Long-term results in malignant pleural mesothelioma treated with neoadjuvant chemotherapy, extrapleural pneumonectomy and intensity-modulated radiotherapy

Our plain-English summary of Long-term results in malignant pleural mesothelioma treated with neoadjuvant chemotherapy, extrapleural pneumonectomy and intensity-modulated radiotherapy, by C. Thieke, N.H. Nicolay, F. Sterzing, et al (Radiation Oncology, 2015).

The study

• Authors: C. Thieke, N.H. Nicolay, F. Sterzing, H. Hoffmann, F. Roeder, S. Safi, J. Debus, P.E. Huber
• Journal: Radiation Oncology
• Published: 2015;10:267
• Cited by: 55 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Introduction: We investigated the clinical outcome and the toxicity of trimodal therapy of malignant pleural mesothelioma (MPM) treated with neoadjuvant chemotherapy, extrapleural pneumonectomy (EPP) and adjuvant intensity-modulated radiotherapy (IMRT).

Methods: Chemotherapy regimens included Cisplatin/Pemetrexed, Carboplatin/Pemetrexed and Cisplatin/Gemcitabine, followed by EPP. 62 patients completed the adjuvant radiotherapy. IMRT was carried out in two techniques, either step&shoot or helical tomotherapy. Median target dose was 48 Gy to 54 Gy. Toxicity was scored with the Common Terminology Criteria (CTC) for Adverse Events. We used Kaplan-Meier method to estimate actuarial rate of locoregional control (LRC), distant control (DC) and overall survival (OS), measured from the date of surgery. Rates were compared using the logrank test. For multivariate analysis the Cox proportional hazard model was used.

Results: The median OS, LRC and DC times were 20.4, 31.4 and 21.4 months. The 1-, 2-, 3-year OS rates were 63, 42, 28 %, the LRC rates were 81, 60, 40 %, and the DC rates were 62, 48, 41 %. We observed no CTC grade 4 or grade 5 toxicity. Step&shoot and helical tomotherapy were equivalent both in dosimetric characteristics and clinical outcome. Biphasic tumor histology was associated with worse clinical outcome compared to epitheloid histology.

Conclusions: Mature clinical results of trimodal treatment for MPM were presented. They indicate that hemithoracic radiotherapy after EPP can be safely administered by either step&shoot IMRT and tomotherapy. However, the optimal prospective patient selection for this aggressive trimodal therapy approach remains unclear. This study can serve as a benchmark for current and future therapy concepts for MPM.

In plain English

This was a retrospective study of 62 patients with malignant pleural mesothelioma treated at Heidelberg University Hospital, Germany, between 2003 and 2010. Each patient received chemotherapy, then surgery removing the affected lung and nearby tissue (extrapleural pneumonectomy), and then completed radiotherapy to that side of the chest using one of two intensity-modulated techniques. The article does not report the patients' asbestos exposure. Counting from the date of surgery, median overall survival was 20.4 months, with 63%, 42% and 28% alive at 1, 2 and 3 years. Only 6 patients were alive when the data were analysed. No grade 4 or grade 5 radiation side effects were seen. One patient had grade 3 radiation pneumonitis that resolved with prednisolone. In the multivariate analysis, biphasic tumor histology and a higher postoperative resection status were linked to worse survival. The two radiotherapy techniques showed no significant difference. The authors concluded that this radiotherapy can be given safely after the surgery by either technique, but that the best way to select patients remains unclear. They noted that patients were selected because they could complete radiotherapy, and that results can only be compared with historical data.

