Initial Provider and Patient-Reported Outcomes of a Phase II Study of Short Course Hypofractionated Proton Beam Therapy Incorporating 18F-DOPA-PET/MRI for Elderly Patients with Newly Diagnosed Glioblastoma

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<h3>Purpose/Objective(s)</h3> Due to poorer prognosis, hypofractionated radiation therapy is considered for elderly patients with newly diagnosed glioblastoma. Targeted radiation delivery with proton beam therapy (PBT) utilizing 18F-DOPA PET to identify biologically aggressive disease may be desirable. We report both provider and patient reported outcomes of a phase II trial evaluating hypofractionated PBT incorporating 18F-DOPA in treatment planning. <h3>Materials/Methods</h3> Patients ≥ 65 with histologically confirmed glioblastoma without contraindications to 18-FDOPA were enrolled. Target volumes were defined by PET (tumor/normal brain SUV ≥2.0) and MRI areas of contrast enhancement (MRI-CE) including surgical cavity. A combined volume of 65 cc or less was treated with 25 (1 cm margin), 30 (MRI-CE), and 35 (PET) GyE over 5 fractions with a simultaneous integrated boost. A combined volume of more than 65 cc was treated with 30 (1 cm margin), 35 (MRI-CE), and 40 (PET) GyE over 10 fractions. Patients received concurrent/adjuvant temozolomide. Provider-reported toxicity was assessed according to CTCAE V4. Patients completed EORTC BN20, QLQ-C30, and MMSE. QOL outcomes were compared with prior published phase III trials (NCT00482677 and NCT00430911). Time to deterioration, defined as a 10-point decrease in the score of the function domain or 10-point increase in score of symptom domain, was evaluated. <h3>Results</h3> Between 5/19 and 10/21, 39 patients were enrolled. 36 (92.3%) patients were IDH1 wt and 3 were IDH1 (7.7%) mt. MGMT promotor methylation was present in 13 (33%). The median clinical follow-up was 5.2 months. Tumors were multifocal in 10 (25.6%) and unifocal in 29 (74.4%). The median tumor diameter was 5.2 cm. Twenty-one patients (53.8%) received 40 GyE in 10 fractions and 18 (46.2%) received 35 GyE in 5 fractions. Baseline adjusted treatment related grade 2+ adverse events were: 8 (20.5%) CNS necrosis, 3 (7.7%) confusion, 1 (2.5%) dysphasia, 9 (23.1%) fatigue, 2 (5.1%) headache, 5 (12.8%) seizure, and 4 (10.2%) alopecia. Grade 3 baseline adjusted treatment related adverse events included 1 (2.6%) confusion, 2 (5.1%) fatigue, and 1 (2.6%) seizure. There were no grade 4/5 events. The median time to deterioration per QLQ-C30 was 6.3 months which was greater compared to the treatment arms (1.2 months, p<0.05) of NCT00482677 trial. At 90 days, there was improved (p<0.05) functioning in global, physical, role, emotional, social domains of QLQ-C30 and visual domain of BN20 for patients receiving PBT versus the supportive care arm of the NCT00430911. <h3>Conclusion</h3> Hypofractionated PBT incorporating 18F-DOPA in elderly patients was feasible with reasonable provider reported toxicity. Patient-reported outcomes compared favorably to prior phase III studies with similar patient populations.