Evidence map›Paper›PMID 26325560›Full record

Observational studyJAMA2015

Integrative Clinical Sequencing in the Management of Refractory or Relapsed Cancer in Youth.

Rajen J Mody, Yi-Mi Wu, Robert J Lonigro, Xuhong Cao, Sameek Roychowdhury, Pankaj Vats, Kevin M Frank, John R Prensner, Irfan Asangani, Nallasivam Palanisamy and 25 more

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

Observational study in JAMA, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 237 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
237citing papers in PubMed, 3 pooled it
17.2field-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

237 citing papers in PubMed, 3 syntheses or guidelines pooled it, 411 citations in OpenAlex.

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  13. Integrated Germline and Somatic Molecular Profiling to Detect Cancer Predisposition Has a High Clinical Impact in Poor-Prognosis Pediatric Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
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177 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

35 authors at 5 institutions in 1 country.

Rajen J ModyDepartment of Pediatrics, University of Michigan, Ann Arbor2Michigan Center for Translational Pathology, University of Michigan, Ann Arbor3Comprehensive Cancer Center, University of Michigan, Ann Arbor.
Yi-Mi WuMichigan Center for Translational Pathology, University of Michigan, Ann Arbor4Department of Pathology, University of Michigan, Ann Arbor.
Robert J LonigroMichigan Center for Translational Pathology, University of Michigan, Ann Arbor3Comprehensive Cancer Center, University of Michigan, Ann Arbor.
Xuhong CaoMichigan Center for Translational Pathology, University of Michigan, Ann Arbor4Department of Pathology, University of Michigan, Ann Arbor5Howard Hughes Medical Institute, University of Michigan, Ann Arbor.
Sameek RoychowdhuryDepartment of Internal Medicine, Ohio State University, Columbus.
Pankaj VatsMichigan Center for Translational Pathology, University of Michigan, Ann Arbor.
Kevin M FrankDepartment of Pediatrics, University of Michigan, Ann Arbor.
John R PrensnerMichigan Center for Translational Pathology, University of Michigan, Ann Arbor7Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts.
Irfan AsanganiMichigan Center for Translational Pathology, University of Michigan, Ann Arbor4Department of Pathology, University of Michigan, Ann Arbor.
Nallasivam PalanisamyMichigan Center for Translational Pathology, University of Michigan, Ann Arbor.
Jonathan R DillmanDepartment of Radiology, University of Michigan, Ann Arbor.
Raja M RabahDepartment of Pathology, University of Michigan, Ann Arbor.
Laxmi Priya KunjuDepartment of Pathology, University of Michigan, Ann Arbor.
Jessica EverettDepartment of Internal Medicine, University of Michigan, Ann Arbor.
Victoria M RaymondDepartment of Internal Medicine, University of Michigan, Ann Arbor.
Yu NingMichigan Center for Translational Pathology, University of Michigan, Ann Arbor.
Fengyun SuMichigan Center for Translational Pathology, University of Michigan, Ann Arbor.
Rui WangMichigan Center for Translational Pathology, University of Michigan, Ann Arbor.
Elena M StoffelDepartment of Internal Medicine, University of Michigan, Ann Arbor.
Jeffrey W InnisDepartment of Pediatrics, University of Michigan, Ann Arbor.
J Scott RobertsDepartment of Health Behavior and Health Education, University of Michigan, Ann Arbor.
Patricia L RobertsonDepartment of Pediatrics, University of Michigan, Ann Arbor3Comprehensive Cancer Center, University of Michigan, Ann Arbor.
Gregory YanikDepartment of Pediatrics, University of Michigan, Ann Arbor3Comprehensive Cancer Center, University of Michigan, Ann Arbor.
Aghiad ChamdinDepartment of Pediatrics, Michigan State University, East Lansing.
James A ConnellyDepartment of Pediatrics, University of Michigan, Ann Arbor3Comprehensive Cancer Center, University of Michigan, Ann Arbor.
Sung ChoiDepartment of Pediatrics, University of Michigan, Ann Arbor3Comprehensive Cancer Center, University of Michigan, Ann Arbor.
Andrew C HarrisDepartment of Pediatrics, University of Michigan, Ann Arbor3Comprehensive Cancer Center, University of Michigan, Ann Arbor.
Carrie KitkoComprehensive Cancer Center, University of Michigan, Ann Arbor.
Rama Jasty RaoDepartment of Pediatrics, University of Michigan, Ann Arbor3Comprehensive Cancer Center, University of Michigan, Ann Arbor.
John E LevineDepartment of Pediatrics, University of Michigan, Ann Arbor3Comprehensive Cancer Center, University of Michigan, Ann Arbor.
Valerie P CastleDepartment of Pediatrics, University of Michigan, Ann Arbor3Comprehensive Cancer Center, University of Michigan, Ann Arbor.
Raymond J HutchinsonDepartment of Pediatrics, University of Michigan, Ann Arbor3Comprehensive Cancer Center, University of Michigan, Ann Arbor.
Moshe TalpazComprehensive Cancer Center, University of Michigan, Ann Arbor6Department of Internal Medicine, Ohio State University, Columbus.
Dan R RobinsonMichigan Center for Translational Pathology, University of Michigan, Ann Arbor4Department of Pathology, University of Michigan, Ann Arbor.
Arul M ChinnaiyanMichigan Center for Translational Pathology, University of Michigan, Ann Arbor3Comprehensive Cancer Center, University of Michigan, Ann Arbor4Department of Pathology, University of Michigan, Ann Arbor5Howard Hughes Medical Institute, University of Michiga.
University of Michigan–Ann Arbor · USMichigan Center for Translational Pathology · USHoward Hughes Medical Institute · USMichigan State University · USThe Ohio State University · US

