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RADI-04. PRETREATMENT VOLUME OF MRI-DETERMINED WHITE MATTER INJURY (WMI) PREDICTS COGNITIVE DECLINE AFTER HIPPOCAMPAL AVOIDANT (HA) WBRT FOR BRAIN METASTASES: SECONDARY ANALYSIS OF NRG ONCOLOGY RTOG 0933
PURPOSE: RTOG 0933 demonstrated benefits to memory following HA-WBRT, supporting the hypothesis of hippocampal radiosensitivity and associated memory specificity. However, some patients demonstrated cognitive decline, suggesting mechanisms outside hippocampal radiosensitivity playing a role. WMI has...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7213231/ http://dx.doi.org/10.1093/noajnl/vdz014.097 |
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author | Bovi, Joseph Pugh, Stephanie Sabesevitz, David Robinson, Clifford Paulson, Eric Mehta, Minesh Gondi, Vinai Kundapur, Vijayananda Pinover, Wayne Chao, Samuel Machtay, Mitchell DeNittis, Albert Laack, Nadia Greenspoon, Jeffrey Mannel, Robert Huang, Jiayi Dominello, Michael Kachnic, Lisa |
author_facet | Bovi, Joseph Pugh, Stephanie Sabesevitz, David Robinson, Clifford Paulson, Eric Mehta, Minesh Gondi, Vinai Kundapur, Vijayananda Pinover, Wayne Chao, Samuel Machtay, Mitchell DeNittis, Albert Laack, Nadia Greenspoon, Jeffrey Mannel, Robert Huang, Jiayi Dominello, Michael Kachnic, Lisa |
author_sort | Bovi, Joseph |
collection | PubMed |
description | PURPOSE: RTOG 0933 demonstrated benefits to memory following HA-WBRT, supporting the hypothesis of hippocampal radiosensitivity and associated memory specificity. However, some patients demonstrated cognitive decline, suggesting mechanisms outside hippocampal radiosensitivity playing a role. WMI has been implicated in RT-induced cognitive decline. This secondary analysis explored the relationship between pre-treatment WMI and memory following HA-WBRT. METHODS AND MATERIALS: 113 patients received HA-WBRT. Standardized cognitive assessments were performed at baseline, 2, 4, and 6 months. The primary endpoint was Hopkins Verbal Learning Test Delayed Recall (HVLT-DR) at 4 mos. Secondary endpoints included HVLT Total Recall (HVLT-TR) and Recognition (HVLT-Recog). Of 113 patients, 34 underwent pre-treatment and 4-month post-treatment HVLT testing and pre-treatment post-contrast volumetric T1 and axial T2/FLAIR MRI. Volumetric analysis of metastatic disease burden and disease-unrelated WMI was conducted on the pre-treatment MRI. Correlational analyses were performed examining the relationship between pre-treatment WMI and HVLT outcomes following HA-WBRT. RESULTS: Correlation was found between larger volumes of pre-treatment WMI and decline in HVLT-Recog (r=.54, p< .05) and a correlational trend was observed between larger volume of pre-treatment WMI and decline in HVLT-DR (r=.31, p=.08). Patients with higher pre-treatment disease burden experienced a greater magnitude of stability or positive shift in HVLT-recall and –delayed recall following HA-WBRT. (r=-.36 and r=-.36, p’s < .05), compared to the magnitude of stability/positive shift in those with lesser disease burden. CONCLUSION: In patients receiving HA-WBRT, pre-treatment-WMI predicts memory decline, suggesting white matter integrity pre-treatment contributes to the pathogenesis of post-WBRT cognitive toxicity independent of hippocampal stem cell radiosensitivity. Less decline or improvement in HVLT following HA-WBRT for patients with higher pre-treatment intracranial metastatic burden supports the importance of WBRT-induced intracranial control on cognition. These imaging biomarkers for cognitive toxicity will be further explored on NRG CC001 and CC003, phase III trials of WBRT with or without HA. |
format | Online Article Text |
id | pubmed-7213231 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-72132312020-07-07 RADI-04. PRETREATMENT VOLUME OF MRI-DETERMINED WHITE MATTER INJURY (WMI) PREDICTS COGNITIVE DECLINE AFTER HIPPOCAMPAL AVOIDANT (HA) WBRT FOR BRAIN METASTASES: SECONDARY ANALYSIS OF NRG ONCOLOGY RTOG 0933 Bovi, Joseph Pugh, Stephanie Sabesevitz, David Robinson, Clifford Paulson, Eric Mehta, Minesh Gondi, Vinai Kundapur, Vijayananda Pinover, Wayne Chao, Samuel Machtay, Mitchell DeNittis, Albert Laack, Nadia Greenspoon, Jeffrey Mannel, Robert Huang, Jiayi Dominello, Michael Kachnic, Lisa Neurooncol Adv Abstracts PURPOSE: RTOG 0933 demonstrated benefits to memory following HA-WBRT, supporting