Hyperthermic intrathoracic chemotherapy after cytoreductive surgery in malignant pleural mesothelioma: a single-center retrospective cohort study suggesting increased morbidity without survival benefit

Our plain-English summary of Hyperthermic intrathoracic chemotherapy after cytoreductive surgery in malignant pleural mesothelioma: a single-center retrospective cohort study suggesting increased morbidity without survival benefit, by N. Baldes, F. Doerr, K. Grapatsas, et al (Journal of Thoracic Disease, 2026).

The study

• Authors: N. Baldes, F. Doerr, K. Grapatsas, B. Hegedüs, M. Metzenmacher, D. Theegarten, C. Taube, M. Schuler, S. Bölükbas
• Journal: Journal of Thoracic Disease
• Published: 2026;18(8):831
• Read it: PubMed · Publisher · Free full text

Abstract

Background: In the multimodal treatment of pleural mesothelioma (PM), hyperthermic intrathoracic chemotherapy (HITOC) has been investigated as an adjunct to cytoreductive surgery (CRS) to potentially improve local tumor control. The study aimed to evaluate the clinical impact of HITOC as an adjunct to CRS, specifically regarding overall survival (OS), postoperative morbidity and mortality, and operative duration.

Methods: This retrospective study compared patients who underwent CRS with HITOC to those without HITOC at our institution between 2010 and 2022. Primary endpoints included OS, operative time, and perioperative morbidity and mortality. Categorical variables were compared using the Fisher's exact test. Survival analyses were performed using the Kaplan-Meier method and compared via the log-rank test.

Results: A total of 114 patients underwent CRS for PM, including 14 with HITOC and 100 without. The mean age was 66 years, and 12 patients were female. The mean operative time was longer in the HITOC group (488 vs. 258 minutes). Postoperative morbidity (Clavien-Dindo Grade ≥ III) was significantly higher with HITOC [43 % vs. 10 %, odds ratio (OR) 6.07, 95 % confidence interval (CI): 1.77-20.76, P=0.007], while in-hospital mortality occurred in two patients (1.8 %), one in each group. Median OS was 13 months in the HITOC group vs. 27 months in the non-HITOC group (P=0.03).

Conclusions: In this retrospective single-center cohort, adjunctive HITOC was associated with significantly longer operative time, higher postoperative morbidity, and inferior OS compared with cytoreduction alone. Given the small HITOC sample size and potential residual confounding, these findings should be interpreted cautiously but raise concerns regarding the routine use of HITOC outside clinical trials and highlight the need for prospective comparative evaluation.

© AME Publishing Company.

In plain English

This retrospective study reviewed pleural mesothelioma patients who had surgery to remove all visible tumor (cytoreductive surgery) at one hospital in Essen, Germany, in 2010-2022. It compared 14 who also got heated cisplatin chemotherapy in the chest (HITOC) with 100 who did not. HITOC operations averaged 488 minutes, versus 258. Serious complications (Clavien-Dindo grade III or higher) affected 43% of HITOC patients and 10% of others (odds ratio 6.07, 95% confidence interval 1.77 to 20.76). One patient in each group died in hospital. Median overall survival was 13 months (95% confidence interval 3.22 to 22.78) with HITOC and 27 months (20.27 to 33.73) without (P=0.03). HITOC patients were older, all had preoperative chemotherapy, and more often had extrapleural pneumonectomy (whole lung removed), an imbalance the authors called a major confounder. Separate small exploratory analyses for lung-sparing operations and for extrapleural pneumonectomy, not powered to detect differences, found no statistically significant differences in complications or survival. Noting the small HITOC group, the authors concluded HITOC showed no survival advantage, was associated with more complications and longer operations, and needs prospective study.

