Brown, Paul D

Abstract Introduction Postoperative radiotherapy is an adjuvant therapy for brain metastases(BrMs) that improves local recurrence(LR). The radiosensitivity index(RSI) is a 10-gene index of pan-cancer molecular radiosensitivity previously validated for predicting radiotherapy response in clinical datasets. In this external validation study, we evaluate RSI as a predictor of local recurrence(LR) after radiotherapy in resected BrM. Methods Patients from University Health Network Toronto(UHN) and McGill University who had a resected BrM and subsequently underwent whole brain radiation(WBRT) or stereotactic radiosurgery(SRS). RSI was calculated using a ranked linear regression model from the weighted expression of 10 radiosensitivity genes, with higher values corresponding to radioresistance. Radiophenotype was determined using a previously validated RSI cutoff of < 0.375 to identify radiosensitive tumors. LR was defined as recurrence in the resection cavity and overall survival(OS) was measured from time of BrM diagnosis. Results 106 BrM patients were included, comprising 29 breast, 37 GI, 33 lung, and 7 melanoma primary sources. Mean age at surgery was 59.2 years, 31.1%(n = 33) were male, 67.9%(n = 72) had WBRT, 23.6%(n = 25) had a subtotal resection, and 30.2%(n = 32) had postoperative chemotherapy. Overall, 34.0%(n = 36) patients had LR. Patients with breast BrMs had median RSI 0.70(IQR:0.55-0.75, 10.3% radiosensitive) with 48.3% LR(n = 14); gastrointestinal BrMs had median RSI 0.43(IQR: 0.35-0.46, 29.7% radiosensitive) and 24.3% LR(n = 9); lung BrMs had median RSI of 0.67(IQR:0.66-0.71, 9% radiosensitive) and 33.3% LR(n = 11); melanoma BrMs had median RSI of 0.72(IQR:0.53-0.92, 0% radiosensitive) and 28.6% LR(n = 2). After adjusting for demographics, primary organ, radiotherapy, resection extent, among others, RSI did not predict LR(p = 0.56) or OS(p = 0.61). Discussion RSI did not predict either LR or OS in patients with surgically resected BrMs status post radiotherapy, further establishing the need for improved predictive scores in this population.