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Incorporating genomic sequencing, counseling into pediatric cancer treatment shows benefit

Date:
September 1, 2015
Source:
JAMA - Journal of the American Medical Association
Summary:
In a study that included children and young adults with relapsed or refractory cancer, incorporation of integrative clinical genomic sequencing data into clinical management was feasible, revealed potentially actionable findings in nearly half of the patients, and was associated with change in treatment and family genetics counseling for a small proportion of patients, according to a study.
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In a study that included children and young adults with relapsed or refractory cancer, incorporation of integrative clinical genomic sequencing data into clinical management was feasible, revealed potentially actionable findings in nearly half of the patients, and was associated with change in treatment and family genetics counseling for a small proportion of patients, according to a study in the September 1 issue of JAMA.

Outcomes of children and young adults with cancer have improved, primarily due to enhanced understanding of tumor biology and due to the clinical application of biological discoveries through multicenter clinical trials. However, survival for many pediatric oncology pa¬tients, including those with recurrent disease or metastatic dis¬ease, remains poor. Advances in genomic sequencing technologies have improved the ability to detect molecular aberrations with greater sensitivity and to identify genomic alterations that can be matched to targeted therapies. However, integrating this data into clinical management in an individualized manner has proven challenging, according to background information in the article.

Arul M. Chinnaiyan, M.D., Ph.D., of the University of Michigan, Ann Arbor, and colleagues studied104 children and young adults (average age, 11 years) with relapsed, refractory, or rare cancer. 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.

Of the 104 screened patients, 102 enrolled with 91 (89 percent) having adequate tumor tissue to complete sequencing. Only the 91 patients were included in all calculations, including 28 (31 percent) with hematological malignancies and 63 (69 percent) with solid tumors. Forty-two patients (46 percent) had actionable findings that changed cancer management: 15 of 28 (54 percent) with hematological malignancies and 27 of 63 (43 percent) with solid tumors. Individualized actions were taken in 23 of the 91 (25 percent) based on clinical sequencing findings, including change in treatment for 14 patients (15 percent) and genetic counseling for 9 patients (10 percent).

Nine of 91 (10 percent) 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.

"Many of these families had no significant family history and would likely have not been referred to genetic counseling under routine clinical care," the authors write. The researchers note that the lack of a control group limited assessing whether better clinical outcomes resulted from integrative clini¬cal sequencing than outcomes that would have occurred with standard care.

Editorial: Improving Patient Outcomes With Cancer Genomics

John M. Maris, M.D., of Children's Hospital of Philadelphia, and colleagues comment on this study in an accompanying editorial.

"The study by Mody and colleagues represents an important contribution to the care of children with cancer. It makes clear that approaches that are rapidly evolving in adults are ap¬plicable to the care of children with cancer. These data strongly suggest that precision medicine enhanced by genetic evalua¬tion may improve the outcomes of children with cancer."


Story Source:

Materials provided by JAMA - Journal of the American Medical Association. Note: Content may be edited for style and length.


Journal References:

  1. Robert W. Schnepp, Kristopher R. Bosse, John M. Maris. Improving Patient Outcomes With Cancer Genomics. JAMA, 2015; 314 (9): 881 DOI: 10.1001/jama.2015.9794
  2. 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, Jonathan R. Dillman, Raja M. Rabah, Laxmi Priya Kunju, Jessica Everett, Victoria M. Raymond, Yu Ning, Fengyun Su, Rui Wang, Elena M. Stoffel, Jeffrey W. Innis, J. Scott Roberts, Patricia L. Robertson, Gregory Yanik, Aghiad Chamdin, James A. Connelly, Sung Choi, Andrew C. Harris, Carrie Kitko, Rama Jasty Rao, John E. Levine, Valerie P. Castle, Raymond J. Hutchinson, Moshe Talpaz, Dan R. Robinson, Arul M. Chinnaiyan. Integrative Clinical Sequencing in the Management of Refractory or Relapsed Cancer in Youth. JAMA, 2015; 314 (9): 913 DOI: 10.1001/jama.2015.10080

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JAMA - Journal of the American Medical Association. "Incorporating genomic sequencing, counseling into pediatric cancer treatment shows benefit." ScienceDaily. ScienceDaily, 1 September 2015. <www.sciencedaily.com/releases/2015/09/150901121001.htm>.
JAMA - Journal of the American Medical Association. (2015, September 1). Incorporating genomic sequencing, counseling into pediatric cancer treatment shows benefit. ScienceDaily. Retrieved May 23, 2017 from www.sciencedaily.com/releases/2015/09/150901121001.htm
JAMA - Journal of the American Medical Association. "Incorporating genomic sequencing, counseling into pediatric cancer treatment shows benefit." ScienceDaily. www.sciencedaily.com/releases/2015/09/150901121001.htm (accessed May 23, 2017).

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