PARENT SESSION

Genomic Maintenance & Repair

(PP356) Pulmonary hilar radioablation: An animal model of radiotoxicity.

Tinnel, Brent^*,1, McGarry, Ronald¹, Mendonca, Marc³, Cummings, Oscar², Chin-Sinex, Helen³, Timmerman, Robert⁴, ¹ Indiana University School of Medicine, Indianapolis, IN, United States³ Indiana University School of Medicine, Indianapolis, IN, United States² Indiana University School of Medicine, Indianapolis, IN, United States⁴ UT Southwestern Medical School, Dallas, TX, United States

ABSTRACT- Purpose/Objective: We have observed radiographic and clinical changes while treating lung tumors with Extracranial Stereotactic Radiotherapy. In order to understand and explore these potential toxicities, we have developed a model of high dose, hypofractionated radiotherapy to the pulmonary hilum using the Leskell Gamma-KnifeTM. Materials/Methods: We selected Sprague-Dawley rats as the host animal for the study. We created a system to treat only the unilateral lung hilum. CT simulation at 1 mm thickness was used to acquire target information. Each animal within a cohort of three would be treated with the same dose of single fraction, Gamma-Knife radiotherapy centered on the right main bronchus. A pilot cohort was treated with 10 Gy prescribed to the 50% isodose line, using two 4 mm collimated 'shots', differing by 1 mm in the Z axis only and observed without any overt toxicity. We then proceeded to treat similar cohorts at escalating doses of 20, 40, then 80 Gy, respectively, in a single fraction. Each cohort was designated for sacrifice and histo-pathological analysis at either an intermediate time of 3-4 months, or a late time of 6 months. Additionally, to observe a potential volume effect, two additional cohorts were treated at the 20, 40, and 80 Gy dose levels using a larger, sigle 8-mm collimmated shot. They were also designated for sacrifice at an interemediate (3-4 month) and late (> 6 month) time interval. Results: From 8/2003 to 8/2004, 34 animals were treated using the organized cohorts described above. The majority of animals thrived and were observed until their designated sacrifice and demonstrated no appreciable changes on plain films or sequential, follow-up CT scans. On histo-pathologic analysis, only animals irradiated with 8-mm collimator (larger volume) and sacrificed at 6 months demonstrated any changes (7/34). Cellular atypia and interstitial pneumonitis were the most common findings. However, 3 of the 7 showed clear bronchial damage and 2 showed vascular damage. One animal had atelectasis related to marked bronchial damage and vascular occlusion. Statistical analysis (Fisher's Exact Test) supports a volume effect (47% of the 8-mm Vs 0% of the 4-mm demonstrated changes, p=0.0001). The time interval from irradiation to any observed changes was also signicant (0% in the 3-4 month groups had changes Vs 39% of the 6 month groups p=0.01). Conclusions: We have successfully utilized the Leksell Gamma-Knife to irradiate the pulmonary hilum in laboratory rats, and verified it as a viable model for study of stereotactic, hypofractionated lung radiotoxicity. We have found that small volumes of very high dose (80 Gy) radiotherapy centered on the bronchus can be well tolerated and in the case of the 4 -mm collimated shots, without apparent histological consequences. However, our observation of severe histo-pathological changes with the 8-mm collimated shots, suggests that radition of the surrounding and supporting stroma are important in the etiology of bronchial or hilar damage.

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