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

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.

NCCN Guidelines Insights: Malignant Pleural Mesothelioma, Version 3.2016

“…These 3 combination regimens can also be used as adjuvant therapy for patients as part of multimodality therapy. 46 Several regimens can also be used as induction therapy as part of a mo-dality regimen, including cisplatin/pemetrexed. 46 The fourth combination regimen is bevacizumab/cisplatin/ pemetrexed, which is only recommended for patients with unresectable disease and should only be considered for patients who are candidates to receive bevacizumab.…”

Overview of treatment related complications in malignant pleural mesothelioma

“…Radiotherapy is recommended by the National Cancer Control Network (NCCN) for patients with resectable MPM post-surgery to improve local control (14). Modern radiotherapy techniques, such as the use of intensity-modulated radiotherapy (IMRT), allows limitation of the high dose area tightly to the target area, sparing radiation exposure of adjacent organs (59). Although usually administered as an adjuvant therapy post-surgery, recently radiation has been proposed as a neo-adjuvant treatment ("SMART" approach) prior to EPP in patients with resectable disease without a significant increase in perioperative mortality (60,61).…”

“…Patients with radiation pneumonitis are often treated with steroids, as this can prevent development of subsequent fibrosis(64). Although the use of IMRT does limit the development of radiation induced lung disease in the remaining lung post EPP, this risk is not completely eliminated(59). IMRT is used successfully for local control in patients undergoing lung-sparing cytoreductive surgery, with recent data suggesting an approximate 30% risk of developing radiation pneumonitis in the treated hemithorax with the use of IMRT post EP/D(65).A 77-year-old woman with a left epithelioid mesothelioma underwent a left EP/D with diaphragmatic reconstruction.…”

Prognostic value of SUVmax on 18F-fluorodeoxyglucose PET/CT scan in patients with malignant pleural mesothelioma

“…Malignant pleural mesothelioma (MPM) is a rare but aggressive tumor that arises from pleural mesothelial cells. The prognosis of patients with MPM is poor, with a median survival of 20-29 months despite tri-modality treatment including surgery, chemotherapy, and radiotherapy [1,2]. Surgical methods (e.g., extra-pleural pneumonectomy [EPP] or pleurectomy/decortication) should be selected in accordance with the patient's condition [3,4].…”