Resection and Surgically Targeted Brain Brachytherapy Without and With Systemic Therapy for Locally Recurrent GBM

Abstract

Recurrent GBM (rGBM) is a diffuse disease, and local treatment alone does not provide durable local control (LC) or prolong overall survival (OS). Hypothesizing resection (R) plus immediate-onset radiation therapy (RT) may achieve durable LC and secondarily improve OS by permitting time for subsequent potentially effective but biologically slower treatments to have an impact, we analyzed R plus surgically targeted radiation therapy (STaRT) using a collagen tile brachytherapy (CTBT) device without or with additional systemic (Sys) therapies.From 2/13-2/18 patients (pts) with locally recurrent GBM were treated on a prospective single arm, single institution trial (NCT03088579) of maximum safe resection and a permanently implanted CTBT device (GammaTile, GT Medical Technologies, Tempe AZ USA). At resection completion at-risk areas of the surgical bed were lined with bioresorbable collagen squares containing four 3.5U Cs 131 seed sources designed to deliver 60-80 Gy at 5 mm deep to the operative bed. Follow up treatments were not specified; no pt. underwent additional local therapy without progression, and no pt. was lost to follow up. We present here the study-specified endpoints of local control (LC), overall survival (OS), and adverse events (AE), and a post hoc, hypothesis-generating analysis of LC and OS by receipt of Sys therapy.28 locally recurrent GBM were treated, 20 at first progression (range 1-3). Median age was 58 years (yrs.) (range 21-80), KPS 80 (60-100), female: male ratio 10:18 (36/64%). MGMT was methylated in 11%, unmethylated in 18%, and unknown in 71%. For all pts., median OS was 10.7 months (mo.) (range .1-42.3), and radiographic LC was 8.8 mo. (range 0.01-34.5). LC (defined as ≤ 15 mm from surgical bed) was maintained in 50% of pts., and no first failure was local. 12 mo. OS was 75% for pts. < 50 yrs. vs. 43% for ≥ 50 yrs. (HR .46, P = 0.009). MGMT, KPS, and sex were non-predictive. After R+GT, 17 pts. received ≥ 1 cycle of Sys therapy, alone or in combination. Sys was bevacizumab (BEV) in 15 pts., temozolomide (TMZ) in 12, and lomustine (CCNU) in 8. Post hoc analysis disclosed a 15.1 mo. OS for pts. receiving ≥ 1 cycle of Sys (Sys+, N = 17) vs. 6.5 mo. for no Sys (Sys-, N = 11) (hazard ratio (HR) .38, P = 0.017). LC was 11.4 mo. for Sys+ and 2.1 mo. for Sys- (HR .44; P = .16). Median OS (mo.) for BEV+ vs. BEV- was 16.7/4.5 (HR .38, P = 0.017), for TMZ+ vs. TMZ- 17.5/6.7 (HR .40, P = 0.025) and for CCNU+ vs. CCNU- 17.5/7.9 (HR .61, P = .25), respectively. Three AE occurred, 1 dehiscence requiring surgery and 2 radiation brain effects treated medically.In this study local treatment alone was insufficient to achieve prolonged OS. Post hoc analysis suggests R+ CTBT + Sys may have potential to impact OS in rGBM. A phase 4 study enrolling rGBM pts opened in 2020 (NCT04427384). The device is FDA cleared for newly diagnosed malignant and all recurrent intracranial neoplasms.P. Nakaji: Stock; GT Medical Technology. D. Brachman: Stock; GT Medical Technology. Uncompensated member; GT Medical Technology. K. Smith: Stock; GT Medical Technology. T. Thomas: Stock; GT Medical Technology. C. Dardis: None. D. Pinnaduwage: None. G. Wallstrom: None. C. Rogers: Research Grant; NCI - ActNOW. Stock; GT Medical Technology. E.F. Youssef: Stock; GT Medical Technology.