Trial reportJournal of clinical oncology : official journal of the American Society of Clinical Oncology2020
Hippocampal Avoidance During Whole-Brain Radiotherapy Plus Memantine for Patients With Brain Metastases: Phase III Trial NRG Oncology CC001.
Trial report in Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 4 registered trials, which are not on this map. Cited by 458 papers, 8 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Randomized Phase III Trial of Memantine and Whole-Brain Radiotherapy With or Without Hippocampal Avoidance in Patients With Brain Metastases
A Phase 2 Prospective Trial of Hippocampal-Sparing Stereotactic Radiosurgery Treatment of Brain Metastases Using CyberKnife
Memantine to Preserve Memory and Neurocognition Following Craniospinal Irradiation- A Randomised Controlled Trial (MEMENTO)
Application of Bevacizumab Combined With Fractionated Stereotactic Radiotherapy (FSRT-Bev) Versus Hippocampus-Avoidant Whole-Brain Radiotherapy With Simultaneous Integrated Boost (HA-WBRT-SIB) in Patients With Extensive Brain Metastases From Lung Adenocarcinoma: A Phase III Randomized Controlled Trial Evaluating Intracranial Control Efficacy and Neurocognitive Function
Who cites it
458 citing papers in PubMed, 8 syntheses or guidelines pooled it, 797 citations in OpenAlex.
- Brain metastases in triple-negative breast cancer: a systematic review of current trends, treatment strategies, and outcomes.Journal of neuro-oncology · 2026Pooled it
- Pooled it
- Redefining neurocognitive outcomes after radiation for brain metastases: a patient-level meta-analysis of recovery following initial decline.Journal of the National Cancer Institute · 2026Pooled it
- Neurocognitive outcomes in patients with brain metastases: a systematic review.The Lancet. Oncology · 2025Pooled it
- The impact of pituitary adenomas on cognitive performance: a systematic review.Frontiers in endocrinology · 2025Pooled it
- Efficacy and safety evaluation of combined therapies incorporating whole-brain radiotherapy in patients with brain metastases: a systematic review and meta-analysis.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Pooled it
- DEGRO guideline for personalized radiotherapy of brain metastases and leptomeningeal carcinomatosis in patients with breast cancer.Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] · 2024Guideline
- Efficacy and safety of EGFR-TKI combined with WBRT vs. WBRT alone in the treatment of brain metastases from NSCLC: a systematic review and meta-analysis.Frontiers in neurology · 2024Pooled it
- Trial
- Memantine to preserve memory and neurocognition following craniospinal irradiation (MEMENTO): a phase 3 randomized controlled trial.BMC cancer · 2026Trial
- Hypofractionated stereotactic radiotherapy versus whole-brain radiotherapy following brain metastasis resection: Results of the ESTRON randomized phase 2 trial.Neuro-oncology · 2025Trial
- Hippocampal Avoidance During Prophylactic Cranial Irradiation for Patients With Small Cell Lung Cancer: Randomized Phase II/III Trial NRG-CC003.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025Trial
- "Hope" Drives Quality of Life in Patients With Brain Metastases, But, the "Hope Center" Remains Elusive: An Analysis of NRG-CC003.International journal of radiation oncology, biology, physics · 2025Trial
- Trial
- Evaluating the heterogeneity of hippocampal avoidant whole brain radiotherapy treatment effect: A secondary analysis of NRG CC001.Neuro-oncology · 2024Trial
- WF-1801: Single-arm pilot study of ramipril for prevention of radiation-induced cognitive decline in glioblastoma patients receiving chemoradiotherapy.Neuro-oncology practice · 2026Article
- Neural-tumor interactions: bidirectional regulatory mechanisms and nervous system-targeted tumor therapeutic strategies.Biomarker research · 2026Review
- The evolution of RTOG and NRG Oncology CNS tumors clinical trials.Journal of neuro-oncology · 2026Review
- Cancer therapy-related cognitive impairment, part 2: from bench to bedside-and back: why candidate therapies for cancer therapy-related cognitive impairment fail to translate.Pharmacological reports : PR · 2026Review
- Coplanar versus non-coplanar volumetric modulated arc therapy for hippocampal avoidance whole brain radiotherapy using Monte Carlo-based planning system.Radiological physics and technology · 2026Article
398 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
31 authors at 20 institutions in 2 countries.
Funding
Abstract
purposeRadiation 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.
methodsThis 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.
resultsBetween 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;
conclusionHA-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.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.