235 - Unveiling Early Radiation Effects on the Hippocampus: ADC Dynamics Reveal Microstructural Changes during Therapy
Presenter(s)
O. Haisraely1, B. Panthi2, E. Konstaniopoulou2, H. E. Langshaw2, S. Thrower3, W. Talpur1, A. M. Elliott1, D. N. Yeboa4, A. C. Paulino1, J. Li5, M. F. F. McAleer5, S. Perni6, D. R. Grosshans4, and C. Chung5; 1Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 2MD ANDERSON CANCER CENTER, Houston, TX, 3Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, 4Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 5Department of Radiation Oncology, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 6Columbia University Vagelos College of Physicians and Surgeons, New York, NY
Purpose/Objective(s): The apparent diffusion coefficient (ADC) is an imaging biomarker reflecting microstructural brain changes due to edema, inflammation, and altered cellular integrity. In glioblastoma (GBM) patients undergoing radiation therapy (RT), ADC variations in the hippocampus may indicate radiation-induced structural changes, even in regions outside the high-dose area. The hippocampus is highly radiosensitive and functionally lateralized, with the left hippocampus involved in verbal memory and the right in spatial and visual memory. The purpose of this study was to characterize early changes in ADC relative to dose exposure to the hippocampus in patients receiving radiotherapy for GBM.
Materials/Methods: A subset of 55 adult GBM patients (median age: 59) from a prospective study using weekly multiparametric MRI for adaptive RT was analyzed. Thirty-eight had left-sided tumors, and 17 had right-sided tumors, with hippocampi outside the 80% isodose line (excluding bilateral or midline tumors). Weekly DWI was performed over six weeks of RT, and longitudinal ADC changes were assessed relative to radiation dose using paired statistical tests and hippocampal dose metrics. In addition, cognitive tests were performed weekly to assess potential neurocognitive effects.
Results: For ipsilateral hippocampi, the mean radiation dose to the left hippocampus increased from 2.08 Gy (Week 1) to 13.1 Gy (Week 6), while the right hippocampus (right-sided tumors) received 2.46 Gy to 12.9 Gy. In contralateral hippocampi, the right hippocampus received 1.67 Gy to 9.5 Gy, and the left hippocampus received 1.24 Gy to 8.67 Gy.
ADC values progressively increased during RT. In left-sided tumors, ADC elevation became significant at Week 4 (0.0086) and remained elevated at Week 5 (0.0031) and Week 6 (0.0029). The right hippocampus exhibited a more gradual ADC increase (0.0018). For contralateral hippocampi, significant ADC increases were observed for the left hippocampus in right-sided tumors between Week 1 and Week 5 (0.017) and for the right hippocampus in left-sided tumors between Week 1 and Week 6 (0.046). A general linear model demonstrated a significant time effect on ADC values (p < 0.001), with both linear (p < 0.001) and nonlinear dose-dependent (p = 0.005) relationships.Conclusion: These findings indicate that hippocampal ADC changes during RT are progressive and dose-dependent, with a delayed onset of significant alterations. A threshold dose for detectable structural changes appears to exist, emphasizing the need for further investigation. Additionally, the correlation between ADC alterations and cognitive function will be presented, providing insight into the clinical implications of these microstructural changes and informing hippocampal-sparing RT strategies.