Updated patterns of failure after multimodality therapy for malignant pleural mesothelioma

Our plain-English summary of Updated patterns of failure after multimodality therapy for malignant pleural mesothelioma, by E.H. Baldini, W.G. Richards, R.R. Gill, et al (The Journal of Thoracic and Cardiovascular Surgery, 2015).

The study

• Authors: E.H. Baldini, W.G. Richards, R.R. Gill, B.M. Goodman, O.K. Winfrey, H.M. Eisen, R.H. Mak, A.B. Chen, D.E. Kozono, R. Bueno, D.J. Sugarbaker
• Journal: The Journal of Thoracic and Cardiovascular Surgery
• Published: 2015;149(5):1374-81
• Cited by: 74 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Objective: We have previously described patterns of failure after extrapleural pneumonectomy and multimodality therapy for malignant pleural mesothelioma and sought to update our results with a larger cohort of recent patients.

Methods: A total of 169 patients underwent extrapleural pneumonectomy without preoperative chemotherapy between 2001 and 2010. Data for treatment, recurrence, and survival were determined from medical records. A thoracic radiologist reviewed postoperative computed tomography or positron emission tomography computed tomography scans to determine sites of recurrence. Time to recurrence was estimated by the Kaplan-Meier method. Rates were compared using the Fisher exact test.

Results: The median age of patients was 62 years. Histology on final pathology was epithelial for 104 patients (62%) and nonepithelial for 65 patients (38%). A total of 132 patients (78%) received heated intraoperative chemotherapy; 77 patients (45%) received adjuvant chemotherapy, and 71 patients (42%) received adjuvant radiation therapy. Most chemotherapy regimens included platinum or pemetrexed. Median radiation therapy dose was 54 Gy. Among 158 evaluable patients, a recurrence developed in 118 (75%). Median follow-up was 83 months, median time to recurrence was 13.1 months, and median survival was 15 months. Sites of first recurrence were in the ipsilateral hemithorax or mediastinum for 54% of patients, in the abdomen for 39% of patients, in the contralateral hemithorax for 28% of patients, and in other distant sites for 5% of patients. Some patients had simultaneous recurrences in multiple sites.

Conclusions: The most common site of recurrence after extrapleural pneumonectomy and planned multimodality therapy remains the ipsilateral hemithorax (including mediastinum), and true distant failure (other than the abdomen or contralateral hemithorax) remains unusual. The distribution of recurrences is strikingly similar to our prior report.

Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

In plain English

This was a retrospective study from Brigham and Women's Hospital in Boston. It looked at where malignant pleural mesothelioma came back after extrapleural pneumonectomy, an operation removing the lung and surrounding lining. It included 169 patients operated on between 2001 and 2010 who had no chemotherapy before surgery. Of these, 132 also received heated chemotherapy during the operation, 77 received chemotherapy afterwards and 71 received radiation. The article does not report the patients' asbestos exposure. Among 158 patients who could be assessed, the cancer returned in 118 (75%), after a median of 13.1 months. Median survival was 15.0 months. First recurrences involved the same side of the chest or the mediastinum in 54% of patients, the abdomen in 39%, the opposite side of the chest in 28%, and other distant sites in 5%. Some patients had several sites. Local recurrence was 39% (27/70) among patients given radiation and 66% (58/88) among those not given it, but the authors stated that formal conclusions cannot be drawn from this comparison. The authors concluded that recurrence patterns were strikingly similar to their 1997 report.

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 review of patient records (single-institution cohort) describing sites and timing of recurrence after surgery-based treatment
• Who was studied: 169 patients with malignant pleural mesothelioma who had extrapleural pneumonectomy with macroscopic complete resection at Brigham and Women's Hospital, Boston, between 2001 and 2010, without preoperative chemotherapy. They were selected from 447 patients in the hospital registry. There were 136 men and 33 women, and median age was 62 years (range 37 to 79).
• Exposure: This is not an asbestos exposure study, and the article does not report asbestos exposure. What it examined was treatment: extrapleural pneumonectomy in all 169 patients; heated intraoperative chemotherapy (cisplatin, with or without gemcitabine) in 132; adjuvant chemotherapy (mostly cisplatin and/or pemetrexed) in 77; and adjuvant radiation therapy in 71, at a median dose of 54 Gy.
• Main results:
  • Among 158 patients evaluable for recurrence, 118 (75%) had documented recurrence. Median time to any recurrence was 13.1 months and median time to local recurrence was 18 months after surgery.
  • Sites of first failure among the 158 evaluable patients (some had more than one site): same side of the chest or mediastinum (local) in 85 (54%), abdomen in 62 (39%), opposite side of the chest in 45 (28%), and other distant sites in 8 (5%).
  • Median overall survival among all 169 patients was 15.0 months. Actuarial 3-year overall survival was 23% (95% CI, 17-30).
  • Crude local recurrence was 39% (27/70) among patients who received radiation and 66% (58/88) among those who did not. Actuarial 3-year local recurrence was 47% (95% CI, 31-63) with radiation and 82% (72%-92%) without it. In multivariate analysis, radiation had a hazard ratio of 0.3 (0.2-0.5) for time to local recurrence. The authors present these comparisons only to generate hypotheses.
  • The distribution of recurrence sites, as a share of all failures, was almost identical to the authors' 1997 series of 49 patients: local 72% versus 67%, abdomen 53% versus 50%, opposite chest 38% versus 33%, and other distant sites 7% versus 8%.
• The authors' conclusion: The authors concluded that their updated results did not show a change in the patterns of failure after multimodality therapy. They wrote that recurrence remains predominantly local and that postoperative hemithoracic radiation therapy is worthy of further study.
• Limitations the authors state:
  • The study was retrospective, and actual delivery of adjuvant chemotherapy and radiation was highly variable.
  • Because mainly fitter patients received additional treatments, the effect of adjuvant radiation or chemotherapy compared with surgery alone could not be assessed. The authors stated that formal conclusions cannot be drawn from the radiation comparisons.
  • Not all recurrences were confirmed by tissue examination.
  • Surveillance with CT or PET scans and specialist radiology review detected many asymptomatic areas. This may have inflated recurrence numbers compared with other reports.

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: Multimodal Therapy, Pleural Mesothelioma, Extrapleural Pneumonectomy (EPP), Chemotherapy, Histology, Pathology, Pemetrexed (Alimta), Median Survival.

Related studies

• Importance of excision repair cross-complementation group 1 and ribonucleotide reductase M1 as prognostic biomarkers in malignant pleural mesothelioma treated with platinum-based induction chemotherapy followed by surgery — L. Frischknecht, M. Meerang, et al. (2015)
• Patterns of failure after trimodality therapy for malignant pleural mesothelioma — E.H. Baldini, A. Recht, et al. (1997)
• Accelerated hemithoracic radiation followed by extrapleural pneumonectomy for malignant pleural mesothelioma — M. de Perrot, R. Feld, et al. (2016)
• Induction chemotherapy, extrapleural pneumonectomy, and adjuvant radiotherapy for malignant pleural mesothelioma: experience of Guy's and St Thomas' hospitals — A. Bille, E. Belcher, et al. (2012)
• 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)
• Induction Therapy for Mesothelioma — I. Opitz, W. Weder (2015)

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