Intraperitoneal chemotherapy for peritoneal surface malignancy: experience with 1,000 patients

Our plain-English summary of Intraperitoneal chemotherapy for peritoneal surface malignancy: experience with 1,000 patients, by E.A. Levine, J.H. Stewart, P. Shen, et al (Journal of the American College of Surgeons, 2014).

The study

• Authors: E.A. Levine, J.H. Stewart, P. Shen, G.B. Russell, B.L. Loggie, K.I. Votanopoulos
• Journal: Journal of the American College of Surgeons
• Published: 2014;218(4):573-85
• Cited by: 229 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Peritoneal dissemination of abdominal malignancy (carcinomatosis) has a clinical course marked by bowel obstruction and death; it traditionally does not respond well to systemic therapy and has been approached with nihilism. To treat carcinomatosis, we use cytoreductive surgery (CS) with hyperthermic intraperitoneal chemotherapy (HIPEC).

Methods: A prospective database of patients has been maintained since 1992. Patients with biopsy-proven peritoneal surface disease were uniformly evaluated for, and treated with, CS and HIPEC. Patient demographics, performance status (Eastern Cooperative Oncology Group), resection status, and peritoneal surface disease were classified according to primary site. Univariate and multivariate analyses were performed. The experience was divided into quintiles and outcomes compared.

Results: Between 1991 and 2013, a total of 1,000 patients underwent 1,097 HIPEC procedures. Mean age was 52.9 years and 53.1% were female. Primary tumor site was appendix in 472 (47.2%), colorectal in 248 (24.8%), mesothelioma in 72 (7.2%), ovary in 69 (6.9%), gastric in 46 (4.6%), and other in 97 (9.7%). Thirty-day mortality rate was 3.8% and median hospital stay was 8 days. Median overall survival was 29.4 months, with a 5-year survival rate of 32.5%. Factors correlating with improved survival on univariate and multivariate analysis (p ≤ 0.0001 for each) were preoperative performance status, primary tumor type, resection status, and experience quintile (p = 0.04). For the 5 quintiles, the 1- and 5-year survival rates, as well as the complete cytoreduction score (R0, R1, R2a) have increased, and transfusions, stoma creations, and complications have all decreased significantly (p < .001 for all).

Conclusions: This largest reported single-center experience with CS and HIPEC demonstrates that prognostic factors include primary site, performance status, completeness of resection, and institutional experience. The data show that outcomes have improved over time, with more complete cytoreduction and fewer serious complications, transfusions, and stomas. This was due to better patient selection and increased operative experience. Cytoreductive surgery with HIPEC represents a substantial improvement in outcomes compared with historical series, and shows that meaningful long-term survival is possible for selected carcinomatosis patients. Multi-institutional cooperative trials are needed to refine the use of CS and HIPEC.

Copyright © 2014 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

In plain English

This article reported one US hospital's results treating cancer spread over the abdominal lining (peritoneal surface disease) with surgery to remove visible tumor plus heated chemotherapy circulated through the abdomen (HIPEC). From a prospective Wake Forest University database, the authors reviewed 1,000 patients given 1,097 HIPEC procedures between 1991 and 2013. Most tumors began in the appendix (472) or colon and rectum (248); 72 patients (7.2%) had mesothelioma. The article did not study asbestos exposure. Overall median survival was 29.4 months; 5-year survival was 31.5% in the results but 32.5% in the abstract. Within 30 days, 3.8% died; the text reported 42% with complications, but a table listed 578 of 1,000. Median survival was 27.1 months for mesothelioma, 63.5 months for appendix and 16.4 months for colorectal tumors. Operations leaving no visible tumor, or only nodules up to 0.5 cm, became more common. Tumor site, completeness of resection, complications, pre-surgery fitness and period of experience were linked to survival. The authors concluded long-term survival is possible and believed better patient selection mainly explained the improvements. They noted no study has compared surgery with and without HIPEC.

