ATLANTA (May 16, 2022) – A prospective, observational clinical study using genetic testing of tumors from high-risk pediatric cancer patients at the Aflac Cancer and Blood Disorders Center of Children’s Healthcare of Atlanta shows most patients tested had a genetic alteration in their tumor that could influence their clinical care, according to a new weighted scoring system developed during the study. The results from the first group of patients enrolled in the study were published in the Journal of Clinical Oncology (JCO) Precision Oncology, led by first author Ryan Summers, MD, Pediatric Hematologist/Oncologist.
“To see an overall impact in 85% of patients and to know that genetic sequencing can have an impact beyond just the selection of a targeted therapy was really validating and gratifying,” says Dr. Summers, a member of the Precision Medicine Program. The program aims to provide more personalized therapeutic choices to cancer patients by identifying genetic changes within a tumor cell.
Kelly Goldsmith, MD, Pediatric Hematologist/Oncologist, Clinical Director of the Precision Medicine Program and principal investigator of the study added, “We were pleased to see similar actionable genetic alterations being identified across many different pediatric tumor types. This paves the way for future precision studies in pediatric and adolescent cancer patients, using more targeted and less toxic therapies that are agnostic to the tumor type.”
The study is a description of the Precision Medicine Program’s experience providing DNA whole exome sequencing and RNA sequencing of tumors to 126 patients with high-risk, newly diagnosed, relapsed, or refractory pediatric brain tumors, hematologic malignancies and extracranial solid tumors utilizing the GEM ExTra comprehensive genomic profiling assay. Genetic sequencing determines the order and composition of the four chemical bases that make up DNA and RNA molecules. Genes are made up of DNA, and RNA carries the information from the DNA to create proteins. In tumors, often the order or composition of DNA or RNA is off, leading to genetic changes such as a gene mutation, which may have disease implications.
The team developed a novel scoring system to determine the multi-dimensional impact of the sequencing results on clinical decisions made by patients, parents, and their physicians. This scoring system assigned points to different components of impact from the genetic sequencing results that influenced one of four areas: targeted therapies, cancer predisposition, targeted therapy availability, and refinement of risk stratification or prognosis.
Based on this scoring system, 85% of patients had at least one impactful finding. About 16% of patients identified with a mutation in the study went on to receive a targeted therapy to treat their cancer. The remaining impact was on confirming rare diagnosis, prognosis and helping families understand genetic risks impacting the entire family. Follow up studies will measure outcomes to determine how patients responded to the therapies.
“I’m excited to see how many patients we’ll be able to directly treat with targeted agents as we move forward into the future and this testing becomes more accessible,” says Dr. Summers.
Using a personalized precision medicine approach, from each patient, the team sequenced both a tumor sample and a germline sample from blood or saliva to determine any alterations within their tumor. Reports from the sequencing were then reviewed by a multidisciplinary team called a “molecular tumor board” made up of oncologists, cancer biologists, pathologists, molecular pathologists, cancer geneticists, genetic counselors and bioinformaticians. If there was an alteration and an identified drug to target it, the team evaluated the available evidence supporting the use of that drug in the scientific literature and used their collective expertise to gauge the weight of the evidence. They then made a recommendation to the treating oncologist.
“Sequencing patients has become the standard of clinical care for adult cancer patients, and I’m excited to be a part of the early adoption of this technology in pediatric cancer patients,” said Dr. Summers, who is also an Assistant Professor in the Emory University School of Medicine Department of Pediatrics.
“We are so thankful to CURE Childhood Cancer who have graciously sponsored our Precision Medicine Program since its inception and made this incredible and invaluable resource available to the pediatric cancer patients of Georgia,” added Dr. Goldsmith, who also serves as an Associate Professor in the Emory University School of Medicine Department of Pediatrics.
In addition to findings from the tumor sequencing, the germline sequencing data was also analyzed through a bioinformatics pipeline to identify mutations in cancer predisposition genes. If a patient carries a mutation in one of these genes, they are known to have a risk of developing some type of cancer. The team also looked at genes that may put a patient at risk for cancer immunodeficiency syndromes. Once all germline data was analyzed in a patient and if an alteration was found, the board recommended to the treating oncologist that the patient receive clinically certified testing to validate their findings with a referral to the Cancer Predisposition Program and a genetic counselor. Consistent with other data reported in scientific literature, 7% of patients in this study had a germline finding.