Advances in genomic sequencing hold enormous opportunities for more precise diagnosis of pediatric cancer and then targeting therapies toward the genetic alterations that are driving individuals’ disease. Yet, researchers must overcome several challenges before precision medicine can improve patients’ outcomes in a meaningful way, according to an editorial published in JAMA co-authored by John Maris, MD, a pediatric oncologist at The Children’s Hospital of Philadelphia, together with post-doctoral fellows Robert Schnepp, MD, PhD, and Kristopher Bosse, MD, also from CHOP.
The commentary addressed results from a study conducted by researchers from the University of Michigan, Ann Arbor, and colleagues appearing in the same issue that included 91 children and young adults with relapsed, refractory, or rare cancer who underwent genetic sequencing and genetic counseling. A multidisciplinary precision medicine tumor board discussed results with families and their physicians and made recommendations when genomic alterations were identified that could be matched to available drug therapies.
The study team found that potentially actionable findings were documented in 42 of 91 cases (46 percent) with sequencing results, and that an action was taken in 23 of these 42 patients (54 percent). Fourteen patients (15 percent) changed therapy, and nine of the 14 with a therapeutic intervention derived clinical benefit.
“This data strongly suggest that precision medicine enhanced by genetic evaluation may improve the outcomes of children with cancer,” the editorial authors stated.
While acknowledging the important contribution of the study results, the editorial authors encouraged cautious optimism because researchers are navigating practical and clinical issues that influence how next-generation sequencing technology may benefit pediatric cancer patients. For example, it can be difficult to obtain high-quality tissue samples from children with relapsed cancer. And then once those tumors are biopsied, the turnaround time until a therapeutic plan can be established may not be quick enough. Meanwhile, the patients’ tumors may progress. The average turnaround time reported by the study team was 53 days.
In order to keep pace with genomic medicine, the editorial authors also called for academic, federal, and industry leaders to develop new models of drug development, as “rare diseases become even more rare” once genetically defined subsets are revealed. Their most troubling concern highlighted by the 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.”