the hypothesis of hippocampal radiosensitivity and associated memory specificity. However, some patients demonstrated cognitive decline, suggesting mechanisms outside hippocampal radiosensitivity playing a role. WMI has been implicated in RT-induced cognitive decline. This secondary analysis explored the relationship between pre-treatment WMI and memory following HA-WBRT. METHODS AND MATERIALS: 113 patients received HA-WBRT. Standardized cognitive assessments were performed at baseline, 2, 4, and 6 months. The primary endpoint was Hopkins Verbal Learning Test Delayed Recall (HVLT-DR) at 4 mos. Secondary endpoints included HVLT Total Recall (HVLT-TR) and Recognition (HVLT-Recog). Of 113 patients, 34 underwent pre-treatment and 4-month post-treatment HVLT testing and pre-treatment post-contrast volumetric T1 and axial T2/FLAIR MRI. Volumetric analysis of metastatic disease burden and disease-unrelated WMI was conducted on the pre-treatment MRI. Correlational analyses were performed examining the relationship between pre-treatment WMI and HVLT outcomes following HA-WBRT. RESULTS: Correlation was found between larger volumes of pre-treatment WMI and decline in HVLT-Recog (r=.54, p< .05) and a correlational trend was observed between larger volume of pre-treatment WMI and decline in HVLT-DR (r=.31, p=.08). Patients with higher pre-treatment disease burden experienced a greater magnitude of stability or positive shift in HVLT-recall and –delayed recall following HA-WBRT. (r=-.36 and r=-.36, p’s < .05), compared to the magnitude of stability/positive shift in those with lesser disease burden. CONCLUSION: In patients receiving HA-WBRT, pre-treatment-WMI predicts memory decline, suggesting white matter integrity pre-treatment contributes to the pathogenesis of post-WBRT cognitive toxicity independent of hippocampal stem cell radiosensitivity. Less decline or improvement in HVLT following HA-WBRT for patients with higher pre-treatment intracranial metastatic burden supports the importance of WBRT-induced intracranial control on cognition. These imaging biomarkers for cognitive toxicity will be further explored on NRG CC001 and CC003, phase III trials of WBRT with or without HA. Oxford University Press 2019-08-12 /pmc/articles/PMC7213231/ http://dx.doi.org/10.1093/noajnl/vdz014.097 Text en © The Author(s) 2019. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Abstracts Bovi, Joseph Pugh, Stephanie Sabesevitz, David Robinson, Clifford Paulson, Eric Mehta, Minesh Gondi, Vinai Kundapur, Vijayananda Pinover, Wayne Chao, Samuel Machtay, Mitchell DeNittis, Albert Laack, Nadia Greenspoon, Jeffrey Mannel, Robert Huang, Jiayi Dominello, Michael Kachnic, Lisa RADI-04. PRETREATMENT VOLUME OF MRI-DETERMINED WHITE MATTER INJURY (WMI) PREDICTS COGNITIVE DECLINE AFTER HIPPOCAMPAL AVOIDANT (HA) WBRT FOR BRAIN METASTASES: SECONDARY ANALYSIS OF NRG ONCOLOGY RTOG 0933 |
title | RADI-04. PRETREATMENT VOLUME OF MRI-DETERMINED WHITE MATTER INJURY (WMI) PREDICTS COGNITIVE DECLINE AFTER HIPPOCAMPAL AVOIDANT (HA) WBRT FOR BRAIN METASTASES: SECONDARY ANALYSIS OF NRG ONCOLOGY RTOG 0933 |
title_full | RADI-04. PRETREATMENT VOLUME OF MRI-DETERMINED WHITE MATTER INJURY (WMI) PREDICTS COGNITIVE DECLINE AFTER HIPPOCAMPAL AVOIDANT (HA) WBRT FOR BRAIN METASTASES: SECONDARY ANALYSIS OF NRG ONCOLOGY RTOG 0933 |
title_fullStr | RADI-04. PRETREATMENT VOLUME OF MRI-DETERMINED WHITE MATTER INJURY (WMI) PREDICTS COGNITIVE DECLINE AFTER HIPPOCAMPAL AVOIDANT (HA) WBRT FOR BRAIN METASTASES: SECONDARY ANALYSIS OF NRG ONCOLOGY RTOG 0933 |
title_full_unstemmed | RADI-04. PRETREATMENT VOLUME OF MRI-DETERMINED WHITE MATTER INJURY (WMI) PREDICTS COGNITIVE DECLINE AFTER HIPPOCAMPAL AVOIDANT (HA) WBRT FOR BRAIN METASTASES: SECONDARY ANALYSIS OF NRG ONCOLOGY RTOG 0933 |
title_short | RADI-04. PRETREATMENT VOLUME OF MRI-DETERMINED WHITE MATTER INJURY (WMI) PREDICTS COGNITIVE DECLINE AFTER HIPPOCAMPAL AVOIDANT (HA) WBRT FOR BRAIN METASTASES: SECONDARY ANALYSIS OF NRG ONCOLOGY RTOG 0933 |
title_sort | radi-04. pretreatment volume of mri-determined white matter injury (wmi) predicts cognitive decline after hippocampal avoidant (ha) wbrt for brain metastases: secondary analysis of nrg oncology rtog 0933 |
topic | Abstracts |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7213231/ http://dx.doi.org/10.1093/noajnl/vdz014.097 |
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