TY - JOUR
T1 - 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
AU - Jaspers, Jaap
AU - Romero, Alejandra Mendez
AU - Hoogeman, Mischa S.
AU - van den Bent, Martin
AU - Wiggenraad, Ruud G. J.
AU - Taphoorn, Martin J. B.
AU - Eekers, Danielle B. P.
AU - Lagerwaard, Frank J.
AU - Calduch, Anna Maria Lucas
AU - Baumert, Brigitta G.
AU - Klein, Martin
N1 - Publisher Copyright:
© Copyright © 2019 Jaspers, Mèndez Romero, Hoogeman, van den Bent, Wiggenraad, Taphoorn, Eekers, Lagerwaard, Lucas Calduch, Baumert and Klein.
PY - 2019/10/1
Y1 - 2019/10/1
N2 - 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 NTCP model published by Gondi et al. 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 EQD2Gy to the bilateral hippocampus was 39.8Gy (95% CI 34.3-44.4Gy), the median dose to 40% of the bilateral hippocampus was 47.2 EQD2Gy. 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.
AB - 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 NTCP model published by Gondi et al. 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 EQD2Gy to the bilateral hippocampus was 39.8Gy (95% CI 34.3-44.4Gy), the median dose to 40% of the bilateral hippocampus was 47.2 EQD2Gy. 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.
KW - NTCP (normal tissue complication probability) model
KW - low grade glioma (LGG)
KW - model verification and validation
KW - neurocognition
KW - memory
KW - late effect of cancer treatment
KW - radiotherapy-adverse effects
KW - WHOLE-BRAIN RADIOTHERAPY
KW - CONFORMAL AVOIDANCE
KW - COGNITIVE FUNCTIONS
KW - PLUS PROCARBAZINE
KW - PRESERVATION
KW - CHEMOTHERAPY
KW - VINCRISTINE
KW - SEQUELAE
KW - MEMORY
U2 - 10.3389/fonc.2019.00991
DO - 10.3389/fonc.2019.00991
M3 - Article
C2 - 31681562
SN - 2234-943X
VL - 9
JO - Frontiers in Oncology
JF - Frontiers in Oncology
M1 - 991
ER -