Hyperthermic Intrathoracic Chemotherapy (HITOC) after Cytoreductive Surgery for Pleural Malignancies-A Retrospective, Multicentre Study

Our plain-English summary of Hyperthermic Intrathoracic Chemotherapy (HITOC) after Cytoreductive Surgery for Pleural Malignancies-A Retrospective, Multicentre Study, by M. Ried, J. Kovács, T. Markowiak, et al (Cancers, 2021).

The study

• Authors: M. Ried, J. Kovács, T. Markowiak, K. Müller, G. Huppertz, M. Koller, H. Winter, L.V. Klotz, R. Hatz, J. Zimmermann, B. Passlick, S. Schmid, M. Hassan, M.E. Eichhorn, H.S. Hofmann
• Journal: Cancers
• Published: 2021;13(18)
• Cited by: 20 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

In the context of quality assurance, the objectives were to describe the surgical treatment and postoperative morbidity (particularly renal insufficiency). A retrospective, multicentre study of patients who underwent cytoreductive surgery (CRS) with cisplatin-based HITOC was performed. The study was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation (GZ: RI 2905/3-1)). Patients (n = 350) with malignant pleural mesothelioma (n = 261; 75%) and thymic tumours with pleural spread (n = 58; 17%) or pleural metastases (n = 31; 9%) were analyzed. CRS was accomplished by pleurectomy/decortication (P/D: n = 77; 22%), extended P/D (eP/D: n = 263; 75%) or extrapleural pneumonectomy (EPP: n = 10; 3%). Patients received cisplatin alone (n = 212; 61%) or cisplatin plus doxorubicin (n = 138; 39%). Low-dose cisplatin (≤125 mg/m2 BSA) was given in 67% of patients (n = 234), and high-dose cisplatin (>125 mg/m2 BSA) was given in 33% of patients (n = 116). Postoperative renal insufficiency appeared in 12% of the patients (n = 41), and 1.4% (n = 5) required temporary dialysis. Surgical revision was necessary in 51 patients (15%). In-hospital mortality was 3.7% (n = 13). Patients receiving high-dose cisplatin were 2.7 times more likely to suffer from renal insufficiency than patients receiving low-dose cisplatin (p = 0.006). The risk for postoperative renal failure is dependent on the intrathoracic cisplatin dosage but was within an acceptable range.

In plain English

This retrospective study from four German centres reviewed 350 patients who, in 2008 to 2019, had surgery removing tumour from the chest lining plus, in the same operation, heated chemotherapy rinsed through the chest (HITOC) with cisplatin, alone or with doxorubicin. Most (261) had malignant pleural mesothelioma; the rest had thymic tumours or other cancers spread to the pleura. The article does not discuss asbestos exposure. Kidney injury after surgery occurred in 41 patients (11.7%); 5 (1.4%) needed temporary dialysis. Adjusted for other treatment factors, the odds of kidney injury were 2.7 times as high with high-dose as low-dose cisplatin (95% confidence interval 1.3 to 5.6). Thirteen patients (3.7%) died in hospital. Unadjusted, the odds of in-hospital death were 12.2 times higher with high-dose than low-dose cisplatin (95% confidence interval 2.6 to 55.8). Complications occurred in 178 patients and 51 needed repeat surgery. The authors concluded that kidney injury risk depends on cisplatin dose. They noted limitations: retrospective design, no comparison group without HITOC, doses varying between centres and over time, and too few deaths for adjusted mortality analysis.

