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JAMA. 2015 Sep 1;314(9):913-25. doi: 10.1001/jama.2015.10080.

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

Author information

1
Department of Pediatrics, University of Michigan, Ann Arbor2Michigan Center for Translational Pathology, University of Michigan, Ann Arbor3Comprehensive Cancer Center, University of Michigan, Ann Arbor.
2
Michigan Center for Translational Pathology, University of Michigan, Ann Arbor4Department of Pathology, University of Michigan, Ann Arbor.
3
Michigan Center for Translational Pathology, University of Michigan, Ann Arbor3Comprehensive Cancer Center, University of Michigan, Ann Arbor.
4
Michigan Center for Translational Pathology, University of Michigan, Ann Arbor4Department of Pathology, University of Michigan, Ann Arbor5Howard Hughes Medical Institute, University of Michigan, Ann Arbor.
5
Department of Internal Medicine, Ohio State University, Columbus.
6
Michigan Center for Translational Pathology, University of Michigan, Ann Arbor.
7
Department of Pediatrics, University of Michigan, Ann Arbor.
8
Michigan Center for Translational Pathology, University of Michigan, Ann Arbor7Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts.
9
Department of Radiology, University of Michigan, Ann Arbor.
10
Department of Pathology, University of Michigan, Ann Arbor.
11
Department of Internal Medicine, University of Michigan, Ann Arbor.
12
Department of Health Behavior and Health Education, University of Michigan, Ann Arbor.
13
Department of Pediatrics, University of Michigan, Ann Arbor3Comprehensive Cancer Center, University of Michigan, Ann Arbor.
14
Department of Pediatrics, Michigan State University, East Lansing.
15
Comprehensive Cancer Center, University of Michigan, Ann Arbor.
16
Comprehensive Cancer Center, University of Michigan, Ann Arbor6Department of Internal Medicine, Ohio State University, Columbus.
17
Michigan 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.

Abstract

IMPORTANCE:

Cancer 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.

OBJECTIVE:

To 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 PARTICIPANTS:

Single-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.

RESULTS:

Of 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.

PMID:
26325560
PMCID:
PMC4758114
DOI:
10.1001/jama.2015.10080
[Indexed for MEDLINE]
Free PMC Article

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