Improved Outcomes with Modern Lung-Sparing Trimodality Therapy in Patients with Malignant Pleural Mesothelioma

Our plain-English summary of Improved Outcomes with Modern Lung-Sparing Trimodality Therapy in Patients with Malignant Pleural Mesothelioma, by F. Shaikh, M.G. Zauderer, D. von Reibnitz, et al (Journal of Thoracic Oncology, 2017).

The study

• Authors: F. Shaikh, M.G. Zauderer, D. von Reibnitz, A.J. Wu, E.D. Yorke, A. Foster, W. Shi, Z. Zhang, P.S. Adusumilli, K.E. Rosenzweig, L.M. Krug, V.W. Rusch, A. Rimner
• Journal: Journal of Thoracic Oncology
• Published: 2017;12(6):993-1000
• Cited by: 52 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Introduction: Higher target conformity and better sparing of organs at risk with modern radiotherapy (RT) may result in higher tumor control and less toxicity. In this study, we compare our institutional multimodality therapy experience of adjuvant chemotherapy and hemithoracic intensity-modulated pleural RT (IMPRINT) with previously used adjuvant conventional RT (CONV) in patients with malignant pleural mesothelioma (MPM) treated with lung-sparing pleurectomy/decortication (P/D).

Methods: We analyzed 209 patients who underwent P/D and adjuvant RT (131 who received CONV and 78 who received IMPRINT) for MPM between 1974 and 2015. The primary end point was overall survival (OS). The Kaplan-Meier method and Cox proportional hazards model were used to calculate OS; competing risks analysis was performed for local failure-free survival and progression-free survival. Univariate analysis and multivariate analysis were performed with relevant clinical and treatment factors.

Results: The median age was 64 years, and 80% of the patients were male. Patients receiving IMPRINT had significantly higher rates of the epithelial histological type, advanced pathological stage, and chemotherapy treatment. OS was significantly higher after IMPRINT (median 20.2 versus 12.3 months, p = 0.001). Higher Karnofsky performance score, epithelioid histological type, macroscopically complete resection, and use of chemotherapy/IMPRINT were found to be significant factors for longer OS in multivariate analysis. No significant predictive factors were identified for local failure or progression. Grade 2 or higher esophagitis developed in fewer patients after IMPRINT than after CONV (23% versus 47%).

Conclusions: Trimodality therapy including adjuvant hemithoracic IMPRINT, chemotherapy, and P/D is associated with promising OS rates and decreased toxicity in patients with MPM. Dose constraints should be applied vigilantly to minimize serious adverse events.

Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

In plain English

This retrospective study reviewed the records of 209 patients with malignant pleural mesothelioma treated at Memorial Sloan Kettering Cancer Center from 1974 to 2015. All had lung-sparing surgery followed by radiation to the chest. It compared 131 patients given older conventional radiation with 78 given a newer, more targeted technique, IMPRINT. Chemotherapy was given to 90% of the IMPRINT group but only 11% of the conventional group. Measured from the start of radiation, median survival was 20.2 months (95% confidence interval 13.5 to 28.2) with IMPRINT and 12.3 months (10.0 to 15.3) with conventional radiation. In multivariate analysis, IMPRINT, higher performance score, epithelioid tumor type and macroscopically complete tumor removal were linked to longer survival. Local failure and disease progression did not differ significantly between the groups. Grade 2 or higher esophagitis affected 23% of IMPRINT and 47% of conventional patients, while fatigue and cough were more common with IMPRINT. The authors concluded this combined treatment was associated with longer survival and less severe toxicity. They noted the study was retrospective, spanned 40 years, and compared groups that differed in several ways.

