Evidence map›Paper›PMID 25897156›Full record

Trial reportJournal of clinical oncology : official journal of the American Society of Clinical Oncology2015

Donepezil for Irradiated Brain Tumor Survivors: A Phase III Randomized Placebo-Controlled Clinical Trial.

Stephen R Rapp, L Doug Case, Ann Peiffer, Michelle M Naughton, Michael D Chan, Volker W Stieber, Dennis F Moore, Steven C Falchuk, James V Piephoff, William J Edenfield and 3 more

Registry-linked trialOpen access · bronzeAbstract readClinical Trial, Phase IIIRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04343157 (UCSD Image-Guided Cognitive-Sparing Radiosurgery for Brain Metastases), which is not on this map. Cited by 126 papers, 10 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
126citing papers in PubMed, 10 pooled it
21.5field-weighted citation impact, top 1% of its field
1 · What the graph read from 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.

2 · The registry

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.

NCT04343157 phase2recruitingnot on this mapstarted 2019, after this paper: background citation

UCSD Image-Guided Cognitive-Sparing Radiosurgery for Brain Metastases: Avoidance of Eloquent White Matter and Hippocampal Regions

TypeinterventionalSponsorJona Hattangadi-GluthRan2019 to 2028Enrolled60ConditionsBrain Metastases, Adult, Neurocognitive Function, CancerArmsCognitive Sparing Brain Stereotactic Radiosurgery (SRS)
3 · Its place in the literature

Who cites it

126 citing papers in PubMed, 10 syntheses or guidelines pooled it, 268 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. 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] · 2024
    Guideline
  4. Pooled it
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  7. Guideline
  8. Pooled it
  9. Pooled it
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  11. Trial
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  14. Hippocampal Avoidance During Whole-Brain Radiotherapy Plus Memantine for Patients With Brain Metastases: Phase III Trial NRG Oncology CC001.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2020
    Trial
  15. Trial
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  18. Article
  19. 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 · 2026
    Article
  20. Obstacles and Trials in Treating Primary Brain Tumors.International journal of molecular sciences · 2026
    Review

66 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 1 institution in 1 country.

