The Novel Radiation Therapy Schedule is Feasible and Safe to Administer to Patients
toxicity, glioblastoma, tumor, elevated cerebral blood volume
RECURRENCES, ADVERSE EVENT, TUMOR, DISEASE, REGRESSION, GLIOBLASTOMA
We next sought to establish whether this nonstandard treatment approach could be feasibly and safely administered to patients with recurrent GBM. To address this question, we designed and completed a prospective pilot study to evaluate the feasibility and toxicity of our novel radiation administration schedule: 7 fractions of 3.96 Gy (QD) followed by 9 fractions of 1.0 Gy (TID; 3.25 h interfraction interval (Methods). We enrolled recurrent glioblastoma patients who were previously treated with definitive neurosurgical biopsy or resection followed by RT, deemed appropriate for re-irradiation; the inclusion and exclusion criteria are provided in Methods. The primary outcome was feasibility, defined as the successful completion of radiation therapy for at least 13 of 14 patients (power calculation described in Methods). Successful completion of radiation was defined as receipt of all scheduled fractions of daily administrations on the same day as the prescribed administration and within 1 h of TID administrations, based on our analysis of the effects of varying the interfraction intervals (Patient characteristics are described in Characteristics of Patients in the Clinical TrialTreatment Related InformationThe toxicity and patient-reported outcomes are described in All Grade Adverse Events Regardless of Attribution at Baseline and Post-Baseline (CTCAE version 5.0)Number of Patients Experiencing Patient-Reported Symptoms and their Impact on Quality of Life in the Clinical Trial (Assessed Using MDASI-BT)*Not all patients completed MDASI-BT, therefore the data from the two timepoints may be from different patients.Median progression-free survival and overall survival were 4.4 months (95% CI 2.4–5.2 months) (Patterns of tumor response and survival of patients treated in the clinical trial. (A) Kaplan-Meier plot for progression-free survival. (B) Kaplan-Meier plot for overall survival. (C) Cox proportional hazards regression model hazard ratios for progression-free survival. (D) Cox proportional hazards regression model hazard ratios for overall survival. (E) Swimmer plot of tumor response. The points indicate the responses at individual time points and the colors indicate the best response for each patient. (F) MRI scans of Patient 6 at the time of radiation therapy planning (left), 3 month follow-up (center) and 6 month follow-up with progression (right) showing a representative example of stable to regressed disease locally within the Planning Target Volume (contour line) but evidence of progressive enhancing, hypercellular disease with elevated cerebral blood volume immediately anterior to the Planning Target Volume. The patient died of disease 5 weeks after this time point. (G) MRI scans of Patient 1 at the time of radiotherapy planning (left) and 1 month follow-up (right) showing an example of a distant progression outside of the radiation therapy field (arrow), with stable to well controlled disease locally within the Planning Target Volume (contour line).Notably, of the 12 patients with pattern of progression data available, 2 patients (17%) had local recurrences and 10 patients (83%) had out-of-field failures. Of these, 5 (42%) were marginal (