The Neutrophil-to-Lymphocyte Ratio (NLR) Predicts the Prognosis of Unresectable Intermediate and Advanced Hepatocellular Carcinoma Treated with Apatinib

References

• FornerA, ReigM, BruixJ. Hepatocellular carcinoma. Lancet. 2018;391(10127):1301–1314. doi:10.1016/S0140-6736(18)30010-229307467
   PubMed Web of Science ®Google Scholar
• IkedaM, MorizaneC, UenoM, OkusakaT, IshiiH, FuruseJ. Chemotherapy for hepatocellular carcinoma: current status and future perspectives. Jpn J Clin Oncol. 2018;48(2):103–114. doi:10.1093/jjco/hyx18029253194
   PubMed Web of Science ®Google Scholar
• ChengAL, KangYK, ChenZ, et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009;10(1):25–34. doi:10.1016/S1470-2045(08)70285-719095497
   PubMed Web of Science ®Google Scholar
• BensonAB, D’AngelicaMI, AbbottDE, et al. Guidelines insights: hepatobiliary cancers, version 2.2019. J Natl Compr Canc Netw. 2019;17(4):302–310. doi:10.6004/jnccn.2019.001930959462
   PubMed Web of Science ®Google Scholar
• KudoM, FinnRS, QinS, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised Phase 3 non-inferiority trial. Lancet. 2018;391(10126):1163–1173. doi:10.1016/S0140-6736(18)30207-129433850
   PubMed Web of Science ®Google Scholar
• MeyerT. Treatment of advanced hepatocellular carcinoma: beyond sorafenib. Lancet Gastroenterol Hepatol. 2018;3(4):218–220. doi:10.1016/S2468-1253(17)30255-829533189
   PubMed Web of Science ®Google Scholar
• YangC, QinS. Apatinib targets both tumor and endothelial cells in hepatocellular carcinoma. Cancer Med. 2018;7(9):4570–4583. doi:10.1002/cam4.166430109780
   PubMed Web of Science ®Google Scholar
• LiJ, QinS, XuJ, et al. Randomized, double-blind, placebo-controlled Phase III trial of apatinib in patients with chemotherapy-refractory advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction. J Clin Oncol. 2016;34(13):1448–1454. doi:10.1200/JCO.2015.63.599526884585
   PubMed Web of Science ®Google Scholar
• HuX, CaoJ, HuW, et al. Multicenter Phase II study of apatinib in non-triple-negative metastatic breast cancer. BMC Cancer. 2014;14(1):820. doi:10.1186/1471-2407-14-82025376790
   PubMed Web of Science ®Google Scholar
• MiaoM, DengG, LuoS, et al. A phase II study of apatinib in patients with recurrent epithelial ovarian cancer. Gynecol Oncol. 2018;148(2):286–290. doi:10.1016/j.ygyno.2017.12.01329248198
   PubMed Web of Science ®Google Scholar
• DuX, ChenD, LinZ, et al. Efficacy of apatinib in advanced hepatocellular carcinoma with lung metastasis: a retrospective, multicenter study. J BUON. 2019;24(5):1956–1963.31786861
   PubMed Web of Science ®Google Scholar
• QinS, LiQ, GuS, et al. Apatinib as second-line or later therapy in patients with advanced hepatocellular carcinoma (AHELP): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Gastroenterol Hepatol. 2021;6(7):559–568. doi:10.1016/S2468-1253(21)00109-633971141
   PubMed Web of Science ®Google Scholar
• ZhangY, FanW, WangY, HuangG, LiJ. Apatinib for patients with sorafenib-refractory advanced hepatitis B virus related hepatocellular carcinoma: results of a Pilot Study. Cancer Control. 2019;26(1):1073274819872216. doi:10.1177/107327481987221631466465
   PubMed Web of Science ®Google Scholar
