Multimodal therapy of epithelioid pleural mesothelioma: improved survival by changing the surgical treatment approach

Our plain-English summary of Multimodal therapy of epithelioid pleural mesothelioma: improved survival by changing the surgical treatment approach, by L.V. Klotz, H. Hoffmann, R. Shah, et al (Translational Lung Cancer Research, 2022).

The study

• Authors: L.V. Klotz, H. Hoffmann, R. Shah, F. Eichhorn, C. Gruenewald, E.L. Bulut, R. Griffo, T. Muley, P. Christopoulos, P. Baum, P. Huber, S. Safi, M. Kriegsmann, M. Thomas, H. Bischoff, H. Winter, M.E. Eichhorn
• Journal: Translational Lung Cancer Research
• Published: 2022;11(11):2230-2242
• Cited by: 28 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: The exact role and type of surgery for malignant pleural mesothelioma (MPM) remains controversial. This study aimed at analyzing a 20-year single center perioperative experience in MPM surgery at our high-volume thoracic surgery center and comparing the overall survival after trimodal extrapleural pneumonectomy (EPP) and extended pleurectomy and decortication combined with hyperthermic intrathoracic chemoperfusion (EPD/HITOC) and adjuvant chemotherapy with that after chemotherapy (CTx) alone.

Methods: Patients with epithelioid MPM treated with neoadjuvant chemotherapy, EPP and adjuvant radiotherapy within a trimodal concept or EPD/HITOC in combination with adjuvant chemotherapy between 2001 and 2018 were included in this retrospective analysis. Surgical cohorts were compared to patients treated with standard chemotherapy.

Results: Overall, 182 patients (69 EPP, 57 EPD/HITOC, 56 CTx) were analyzed. Due to occupational exposure to asbestos for most of the patients, 154 patients (84.6%) were male. The patients in the surgical cohorts were significantly younger than those in the CTx cohort. There was no significant difference between the proportion of patient age and side. The median overall survival of the EPD/HITOC cohort with 38.1 months was significantly longer than that of the EPP and CTx cohorts (24.0 and 15.8 months). Better survival was significantly associated with an ECOG 0 performance status, age below 70 years, and negative lymph node status. In the multivariate analysis, EPD/HITOC was significantly associated with improved overall survival. Perioperative morbidity was lower in the EPD/HITOC group than in the EPP cohort.

Conclusions: EPD/HITOC is feasible and safe for localized epithelioid pleural mesothelioma. Changing the surgical approach to a less radical lung-sparing technique may improve overall survival compared to trimodal EPP.

2022 Translational Lung Cancer Research. All rights reserved.

In plain English

This retrospective study from Heidelberg, Germany, compared three treatments in 182 patients with epithelioid malignant pleural mesothelioma. Sixty-nine had extrapleural pneumonectomy (EPP, removal of the lung and lining) in 2001 to 2012; all had chemotherapy beforehand and 57 radiotherapy afterward. Fifty-seven had lung-sparing extended pleurectomy and decortication with heated chemotherapy washed through the chest (EPD/HITOC) in 2014 to 2018; 43 then had chemotherapy. Fifty-six had chemotherapy alone. More than 60% had prior asbestos exposure, which was not analyzed. Median overall survival was 38.1 months (95% confidence interval 30.3 to 45.9) after EPD/HITOC and 24.0 months (95% CI 16.9 to 31.1) after EPP. For chemotherapy alone, the article reports 15.8 and 15.5 months. Compared with chemotherapy alone, EPD/HITOC was linked with a lower risk of death after adjustment (hazard ratio 0.428, 95% CI 0.245 to 0.748), while EPP was not significantly linked. Complications around surgery affected 36.2% of EPP patients and 11 EPD/HITOC patients, reported as 18%. The authors concluded survival improved after the change to lung-sparing surgery. They noted possible bias in how patients were chosen for treatment.

