC), by M. Desantis, J.L. Bernard, V. Casanova, et al (Langenbeck's Archives of Surgery, 2015).

The study

• Authors: M. Desantis, J.L. Bernard, V. Casanova, M. Cegarra-Escolano, E. Benizri, A.M. Rahili, D. Benchimol, J.M. Bereder
• Journal: Langenbeck's Archives of Surgery
• Published: 2015;400(1):37-48
• Cited by: 61 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Purpose: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are a novel curative treatment option for selected patients with peritoneal carcinomatosis (PC). We aimed to report the mortality rate and the most frequent grade III-IV adverse events and to identify associated prognostic markers. We report oncological outcomes and major prognostic factors influencing overall survival (OS) and disease-free survival.

Methods: A total of 401 CRS plus HIPEC procedures were performed on 356 patients. Mortality, grade III-IV adverse events, OS, disease-free survival, and prognostic factors were studied.

Results: Based on Common Terminology Criteria for Adverse Events (CTCAE of the National Cancer Institute 2006), mortality rate was 1 % and overall rate of morbidity grade III-IV was 12.5 %. In multivariate analysis, only the number of digestive anastomoses (>1) significantly correlated with adverse events with an odds ratio of 2.8 (p = 0.032). OS was related to histological type of PC, with a median survival reaching 47.6 months for PC of ovarian cancer origin, 45.8 months for that of colorectal origin, 64.2 months for peritoneal mesothelioma, and 8.1 months for PC of gastric cancer origin. Over half the patients with pseudomyxoma are still alive. Major prognostic factors influencing survival were histological type, World Health Organization performance status (WHO PS) (hazard ratio (HR) = 3.56), operating time (HR = 0.45), previous chemotherapy (HR = 2.04), number of peritonectomies (HR = 2.03), and completeness of cytoreduction score (HR = 3.12). Disease-free survival across all groups was 16.8 months.

Conclusion: The low mortality rate and 12.5 % grade III-IV morbidity of CRS and HIPEC are acceptable when weighed against overall oncologic survival. This multimodal treatment appears feasible for selected patients and trained centers.

In plain English

This single-hospital study from Nice, France, reported on 401 operations on 356 patients between December 1999 and June 2011. All had disease of the abdominal lining: mostly cancer spread from another organ (peritoneal carcinomatosis), but also peritoneal mesothelioma, pseudomyxoma peritonei and sarcomatosis. Treatment was surgery to remove visible tumor, then heated chemotherapy circulated through the abdomen (HIPEC). Most procedures were for cancer spread from the ovary or the colon and rectum. Eighteen procedures were for peritoneal mesothelioma, treated with cisplatin and doxorubicin. The article does not discuss asbestos. Four patients died in hospital, 1% of the 401 procedures. Severe (grade III–IV) complications followed 12.5% of procedures, affecting 50 patients. More than one bowel join was linked to complications (odds ratio 2.8, 95% confidence interval 1.09 to 7.2). Survival differed by cancer type. The 15 mesothelioma patients in the survival table had a median overall survival of 64.2 months. Median disease-free survival for the whole group was 16.8 months. The authors concluded these rates were acceptable given the benefits against the cancer. They noted the study excluded inoperable patients and those who had palliative surgery.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Single-center (monocentric) series of consecutive cytoreductive surgery plus HIPEC procedures, with univariate and multivariate analyses of complications and survival
• Who was studied: 356 patients who underwent 401 CRS plus HIPEC procedures at the CHU of Nice, France, December 1999 to June 2011. Eligible patients had a confirmed diagnosis of peritoneal disease: mesothelioma, pseudomyxoma peritonei, peritoneal carcinomatosis of colorectal, ovarian or gastric origin, or abdominal sarcomatosis. Across the 401 procedures, the article reports 197 cases of carcinomatosis from ovarian cancer, 80 from colorectal cancer, 39 pseudomyxoma peritonei, 18 peritoneal mesotheliomas, 14 from gastric cancer, 15 peritoneal sarcomatoses and 38 others. Median age was 56.9 years (range 22 to 75).
• Exposure: Not an asbestos exposure study. The factor studied was the treatment: cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy at 43 °C. Peritoneal mesothelioma was treated with cisplatin combined with doxorubicin.
• Main results:
  • Death in hospital after the procedure: four patients, a rate of 1% of the 401 procedures.
  • Grade III–IV complications (all procedures): 12.5%. 50 patients had 271 complications of grade III–IV.
  • In multivariate analysis, more than one gastrointestinal anastomosis was the only factor significantly associated with complications and death: odds ratio 2.8 (95% CI 1.09 to 7.2), p equal to 0.032.
  • Peritoneal mesothelioma patients: median overall survival 64.2 months. In the survival table this group numbered 15, with 3-year survival of 69.2% and 5-year survival of 57.7%.
  • In multivariate analysis, histological type was associated with overall survival. The hazard ratio was 0.304 (95% CI 0.112 to 0.827) for pseudomyxoma peritonei and 6.191 (95% CI 2.14 to 17.89, p equal to 0.001) for peritoneal mesothelioma. The article does not state the reference group.
  • Incomplete cytoreduction (CCS-2 to CCS-3) was associated with lower overall survival: hazard ratio 3.12 (95% CI 1.46 to 6.59), p equal to 0.003.
  • Median disease-free survival across the whole group was 16.8 months. In the disease-free survival table, the 17 mesothelioma patients had a median of 54.2 months.
• The authors' conclusion: The authors concluded that the morbidity and mortality of CRS plus HIPEC in their series were acceptable given the oncological benefits, and that the treatment appears feasible for selected patients in trained centers.
• Limitations the authors state:
  • The design excluded patients who were inoperable or who had palliative surgery, which the authors call a bias.
  • The apparent benefit of previous systemic chemotherapy may reflect selection bias.
  • Disease-free survival is harder to interpret because recurrence patterns vary by cancer type and the timing of recurrence is difficult to determine.

Topics

Medical terms in this study, explained in our Lexicon: Cytoreductive Surgery, HIPEC, Overall Survival, Disease-Free Survival, Multivariate Analysis, Odds Ratio, Median Survival, Ovarian Cancer.

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• Outcomes of Cytoreductive Surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) in patients older than 70 years; survival benefit at considerable morbidity and mortality — K.I. Votanopoulos, N.A. Newman, et al. (2013)
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