Interpretation of NCCN clinical practice guidelines for hepatocellular carcinoma, version 2.2023

doi:10.16139/j.1007-9610.2024.02.02

Abstract

Abstract:

The National Comprehensive Cancer Network (NCCN), as the world's leading non-profit consortium in the field of oncology, continues to update clinical practice guidelines for multiple malignancies annually and has become a benchmark for clinical practice guidelines in oncology worldwide. Currently, the NCCN clinical practice guidelines for hepatocellular carcinoma have been updated to version 2.2023, as compared with version 1.2023 of its main updates for the content of the discussion section. The NCCN guidelines for hepatobiliary cancers have been reorganized to separate guidelines for biliary tract cancers and hepatocellular carcinoma since version 1.2023. The main updates focus on tumor screening, diagnosis, surgery, adjuvant therapy, locoregional therapy, systemic therapy, and so on. The molecular testing was added for the first time. Therefore, the updates of version 1.2023 were highlighted again in the new version 2.2023. This article interpreted the new guidelines and focused on the aspects of updates.

Key words: Hepatocellular carcinoma, National Comprehensive Cancer Network(NCCN), Guidelines, Update

CLC Number:

R735.7

SHI Chunchao, WANG Kui. Interpretation of NCCN clinical practice guidelines for hepatocellular carcinoma, version 2.2023[J]. Journal of Surgery Concepts & Practice, 2024, 29(02): 99-105.