Stephen R RappStephen R. Rapp, L. Doug Case, Ann Peiffer, Michelle M. Naughton, Michael D. Chan, and Edward G. Shaw, Wake Forest School of Medicine and Wake Forest Community Clinical Oncology Program Research Base; Volker W. Stieber, Novant Health System, Winston-Salem, NC; Dennis F. Moore Jr, Wichita Community Clinical Oncology Program, Wichita, KS; Steven C. Falchuk, Christiana Care Health Services, Newark, DE; James V. Piephoff, Mercy Hospital, St Louis, MO; William J. Edenfield and Jeffrey K. Giguere, Cancer Center of Carolinas, Greenville, SC; and Monica E. Loghin, University of Texas MD Anderson Cancer Center, Houston, TX. srapp@wakehealth.edu.
L Doug CaseStephen R. Rapp, L. Doug Case, Ann Peiffer, Michelle M. Naughton, Michael D. Chan, and Edward G. Shaw, Wake Forest School of Medicine and Wake Forest Community Clinical Oncology Program Research Base; Volker W. Stieber, Novant Health System, Winston-Salem, NC; Dennis F. Moore Jr, Wichita Community Clinical Oncology Program, Wichita, KS; Steven C. Falchuk, Christiana Care Health Services, Newark, DE; James V. Piephoff, Mercy Hospital, St Louis, MO; William J. Edenfield and Jeffrey K. Giguere, Cancer Center of Carolinas, Greenville, SC; and Monica E. Loghin, University of Texas MD Anderson Cancer Center, Houston, TX.
Ann PeifferStephen R. Rapp, L. Doug Case, Ann Peiffer, Michelle M. Naughton, Michael D. Chan, and Edward G. Shaw, Wake Forest School of Medicine and Wake Forest Community Clinical Oncology Program Research Base; Volker W. Stieber, Novant Health System, Winston-Salem, NC; Dennis F. Moore Jr, Wichita Community Clinical Oncology Program, Wichita, KS; Steven C. Falchuk, Christiana Care Health Services, Newark, DE; James V. Piephoff, Mercy Hospital, St Louis, MO; William J. Edenfield and Jeffrey K. Giguere, Cancer Center of Carolinas, Greenville, SC; and Monica E. Loghin, University of Texas MD Anderson Cancer Center, Houston, TX.
Michelle M NaughtonStephen R. Rapp, L. Doug Case, Ann Peiffer, Michelle M. Naughton, Michael D. Chan, and Edward G. Shaw, Wake Forest School of Medicine and Wake Forest Community Clinical Oncology Program Research Base; Volker W. Stieber, Novant Health System, Winston-Salem, NC; Dennis F. Moore Jr, Wichita Community Clinical Oncology Program, Wichita, KS; Steven C. Falchuk, Christiana Care Health Services, Newark, DE; James V. Piephoff, Mercy Hospital, St Louis, MO; William J. Edenfield and Jeffrey K. Giguere, Cancer Center of Carolinas, Greenville, SC; and Monica E. Loghin, University of Texas MD Anderson Cancer Center, Houston, TX.
Michael D ChanStephen R. Rapp, L. Doug Case, Ann Peiffer, Michelle M. Naughton, Michael D. Chan, and Edward G. Shaw, Wake Forest School of Medicine and Wake Forest Community Clinical Oncology Program Research Base; Volker W. Stieber, Novant Health System, Winston-Salem, NC; Dennis F. Moore Jr, Wichita Community Clinical Oncology Program, Wichita, KS; Steven C. Falchuk, Christiana Care Health Services, Newark, DE; James V. Piephoff, Mercy Hospital, St Louis, MO; William J. Edenfield and Jeffrey K. Giguere, Cancer Center of Carolinas, Greenville, SC; and Monica E. Loghin, University of Texas MD Anderson Cancer Center, Houston, TX.
Volker W StieberStephen R. Rapp, L. Doug Case, Ann Peiffer, Michelle M. Naughton, Michael D. Chan, and Edward G. Shaw, Wake Forest School of Medicine and Wake Forest Community Clinical Oncology Program Research Base; Volker W. Stieber, Novant Health System, Winston-Salem, NC; Dennis F. Moore Jr, Wichita Community Clinical Oncology Program, Wichita, KS; Steven C. Falchuk, Christiana Care Health Services, Newark, DE; James V. Piephoff, Mercy Hospital, St Louis, MO; William J. Edenfield and Jeffrey K. Giguere, Cancer Center of Carolinas, Greenville, SC; and Monica E. Loghin, University of Texas MD Anderson Cancer Center, Houston, TX.
Dennis F MooreStephen R. Rapp, L. Doug Case, Ann Peiffer, Michelle M. Naughton, Michael D. Chan, and Edward G. Shaw, Wake Forest School of Medicine and Wake Forest Community Clinical Oncology Program Research Base; Volker W. Stieber, Novant Health System, Winston-Salem, NC; Dennis F. Moore Jr, Wichita Community Clinical Oncology Program, Wichita, KS; Steven C. Falchuk, Christiana Care Health Services, Newark, DE; James V. Piephoff, Mercy Hospital, St Louis, MO; William J. Edenfield and Jeffrey K. Giguere, Cancer Center of Carolinas, Greenville, SC; and Monica E. Loghin, University of Texas MD Anderson Cancer Center, Houston, TX.
Steven C FalchukStephen R. Rapp, L. Doug Case, Ann Peiffer, Michelle M. Naughton, Michael D. Chan, and Edward G. Shaw, Wake Forest School of Medicine and Wake Forest Community Clinical Oncology Program Research Base; Volker W. Stieber, Novant Health System, Winston-Salem, NC; Dennis F. Moore Jr, Wichita Community Clinical Oncology Program, Wichita, KS; Steven C. Falchuk, Christiana Care Health Services, Newark, DE; James V. Piephoff, Mercy Hospital, St Louis, MO; William J. Edenfield and Jeffrey K. Giguere, Cancer Center of Carolinas, Greenville, SC; and Monica E. Loghin, University of Texas MD Anderson Cancer Center, Houston, TX.
James V PiephoffStephen R. Rapp, L. Doug Case, Ann Peiffer, Michelle M. Naughton, Michael D. Chan, and Edward G. Shaw, Wake Forest School of Medicine and Wake Forest Community Clinical Oncology Program Research Base; Volker W. Stieber, Novant Health System, Winston-Salem, NC; Dennis F. Moore Jr, Wichita Community Clinical Oncology Program, Wichita, KS; Steven C. Falchuk, Christiana Care Health Services, Newark, DE; James V. Piephoff, Mercy Hospital, St Louis, MO; William J. Edenfield and Jeffrey K. Giguere, Cancer Center of Carolinas, Greenville, SC; and Monica E. Loghin, University of Texas MD Anderson Cancer Center, Houston, TX.
William J EdenfieldStephen R. Rapp, L. Doug Case, Ann Peiffer, Michelle M. Naughton, Michael D. Chan, and Edward G. Shaw, Wake Forest School of Medicine and Wake Forest Community Clinical Oncology Program Research Base; Volker W. Stieber, Novant Health System, Winston-Salem, NC; Dennis F. Moore Jr, Wichita Community Clinical Oncology Program, Wichita, KS; Steven C. Falchuk, Christiana Care Health Services, Newark, DE; James V. Piephoff, Mercy Hospital, St Louis, MO; William J. Edenfield and Jeffrey K. Giguere, Cancer Center of Carolinas, Greenville, SC; and Monica E. Loghin, University of Texas MD Anderson Cancer Center, Houston, TX.
Jeffrey K GiguereStephen R. Rapp, L. Doug Case, Ann Peiffer, Michelle M. Naughton, Michael D. Chan, and Edward G. Shaw, Wake Forest School of Medicine and Wake Forest Community Clinical Oncology Program Research Base; Volker W. Stieber, Novant Health System, Winston-Salem, NC; Dennis F. Moore Jr, Wichita Community Clinical Oncology Program, Wichita, KS; Steven C. Falchuk, Christiana Care Health Services, Newark, DE; James V. Piephoff, Mercy Hospital, St Louis, MO; William J. Edenfield and Jeffrey K. Giguere, Cancer Center of Carolinas, Greenville, SC; and Monica E. Loghin, University of Texas MD Anderson Cancer Center, Houston, TX.
Monica E LoghinStephen R. Rapp, L. Doug Case, Ann Peiffer, Michelle M. Naughton, Michael D. Chan, and Edward G. Shaw, Wake Forest School of Medicine and Wake Forest Community Clinical Oncology Program Research Base; Volker W. Stieber, Novant Health System, Winston-Salem, NC; Dennis F. Moore Jr, Wichita Community Clinical Oncology Program, Wichita, KS; Steven C. Falchuk, Christiana Care Health Services, Newark, DE; James V. Piephoff, Mercy Hospital, St Louis, MO; William J. Edenfield and Jeffrey K. Giguere, Cancer Center of Carolinas, Greenville, SC; and Monica E. Loghin, University of Texas MD Anderson Cancer Center, Houston, TX.
Edward G ShawStephen R. Rapp, L. Doug Case, Ann Peiffer, Michelle M. Naughton, Michael D. Chan, and Edward G. Shaw, Wake Forest School of Medicine and Wake Forest Community Clinical Oncology Program Research Base; Volker W. Stieber, Novant Health System, Winston-Salem, NC; Dennis F. Moore Jr, Wichita Community Clinical Oncology Program, Wichita, KS; Steven C. Falchuk, Christiana Care Health Services, Newark, DE; James V. Piephoff, Mercy Hospital, St Louis, MO; William J. Edenfield and Jeffrey K. Giguere, Cancer Center of Carolinas, Greenville, SC; and Monica E. Loghin, University of Texas MD Anderson Cancer Center, Houston, TX.
Wake Forest University · US

