胃癌高通量测序临床应用中国专家共识

中国抗癌协会胃癌专业委员会

doi:10.12354/j.issn.1000-8179.2023.20230030

胃癌高通量测序临床应用中国专家共识

doi: 10.12354/j.issn.1000-8179.2023.20230030

中国抗癌协会胃癌专业委员会^,

详细信息

通讯作者:
徐惠绵　xuhuimian@126.com

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出版历程
- 收稿日期: 2023-01-09
- 录用日期: 2023-02-28
- 修回日期: 2023-02-16

Chinese expert consensus on the clinical application of next-generation sequencing for gastric cancer

China Anti-Cancer Association Commitee of Gastric Cancer^,

More Information

Corresponding author: Huimian Xu; E-mail: xuhuimian@126.com

摘要

摘要: 胃癌是消化系统最常见的恶性肿瘤之一，异质性较强，具有复杂的分子特征。HER2、MSI、TMB和NTRK融合等肿瘤相关标志物及分子病理学检测革新了胃癌诊疗模式。根据患者的病理特征和基因检测结果进一步筛选靶向和免疫药物的潜在获益人群，是胃癌精准治疗的未来发展方向。高通量测序（next-generation sequencing，NGS）在胃癌诊断、治疗方案选择、预后监测中发挥着日益重要的作用。然而，国内目前对胃癌NGS的理解与应用尚有不足。中国抗癌协会胃癌专业委员会专家组基于循证医学证据制定《胃癌高通量测序临床应用中国专家共识》，旨在提高中国临床医生与患者对于胃癌NGS的认识，以指导与规范其在国内的临床应用。
- 胃癌 /
- 精准诊疗 /
- 高通量测序 /
- 专家共识
Abstract: Gastric cancer is one of the most common malignant tumors in the digestive system, with high heterogeneity and complex molecular characteristics. The emergence of tumor-associated biomarkers, such as HER2, MSI, TMB, and NTRK fusion, and molecular pathological diagnostics have revolutionized the diagnosis and treatment methods of gastric cancer. Screening potential beneficiaries of targeted therapies and immunotherapies based on pathological characteristics and genetic testing results may be a future direction for developing precise treatments for gastric cancer. Next-generation sequencing (NGS) plays an increasingly important role in diagnosing, selecting treatment strategies, and prognostic monitoring of gastric cancer. However, the NGS of gastric cancer remains poorly understood in China. Hence, China Anti-Cancer Association Commitee of Gastric Cancer formulated the Chinese expert consensus on the NGS of gastric cancer based on evidence-based medicine to improve the understanding of clinicians and patients on the NGS of gastric cancer and to guide and standardize its clinical applications in China.
- gastric cancer /
- precise diagnosis and treatment /
- next-generation sequencing (NGS) /
- expert consensus

HTML全文

表 1 共识推荐等级

推荐等级	证据类别标准
Ⅰ级推荐	基于高级别证据，专家组意见高度一致
Ⅱ级推荐	基于高级别证据，专家组意见基本一致
	基于低级别证据，专家组意见高度一致
Ⅲ级推荐	基于低级别证据，专家组意见基本一致
不推荐	专家组存在意见分歧

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表 2 遗传性胃癌筛查基因

证据来源	遗传性疾病类型	筛查基因
van der Post等^[8]	HDGC	CDH1
Sahasrabudhe等^[9]	HDGC	CTNNA1、PALB2、RAD51C
Li等^[10]	GAPPS	APC
Latham等^[12]	LS	MLH1、MSH2、MSH6、PMS2、EPCAM
MacFarland等^[13]	JPS	SMAD4、BMPR1A
Jiang等^[14]	PJS	STK11
Buckley等^[15]	HBOCS	BRCA1、BRCA2
Dinarvand等^[16]	FAP	APC
Aelvoet等^[17]	MAP	MUTYH
2022 V2版NCCN指南（胃癌证据不足）	共济失调毛细血管扩张症	ATM
2022 V2版NCCN指南（胃癌证据不足）	布鲁姆综合征	BLM/RECQL3
2022 V2版NCCN指南（胃癌证据不足）	李-佛美尼综合征	TP53
2022 V2版NCCN指南（胃癌证据不足）	着色性干皮症	7种不同的基因
2022 V2版NCCN指南（胃癌证据不足）	多发性错构瘤综合征	PTEN

