Hyperthermic Intrathoracic Chemoperfusion for Malignant Pleural Mesothelioma: Systematic Review and Meta-Analysis

Our plain-English summary of Hyperthermic Intrathoracic Chemoperfusion for Malignant Pleural Mesothelioma: Systematic Review and Meta-Analysis, by T. Järvinen, J. Paajanen, I. Ilonen, et al (Cancers, 2021).

The study

• Authors: T. Järvinen, J. Paajanen, I. Ilonen, J. Räsänen
• Journal: Cancers
• Published: 2021;13(14)
• Type of article: Review
• Cited by: 18 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is an aggressive malignancy of the pleural lining with exceptionally poor survival. Hyperthermic intrathoracic chemoperfusion (HITHOC) is commonly used with surgery in limited disease. However, data on its effect on survival are limited. In this systematic review and meta-analysis, we analyzed a total of 11 observational articles. HITHOC was compared to control arm that did not receive HITHOC in three studies including 762 patients. The pooled analysis of these studies revealed an SMD of 0.24, with 95% CI of 0.06-0.41 favoring the HITHOC group, reaching statistical significance. The survival effect of HITHOC in epithelioid MPM vs. non-epithelioid MPM was analyzed in four studies. Pooled analysis showed an SMD of 0.79 (95% CI = 0.48-1.10) favoring epithelioid MPM. Based on available data, there seems to be a benefit with HITHOC in regards to overall survival in the treatment of all mesothelioma patients. Multicenter randomized controlled trials are needed to validate and standardize this treatment approach.

In plain English

This was a systematic review and meta-analysis of earlier studies, not a new study of patients. The authors searched Embase, Medline and the Cochrane library up to January 2021 for studies of hyperthermic intrathoracic chemoperfusion (HITHOC) in malignant pleural mesothelioma. In HITHOC, heated chemotherapy, mostly cisplatin, is circulated in the chest during surgery. Eleven observational studies were included, and none was a randomized trial. The authors pooled the studies that compared patients who did and did not receive HITHOC (762 patients). They reported a standardized effect size for overall survival of 0.24 (95% CI 0.06 to 0.41) favoring HITHOC, with marked differences between studies. Across four studies, patients with epithelioid mesothelioma survived longer than those with other subtypes (effect size 0.79, 95% CI 0.48 to 1.10). Reported overall complication rates ranged from 16.7 to 62.9%. The authors said they mostly could not tell whether complications came from the surgery, the HITHOC, or both. They concluded there is a signal of benefit with HITHOC, but that higher-quality data, including randomized trials, are needed.

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 observational studies, following PRISMA guidelines; random effects model
• Who was studied: 11 observational studies of adults with malignant pleural mesothelioma treated with HITHOC, published 2006 to 2021: six from the USA, three from Italy, one from the Netherlands, one from Germany. Study sizes ranged from 6 to 503 patients. Literature was searched up to January 2021 in Embase, Medline and Cochrane library.
• Exposure: Treatment studied (not asbestos exposure): hyperthermic intrathoracic chemotherapy given with surgery. The surgery was extrapleural pneumonectomy, pleurectomy/decortication, or partial pleurectomy. Cisplatin was used in all included studies, in some combined with adriamycin/doxorubicin, epirubicin or gemcitabine. Temperatures were 40 to 42.5 degrees C, for 60 or 90 minutes.
• Main results:
  • In studies comparing HITHOC with no HITHOC (762 patients), the pooled standardized mean difference (Hedges' g, calculated from median overall survival, group sizes and p values) was 0.24, 95% CI 0.06 to 0.41, favoring the HITHOC group.
  • Heterogeneity between the studies in the HITHOC vs no-HITHOC analysis was marked (I-squared 66%, p = 0.03).
  • One included study (van Sandick et al.) reported markedly worse survival with HITHOC plus surgery without radiotherapy than with extrapleural pneumonectomy plus hemithoracic radiotherapy without HITHOC. The authors considered this result greatly confounded by the other treatment differences between the groups.
  • In four studies of HITHOC-treated patients, epithelioid mesothelioma had better survival than non-epithelioid mesothelioma: pooled SMD 0.79 (95% CI 0.48 to 1.10). The authors described this as a borderline large effect. Heterogeneity was negligible (I-squared 0%).
  • Reported rates of any complication ranged from 16.7 to 62.9% across studies. Cardiac complications ranged from 7.7 to 34.1%, acute kidney injury from 3.3% to 75.7%, and reoperation from 2.0% to 40%. Median hospital stay was 8 to 26 days.
• The authors' conclusion: The authors concluded that there is a signal of benefit with HITHOC in malignant pleural mesothelioma patients, but that higher-quality data are needed for a definitive conclusion. They called for multicenter randomized controlled trials.
• Limitations the authors state:
  • No randomized trials exist, so only retrospective data were pooled. The analysis is subject to the same biases as the included studies and risks amplifying them.
  • Few studies, with a limited number of patients, could be included in the HITHOC vs no-HITHOC survival comparison.
  • The studies differed in surgery, other treatments such as radiotherapy, chemotherapy agents, and HITHOC temperatures and durations.
  • Complication reporting and definitions varied widely between studies. It was mostly not possible to tell whether complications came from surgery, HITHOC, or both.
  • No included study comparing HITHOC with no HITHOC reported survival for epithelioid patients alone, so the effect of HITHOC in that subtype remains unknown.

Topics

Medical terms in this study, explained in our Lexicon: Intrathoracic, Pleural Mesothelioma, Systematic Review, Meta-Analysis, Statistical Significance, Epithelioid, Non-epithelioid, Overall Survival.

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• Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for malignant peritoneal mesothelioma: a systematic review and meta-analysis — J.H. Helm, J.T. Miura, et al. (2015)
• Risk factors for postoperative acute kidney injury after cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy: a meta-analysis and systematic review — D. Chen, Y. Ma, et al. (2025)
• Institutional learning curve of cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion for peritoneal malignancies — P.M. Polanco, Y. Ding, et al. (2015)
• A contemporary analysis of morbidity and outcomes in cytoreduction/hyperthermic intraperitoneal chemoperfusion — M. Haslinger, V. Francescutti, et al. (2013)

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