2024年《NCCN胃癌临床实践指南》更新要点解读

doi:10.12114/j.issn.1007-9572.2024.0405

摘要/Abstract

摘要： 2024年，美国国立综合癌症网络（NCCN）先后更新了3版《胃癌临床实践指南》。这些更新内容涵盖了胃癌诊疗和随访监测的多个关键领域，不仅提升了二代测序在胃癌精准治疗中的地位，完善了新增EB病毒（EBV）检测和晚期一线免疫治疗的限定条件，还调整了新辅助免疫治疗术前用药的周期，新增了一种神经营养酪氨酸受体激酶（NTRK）靶向治疗药物，并细化了术后营养缺乏监测和补充的项目，更为重要的是首次增加了早期胃癌的内镜治疗和晚期胃癌单一腹膜转移的诊疗路径，并较为详细地阐述了几个新兴的外科联合腹腔内治疗的应用原则。更新的内容充分体现了精准化、个体化、多学科治疗的趋势。本文将对指南中有关诊断、外科治疗、系统治疗、随访监测等方面进行重点解读，以期为临床实践提供指导和帮助。

关键词: 胃癌, 美国国立综合癌症网络, 临床实践指南, 治疗, 随访, 更新

Abstract:

In 2024, the National Comprehensive Cancer Network (NCCN) has updated three editions of the Clinical Practice Guidelines for Gastric Cancer. These updates encompass multiple crucial areas of diagnosis, treatment, and follow-up monitoring for gastric cancer. It elevates the significance of next-generation sequencing in precision therapy for gastric cancer, refines the limitations for Epstein-Barr virus (EBV) testing and first-line immunotherapy in advanced stages. Adjustments have been made to the preoperative medication cycle for neoadjuvant immunotherapy, a new NTRK-targeted therapy drug was added in the second-line therapy, and a more detailed approach to postoperative monitoring and supplementation for nutritional deficiencies has been introduced. Notably, this version marks the first inclusion of endoscopic treatment pathways for early-stage gastric cancer and diagnostic and treatment pathways for single peritoneal metastasis in advanced gastric cancer. Additionally, it provides a comprehensive elaboration on the application principles of several emerging surgical techniques combined with intraperitoneal treatments. The updated content fully embodies the trend towards precision, personalized, and multidisciplinary treatment. This article will focus on the diagnosis, surgical treatment, systemic treatment, follow-up monitoring and other aspects of the guideline, in order to provide guidance and help for clinical practice.

Key words: Stomach neoplasms, NCCN, Clinical practice guidelines, Treatment, Follow-up, Update

中图分类号:

R 735.2

马桂芬,章倩,孙菁. 2024年《NCCN胃癌临床实践指南》更新要点解读[J]. 中国全科医学, 2025, 28(14): 1681-1688. DOI: 10.12114/j.issn.1007-9572.2024.0405.
MA Guifen,ZHANG Qian,SUN Jing. Interpretation of the Key Updates in the Latest Version of 2024 NCCN Clinical Practice Guidelines for Gastric Cancer[J]. Chinese General Practice, 2025, 28(14): 1681-1688. DOI: 10.12114/j.issn.1007-9572.2024.0405.