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表 3 NTRK融合检测技术特征和优劣势比较

方法	敏感性	特异性	检测NTRK1/2/3	鉴定融合伴侣	确定表达	筛查
IHC	高^a	高^b	是	否	是	是
FISH	高	高	独立探针^c	否	否	否
RNA-based	高	高	是	是	是	是
DNA-based^*	中等	高	是	是	否	是
^a：假阴性主要来源于NTRK3融合；^b：在没有平滑肌/神经元分化的情况下；^c：NTRK基因的3个亚型需要3组探针；^*：通过基于DNA的方法检测到的重排可能不会导致融合表达。

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表 4 基于NGS的胃癌组织和液态分子检测内容和时机

患者分层	标志物	检测意义	样本类型和推荐等级
Ⅰ～Ⅳ期所有患者	ERBB2扩增	抗HER2靶向治疗疗效预测	组织（Ⅱ级）/血液（Ⅱ级）
Ⅰ～Ⅳ期所有患者	MSI-H	LS遗传评估，早期无法化疗获益，晚期ICIs疗效预测	组织（Ⅰ级）
Ⅰ～Ⅲ期术后辅助治疗	MRD	术后复发监测	血液（Ⅲ级）
Ⅱ～Ⅳ期接受化疗的患者	DPYD基因多态性	氟尿嘧啶剂量调整	血液（Ⅲ级）
Ⅱ～Ⅳ期接受化疗的患者	UGT1A1基因多态性	伊立替康剂量调整	血液（Ⅲ级）
晚期患者治疗阶段	ctDNA	疗效预测和耐药评估	血液（Ⅲ级）
标准治疗失败的晚期患者	NTRK1/2/3融合和点突变	NTRK抑制剂靶向治疗疗效和耐药评估	组织（Ⅱ级）
	TMB	晚期患者ICIs治疗疗效预测	组织（Ⅱ级）
	EBV	ICIs治疗潜在获益，分子分型	组织（Ⅲ级）
	POLE/POLD	ICIs治疗正相关	组织（Ⅲ级）
	TP53、B2M、JAK1/2、PTEN	ICIs治疗负相关	组织（Ⅲ级）
	EGFR/MDM2/MDM4扩增、DNMT3A	ICIs治疗超进展	组织（Ⅲ级）
	RTK-RAS-PI3K突变、CCNE1扩增	抗HER2治疗原发继发耐药	组织（Ⅲ级）
	BRAF V600E	BRAF/MEK抑制剂治疗获益	组织（Ⅲ级）
	FGFR2/EGFR/MET扩增、RET/ROS1/ALK融合	TKIs抑制剂疗效预测	组织（Ⅲ级）
	NRG1融合	NRG1抑制剂疗效评估	组织（Ⅲ级）

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参考文献(72)

