scholarly journals Association of pre-treatment hippocampal volume with neurocognitive function in patients treated with hippocampal avoidance whole brain radiotherapy for brain metastases: Secondary analysis of NRG Oncology/RTOG 0933

2021 ◽  
pp. 100859
Author(s):  
Christopher D Abraham ◽  
Stephanie L Pugh ◽  
Joseph A Bovi ◽  
Vinai Gondi ◽  
Minesh P Mehta ◽  
...  
2020 ◽  
Author(s):  
Wen-Chi Yang ◽  
Ya-Fang Chen ◽  
Chi-Cheng Yang ◽  
Pei-Fang Wu ◽  
Hsing-Min Chan ◽  
...  

Abstract Background Hippocampal avoidance whole-brain radiotherapy (HA-WBRT) shows potential for neurocognitive preservation. This study aimed to evaluate whether HA-WBRT or conformal WBRT (C-WBRT) is better for preserving neurocognitive function. Methods This single-blinded randomized phase II trial enrolled patients with brain metastases and randomly assigned them to receive HA-WBRT or C-WBRT. Primary endpoint is decline of the Hopkins Verbal Learning Test–Revised (HVLT-R) delayed recall at 4 months after treatment. Neurocognitive function tests were analyzed with a mixed effect model. Brain progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Results From March 2015 to December 2018, seventy patients were randomized to yield a total cohort of 65 evaluable patients (33 in the HA-WBRT arm and 32 in the C-WBRT arm) with a median follow-up of 12.4 months. No differences in baseline neurocognitive function existed between the 2 arms. The mean change of HVLT-R delayed recall at 4 months was −8.8% in the HA-WBRT arm and +3.8% in the C-WBRT arm (P = 0.31). At 6 months, patients receiving HA-WBRT showed favorable perpetuation of HVLT-R total recall (mean difference = 2.60, P = 0.079) and significantly better preservation of the HVLT-R recognition-discrimination index (mean difference = 1.78, P = 0.019) and memory score (mean difference = 4.38, P = 0.020) compared with patients undergoing C-WBRT. There were no differences in Trail Making Test Part A or Part B or the Controlled Oral Word Association test between the 2 arms at any time point. There were no differences in brain PFS or OS between arms as well. Conclusion Patients receiving HA-WBRT without memantine showed better preservation in memory at 6-month follow-up, but not in verbal fluency or executive function.


2020 ◽  
Author(s):  
Wen-Chi Yang ◽  
Ya-Fang Chen ◽  
Chi-Cheng Yang ◽  
Pei-Fang Wu ◽  
Hsing-Min Chan ◽  
...  

AbstractBackgroundHippocampal avoidance whole-brain radiotherapy (HA-WBRT) shows potential for neurocognitive preservation. This study aimed to evaluate whether HA-WBRT or conformal WBRT is better for preserving neurocognitive function.MethodsThis single-blinded randomized phase II trial enrolled patients with brain metastases and randomly assigned to receive HA-WBRT or conformal WBRT. Primary end point is the decline of Hopkins Verbal Learning Test–Revised (HVLT-R) Delayed Recall at 4 months after treatment. Neurocognitive function tests were analyzed with a mixed effect model. Brain progression free survival (BPFS) and overall survival (OS) were estimated using the Kaplan–Meier method.ResultsPatients were enrolled from March 2015 to December 2018 with a median follow-up of 12.4 months. A total of 70 patients were randomized. No differences in baseline neurocognitive function existed between the two arms. There were no differences in any neurocognitive assessments at four months. At six months, patients receiving HA-WBRT showed favorable perpetuation of HVLT-R total recall (mean difference = 2.60, p = 0.079) and significantly better preservation of the HVLT-R recognition-discrimination index (mean difference = 1.78, p = 0.019) and memory score (mean difference = 4.38, p = 0.020) compared with patients undergoing conformal WBRT. There were no differences in TMT part A, part B, or the COWA test between the two arms at any time point. There were no differences in BPFS or OS between arms as well.ConclusionsPatients receiving HA-WBRT without Memantine showed better preservation in late verbal memory, but not in verbal fluency or executive function.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21096-e21096
Author(s):  
Ruizhe Xu ◽  
Ye Tian ◽  
Bo Zhang