Funding

Wake Forest NCORP Research BaseUG1CA189824 · NCI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI Emily Van Meter Dressler, GLENN J LESSER · 2014 to 2026
$57.9M
Tumor Tissue CoreP30CA012197 · NCI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI Ruben A. Mesa · 1985 to 2026
$55.4M
Comprehensive Cancer Center of Wake Forest University CCOP Research BaseU10CA081851 · NCI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI SHAW, EDWARD G · 1999 to 2013
$22.0M
Phase III Study of Donepezil in the Irradiated BrainR01NR009675 · NINR · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI RAPP, STEPHEN R · 2007 to 2010
$1.4M
NCI NIH HHS 2U10CA081851NCI NIH HHS P30 CA012197NCI NIH HHS U10 CA081851NCI NIH HHS UG1 CA189824NINR NIH HHS 5R01NR009675NINR NIH HHS R01 NR009675
6 · The paper itself

Abstract

purposeNeurotoxic effects of brain irradiation include cognitive impairment in 50% to 90% of patients. Prior studies have suggested that donepezil, a neurotransmitter modulator, may improve cognitive function. PATIENTS AND

methodsA total of 198 adult brain tumor survivors ≥ 6 months after partial- or whole-brain irradiation were randomly assigned to receive a single daily dose (5 mg for 6 weeks, 10 mg for 18 weeks) of donepezil or placebo. A cognitive test battery assessing memory, attention, language, visuomotor, verbal fluency, and executive functions was administered before random assignment and at 12 and 24 weeks. A cognitive composite score (primary outcome) and individual cognitive domains were evaluated.

resultsOf this mostly middle-age, married, non-Hispanic white sample, 66% had primary brain tumors, 27% had brain metastases, and 8% underwent prophylactic cranial irradiation. After 24 weeks of treatment, the composite scores did not differ significantly between groups (P = .48); however, significant differences favoring donepezil were observed for memory (recognition, P = .027; discrimination, P = .007) and motor speed and dexterity (P = .016). Significant interactions between pretreatment cognitive function and treatment were found for cognitive composite (P = .01), immediate recall (P = .05), delayed recall (P = .004), attention (P = .01), visuomotor skills (P = .02), and motor speed and dexterity (P < .001), with the benefits of donepezil greater for those who were more cognitively impaired before study treatment.

conclusionTreatment with donepezil did not significantly improve the overall composite score, but it did result in modest improvements in several cognitive functions, especially among patients with greater pretreatment impairments.

Indexed as

AdultAgedAged, 80 and overBrain NeoplasmsCholinesterase InhibitorsCognition DisordersCombined Modality TherapyDonepezilDouble-Blind MethodFemaleHumansIndansLearningMaleMemoryMiddle AgedCholinesterase InhibitorsDonepezilIndansPiperidines

Identifiers

PMID25897156
PMCPMC4429174
OpenAlexW2154563173

What OpenQuestion holds

Textmetadata
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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.