Phase II Study Of Proton Radiation Therapy For Lower Grade Gliomas

Abstract

To evaluate the role of proton therapy in the management of patients with lower grade gliomas in regard to progression free survival (PFS) and treatment toxicity WHO 2007 grade II glioma patients and IDH mutant grade III glioma patients indicated for radiation therapy were enrolled in a prospective single arm trial of involved field proton therapy receiving a dose of 54 Gy (RBE) in 30 fractions if grade II, and 59.4 Gy (RBE) in 33 fractions if grade III. No prior cranial irradiation was permitted. Comprehensive baseline and regular post treatment evaluations of neuroendocrine function, neurocognitive functions, quality of life (QOL), and PFS were performed. Among 60 patients (median age 40.8 years) who received proton therapy, 28 (47%) were men, and 39 (65%) were WHO Grade II. Forty-one patients (68%) were treated at initial diagnosis and 19 (32%) patients were treated at the time of progression. Primary tumor locations were frontal (32; 53%), temporal (10; 17%), parietal (7; 12%), and occipital (1; 2%) lobes, thalamus (1; 2%), and 9 patients (15%) with tumor involving temporal lobe and one or more adjacent lobes. All patients tolerated the delivery of proton therapy without difficulty. Median follow-up after proton therapy was 3.1 years among 47 progression-free patients with ongoing follow-up. Progression-free survival at 5-years was 71%. 5-year PFS for grade II gliomas (n = 39) was 67% and for favorable grade III (n = 21) was 78%. New endocrine dysfunction was detected in 3 patients (5%). The axes affected were thyroid (2%), testosterone (4% of men), and cortisol (2%). The mean pituitary doses for patients with new endocrine dysfunction were 0 Gy, 21.0 Gy, and 0 Gy, respectively. Of the 34 patients with at-risk pituitary (mean dose >0 Gy), the median pituitary mean dose was 14.58 Gy (range: 0.01 – 48.29 Gy). There was one grade 4 case of central nervous system necrosis (2%) which was biopsy proven; there were no grade 3 toxicities. The most common grade 2 toxicities were fatigue (15%), dermatitis (5%), and headache (3%). QOL assessment by FACT-Brain showed modest improvement at 2 years follow-up (n = 46) with mean increase of 3.5 in total score from baseline, but the mean score returned to baseline level at 4 years (n = 20). Early results demonstrate that lower grade glioma patients tolerate proton therapy with very few toxicities. There were minimal neuroendocrine deficiencies and no evidence for early decline in QOL which may be partially attributable to limited integral dose to the brain and pituitary by use of proton therapy. Neurocognitive function is yet to be reported. PFS is equivalent to that of photon-based therapy.