Fine Motor Skill Decline after Brain RT – A Multivariate Normal Tissue Complication Probability Study of a Prospective Trial

Abstract

AbstractPurposeBrain radiotherapy can impair fine motor skills (FMS). FMS are essential for activities of daily living, enabling hand-eye coordination for manipulative movements. We developed normal tissue complication probability (NTCP) models for decline in FMS after fractionated brain RT.MethodsOn a prospective trial, 44 primary brain tumor patients received fractioned RT, underwent high-resolution volumetric MRI and diffusion tensor imaging, and comprehensive FMS assessments (Delis-Kaplan Executive Function System Trail Making Test Motor Speed [DKEFS-MS], and Grooved Pegboard Dominant/Non-Dominant Hands [PDH/PNDH]) at baseline and 6 months post-RT. Regions of interest subserving motor function (including cortex, superficial white matter, thalamus, basal ganglia, and white matter tracts) were autosegmented using validated methods and manually verified. Dosimetric and clinical variables were included in multivariate NTCP models, using automated bootstrapped logistic regression, least absolute shrinkage and selection operator (LASSO) logistic regression, and random forests with nested cross-validation.ResultsHalf of patients showed decline on PNDH, 17 of 42 (40.4%) on PDH, and 11 of 44 (25%) on DKEFS-TM. Automated bootstrapped logistic regression selected a one-term model including maximum dose to dominant postcentral white matter. LASSO selected this term and steroid use. The top five variables in random forest were all dosimetric: mean and maximum dose to dominant corticospinal tract; maximum dose to dominant thalamus; mean dose to dominant caudate; maximum dose to dominant postcentral white matter. This technique performed best with AUC 0.69 (95% CI 0.68 – 0.70) on nested cross-validation.ConclusionWe present the first NTCP models for FMS impairment after brain RT. Dose to several supratentorial motor-associated ROIs correlated with decline in dominant hand fine motor dexterity in primary brain tumor patients, outperforming clinical variables. These data can guide prospective fine motor-sparing strategies for brain RT.