参考文献 63

[16]	SETIA N, AHN S, HAN H S, et al. Predictive value of WHO classification for PD-L1 and Her2/Neu expression and distinct associations with protein expression based classification in gastric carcinoma[J]. Hum Pathol，2019，94：64-70. DOI：10.1016/j.humpath.2019.10.008.
[17]	KANG W, TO K F. Are epstein-barr virus-positive and-negative gastric carcinomas，with lymphoid stroma，single entity or different entities?[J]. Clin Gastroenterol Hepatol，2015，13(10)：1745-1747. DOI：10.1016/j.cgh.2015.06.024.
[18]	NAKANO H, SAITO M, NAKAJIMA S, et al. PD-L1 overexpression in EBV-positive gastric cancer is caused by unique genomic or epigenomic mechanisms[J]. Sci Rep，2021，11(1)：1982. DOI：10.1038/s41598-021-81667-w.
[19]	HISSONG E, RAMRATTAN G, ZHANG P, et al. Gastric carcinomas with lymphoid stroma：an evaluation of the histopathologic and molecular features[J]. Am J Surg Pathol，2018，42(4)：453-462. DOI：10.1097/PAS.0000000000001018.
[20]	Information Committee of The Korean Gastric Cancer Association. Korean gastric cancer association-led nationwide survey on surgically treated gastric cancers in 2019[J]. J Gastric Cancer，2021，21(3)：221-235. DOI：10.5230/jgc.2021.21.e27.
[21]	KAKEJI Y, ISHIKAWA T, SUZUKI S, et al. A retrospective 5-year survival analysis of surgically resected gastric cancer cases from the Japanese Gastric Cancer Association nationwide registry（2001-2013）[J]. Gastric Cancer，2022，25(6)：1082-1093. DOI：10.1007/s10120-022-01317-6.
[22]	王胤奎，李子禹，陕飞，等. 我国早期胃癌的诊治现状——来自中国胃肠肿瘤外科联盟数据的启示[J]. 中华胃肠外科杂志，2018，21(2)：168-174. DOI：10.3760/cma.j.issn.1671-0274.2018.02.010.
[23]	ASGE Standards of Practice Committee, FORBES N, ELHANAFI S E, et al. American Society for Gastrointestinal Endoscopy guideline on endoscopic submucosal dissection for the management of early esophageal and gastric cancers：summary and recommendations[J]. Gastrointest Endosc，2023，98(3)：271-284. DOI：10.1016/j.gie.2023.03.015.
[24]	PIMENTEL-NUNES P, LIBÂNIO D, BASTIAANSEN B A J, et al. Endoscopic submucosal dissection for superficial gastrointestinal lesions：European Society of Gastrointestinal Endoscopy（ESGE）Guideline-Update 2022[J]. Endoscopy，2022，54(6)：591-622. DOI：10.1055/a-1811-7025.
[25]	HASUIKE N, ONO H, BOKU N, et al. A non-randomized confirmatory trial of an expanded indication for endoscopic submucosal dissection for intestinal-type gastric cancer（cT1a）：the Japan Clinical Oncology Group study（JCOG0607）[J]. Gastric Cancer，2018，21(1)：114-123.
[1]	BRAY F, LAVERSANNE M, SUNG H, et al. Global cancer statistics 2022：GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin，2024，74(3)：229-263. DOI：10.3322/caac.21834.
[2]	郑荣寿，陈茹，韩冰峰，等. 2022年中国恶性肿瘤流行情况分析[J]. 中华肿瘤杂志，2024，46(3)：221-231. DOI：10.3760/cma.j.cn112152-20240119-00035.
[3]	ZENG H M, ZHENG R S, SUN K X, et al. Cancer survival statistics in China 2019-2021：a multicenter，population-based study[J]. J Natl Cancer Cent，2024，4(3)：203-213. DOI：10.1016/j.jncc.2024.06.005.
[4]	SALIPANTE S J, SCROGGINS S M, HAMPEL H L, et al. Microsatellite instability detection by next generation sequencing[J]. Clin Chem，2014，60(9)：1192-1199. DOI：10.1373/clinchem.2014.223677.
