Multimodal Treatment of Pleural Mesothelioma with Cytoreductive Surgery and Hyperthermic Intrathoracic Chemotherapy: Impact of Additive Chemotherapy

Our plain-English summary of Multimodal Treatment of Pleural Mesothelioma with Cytoreductive Surgery and Hyperthermic Intrathoracic Chemotherapy: Impact of Additive Chemotherapy, by L.V. Klotz, J. Zimmermann, K. Müller, et al (Cancers, 2024).

The study

• Authors: L.V. Klotz, J. Zimmermann, K. Müller, J. Kovács, M. Hassan, M. Koller, S. Schmid, G. Huppertz, T. Markowiak, B. Passlick, H.S. Hofmann, H. Winter, R.A. Hatz, M.E. Eichhorn, M. Ried
• Journal: Cancers
• Published: 2024;16(8)
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Cytoreductive surgery (CRS) combined with hyperthermic intrathoracic chemoperfusion (HITOC) is a promising treatment strategy for pleural mesothelioma (PM). The aim of this study was to evaluate the impacts of this multimodal approach in combination with systemic treatment on disease-free survival (DFS) and overall survival (OS). In this retrospective multicenter study, clinical data from patients after CRS and HITOC for PM at four high-volume thoracic surgery departments in Germany were analyzed. A total of 260 patients with MPM (220 epithelioid, 40 non-epithelioid) underwent CRS and HITOC as part of a multimodal treatment approach. HITOC was administered with cisplatin alone (58.5%) or cisplatin and doxorubicin (41.5%). In addition, 52.1% of patients received neoadjuvant and/or adjuvant chemotherapy. The median follow-up was 48 months (IQR = 38 to 58 months). In-hospital mortality was 3.5%. Both the resection status (macroscopic complete vs. incomplete resection) and histologic subtype (epithelioid vs. non-epithelioid) had significant impacts on DFS and OS. In addition, adjuvant chemotherapy (neoadjuvant/adjuvant) significantly increased DFS (p = 0.003). CRS and HITOC within a multimodal treatment approach had positive impacts on the survival of patients with epithelioid PM after macroscopic complete resection. The addition of chemotherapy significantly prolonged the time to tumor recurrence or progression.

In plain English

This retrospective study reviewed 260 patients with pleural mesothelioma treated from 2008 to 2019 at four German thoracic surgery departments. All had surgery to remove visible tumor (cytoreductive surgery). In the same operation, heated chemotherapy was circulated through the chest (HITOC), using cisplatin alone or with doxorubicin. 136 patients (52.3%) also received chemotherapy before and/or after surgery. Most (220) had the epithelioid subtype, and 171 had recorded asbestos exposure. In-hospital mortality was 3.5%. Median overall survival was 27 months (95% CI 21.9 to 32.1) and median disease-free survival 13 months (95% CI 11.0 to 15.0); the estimated 5-year overall survival rate was 22%. In the multivariable analysis, complete removal of visible tumor and the epithelioid subtype were associated with longer overall and disease-free survival. Additional chemotherapy was associated with longer disease-free survival (hazard ratio 0.64, 95% CI 0.47 to 0.85) but not significantly with overall survival. The authors concluded the approach had a positive impact on survival, especially for epithelioid tumors after complete resection. They named the retrospective design, multiple centers over a long period, and patient selection as limitations.

