Extrapulmonary Soft-Tissue Fibrosis Resulting From Hypofractionated Stereotactic Body Radiotherapy for Pulmonary Nodular Lesions

Purpose: To clarify the incidence, symptoms, and timing of extrapulmonary fibrosis developing after hypofractionated stereotactic body radiotherapy. Patients and Methods: We analyzed 379 consecutive patients who underwent stereotactic body radiotherapy for lung tumors at four institutions between February 2001 and March 2007. The median follow-up time was 29 months (range, 1-72). We investigated the subjective and objective characteristics of the extrapulmonary masses, redelineated the origin tissue of each on the treatment planning computed tomography scan, and generated dose-volume histograms. Results: In 9 patients (2.4%), extrapulmonary masses were found 3-36 months (median, 14) after irradiation. Coexisting swelling occurred in 3 patients, chest pain in 2, thumb numbness in 1, and arm edema in 1 patient. Extrapulmonary masses occurred in 5 (5.4%) of 92 and 4 (1.4%) of 287 patients irradiated with a 62.5-Gy and 48.0-Gy isocenter dose, respectively. The mean and maximal dose to the origin tissue was 25.8-53.9 Gy (median, 43.7) and 47.5-62.5 Gy (median, 50.2), respectively. In 5 of 9 patients, the standardized uptake values on 18F-fluorodeoxyglucose-positron emission tomography was 1.8-2.8 (median, 2.2). Percutaneous needle biopsy was performed in 3 patients, and all the specimens showed benign fibrotic changes without malignant cells. Conclusion: All patients should be carefully followed after stereotactic body radiotherapy. The findings of any new lesion should prompt an assessment for radiation-induced extrapulmonary fibrosis before an immediate diagnosis of recurrence is made. Careful beam-shape modification and dose prescription near the thoracic outlet are required to prevent forearm neuropathy and lymphedema.