Purpose Brain 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. Methods On 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. Results Half of patients showed decline on PNDH, 11 of 44 (25%) on DKEFS TM, and 17 of 42 (40.4%) on PDH. 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 dose to dominant corticospinal tract; maximum dose to dominant thalamus; max dose to dominant corticospinal tract; 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, and 0.70 (95% 0.47 – 0.84) on out of bag observations for the final model. Conclusion We present the first NTCP models for FMS impairment after brain RT. Dose to several supratentorial motor associated ROIs correlated with decline on PDH tests in primary brain tumor patients, outperforming clinical variables. These data can guide prospective fine motor-sparing strategies for brain RT.

The authors have declared no competing interest.

This work was supported by the National Institutes of Health 1TL1TR001443, 1KL2TR001444, R01 CA238783-01

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