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, multicentre study of surgical treatment and short-term (in-hospital) outcomes
• Who was studied: 350 patients (of 359 treated) who had cytoreductive surgery with cisplatin-based HITOC at four German university thoracic surgery centres between January 2008 and December 2019. 261 had malignant pleural mesothelioma, 58 had stage IVa thymic tumours and 31 had secondary pleural metastases.
• Exposure: Not asbestos. The study examined a treatment: hyperthermic intrathoracic chemotherapy after cytoreductive surgery. 212 patients received cisplatin alone and 138 received cisplatin plus doxorubicin. Cisplatin dose was grouped as low (125 mg/m2 body surface area or less) or high (more than 125 mg/m2).
• Main results:
  • 234 patients (about 67%) received low-dose cisplatin (125 mg/m2 or less) and about 33% received high-dose cisplatin.
  • 41 of 350 patients (11.7%) developed postoperative renal insufficiency.
  • Of the 41 patients with renal insufficiency, 23 had stage I acute kidney injury, 10 had stage II and 8 had stage III.
  • Five patients (1.4%) needed temporary dialysis after surgery, all with stage III acute kidney injury.
  • In a multivariable logistic regression, the odds of renal insufficiency were 2.7 times as high in patients receiving high-dose cisplatin as in those receiving low-dose cisplatin (odds ratio 2.73, 95% CI 1.3 to 5.6; p = 0.006). The article describes this as being '2.7 times more likely'.
  • In the same multivariable model, the odds of renal insufficiency were 8.3 times as high in patients receiving medicamentous cytoprotection as in those not receiving it (95% CI 2.4 to 29.5; p = 0.001).
  • In the same multivariable model, the odds of renal insufficiency were 6.3 times as high in patients without perioperative fluid balancing (95% CI 1.6 to 25.5; p = 0.009).
  • In-hospital mortality was 3.7% (13 patients). Six deaths were attributed to surgical complications and seven to nonsurgical complications.
  • In a univariable (unadjusted) logistic regression, the odds of in-hospital death were 12.2 times higher in patients given high-dose cisplatin than in those given low-dose cisplatin (95% CI 2.6 to 55.8; p = 0.001). Table 4 lists 2 deaths among low-dose patients and 11 among high-dose patients.
  • Postoperative complications occurred in 178 patients (51%).
  • 51 patients (15%) needed surgical revision.
• The authors' conclusion: The authors concluded that the risk of renal insufficiency after cytoreductive surgery with HITOC depends on the cisplatin dosage.
• Limitations the authors state:
  • The study was retrospective and analysed a selected group of patients.
  • Chemotherapy doses differed between study centres and changed over time.
  • There was no control group of patients who had the surgery without HITOC.
  • Long-term data were not yet available.
  • Data on cytoprotective drugs were not uniform across centres.
  • Because few patients died, no multivariable analysis of in-hospital mortality could be done.

Topics

Medical terms in this study, explained in our Lexicon: Intrathoracic, Chemotherapy, Cytoreductive Surgery, Cisplatin, Pleural Mesothelioma, Pleurectomy/Decortication (P/D), Extrapleural Pneumonectomy (EPP), Doxorubicin.

Related studies

• Multimodal Treatment of Pleural Mesothelioma with Cytoreductive Surgery and Hyperthermic Intrathoracic Chemotherapy: Impact of Additive Chemotherapy — L.V. Klotz, J. Zimmermann, et al. (2024)
• Hyperthermic intrathoracic chemotherapy after cytoreductive surgery in malignant pleural mesothelioma: a single-center retrospective cohort study suggesting increased morbidity without survival benefit — N. Baldes, F. Doerr, et al. (2026)
• Cytoreductive surgery and hyperthermic intrathoracic chemotherapy perfusion for malignant pleural tumours: perioperative management and clinical experience — M. Ried, T. Potzger, et al. (2013)
• Pressurized intrathoracic aerosol chemotherapy (PITAC) for malignant pleural mesothelioma-ex vivo evaluation of optimal treatment conditions and comparison with hyperthermic intrathoracic chemotherapy (HITOC) — K. Flöthmann, N. Zinne, et al. (2026)
• 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)
• Pharmacokinetics of doxorubicin and cisplatin used in intraoperative hyperthermic intrathoracic chemotherapy after cytoreductive surgery for malignant pleural mesothelioma and pleural thymoma — S. van Ruth, O. van Tellingen, et al. (2003)

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