Neurocognitive outcomes in pediatric brain tumor survivors treated with proton radiotherapy: a study from the Pediatric Proton/Photon Consortium Registry (PPCR)

Abstract

<h3>Objectives</h3> Radiation (RT), while an essential component of curative treatment, is associated with negative long-term cognitive sequelae. We examined cognitive functioning at follow-up in patients <22 years treated with proton RT for a primary brain tumor. <h3>Methods</h3> Patients enrolled on the PPCR between 9/2012-11/2020 were assessed at baseline and follow-up using age-appropriate Weschler measures for intellectual ability [full scale intelligence quotient (FSIQ)] from cognitive functioning index scores. We used univariate linear regression to analyze the relationship over time between cognitive outcomes and patient characteristics of gender, age at RT, tumor location, RT target (CSI vs. focal), dose, and chemotherapy. <h3>Results</h3> Of 298 patients assessed at baseline, 58 had granular data entered at both baseline and follow-up. Median age at RT was 8.9 years (2.3-21.5). Patients received RT for tumors present in posterior fossa (43%), supratentorial (38%), and midline (19%) locations. Median time from RT to follow-up neurocognitive assessment was 2.9 years (1.2-9.9). Overall, mean FSIQ declined from 104.0 to 99.1 (p=0.02) and mean processing speed declined from 96.4 to 91.1 (p=0.04). Change in other index scores were not significant. Patients that received CSI had a significant 6.4pts decline in FSIQ (p=0.01) while those who received focal RT maintained similar scores at both timepoints (105.5 vs 102.9, p=0.2). Patient characteristics of age <6 years at RT, posterior fossa or midline tumor location, CSI dose >36GyE, and total dose >54GyE all correlated to statistically significant FSIQ decline relative to their counterparts. Notably, those who received a CSI dose of >36GyE lost 10.2pts relative to those with <36GyE (p=0.03). <h3>Conclusion</h3> At 2.9-years after RT, mean cognitive scores remained in the average range. Declines in scores were found among patients that are younger at RT, received CSI, or have a non-supratentorial tumor. Additional school and IEP data will be presented at the meeting.