Trial reportInternational journal of radiation oncology, biology, physics2023
Sustained Preservation of Cognition and Prevention of Patient-Reported Symptoms With Hippocampal Avoidance During Whole-Brain Radiation Therapy for Brain Metastases: Final Results of NRG Oncology CC001.
Trial report in International journal of radiation oncology, biology, physics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 42 papers, 3 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
42 citing papers in PubMed, 3 syntheses or guidelines pooled it, 52 citations in OpenAlex.
- 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
- 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
- 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
- Factors Associated With Perceived Cognitive Dysfunction in Patients With Primary Brain Tumors: The Utility of the Neuro-QoL Cognition Function Scale.Cancer medicine · 2026Observational
- 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
- Methodology of analysis of cognitive impairment in longitudinal randomized clinical trials in oncology: a scoping review.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2026Article
- Review
- Feasibility and utility of a tablet-based digital neurocognitive assessment following radiosurgery for brain metastases.Scientific reports · 2026Article
- Review
- Closed, pumpless microphysiological system with unidirectional flow for co-culture and focal irradiation.RSC advances · 2026Article
- Radiation-Induced Neurodegeneration.Biomedicines · 2026Review
- The evolving landscape of brain metastasis: volume II.Trends in cancer · 2026Review
- Safety and efficacy of delivering systemic treatments concomitantly with whole-brain radiotherapy: a prospective, observational, single-institution study.Exploration of targeted anti-tumor therapy · 2026Article
- Stereotactic versus hippocampal avoidance whole-brain radiotherapy combined with immune checkpoint inhibitors for multiple brain metastases in non-small cell lung cancer: a multi-center retrospective study.Frontiers in oncology · 2026Article
- Prophylactic Cranial Irradiation in Small Cell Lung Cancer: Evolution of Evidence, Current Status, and Future Directions.Current issues in molecular biology · 2025Review
- Radiotherapy-induced neurocognitive decline among adult intracranial tumor patients: A voxel-based approach.Neuro-oncology · 2025Article
- Clinical Parameters Associated With Intracranial Progression Burden Following an Initial Stereotactic Radiosurgery Course in a Multi-institutional Brain Metastases Cohort.Advances in radiation oncology · 2025Article
- Radioprotectors & mitigators in radiation therapy: Harnessing diverse pathways for optimizing clinical outcomes.The Indian journal of medical research · 2025Review
- Repeat stereotactic radiosurgery for recurrent brain metastases: a retrospective comparison of local progression and distant brain metastases after prior radiosurgery.Journal of neuro-oncology · 2025Article
Corrections and comments
- Erratum issued
Authors and funding
19 authors at 16 institutions in 2 countries.
Funding
Abstract
purposeInitial report of NRG Oncology CC001, a phase 3 trial of whole-brain radiation therapy plus memantine (WBRT + memantine) with or without hippocampal avoidance (HA), demonstrated neuroprotective effects of HA with a median follow-up of fewer than 8 months. Herein, we report the final results with complete cognition, patient-reported outcomes, and longer-term follow-up exceeding 1 year. METHODS AND MATERIALS: Adult patients with brain metastases were randomized to HA-WBRT + memantine or WBRT + memantine. The primary endpoint was time to cognitive function failure, defined as decline using the reliable change index on the Hopkins Verbal Learning Test-Revised (HVLT-R), Controlled Oral Word Association, or the Trail Making Tests (TMT) A and B. Patient-reported symptom burden was assessed using the MD Anderson Symptom Inventory with Brain Tumor Module and EQ-5D-5L.
resultsBetween July 2015 and March 2018, 518 patients were randomized. The median follow-up for living patients was 12.1 months. The addition of HA to WBRT + memantine prevented cognitive failure (adjusted hazard ratio, 0.74, P = .016) and was associated with less deterioration in TMT-B at 4 months (P = .012) and HVLT-R recognition at 4 (P = .055) and 6 months (P = .011). Longitudinal modeling of imputed data showed better preservation of all HVLT-R domains (P < .005). Patients who received HA-WBRT + Memantine reported less symptom burden at 6 (P < .001 using imputed data) and 12 months (P = .026 using complete-case data; P < .001 using imputed data), less symptom interference at 6 (P = .003 using complete-case data; P = .0016 using imputed data) and 12 months (P = .0027 using complete-case data; P = .0014 using imputed data), and fewer cognitive symptoms over time (P = .043 using imputed data). Treatment arms did not differ significantly in overall survival, intracranial progression-free survival, or toxicity.
conclusionsWith median follow-up exceeding 1 year, HA during WBRT + memantine for brain metastases leads to sustained preservation of cognitive function and continued prevention of patient-reported neurologic symptoms, symptom interference, and cognitive symptoms with no difference in survival or toxicity.
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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.