HITOCH After Surgery Appears Safe, May Improve Survival in Mesothelioma

Data from 6 studies showed a survival benefit that ranged from 13 to 35 months in patients who received HITOCH vs 11 to 22.8 months in patients who did not receive HITOCH.

Hyperthermic intrathoracic chemotherapy (HITOCH) added to macroscopic complete resection (MCR) showed potential improvements to survival outcomes while appearing safe and feasible in patients with malignant pleural mesothelioma (MPM), according to findings from a systematic review (CRD42024588823) published in the World Journal of Surgical Oncology.¹

Data from 6 studies showed a survival benefit that ranged from 13 to 35 months in patients who received HITOCH vs 11 to 22.8 months in patients who did not receive HITOCH.

A prospective phase 2 study reported a median overall survival (OS) of 12.8 months in all patients; the median OS in patients treated with HITOCH was 13.1 months vs 11.0 in patients treated without hyperthermic intrapleural cisplatin perfusion (P = .01).² This study concluded that adding HITOCH conferred a survival benefit.

In a cohort study of 103 patients who had cytoreductive surgery, the HITOCH group demonstrated an improved interval to recurrence at 27.1 months vs 12.8 months without HITOCH; median OS was also improved at 35.3 months vs 22.8 months, respectively.³

In a study that compared 19 patients with metastatic malignant pleural effusions (MPEs) who received hyperthermic intraperitoneal chemotherapy (HIPEC) after surgical interventions with historical control groups, intrapleural HIPEC with cytoreduction significantly improved survival.⁴ The median survival was 15.4 months in the HITOCH group vs 6 months and 8 months in the control groups.

Investigators of another study evaluated 14 patients with MPM and found there was no operative mortality in the pleurectomy decortication group plus HITOCH group or the extra-pleural pneumonectomy group.⁵

Investigators of a different study compared 5 patients who underwent MCR for MPM with 3 patients in a contemporary control group and found that, at 9 months, 4 patients and 1 patient were alive, respectively.⁶ Complications of grades 3 or 4 were observed in 1 patient in the HITOCH group and 0 patients in the non-HITOCH group.

Another study evaluated 55 patients with localized MPM, including 30 who received only surgery and 25 who had surgery followed by HITOCH with cisplatin.⁷ Investigators found an OS of 28 months (95% CI, 21.5-34.5) with HITOCH compared with 22 months (95% CI, 17.5-26.5) in the surgery only group. The 30-day mortality rate was 0% vs 3.3%, respectively.

The only study to find results that were not favorable for HITOCH showed 29 months of survival with extra-pleural pneumonectomy/postoperative hemi-thoracic radiation and 11 months with HITOCH.⁸

Study author Mohammed Abdel-gayed, in the Cardiothoracic Surgery Department at Ain Shams University Hospital in Cairo, Egypt, and fellow authors, stated in the paper, “Despite the heterogeneity, small number of cases, and lack of prospective randomized controlled trials, the body of evidence identified in this work demonstrates that HITHOC added to MCR in patients with [MPM] is safe and feasible.”¹

A total of 305 studies that fulfilled the minimum standards of quality were identified, of which 21 were relevant to the topic of the systematic review. There were 7 studies that provided the best evidence to determine whether performing HITOCH after MCR led to improved survival.

Studies that were included were originally written in English and compared HITOCH with non-HITOCH therapy after surgery for patients with mesothelioma only; investigators permitted studies that assessed different types of radical surgery if a comparison was available between HITOCH and non-HITOCH cases.

Exclusion criteria included duplicate studies, conference articles, articles unrelated to HITOCH, intervention studies, articles with unavailable full texts or gray literature, and studies without a design suitable for the objective of this review.

“Possible improvement in recurrence-free survival and [OS] warrant investigation in a randomized controlled trial,” Abdel-gayed and coauthors concluded.¹

References

1. Elsayed HH, Elanany MEE, ElSayegh MT, Hassaballa AS, Abdel-gayed M. Hyperthermic intrathoracic chemotherapy in patients with malignant pleural mesothelioma after cytoreductive surgical procedures: a systematic review. World J Surg Oncol. 2025;23(1):132. Published 2025 Apr 9. doi:10.1186/s12957-025-03748-8
2. Tilleman TR, Richards WG, Zellos L, et al. Extrapleural pneumonectomy followed by intracavitary intraoperative hyperthermic cisplatin with pharmacologic cytoprotection for treatment of malignant pleural mesothelioma: a phase II prospective study. J Thorac Cardiovasc Surg. 2009;138(2):405-411. doi:10.1016/j.jtcvs.2009.02.046
3. Sugarbaker DJ, Gill RR, Yeap BY, et al. Hyperthermic intraoperative pleural cisplatin chemotherapy extends interval to recurrence and survival among low-risk patients with malignant pleural mesothelioma undergoing surgical macroscopic complete resection. J Thorac Cardiovasc Surg. 2013;145(4):955-963. doi:10.1016/j.jtcvs.2012.12.037
4. Işık AF, Sanli M, Yılmaz M, et al. Intrapleural hyperthermic perfusion chemotherapy in subjects with metastatic pleural malignancies. Respir Med. 2013;107(5):762-767. doi:10.1016/j.rmed.2013.01.010
5. Ishibashi H, Kobayashi M, Takasaki C, Okubo K. Interim results of pleurectomy/decortication and intraoperative intrapleural hyperthermic cisplatin perfusion for patients with malignant pleural mesothelioma intolerable to extrapleural pneumonectomy. Gen Thorac Cardiovasc Surg. 2015;63(7):395-400. doi:10.1007/s11748-015-0535-x
6. Patel MD, Damodaran D, Rangole A, et al. Hyperthermic intrathoracic chemotherapy (HITHOC) for pleural malignancies-experience from Indian centers. Indian J Surg Oncol. 2019;10(Suppl 1):91-98. doi:10.1007/s13193-018-0859-y
7. Elsayed HH, Sharkawy HY, Ahmed MA, Abdel-Gayed M, Eldewer M. Effect of intraoperative hyperthermic intrathoracic chemotherapy after pleurectomy decortication for treatment of malignant pleural mesothelioma: a comparative study. Updates Surg. 2024;76(8):2893-2901. doi:10.1007/s13304-024-01986-1
8. van Sandick JW, Kappers I, Baas P, Haas RL, Klomp HM. Surgical treatment in the management of malignant pleural mesothelioma: a single institution's experience. Ann Surg Oncol. 2008;15(6):1757-1764. doi:10.1245/s10434-008-9899-9