• RizzoA, RicciAD, BrandiG. Atezolizumab in advanced hepatocellular carcinoma: good things come to those who wait. Immunotherapy. 2021;13(8):637–644. doi:10.2217/imt-2021-002633820447
   PubMed Web of Science ®Google Scholar
• MeiK, QinS, ChenZ, LiuY, WangL, ZouJ. Camrelizumab in combination with apatinib in second-line or above therapy for advanced primary liver cancer: cohort a report in a multicenter phase Ib/II trial. J Immunother Cancer. 2021;9(3):e002191. doi:10.1136/jitc-2020-00219133741732
   PubMed Web of Science ®Google Scholar
• RingelhanM, PfisterD, O’ConnorT, PikarskyE, HeikenwalderM. The immunology of hepatocellular carcinoma. Nat Immunol. 2018;19(3):222–232. doi:10.1038/s41590-018-0044-z29379119
   PubMed Web of Science ®Google Scholar
• EndigJ, Buitrago-MolinaLE, MarhenkeS, et al. Dual role of the adaptive immune system in liver injury and hepatocellular carcinoma development. Cancer Cell. 2016;30(2):308–323. doi:10.1016/j.ccell.2016.06.00927478039
   PubMed Web of Science ®Google Scholar
• YangY, WangC, SunH, JiangZ, ZhangY, PanZ. Apatinib prevents natural killer cell dysfunction to enhance the efficacy of anti-PD-1 immunotherapy in hepatocellular carcinoma. Cancer Gene Ther. 2021;28(1–2):89–97. doi:10.1038/s41417-020-0186-732533100
   PubMed Web of Science ®Google Scholar
• MotomuraT, ShirabeK, ManoY, et al. Neutrophil-lymphocyte ratio reflects hepatocellular carcinoma recurrence after liver transplantation via inflammatory microenvironment. J Hepatol. 2013;58(1):58–64. doi:10.1016/j.jhep.2012.08.01722925812
   PubMed Web of Science ®Google Scholar
• LimayeAR, ClarkV, Soldevila-PicoC, et al. Neutrophil-lymphocyte ratio predicts overall and recurrence-free survival after liver transplantation for hepatocellular carcinoma. Hepatol Res. 2013;43(7):757–764. doi:10.1111/hepr.1201923193965
   PubMed Web of Science ®Google Scholar
• GomezD, FaridS, MalikHZ, et al. Preoperative neutrophil-to-lymphocyte ratio as a prognostic predictor after curative resection for hepatocellular carcinoma. World J Surg. 2008;32(8):1757–1762. doi:10.1007/s00268-008-9552-618340479
   PubMed Web of Science ®Google Scholar
• BruixJ, ChengAL, MeinhardtG, NakajimaK, De SanctisY, LlovetJ. Prognostic factors and predictors of sorafenib benefit in patients with hepatocellular carcinoma: analysis of two phase III studies. J Hepatol. 2017;67(5):999–1008. doi:10.1016/j.jhep.2017.06.02628687477
   PubMed Web of Science ®Google Scholar
• HouZ, ZhuK, YangX, et al. Apatinib as first-line treatment in patients with advanced hepatocellular carcinoma: a phase II clinical trial. Ann Transl Med. 2020;8(17):1047. doi:10.21037/atm-20-299033145266
   PubMed Web of Science ®Google Scholar
• LlovetJM, RicciS, MazzaferroV, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359(4):378–390. doi:10.1056/NEJMoa070885718650514
   PubMed Web of Science ®Google Scholar
• BruixJ, QinS, MerleP, et al. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017;389(10064):56–66. doi:10.1016/S0140-6736(16)32453-927932229
   PubMed Web of Science ®Google Scholar
• Abou-AlfaGK, MeyerT, ChengAL, et al. Cabozantinib in patients with advanced and progressing hepatocellular carcinoma. N Engl J Med. 2018;379(1):54–63. doi:10.1056/NEJMoa171700229972759
   PubMed Web of Science ®Google Scholar
