scholarly journals Verification of Low Risk for Perihippocampal Recurrence in Patients with Brain Metastases Who Received Whole-Brain Radiotherapy with Hippocampal Avoidance

2019 ◽  
Vol 51 (2) ◽  
pp. 568-575 ◽  
Author(s):  
Youngkyong Kim ◽  
Sung Hwan Kim ◽  
Jong Hoon Lee ◽  
Dae Gyu Kang
Keyword(s):  
Brain Metastases ◽  
Whole Brain Radiotherapy ◽  
Low Risk ◽  
Whole Brain ◽  
Brain Radiotherapy ◽  
Hippocampal Avoidance

scholarly journals Hippocampal Avoidance During Whole-Brain Radiotherapy Plus Memantine for Patients With Brain Metastases: Phase III Trial NRG Oncology CC001

2020 ◽  
Vol 38 (10) ◽  
pp. 1019-1029 ◽  
Author(s):  
Paul D. Brown ◽  
Vinai Gondi ◽  
Stephanie Pugh ◽  
Wolfgang A. Tome ◽  
Jeffrey S. Wefel ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Brain Metastases ◽  
Whole Brain Radiotherapy ◽  
Phase Iii ◽  
Reliable Change Index ◽  
Whole Brain ◽  
Phase Iii Trial ◽  
Brain Radiotherapy ◽  
Hippocampal Avoidance ◽  
Patient Reported

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.

scholarly journals Hippocampal avoidance whole-brain radiotherapy without memantine in preserving neurocognitive function for brain metastases: a phase II blinded randomized trial

2020 ◽  
Author(s):  
Wen-Chi Yang ◽  
Ya-Fang Chen ◽  
Chi-Cheng Yang ◽  
Pei-Fang Wu ◽  
Hsing-Min Chan ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Phase Ii ◽  
Whole Brain Radiotherapy ◽  
Neurocognitive Function ◽  
Mean Difference ◽  
Whole Brain ◽  
Delayed Recall ◽  
Brain Radiotherapy ◽  
Hippocampal Avoidance

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.

scholarly journals Distribution of brain metastases: low-risk metastasis areas may be avoided when treating with whole-brain radiotherapy

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Binwei Lin ◽  
Dan Huang ◽  
Xiyue Yang ◽  
Yu Zhang ◽  
Feng Gang ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Whole Brain Radiotherapy ◽  
Low Risk ◽  
Whole Brain ◽  
Brain Radiotherapy

scholarly journals Randomised prospective phase II trial in multiple brain metastases comparing outcomes between hippocampal avoidance whole brain radiotherapy with or without simultaneous integrated boost: HA-SIB-WBRT study protocol

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Brendan Seng Hup Chia ◽  
Jing Yun Leong ◽  
Ashley Li Kuan Ong ◽  
Cindy Lim ◽  
Shi Hui Poon ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Whole Brain Radiotherapy ◽  
Target Lesion ◽  
Whole Brain ◽  
Tumour Control ◽  
Multiple Brain Metastases ◽  
Brain Radiotherapy ◽  
Hippocampal Avoidance ◽  
Integrated Boost

Abstract Background Recent evidence supports hippocampal avoidance with whole brain radiotherapy (HA-WBRT) as the recommended treatment option in patients with good prognosis and multiple brain metastases as this results in better neurocognitive preservation compared to whole brain radiotherapy. However, there is often poor tumour control with this technique due to the low doses given. Stereotactic Radiosurgery (SRS), a form of focused radiotherapy which is given to patients who have a limited number of brain metastases, delivers a higher radiation dose to the metastases resulting in better target lesion control. With improvements in radiation technology, advanced dose-painting techniques now allow a simultaneous integrated boost (SIB) dose to lesions whilst minimising doses to the hippocampus to potentially improve brain tumour control and preserve cognitive outcomes. This technique is abbreviated to HA-SIB-WBRT or HA-WBRT+SIB. Methods We hypothesise that the SIB in HA-SIB-WBRT (experimental arm) will result in better tumour control compared to HA-WBRT (control arm). This may also lead to better intracranial disease control as well as functional and survival outcomes. We aim to conduct a prospective randomised phase II trial in patients who have good performance status, multiple brain metastases (4–25 lesions) and a reasonable life expectancy (> 6 months). These patients will be stratified according to the number of brain metastases and randomised between the 2 arms. We aim for a recruitment of 100 patients from a single centre over a period of 2 years. Our primary endpoint is target lesion control. These patients will be followed up over the following year and data on imaging, toxicity, quality of life, activities of daily living and cognitive measurements will be collected at set time points. The results will then be compared across the 2 arms and analysed. Discussion Patients with brain metastases are living longer. Maintaining functional independence and intracranial disease control is thus increasingly important. Improving radiotherapy treatment techniques could provide better control and survival outcomes whilst maintaining quality of life, cognition and functional capacity. This trial will assess the benefits and possible toxicities of giving a SIB to HA-WBRT. Trial registration Clinicaltrials.gov identifier: NCT04452084. Date of registration 30th June 2020.

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