Predictors of tumour dynamics over a 6-week course of concurrent chemoradiotherapy for glioblastoma and the impact on survival

Abstract

We present the final analyses of tumour dynamics and their prognostic significance during a 6-week course of concurrent chemoradiotherapy (chemoRT) for glioblastoma (GBM) in the GLIO study. This is a prospective serial MR imaging study in 129 patients with GBM who had MRIs obtained at RT planning (F0), fraction-10 (F10), fraction-20 (F20), and 1-month post-RT. Tumour dynamics assessed included gross tumour volume (GTV) relative to F0 (Vrel), and tumour migration distance (dmigration). Covariables evaluated included: corpus callosum involvement, extent of surgery, MGMT methylation and IDH mutation status. The median Vrel were 0.85 (range: 0.25-2.29) at F10, 0.79 (range: 0.09-2.22) at F20 and 0.78 (range: 0.13-4.27) at P1M. The median dmigration were 4.7mm (range: 1.1-20.4mm) at F10, 4.7mm (range: 0.8-20.7mm) at F20 and 6.1mm (range: 0.0-45.5mm) at P1M. Compared to patients who had corpus callosum involvement (n=26), those without corpus callosum involvement (n=103) had significant Vrel reduction at F20 (P=0.03) and smaller dmigration at F20 (P=0.007). Compared to patients who had biopsy alone (n=19) and subtotal resection (n=71), those who had gross total resection (n=38) had significant Vrel reduction at F10 (P=0.001) and F20 (P=0.001) and a smaller dmigration at F10 (P=0.03) and F20 (P=0.002). MGMT methylation and IDH mutation status were not significantly associated with tumour dynamics. The median progression free survival and overall survival (OS) were 8.5 months (95%CI=6.9-9.9) and 20.4 months (95%CI=17.6-25.2). In multivariable analyses, patients with Vrel≥1.33 at F10 had worse OS (HR=4.6; 95%CI=1.8-11.4; P=0.001), while patients with dmigration≥5mm at 1-month post-RT had worse PFS (HR=1.76; 95%CI=1.08-2.87) and OS (HR=2.2; 95%CI=1.2-4.0; P=0.007). Corpus callosum involvement and extent of surgery are independent predictors of tumour dynamics during RT and can enable patient selection for adaptive RT strategies. Significant tumour enlargement at F10 and tumour migration 1-month post-RT were associated with poorer OS.