Clinical Investigation
Pleural Intensity-Modulated Radiotherapy for Malignant Pleural Mesothelioma

https://doi.org/10.1016/j.ijrobp.2011.09.027Get rights and content

Purpose

In patients with malignant pleural mesothelioma who are unable to undergo pneumonectomy, it is difficult to deliver tumoricidal radiation doses to the pleura without significant toxicity. We have implemented a technique of using intensity-modulated radiotherapy (IMRT) to treat these patients, and we report the feasibility and toxicity of this approach.

Methods and Materials

Between 2005 and 2010, 36 patients with malignant pleural mesothelioma and two intact lungs (i.e., no previous pneumonectomy) were treated with pleural IMRT to the hemithorax (median dose, 46.8 Gy; range, 41.4–50.4) at Memorial Sloan-Kettering Cancer Center.

Results

Of the 36 patients, 56% had right-sided tumors. The histologic type was epithelial in 78%, sarcomatoid in 6%, and mixed in 17%, and 6% had Stage I, 28% had Stage II, 33% had Stage III, and 33% had Stage IV. Thirty-two patients (89%) received induction chemotherapy (mostly cisplatin and pemetrexed); 56% underwent pleurectomy/decortication before IMRT and 44% did not undergo resection. Of the 36 patients evaluable for acute toxicity, 7 (20%) had Grade 3 or worse pneumonitis (including 1 death) and 2 had Grade 3 fatigue. In 30 patients assessable for late toxicity, 5 had continuing Grade 3 pneumonitis. For patients treated with surgery, the 1- and 2-year survival rate was 75% and 53%, and the median survival was 26 months. For patients who did not undergo surgical resection, the 1- and 2-year survival rate was 69% and 28%, and the median survival was 17 months.

Conclusions

Treating the intact lung with pleural IMRT in patients with malignant pleural mesothelioma is a safe and feasible treatment option with an acceptable rate of pneumonitis. Additionally, the survival rates were encouraging in our retrospective series, particularly for the patients who underwent pleurectomy/decortication. We have initiated a Phase II trial of induction chemotherapy with pemetrexed and cisplatin with or without pleurectomy/decortication, followed by pleural IMRT to prospectively evaluate the toxicity and survival.

Introduction

Malignant pleural mesothelioma (MPM) is difficult to treat because of its locally aggressive behavior. Controversy surrounds the optimal treatment of early-stage mesothelioma; however, studies using multimodality therapy have shown promising local control and survival. Because the most common site of treatment failure for MPM is the ipsilateral hemithorax, optimizing local control provides the best chance for long-term survival.

Two types of surgery are performed for mesothelioma: extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D). EPP involves en bloc resection of the entire pleura, lung, diaphragm, and ipsilateral half of the pericardium. P/D involves resection of all gross tumor without removing the lung. Neither P/D nor EPP alone offers adequate long-term local control or survival. After EPP, adjuvant hemithoracic radiotherapy (RT) to the chest cavity has been shown to improve local control and survival; however, distant failure remains a problem. A number of studies have investigated whether more advanced RT techniques, such as intensity-modulated RT (IMRT), lead to better local control than standard RT after EPP. However, IMRT can be associated with increased toxicity, including fatal pneumonitis, if radiation exposure to the remaining lung is not carefully restricted 1, 2, 3.

More recently, enthusiasm for EPP has waned, particularly because this surgery is associated with increased morbidity and mortality relative to P/D. A report compiling the data from 663 MPM patients treated surgically suggested that those who underwent EPP had inferior survival compared with patients who underwent P/D (4). Although that analysis was subject to significant retrospective biases, it has had a major influence on the practice of many thoracic surgeons. However, with P/D, local control remains the primary issue and RT is more challenging to administer because of the risk of pneumonitis in the intact lung. Our previous institutional experience with standard pleural RT was not promising (5). The difference in the effectiveness of RT in these situations can be partially explained because complete removal of the ipsilateral lung with EPP allows the delivery of greater radiation doses. However, implementation of an IMRT technique could enable greater doses to be administered even with an intact lung and thus might improve efficacy. The present study reports on our experience using a novel technique to treat the pleura with IMRT.

Section snippets

Methods and Materials

A total of 36 patients with biopsy-proven MPM underwent IMRT to the hemithorax without pneumonectomy at the Memorial Sloan-Kettering Cancer Center between 2005 and 2010. Of these 36 patients, 11 were enrolled in a Memorial Sloan-Kettering Cancer Center institutional review board–approved feasibility protocol. The others were treated after the feasibility of the technique had been established. Their records were reviewed with an institutional review board waiver. Not all patients were candidates

Results

The median radiation dose was 4,680 cGy (range, 4,140–5,040). The incidence of acute treatment-related toxicity is listed in Table 2. The patients were able to complete treatment with medical support and without the need for treatment breaks. No patients required intravenous hydration during treatment. One patient required the placement of a percutaneous endoscopic gastrostomy tube before the initiation of RT because of a poor nutritional status and was able to maintain an adequate nutritional

Discussion

Our results have demonstrated that pleural IMRT for patients with MPM and an intact ipsilateral lung is a feasible treatment option with an acceptable toxicity profile. Historically, our institution has favored EPP, followed by adjuvant hemithorax RT for treatment of MPM. In a Phase II trial, the median survival was 17 months using this treatment paradigm (15). The RT was well tolerated, because removal of the ipsilateral lung during EPP minimized pleural toxicity. The median overall survival

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