[5]	ZHANG L, WANG Y K, LI Z W, 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. DOI：10.1186/s13000-021-01099-y.
[6]	BÜTTN2ER R, LONGSHORE J W, 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.
[7]	RHA S Y, LEE C K, KIM H S, 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(16_suppl)：4001. DOI：10.1200/jco.2022.40.16_suppl.4001.
[8]	中国抗癌协会肿瘤精准治疗专业委员会，沈琳. 二代测序技术在消化系统肿瘤临床应用的中国专家共识[J]. 肿瘤综合治疗电子杂志，2024，10(1)：69-92. DOI：10.12151/JMCM.2024.01-11.
[9]	中国抗癌协会胃癌专业委员会. 胃癌高通量测序临床应用中国专家共识[J]. 中国肿瘤临床，2023，50(6)：309-318. DOI：10.12354/j.issn.1000-8179.2023.20230030.
[10]	SOUSA H, PINTO-CORREIA A L, MEDEIROS R, et al. Epstein-Barr virus is associated with gastric carcinoma：the question is what is the significance?[J]. World J Gastroenterol，2008，14(27)：4347-4351. DOI：10.3748/wjg.14.4347.
[26]	TAKIZAWA K, ONO H, HASUIKE N, et al. A nonrandomized，single-arm confirmatory trial of expanded endoscopic submucosal dissection indication for undifferentiated early gastric cancer：Japan Clinical Oncology Group study（JCOG1009/1010）[J]. Gastric Cancer，2021，24(2)：479-491.
[27]	ZHENG Z, YIN J, LI Z Y, et al. Protocol for expanded indications of endoscopic submucosal dissection for early gastric cancer in China：a multicenter，ambispective，observational，open-cohort study[J]. BMC Cancer，2020，20(1)：801. DOI：10.1186/s12885-020-07312-3.
[28]	中国抗癌协会胃癌专业委员会. 胃癌腹膜转移诊治中国专家共识（2023版）[J]. 中华胃肠外科杂志，2023，26(8)：717-728. DOI：10.3760/cma.j.cn441530-20230608-00196.
[29]	GONG Y B, WANG P L, ZHU Z, et al. Benefits of surgery after neoadjuvant intraperitoneal and systemic chemotherapy for gastric cancer patients with peritoneal metastasis：a meta-analysis[J]. J Surg Res，2020，245：234-243. DOI：10.1016/j.jss.2019.07.044.
[30]	BADGWELL B, BLUM M, DAS P, et al. PhaseⅡ trial of laparoscopic hyperthermic intraperitoneal chemoperfusion for peritoneal carcinomatosis or positive peritoneal cytology in patients with gastric adenocarcinoma[J]. Ann Surg Oncol，2017，24(11)：3338-3344. DOI：10.1245/s10434-017-6047-4.
[31]	YONEMURA Y, ISHIBASHI H, HIRANO M, et al. Effects of neoadjuvant laparoscopic hyperthermic intraperitoneal chemotherapy and neoadjuvant intraperitoneal/systemic chemotherapy on peritoneal metastases from gastric cancer[J]. Ann Surg Oncol，2017，24(2)：478-485. DOI：10.1245/s10434-016-5487-6.
[32]	YANG X J, HUANG C Q, SUO T, et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy improves survival of patients with peritoneal carcinomatosis from gastric cancer：final results of a phaseⅢ randomized clinical trial[J]. Ann Surg Oncol，2011，18(6)：1575-1581.
[33]	BONNOT P E, PIESSEN G, KEPENEKIAN V, et al. Cytoreductive Surgery with or without Hyperthermic Intraperitoneal Chemotherapy for Gastric Cancer With Peritoneal Metastases（CYTO-CHIP study）：a Propensity Score Analysis[J]. J Clin Oncol，2019，37(23)：2028-2040.
[34]	ALYAMI M, BONNOT P E, MERCIER F, et al. Pressurized intraperitoneal aerosol chemotherapy（PIPAC）for unresectable peritoneal metastasis from gastric cancer[J]. Eur J Surg Oncol，2021，47(1)：123-127. DOI：10.1016/j.ejso.2020.05.021.
