Locoregional Control of Pleural Mesothelioma Following Postoperative Image-Guided Radiotherapy With Patterns of Failure Using 18FDG-PET/CT Scan-Based Analysis

Abstract

The incidence of mesothelioma is increasing throughout the world and little progress has been made in finding an effective treatment, primarily due to late diagnosis, inadequate staging and difficulty in controlling local disease. The high mortality rate has not significantly improved with more radical surgery or new systemic therapies, but there is growing evidence that a trimodality approach using postoperative radiotherapy may be curative in selected patients. Mesothelioma is characterized by locoregional growth that spreads beyond the reach of surgery, and newer techniques of image-guided radiotherapy (IGRT) require evaluation in this disease. To document locoregional control from high dose radiotherapy following major surgery in pleural mesothelioma patients who have PET scans accurately reflecting disease distribution. Fourteen consecutive patients were treated with postoperative radiotherapy to regions of residual macroscopic disease with doses of 45–60 Gy from July 2003 to May 2006. 3D-conformal or intensity-modulated radiotherapy techniques were used with PET/CT fusion IGRT. All had pre-treatment PET scans and post-treatment imaging, including followup PET or PET/CT scans in 11 cases. Surgery consisted of pleurectomy/decortication in 13, all but one being incomplete resections combined with intraoperative phototherapy, and 1 extrapleural pneumonectomy (EPP). There were 11 patients with epithelioid and 3 with biphasic mesothelioma, and all patients had 18FDG-avid disease on PET scanning. There were no in-field relapses within the planning target volume (PTV) confirmed with PET scan coregistration, resulting in a local control rate of 100% at a median followup of 10 months post-radiotherapy. Relapses outside the PTV were found in 11 cases, all in multiple sites. Many were in areas deemed at moderate risk and not included in the PTV in order to meet strict dose constraint criteria and minimize the risk of major radiation toxicities. No patient died as a consequence of radiotherapy, and radiation morbidity was seen in 2 cases, with transient grade 2 pneumonitis and liver injury. Both patients remain well and disease-free 30 months after surgery. One patient died without recurrence 13 months after EPP. Six received palliative chemotherapy for distant relapse and only one patient had neoadjuvant chemotherapy. Additional palliative radiotherapy was given to two patients. Radiation therapy is an effective modality in the treatment of mesothelioma and high doses can be administered safely using modern technological advances in planning and delivery. Suitable patients should undergo surgery to resect all gross disease and accurately define target areas for postoperative IGRT, and PET/CT scans should be fused with simulation CT scans to optimize planning volumes.