Figures/Tables 1

Tab 1

References 38

[1]	QIU H, CAO S, XU R. Cancer incidence, mortality, and burden in China: a time-trend analysis and comparison with the United States and United Kingdom based on the global epidemiological data released in 2020[J]. Cancer Commun (Lond), 2021, 41(10):1037-1048.
[2]	LLOVET J M, KELLEY R K, VILLANUEVA A, et al. Hepatocellular carcinoma[J]. Nat Rev Dis Primers, 2021, 7(1):6. doi: 10.1038/s41572-020-00240-3 pmid: 33479224
[3]	MARRERO J A, KULIK L M, SIRLIN C, et al. Diagnosis, staging, and management of hepatocellular carcinoma: 2018 practice guidance by the American Association for the study of liver diseases[J]. Hepatology, 2018,68:723-750.
[4]	European Association for the Study of the Liver, European Organisation for Research and Treatment of Cancer, European Association for the Study of the Liver. (EASL)-EORTC clinical practice guidelines: management of hepatocellular carcinoma[J]. J Hepatol, 2012,56:908-943.
[5]	COLLI A, FRAQUELLI M, CASAZZA G, et al. Accuracy of ultrasonography, spiral CT, magnetic resonance, and alpha-fetoprotein in diagnosing hepatocellular carcinoma: a systematic review[J]. Am J Gastroenterol, 2006,101:513-523.
[6]	IOANNOU G N. HCC surveillance after SVR in patients with F3/F4 fibrosis[J]. J Hepatol, 2021, 74(2):458-465. doi: 10.1016/j.jhep.2020.10.016 pmid: 33303216
[7]	LOK A S, STERLING R K, EVERHART J E, et al. Des-gamma-carboxy prothrombin and alpha-fetoprotein as biomarkers for the early detection of hepatocellular carcinoma[J]. Gastroenterology, 2010, 138(2):493-502. doi: 10.1053/j.gastro.2009.10.031 pmid: 19852963
[8]	YANG J D, ADDISSIE B D, MARA K C, et al. GALAD score for hepatocellular carcinoma detection in comparison with liver ultrasound and proposal of GALADUS score[J]. Cancer Epidemiol Biomarkers Prev, 2019, 28(3):531-538.
[9]	FOWLER K J, POTRETZKE T A, HOPE T A, et al. LI-RADS M (LR-M): definite or probable malignancy, not specific for hepatocellular carcinoma[J]. Abdom Radiol (NY), 2018, 43(1):149-157. doi: 10.1007/s00261-017-1196-2 pmid: 28580538
[10]	DIETRICH C F, NOLSØE C P, BARR R G, et al. Guidelines and good clinical practice recommendations for contrast enhanced ultrasound (CEUS) in the liver - update 2020: WFUMB in cooperation with EFSUMB, AFSUMB, AIUM, and FLAUS[J]. Ultrasound Med Biol, 2020,46:2579-2604.
[11]	SUN D W, AN L, WEI F, et al. Prognostic significance of parameters from pretreatment (18)F-FDG PET in hepatocellular carcinoma: a meta-analysis[J]. Abdom Radiol (NY), 2016,41:33-41.
[12]	CHILDS A, ZAKERI N, MA Y T, et al. Biopsy for advanced hepatocellular carcinoma: results of a multicentre UK audit[J]. Br J Cancer, 2021, 125(10):1350-1355.
[13]	SANTAMBROGIO R, KLUGER M D, COSTA M, et al. Hepatic resection for hepatocellular carcinoma in patients with Child-Pugh's A cirrhosis: is clinical evidence of portal hypertension a contraindication?[J]. HPB (Oxford), 2013, 15(1):78-84.
[14]	GLANTZOUNIS G K, PALIOURAS A, STYLIANIDI M C, et al. The role of liver resection in the management of intermediate and advanced stage hepatocellular carcinoma. A systematic review[J]. Eur J Surg Oncol, 2018,44:195-208.
[15]	BROUQUET A, ANDREOU A, SHINDOH J, et al. Me-thods to improve resectability of hepatocellular carcinoma[J]. Recent Results Cancer Res, 2013,190:57-67.
[16]	FABER W, STOCKMANN M, SCHIRMER C, et al. Significant impact of patient age on outcome after liver resection for HCC cirrhosis[J]. Eur J Surg Oncol, 2014,40:208-213.
[17]	QIN S, CHEN M, CHENG A L, et al. IMbrave050 investigators. Atezolizumab plus bevacizumab versus active surveillance in patients with resected or ablated high-risk hepatocellular carcinoma (IMbrave050): a randomised, open-label, multicentre, phase 3 trial[J]. Lancet, 2023, 402(10415):1835-1847.
[18]	CHEN M S, LI J Q, ZHENG Y, et al. A prospective randomized trial comparing percutaneous local ablative therapy and partial hepatectomy for small hepatocellular carcinoma[J]. Ann Surg, 2006,243:321-328.
[19]	FENG K, YAN J, LI X, et al. A randomized controlled trial of radiofrequency ablation and surgical resection in the treatment of small hepatocellular carcinoma[J]. J Hepatol, 2012,57:794-802.
[20]	PENG Z W, ZHANG Y J, LIANG H H, et al. Recurrent hepatocellular carcinoma treated with sequential transcatheter arterial chemoembolization and RF ablation versus RF ablation alone: a prospective randomized trial[J]. Radiology, 2012, 262(2):689-700.
[21]	BRUIX J, TAKAYAMA T, MAZZAFERRO V, et al. Adjuvant sorafenib for hepatocellular carcinoma after resection or ablation (STORM): a phase 3, randomised, doubleblind, placebo-controlled trial[J]. Lancet Oncol, 2015, 16(13):1344-1354.
[22]	SALEM R, LEWANDOWSKI R J, MULCAHY M F, et al. Radioembolization for hepatocellular carcinoma using Yttrium-90 microspheres: a comprehensive report of long-term outcomes[J]. Gastroenterology, 2010, 138(1):52-64. doi: 10.1053/j.gastro.2009.09.006 pmid: 19766639
[23]	GARIN E, TSELIKAS L, GUIU B, et al. Personalised versus standard dosimetry approach of selective internal radiation therapy in patients with locally advanced hepatocellular carcinoma (DOSISPHERE-01): a randomised, multicentre, open-label phase 2 trial[J]. Lancet Gastroenterol Hepatol, 2021, 6(1):17-29.
[24]	VILGRAIN V, PEREIRA H, ASSENAT E, et al. Efficacy and safety of selective internal radiotherapy with yttrium-90 resin microspheres compared with sorafenib in locally advanced and inoperable hepatocellular carcinoma (SARAH): an open-label randomised controlled phase 3 trial[J]. Lancet Oncol, 2017, 18(12):1624-1636. doi: S1470-2045(17)30683-6 pmid: 29107679
[25]	CHOW P K H, GANDHI M, TAN S B, et al. SIRveNIB: selective internal radiation therapy versus sorafenib in Asia-Pacific patients with hepatocellular carcinoma[J]. J Clin Oncol, 2018, 36(19):1913-1921.
[26]	RICKE J, KLÜMPEN H J, AMTHAUER H, et al. Impact of combined selective internal radiation therapy and sorafenib on survival in advanced hepatocellular carcinoma[J]. J Hepatol, 2019,71:1164-1174.
[27]	HOFFE S E, FINKELSTEIN S E, RUSSELL M S, et al. Nonsurgical options for hepatocellular carcinoma: evolving role of external beam radiotherapy[J]. Cancer Control, 2010,17:100-110.
[28]	WAHL D R, STENMARK M H, TAO Y, et al. Outcomes after stereotactic body radiotherapy or radiofrequency ablation for hepatocellular carcinoma[J]. J Clin Oncol, 2016, 34(5):452-459. doi: 10.1200/JCO.2015.61.4925 pmid: 26628466
[29]	HASAN S, ABEL S, VERMA V, et al. Proton beam therapy versus stereotactic body radiotherapy for hepatocellular carcinoma: practice patterns, outcomes, and the effect of biologically effective dose escalation[J]. J Gastro-intest Oncol, 2019, 10(5):999-1009.
[30]	QI W X, FU S, ZHANG Q, et al. Charged particle therapy versus photon therapy for patients with hepatocellular carcinoma: a systematic review and meta-analysis[J]. Radiother Oncol, 2015,114:289-295.
[31]	SOLIMAN H, RINGASH J, JIANG H, et al. Phase Ⅱ trial of palliative radiotherapy for hepatocellular carcinoma and liver metastases[J]. J Clin Oncol, 2013 ;31(31):3980-3986.
[32]	BENSON A B, D’ANGELICA M I, ABRAMS I, et al. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Hepatobiliary cancers,Version 1.2023[EB/OL]. (2023-3-10)[2023-6-30]. https://www.nccn.org/guidelines.
[33]	BENSON A B, D’ANGELICA M I, ABBOTT D E, et al. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®). Hepatobiliary cancers,Version 5.2022[EB/OL]. (2023-1-13)[2023-6-30]. https://www.nccn.org/guidelines.
[34]	QIN S, CHAN S L, GU S, et al. Camrelizumab plus rivo-ceranib versus sorafenib as first-line therapy for unresec-table hepatocellular carcinoma (CARES-310): a randomised, open-label, international phase 3 study[J]. Lancet, 2023, 402(10408):1133-1146.
[35]	EL-KHOUEIRY A B, SANGRO B, YAU T, et al. Ni-volumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial[J]. Lancet, 2017,389:2492-2502.
[36]	ZHU A X, FINN R S, EDELINE J, et al. Pembrolizumab in patients with advanced hepatocellular carcinoma pre-viously treated with sorafenib (KEYNOTE-224): a nonrandomised, open-label phase 2 trial[J]. Lancet Oncol, 2018, 19(7):940-952.
[37]	CHENG A L, QIN S, IKEDA M, et al. Updated efficacy and safety data from IMbrave150: atezolizumab plus bevacizumab vs. sorafenib for unresectable hepatocellular carcinoma[J]. J Hepatol, 2022, 76(4):862-873.
[38]	FINN R S, RYOO B Y, MERLE P, et al. Pembrolizumab as second-line therapy in patients with advanced hepatocellular carcinoma in KEYNOTE-240: a randomized, doubleblind, phase Ⅲ trial[J]. J Clin Oncol, 2020,38:193-202.