[1]	Zheng RS, Zhang SW, Zeng HM, et al. Cancer incidence and mortality in China, 2016[J]. J Natl Cancer Cent, 2022, 2(1):1-9. doi: 10.1016/j.jncc.2022.02.002
[2]	Zeng HM, Chen WQ, Zheng RS, et al. Changing cancer survival in China during 2003-15: a pooled analysis of 17 population-based cancer registries[J]. Lancet Glob Health, 2018, 6(5):e555-e567. doi: 10.1016/S2214-109X(18)30127-X
[3]	中国临床肿瘤学会指南工作委员会.胃癌诊疗指南2022[M].北京:人民卫生出版社,2022:15-17.
[4]	中国抗癌协会.中国肿瘤整合诊治指南-胃癌(2022)[M].天津: 天津科学技术出版社,2022:30-31.
[5]	Ajani JA, D'Amico TA, Bentrem DJ, et al. Gastric cancer, version 2.2022, NCCN clinical practice guidelines in oncology[J]. J Natl Compr Canc Netw, 2022, 20(2):167-192. doi: 10.6004/jnccn.2022.0008
[6]	Yang Y, Zhang WQ, Yao JH, et al. First-line treatment of apatinib in elderly patient of advanced gastric carcinoma: a case report of NGS-driven targeted therapy[J]. Cancer Biol Ther, 2018, 19(5):355-358. doi: 10.1080/15384047.2018.1423917
[7]	Carneiro F, Oliveira C, Seruca R. Pathology and genetics of familial gastric cancer[J]. Int J Surg Pathol, 2010, 18(3 Suppl): 33S-36S.
[8]	van der Post RS, Vogelaar IP, Carneiro F, et al. Hereditary diffuse gastric cancer: updated clinical guidelines with an emphasis on germline CDH1 mutation carriers[J]. J Med Genet, 2015, 52(6):361-374. doi: 10.1136/jmedgenet-2015-103094
[9]	Sahasrabudhe R, Lott P, Bohorquez M, et al. Germline mutations in PALB2, BRCA1, and RAD51C, which regulate DNA recombination repair, in patients with gastric cancer[J]. Gastroenterology, 2017, 152(5):983-986. doi: 10.1053/j.gastro.2016.12.010
[10]	Li J, Woods SL, Healey S, et al. Point mutations in exon 1B of APC reveal gastric adenocarcinoma and proximal polyposis of the stomach as a familial adenomatous polyposis variant[J]. Am J Hum Genet, 2016, 98(5):830-842. doi: 10.1016/j.ajhg.2016.03.001
[11]	Carvalho J, Oliveira P, Senz J, et al. Redefinition of familial intestinal gastric cancer: clinical and genetic perspectives[J]. J Med Genet, 2021, 58(1):1-11. doi: 10.1136/jmedgenet-2019-106346
[12]	Latham A, Srinivasan P, Kemel Y, et al. Microsatellite instability is associated with the presence of lynch syndrome pan-cancer[J]. J Clin Oncol, 2019, 37(4):286-295. doi: 10.1200/JCO.18.00283
[13]	MacFarland SP, Ebrahimzadeh JE, Zelley K, et al. Phenotypic differences in juvenile polyposis syndrome with or without a disease-causing SMAD4/BMPR1A variant[J]. Cancer Prev Res (Phila), 2021, 14(2):215-222. doi: 10.1158/1940-6207.CAPR-20-0348
[14]	Jiang YL, Zhao ZY, Li BR, et al. STK11 gene analysis reveals a significant number of splice mutations in Chinese PJS patients[J]. Cancer Genet, 2019, 230:47-57. doi: 10.1016/j.cancergen.2018.11.008
[15]	Buckley KH, Niccum BA, Maxwell KN, et al. Gastric cancer risk and pathogenesis in BRCA1 and BRCA2 carriers[J]. Cancers (Basel), 2022, 14(23):5953. doi: 10.3390/cancers14235953
[16]	Dinarvand P, Davaro EP, Doan JV, et al. Familial adenomatous polyposis syndrome: an update and review of extraintestinal manifestations[J]. Arch Pathol Lab Med, 2019, 143(11):1382-1398. doi: 10.5858/arpa.2018-0570-RA
[17]	Aelvoet AS, Buttitta F, Ricciardiello L, et al. Management of familial adenomatous polyposis and MUTYH-associated polyposis; new insights[J]. Best Pract Res Clin Gastroenterol, 2022, 58/59:101793. doi: 10.1016/j.bpg.2022.101793
[18]	Bass AJ, Thorsson V, Shmulevich I, et al. Comprehensive molecular characterization of gastric adenocarcinoma[J]. Nature, 2014, 513(7517):202-209
[19]	Cristescu R, Lee J, Nebozhyn M, et al. Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes[J]. Nat Med, 2015, 21(5):449-456. doi: 10.1038/nm.3850
[20]	Sheng WQ, Huang D, Ying JM, et al. HER2 status in gastric cancers: a retrospective analysis from four Chinese representative clinical centers and assessment of its prognostic significance[J]. Ann Oncol, 2013, 24(9):2360-2364. doi: 10.1093/annonc/mdt232