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 single-center cohort study comparing three treatment groups, drawn from a prospectively maintained database
• Who was studied: 182 patients with epithelioid malignant pleural mesothelioma treated at Thoraxklinik Heidelberg, Germany. The groups were: 69 with EPP (February 2001 to June 2012), 57 with EPD/HITOC (January 2014 to August 2018), and 56 with chemotherapy alone (February 2014 to December 2018). Patients with biphasic or sarcomatoid tumors were excluded. Between 84% and 86% of each group were male.
• Exposure: The study compared treatments, not asbestos exposure. The three treatments were: (1) trimodal EPP, where all 69 patients had chemotherapy before surgery and 57 of 69 (83%) had radiotherapy afterward; (2) extended pleurectomy and decortication with hyperthermic intrathoracic cisplatin chemoperfusion, after which 43 of 57 (75%) had adjuvant chemotherapy; and (3) palliative chemotherapy alone. More than 60% of patients had prior asbestos exposure.
• Main results:
  • In the EPD/HITOC group, median overall survival was 38.1 months (95% CI 30.3 to 45.9). This was significantly longer than in the EPP group (P=0.01) and the chemotherapy-alone group (P less than 0.001).
  • In the EPP group, median overall survival was 24 months (95% CI 16.9 to 31.1). In the chemotherapy-alone group it was 15.8 months (P=0.028). Table 1 gives 15.5 months (95% CI 11.8 to 19.1) for the chemotherapy group.
  • Within the EPP group, median survival was 26.8 months for patients who completed radiotherapy and 14.6 months for those who did not. This difference was not statistically significant (P=0.119).
  • In the multivariate analysis of all 182 patients, with chemotherapy alone as the reference group: EPD/HITOC had a hazard ratio of 0.428 (95% CI 0.245 to 0.748, P=0.003). EPP had a hazard ratio of 0.806 (95% CI 0.467 to 1.393, P=0.440), which was not significant.
  • In unadjusted survival comparisons of all patients, better survival was significantly associated with ECOG 0 performance status, age 70 or below, and no lymph node metastasis. In the multivariate model, none of these factors was statistically significant.
  • Complications around surgery occurred in 36.2% of EPP patients (25 of 69) and in 11 EPD/HITOC patients, which the article reports as 18% (P=0.0475). Reoperation was needed in 26.1% of EPP patients (18) and in 4 EPD/HITOC patients, reported as 6.5% (P=0.005).
  • No EPD/HITOC patient died within 30 or 90 days. In the EPP group, 30-day mortality was 2.9% and 90-day mortality was 5.8% (4 of 69).
  • In the EPD/HITOC group, macroscopically complete resection was achieved in 51 of 57 patients (89%).
• The authors' conclusion: The authors concluded that survival of patients with epithelioid pleural mesothelioma improved after their center changed from maximal radical surgery to lung-sparing surgery with HITOC and adjuvant chemotherapy. They also concluded that lung-sparing surgery should be performed in carefully selected patients after a multidisciplinary decision.
• Limitations the authors state:
  • The retrospective design introduced selection bias over the long study period. Patients with other illnesses or a high tumor burden were not offered surgery, so the groups were not evenly distributed.
  • Differences in performance status between the three groups may have influenced survival.
  • Clinical tumor stages in the chemotherapy group were compared with pathological stages in the surgical groups. This may have understaged the chemotherapy group.
  • The effect of HITOC itself on survival could not be assessed because there was no control group.
  • Improvements over time in care around surgery and in treatment of recurrence may have influenced survival in the later EPD/HITOC group.

Topics

Medical terms in this study, explained in our Lexicon: Multimodal Therapy, Epithelioid, Pleural Mesothelioma, Thoracic Surgery, Overall Survival, Extrapleural Pneumonectomy (EPP), Intrathoracic, Chemotherapy.

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• Multimodal therapy of malignant pleural mesothelioma: is the replacement of radical surgery imminent? — J. Lindenmann, V. Matzi, et al. (2013)
• Paclitaxel-loaded expansile nanoparticles in a multimodal treatment model of malignant mesothelioma — M.D. Schulz, K.A. Zubris, et al. (2011)
• Multimodal Treatment of Malignant Pleural Mesothelioma: Real-World Experience with 112 Patients — A. Holzknecht, O. Illini, et al. (2022)
• Multimodal treatment for malignant pleural mesothelioma — R.C. Rintoul, T. Treasure, et al. (2015)
• Techniques of surgery and radiotherapy for multimodal treatment of pleural mesothelioma — P. Bonnette (2011)

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