一线系统治疗
优先推荐方案	其他推荐方案	特定情况下有用方案
阿替利珠单抗+贝伐珠单抗（仅适用于肝功能Child-Pugh A级；1类证据）；替西木单抗（tremelimumab）+度伐利尤单抗（1类证据）。	索拉非尼[肝功能为Child-Pugh A级（1类证据）或B7级]；仑伐替尼（lenvatinib）（仅适用于肝功能Child-Pugh A级，1类证据）；度伐利尤单抗（1类证据）；帕博利珠单抗（2B类证据）。	纳武利尤单抗（仅适用于肝功能Child-Pugh B级）；阿替利珠单抗+贝伐珠单抗（仅适用于肝功能Child-Pugh B级）；纳武利尤单抗+伊匹木单抗（适用于TMB-H肿瘤，2B类证据）。
二线系统治疗
可选方案	其他推荐方案	特定情况下有用方案
瑞戈非尼（regorafenib）（仅适用于肝功能Child- Pugh A级，1类证据）；卡波替尼（cabozantinib)（仅适用于肝功能Child- Pugh A级，1类证据）；仑伐替尼（仅适用于肝功能Child-Pugh A级）；索拉非尼（sorafenib)（肝功能Child-Pugh A级或B7级）。	纳武利尤单抗+伊匹木单抗（仅适用于肝功能Child-Pugh A级）；帕博利珠单抗（仅适用于肝功能Child-Pugh A级）。	雷莫芦单抗（仅适用于AFP≥400 μg/L且肝功能Child-Pugh A级，1类证据）；纳武利尤单抗（适用于肝功能Child-Pugh B级）；多塔利单抗（dostarlimab）（适用于MSI-H/错配修复缺陷(deficiency mismatch repair, dMMR)肿瘤，2B类证据）；塞尔帕替尼（selpercatinib）（适用于RET转染重排基因融合阳性肿瘤，2B类证据）；纳武利尤单抗+伊匹木单抗（适用于TMB-H肿瘤，标准疗法难治性疾病或没有可用标准治疗方案者，2B类证据）。