[21]	Zhang LL, Hamdani O, Gjoerup O, et al. ERBB2 copy number as a quantitative biomarker for real-world outcomes to anti-human epidermal growth factor receptor 2 therapy in advanced gastroesophageal adenocarcinoma[J]. JCO Precis Oncol, 2022, 6:e2100330.
[22]	Kuboki Y, Yamashita S, Niwa T, et al. Comprehensive analyses using next-generation sequencing and immunohistochemistry enable precise treatment in advanced gastric cancer[J]. Ann Oncol, 2016, 27(1):127-133. doi: 10.1093/annonc/mdv508
[23]	Ross DS, Zehir A, Cheng DT, et al. Next-generation assessment of human epidermal growth factor receptor 2 (ERBB2) amplification status: clinical validation in the context of a hybrid capture-based, comprehensive solid tumor genomic profiling assay[J]. J Mol Diagn, 2017, 19(2):244-254. doi: 10.1016/j.jmoldx.2016.09.010
[24]	Janjigian YY, Sanchez-Vega F, Jonsson P, et al. Genetic predictors of response to systemic therapy in esophagogastric cancer[J]. Cancer Discov, 2018, 8(1):49-58. doi: 10.1158/2159-8290.CD-17-0787
[25]	Nakamura Y, Kawazoe A, Lordick F, et al. Biomarker-targeted therapies for advanced-stage gastric and gastro-oesophageal junction cancers: an emerging paradigm[J]. Nat Rev Clin Oncol, 2021, 18(8):473-487. doi: 10.1038/s41571-021-00492-2
[26]	Mitani S, Kawakami H. Emerging targeted therapies for HER2 positive gastric cancer that can overcome trastuzumab resistance[J]. Cancers (Basel), 2020, 12(2):400. doi: 10.3390/cancers12020400
[27]	Pietrantonio F, Miceli R, Raimondi A, et al. Individual patient data meta-analysis of the value of microsatellite instability As a biomarker in gastric cancer[J]. J Clin Oncol, 2019, 37(35):3392-3400. doi: 10.1200/JCO.19.01124
[28]	Hause RJ, Pritchard CC, Shendure J, et al. Classification and characterization of microsatellite instability across 18 cancer types[J]. Nat Med, 2016, 22(11):1342-1350. doi: 10.1038/nm.4191
[29]	Salipante SJ, Scroggins SM, Hampel HL, et al. Microsatellite instability detection by next generation sequencing[J]. Clin Chem, 2014, 60(9):1192-1199. doi: 10.1373/clinchem.2014.223677
[30]	Zhang L, Wang YK, Li ZW, et al. Clinicopathological features of tumor mutation burden, Epstein-Barr virus infection, microsatellite instability and PD-L1 status in Chinese patients with gastric cancer[J]. Diagn Pathol, 2021, 16(1):38.
[31]	Sha D, Jin ZH, Budczies J, et al. Tumor mutational burden as a predictive biomarker in solid tumors[J]. Cancer Discov, 2020, 10(12):1808-1825.
[32]	Ritterhouse LL. Tumor mutational burden[J]. Cancer Cytopathol, 2019, 127(12):735-736. doi: 10.1002/cncy.22174
[33]	Merino DM, McShane LM, Fabrizio D, et al. Establishing guidelines to harmonize tumor mutational burden (TMB): in silico assessment of variation in TMB quantification across diagnostic platforms: phase I of the Friends of Cancer Research TMB Harmonization Project[J]. J Immunother Cancer, 2020, 8(1):e000147. doi: 10.1136/jitc-2019-000147
[34]	Samstein RM, Lee CH, Shoushtari AN, et al. Tumor mutational load predicts survival after immunotherapy across multiple cancer types[J]. Nat Genet, 2019, 51(2):202-206. doi: 10.1038/s41588-018-0312-8
[35]	Wang F, Wei XL, Wang FH, et al. Safety, efficacy and tumor mutational burden as a biomarker of overall survival benefit in chemo-refractory gastric cancer treated with toripalimab, a PD-1 antibody in phase Ib/II clinical trial NCT02915432[J]. Ann Oncol, 2019, 30(9):1479-1486. doi: 10.1093/annonc/mdz197
[36]	Marabelle A, Fakih M, Lopez J, et al. Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study[J]. Lancet Oncol, 2020, 21(10):1353-1365. doi: 10.1016/S1470-2045(20)30445-9