[11]	JÁCOME A A, LIMA E M, KAZZI A I, et al. Epstein-Barr virus-positive gastric cancer：a distinct molecular subtype of the disease?[J]. Rev Soc Bras Med Trop，2016，49(2)：150-157. DOI：10.1590/0037-8682-0270-2015.
[12]	NETWORK C G A R. Comprehensive molecular characterization of gastric adenocarcinoma[J]. Nature，2014，513(7517)：202-209. DOI：10.1038/nature13480.
[13]	SASAKI S, NISHIKAWA J, SAKAI K, et al. EBV-associated gastric cancer evades T-cell immunity by PD-1/PD-L1 interactions[J]. Gastric Cancer，2019，22(3)：486-496.
[14]	KONDO A, SHINOZAKI-USHIKU A, ROKUTAN H, et al. Loss of viral genome with altered immune microenvironment during tumour progression of Epstein-Barr virus-associated gastric carcinoma[J]. J Pathol，2023，260(2)：124-136. DOI：10.1002/path.6067.
[15]	LIM H, PARK Y S, LEE J H, et al. Features of gastric carcinoma with lymphoid stroma associated with epstein-barr virus[J]. Clin Gastroenterol Hepatol，2015，13(10)：1738-1744.e2.
[35]	KOEMANS W J, VAN DER KAAIJ R T, BOOT H, et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy versus palliative systemic chemotherapy in stomach cancer patients with peritoneal dissemination，the study protocol of a multicentre randomised controlled trial（PERISCOPE Ⅱ）[J]. BMC Cancer，2019，19(1)：420. DOI：10.1186/s12885-019-5640-2.
[36]	CASELLA F, BENCIVENGA M, ROSATI R, et al. Pressurized intraperitoneal aerosol chemotherapy（PIPAC）in multimodal therapy for patients with oligometastatic peritoneal gastric cancer：a randomized multicenter phase Ⅲ trial PIPAC VEROne[J]. Pleura Peritoneum，2022，7(3)：135-141. DOI：10.1515/pp-2022-0111.
[37]	KANG Y K, BOKU N, SATOH T, et al. Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to，or intolerant of，at least two previous chemotherapy regimens（ONO-4538-12，ATTRACTION-2）：a randomised，double-blind，placebo-controlled，phase 3 trial[J]. Lancet，2017，390(10111)：2461-2471.
[38]	JANJIGIAN Y Y, SHITARA K, MOEHLER M, et al. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric，gastro-oesophageal junction，and oesophageal adenocarcinoma（CheckMate 649）：a randomised，open-label，phase 3 trial[J]. Lancet，2021，398(10294)：27-40.
[39]	XU J M, JIANG H P, PAN Y Y, et al. Sintilimab plus chemotherapy for unresectable gastric or gastroesophageal junction cancer：the ORIENT-16 randomized clinical trial[J]. JAMA，2023，330(21)：2064-2074. DOI：10.1001/jama.2023.19918.
[40]	QIU M Z, OH D Y, KATO K, et al. Tislelizumab plus chemotherapy versus placebo plus chemotherapy as first line treatment for advanced gastric or gastro-oesophageal junction adenocarcinoma：rationale-305 randomised，double blind，phase 3 trial[J]. BMJ，2024，385：e078876. DOI：10.1136/bmj-2023-078876.
[41]	SHITARA K, VAN CUTSEM E, BANG Y J, et al. Efficacy and safety of pembrolizumab or pembrolizumab plus chemotherapy vs chemotherapy alone for patients with first-line，advanced gastric cancer：the KEYNOTE-062 phase 3 randomized clinical trial[J]. JAMA Oncol，2020，6(10)：1571-1580. DOI：10.1001/jamaoncol.2020.3370.
