A pilot trial of high-dose-rate intraoperative radiation therapy for malignant pleural mesothelioma
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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2017, The Lancet OncologyCitation Excerpt :Based on a previous study,30 doses greater than 40 Gy could be considered high since this is the minimum dose required to have a long-lasting effect on the tumour. Following a trial30,31 that showed that intraoperative radiotherapy was not an effective treatment option for patients with malignant pleural mesothelioma and conferred a high risk of empyema, a group led by Rusch and Rosenzweig31,32 developed 3D-conformal radiotherapy (3DCRT) to optimise the delivery of 54 Gy (total dose) in 30 daily fractions over 6 weeks to the entire hemithorax after extrapleural pneumonectomy. The use of adjuvant high-dose hemithoracic radiotherapy was reported in a prospective phase 2 trial.32
Current Treatment of Mesothelioma: Extrapleural Pneumonectomy Versus Pleurectomy/Decortication
2016, Thoracic Surgery ClinicsMeta-analysis of survival after pleurectomy decortication versus extrapleural pneumonectomy in mesothelioma
2015, Annals of Thoracic SurgeryCitation Excerpt :Upon further detailed review, 71 publications were excluded; 38 due to evaluation of 1 surgical procedure and lack of a separate report of outcome data for the surgical procedures of interest, 25 papers were reanalyses of data or reviews, 7 papers measured other outcomes, and 1 paper reported 30-day survival data only. Twenty-seven articles were included [6–32], of which five [8, 9; 26–28] overlapped and relied on the same source populations and were therefore considered as 2 distinct data sets, bringing the number of distinct data sets to 24 (Table 1), for a total of 1,512 patients treated with P/D, and 1,391 treated with EPP. Several studies reported the percentage of patients who received other treatments either before or after surgery; the data are also included in Table 1.
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