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For Some Children with Cancer, Genomic Information May Help Guide Treatment Decisions

, by NCI Staff

Researchers are testing whether using DNA and RNA sequencing can help manage the care of children and young adults with cancer.

Credit: iStock

Using genomic tools to analyze tumors in children and young adults with difficult-to-treat cancers may help doctors select the most appropriate treatments for some of these patients, a new study suggests.

The study, published September 1 in the Journal of the American Medical Association, tested the feasibility of using DNA and RNA sequencing to help manage the care of children and young adults with rare and aggressive cancers. The approach, increasingly known as precision medicine, aims to identify treatments for patients with cancer based on the specific molecular characteristics of their tumors. 

To begin, researchers at the University of Michigan Comprehensive Cancer Center and the C.S. Mott Children’s Hospital sequenced genetic material from 91 children and young adults with refractory, relapsed, and rare cancers. The median age of participants in the study was 11.5 years old.

Patients had DNA and RNA from their tumors sequenced, as well as DNA from normal cells. The sequencing was limited to the protein-coding genes, or the exomes, where most of the disease-related alterations in childhood cancers are found.

Results of the sequencing studies were reviewed by a precision medicine tumor board. The group—which included oncologists specializing in pediatric and young adult cancers, pathologists, bioinformatics specialists, and genetic counselors—identified what they called “potentially actionable findings” and made recommendations about treatment to families and their physicians.

Potentially actionable findings were defined as  tumor-specific gene changes that could either affect the patient’s diagnosis or identify potential treatment choices, or inherited genetic mutations that could affect the future risk of cancer among patients and their family members.

The doctors were able to act on the sequencing results for 23 of the 91 patients. For 14 patients, sequencing revealed information, such as a genetic mutation, that led to a change in their therapy. Of these patients, nine experienced either a partial or complete remission that lasted for 6 months or longer or remained in remission after the therapy change. Nine patients and families with actionable genetic findings agreed to genetic counseling and screening.

The diagnoses of two patients in the study were changed following the discovery of chromosomal abnormalities in their tumors. In another nine patients, the sequencing revealed an inherited genetic mutation that the researchers concluded was clinically relevant to the patient and, possibly, their family members. All of these patients and their family members agreed to receive formal genetic counseling about future cancer risk.

“We were excited to see an actionable finding in such a substantial percentage of patients, and we think it could potentially be higher over time,” said Arul Chinnaiyan, M.D., Ph.D., director of the Michigan Center for Translational Pathology and the study’s senior author, in a news release.

“These are patients who had exhausted all proven therapeutic options or who had an extremely rare diagnosis,” he continued. “If we can find a clinically actionable event and have a chance to act upon it, we show in this study that it can have a big impact on that patient.”

Dr. Chinnaiyan and his colleagues cautioned, however, that they could not determine whether their approach of sequence-directed disease management had improved the outcomes of the patients compared to the standard of care.

Nonetheless, the study findings “strongly suggest that precision medicine enhanced by genetic evaluation may improve the outcomes of children with cancer,” wrote the authors of an accompanying editorial, Robert W. Schnepp, M.D., Ph.D., Kristopher R. Bosse, M.D., and John M. Maris, M.D., of the University of Pennsylvania and the Children’s Hospital of Philadelphia.   

The study also highlights some challenges associated with using precision medicine approaches in the clinic, they cautioned. For example, the median turnaround time of 53 days from biopsy to an actionable therapeutic plan would need to be shortened considerably “if the information is going to meaningfully guide clinical decisions,” they wrote.

Future next-generation sequencing-based cancer clinical trials, they continued, “should be designed with strict, protocol-defined mutation-drug matches to rigorously test the utility of precision medicine both in patients with refractory disease and with newly diagnosed cancer.”

A “troubling” finding of the new study was the “number of children with currently incurable refractory cancer and a potentially actionable finding in which the investigators simply could not find a drug that might have provided some measure of antitumor benefit,” the editorialists wrote. Lack of information about proper dosing of a drug in children and no appropriate clinical trials for these patients contributed to this problem, they observed.

Nevertheless, the study “represents an important contribution to the care of children with cancer,” Dr. Schnepp and his colleagues concluded. “It makes clear that approaches that are rapidly evolving in adults are applicable to the care of children with cancer.”

Related Resources

Childhood Cancers

NCI and the Precision Medicine Initiative

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