[42]	RHA S Y, OH D Y, YAÑEZ P, et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for HER2-negative advanced gastric cancer（KEYNOTE-859）：a multicentre，randomised，double-blind，phase 3 trial[J]. Lancet Oncol，2023，24(11)：1181-1195. DOI：10.1016/S1470-2045(23)00515-6.
[43]	YUAN S Q, NIE R C, JIN Y, et al. Perioperative toripalimab and chemotherapy in locally advanced gastric or gastro-esophageal junction cancer：a randomized phase 2 trial[J]. Nat Med，2024，30(2)：552-559. DOI：10.1038/s41591-023-02721-w.
[44]	JANJIGIAN Y Y, KAWAZOE A, BAI Y X, et al. Pembrolizumab plus trastuzumab and chemotherapy for HER2-positive gastric or gastro-oesophageal junction adenocarcinoma：interim analyses from the phase 3 KEYNOTE-811 randomised placebo-controlled trial[J]. Lancet，2023，402(10418)：2197-2208. DOI：10.1016/S0140-6736(23)02033-0.
[45]	DING X W, WANG X J, LI B, et al. PERSIST：a multicenter，randomized phaseⅡ trial of perioperative oxaliplatin and S-1（SOX）with or without sintilimab in resectable locally advanced gastric/gastroesophageal junction cancer（GC/GEJC）[J]. J Clin Oncol，2023，41(4_suppl)：364. DOI：10.1200/jco.2023.41.4_suppl.364.
[46]	AL-BATRAN S E, LORENZEN S, THUSS-PATIENCE P C, et al. Surgical and pathological outcome，and pathological regression，in patients receiving perioperative atezolizumab in combination with FLOT chemotherapy versus FLOT alone for resectable esophagogastric adenocarcinoma：interim results from DANTE，a randomized，multicenter，phase Ⅱb trial of the FLOT-AIO German Gastric Cancer Group and Swiss SAKK[J]. J Clin Oncol，2022，40(16_suppl)：4003.
[47]	JANJIGIAN Y Y, AL-BATRAN S E, WAINBERG Z A, et al. Pathological complete response（pCR）to 5-fluorouracil，leucovorin，oxaliplatin and docetaxel（FLOT）with or without durvalumab（D）in resectable gastric and gastroesophageal junction cancer（GC/GEJC）：subgroup analysis by region from the phase 3，randomized，double-blind MATTERHORN study[J]. J Clin Oncol，2024，42(3_suppl)：LBA246. DOI：10.1200/jco.2024.42.3_suppl.lba246.
[48]	KANG Y K, TERASHIMA M, KIM Y W, et al. Adjuvant nivolumab plus chemotherapy versus placebo plus chemotherapy for stageⅢ gastric or gastro-oesophageal junction cancer after gastrectomy with D2 or more extensive lymph-node dissection（ATTRACTION-5）：a randomised，multicentre，double-blind，placebo-controlled，phase 3 trial[J]. Lancet Gastroenterol Hepatol，2024，9(8)：705-717. DOI：10.1016/S2468-1253(24)00156-0.
[49]	SHITARA K, RHA S Y, WYRWICZ L S, et al. Neoadjuvant and adjuvant pembrolizumab plus chemotherapy in locally advanced gastric or gastro-oesophageal cancer（KEYNOTE-585）：an interim analysis of the multicentre，double-blind，randomised phase 3 study[J]. Lancet Oncol，2024，25(2)：212-224. DOI：10.1016/S1470-2045(23)00541-7.
[50]	CHAO J, FUCHS C S, SHITARA K, et al. Assessment of pembrolizumab therapy for the treatment of microsatellite instability-high gastric or gastroesophageal junction cancer among patients in the KEYNOTE-059，KEYNOTE-061，and KEYNOTE-062 clinical trials[J]. JAMA Oncol，2021，7(6)：895-902.
[51]	MARABELLE A, LE D T, ASCIERTO P A, et al. Efficacy of pembrolizumab in patients with noncolorectal high microsatellite instability/mismatch repair-deficient cancer：results from the phaseⅡ KEYNOTE-158 study[J]. J Clin Oncol，2020，38(1)：1-10.
