Abstract
IntroductionWe 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).MethodsChemotherapy 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.ResultsThe 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.ConclusionsMature 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13014-015-0575-5) contains supplementary material, which is available to authorized users.
Highlights
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)
With respect to chemotherapy regimens, Pemetrexed combined with Cisplatin has been established [1]; in surgery approaches, extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D) have been technically advanced resulting in tolerable toxicity [2]; the introduction of intensity-modulated radiotherapy (IMRT) allows to conform the high dose area tightly to the target volume and spare adjacent organs at risk [3]
Patient characteristics Between 2003 and 2010, 62 patients completed postoperative radiotherapy after EPP in a trimodal treatment setting in our institution
Summary
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). With respect to chemotherapy regimens, Pemetrexed combined with Cisplatin has been established [1]; in surgery approaches, extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D) have been technically advanced resulting in tolerable toxicity [2]; the introduction of intensity-modulated radiotherapy (IMRT) allows to conform the high dose area tightly to the target volume and spare adjacent organs at risk [3]. Despite these individual advancements the optimal combination and treatment strategy for each individual patient still remains unclear. Evaluations of the clinical outcome of cohorts treated systematically by a certain regimen are relevant to assess its potential and the associated risks for the patients
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