Purpose/Objective(s): Cancer-related cognitive impairment (CRCI) is relatively common after treatment of primary and metastatic brain tumors, however the temporality of cognitive decline after radiation therapy (RT) is not well defined, with reports of both early (<4 months) and late onset (>12 months) symptoms. Identifying dosimetric parameters predictive of CRCI is difficult due to the heterogeneity of patient characteristics, as well as inadequate documentation of confounding factors. Memory function is especially susceptible to radiation effect after treatment. The objective of this study is to correlate volumetric radiation doses received by critical neuroanatomic structures to post-RT memory impairment. Materials/Methods: Between 2008 and 2011, 53 patients with primary brain malignancies were treated with conventionally fractionated RT on a prospectively accrued clinical trial performed at our institution (WFU97100/91105). Tumor types included glioblastoma (13%), primitive neuroectodermal tumors (21%), and low grade/benign tumors (66%).Ten patients received whole brain RT with region boost, all other patients received partial brain RT. The median radiation dose was 54.0 Gy (range = 40.0-60.6 Gy) delivered in 1.8 Gy/fraction (range = 1.5-2.5 Gy/fraction). Dose-volume histogram analysis was performed for the hippocampus, parahippocampus, amygdala, and fusiform gyrus. Hopkins Verbal Learning Test-Revised (HVLT-R) scores were obtained at least 6 months after RT. Impairment was defined as a HVLT-R immediate recall score 15, based upon studies reporting optimal sensitivity and specificity for detecting impairment using HVLT-R cut-off scores of 14.5-15.5. For each anatomic region, serial regression was performed to correlate volume receiving a given dose (VD(Gy)) with memory impairment. Results: Hippocampal V53.4Gy -V60.9Gy significantly predicted post-RT memory impairment (P < 0.05). Within this range, the hippocampal V55Gy was the most significant predictor (P = 0.004). Hippocampal V55Gy of 0%, 25%, and 50% were associated with post-RT impairment rates of 14.9% (95% CIZ7.2% -28.7%), 45.9% (95% CIZ24.7% -68.6%), and 80.6% (95% CI = 39.2% -96.4%), respectively. Dose received by the fusiform gyrus was a significant predictor of impairment, with the most significant relationship at V46.5Gy (P = 0.003). No statistically significant relationship was observed for the amygdala or parahippocampus. Conclusion: Injury to the hippocampus plays a fundamental role in CRCI. This analysis provides dosimetric guidelines to limit cognitive decline after cranial RT. The hippocampal V55Gy is a significant predictor for impairment and limiting dose below 55 Gy may minimize treatment related neuro-cognitive toxicity.
Okoukoni, C., McTyre, E., Peiffer, A. M., Hinson, W., Strowd, R. E., Rapp, S., & Chan, M. D. (2016). Hippocampal Dosimetry Predicts for Cancer-Related Cognitive Impairment in Patients Treated With Cranial Radiation Therapy: Dosimetric Results of a Prospective Clinical Trial. International Journal of Radiation Oncology*Biology*Physics, 96(2), S90–S91. https://doi.org/10.1016/j.ijrobp.2016.06.228