肝细胞癌围手术期放射治疗的研究进展

摘要/Abstract

摘要： 肝细胞癌（hepatocellular carcinoma,HCC）是原发性肝癌的主要病理类型,发病率高且预后差,通过合理有序的多学科综合治疗能大大提高HCC患者的疗效。手术切除是HCC主要的治疗手段之一,但面临着术后高复发的问题。随着放射治疗技术的发展、成熟,放射治疗在HCC治疗中得到广泛应用。手术与放射治疗的联合应用能有效减少疾病复发、延长患者生存期。HCC围手术期放射治疗研究数据表明,对于窄切缘（<1cm）手术和微血管侵犯患者,术后或术中放射治疗可弥补手术不足,取得与宽切缘根治手术相似的疗效;伴门静脉癌栓的可切除HCC患者,术前新辅助放射治疗联合手术切除或术后放射治疗可显著改善患者预后;等候肝移植期间,体部立体定向放射治疗作为桥接治疗手段可安全有效地控制肿瘤进展,维持患者的移植候选状态。需继续开展包括放射治疗在内的综合治疗模式的前瞻性研究,从而继续进一步提高HCC患者的生存率。

关键词: 肝细胞癌, 放射治疗, 围手术期

Abstract: Hepatocellular carcinoma (HCC) is the main type of primary liver cancer with high incidence and poor prognosis. The long-term benefit of patients can be maximized by orderly multidisciplinary comprehensive treatment. Surgery is one of the main treatment methods for HCC, but it faces high risk of postoperative recurrence. With the development of radiotherapy technology, radiotherapy has been widely used in the treatment of HCC. The combined application of surgery and radiotherapy can effectively reduce disease recurrence and prolong patient survival. Evidence from perioperative radiotherapy for HCC shows that: for narrow-margin surgery and microvascular invasion, postoperative or intraoperative radiotherapy can make up for the insufficiency of surgery and achieve similar efficacy as wide-margin surgery; for resectable HCC with portal vein tumor thrombus, neoadjuvant radiotherapy combined with surgical resection or postoperative radiotherapy can significantly improve the prognosis; while waiting for liver transplantation, stereotactic body radiotherapy as bridging therapy can safely and effectively delay tumor progression and prevent drop-out from the waitlist. Prospective research on multidisciplinary treatment modality including radiotherapy will continue to improve the survival rate for patients with HCC.

Key words: Hepatocellular carcinoma, Radiotherapy, Perioperative

李丽娟, 董德左, 王洪智, 朱向高, 王维虎. 肝细胞癌围手术期放射治疗的研究进展[J]. 肝癌电子杂志, 2022, 9(4): 20-25.

Li Lijuan, Dong Dezuo, Wang Hongzhi, Zhu Xianggao, Wang Weihu^*. Development and evidence of perioperative radiotherapy for hepatocellular carcinoma[J]. Electronic Journal of Liver Tumor, 2022, 9(4): 20-25.

