RTRB-17: NEURAL PROGENITOR CELL (NPC) SPARING RADIATION THERAPY PLUS TEMOZOLOMIDE IN NEWLY DIAGNOSED GLIOBLASTOMA (GBM) ASSOCIATED WITH COGNITIVE FUNCTION BUT NOT TUMOR OUTCOMES: RESULTS OF A SINGLE ARM PROSPECTIVE CLINICAL TRIAL

BACKGROUND: NPC may be associated with neuro-cognitive sequelae of RT, but may contribute to GBM recurrence. This prospective trial limited RT dose to NPC niches to evaluate the impact on neuro-cognitive function, tumor recurrence, and survival in newly diagnosed GBM. METHODS: 30 adults with newly diagnosed GBM and KPS > 60 enrolled. Each received 60 Gy in 30 fractions with concurrent/adjuvant temozolomide. Standard planning target volumes (PTV) delineated. Subventricular zone (SVZ, 0.5 cm adjacent to lateral wall of lateral ventricle) and hippocampus (expanded 5 mm) defined as NPC niches. IMRT limited RT dose to NPC niches without compromising PTV dose. Tests of global cognitive function, processing speed, verbal learning/memory, and executive function obtained at baseline, 6, 12, 24 months. OS/PFS estimated using Kaplan-Meier method. Cox regression model evaluated relationships between performance on cognitive testing, radiation doses to NPC regions, survival outcomes. RESULTS: 16 men, 14 women; 17 gross total resection, 13 subtotal resection; 8 MGMT methylated, 11 unmethylated, 10 unknown; 6 multifocal. Median OS: 15.9 months (95% CI 12.6-35.4). Median PFS: 7.3 months (95% CI 4.8-9.3 months). Mean dose to ipsilateral and contralateral hippocampus: 43.8 Gy (range 9.0 - 61.4) and 17.3 Gy (range 1.7 - 40.2), respectively. Mean dose to ipsilateral and contralateral SVZ: 38.9 Gy (range 6 - 56.2) and 20.5 Gy (range 4.4 - 48.0), respectively. At a minimum FU of 13 months, 2 patients recurred in spared NPC volume. Higher mean RT dose to bilateral SVZ was associated with greater deterioration in performance between baseline and 6 /12 months on processing speed (Coding, p = 0.03). No relationship between RT dose to NPC niches and PFS, OS, or recurrence patterns. CONCLUSIONS: This prospective trial suggests a relationship between RT dose to NPC niches and neuro-psychological function in newly diagnosed GBM without a detrimental effect on recurrence or survival outcomes.