Evidence map›Paper›PMID 27197003›Full record

ReviewBritish journal of clinical pharmacology2016

Recommendations for genetic testing to reduce the incidence of anthracycline-induced cardiotoxicity.

Folefac Aminkeng, Colin J D Ross, Shahrad R Rassekh, Soomi Hwang, Michael J Rieder, Amit P Bhavsar, Anne Smith, Shubhayan Sanatani, Karen A Gelmon, Daniel Bernstein and 4 more

Open access · bronzeAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in British journal of clinical pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
114citing papers in PubMed, 4 pooled it
15.9field-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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

114 citing papers in PubMed, 4 syntheses or guidelines pooled it, 230 citations in OpenAlex.

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 6 institutions in 4 countries.

Folefac AminkengCentre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
Colin J D RossChild & Family Research Institute, University of British Columbia, Vancouver, BC, Canada.
Shahrad R RassekhChild & Family Research Institute, University of British Columbia, Vancouver, BC, Canada.
Soomi HwangFaculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada.
Michael J RiederDepartment of Pediatrics, University of Western Ontario, London, ON, Canada.
Amit P BhavsarChild & Family Research Institute, University of British Columbia, Vancouver, BC, Canada.ORCID 0000-0003-3336-9288
Anne SmithChild & Family Research Institute, University of British Columbia, Vancouver, BC, Canada.
Shubhayan SanataniChild & Family Research Institute, University of British Columbia, Vancouver, BC, Canada.
Karen A GelmonBritish Columbia Cancer Agency, Vancouver, BC, Canada.
Daniel BernsteinDepartment of Pediatrics, Division of Cardiology, Stanford University, Stanford, CA, USA.
Michael R HaydenCentre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
Ursula AmstutzChild & Family Research Institute, University of British Columbia, Vancouver, BC, Canada.
Bruce C CarletonChild & Family Research Institute, University of British Columbia, Vancouver, BC, Canada.
CPNDS Clinical Practice Recommendations Group
University of British Columbia · CAAgency for Science, Technology and Research · SGBC Cancer Agency · CAStanford Medicine · USUniversity of Bern · CHWestern University · CA

Funding

CIHR FRN 114403
6 · The paper itself

Abstract

aimsAnthracycline-induced cardiotoxicity (ACT) occurs in 57% of treated patients and remains an important limitation of anthracycline-based chemotherapy. In various genetic association studies, potential genetic risk markers for ACT have been identified. Therefore, we developed evidence-based clinical practice recommendations for pharmacogenomic testing to further individualize therapy based on ACT risk.

methodsWe followed a standard guideline development process, including a systematic literature search, evidence synthesis and critical appraisal, and the development of clinical practice recommendations with an international expert group.

resultsRARG rs2229774, SLC28A3 rs7853758 and UGT1A6 rs17863783 variants currently have the strongest and the most consistent evidence for association with ACT. Genetic variants in ABCC1, ABCC2, ABCC5, ABCB1, ABCB4, CBR3, RAC2, NCF4, CYBA, GSTP1, CAT, SULT2B1, POR, HAS3, SLC22A7, SCL22A17, HFE and NOS3 have also been associated with ACT, but require additional validation. We recommend pharmacogenomic testing for the RARG rs2229774 (S427L), SLC28A3 rs7853758 (L461L) and UGT1A6*4 rs17863783 (V209V) variants in childhood cancer patients with an indication for doxorubicin or daunorubicin therapy (Level B - moderate). Based on an overall risk stratification, taking into account genetic and clinical risk factors, we recommend a number of management options including increased frequency of echocardiogram monitoring, follow-up, as well as therapeutic options within the current standard of clinical practice.

conclusionsExisting evidence demonstrates that genetic factors have the potential to improve the discrimination between individuals at higher and lower risk of ACT. Genetic testing may therefore support both patient care decisions and evidence development for an improved prevention of ACT.

Indexed as

Genetic TestingAnthracyclinesCardiotoxicityEvidence-Based MedicineGenetic Predisposition to DiseaseHumansMultidrug Resistance-Associated Protein 2Risk FactorsABCC2 protein, humanAnthracyclinesMultidrug Resistance-Associated Protein 2anthracyclinecancercardiotoxicityguidelinesheart-failurepharmacogenomics

Identifiers

PMID27197003
PMCPMC5338111
OpenAlexW2385169442

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.