Hyperthermic Intrathoracic Chemoperfusion and the Role of Adjunct Immunotherapy for the Treatment of Pleural Mesothelioma

Our plain-English summary of Hyperthermic Intrathoracic Chemoperfusion and the Role of Adjunct Immunotherapy for the Treatment of Pleural Mesothelioma, by S.L. Kong, Z. Feng, S. Kim, et al (Biomolecules, 2025).

The study

• Authors: S.L. Kong, Z. Feng, S. Kim, E.K. Ha, K. Kamel, M. Becich, J.D. Luketich, A. Pennathur
• Journal: Biomolecules
• Published: 2025;15(5)
• Type of article: Review
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Pleural mesothelioma (PM) is an aggressive cancer originating from the mesothelial lining of the pleura, with a rising global incidence since the mid-20th century due to asbestos and erionite exposure. PM accounts for 80-90% of all mesothelioma cases and is histologically classified into three subtypes-epithelioid, sarcomatoid, and biphasic- with epithelioid carrying the most favorable prognosis. Despite advances in surgery, chemotherapy, radiotherapy, and immunotherapy, PM prognosis remains poor, necessitating more effective, multimodal strategies. Hyperthermic intrathoracic chemoperfusion (HITHOC) has emerged as a promising adjunct to cytoreductive surgery by delivering heated chemotherapy directly to the pleural cavity, potentially improving survival-especially in patients with epithelioid PM. Combining HITHOC with post-surgical immunotherapy represents a novel approach to enhancing both local and systemic anti-tumor responses and targeting microscopic disease and distant metastases. This review explores surgical outcomes after surgery for PM, the therapeutic synergy of HITHOC and immunotherapy, ongoing clinical trials evaluating this multimodal strategy, and its implications for future patient care.

In plain English

This article was a review, not a new study. The authors summarized published research and ongoing clinical trials on treating pleural mesothelioma, a cancer of the lining of the chest cavity (the pleura) that they described as linked to breathing asbestos and erionite fibers. They focused on hyperthermic intrathoracic chemoperfusion (HITHOC), in which heated chemotherapy is put directly into the chest cavity after surgery, and on immunotherapy. The authors reported that there were no randomized controlled trials of HITHOC for pleural malignancies and that the evidence on its benefits was mixed. They also reported that European (ESMO) and US (NCCN) guidelines did not include HITHOC in standard treatment. They described a Phase II trial by Lee et al. of 24 patients, most given immunotherapy before surgery that included HITHOC. Serious (grade 3 or higher) immune side effects occurred in 8% of patients given one drug and 27% given two drugs. The authors concluded that combining HITHOC with immunotherapy offered a promising avenue. They added that it should be further evaluated in Phase II and III trials before conclusions are drawn.

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: narrative review of published studies and ongoing clinical trials; no new patient data
• Who was studied: Published studies and clinical trials of patients with pleural mesothelioma (PM), a cancer the authors describe as linked to breathing asbestos and erionite fibers; the authors studied no patients of their own
• Exposure: Treatments for pleural mesothelioma: surgery (extrapleural pneumonectomy or extended pleurectomy/decortication), hyperthermic intrathoracic chemoperfusion (HITHOC) with drugs such as cisplatin, doxorubicin and mitomycin C, chemotherapy, and immunotherapy (immune checkpoint inhibitors, dendritic cell vaccines, CAR-T cells), especially HITHOC combined with immunotherapy
• Main results:
  • The authors reported that there were no randomized controlled trials of HITHOC for pleural malignancies and that evidence on its benefits in PM was mixed
  • The authors reported that ESMO and NCCN guidelines did not include HITHOC in recommended standard treatment for PM
  • As described in the review, a Phase II study by Tilleman et al. reported longer median survival in 92 patients treated with HITHOC than in 29 patients treated without it (13.1 vs. 1.0 months, p = 0.01). By contrast, Van Sandick et al. reported markedly worse survival with HITHOC and either EPP or EPD without radiation therapy, compared with EPP and hemithoracic radiation therapy without HITHOC
  • As described in the review, a meta-analysis by Zhao et al. found average median survival time significantly longer in patients treated with HITHOC than in those without HITHOC
  • As described in the review, the Phase II Window of Opportunity trial by Lee et al. enrolled 24 patients: 9 were given durvalumab alone, 11 durvalumab plus tremelimumab, and 4 no immunotherapy before surgery that included HITHOC. At 34.1 months of follow-up, median overall survival was not reached in the combination group and was 14.0 months in the durvalumab-alone group
  • In the Lee et al. trial, tumor pathologic response occurred in 35.3% of patients who received immunotherapy and surgery
  • In the Lee et al. trial, immune side effects of grade 3 or higher occurred in 8% of patients given one drug (monotherapy) and 27% of patients given the two-drug combination
  • The authors noted that hyperthermia could both enhance and detract from the efficacy of immunotherapy
• The authors' conclusion: The authors concluded that combining treatments, particularly HITHOC with immune checkpoint inhibitors, offers a promising avenue. They stated that this approach should be further evaluated in Phase II and III clinical trials before conclusions are drawn.
• Limitations the authors state:
  • The authors noted that several ongoing Phase II trials of immunotherapy with surgery do not specify whether HITHOC is included
  • The authors noted that the NICITA trial does not specifically evaluate combining HITHOC with immunotherapy after surgery
  • The authors noted that the evidence favoring EPD over EPP comes from retrospective studies or meta-analyses, with no randomized trials

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Intrathoracic, Immunotherapy, Pleural Mesothelioma, Pleura, erionite, Mesothelioma, Epithelioid, Sarcomatoid.

Related studies

• Institutional learning curve of cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion for peritoneal malignancies — P.M. Polanco, Y. Ding, et al. (2015)
• Effect of intraoperative hyperthermic intrathoracic chemotherapy after pleurectomy decortication for treatment of malignant pleural mesothelioma: a comparative study — H.H. Elsayed, H.Y. Sharkawy, et al. (2024)
• Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemoperfusion in Adolescent and Young Adults with Peritoneal Metastases — M. Dhir, L. Ramalingam, et al. (2017)
• First report of pleural mesothelioma treated with cytoreductive surgery and hyperthermic intrathoracic chemotherapy in Kazakhstan: a case report — K. Nurtas, D. Alexandr, et al. (2026)
• A contemporary analysis of morbidity and outcomes in cytoreduction/hyperthermic intraperitoneal chemoperfusion — M. Haslinger, V. Francescutti, et al. (2013)
• Adjuvant dendritic cell-based immunotherapy after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients with malignant peritoneal mesothelioma: a phase II clinical trial — M.V. Dietz, K.L.A. Quintelier, et al. (2023)

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