[37]	Büttner R, Longshore JW, López-Ríos F, et al. Implementing TMB measurement in clinical practice: considerations on assay requirements[J]. ESMO Open, 2019, 4(1):e000442. doi: 10.1136/esmoopen-2018-000442
[38]	Bai YZ, Xie T, Wang ZH, et al. Efficacy and predictive biomarkers of immunotherapy in Epstein-Barr virus-associated gastric cancer[J]. J Immunother Cancer, 2022, 10(3):e004080. doi: 10.1136/jitc-2021-004080
[39]	Zhu MY, Cui HY, Zhang L, et al. Assessment of POLE and POLD1 mutations as prognosis and immunotherapy biomarkers for stomach adenocarcinoma[J]. Transl Cancer Res, 2022, 11(1):193-205. doi: 10.21037/tcr-21-1601
[40]	Kwon M, Hong JY, Kim ST, et al. Association of serine/threonine kinase 11 mutations and response to programmed cell death 1 inhibitors in metastatic gastric cancer[J]. Pathol Res Pract, 2020, 216(6):152947. doi: 10.1016/j.prp.2020.152947
[41]	Wang JY, Xiu J, Baca Y, et al. Distinct genomic landscapes of gastroesophageal adenocarcinoma depending on PD-L1 expression identify mutations in RAS-MAPK pathway and TP53 as potential predictors of immunotherapy efficacy[J]. Ann Oncol, 2021, 32(7):906-916.
[42]	Champiat S, Dercle L, Ammari S, et al. Hyperprogressive disease is a new pattern of progression in cancer patients treated by anti-PD-1/PD-L1[J]. Clin Cancer Res, 2017, 23(8):1920-1928. doi: 10.1158/1078-0432.CCR-16-1741
[43]	Drilon A, Laetsch TW, Kummar S, et al. Efficacy of larotrectinib in TRK fusion-positive cancers in adults and children[J]. N Engl J Med, 2018, 378(8):731-739. doi: 10.1056/NEJMoa1714448
[44]	Marchiò C, Scaltriti M, Ladanyi M, et al. ESMO recommendations on the standard methods to detect NTRK fusions in daily practice and clinical research[J]. Ann Oncol, 2019, 30(9):1417-1427. doi: 10.1093/annonc/mdz204
[45]	Xu CW, Si L, Wang WX, et al. Expert consensus on the diagnosis and treatment of NTRK gene fusion solid tumors in China[J]. Thorac Cancer, 2022, 13(21):3084-3097. doi: 10.1111/1759-7714.14644
[46]	Cocco E, Schram AM, Kulick A, et al. Resistance to TRK inhibition mediated by convergent MAPK pathway activation[J]. Nat Med, 2019, 25(9):1422-1427. doi: 10.1038/s41591-019-0542-z
[47]	Sun YR, Choong-Kun L, Hyo SK, et al. The first report of K-Umbrella Gastric Cancer Study: An open label, multi-center, randomized, biomarker-integrated trial for second-line treatment of advanced gastric cancer(AGC)[J]. J Clin Oncol, 2022, 40(Suppl_16):abstr 4001.
[48]	Zhou CF, Ma T, Su Y, et al. UGT1A1 gene polymorphisms and the toxicities of FOLFIRI in Chinese Han patients with gastrointestinal cancer[J]. Anticancer Agents Med Chem, 2013, 13(2):235-241. doi: 10.2174/1871520611313020008
[49]	He MM, Zhang DS, Wang F, et al. Phase II trial of S-1 plus leucovorin in patients with advanced gastric cancer and clinical prediction by S-1 pharmacogenetic pathway[J]. Cancer Chemother Pharmacol, 2017, 79(1):69-79.
[50]	Subbiah V, Wolf J, Konda B, et al. Tumour-agnostic efficacy and safety of selpercatinib in patients with RET fusion-positive solid tumours other than lung or thyroid tumours (LIBRETTO-001): a phase 1/2, open-label, basket trial[J]. Lancet Oncol, 2022, 23(10):1261-1273.
[51]	Subbiah V, Lassen U, Élez E, et al. Dabrafenib plus trametinib in patients with BRAF^V600E-mutated biliary tract cancer (ROAR): a phase 2, open-label, single-arm, multicentre basket trial[J]. Lancet Oncol, 2020, 21(9):1234-1243. doi: 10.1016/S1470-2045(20)30321-1
[52]	Wang Y, Shi T, Wang X, et al. FGFR2 alteration as a potential therapeutic target in poorly cohesive gastric carcinoma[J]. J Transl Med, 2021, 19(1):401. doi: 10.1186/s12967-021-03079-8
[53]	Dutton SJ, Ferry DR, Blazeby JM, et al. Gefitinib for oesophageal cancer progressing after chemotherapy (COG): a phase 3, multicentre, double-blind, placebo-controlled randomised trial[J]. Lancet Oncol, 2014, 15(8):894-904. doi: 10.1016/S1470-2045(14)70024-5
