Whole brain radiotherapy and association with rapid brain aging as determined by anatomic surface morphology.

e14007 Background: Brain metastases are the most common intracranial tumors in adults and are associated with significant morbidity and mortality. Whole brain radiotherapy (WBRT) is used frequently in patients for palliation, but can result in neurocognitive deficits. While dose-dependent injury to individual areas such as the hippocampus have been demonstrated, global structural changes after WBRT remain to be studied. Our group previously published a magnetic resonance imaging (MRI) deep learning model based on anatomic brain surface morphology to accurately predict brain age in healthy subjects. We now report the effect of WBRT on aging pace of the irradiated brain. Methods: We studied patients with brain metastases and examined MRI brain anatomic surface data before and after WBRT. We implemented a graph convolutional neural network model to estimate patient’s brain age. We further developed a mixed-effects linear model to compare age of whole brain and substructures before and after WBRT, written as follows: ΔAge = c + β(ΔScan) + 1|patient_ID; where for each patient, ΔAge = [(model_predicted_age_at_follow up – actual_age_at_follow up) – (model_predicted_age_pre_treatment – actual_age_pre_treatment)], ΔScan = time interval between pre-and post-treatment MRI scans, β = aging coefficient (β =0 corresponds to normal aging), and c = intercept (model_predicted_age_pre_treatment – actual_age_pre_treatment). Results: 56 patients were analyzed. The median age was 62 (range 32 – 85). Two-thirds of patients were female. Primary organ site was breast or lung in 87% of cases and 77% of patients had five or more metastases. Median radiation dose was 30Gy (range 25 – 37.5Gy). Results of aging analysis are presented in Table. Small c values demonstrate that model accurately predicted age pre-treatment. The whole brain and substructures underwent rapid aging compared to normal aging pace (β>>0). Based on median follow up of 6.3 months, the whole brain aged approximately 4.94 years, the cortex aged approximately 4.53 years, the subcortical structures aged approximately 5.94 years, and the hippocampus aged approximately 5.17 years. Conclusions: Our findings suggest that WBRT causes the brain and its substructures to age at a pace of 9-11x of the normal aging pace, mirroring deficits in long-term neurocognition seen post-treatment. Given post-treatment aging pace and increasing survival for many patients with brain metastases, WBRT needs to be used judiciously. [Table: see text]