Clinical investigation
Lung
Influence of Radiotherapy Technique and Dose on Patterns of Failure for Mesothelioma Patients After Extrapleural Pneumonectomy

Presented in part at the 47th Annual Meeting of the American Society for Therapeutic Radiology and Oncology (ASTRO), October 16–20, 2005, Denver, CO; and the 2006 Annual Meeting of the American Society of Clinical Oncology, June 2-6, 2006, Atlanta, GA.
https://doi.org/10.1016/j.ijrobp.2007.02.047Get rights and content

Purpose: Extrapleural pneumonectomy (EPP) is an effective treatment of malignant pleural mesothelioma. We compared the outcomes after moderate-dose hemithoracic radiotherapy (MDRT) and high-dose hemithoracic RT (HDRT) after EPP for malignant pleural mesothelioma.

Methods and Materials: Between July 1994 and April 2004, 39 patients underwent EPP and adjuvant RT at Dana-Farber Cancer Institute/Brigham and Women’s Hospital. Between 1994 and 2002, MDRT, including 30 Gy to the hemithorax, 40 Gy to the mediastinum, and boosts to positive margins or nodes to 54 Gy, was given, generally with concurrent chemotherapy. In 2003, HDRT to 54 Gy with a matched photon/electron technique was given, with sequential chemotherapy.

Results: A total of 39 patients underwent RT after EPP. The median age was 59 years (range, 44–77). The histologic type was epithelial in 25 patients (64%) and mixed or sarcomatoid in 14 patients (36%). Of the 39 patients, 24 underwent MDRT and 15 (39%) HDRT. The median follow-up was 23 months (range, 6–71). The median overall survival was 19 months (95% confidence interval, 14–24). The median time to distant failure (DF) and local failure (LF) was 20 months (95% confidence interval, 14–26) and 26 months (95% confidence interval, 16–36), respectively. On univariate and multivariate analyses, only a mixed histologic type was predictive of inferior DF (p <0.006) and overall survival (p <0.004). The RT technique was not predictive of LF, DF, or overall survival. The LF rate was 50% (12 of 24) after MDRT and 27% (4 of 15) after HDRT (p = NS). Four patients who had undergone HDRT were alive and without evidence of disease at the last follow-up.

Conclusions: High-dose hemithoracic RT appears to limit in-field LF compared with MDRT. However, DF remains a significant challenge, with one-half of our patients experiencing DF.

Introduction

Malignant pleural mesothelioma is a disease that affects 2,000–3,000 new patients annually in the United States (2). It is often a rapidly progressive disease, and the median survival is 12 months (3). Patients with localized disease are candidates for surgical resection of gross disease using extrapleural pneumonectomy (EPP). We have previously shown that trimodality therapy consisting of EPP, adjuvant systemic therapy, and radiotherapy (RT) is feasible and can produce a median survival of 19 months (4).

An analysis of the patterns of failure after the trimodality approach could help direct future treatment strategies. We previously published a report describing the patterns of failure after our trimodality approach and noted a significant component of both local failure (LF) and distant failure (DF) (5). Of the LFs, many were within the resected hemithorax or “in-field” failures. Since then, we have used two successive approaches in an attempt to decrease the rate of in-field failure. The first approach was to add concurrent radiosensitizing platinum-based chemotherapy to moderate-dose hemithoracic RT (MDRT). The second, more recent, approach was to use high-dose hemithoracic RT (HDRT), as proposed by investigators from Memorial Sloan-Kettering Cancer Center (MSKCC) (1). In this publication, we report the updated patterns of failure and patient outcomes after treatment with these new approaches.

Section snippets

Methods and Materials

Between July 1994 and April 2004, 39 patients underwent trimodality therapy at the Dana-Farber Cancer Institute/Brigham and Women’s Hospital. During this period, 412 patients had undergone EPP for mesothelioma at Brigham and Women’s Hospital. Many of these patients came from out of state or other countries and could not stay locally for their RT. Only patients who received their RT at Dana-Farber Cancer Institute/Brigham and Women’s Hospital were included in this analysis.

The medical records of

Results

Thirty-nine patients underwent trimodality therapy at Dana-Farber Cancer Institute/Brigham and Women’s Hospital between July 1994 and August 2005. Most patients were men (77%). The median age was 59 years (range, 44–77). A predominance of patients had an epithelial histologic type (64%) and right-sided disease (59%). Detailed patient characteristics, including stage and lymph node status and details of chemotherapy, are given in Table 1.

Of the 39 patients, 24 were treated with MDRT and 15 were

Discussion

Extrapleural pneumonectomy has been used to treat pleural mesothelioma for some time with mixed results. In the initial lung cancer study group in which EPP was performed without adjuvant therapy, the median survival was 10 months (9), similar to results with the best supportive care. At that time, surgical morbidity and mortality were significant, and it was difficult to deliver adjuvant therapy. As the surgical techniques improved and limited perioperative mortality to <10% (10), the need for

Conclusions

Mesothelioma remains a challenging disease to treat, with few long-term survivors. However, an increase in the dose intensity of RT appears to decrease the local recurrence rate. Improvements in RT techniques such as the use of IMRT will perhaps improve these results further. Finally, more active systemic therapy is necessary, and the optimal temporal combination of RT and chemotherapy needs to be determined.

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Supported in part by International Mesothelioma Program.

Conflict of interest: none.

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