Impact of Delay in Initiation of Radiation Therapy in Newly Diagnosed Glioblastoma Patients after Gross Total Resection

Abstract

Newly diagnosed glioblastoma (GBM) is treated with surgery followed by radiation therapy (RT) and temozolomide (TMZ). We evaluated the impact on clinical outcomes of a delay in the initiation of RT for newly diagnosed GBM patients who have undergone a gross total resection (GTR). Consecutive GBM patients who underwent GTR and were treated at our institution from 2005-2014 were investigated. Patient, tumor, and treatment details were abstracted from the electronic medical record. A delay in RT start was defined as interval from surgery to RT initiation of over 5 weeks (35 days). Kaplan-Meier and Cox proportional hazards modeling were used to evaluate overall survival (OS) and recurrence-free survival (RFS). We identified 179 GBM patients with a median age of 59 years (range 22-87) who underwent GTR. 94% had KPS ≥ 70. Median RT dose was 60 Gy and 93% received concurrent TMZ with RT. Among 110 patients with known MGMT methylation status, 51% were methylated. The median interval from diagnosis to RT start was 28 days (range 10-93) and 32 patients (17%) had an RT delay (start > 5 weeks after diagnosis). There was an explicit medical reason for delay (e.g. wound healing, hospitalization, management of other malignancy) in 7 patients. Among those with RT delay, MGMT was methylated in 47%. Median age was 59 years versus 58 years in those without a delay (p = 0.4). 90% had KPS ≥ 70 versus 95% of those without RT delay (p = 0.4). On univariable analysis (UVA), a delay in RT start was associated with inferior OS (HR 1.66, 95% CI 1.05-2.66, p=0.03). Crude median OS was 19.5 months for patients with RT delay vs. 26.9 months in patients without RT delay. On multivariable analysis (MVA) with RT delay, age, MGMT methylation status, and KPS < 70 as covariates, age (AHR 1.05, 95% CI 1.03-1.08, p < 0.001) was significantly associated with OS and MGMT methylation was near-significant (AHR 0.63, 0.37-1.07, p = 0.09), while RT delay was not significant (AHR 0.83, 95% CI 0.41-1.65, p = 0.59). RT delay was associated with inferior RFS on UVA (HR 1.65, 95% CI 1.09-2.51, p = 0.02), but this did not hold on MVA (AHR 0.96, 0.54-1.70, p=0.9). Age (AHR 1.02, 95% CI 1.00-1.05, p = 0.02) and MGMT methylation (AHR 0.44, 95% CI 0.28-0.70, p<0.001) were associated with improved RFS. Among GBM patients with GTR, patients with RT delay > 5 weeks had inferior OS and RFS relative to patients without a delay, but there was no significant difference after adjustment for clinical covariates.