Comprehensive genetic panel (CGP) testing generally requires 20% or more percent tumor nuclei (%TN) of the analyzed tissues to achieve assay performance comparable to validated specifications. Pathologists play a crucial role in ensuring that the optimal results are achieved by accurately assigning %TN content of the available specimens and selecting the best material to submit for sequencing. This study addresses the issues in evaluating %TN, such as intra-observer variability, and examines whether focused training and feedback can improve the pathologist performance. Nine referring institution (RI) pathologists (all board-certificated, working at the Core Institute and the alignment hospitals under the National Cancer Genome scheme) evaluated 18 tumors, which had undergone CGP testing with the FoundationOne CDx assay. The %TN estimations by RI pathologists were compared with two standards: %TN assigned by the tumor sequencing institution's (TSI) pathologist (a board-certified pathologist at Foundation Medicine Inc.), and the computational %TN estimated from the mutant allele frequencies after sequencing was completed. The pathologists generally overestimated %TN in the first pre-training round of the evaluation, and the differences in the averaged %TN from the TSI and computational standards were statistically significant. However, the pos-training second-round results became significantly concordant to the standards. This study suggests that %TN content is empirically overestimated but the evaluation skill can be improved by providing a training and feedback program from the testing facility on subsequent specimens.

中文翻译：

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简要报告：计算用于综合癌症面板测试的肿瘤细胞核含量

综合基因组 (CGP) 测试通常需要 20% 或更多百分比的被分析组织的肿瘤细胞核 (%TN) 才能实现与经过验证的规范相当的检测性能。病理学家通过准确分配可用标本的 %TN 含量并选择最佳材料提交测序，在确保获得最佳结果方面发挥着至关重要的作用。这项研究解决了评估 %TN 的问题，例如观察者内部的变异性，并检查集中培训和反馈是否可以提高病理学家的表现。九名转诊机构 (RI) 病理学家（均获得董事会认证，在核心研究所和国家癌症基因组计划下的对齐医院工作）评估了 18 种肿瘤，这些肿瘤已通过 FoundationOne CDx 检测进行了 CGP 测试。RI 病理学家的 %TN 估计值与两个标准进行了比较：由肿瘤测序机构 (TSI) 病理学家（Foundation Medicine Inc. 的董事会认证病理学家）分配的 %TN，以及根据突变等位基因频率估计的计算 %TN测序完成。病理学家通常在第一轮预训练评估中高估了 %TN，与 TSI 和计算标准的平均 %TN 差异具有统计学意义。但是，训练后第二轮结果与标准显着一致。该研究表明，经验上高估了 %TN 含量，但可以通过提供测试设施对后续样本的培训和反馈计划来提高评估技能。