Impact of Age on Early Volumetric Changes in Adults with Low-Grade or Benign Intracranial Neoplasms Treated With External Beam Radiation Therapy

Abstract

Patients receiving external beam (EB) radiation therapy (RT) for intracranial tumors are at risk for neurocognitive function (NCF) decline. This is particularly evident in patients receiving whole brain radiation therapy (WBRT). There is a growing interest in demonstrating imaging surrogates that can help predict and quantify changes in NCF. Prospective studies have demonstrated a hippocampal (HC) dose-dependent NCF decline at 18 months in patients receiving partial brain radiation. Additionally, emerging data has suggested HC volume loss in patients treated with WBRT can be seen as early as 4 months post-treatment. This work is aimed at evaluating early HC volume changes in patients with low-grade gliomas (LGG) or benign intracranial neoplasms receiving partial volume EB-RT. We performed an Institutional Review Board-approved retrospective review of seven patients treated between 2014 and 2015 who had a pre- and post-radiation (> 1 month) MRI scan. In particular, high resolution, 3D spoiled gradient echo T1 sequences were required such that the hippocampus was well visualized. 28 HC were manually segmented by a single blinded investigator (TD); 14 on MRIs obtained prior to radiation and 14 at a median time of 3 (range 1-6) months post-RT. Dose was evaluated based on each of the 14 pre-treatment HC contours, which were co-registered to the treatment planning CT scan. The R2 statistic and the Student’s T test were used to evaluate the impact of dose and age on HC volume changes, respectively. Median age was 58 (range 35-78) years. One patient had a LGG, and the remainder had meningiomas. The LGG patient received concurrent temozolomide with RT, whereas the meningioma patients were treated with RT alone. The median prescription dose was 57.6 (range 20-63) Gy. The mean doses for the 14 individual HC ranged from 4 – 36.4 Gy (median 14.9 Gy). The mean pre- and post-treatment HC volumes for the cohort were 2.47 cm3 and 2.46 cm3, respectively. We did not observe any correlation between the HC dose and the HC volume change (Linear fit: Slope of trend line = 0.26, R2 = 0.1). The population was then divided by the median age, and patients were evaluated separately via a paired, two-tailed Student’s T test. Mean decrease in HC volume was 0.17 cm3 (relative change -6.9%, P = 0.03) in patients at or above the median age of 58 years. Patients younger than 58 years had a relative increase in HC volume. Despite widely varying mean HC doses, dose-dependent early HC volumetric changes were not identified. However, when stratified by age, there was a clear and statistically significant decline in HC volume in the cohort of patients 58 years or older. Further work with long-term follow-up in this population is ongoing.