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-institution study of consecutive patients who completed trimodal treatment (chemotherapy, extrapleural pneumonectomy, radiotherapy)
• Who was studied: 62 patients with malignant pleural mesothelioma (52 male, 10 female; median age at diagnosis 57.9 years; 44 epitheloid and 18 biphasic histology) who completed postoperative radiotherapy after extrapleural pneumonectomy at Heidelberg University Hospital, Germany, between 2003 and 2010
• Exposure: The article does not report asbestos exposure. What it studied was treatment: neoadjuvant chemotherapy with Cisplatin/Pemetrexed (30 patients), Carboplatin/Pemetrexed (23) or Cisplatin/Gemcitabine (9), then extrapleural pneumonectomy, then hemithoracic intensity-modulated radiotherapy (step&shoot in 41 patients, helical tomotherapy in 21) with median target dose of 48 to 54 Gy
• Main results:
  • Median overall survival for all 62 patients was 20.4 months (measured from surgery). Overall survival at 1, 2 and 3 years was 63%, 42% and 28%.
  • Median locoregional control (no relapse within the treated side of the chest) was 31.4 months. Locoregional control at 1, 2 and 3 years was 81%, 60% and 40%.
  • Median distant control (no relapse outside the treated side of the chest) was 21.4 months. Distant control at 1, 2 and 3 years was 62%, 48% and 41%.
  • Median follow-up was 17.0 months. Only 6 patients were still alive at the time of analysis.
  • No grade 4 or grade 5 side effects of radiotherapy were observed among the 62 patients.
  • One patient developed symptomatic radiation pneumonitis (grade 3), which resolved completely with prednisolone.
  • For overall survival in multivariate analysis, the only two significant variables were postoperative resection status R (per higher status HR 3.9; 95% CI 1.3 to 12.2; p = 0.01) and biphasic histology (HR 2.2; 95% CI 1.2 to 5.4; p = 0.03).
  • Male gender tended toward worse overall survival but did not reach significance (HR 1.7; 95% CI 0.7 to 4.9; p = 0.2).
  • For locoregional control, no variable tested reached significance in multivariate analysis.
  • For distant control, higher R status (HR 10.9; 95% CI 1.3 to 76.2; p = 0.02) and biphasic histology (HR 7.4; 95% CI 2.2 to 25.4; p = 0.003) were significantly associated with worse outcome.
  • The step&shoot and helical tomotherapy radiotherapy techniques showed no significant difference in dose characteristics or in clinical outcome.
• The authors' conclusion: The authors concluded that hemithoracic radiotherapy after extrapleural pneumonectomy can be safely given by either step&shoot IMRT or tomotherapy, but that the optimal selection of patients for this aggressive trimodal therapy remains unclear.
• Limitations the authors state:
  • Patients were selected in that they were able to receive radiotherapy after chemotherapy and surgery.
  • The decision to give radiotherapy was made individually after surgery, so there was no strict intention-to-treat for trimodal therapy from the beginning.
  • Because surgery was done at several hospitals, patients who had surgery without radiotherapy could not be included in the analysis.
  • The results can only be compared with historical data.

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: Pleural Mesothelioma, Neoadjuvant Therapy, Extrapleural Pneumonectomy (EPP), Intensity-Modulated Radiation Therapy (IMRT), Chemotherapy, Cisplatin, Pemetrexed (Alimta), Carboplatin.

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• Impact of Neoadjuvant and Adjuvant Pleural Intensity-Modulated Radiotherapy in Multimodality Treatment for Malignant Pleural Mesothelioma — B. Mosleh, S. Schwarz, et al. (2025)
• Intensity-modulated radiotherapy after extrapleural pneumonectomy in the combined-modality treatment of malignant pleural mesothelioma — A. Chi, Z. Liao, et al. (2011)
• Accelerated hemithoracic radiation followed by extrapleural pneumonectomy for malignant pleural mesothelioma — M. de Perrot, R. Feld, et al. (2016)
• Intensity-modulated radiotherapy and volumetric-modulated arc therapy for malignant pleural mesothelioma after extrapleural pleuropneumonectomy — J. Krayenbuehl, O. Riesterer, et al. (2013)
• Extra-pleural pneumonectomy in the era of image-guided intensity-modulated radiotherapy — M. Trovo, D. Franceschini, et al. (2019)

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