Pulmonary Hilar Stereotactic Body Radiation Therapy in the Rat

Abstract

Stereotactic Body Radiation therapy (SBRT) is an emerging modality of treatment for early stage non-small cell lung carcinoma. Concerns have arisen related to increased toxicities for medial tumors. We have developed a model of high dose, hypofractionated radiotherapy to the pulmonary hilum using the Leksell Gamma-Knife. Sprague-Dawley rats received hypofractionated SBRT to the unilateral lung hilum using a custom immobilization device on the Gamma Knife. Each animal was individually scanned, treatment planned, and treated with either two 4 mm or one 8 mm collimated shots at escalating doses of 20, 40, and 80 Gy to the 50% isodose volume, encompassing the right mainstem bronchus. All animals were carefully followed post-treatment and imaged by plain film and CT. In addition, histopathological analysis of all rats was performed at selected time points. Animals treated with 4 mm collimated shots demonstrated no appreciable changes on plain films or sequential, follow-up CT scans, or histopathologically. Animals irradiated with the 8 mm collimator were less active, gained weight at a reduced rate, and demonstrated histopathological changes in 7/34 animals six months post-irradiation. Cellular atypia and interstitial pneumonitis were found, three of the seven of the animals showed clear bronchial damage and two showed vascular damage. Significant volume and time effects were found. Utilizing a novel Gamma Knife based animal model to study SBRT toxicity, it was found that the bronchus will tolerate small volumes of very high dose radiotherapy. It was postulated that radiation of the surrounding support stroma and normal tissue are important in the etiology of bronchial or hilar damage.