Genomic profiling is increasingly used for solid tumors in adults and for pediatric brain tumors and blood cancers, allowing treatments to be matched to patients’ mutations. But for children with solid tumors, genomic fingerprinting has been elusive, because these cancers are so varied and individually so rare. Therapies therefore remain non-specific: chemotherapy, surgery, and/or radiation.
A new study, using a newly developed set of clinical-grade tests, now makes the case for genomic profiling of pediatric solid tumors. Applying the tests in a real-time clinical setting, researchers at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center were able to match children, teens, and young adults with a variety of solid tumors to a targeted, precision drug about 70 percent of the time, sometimes improving their outcomes.
Capturing tumors’ genetic fingerprints
Study leaders Alanna Church, MD, associate director of the Laboratory for Molecular Pediatric Pathology (LaMPP) at Boston Children’s Hospital, Laura Corson, PhD, and Katherine A. Janeway, MD, MMSc, director of Clinical Genomics at Dana-Farber and Boston Children’s, combined two clinical-grade tests.
One test, OncoPanel, was previously developed primarily for adult cancer but incorporated input from Janeway, Church, and other pediatric oncologists and pathologists. The other, an RNA sequencing test Church and her colleagues developed for pediatric brain and solid tumors, looks for gene fusions, which are important drivers of pediatric cancers.
As described in Nature Medicine, 345 patients ages 30 and younger from 12 different institutions underwent genomic testing. All had relapsed, refractory, or high-risk extracranial solid tumors. Among them, there were 59 different tumor types, most commonly osteosarcoma, rhabdomyosarcoma, and Ewing sarcoma. Some of the cancers are so rare that they affected just one patient.
Genetically targeted therapy for pediatric solid tumors
Overall, 298 patients (86 percent) had genetic alterations with the potential to influence their care, and in 240 (70 percent), the tumor’s genetic profile could be used to choose a targeted therapy. Oncologists went on to use precision therapies in 29 patients, seven of whom had significant responses. In addition, 209 patients (61 percent) had diagnostically useful findings, and 56 (16 percent) had findings that changed their prognosis. In 17 cases, the identified alterations clarified the patient’s diagnosis.
In contrast to adult cancers, which result from somatic mutations, the most impactful test findings in these youth were gene fusions, in which broken DNA segments fuse together to form an entirely new gene. Six of the seven successfully treated patients in this study had gene fusions.
“It’s an exciting time because there are so many new drugs that can target these fusions and we have new tests that can reliably detect them,” says Church.
A new standard of care?
The study is the most comprehensive to date to show that treatment selection based on genomic profiling is possible for pediatric solid tumors.
“Our study was intended to mimic what would happen in clinical practice — enrolling children in real time, using tests that would be available in clinical laboratories, and returning results,” says Church. “We were able to show a benefit of genomic profiling for a broad range of tumors.”
While not yet widespread elsewhere, such profiling has been standard at Dana-Farber/Boston Children’s for the past several years and has changed day-to-day practice.
“These aren’t the only tests available that could accomplish the same result,” notes Janeway. “What we did was carefully apply a testing strategy and look at the impact. This strategy optimally uses the tumor tissue obtained in the course of routine clinical care. Similar genomic profiling is available in several clinical labs and its cost is relatively low, in the realm of things we do every day in the care of patients with cancer.”
Church and Janeway hope their work will help make genomic profiling a standard of care for new or relapsed pediatric solid tumors, reimbursable by insurance — just as it is for adults.
“We know there are patients who aren’t getting access to these tests because insurance does not reimburse them consistently,” says Church. “We want to broaden access to genomic profiling for every child with a solid tumor.”
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