Germline genetic testing trends in pediatric cancer patients: A SEER registry analysis

Germline pathogenic variants (PVs) are reported to occur in 8-16% of pediatric cancer patients, and have important implications for potential treatment modifications, cancer surveillance, and family cascade testing. Data are lacking on the utilization and results of germline testing in pediatric oncology patients. We utilized statewide SEER registry data from California and Georgia to identify patients aged < 19 years diagnosed with cancer between January 1, 2013, and December 31, 2019. Linked germline genetic tests pooled from four laboratories (Ambry Genetics, Bioreference/GeneDx, Labcorp/Invitae, and Myriad Genetics) were reviewed. Results were evaluated by cancer type, demographic information, and year of diagnosis using descriptive and multivariable logistic regression analyses. PV prevalence was assessed by affected gene. Among 16,613 analyzed patients, 344 (2%) underwent germline testing. Testing rate was highest in patients with carcinomas (4.6%) and lowest in those with hematologic malignancies (0.3%). Testing rates increased from 0.7% in 2013 to 4.0% in 2019. Patients in the fifth quintile (highest) socioeconomic level had the highest testing rate (2.9%) (OR 1.58, 95% confidence interval 1.07-2.31, p=0.020 vs. the first quintile (lowest)). Testing was higher in non-Hispanic white and Asian patients compared to other races, however, this was not statistically significant in multivariable analysis. Of the patients who underwent testing, 75/344 (22%) had a germline PV. TP53 was the most frequently tested gene. RB1 and TP53 had the highest yield of PVs amongst patients tested (12/151 and 12/241 respectively). To our knowledge, this is the first population level report of germline genetic testing in pediatric cancer patients. While the rate of germline testing increased significantly from 2013-2019, the rate in 2019 rate remained low at 4%. Higher rates of testing were seen in solid malignancies, which coincides with previous reports of higher germline PV prevalence in solid tumor patients. Germline testing utilization varied by socioeconomic quintile but not by race or ethnicity. These results establish a population-level baseline for germline testing rate and results in pediatric cancer patients; identify testing gaps and disparities; and demonstrate an urgent need for education about germline testing for patients and their families.