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 multicenter study of clinical records (from the German HITOC study database)
• Who was studied: 260 patients with a primary diagnosis of pleural mesothelioma (220 epithelioid, 35 biphasic, 5 sarcomatoid) treated at four high-volume thoracic surgery departments in Germany between 2008 and 2019. Follow-up data were updated until November 2021. Mean age was 65.5 years and 81.2% were male.
• Exposure: The exposure studied was treatment. Patients had cytoreductive surgery (pleurectomy/decortication, extended pleurectomy/decortication, or in 2.7% extrapleural pneumonectomy) combined with hyperthermic intrathoracic chemotherapy (HITOC). HITOC used cisplatin alone (58.5%) or cisplatin plus doxorubicin (41.5%). Some patients also had additive chemotherapy, defined as chemotherapy before and/or after surgery. Asbestos exposure was recorded as a patient characteristic: yes in 171 (65.8%), no in 56 (21.5%), and missing or unknown in 33.
• Main results:
  • Asbestos exposure was recorded in 171 of 260 patients (65.8%). It was recorded as absent in 56 (21.5%).
  • 136 of the 260 patients (52.3%) received additive chemotherapy (before and/or after surgery).
  • In-hospital mortality was 3.5% (9 of 260 patients).
  • Complications requiring surgical intervention occurred in 37 patients (14.2%).
  • For the whole cohort, median overall survival was 27 months (95% CI 21.9 to 32.1, n = 258). Overall survival rates at 1, 3 and 5 years were 82%, 40% and 22%.
  • For the whole cohort, median disease-free survival was 13 months (95% CI 11.0 to 15.0, n = 259). Disease-free survival rates at 1, 3 and 5 years were 52%, 15% and 5%.
  • Median overall survival was 31 months (95% CI 25.9 to 36.1) in patients with the epithelioid subtype and 14 months (95% CI 10.8 to 17.2) in the non-epithelioid subtype (p less than 0.001).
  • Patients with macroscopic complete resection were compared with those with incomplete (R2) resection. Overall survival was 31 vs 15 months (p less than 0.001). Disease-free survival was 14 vs 8 months (p = 0.008).
  • In the single-factor comparison, patients with additive chemotherapy were compared with those without. Median overall survival was 32 vs 21 months (p = 0.020). Median disease-free survival was 15 vs 9 months (p less than 0.001).
  • In the multivariable Cox analysis, resection status and histologic subtype remained significant for overall survival (both p less than 0.001). They also remained significant for disease-free survival (p = 0.010 and p less than 0.001).
  • In the multivariable analysis, additive chemotherapy was significantly associated with disease-free survival (HR 0.64, 95% CI 0.47 to 0.85, p = 0.003). It was not significantly associated with overall survival (HR 0.79, 95% CI 0.56 to 1.12, p = 0.184).
  • High-dose versus low-dose cisplatin made no statistically significant difference to overall survival (39 vs 25 months, p = 0.103).
• The authors' conclusion: The authors concluded that cytoreductive surgery and HITOC within a multimodal approach had a positive impact on survival of patients with pleural mesothelioma, especially those with the epithelioid subtype and after macroscopic complete resection. They also concluded that adding chemotherapy significantly affected the interval to tumor recurrence.
• Limitations the authors state:
  • The study was retrospective, and patients were treated at different institutions over a long period of time.
  • Decision making and the selection criteria for surgical candidates may have influenced the results on complications, complete resection, disease-free survival and overall survival.
  • No difference was found between chemotherapy given before surgery and after surgery. The authors suggested this may be due to the small number of patients who received chemotherapy before surgery.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Cytoreductive Surgery, Intrathoracic, Chemotherapy, Disease-Free Survival, Overall Survival, Thoracic Surgery, Epithelioid.

Related studies

• Hyperthermic Intrathoracic Chemotherapy (HITOC) after Cytoreductive Surgery for Pleural Malignancies-A Retrospective, Multicentre Study — M. Ried, J. Kovács, et al. (2021)
• Cytoreductive surgery and hyperthermic intrathoracic chemotherapy perfusion for malignant pleural tumours: perioperative management and clinical experience — M. Ried, T. Potzger, et al. (2013)
• 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)
• Present and future of cytoreductive surgery and hyperthermic intrathoracic chemotherapy for pleural metastases: a narrative review — A. Hajja, M. Atout, et al. (2026)
• Malignant pleural mesothelioma treated with cytoreductive video-assisted thoracic surgery plus hyperthermic intrathoracic chemotherapy: a case report — D. Li, Y. Cao, et al. (2024)

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