参考文献

[1] ZHENG R, ZHANG S, ZENG H, et al.Cancer incidence and mortality in China, 2016[J]. J Natl Cancer Cent, 2022, 2(1): 2-11.
[2] MORISE Z, KAWABE N, TOMISHIGE H, et al.Recent advances in liver resection for hepatocellular carcinoma[J]. Front Surg, 2014, 1: 21.
[3] FORNER A, LLOVET J M, BRUIX J.Hepatocellular carcinoma[J]. Lancet, 2012, 379(9822): 1245-1255.
[4] FAN S T, MAU L C, POON R T, et al.Continuous improvement of survival outcomes of resection of hepatocellular carcinoma: a 20-year experience[J]. Ann Surg, 2011, 253(4): 745-758.
[5] WANG L, WANG W, YAO X, et al.Postoperative adjuvant radiotherapy is associated with improved survival in hepatocellular carcinoma with microvascular invasion[J]. Oncotarget, 2017, 8(45): 79971-79981.
[6] WANG L, CHEN B, LI Z, et al.Optimal postoperative adjuvant treatment strategy for HBV-related hepatocellular carcinoma with microvascular invasion: a propensity score analysis[J]. Onco Targets Ther, 2019, 12: 1237-1247.
[7] WANG L, WANG W, RONG W, et al.Postoperative adjuvant treatment strategy for hepatocellular carcinoma with microvascular invasion: a non-randomized interventional clinical study[J]. BMC Cancer, 2020, 20(1): 614.
[8] WANG W H, WANG Z, WU J X, et al.Survival benefit with IMRT following narrow-margin hepatectomy in patients with hepatocellular carcinoma close to major vessels[J]. Liver Int, 2015, 35(12): 2603-2610.
[9] CHEN B, WU J X, CHENG S H, et al.Phase 2 Study of Adjuvant Radiotherapy Following Narrow-Margin Hepatectomy in Patients With HCC[J]. Hepatology, 2021, 74(5): 2595-2604.
[10] WEI X, JIANG Y, ZHANG X, et al.Neoadjuvant Three-Dimensional Conformal Radiotherapy for Resectable Hepatocellular Carcinoma With Portal Vein Tumor Thrombus: A Randomized, Open-Label, Multicenter Controlled Study[J]. J Clin Oncol, 2019, 37(24): 2141-2151.
[11] SUN J, YANG L, SHI J, et al.Postoperative adjuvant IMRT for patients with HCC and portal vein tumor thrombus: An open-label randomized controlled trial[J]. Radiother Oncol, 2019, 140: 20-25.
[12] COLECCHIA A, SCHIUMERINI R, CUCCHETTI A, et al.Prognostic factors for hepatocellular carcinoma recurrence[J]. World J Gastroenterol, 2014, 20(20): 5935-5950.
[13] SHINDOH J, HASEGAWA K, INOUE Y, et al.Risk factors of post-operative recurrence and adequate surgical approach to improve long-term outcomes of hepatocellular carcinoma[J]. HPB (Oxford), 2013, 15(1): 31-39.
[14] LIM K C, CHOW P K, ALLEN J C, et al.Microvascular invasion is a better predictor of tumor recurrence and overall survival following surgical resection for hepatocellular carcinoma compared to the Milan criteria[J]. Ann Surg, 2011, 254(1): 108-113.
[15] RODRIGUEZ-PERALVAREZ M, LUONG T V, ANDREANA L, et al.A systematic review of microvascular invasion in hepatocellular carcinoma: diagnostic and prognostic variability[J]. Ann Surg Oncol, 2013, 20(1): 325-339.
[16] ZHAO W C, FAN L F, YANG N, et al.Preoperative predictors of microvascular invasion in multinodular hepatocellular carcinoma[J]. Eur J Surg Oncol, 2013, 39(8): 858-864.
[17] SHI C, ZHAO Q, LIAO B, et al.Anatomic resection and wide resection margin play an important role in hepatectomy for hepatocellular carcinoma with peritumoural micrometastasis[J]. ANZ J Surg, 2019, 89(11): E482-E486.
[18] YANG J, LIANG H, HU K, et al.The effects of several postoperative adjuvant therapies for hepatocellular carcinoma patients with microvascular invasion after curative resection: a systematic review and meta-analysis[J]. Cancer Cell Int, 2021, 21(1): 92.
[19] SHI C, LI Y, GENG L, et al.Adjuvant stereotactic body radiotherapy after marginal resection for hepatocellular carcinoma with microvascular invasion: A randomised controlled trial[J]. Eur J Cancer, 2022, 166: 176-184.
[20] LEE J, SEONG J.The role of postoperative radiotherapy in hepatocellular carcinoma[J]. Hepatobiliary Surg Nutr, 2022, 11(1): 123-125.
[21] MIAO X Y, HU J X, DAI W D, et al.Null-margin mesohepatectomy for centrally located hepatocellular carcinoma in cirrhotic patients[J]. Hepatogastroenterology, 2011, 58(106): 575-582.
[22] LIU L, SHUI Y, YU Q, et al.Narrow-Margin Hepatectomy Resulted in Higher Recurrence and Lower Overall Survival for R0 Resection Hepatocellular Carcinoma[J]. Front Oncol, 2020, 10: 610636.
[23] MINAGAWA M, MAKUUCHI M.Treatment of hepatocellular carcinoma accompanied by portal vein tumor thrombus[J]. World J Gastroenterol, 2006, 12(47): 7561-7567.
[24] BIALECKI E S, DI BISCEGLIE A M. Clinical presentation and natural course of hepatocellular carcinoma[J]. Eur J Gastroenterol Hepatol, 2005, 17(5): 485-489.
