International Journal of Radiation Oncology*Biology*Physics
Rapid communicationFatal pneumonitis associated with intensity-modulated radiation therapy for mesothelioma
Introduction
Pleural mesothelioma is a largely fatal disease with an aggressive clinical course and a high mortality rate using currently available therapy. Median survival is 12 months (1). Death is often caused by local progression ultimately resulting in respiratory failure. There is no clear standard of care for mesothelioma, and the relatively low incidence of the disease has made the conduct of randomized controlled studies with adequate numbers of patients difficult.
A minority of patients with mesothelioma have disease limited to the chest and are therefore candidates for aggressive surgical resection. Extrapleural pneumonectomy (EPP) has been associated with better local control than pleurectomy/decortication (2, 3). However, even with EPP, 80% of patients experience local tumor progression (2). Because of this, aggressive combined approaches utilizing adjuvant chemotherapy and conventional radiation therapy (trimodality therapy) have been attempted. In our earlier experience with trimodality therapy including EPP, hemithoracic radiation, and chemotherapy, the 5-year survival rate was only 14% (4). Therefore, new avenues for improvements in local and systemic therapies have been attempted.
In 2003, preliminary results were published describing the utilization of intensity-modulated radiotherapy (IMRT) in the adjuvant setting after EPP. These preliminary results suggested that IMRT could be safely administered and could provide a local control rate of greater than 80% (5, 6, 7), far better than other series of adjuvant radiation therapy using conventional techniques (8, 9). Based on these promising results, this technique was initiated at the Dana-Farber Cancer Institute/Brigham and Women’s Hospital. In this report we describe our initial experience, which demonstrated a high treatment-related mortality rate from pneumonitis.
Section snippets
Methods and materials
From December 2004 to August 2005, 13 patients were treated with IMRT after EPP and adjuvant chemotherapy at the Dana-Farber Cancer Institute/Brigham and Women’s Hospital. All patients underwent preoperative mediastinoscopy, computed tomography (CT), magnetic resonance imaging, and positron emission tomography (PET) scans to determine resectability. Surgeons in the division of thoracic surgery at Brigham and Women’s Hospital performed an EPP. Twelve of 13 patients received intraoperative
Results
Thirteen patients with resected mesothelioma were treated with IMRT after EPP and adjuvant chemotherapy from December 2004 to September 2005. The median age of the patients was 66 years (range, 39–68 years). There were 11 men and 2 women. The complete patient characteristics are listed in Table 2.
Discussion
This small series demonstrates an unacceptably high rate of fatal pneumonitis after EPP with intraoperative cisplatin, adjuvant cisplatin/pemetrexed, and IMRT to a dose of 54 Gy delivered to the hemithorax.
We have sought to determine why this regimen was so much more toxic than expected. There are several possible explanations, and the true answer may lie in one or more of the following possibilities. The first possible explanation is that the addition of intrapleural or systemic chemotherapy
Acknowledgments
Special thanks to Drs. Harvey Mamon and Bruce Johnson for their critical reading of the manuscript.
References (30)
- et al.
The role of extrapleural pneumonectomy in malignant pleural mesothelioma
J Thorac Cardiovasc Surg
(1991) - et al.
Resection margins, extrapleural nodal status, and cell type determine postoperative long-term survival in trimodality therapy of malignant pleural mesotheliomaResults in 183 patients
J Thorac Cardiovasc Surg
(1999) - et al.
Intensity-modulated radiotherapy following extrapleural pneumonectomy for the treatment of malignant mesotheliomaClinical implementation
Int J Radiat Oncol Biol Phys
(2003) - et al.
Intensity-modulated radiation therapyA novel approach to the management of malignant pleural mesothelioma
Int J Radiat Oncol Biol Phys
(2003) - et al.
A phase II trial of surgical resection and adjuvant high-dose hemithoracic radiation for malignant pleural mesothelioma
J Thorac Cardiovasc Surg
(2001) - et al.
Hemithoracic radiation after extrapleural pneumonectomy for malignant pleural mesothelioma
Int J Radiat Oncol Biol Phys
(2003) - et al.
Analysis of radiation-induced liver disease using the Lyman NTCP model
Int J Radiat Oncol Biol Phys
(2002) - et al.
Radiation pneumonitis as a function of mean lung doseAn analysis of pooled data of 540 patients
Int J Radiat Oncol Biol Phys
(1998) - et al.
Radiation-induced pulmonary toxicityA dose–volume histogram analysis in 201 patients with lung cancer
Int J Radiat Oncol Biol Phys
(2001) - et al.
CTCAE v3.0: Development of a comprehensive grading system for the adverse effects of cancer treatment
Semin Radiat Oncol
(2003)
Gemcitabine and paclitaxel associated pneumonitis in non–small cell lung cancerReport of a phase I/II dose-escalating study
Eur J Cancer
Phase I study of twice-weekly gemcitabine and concurrent thoracic radiation for patients with locally advanced non–small-cell lung cancer
Int J Radiat Oncol Biol Phys
Interaction of pemetrexed disodium (ALIMTA, multitargeted antifolate) and irradiation in vitro
Int J Radiat Oncol Biol Phys
Dose–volume histogram and 3-D treatment planning evaluation of patients with pneumonitis
Int J Radiat Oncol Biol Phys
Estimation of pneumonitis risk in three-dimensional treatment planning using dose–volume histogram analysis
Int J Radiat Oncol Biol Phys
Cited by (315)
Comprehensive clinical overview of malignant pleural mesothelioma
2024, Respiratory MedicineRole of radiotherapy in the management of rare solid thoracic tumors of the adults
2023, Cancer/RadiotherapieWhat's Current and What's New in Mesothelioma?
2022, Clinical OncologyResponse Evaluation Following Radiation Therapy With <sup>18</sup>F-FDG PET/CT: Common Variants of Radiation-Induced Changes and Potential Pitfalls
2022, Seminars in Nuclear MedicineCitation Excerpt :Due its rarity, detailed recommendations regarding the use of RT in MPM lack.126 Adopting RT for MPM was further deferred due to the initial experiences of hemithoracic IMRT in MPM after extrapleural pneumonectomy (EPP), in which 50% of treated patients developed fatal pneumonitis in the contralateral lung.127 Since then, dose constraints have been significantly modified and the incidence of severe pneumonitis has been greatly reduced.126
Pleural Tumors
2022, Oncologic Imaging: A Multidisciplinary Approach