LMAP-20 EVIDENCE-BASED MULTIVARIATE NORMAL TISSUE COMPLICATION PROBABILITY (NTCP) STUDY OF DOMAIN-SPECIFIC COGNITIVE DECLINE AFTER PARTIAL BRAIN RT

Beyond the hippocampus, there are no evidence-based dose constraints for eloquent structures which subserve memory and attention/processing speed. We performed a multivariate normal tissue complication probability analysis of post-RT neurocognitive decline, examining dosimetric predictors of eloquent brain regions in a prospective longitudinal clinical trial. 78 patients with primary brain tumors receiving fractionated RT completed a comprehensive neurocognitive evaluation and high-resolution volumetric and diffusion MRI at baseline and 6 months post-RT. Image processing using validated automated segmentation parcellated individual white matter (WM) tracts, cortical regions, and hippocampi. Neurocognitive test performance was scored using reliable change indices adjusted for practice effects: negative scores indicate decline. Univariate logistic regression and multivariate model building were performed. On univariate analysis mean and max dose to multiple regions of the corpus callosum (CC) correlated with attention/processing speed decline including Dmax to anterior CC (p=0.011) and central CC (p=0.010), and Dmax/Dmean to mid-anterior CC (p=0.006 and 0.010). Dmean to left fornix was associated with memory decline (p=0.023), as were increasing age and chemotherapy. On multivariate analysis for attention, automated bootstrapped logistic regression showed the most frequently selected variable was Dmean to mid-anterior CC. Performance at nested cross-validation by AUC was 0.80 (0.75-0.84); LASSO model performance by AUC was 0.76 (0.72-0.81) with Dmean to the mid-anterior CC being the most frequent variable. The top five most important variables in Random Forest were Dmean to mid-anterior CC, all WM, combined CC and Dmax to CC and posterior CC. Model performance by AUC was 0.66 (0.60-0.71). We present the first, to our knowledge, multivariate NTCP model for decline in attention/processing speed, and dosimetric predictors of memory decline beyond the hippocampus. Dose to several eloquent ROIs significantly correlated with post-RT impairment. These data can guide future cognitive-sparing strategies for brain RT.