Evidence map›Paper›PMID 34396283›Full record

ArticleJACC. CardioOncology2020

Machine Learning Identifies Clinical and Genetic Factors Associated With Anthracycline Cardiotoxicity in Pediatric Cancer Survivors.

Marie-A Chaix, Neha Parmar, Caroline Kinnear, Myriam Lafreniere-Roula, Oyediran Akinrinade, Roderick Yao, Anastasia Miron, Emily Lam, Guoliang Meng, Anne Christie and 15 more

Registry-linked trialAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in JACC. CardioOncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01805778 (Novel Approaches to the Prediction, Diagnosis and Treatment of Cardiac Late Effects in Survivors of Childhood Cancer), which is not on this map. Cited by 39 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed, 4 pooled it
–field-weighted citation impact
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.

NCT01805778 completednot on this map

Novel Approaches to the Prediction, Diagnosis and Treatment of Cardiac Late Effects in Survivors of Childhood Cancer: A Multi-centre Observational Study

TypeobservationalSponsorThe Hospital for Sick ChildrenRan2012 to 2018Enrolled1,128ConditionsAnthracycline-induced Cardiotoxicity
3 · Its place in the literature

Who cites it

39 citing papers in PubMed, 4 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Article
  6. Review
  7. Review
  8. Review
  9. Article
  10. Article
  11. Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Review
  17. Review
  18. Review
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

25 authors.

Marie-A ChaixGenetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Neha ParmarGenetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Caroline KinnearGenetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Myriam Lafreniere-RoulaTed Rogers Computational Medicine Program, University Health Network, Toronto, Ontario, Canada.
Oyediran AkinrinadeGenetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Roderick YaoGenetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Anastasia MironGenetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Emily LamGenetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Guoliang MengDevelopmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Anne ChristieGenetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Ashok Kumar ManickarajDepartment of Molecular Genetics, University of Toronto, Ontario, Canada.
Stacey MarjerrisonDepartment of Pediatrics, McMaster University Children's Hospital, Hamilton, Ontario, Canada.
Rejane DillenburgDepartment of Pediatrics, McMaster University Children's Hospital, Hamilton, Ontario, Canada.
Mylène BassalDepartment of Pediatrics, Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, Ontario, Canada.
Jane LougheedDepartment of Pediatrics, Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, Ontario, Canada.
Shayna ZelcerDepartment of Pediatrics, Children's Hospital, London Health Sciences Centre, London, Ontario, Canada.
Herschel RosenbergDepartment of Pediatrics, Children's Hospital, London Health Sciences Centre, London, Ontario, Canada.
David HodgsonRadiation Medicine Program, Princess Margaret Cancer Centre, Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada.
Leonard SenderDepartment of Pediatrics, Children's Hospital of Orange County, Orange, California, USA.
Paul KantorDepartment of Pediatrics, Children's Hospital of Los Angeles, Los Angeles, California, USA.
Cedric ManlhiotDepartment of Pediatrics, Johns Hopkins Medical Center, Baltimore, Maryland, USA.
James EllisDevelopmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Luc MertensDepartment of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
Paul C NathanDepartment of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
Seema MitalGenetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDespite known clinical risk factors, predicting anthracycline cardiotoxicity remains challenging.

objectivesThis study sought to develop a clinical and genetic risk prediction model for anthracycline cardiotoxicity in childhood cancer survivors.

methodsWe performed exome sequencing in 289 childhood cancer survivors at least 3 years from anthracycline exposure. In a nested case-control design, 183 case patients with reduced left ventricular ejection fraction despite low-dose doxorubicin (≤250 mg/m

resultsThirty-one genes were differentially enriched for variants between case patients and control patients (p < 0.001). Only 42.6% case patients harbored a variant in these genes compared to 89.6% control patients (odds ratio: 0.09; 95% confidence interval: 0.04 to 0.17; p = 3.98 × 10

conclusionsOur study identified variants in cardiac injury pathway genes that protect against cardiotoxicity and informed the development of a prediction model for delayed anthracycline cardiotoxicity, and it also provided new targets in autophagy genes for the development of cardio-protective drugs. (Preventing Cardiac Sequelae in Pediatric Cancer Survivors [PCS2]; NCT01805778).

Indexed as

anthracyclineAUC, area under the curvecancer survivorshipcardiomyopathyCI, confidence intervalDMSO, dimethyl sulfoxideDOX, doxorubicinechocardiographygenomicsGSEA, gene set enrichment analysisH2AX, H2A family member XhiPSC-CM, human induced pluripotent stem cell–derived cardiomyocyteIC50, half-maximal inhibitory concentrationLVEF, left ventricular ejection fractionLV, left ventricularmachine learningMAF, minor allele frequencymRNA, messenger RNAOR, odds ratioPGP, Personal Genome ProjectRF, random forestrisk predictionSKAT, sequence kernel association testSNV, single-nucleotide variant

Identifiers

PMID34396283
PMCPMC8352204

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

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.