e21096 MRI-based Radiomics signature for the Prediction of Response of Lung Cancer Brain Metastases After Whole-Brain Radiotherapy Background: Local response prediction for brain metastases (BMs) from lung cancer after Whole-Brain Radiotherapy (WBRT) is challenging, as existing criteria are based solely on unidimensional measurements. This study sought to determine whether radiomic features of lung cancer BMs derived from pre-treatment magnetic resonance imaging (MRI) could be used to predict local response following WBRT. Methods: A total of 88 Lung Cancer patients with BMs treated with WBRT were analyzed. After volumes of interest were drawn, 944 radiomic features including first-order, shape, Gray Level Co-occurrence Matrix (GLCM), Gray Level Dependence Matrix (GLDM), Gray Level Run Length Matrix (GLRLM), Gray Level Size Zone Matrix (GLSZM), Neighborhood Gray Tone Difference Matrix (NGTDM), and Laplacian of Gaussian (LoG) features were extracted, using the baseline pre-treatment post-contrast T1 (T1c) and T2 fluid-attenuated inversion recovery (FLAIR) MRI sequences, respectively. Local response status was determined by contrasting the baseline and follow-up MRI according to the RANO-BM criteria. The independent samples t test or Mann-Whitney U test, and then least absolute shrinkage and selection operator (LASSO) were used for dimensionality reduction and feature selection. An adaboost classifier was trained using the selected radiomic features and evaluated using the area under the receiver operating characteristic curve (AUC) in both the training and testing sets. Other discrimination metrics, including classification accuracy, positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity, were also calculated. Results: The optimal radiomics signature was developed based on a multivariable logistic regression with 4, 5, 6 radiomic features on T1c, T2 FLAIR and T1c+T2 FLAIR, respectively. The radiomics model based on T1c features presented the AUC of (0.920 vs. 0.805, respectively) for both the training and testing sets, followed by T2 FLAIR features (0.893 vs. 0.701, respectively), and T1c+T2 FLAIR features (0.971 vs. 0.857, respectively). The classification accuracy of the radiomics model also well predicted the local response of BMs for both the the training and testing sets (T1c: 82.9% vs. 77.8%, T2 FLAIR: 82.9% vs. 77.8%, T1c+T2 FLAIR: 90.0% vs. 77.8%, respectively). Conclusions: Radiomics holds promise for predicting local tumor response following WBRT in patients with lung cancer and brain metastases. A predictive model built on radiomic features from an institutional cohort performed well on cross-validation testing. These results warrant further validation in independent datasets. Such work could prove invaluable for guiding management of individual patients and assessing outcomes of novel interventions.


2020 ◽  
Vol 38 (10) ◽  
pp. 1019-1029 ◽  
Author(s):  
Paul D. Brown ◽  
Vinai Gondi ◽  
Stephanie Pugh ◽  
Wolfgang A. Tome ◽  
Jeffrey S. Wefel ◽  
...  

PURPOSE Radiation dose to the neuroregenerative zone of the hippocampus has been found to be associated with cognitive toxicity. Hippocampal avoidance (HA) using intensity-modulated radiotherapy during whole-brain radiotherapy (WBRT) is hypothesized to preserve cognition. METHODS This phase III trial enrolled adult patients with brain metastases to HA-WBRT plus memantine or WBRT plus memantine. The primary end point was time to cognitive function failure, defined as decline using the reliable change index on at least one of the cognitive tests. Secondary end points included overall survival (OS), intracranial progression-free survival (PFS), toxicity, and patient-reported symptom burden. RESULTS Between July 2015 and March 2018, 518 patients were randomly assigned. Median follow-up for alive patients was 7.9 months. Risk of cognitive failure was significantly lower after HA-WBRT plus memantine versus WBRT plus memantine (adjusted hazard ratio, 0.74; 95% CI, 0.58 to 0.95; P = .02). This difference was attributable to less deterioration in executive function at 4 months (23.3% v 40.4%; P = .01) and learning and memory at 6 months (11.5% v 24.7% [ P = .049] and 16.4% v 33.3% [ P = .02], respectively). Treatment arms did not differ significantly in OS, intracranial PFS, or toxicity. At 6 months, using all data, patients who received HA-WBRT plus memantine reported less fatigue ( P = .04), less difficulty with remembering things ( P = .01), and less difficulty with speaking ( P = .049) and using imputed data, less interference of neurologic symptoms in daily activities ( P = .008) and fewer cognitive symptoms ( P = .01). CONCLUSION HA-WBRT plus memantine better preserves cognitive function and patient-reported symptoms, with no difference in intracranial PFS and OS, and should be considered a standard of care for patients with good performance status who plan to receive WBRT for brain metastases with no metastases in the HA region.


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