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: Retrospective single-center cohort study comparing cytoreductive surgery with versus without HITOC
• Who was studied: All consecutive patients who had cytoreductive surgery (pleurectomy/decortication, extended pleurectomy/decortication, or extrapleural pneumonectomy) for histologically confirmed pleural mesothelioma at University Medicine Essen—Ruhrlandklinik, Germany, from January 2010 to December 2022. There were 114 patients: 14 with HITOC and 100 without. Mean age was 66 years and 12 were female.
• Exposure: This was a treatment study, not a study of asbestos exposure. The treatment examined was hyperthermic intrathoracic chemotherapy (HITOC) after cytoreductive surgery: cisplatin 175 mg per square meter of body surface area, target inflow temperature 41 to 42 degrees Celsius, for 60 minutes. It was compared with the same surgery without chemoperfusion.
• Main results:
  • Mean operative time was 488 minutes in the HITOC group and 258 minutes in the non-HITOC group. Operative time was missing for 13 non-HITOC patients.
  • Postoperative complications of Clavien-Dindo grade III or higher occurred in 43% of the HITOC group and 10% of the non-HITOC group (OR 6.07, 95% CI 1.77 to 20.76, P=0.007).
  • In-hospital mortality was 2 of 114 patients (1.8%), one in each group. 90-day mortality was 7.1% in the HITOC group and 4% in the non-HITOC group.
  • Median overall survival was 13 months (95% CI 3.22 to 22.78) in the HITOC group and 27 months (95% CI 20.27 to 33.73) in the non-HITOC group (P=0.03).
  • The groups differed at baseline. HITOC patients were older (mean 70.9 vs. 65.9 years, P=0.03). All HITOC patients had preoperative chemotherapy, compared with 67% of non-HITOC patients. HITOC patients more often had extrapleural pneumonectomy (42.9% vs. 15.0%), and none had standard pleurectomy/decortication.
  • In exploratory subgroup analyses with two strata, pooled lung-sparing procedures and extrapleural pneumonectomy, neither major complications nor survival differed significantly between HITOC and non-HITOC patients. Median overall survival was 22 vs. 28 months among lung-sparing patients (P=0.37) and 11 vs. 27 months among extrapleural pneumonectomy patients (P=0.08). The authors said the subgroup was small and the analysis was not powered to detect subgroup-specific differences.
• The authors' conclusion: The authors concluded that in this retrospective cohort, adjunctive HITOC did not show a survival advantage and was associated with increased morbidity and operative duration. They said this argues against routine HITOC in their institutional setting, but that definitive conclusions require prospective comparative studies.
• Limitations the authors state:
  • The retrospective, non-randomized design is vulnerable to residual confounding.
  • The HITOC group was small (n=14), limiting statistical power, precision, and adjustment for covariates. Multivariable regression and propensity score matching were not performed.
  • The higher proportion of extrapleural pneumonectomy in the HITOC group is a major confounder that limits causal interpretation.
  • The surgical subgroup analyses were small and not powered to detect subgroup-specific differences.
  • Detailed information on postoperative systemic therapy was not consistently available and could not be accounted for in survival analyses.
  • HITOC patients were older, which may have contributed to higher morbidity and lower survival.
  • Other intraoperative local therapies varied by surgeon preference.
  • Perfusion details and completeness of cytoreduction were not analyzed as effect modifiers.
  • As a single-institution study, generalizability is limited.

Topics

Medical terms in this study, explained in our Lexicon: Intrathoracic, Chemotherapy, Cytoreductive Surgery, Pleural Mesothelioma, Cohort Study, Overall Survival, Odds Ratio, confidence interval.

Related studies

• 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)
• Hyperthermic Intrathoracic Chemotherapy (HITOC) after Cytoreductive Surgery for Pleural Malignancies-A Retrospective, Multicentre Study — M. Ried, J. Kovács, et al. (2021)
• Repeat cytoreductive surgery and heated intraperitoneal chemotherapy may offer survival benefit for intraperitoneal mesothelioma: a single institution experience — J. Wong, A.L. Koch, et al. (2014)
• Assessing morbidity, mortality, and survival in patients with peritoneal carcinomatosis undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy — J.S.A. Vallejo, F.L. Queiroz, et al. (2023)
• Influence of the effectiveness of sarcopenia on postoperative major complications after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients with peritoneal surface malignancy: a retrospective cohort study — N. Havan, S. Gülmez, et al. (2025)
• Repeated cytoreductive surgery and Hyperthermic Intraperitoneal Chemotherapy in patients with peritoneal carcinomatosis: A retrospective cohort study — C. Paasch, G. De Santo, et al. (2021)

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