Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for malignant peritoneal mesothelioma: a systematic review and meta-analysis

Our plain-English summary of Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for malignant peritoneal mesothelioma: a systematic review and meta-analysis, by J.H. Helm, J.T. Miura, J.A. Glenn, et al (Annals of Surgical Oncology, 2015).

The study

• Authors: J.H. Helm, J.T. Miura, J.A. Glenn, R.K. Marcus, G. Larrieux, T.T. Jayakrishnan, A.E. Donahue, T.C. Gamblin, K.K. Turaga, F.M. Johnston
• Journal: Annals of Surgical Oncology
• Published: 2015;22(5):1686-93
• Type of article: Meta-analysis, Systematic review
• Cited by: 189 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Due to the increased adoption of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), patients with malignant peritoneal mesothelioma (MPM) have seen improved outcomes. We aimed to evaluate and synthesize the recent published literature.

Methods: The review was conducted according to the recommendation of the Meta-Analysis of Observational Studies in Epidemiology group with prespecified inclusion and exclusion criteria. The DEALE method was used to combine mortality rates, and imputation techniques were used to calculate standard errors. Meta-regression techniques were used to synthesize data. Publication bias was assessed using funnel plots.

Results: Of 6,528 citations collected, 20 articles reporting on 1,047 patients were included in the analysis. The median age was 51 years (interquartile range 49-55), with 59 % (54-67) female. The median peritoneal carcinomatosis index score was 19 (16-23). Complete cytoreduction (CC0, 1) was performed in 67 % (46-93 %) of patients. Pooled estimates of survival yielded a 1-, 3- and 5-year survival of 84, 59, and 42 %, respectively. Patients receiving early postoperative intraperitoneal chemotherapy [EPIC] (44 %) and those receiving cisplatin intraperitoneal chemotherapy alone (48 %) or in combination (44 %) had an improved 5-year survival.

Conclusions: While CRS + HIPEC has led to an improved survival for patients with MPM compared to historic data, heterogeneity of studies precludes generalizable inferences. EPIC chemotherapy and cisplatin chemoperfusion may infer survival benefit.

In plain English

This article was a systematic review and meta-analysis of published studies on cytoreductive surgery (removing visible tumor) combined with hyperthermic intraperitoneal chemotherapy (heated chemotherapy circulated through the abdomen) for malignant peritoneal mesothelioma. From 6,528 citations, the authors included 20 articles covering 1,047 patients, published between 1992 and 2013 in eight countries. The review did not examine asbestos exposure. Pooled estimates gave expected survival of 84% at 1 year, 59% at 3 years and 42% at 5 years, with wide uncertainty ranges (14 to 100% at 5 years). Expected 5-year survival was 45% in the 7 studies that also used early postoperative intraperitoneal chemotherapy and 39% in the 13 that did not, with wide, overlapping ranges. Deaths around the operation were 0 to 5% in most studies, but two groups reported 12% and 20%. The authors concluded that the treatment improved survival compared with historic data and was safe in experienced centers, but that differences between studies prevented generalizable conclusions. They noted that including only English-language studies, with no unpublished or gray literature, opened the review to a high risk of publication bias.

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: Systematic review and meta-analysis of published studies (15 retrospective studies, 4 clinical trials, 1 prospective cohort), using random effects modeling
• Who was studied: 1,047 patients with malignant peritoneal mesothelioma who underwent cytoreductive surgery and HIPEC, from 20 articles (selected from 6,528 citations) published between 1992 and 2013 in eight countries. Median age 51 years (interquartile range 49 to 55); 59% female.
• Exposure: Not asbestos exposure. The review studied a treatment: cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC), with or without early postoperative intraperitoneal chemotherapy (EPIC), using various drugs. The most frequent was a combination of cisplatin, doxorubicin and mitomycin.
• Main results:
  • For all 20 studies, the summarized mortality rate was 0.17 (0, 0.39). Predicted overall survival was 84% (68 to 100) at 1 year and 42% (14 to 100) at 5 years.
  • The pooled 3-year survival was 59%. This figure is given only in the article's abstract.
  • Median overall survival ranged from 19 to 92 months in the 11 studies that reported it.
  • Expected 5-year survival was 45% (11 to 100) in the 7 studies that used EPIC and 39% (6 to 100) in the 13 studies that did not.
  • In the 3 studies using cisplatin only, expected 5-year survival was 49% (mortality rate 0.14). In the 11 studies using drug combinations including doxorubicin, mitomycin-C and cisplatin, it was 45%.
  • Complete cytoreduction was performed in 67% (46 to 93%) of patients.
  • Operative mortality was 0 to 5% in most studies, but two groups reported 12% and 20%. Morbidity ranged from 8.3% to 90% in the 14 studies reporting it.
• The authors' conclusion: The authors concluded that current evidence supports continued use of CRS and HIPEC, which they described as safe and best when used by experienced centers. They also concluded that heterogeneity of studies precludes generalizable inferences. In the abstract they wrote that EPIC and cisplatin chemoperfusion may confer survival benefit, while in the discussion they stated that the utility of EPIC has yet to be determined.
• Limitations the authors state:
  • The included studies differed in how they classified regimens, which variables they assessed, and how they reported toxicity.
  • The searches had no language limits, but only English-language studies were eligible for inclusion, and no unpublished or gray literature was included. The authors said this opens the review to a high risk of publication bias.
  • The calculations relied on assumptions and on the reviewers' judgment in choosing among effect measures.
  • There was no uniform morbidity classification system across studies, so morbidity figures should be interpreted cautiously.
  • No randomized controlled studies of MPM management exist.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma, Peritoneal mesothelioma.

Medical terms in this study, explained in our Lexicon: Cytoreductive Surgery, HIPEC, Peritoneal Mesothelioma, Systematic Review, Meta-Analysis, Epidemiology, Chemotherapy, Cisplatin.

Related studies

• Iterative cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for recurrent or progressive diffuse malignant peritoneal mesothelioma: clinicopathologic characteristics and survival outcome — C. Ihemelandu, L. Bijelic, et al. (2015)
• Conversion to Complete Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Malignant Peritoneal Mesothelioma After Bidirectional Chemotherapy — F. Le Roy, M. Gelli, et al. (2017)
• The Role of Ki-67 and Pre-cytoreduction Parameters in Selecting Diffuse Malignant Peritoneal Mesothelioma (DMPM) Patients for Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) — S. Kusamura, P.A. Torres Mesa, et al. (2016)
• A Novel Tool for Predicting Major Complications After Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy — J.M. Baumgartner, T.G. Kwong, et al. (2016)
• Early recurrence after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) — G.H.C. Tan, C.S. Chia, et al. (2018)
• Is Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy Justified for Biphasic Variants of Peritoneal Mesothelioma? Outcomes from the Peritoneal Surface Oncology Group International Registry — K.I. Votanopoulos, P. Sugarbaker, et al. (2018)

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