Predictors of Tumor Dynamics during a 6-Week Course of Chemoradiotherapy for Glioblastoma

Abstract

Our prior imaging studies have shown geometrically meaningful inter-fraction tumor dynamics specific to glioblastoma (GBM). We aim to identify predictors associated with tumor dynamics during a 6-week course of concurrent chemoradiotherapy (CRT) for GBM. Patients enrolled in a prospective serial magnetic resonance imaging (MRI) study were reviewed. All patients were treated with 54-60 Gy in 30 fractions. The gross tumor volume (GTV) included the surgical cavity and T1c enhanced residual tumor; clinical tumor volume (CTV) included GTV with a 15mm isotropic expansion, respecting anatomical boundaries; planning target volume (PTV) was 4mm expansion. MRIs were obtained at RT planning (F0), fraction 10 (F10), and fraction 20 (F20). Tumor dynamic metrics (relative to F0) assessed included the GTV volume (Vrel), Hausdorff distance (dH) and migration distance (dM). dH is the average distance between two datasets in metric space. dM is the maximum linear displacement of the GTV in any direction. Factors to be determined associated with tumor dynamics included: age, sex, corpus callosum (CC) involvement, extent of surgery (gross total resection (GTR), subtotal resection (STR) or biopsy alone (Bx)), MGMT methylation and IDH mutation status. A total of 129 patients were reviewed. Median GTV was 20.9cc at F0, 17.6cc at F10 (Vrel 0.85), and 16.1cc at F20 (Vrel 0.78). Patients without CC involvement had more marked GTV volume reduction: Vrel 0.82 vs 1.02 with CC involvement at F10 (P = 0.05), and Vrel 0.77 vs 0.88 with CC involvement at F20 (P = 0.03). Patients with GTR (vs STR vs Bx) had more marked GTV volume reduction across all time points: Vrel 0.78, 0.85 and 1.07 respectively at F10 (P = 0.001), and Vrel 0.69, 0.80, 1.04 respectively at F20 (P = 0.001). The median dH was 8.1mm at F10 and 9.2mm at F20. Patients with CC involvement (vs without CC involvement) had a larger dH: 54% vs 25% had dH>10mm respectively at F10 (P = 0.03), and 73% vs 28% had dH>10mm respectively at F20 (P<0.005). Patients with a GTR had smaller dH at both F10 (P = 0.02) and F20 (P = 0.006). At F20, 20%, 47% and 37% of patients with GTR, STR and Bx had dH>10mm (P = 0.04). The median dM were 4.7mm at F10 and 4.7mm at F20. Patients with CC involvement (vs without CC involvement) had larger dM: 41% vs 12% had dM >10mm respectively at F10 (P = 0.01), and 45% vs 9% had dM >10mm respectively at F20 (P<0.001). Patients with GTR had smaller dM at F10 (P = 0.03) and F20 (P0.002). At F20, 0%, 25% and 19% of patients with GTR, STR and Bx had dM>10mm (P = 0.002). Age, sex, MGMT methylation and IDH mutation status were not associated with Vrel, dH and dM at F10 and F20. We identified CC involvement and extent of surgery to be associated with tumor dynamics at F10 and F20 over the course of CRT for GBM. This offers opportunities to better select patients who may benefit from earlier/ more frequent RT replan/ adaptation to ensure adequate tumor coverage, or to reduce RT toxicities.