Funding

Sequencing, Analysis, and Interpretation of SequencingUM1HG006508 · NHGRI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CHINNAIYAN, ARUL M, PIENTA, KENNETH J. · 2013 to 2016
$7.8M
Howard Hughes Medical InstituteNHGRI NIH HHS 1UM1HG006508NHGRI NIH HHS UM1 HG006508
6 · The paper itself

Abstract

importanceCancer is caused by a diverse array of somatic and germline genomic aberrations. Advances in genomic sequencing technologies have improved the ability to detect these molecular aberrations with greater sensitivity. However, integrating them into clinical management in an individualized manner has proven challenging.

objectiveTo evaluate the use of integrative clinical sequencing and genetic counseling in the assessment and treatment of children and young adults with cancer. DESIGN, SETTING, AND

participantsSingle-site, observational, consecutive case series (May 2012-October 2014) involving 102 children and young adults (mean age, 10.6 years; median age, 11.5 years, range, 0-22 years) with relapsed, refractory, or rare cancer. EXPOSURES: Participants underwent integrative clinical exome (tumor and germline DNA) and transcriptome (tumor RNA) sequencing and genetic counseling. Results were discussed by a precision medicine tumor board, which made recommendations to families and their physicians. MAIN OUTCOMES AND MEASURES: Proportion of patients with potentially actionable findings, results of clinical actions based on integrative clinical sequencing, and estimated proportion of patients or their families at risk of future cancer.

resultsOf the 104 screened patients, 102 enrolled with 91 (89%) having adequate tumor tissue to complete sequencing. Only the 91 patients were included in all calculations, including 28 (31%) with hematological malignancies and 63 (69%) with solid tumors. Forty-two patients (46%) had actionable findings that changed their cancer management: 15 of 28 (54%) with hematological malignancies and 27 of 63 (43%) with solid tumors. Individualized actions were taken in 23 of the 91 (25%) based on actionable integrative clinical sequencing findings, including change in treatment for 14 patients (15%) and genetic counseling for future risk for 9 patients (10%). Nine of 91 (10%) of the personalized clinical interventions resulted in ongoing partial clinical remission of 8 to 16 months or helped sustain complete clinical remission of 6 to 21 months. All 9 patients and families with actionable incidental genetic findings agreed to genetic counseling and screening. CONCLUSIONS AND RELEVANCE: In this single-center case series involving young patients with relapsed or refractory cancer, incorporation of integrative clinical sequencing data into clinical management was feasible, revealed potentially actionable findings in 46% of patients, and was associated with change in treatment and family genetic counseling for a small proportion of patients. The lack of a control group limited assessing whether better clinical outcomes resulted from this approach than outcomes that would have occurred with standard care.

Indexed as

Genetic CounselingAdolescentChildChild, PreschoolChromosome AberrationsFamilyFeasibility StudiesGene FusionHematologic NeoplasmsHumansIncidental FindingsInfantInfant, NewbornMolecular Targeted TherapyNeoplasm Recurrence, LocalNeoplasms

Identifiers

PMID26325560
PMCPMC4758114
OpenAlexW1911918948

What OpenQuestion holds

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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.