Pentoxifylline and Vitamin E in Preventing Pneumonitis Using Stereotactic Ablative Radiotherapy in Previously Irradiated Patients

Abstract

Despite radiotherapeutic advancements, patients with non-small cell lung cancer (NSCLC) experience recurrence rates from 30-40% (1) (2). For these cases, stereotactic ablative radiotherapy (SABR) is an attractive retreatment option as studies have reported upwards of 96% local control rates at 3 years follow up (3) (4). However, thoracic reirradiation poses threat for radiation-induced pneumonitis. Particularly, the rate of grade 3 pneumonitis from institutional data was 30% in patients undergoing SABR for recurrent thoracic malignancies (4). Prior studies have tried to mitigate SABR toxicities with administration of pentoxifylline (Ptx) and vitamin E (VE), which has reduced lung damage in breast cancer patients (5) (6). The addition of Ptx and VE in retreatment of NSCLC may similarly reduce radiation-induced pneumonitis. The purpose of this study is to prospectively evaluate the efficacy of Ptx and VE in reducing grade 3 pneumonitis in patients undergoing SABR with loco-regionally recurrent lung cancer or new lung primary tumors in the setting of prior thoracic radiation. We hypothesize that these patients will experience rates of grade 3 pneumonitis lower than 30% at 3, 6, and 12-months post-treatment follow up. Patients who received radiation for a prior thoracic malignancy with a diagnosis of a recurrent or new NSCLC were recruited from our institution. Ptx and VE were administered at the time of simulation, approximately 1 week prior to starting treatment and continued for 12 weeks after the completion of treatment. SABR was delivered using standard stereotactic techniques to a dose of 5000 cGy at 1000 cGy per fraction over 2 weeks. The following demographic information was collected: baseline performance status, time interval between initial radiation and retreatment radiation, central or peripheral recurrent tumor, and pre-treatment FEV1. Patients were assessed clinically and radiographically for grades of pneumonitis at 3, 6, and 12-months post treatment. Demographic and follow-up data were collected from the initial cohort of 40 patients. There were no statistically significant correlations between pretreatment characteristics and pneumonitis. 92% of participants were medication compliant. Crude rates of pneumonitis at any time point were grade 1 (23%), grade 2 (10%), and grade 3 (2%). Only one of our patients experienced grade 3 pneumonitis. The rate of grade 3 pneumonitis in our Ptx and vitamin E treated cohort was significantly less than 30% at 3-months (p = 0.001), 6-months (p = 0.001), and 12-months (p = 0.014) post-treatment. Thus, we conclude that Ptx and VE are safe interventions that may prophylactically reduce rates of grade 3 pneumonitis for patients receiving subsequent SABR for recurrent NSCLC. Additional studies should be performed to evaluate the use in of Ptx and VE in the retreatment setting.