Large volume re-irradiation with bevacizumab is a feasible salvage option for patients with refractory high-grade glioma

Abstract

BACKGROUND: Clinical studies of re-irradiation (ReRT) for relapsed high-grade glioma (HGG) have generally reported the use of small volume ReRT techniques such as stereotactic radiosurgery in selected patients with isolated focal relapse. This study reports the outcome with large-volume ReRT to manage the more common mescenario of extensive diffuse relapse of HGG. METHODS: All HGG patients managed with an overlapping second course of radiation therapy (RT) for refractory progression of HGG between October 2009 and April 2013 were included. ReRT was initially used with bevacizumab (BEV), then used when disease was refractory to BEV, and finally used upfront with BEV-naive patients. Tumor volume (GTV) and specific RT dosimetry factors, including the target volume treated (PTV), and cumulative RT dose maximum (Dmax), were analyzed. Median survival post ReRT was calculated using the Kaplan-Meier method and SPPS v19 software. RESULTS: Eighteen HGG participants with refractory, bulky contrast-enhancing disease received ReRT. Thirteen participants had a maximum tumor diameter >5 cm, and median GTV was 54 cm(3). Seven participants had BEV-refractory disease, and 8 participants were BEV naive. ReRT dose was 35-40 Gy in 15 fractions; median PTV was 133 cm(3), and median Dmax was 98.2 Gy. Median survival post ReRT for all participants was 8 months (95%CI, 5.8-10.2 months); with 10 months and 3 months for the BEV-naive and BEV-refractory participants, respectively (P = .024). Two early participants, who were managed without BEV, were later salvaged with BEV, including one who required craniotomy for radiation necrosis at 6 weeks post RT. No other significant morbidity was reported. CONCLUSION: ReRT combined with BEV is a feasible salvage treatment option for diffuse refractory HGG.