[25] CHAN S L, CHONG C C, CHAN A W, et al.Management of hepatocellular carcinoma with portal vein tumor thrombosis: Review and update at 2016[J]. World J Gastroenterol, 2016, 22(32): 7289-7300.
[26] ZUCMAN-ROSSI J, VILLANUEVA A, NAULT J C, et al.Genetic Landscape and Biomarkers of Hepatocellular Carcinoma[J]. Gastroenterology, 2015, 149(5): 1226-1239.
[27] CHENG S, CHEN M, CAI J, et al.Chinese Expert Consensus on Multidisciplinary Diagnosis and Treatment of Hepatocellular Carcinoma with Portal Vein Tumor Thrombus (2018 Edition)[J]. Liver Cancer, 2020, 9(1): 28-40.
[28] KOREAN LIVER CANCER ASSOCIATION (KLCA); NATIONAL CANCER CENTER (NCC), GOYANG KOREA. 2018 Korean Liver Cancer Association-National Cancer Center Korea Practice Guidelines for the Management of Hepatocellular Carcinoma[J]. Korean J Radiol, 2019, 20(7): 1042-1113.
[29] SHI J, LAI E C, LI N, et al.Surgical treatment of hepatocellular carcinoma with portal vein tumor thrombus[J]. Ann Surg Oncol, 2010, 17(8): 2073-2080.
[30] CHOE J W, LEE H Y, RIM C H.Will the collaboration of surgery and external radiotherapy open new avenues for hepatocellular carcinoma with portal vein thrombosis?[J]. World J Gastroenterol, 2022, 28(7): 704-714.
[31] YOON S M, RYOO B Y, LEE S J, et al.Efficacy and Safety of Transarterial Chemoembolization Plus External Beam Radiotherapy vs Sorafenib in Hepatocellular Carcinoma With Macroscopic Vascular Invasion: A Randomized Clinical Trial[J]. JAMA Oncol, 2018, 4(5): 661-669.
[32] HUO Y R, ESLICK G D.Transcatheter Arterial Chemoembolization Plus Radiotherapy Compared With Chemoembolization Alone for Hepatocellular Carcinoma: A Systematic Review and Meta-analysis[J]. JAMA Oncol, 2015,1(6):756-765.
[33] SOIN A S, BHANGUI P, KATARIA T, et al.Experience With LDLT in Patients With Hepatocellular Carcinoma and Portal Vein Tumor Thrombosis Postdownstaging[J]. Transplantation, 2020, 104(11): 2334-2345.
[34] KULIK L, HEIMBACH J K, ZAIEM F, et al.Therapies for patients with hepatocellular carcinoma awaiting liver transplantation: A systematic review and meta-analysis[J]. Hepatology, 2018, 67(1): 381-400.
[35] AGOPIAN V G, MORSHEDI M M, MCWILLIAMS J, et al.Complete pathologic response to pretransplant locoregional therapy for hepatocellular carcinoma defines cancer cure after liver transplantation: analysis of 501 consecutively treated patients[J]. Ann Surg, 2015, 262(3): 536-545.
[36] HABIB A, DESAI K, HICKEY R, et al.Locoregional therapy of hepatocellular carcinoma[J]. Clin Liver Dis, 2015, 19(2): 401-420.
[37] JANG W I, BAE S H, KIM M S, et al.A phase 2 multicenter study of stereotactic body radiotherapy for hepatocellular carcinoma: Safety and efficacy[J]. Cancer, 2020, 126(2): 363-372.
[38] RIM C H, KIM H J, SEONG J.Clinical feasibility and efficacy of stereotactic body radiotherapy for hepatocellular carcinoma: A systematic review and meta-analysis of observational studies[J]. Radiother Oncol, 2019, 131: 135-144.
[39] HASAN S, ABEL S, UEMURA T, et al.Liver transplant mortality and morbidity following preoperative radiotherapy for hepatocellular carcinoma[J]. HPB (Oxford), 2020, 22(5): 770-778.
[40] UEMURA T, KIRICHENKO A, BUNKER M, et al.Stereotactic Body Radiation Therapy: A New Strategy for Loco-Regional Treatment for Hepatocellular Carcinoma While Awaiting Liver Transplantation[J]. World J Surg, 2019, 43(3): 886-893.
[41] SAPISOCHIN G, BARRY A, DOHERTY M, et al.Stereotactic body radiotherapy vs. TACE or RFA as a bridge to transplant in patients with hepatocellular carcinoma. An intention-to-treat analysis[J]. J Hepatol, 2017, 67(1): 92-99.
[42] ALBERDA W J, VERHOEF C, NUYTTENS J J, et al.Intraoperative radiation therapy reduces local recurrence rates in patients with microscopically involved circumferential resection margins after resection of locally advanced rectal cancer[J]. Int J Radiat Oncol Biol Phys, 2014, 88(5): 1032-1040.
[43] KONIG L, LANG K, HEIL J, et al.Acute Toxicity and Early Oncological Outcomes After Intraoperative Electron Radiotherapy (IOERT) as Boost Followed by Whole Breast Irradiation in 157 Early Stage Breast Cancer Patients-First Clinical Results From a Single Center[J]. Front Oncol, 2019, 9: 384.
[44] WU Y L, ZHAI Y, LI M, et al.Long-Term Outcome of Centrally Located Hepatocellular Carcinomas Treated by Radical Resection Combined With Intraoperative Electron Radiotherapy (IOERT)[J]. Front Oncol, 2022, 12: 773301.
[45] WANG L, LIU Y, RONG W, et al.The role of intraoperative electron radiotherapy in centrally located hepatocellular carcinomas treated with narrow-margin (<1 cm) hepatectomy: a prospective, phase 2 study[J]. Hepatobiliary Surg Nutr, 2022, 11(4): 515-529.