The Role of Hyperthermic Intrathoracic Chemotherapy (HITHOC) in Thoracic Tumors

Our plain-English summary of The Role of Hyperthermic Intrathoracic Chemotherapy (HITHOC) in Thoracic Tumors, by F. Danuzzo, M.C. Sibilia, S. Vaquer, et al (Cancers, 2024).

The study

• Authors: F. Danuzzo, M.C. Sibilia, S. Vaquer, A. Cara, E.M. Cassina, L. Libretti, E. Pirondini, F. Raveglia, A. Tuoro, F. Petrella
• Journal: Cancers
• Published: 2024;16(14)
• Type of article: Review
• Cited by: 16 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Pleural mesothelioma (PM) is a rare but aggressive thoracic tumor with a poor prognosis. Multimodal treatment-including induction chemotherapy, aggressive surgical resection, radiotherapy and immunotherapy in selected cases-currently represents the best therapeutic option. Single-center studies advocate hyperthermic intrathoracic chemotherapy (HITHOC) during surgical resection as an additional therapeutic option, although its impact on post-operative morbidity and survival has not yet been evaluated on a larger scale. HITHOC can be applied not only in the case of mesothelioma, but also in the case of thymoma with pleural involvement or-in very selected cases-in patients with secondary pleural metastases. Despite favorable outcomes and reduced clinical risks, there is no uniform approach to HITHOC, and a wide variety of indications and technical applications are still reported. Based on available data, HITHOC seems to offer a clear benefit in regard to overall survival of all mesothelioma patients; however, multicenter randomized controlled trials are required to validate and standardize this approach. The aim of this review is to focus on the present role of HITHOC in thoracic tumors with pleural involvement as well as on future challenges, particularly in the light of possible combined therapy of thoracic tumors still presenting poor prognoses.

In plain English

This article was a narrative review of published research on hyperthermic intrathoracic chemotherapy (HITHOC), written by thoracic surgeons in Monza, Italy. HITHOC is heated chemotherapy, most often cisplatin, given inside the chest cavity during surgery. The article did not study asbestos exposure. The review covered pleural mesothelioma, thymic tumors that had spread to or recurred in the pleura, advanced lung cancer, and pleural effusions from breast and ovarian cancer. It reported that a 2017 meta-analysis found no deaths around the time of surgery or linked to HITHOC within 30 or 90 days. In five comparative studies, mesothelioma patients given HITHOC had longer overall and disease-free survival. A later meta-analysis found an effect favoring HITHOC, notably in the epithelioid subtype, but could not definitively conclude that all mesothelioma patients benefited. Data for breast and ovarian cancer were described as inadequate. The authors concluded that HITHOC is a feasible, safe and promising option within combined treatment. They noted that most studies were small or retrospective, that there was no agreed protocol, and that multicenter 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: Narrative review of published studies (no search methods or new patient data reported)
• Who was studied: Published studies, case series and case reports (tables span 1970 to 2021) on HITHOC in pleural mesothelioma, thymoma or thymic carcinoma with pleural involvement, locally advanced lung cancer, and malignant pleural effusion from breast and ovarian cancer; review authors from the Department of Thoracic Surgery, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy
• Exposure: No asbestos exposure was studied. The treatment reviewed was heated intrathoracic chemotherapy, most often cisplatin, sometimes combined with doxorubicin or mitomycin C, given with surgery
• Main results:
  • A 2017 systematic review and meta-analysis of 21 articles (Zhao et al.), as reported by this review, found no perioperative or HITHOC-associated mortality at 30 or 90 days
  • In five studies comparing mesothelioma patients who did and did not receive HITHOC with surgery, both overall survival and disease-free survival were longer in those given HITHOC, as reported by this review
  • Across studies of mesothelioma cited by the review, median overall survival with surgery plus HITHOC ranged from 11 to 75 months and disease-free survival from 7.2 to 57 months. For surgery alone, overall survival ranged from 5 to 36 months
  • A more recent meta-analysis (Järvinen et al.) could not definitively conclude that all mesothelioma patients benefited. It found a statistically significant effect favoring HITHOC, particularly in the epithelioid subtype
  • For thymoma pleural recurrences, a retrospective study (Aprile et al., 2020) comparing surgery plus HITHOC with surgery alone found similar post-operative morbidity, no procedure-related mortality and similar survival, but significantly different local disease-free intervals
  • For non-small-cell lung cancer with malignant pleural effusion, a 2019 systematic review of 4 articles (21 patients) reported median survival of 18 months, with 62% alive at 1 year and 28.5% at 2 years. That review judged the evidence weak
  • A pooled analysis of seven studies (169 breast cancer and 8 ovarian cancer patients) reported local control rates at 4 weeks of 59.1% for breast cancer and 87.5% for ovarian cancer patients
• The authors' conclusion: The authors concluded that HITHOC has been reported to be feasible and safe and is a promising option within multimodal treatment of pleural malignancies. In their view it improves local tumor control and survival. They added that prospective multicenter randomized studies are needed to standardize protocols
• Limitations the authors state:
  • Most available studies are case series, feasibility studies or retrospective studies with small numbers of patients
  • There is no consensus and there are no guidelines on protocols. Surgery, patient selection, drugs, doses, temperature, perfusion time and machines all vary
  • HITHOC's role has not been addressed in the latest ERS/EACTS/ESTS/ESCRO guidelines on pleural mesothelioma
  • Data on HITHOC for breast and ovarian cancer pleural effusions remain inadequate

Topics

Medical terms in this study, explained in our Lexicon: Intrathoracic, Chemotherapy, Pleural Mesothelioma, Prognosis, Surgical Resection, Immunotherapy, Mesothelioma, Overall Survival.

Related studies

• Hyperthermic intrathoracic chemotherapy (HITHOC) should be included in the guidelines for malignant pleural mesothelioma — M. Migliore, M. Ried, et al. (2021)
• Impact of hyperthermic intrathoracic chemotherapy (HITHOC) during resection of pleural mesothelioma on patient survival — I.A. Elliott, H. He, et al. (2023)
• Malignant pleural mesothelioma treated with cytoreductive video-assisted thoracic surgery plus hyperthermic intrathoracic chemotherapy: a case report — D. Li, Y. Cao, et al. (2024)
• Induction Chemotherapy Followed by Pleurectomy Decortication and Hyperthermic Intraoperative Chemotherapy (HITHOC) for Early-Stage Epitheliod Malignant Pleural Mesothelioma-A Prospective Report — S. Bongiolatti, F. Mazzoni, et al. (2021)
• Cytoreductive surgery and intraoperative hyperthermic intrathoracic chemotherapy in patients with malignant pleural mesothelioma or pleural metastases of thymoma — E. de Bree, S. van Ruth, et al. (2002)
• Cytoreductive surgery and hyperthermic intrathoracic chemotherapy perfusion for malignant pleural tumours: perioperative management and clinical experience — M. Ried, T. Potzger, et al. (2013)

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