• Sanchez-SalcedoP, De-torresJP, Martinez-UrbistondoD, et al. The neutrophil to lymphocyte and platelet to lymphocyte ratios as biomarkers for lung cancer development. Lung Cancer.2016;97:28–34. doi:10.1016/j.lungcan.2016.04.01027237024
   PubMed Web of Science ®Google Scholar
• AbsengerG, SzkanderaJ, PichlerM, et al. A derived neutrophil to lymphocyte ratio predicts clinical outcome in stage II and III colon cancer patients. Br J Cancer. 2013;109(2):395–400. doi:10.1038/bjc.2013.34623820252
   PubMed Web of Science ®Google Scholar
• BaltaS, UnluM, ArslanZ, DemırkolS. Neutrophil-to-lymphocyte ratio in prognosis of gastric cancer. J Gastric Cancer. 2013;13(3):196–197. doi:10.5230/jgc.2013.13.3.19624156042
   PubMedGoogle Scholar
• DiricanA, KucukzeybekBB, AlacaciogluA, et al. Do the derived neutrophil to lymphocyte ratio and the neutrophil to lymphocyte ratio predict prognosis in breast cancer?Int J Clin Oncol. 2015;20(1):70–81. doi:10.1007/s10147-014-0672-824532163
   PubMed Web of Science ®Google Scholar
• FengJF, HuangY, LiuJS. Combination of neutrophil lymphocyte ratio and platelet lymphocyte ratio is a useful predictor of postoperative survival in patients with esophageal squamous cell carcinoma. Onco Targets Ther. 2013;6:1605–1612.24403837
   PubMed Web of Science ®Google Scholar
• HuH, YaoX, XieX, et al. Prognostic value of preoperative NLR, dNLR, PLR and CRP in surgical renal cell carcinoma patients. World J Urol. 2017;35(2):261–270. doi:10.1007/s00345-016-1864-927255479
   PubMed Web of Science ®Google Scholar
• McNamaraMG, TempletonAJ, MagantiM, et al. Neutrophil/lymphocyte ratio as a prognostic factor in biliary tract cancer. Eur J Cancer. 2014;50(9):1581–1589. doi:10.1016/j.ejca.2014.02.01524630393
   PubMed Web of Science ®Google Scholar
• LuSD, WangYY, PengNF, et al. Preoperative ratio of neutrophils to lymphocytes predicts postresection survival in selected patients with early or intermediate stage hepatocellular carcinoma. Medicine. 2016;95(5):e2722. doi:10.1097/MD.000000000000272226844516
   PubMed Web of Science ®Google Scholar
• BishayeeA. The role of inflammation and liver cancer. Adv Exp Med Biol. 2014;816:401–435.24818732
   PubMed Web of Science ®Google Scholar
• LiangW, FerraraN. The complex role of neutrophils in tumor angiogenesis and metastasis. Cancer Immunol Res. 2016;4(2):83–91. doi:10.1158/2326-6066.CIR-15-031326839309
   PubMed Web of Science ®Google Scholar
• Ménétrier-CauxC, Ray-CoquardI, BlayJY, CauxC. Lymphopenia in cancer patients and its effects on response to immunotherapy: an opportunity for combination with cytokines?J Immunother Cancer. 2019;7(1):85.30922400
   PubMed Web of Science ®Google Scholar
• ShigetaK, DattaM, HatoT, et al. Dual programmed death receptor-1 and vascular endothelial growth factor receptor-2 blockade promotes vascular normalization and enhances antitumor immune responses in hepatocellular carcinoma. Hepatology. 2020;71(4):1247–1261. doi:10.1002/hep.3088931378984
   PubMed Web of Science ®Google Scholar
• SocinskiMA, JotteRM, CappuzzoF, et al. Atezolizumab for first-line treatment of metastatic nonsquamous NSCLC. N Engl J Med. 2018;378(24):2288–2301. doi:10.1056/NEJMoa171694829863955
   PubMed Web of Science ®Google Scholar