A pilot trial of high-dose-rate intraoperative radiation therapy for malignant pleural mesothelioma

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Abstract

Purpose

To report results of a phase II trial of high-dose-rate intra-operative radiation therapy (HDR-IORT) for malignant pleural mesothelioma (MPM).

Methods and materials

Seven patients had extrapleural pneumonectomy with IORT (EPP/IORT) and 6 patients had pleurectomy/decortication with IORT (PD/IORT) between 1994 and 1996. IORT was delivered with 192Ir using a customized applicator with a remote afterloader. A median of 3 sites were treated to a median area of 143 cm2. A dose of 1500 cGy was prescribed at each site, with 1000 cGy delivered to the mediastinum. Postoperative external beam radiation therapy (EBRT) was given 3–5 weeks later. Median follow-up was 8 months (range, 1–84 months).

Results

Five patients developed local failure. Two-year local control and survival rates were 35% and 23%, respectively. Mortality was 2/13 (15%), 1 from each surgical group. Serious complications requiring further intervention occurred in 3/6 (50%) of the EPP/IORT group and 1/5 (20%) of the PD/IORT group.

Conclusions

HDR-IORT after EPP for MPM is prohibitively toxic and has been abandoned, while its use with PD remains in question.

Introduction

Malignant pleural mesothelioma (MPM) is a rare neoplasm with a poor prognosis. Median survival ranges from 4 to 18 months [1], [2]. Neither aggressive single modality nor multimodality therapies have been able to significantly improve survival rates. Given the prevalence of locoregional recurrences in treated patients, an important goal in the management of this tumor has been focused on achieving local control.

The use of brachytherapy for MPM has been explored as a component of multimodality treatments with the specific aim of improving local control rates [2], [3], [4], [5], [6]. Intraoperative radiation therapy (IORT) was investigated at MSKCC as part of a phase II trial. Patients underwent extrapleural pneumonectomy (EPP), or pleurectomy/decortication (PD) if EPP was not feasible, brachytherapy and high-dose hemithoracic radiation up to 54 Gy. The use of external beam radiation therapy (EBRT) has previously been reported (2). The outcomes of treatment with high-dose-rate (HDR) IORT are presented in this report.

Section snippets

Methods and materials

The cohort of patients described in this report were part of a previously described phase II trial at MSKCC evaluating the feasibility of EPP or PD combined with IORT and postoperative high-dose EBRT [2], [6]. Patients were eligible for the trial if they had potentially resectable, biopsy-proven MPM, no evidence of T4 or N3 disease on physical examination or CT/MRI, no metastatic disease, no prior treatment, and a Karnofsky performance status (KPS) ⩾80.

Eligible patients underwent surgical

Results

Thirteen patients received HDR-IORT as part of surgical treatment of MPM from 1994 to 1996. Of these 13 patients, 7 had EPP and 6 had PD, all treated with IORT.

Five of the patients were treated at 2 sites, 6 patients were treated at 3 sites, 1 patient was treated at 4 sites, and 1 patient was treated at 5 sites. The target dimensions ranged from 3 × 3 to 23 × 17 cm, with a median area of 143 cm2. A median of 12 channels were used (range, 4–24) with a median of 14 source positions (range, 4–21)

Discussion

The use of HDR-IORT after surgery led to unacceptable toxicity in the treatment of MPM, most notably in those patients undergoing EPP. There are a number of possible explanations for the degree of morbidity seen in this series of patients. The dose of IORT, 1500 cGy, may be too high, especially when multiple sites are treated. Surgery with EPP already carries significant morbidity. The addition of IORT appears to increase the risks to an unacceptable level. Ultimately, the degree of toxicity

Conclusion

The addition of IORT to surgery for MPM did not appear to provide a clear local control or survival benefit in our series at MSKCC. The local control rates and overall survival we report here are on a small number of patients and therefore must be interpreted with caution. However, given the morbidity seen and the extended operative time, this approach has been abandoned at MSKCC as an adjunct to EPP in the treatment of MPM. This change in treatment philosophy was also implemented in response

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