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 series of treated patients drawn from a prospectively maintained database (surgical outcomes study). The authors compared outcomes across five consecutive groups of 200 patients and used survival analyses with univariate and multivariate testing.
• Who was studied: 1,000 patients with biopsy-proven peritoneal surface disease who underwent 1,097 HIPEC procedures at Wake Forest University School of Medicine Baptist Hospital, Winston-Salem, NC, between 1991 and 2013. The primary sites were appendix 472 (47.2%), colorectal 248 (24.8%), mesothelioma 72 (7.2%), ovary 69 (6.9%), gastric 46 (4.6%) and other 97 (9.7%). The authors' discussion concerns peritoneal mesothelioma.
• Exposure: No asbestos or fiber exposure was studied. The factor studied was treatment: cytoreductive surgery (removal of visible tumor) combined with hyperthermic intraperitoneal chemotherapy, mostly using mitomycin C. Since 2004, mesothelioma cases received cisplatin 250 mg/M2 with sodium thiosulfate.
• Main results:
  • For all 1,000 patients, the median follow-up was 54.1 months and the median overall survival was 29.4 months.
  • For all patients, the Results section gave overall survival of 72.3% at 1 year, 44.6% at 3 years, 31.5% at 5 years, 18.1% at 10 years and 10.7% at 15 years. The article's abstract instead gives a 5-year survival rate of 32.5%.
  • Median survival differed significantly by primary site (p = 0.0001): appendix 63.5 months, colorectal 16.4 months, gastric 6.1 months, mesothelioma 27.1 months, ovary 28.5 months and sarcoma 28.1 months.
  • For all patients, the text gave 30-day postoperative morbidity of 42% and 30-day mortality of 3.8% (38 patients died within 30 days). Table 1, however, lists 578 of 1,000 patients as having complications and 422 as not.
  • Mortality rates did not change significantly across the five experience periods.
  • The authors defined complete resection as R0, R1 or R2a, where R2a means minimal residual tumor with nodules up to 0.5 cm. This rate rose with each successive group of 200 patients: 55.0%, 74.0%, 76.4%, 83% and 88.3% (p less than 0.001).
  • In multivariate analysis, the independent predictors of overall survival were tumor histology (primary site), resection status, complications and performance status. The table also lists experience quintile (p = 0.043).
• The authors' conclusion: The authors concluded that long-term survival is possible after a diagnosis of peritoneal surface disease and that approaching such patients with therapeutic nihilism is no longer appropriate. They believed better patient selection, rather than improved surgical technique, primarily accounted for the improved outcomes over time.
• Limitations the authors state:
  • The authors stated that no study has compared cytoreductive surgery with versus without HIPEC.
  • The authors stated that for most primary tumor sites, the optimal perfusion time, dose, temperature and drug are not based on class I data.
  • The authors acknowledged that the good survival after repeat procedures reflects selection bias in choosing patients for them.

Topics

Medical terms in this study, explained in our Lexicon: Chemotherapy, Systemic Therapy, Cytoreductive Surgery, HIPEC, Biopsy, Performance Status, Mesothelioma, Median Overall Survival.

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• What made hyperthermic intraperitoneal chemotherapy an effective curative treatment for peritoneal surface malignancy: A 25-year experience with 1,125 procedures — G. Passot, D. Vaudoyer, et al. (2016)
• Outcomes of repeat cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for the treatment of peritoneal surface malignancy — K.I. Votanopoulos, C. Ihemelandu, et al. (2012)
• Cytoreductive surgery with intraperitoneal hyperthermic chemotherapy for malignant peritoneal mesothelioma: mitomycin versus cisplatin — A.U. Blackham, P. Shen, et al. (2010)
• Peritoneal carcinomatosis from unusual cancer origins: Is there a role for hyperthermic intraperitoneal chemotherapy? — C. Honoré, D. Goéré, et al. (2016)
• Iterative cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for recurrent peritoneal metastases — T.C. Chua, L.E. Quinn, et al. (2013)
• Evaluation of the cost-effectiveness of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (peritonectomy) at the St George Hospital peritoneal surface malignancy program — T.C. Chua, S. Martin, et al. (2010)

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