TY - JOUR
T1 - Pretreatment Volume of MRI-Determined White Matter Injury Predicts Neurocognitive Decline After Hippocampal Avoidant Whole-Brain Radiation Therapy for Brain Metastases
T2 - Secondary Analysis of NRG Oncology Radiation Therapy Oncology Group 0933
AU - Bovi, Joseph A.
AU - Pugh, Stephanie L.
AU - Sabsevitz, David
AU - Robinson, Clifford G.
AU - Paulson, Eric
AU - Mehta, Minesh P.
AU - Gondi, Vinai
AU - Kundapur, Vijayananda
AU - Shahin, Mark S.
AU - Chao, Samuel T.
AU - Machtay, Mitch
AU - DeNittis, Albert S.
AU - Laack, Nadia N.
AU - Greenspoon, Jeffrey N.
AU - Moore, Kathleen N.
AU - Huang, Jiayi
AU - Dominello, Michael M.
AU - Kachnic, Lisa A.
N1 - Publisher Copyright:
© 2019
PY - 2019/10/1
Y1 - 2019/10/1
N2 - Purpose: NRG Oncology's RTOG 0933 demonstrated benefits to memory preservation after hippocampal avoidant whole-brain radiation therapy (HA-WBRT), the avoidance of radiation dose to the hippocampus (using intensity modulated radiation planning and delivery techniques) during WBRT, supporting the hypothesis of hippocampal radiosensitivity and associated memory specificity. However, some patients demonstrated cognitive decline, suggesting mechanisms outside hippocampal radiosensitivity play a role. White matter injury (WMI) has been implicated in radiation therapy–induced neurocognitive decline. This secondary analysis explored the relationship between pretreatment WMI and memory after HA-WBRT. Methods and Materials: Volumetric analysis of metastatic disease burden and disease-unrelated WMI was conducted on the pretreatment magnetic resonance image. Correlational analyses were performed examining the relationship between pretreatment WMI and Hopkins Verbal Learning Test-Revised (HVLT-R) outcomes at baseline and 4 months after HA-WBRT. Results: In the study, 113 patients received HA-WBRT. Of 113 patients, 33 underwent pretreatment and 4-month posttreatment HVLT testing and pretreatment postcontrast volumetric T1 and axial T2/fluid-attenuated inversion recovery magnetic resonance imaging. Correlation was found between larger volumes of pretreatment WMI and decline in HVLT-R recognition (r = 0.54, P <.05), and a correlational trend was observed between larger volume of pretreatment WMI and decline in HVLT-R delayed recall (r = 0.31, P =.08). Patients with higher pretreatment disease burden experienced a greater magnitude of stability or positive shift in HVLT-R recall and delayed recall after HA-WBRT (r = –0.36 and r = –0.36, P <.05), compared to the magnitude of stability or positive shift in those with lesser disease burden. Conclusions: In patients receiving HA-WBRT for brain metastases, extent of pretreatment WMI predicts posttreatment memory decline, suggesting a mechanism for radiation therapy–induced neurocognitive toxicity independent of hippocampal stem cell radiosensitivity. Stability or improvement in HVLT after HA-WBRT for patients with higher pretreatment intracranial metastatic burden supports the importance of WBRT-induced intracranial control on neurocognition.
AB - Purpose: NRG Oncology's RTOG 0933 demonstrated benefits to memory preservation after hippocampal avoidant whole-brain radiation therapy (HA-WBRT), the avoidance of radiation dose to the hippocampus (using intensity modulated radiation planning and delivery techniques) during WBRT, supporting the hypothesis of hippocampal radiosensitivity and associated memory specificity. However, some patients demonstrated cognitive decline, suggesting mechanisms outside hippocampal radiosensitivity play a role. White matter injury (WMI) has been implicated in radiation therapy–induced neurocognitive decline. This secondary analysis explored the relationship between pretreatment WMI and memory after HA-WBRT. Methods and Materials: Volumetric analysis of metastatic disease burden and disease-unrelated WMI was conducted on the pretreatment magnetic resonance image. Correlational analyses were performed examining the relationship between pretreatment WMI and Hopkins Verbal Learning Test-Revised (HVLT-R) outcomes at baseline and 4 months after HA-WBRT. Results: In the study, 113 patients received HA-WBRT. Of 113 patients, 33 underwent pretreatment and 4-month posttreatment HVLT testing and pretreatment postcontrast volumetric T1 and axial T2/fluid-attenuated inversion recovery magnetic resonance imaging. Correlation was found between larger volumes of pretreatment WMI and decline in HVLT-R recognition (r = 0.54, P <.05), and a correlational trend was observed between larger volume of pretreatment WMI and decline in HVLT-R delayed recall (r = 0.31, P =.08). Patients with higher pretreatment disease burden experienced a greater magnitude of stability or positive shift in HVLT-R recall and delayed recall after HA-WBRT (r = –0.36 and r = –0.36, P <.05), compared to the magnitude of stability or positive shift in those with lesser disease burden. Conclusions: In patients receiving HA-WBRT for brain metastases, extent of pretreatment WMI predicts posttreatment memory decline, suggesting a mechanism for radiation therapy–induced neurocognitive toxicity independent of hippocampal stem cell radiosensitivity. Stability or improvement in HVLT after HA-WBRT for patients with higher pretreatment intracranial metastatic burden supports the importance of WBRT-induced intracranial control on neurocognition.
UR - http://www.scopus.com/inward/record.url?scp=85070868115&partnerID=8YFLogxK
U2 - 10.1016/j.adro.2019.07.006
DO - 10.1016/j.adro.2019.07.006
M3 - Article
C2 - 31673651
AN - SCOPUS:85070868115
SN - 2452-1094
VL - 4
SP - 579
EP - 586
JO - Advances in Radiation Oncology
JF - Advances in Radiation Oncology
IS - 4
ER -