Present status of germline findings in precision medicine for Japanese cancer patients: issues in the current system
Present status of germline findings in precision medicine for Japanese cancer patients: issues in the current system
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日本癌症患者精准医学种系研究的现状：当前系统中的问题
DOI：
10.1093/jjco/hyac046
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发表时间：
2022
影响因子：
2.4
通讯作者：
Seriz
中科院分区：
文献类型：
--
作者：
Higashigawa Satomi;Matsubayashi Hiroyuki;Kiyozumi Yoshimi;Kado Nobuhiro;Nishimura Seiichiro;Oishi Takuma;Sugino Takashi;Fushiki Kunihiro;Shirasu Hiromichi;Yasui Hirofumi;Mamesaya Nobuaki;Fukuzaki Naomi;Kunitomo Kana;Horiuchi Yasue;Kenmotsu Hirotsugu;Seriz
自2019年以来，日本的国家保险已经涵盖了精准癌症医学;然而，迄今为止，生殖系研究结果尚未得到充分报道。本研究的目的是评估日本精准癌症医学的现状，并提出种系发现分析和披露的问题。方法通过病例系列研究，检查了296例晚期癌症病例中52个基因的种系发现。结果Oncoguide™ NCC Oncopanel对6例（2.0%）病例进行了种系检测，但未报告种系发现。剩下的290例（98.0%）病例通过FoundationOne® CDx（仅肿瘤检测）进行分析，该检测识别出404种致病性变异;在16例（5.5%）肿瘤中识别出BRCA 1/2。我们的机构算法在34例病例中提出了39个候选生殖系发现，而公共算法列出了至少91个候选生殖系发现。先前已鉴定出4个生殖系发现（BRCA 1：3和ATM：1）。30例候选生殖系结果（不包括这些已知生殖系结果）病例中有9例拒绝或推迟生殖系检测。在接受咨询的16例患者中，只有4例进行了生殖细胞检测，这4例患者发现了3个生殖细胞检测结果（BRCA 2、CDK 4和RAD 51 C），总共发现了8个（2.7%）生殖细胞检测结果。拒绝遗传咨询和/或生殖细胞检测的原因包括额外的医院就诊，增加生殖细胞检测的费用，由于有限的国家保险覆盖范围，病人的身体状况差，没有已知的家庭成员与可能的生殖细胞finding.ConclusionsIn目前日本精密癌症医学，只有一小部分的患者进行生殖细胞检测，并证明生殖细胞发现。目前的研究结果表明，需要更早的精准癌症药物适应症，更广泛的保险覆盖范围和更有效的生殖细胞发现预测算法，以增加生殖细胞检测的数量并改善后续管理。
ObjectiveSince 2019, precision cancer medicine has been covered by national insurance in Japan; however, to date, germline findings have not been fully reported. The aim of this study was to evaluate the current status and raise a problem of germline finding analysis and disclosure in Japanese precision cancer medicine.MethodsGermline findings of 52 genes were examined in 296 cases with advanced cancer by a case series study.ResultsSix (2.0%) cases were examined by the Oncoguide™ NCC Oncopanel with germline testing, but no germline findings were reported. The remaining 290 (98.0%) cases were analyzed by FoundationOne® CDx (tumor-only testing), which recognized 404 pathogenic variants; those ofBRCA1/2were recognized in 16 (5.5%) tumors. Our institutional algorithm suggested 39 candidate germline findings in 34 cases, while the public algorithm listed at least 91 candidate germline findings. Four germline findings had been previously identified (BRCA1: 3 andATM: 1). Nine of 30 cases with candidate germline findings excluding these known germline findings refused or deferred germline testing. Only 4 of 16 cases that received counseling underwent germline testing, and those 4 revealed 3 germline findings (BRCA2,CDK4andRAD51C); in total, 8 (2.7%) germline findings were revealed. Reasons for refusing genetic counseling and/or germline testing included extra hospital visits, added expense for germline testing due to limited national insurance coverage, poor patient physical condition and no known family members associated with the possible germline finding.ConclusionsIn current Japanese precision cancer medicine, only a small fraction of the patients undergoes germline testing and demonstrated germline finding. The current results suggested a need for earlier indications for precision cancer medicine, broader insurance coverage and more efficient germline finding prediction algorithms, to increase the number of germline testings and to improve the following managements.