Phase II Trial of Proton Therapy vs. Photon IMRT for GBM: Secondary Analysis Comparison of Progression Free Survival between RANO vs. Clinical Assessment

Background This secondary image analysis of a randomized trial of proton radiotherapy (PT) vs. photon intensity modulated radiotherapy (IMRT) compares tumor progression based on clinical radiological assessment vs. Response Assessment in Neuro-Oncology (RANO). Methods Eligible patients were enrolled in the randomized trial and had MR imaging at baseline and follow-up beyond 12 weeks from completion of radiotherapy. ‘Clinical progression’ was based on a clinical radiology report of progression and/or change in treatment for progression. Results Of 90 enrolled patients, 66 were evaluable. Median clinical progression-free survival (PFS) was 10.8 (Range: 9.4-14.7) months; 10.8 months IMRT vs. 11.2 months PT (p=0.14). Median RANO PFS was 8.2 (Range: 6.9, 12): 8.9 months IMRT vs. 6.6 months PT (p=0.24). RANO PFS was significantly shorter than clinical PFS overall (p=0.001) and for both the IMRT (p=0.01) and PT (p=0.04) groups. There were 31 (46.3%) discrepant cases of which 17 had RANO progression more than a month prior to clinical progression, and 14 had progression by RANO but not clinical criteria. Conclusion Based on this secondary analysis of a trial of PT vs. IMRT for GBM, while no difference in PFS was noted relative to treatment technique, RANO criteria identified progression more often and earlier than clinical assessment. This highlights the disconnect between measures of tumor response in clinical trials versus clinical practice. With growing efforts to utilize real-world data and personalized treatment with timely adaptation, there is a growing need to improve the consistency of determining tumor progression within clinical trials and clinical practice.