AUTHOR=Jaspers Jaap , Mèndez Romero Alejandra , Hoogeman Mischa S. , van den Bent Martin , Wiggenraad Ruud G. J. , Taphoorn Martin J. B. , Eekers Danielle B. P. , Lagerwaard Frank J. , Lucas Calduch Anna Maria , Baumert Brigitta G. , Klein Martin 

TITLE=Evaluation of the Hippocampal Normal Tissue Complication Model in a Prospective Cohort of Low Grade Glioma Patients—An Analysis Within the EORTC 22033 Clinical Trial

JOURNAL=Frontiers in Oncology

VOLUME=Volume 9 - 2019

YEAR=2019

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2019.00991

DOI=10.3389/fonc.2019.00991

ISSN=2234-943X

ABSTRACT=Purpose:
To evaluate the performance of the hippocampal normal tissue complication model that relates dose to the bilateral hippocampus to memory impairment at 18 months post- treatment in a population of low-grade glioma (LGG) patients. 
Methods: 
LGG patients treated within the radiotherapy-only arm of the EORTC 22033-26033 trial were analyzed. Hippocampal dose parameters were calculated from the original radiotherapy plans. Difference in Rey Verbal Auditory Learning test delayed recall (AVLT-DR) performance pre-and 18 (+/- 4) months post-treatment was compared to reference data from the Maastricht Aging study. The Gondi model was applied to the dosimetric data and model predictions were compared to actual neurocognitive outcome. 
Results: 
A total of 29 patients met inclusion criteria. Mean dose in EQD2 Gy to the bilateral hippocampus was 39.8 Gy (95%CI 34.3–44.4 Gy), the median dose to 40% of the bilateral hippocampus was 47.2 EQD2 Gy. The model predicted a risk of memory impairment exceeding 99% in 22 patients. However, only seven patients were found to have a significant decline in AVLT-dr score. 
Conclusions:
In this dataset of only LGG patients treated with radiotherapy the hippocampus NTCP model did not perform as expected to predict cognitive decline based on dose to 40% of the bilateral hippocampus. Caution should be taken when extrapolating this model outside of the range of dose-volume parameters in which it was developed.