Impact of hyperthermic intrathoracic chemotherapy (HITHOC) during resection of pleural mesothelioma on patient survival

Our plain-English summary of Impact of hyperthermic intrathoracic chemotherapy (HITHOC) during resection of pleural mesothelioma on patient survival, by I.A. Elliott, H. He, N.S. Lui, et al (Journal of Thoracic Disease, 2023).

The study

• Authors: I.A. Elliott, H. He, N.S. Lui, D.Z. Liou, B.A. Guenthart, J.B. Shrager, M.F. Berry, L.M. Backhus
• Journal: Journal of Thoracic Disease
• Published: 2023;15(11):6140-6150
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Pleural mesothelioma (PM) is rare but portends a poor prognosis. Multimodal treatment, including aggressive surgical resection, may offer the best chance of treatment response and improved survival. Single-center studies suggest that hyperthermic intrathoracic chemotherapy (HITHOC) during surgical resection improves outcomes, but the impact of HITHOC on postoperative morbidity and survival has not been examined on a larger scale.

Methods: The National Cancer Database was queried for patients undergoing resection for PM from 2006-2017. Patients were excluded if staging or survival data was incomplete. After propensity-score matching, patients who underwent HITHOC were compared to patients who did not (case-control study). Perioperative outcomes and survival were analyzed.

Results: The final cohort consisted of 3,232 patients; of these, 365 patients underwent HITHOC. After propensity-score matching, receipt of HITHOC was associated with increased length of stay (12 vs. 7 days, P<0.001) and increased 30-day readmissions (9.9% vs. 4.9%, P=0.007), but decreased 30-day mortality (3.2% vs. 6.0%, P=0.017) and 90-day mortality (7.5% vs. 10.9%). Kaplan-Meier modeling demonstrated that HITHOC was associated with improved survival in the overall cohort (median 20.5 vs. 16.8 months, P=0.001). In multivariable analysis, HITHOC remained associated with improved overall survival [hazard ratio (HR) =0.80; 95% confidence interval (CI): 0.69-0.92; P=0.002], and this persisted in the propensity-matched analysis (HR =0.73; 95% CI: 0.61-0.88; P=0.001).

Conclusions: Using a large national database, we describe the impact of HITHOC on survival in patients with PM. Despite observed increased short-term morbidity, in multivariable analysis HITHOC was associated with an overall survival advantage for patients undergoing surgical resection of PM.

2023 Journal of Thoracic Disease. All rights reserved.

In plain English

This retrospective study used the US National Cancer Database to compare patients who had surgery for pleural mesothelioma from 2006 to 2017 with and without chemotherapy given during the operation. The authors took this to mean heated chest chemotherapy (HITHOC). Of 3,232 patients, 365 received HITHOC. The HITHOC group stayed in hospital longer and was more often readmitted within 30 days. After matching similar patients, deaths within 30 days (3.2% vs. 6.0%) and within 90 days (7.5% vs. 10.9%) were lower in the HITHOC group. Median survival was 20.5 vs. 16.8 months in the full group. In the matched groups, the difference between the survival curves was not statistically significant (18.5 vs. 17.9 months). After adjusting for other factors, HITHOC was associated with a lower risk of death: hazard ratio 0.80 (95% confidence interval 0.69 to 0.92) overall, and 0.73 (0.61 to 0.88) in matched groups. The authors concluded that HITHOC was independently associated with improved survival and that further investigation is supported. They noted possible coding errors, selection bias and uncontrolled confounding, and that the chemotherapy used and exact operation were unknown.

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 analysis of a national cancer database, with propensity-score matching and multivariable Cox survival models
• Who was studied: 3,232 patients in the US National Cancer Database who underwent surgical resection for pleural mesothelioma from 2006 to 2017; 365 received HITHOC. The propensity-matched groups were 312 HITHOC and 468 non-HITHOC patients.
• Exposure: The exposure studied was a treatment, not asbestos: intraoperative chemotherapy coded in the database, assumed by the authors to be HITHOC. The specific drug and method could not be determined. The article reports no asbestos exposure or fiber data.
• Main results:
  • Of the 3,232 patients, 365 (11.3%) received HITHOC.
  • In the overall cohort, HITHOC patients had longer hospital stays (median 12 vs. 6 days, P<0.001) and more 30-day readmissions (9.9% vs. 5.2%, P<0.001). In the matched cohort the figures were 12 vs. 7 days and 9.9% vs. 4.9% (P=0.007).
  • In the overall cohort, 30-day mortality was 2.8% with HITHOC vs. 5.3% without (P=0.059, not statistically significant). 90-day mortality was 6.6% vs. 12.4% (P=0.002).
  • In the propensity-matched cohort, 30-day mortality was 3.2% with HITHOC vs. 6.0% without (P=0.017). 90-day mortality was 7.5% vs. 10.9% (P=0.046).
  • Unadjusted (Kaplan-Meier) median survival in the overall cohort was 20.5 months with HITHOC vs. 16.8 months without (P=0.001).
  • In the propensity-matched cohort, the Kaplan-Meier survival difference was not statistically significant (P=0.119); median survival was 18.5 vs. 17.9 months.
  • In multivariable analysis of the overall cohort, HITHOC was associated with improved survival: hazard ratio 0.80 (95% CI 0.69 to 0.92), P=0.002.
  • In multivariable analysis of the propensity-matched cohort, HITHOC was associated with a lower risk of death: hazard ratio 0.73 (95% CI 0.61 to 0.88), P=0.001.
  • In the 1,912 patients with epithelioid histology, median survival was 23.1 vs. 20.9 months (Kaplan-Meier P=0.0116). The multivariable hazard ratio for HITHOC was 0.84 (95% CI 0.70 to 1.00), P=0.050; the table does not mark this value as below the P<0.05 significance threshold.
  • In the 1,632 patients coded as having total surgical removal of the primary site or radical surgery, the hazard ratio for HITHOC was 0.76 (95% CI 0.64 to 0.90), P=0.001. After propensity matching within this subgroup it was 0.72 (95% CI 0.58 to 0.90), P=0.004.
• The authors' conclusion: The authors concluded that HITHOC was independently associated with improved survival after surgical resection of pleural mesothelioma, and that this supports further investigation of its use.
• Limitations the authors state:
  • The data may contain coding and data-collection errors, selection bias between treatment groups, and confounding by variables not controlled for.
  • The specific type and manner of the intraoperative chemotherapy could not be determined.
  • The database does not distinguish extrapleural pneumonectomy from extended pleurectomy/decortication, so the exact operation could not be known or controlled for.
  • The HITHOC group may have been biased toward patients receiving more aggressive surgery, which could confound the apparent benefit.
  • The lower short-term mortality with HITHOC may reflect selection of healthier patients that matching did not control for.
  • Recurrence and disease-free survival could not be analyzed because the database does not report them.

Topics

Medical terms in this study, explained in our Lexicon: Intrathoracic, Chemotherapy, Pleural Mesothelioma, Prognosis, Surgical Resection, Staging, Case-Control Study, 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)
• The Role of Hyperthermic Intrathoracic Chemotherapy (HITHOC) in Thoracic Tumors — F. Danuzzo, M.C. Sibilia, et al. (2024)
• 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)
• Hyperthermic intraoperative pleural cisplatin chemotherapy extends interval to recurrence and survival among low-risk patients with malignant pleural mesothelioma undergoing surgical macroscopic complete resection — D.J. Sugarbaker, R.R. Gill, et al. (2013)
• 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)

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