Any Radiation Dose to the Hippocampus Leads to Local Volume Loss in a Dose-Time-Dependent Way

Nagtegaal, S., David, S., Philippens, M., Leemans, A., Verhoeff, J.

International Journal of Radiation Oncology Biology Physics 105 (1), p. E104-E105


In many progressive non-oncological brain diseases, the rate of hippocampal volume loss determines the severity of the disease. Radiotherapy (RT) has a solid place in the treatment of brain malignancies. However, with increased survival after cancer treatment, subsequent cognitive and executional impairments lead to a marked decrease in the patient’s quality of life after RT. The leading hypothesis of post-RT cognitive decline is that of high susceptibility of the hippocampus (HC) to radiation-induced damage. In this work, we present the results of superior quality MRI volumetric measurements of the HC at different time points in glioma patients treated with RT, under the hypothesis that volume loss relates to applied dose.

From 419 patients, we meticulously selected 15 patients with high quality clinical follow-up scans who were treated with RT for glioma (grade II-IV) in our institution. The CAT12 (Computational Anatomy Toolbox) was used for the automated preprocessing and segmentation of clinical 3T T1 scans. All scans were bias-field inhomogeneity and noise corrected, and then segmented. An expanded PTV volume was censored from analysis. The rate of HC volume loss was determined with non-parametric permutation tests for volume, time, and dose. Doses were converted to EQD2, and age and sex were included as covariates of no interest.

The mean total volume of the HC at baseline was 3989 mm3. The mean total volume loss in 12 months was 245 mm3 (6.6%) and 255 mm3 (6.0%) for the left and right HC respectively. The corrected rates of HC volume loss per Gy are shown in Table 1.

This study shows that the HC is susceptible to radiation-induced volume loss, and that it is dependent on both time and dose. This effect is comparable with HC volume loss and subsequent cognitive and executional impairments in major depression, dementia, and Alzheimer’s disease. The rate in which the HC volume decreases with time and dose may help determine the adequate radiation treatment regimen. In all cases, but especially when the expected survival is years, the dose to the HC should be kept to a minimum, in order to reduce the risk of cognitive decline. Estimated survival can be used to determine a patient tailored safe dose, e.g. 40 Gy for 15 months and 10 Gy for 60 months, in order to prevent mild cognitive impairment. HC sparing should be a crucial aspect in the treatment of brain tumors. Luckily, novel techniques like proton therapy, VMAT and image-guided RT allow for very precise irradiation of the tumor area. Thereby future cognitive symptoms after RT may be diminished further, vastly improving the quality of life of brain tumor patients.