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 one institution's database, comparing two radiation techniques after lung-sparing surgery
• Who was studied: 209 patients with malignant pleural mesothelioma treated at Memorial Sloan Kettering Cancer Center, New York, between 1974 and 2015, who had lung-sparing surgery and radiation after surgery. Median age was 64 and the male to female ratio was 4:1. 131 received conventional radiation and 78 received IMPRINT.
• Exposure: Treatments, not asbestos exposure, were studied. All patients had lung-sparing surgery (extended pleurectomy/decortication, pleurectomy/decortication, or partial pleurectomy), followed by either conventional radiation or intensity-modulated pleural radiation therapy (IMPRINT). Most IMPRINT patients also received platinum/pemetrexed chemotherapy.
• Main results:
  • All endpoints, including overall survival, were measured from the start of radiation therapy.
  • Median overall survival was 20.2 months (95% CI 13.5 to 28.2) in the IMPRINT group and 12.3 months (95% CI 10.0 to 15.3) in the conventional radiation group.
  • Survival at 1 and 2 years was 69% and 42% for IMPRINT patients, and 50% and 20% for conventional radiation patients.
  • In the multivariate analysis, four factors were significantly associated with longer overall survival: Karnofsky performance score above 80%, epithelioid histology, macroscopically complete resection, and IMPRINT. For IMPRINT versus conventional radiation, Table 2 gives a hazard ratio of 0.66 (95% CI 0.47 to 0.92).
  • Chemotherapy was associated with improved survival in the univariate analysis (HR 0.63, 95% CI 0.46 to 0.86). It did not enter the final multivariate model because it was highly correlated with radiation technique: 90% of IMPRINT patients and 11% of conventional patients received it.
  • The IMPRINT group differed from the conventional group. Among IMPRINT patients, 65% were older than 64 (45% in the conventional group), 50% had a performance score above 80 (31%), 86% had epithelioid histology (59%), and 76% had advanced pathological stage (49%).
  • Local failure occurred in 116 patients (56% of all patients). Cumulative incidence of local failure at 1 and 2 years was 42% and 60% for IMPRINT and 34% and 47% for conventional radiation. The difference was not statistically significant.
  • Disease progressed in 145 patients (69%). Cumulative incidence of progression at 1 and 2 years was 53% and 72% for IMPRINT and 47% and 69% for conventional radiation. The difference was not statistically significant.
  • Grade 2 or higher side effects: IMPRINT patients had more fatigue (47% versus 16%) and cough (18% versus 2%). Conventional radiation patients had more esophagitis (47% versus 23% with IMPRINT).
  • Grade 2 or higher radiation pneumonitis occurred in 26% of IMPRINT patients and 35% of conventional patients. This difference was not statistically significant.
  • There were 4 possibly toxicity-related deaths in the conventional group, two of them from grade 5 radiation pneumonitis, and 2 in the IMPRINT group.
• The authors' conclusion: The authors concluded that IMPRINT, given together with modern chemotherapy and lung-sparing surgery, is associated with higher overall survival and lower rates of severe toxicity than lung-sparing surgery and conventional radiation alone.
• Limitations the authors state:
  • The study was retrospective and covered patients treated over 40 years, during which radiation, medical and surgical oncology changed significantly.
  • The groups differed. The IMPRINT group had some more favorable characteristics (higher performance score, more epithelioid tumors, more chemotherapy) and some less favorable ones (older age, more advanced pathologic stage).
  • Closer follow-up and more accurate imaging in recent years may have detected recurrences earlier, which may explain the lack of difference in local failure and progression.
  • Toxicity rates may be inaccurate, especially for patients treated before electronic medical records. Better recent documentation may explain the higher rates of cough and fatigue recorded with IMPRINT.
  • Grading of radiation pneumonitis is somewhat subjective. A larger cohort may be needed to show a significant difference in pneumonitis.
  • The marginal associations of left-sided disease and female sex with progression should not be overinterpreted.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Trimodality Therapy, Pleural Mesothelioma, Multimodal Therapy, Chemotherapy, Pleurectomy/Decortication (P/D), Overall Survival, Progression-Free Survival, Multivariate Analysis.

Related studies

• Optimal gross tumor volume definition in lung-sparing intensity modulated radiotherapy for pleural mesothelioma: an in silico study — A. Botticella, G. Defraene, et al. (2016)
• A feasibility study evaluating Surgery for Mesothelioma After Radiation Therapy: the "SMART" approach for resectable malignant pleural mesothelioma — B.C. Cho, R. Feld, et al. (2014)
• Mesothelioma at era of helical tomotherapy: results of two institutions in combining chemotherapy, surgery and radiotherapy — A. Sylvestre, M.A. Mahé, et al. (2011)
• Disease-Related Outcomes and Toxicities of Intensity Modulated Radiation Therapy After Lung-Sparing Pleurectomy for Malignant Pleural Mesothelioma: A Systematic Review — R. Patel, E.B. Ludmir, et al. (2020)
• Long-term outcomes of intensity-modulated radiotherapy following extra-pleural pneumonectomy for malignant pleural mesothelioma — Y. Matsuo, K. Shibuya, et al. (2017)
• Patterns of failure, toxicity, and survival after extrapleural pneumonectomy and hemithoracic intensity-modulated radiation therapy for malignant pleural mesothelioma — D.R. Gomez, D.S. Hong, et al. (2013)

Browse more research in Journal of Thoracic Oncology, or return to medical research.