Biological Dose Escalation—Do We Have a New Window of Opportunity in High-Grade Glioma?—A Feasibility Study

Abstract

Despite multimodality treatment in high-grade glioma (HGG) involving maximal safe resection and adjuvant chemoradiotherapy, the prognosis remains dismal. In this study, we aimed to evaluate a method of biological enhancement by combining dose escalation with a condensed overall treatment time, aiming for maximal cytoreduction as a surrogate for improved outcomes. Hypofractionation has the dual advantage of enhanced cell kill with reduced overall treatment time. To this effect, we have employed a study involving hypofractionated simultaneous integrated boost (SIB) versus conventional treatment. As a secondary objective, we evaluated volumetric modulated arc therapy (VMAT) and intensity modulated radiotherapy (IMRT) in terms of optimal delivery technique for SIB boost. Forty patients were randomized into two arms, the study arm received 60 Gy in 25 fractions and the standard arm received 60 Gy in 30 fractions with concurrent and adjuvant temozolomide. The patients were assessed radiologically for tumor cytoreduction and acute toxicity parameters weekly during treatment, 6 weeks post-treatment, and 3 monthly follow-up. All patients were planned using VMAT and IMRT techniques in the study arm for the comparison of treatment time and dosimetric efficiency. However, the treatment was performed through VMAT technique. Data were analyzed using simple descriptive statistics including Student's t-tests, proportion tests, and Pearson correlation for association. The total sample size was estimated at 40, with 20 samples per group, providing a statistical power of 81% and a significance level (p-value) of 0.05. It was observed that tumor cytoreduction was significantly enhanced in a subgroup of patients in the study arm with smaller volume residual disease (p = 0.04) that was found at 6 weeks post-treatment evaluation. The tolerance, toxicity, and compliance were comparable in both arms. During the dosimetric evaluation, it was determined that VMAT had a significantly lower hot spot compared to the IMRT plan (64.22 Gy vs. 64.75 Gy, p = 0.02). It was also observed that the delivery with VMAT was faster and involved a lesser number of monitor units (555.7 MU vs. 679.6MU, p = 0.001). The hypofractionated SIB radiotherapy using the VMAT technique can provide a feasible method of biological dose enhancement without compromising toxicity and might have the future potential to improve local control in HGG.