[54]	Catenacci DVT, Tebbutt NC, Davidenko I, et al. Rilotumumab plus epirubicin, cisplatin, and capecitabine as first-line therapy in advanced MET-positive gastric or gastro-oesophageal junction cancer (RILOMET-1): a randomised, double-blind, placebo-controlled, phase 3 trial[J]. Lancet Oncol, 2017, 18(11):1467-1482. doi: 10.1016/S1470-2045(17)30566-1
[55]	Pantel K, Alix-Panabières C. Liquid biopsy and minimal residual disease-latest advances and implications for cure[J]. Nat Rev Clin Oncol, 2019, 16(7):409-424. doi: 10.1038/s41571-019-0187-3
[56]	中国抗癌协会肿瘤标志专业委员会.ctDNA高通量测序临床实践专家共识(2022年版)[J].中国癌症防治杂志,2022,14(3):240-252.
[57]	Leal A, van Grieken NCT, Palsgrove DN, et al. White blood cell and cell-free DNA analyses for detection of residual disease in gastric cancer[J]. Nat Commun, 2020, 11(1):525. doi: 10.1038/s41467-020-14310-3
[58]	Yang J, Gong YH, Lam VK, et al. Deep sequencing of circulating tumor DNA detects molecular residual disease and predicts recurrence in gastric cancer[J]. Cell Death Dis, 2020, 11(5):346. doi: 10.1038/s41419-020-2531-z
[59]	Pascual J, Attard G, Bidard FC, et al. ESMO recommendations on the use of circulating tumour DNA assays for patients with cancer: a report from the ESMO Precision Medicine Working Group[J]. Ann Oncol, 2022, 33(8):750-768. doi: 10.1016/j.annonc.2022.05.520
[60]	Wang HX, Li BF, Liu ZT, et al. HER2 copy number of circulating tumour DNA functions as a biomarker to predict and monitor trastuzumab efficacy in advanced gastric cancer[J]. Eur J Cancer, 2018, 88:92-100. doi: 10.1016/j.ejca.2017.10.032
[61]	Nakamura Y, Taniguchi H, Ikeda M, et al. Clinical utility of circulating tumor DNA sequencing in advanced gastrointestinal cancer: SCRUM-Japan GI-SCREEN and GOZILA studies[J]. Nat Med, 2020, 26(12):1859-1864. doi: 10.1038/s41591-020-1063-5
[62]	Pectasides E, Stachler MD, Derks S, et al. Genomic heterogeneity as a barrier to precision medicine in gastroesophageal adenocarcinoma[J]. Cancer Discov, 2018, 8(1):37-48. doi: 10.1158/2159-8290.CD-17-0395
[63]	Maron SB, Chase LM, Lomnicki S, et al. Circulating tumor DNA sequencing analysis of gastroesophageal adenocarcinoma[J]. Clin Cancer Res, 2019, 25(23):7098-7112. doi: 10.1158/1078-0432.CCR-19-1704
[64]	Newman AM, Bratman SV, To J, et al. An ultrasensitive method for quantitating circulating tumor DNA with broad patient coverage[J]. Nat Med, 2014, 20(5):548-554.
[65]	Parikh AR, Mojtahed A, Schneider JL, et al. Serial ctDNA monitoring to predict response to systemic therapy in metastatic gastrointestinal cancers[J]. Clin Cancer Res, 2020, 26(8):1877-1885.
[66]	Zhang Q, Luo J, Wu S, et al. Prognostic and predictive impact of circulating tumor DNA in patients with advanced cancers treated with immune checkpoint blockade[J]. Cancer Discov, 2020, 10(12):1842-1853.
[67]	Wang DS, Liu ZX, Lu YX, et al. Liquid biopsies to track trastuzumab resistance in metastatic HER2-positive gastric cancer[J]. Gut, 2019, 68(7):1152-1161. doi: 10.1136/gutjnl-2018-316522
[68]	Zhang C, Chen ZH, Chong XY, et al. Clinical implications of plasma ctDNA features and dynamics in gastric cancer treated with HER2-targeted therapies[J]. Clin Transl Med, 2020, 10(8):e254.
[69]	Park HJ, Kim KW, Pyo J, et al. Incidence of pseudoprogression during immune checkpoint inhibitor therapy for solid tumors: a systematic review and meta-analysis[J]. Radiology, 2020, 297(1):87-96. doi: 10.1148/radiol.2020200443
[70]	二代测序临床报告解读肿瘤学专家组.肿瘤二代测序临床报告解读共识[J].循证医学,2022,22(2):65-79.
[71]	Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology[J]. Genet Med, 2015, 17(5):405-424. doi: 10.1038/gim.2015.30
[72]	Yu PF, Wang YS, Yu YF, et al. Deep targeted sequencing and its potential implication for cancer therapy in Chinese patients with gastric adenocarcinoma[J]. Oncologist, 2021, 26(5):e756-e768.