PO.CL06.03 · 临床研究
儿科癌症患者胚系基因检测趋势：一项SEER登记分析
Germline genetic testing trends in pediatric cancer patients: A SEER registry analysis
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
据报道，胚系致病性变异（PV）发生于8-16%的儿科癌症患者，对潜在的治疗方案调整、癌症监测及家系级联检测具有重要意义。目前缺乏关于儿科肿瘤患者胚系检测利用情况及结果的数据。我们利用来自加利福尼亚州和佐治亚州的全州SEER登记数据，识别2013年1月1日至2019年12月31日期间被诊断为癌症、年龄 < 19岁的患者。审阅了汇总自四家实验室（Ambry Genetics、Bioreference/GeneDx、Labcorp/Invitae和Myriad Genetics）的关联胚系基因检测。使用描述性分析及多变量logistic回归分析，按癌症类型、人口统计学信息及诊断年份对结果进行评估。按受累基因评估PV患病率。在16,613例被分析的患者中，344例（2%）接受了胚系检测。癌（carcinoma）患者的检测率最高（4.6%），血液系统恶性肿瘤患者最低（0.3%）。检测率从2013年的0.7%上升至2019年的4.0%。处于第五五分位数（最高）社会经济水平的患者检测率最高（2.9%）（OR 1.58，95%置信区间1.07-2.31，p=0.020，对比第一五分位数（最低））。非西班牙裔白人及亚裔患者的检测率高于其他种族，但在多变量分析中该差异无统计学意义。在接受检测的患者中，75/344（22%）携带胚系PV。TP53是检测频率最高的基因。在受检患者中，RB1和TP53的PV检出率最高（分别为12/151和12/241）。据我们所知，这是首个关于儿科癌症患者胚系基因检测的人群水平报告。虽然胚系检测率从2013年至2019年显著上升，但2019年的检测率仍低至4%。实体恶性肿瘤的检测率较高，这与此前关于实体瘤患者胚系PV患病率较高的报告一致。胚系检测的利用因社会经济五分位数而异，但不因种族或族裔而异。这些结果为儿科癌症患者的胚系检测率及结果建立了人群水平的基线；识别了检测缺口及差异；并证明了对患者及其家庭开展胚系检测教育的迫切需求。
查看英文原文 English abstract
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.
利益披露 Disclosure
C. Johns, None..
M. Huang, None..
R. Hodan, None..
M. McGuinness, None..
A. W. Kurian, None..
R. Saab, None.