[52]	MURO K, KAWAKAMI H, KADOWAKI S, et al. 1513MO A phaseⅡ study of nivolumab plus low dose ipilimumab as first-line therapy in patients with advanced gastric or esophago-gastric junction MSI-H tumor：first results of the NO LIMIT study（WJOG13320G/CA209-7W7）[J]. Ann Oncol，2023，34：S852-853. DOI：10.1016/j.annonc.2023.09.1426.
[53]	ANDRÉ T, TOUGERON D, PIESSEN G, et al. Neoadjuvant nivolumab plus ipilimumab and adjuvant nivolumab in localized deficient mismatch repair/microsatellite instability-high gastric or esophagogastric junction adenocarcinoma：the GERCOR NEONIPIGA phaseⅡ study[J]. J Clin Oncol，2023，41(2)：255-265. DOI：10.1200/JCO.22.00686.
[54]	PIETRANTONIO F, RAIMONDI A, LONARDI S, et al. INFINITY：a multicentre，single-arm，multi-cohort，phaseⅡ trial of tremelimumab and durvalumab as neoadjuvant treatment of patients with microsatellite instability-high（MSI）resectable gastric or gastroesophageal junction adenocarcinoma（GAC/GEJAC）[J]. J Clin Oncol，2023，41(4_suppl)：358. DOI：10.1200/jco.2023.41.4_suppl.358.
[55]	LUDFORD K, HO W J, THOMAS J V, et al. Neoadjuvant pembrolizumab in localized microsatellite instability high/deficient mismatch repair solid tumors[J]. J Clin Oncol，2023，41(12)：2181-2190. DOI：10.1200/JCO.22.01351.
[56]	GATALICA Z, XIU J, SWENSEN J, et al. Molecular characterization of cancers with NTRK gene fusions[J]. Mod Pathol，2019，32(1)：147-153. DOI：10.1038/s41379-018-0118-3.
[57]	ARNOLD A, DAUM S, VON WINTERFELD M, et al. Analysis of NTRK expression in gastric and esophageal adenocarcinoma（AGE）with pan-TRK immunohistochemistry[J]. Pathol Res Pract，2019，215(11)：152662. DOI：10.1016/j.prp.2019.152662.
[58]	SHINOZAKI-USHIKU A, ISHIKAWA S, KOMURA D, et al. The first case of gastric carcinoma with NTRK rearrangement：identification of a novel ATP1B-NTRK1 fusion[J]. Gastric Cancer，2020，23(5)：944-947. DOI：10.1007/s10120-020-01061-9.
[59]	SOLOMON B J, DRILON A, LIN J J, et al. 1372P Repotrectinib in patients（pts）with NTRK fusion-positive（NTRK+）advanced solid tumors，including NSCLC：update from the phaseⅠ/Ⅱ TRIDENT-1 trial[J]. Ann Oncol，2023，34：S787-788. DOI：10.1016/j.annonc.2023.09.2405.
[60]	中华医学会外科学分会胃肠外科学组，中华医学会外科学分会结直肠外科学组，中国医师协会外科医师分会上消化道外科医师委员会. 胃肠外科病人围手术期全程营养管理中国专家共识（2021版）[J]. 中国实用外科杂志，2021，41(10)：1111-1125. DOI：10.19538/j.cjps.issn1005-2208.2021.10.05.
[61]	HU Y F, KIM H I, HYUNG W J, et al. Vitamin B（12）deficiency after gastrectomy for gastric cancer：an analysis of clinical patterns and risk factors[J]. Ann Surg，2013，258(6)：970-975. DOI：10.1097/SLA.0000000000000214.
[62]	KIM H I, HYUNG W J, SONG K J, et al. Oral vitamin B12 replacement：an effective treatment for vitamin B12 deficiency after total gastrectomy in gastric cancer patients[J]. Ann Surg Oncol，2011，18(13)：3711-3717.
[63]	JEONG O, PARK Y K. Effect of intravenous iron supplementation for acute postoperative anemia in patients undergoing gastrectomy for gastric carcinoma：a pilot study[J]. Ann Surg Oncol，2014，21(2)：547-552. DOI：10.1245/s10434-013-3238-5.