| Objective: To investigate the prognostic value of the sum of tumor number and maximum tumor size(N + S)and preoperative neutrophil-to-lymphocyte ratio(NLR)in patients with hepatocellular carcinoma(HCC)undergoing liver resection(LR),and the effect of postoperative adjuvant therapy on the early recurrence of HCC with microvascular invasion(MVI)after hepatectomy.Methods: The prognostic analysis and comparison of HCC patients undergoing LR was carried out among Barcelona Clinic Liver Cancer(BCLC)-B HCC patients stratified by N + S and BCLC-A patients with multinodular HCC(MNHCC),single HCC patients treated with anatomical resection(AR)or non-anatomical resection(NAR)in different preoperative NLR levels,and MVI-positive single HCC patients treated with or without postoperative adjuvant therapy,respectively.Results: Among 118 patients undergoing LR for BCLC-B HCC,patients with N + S ≤ 10 had a better prognosis.In addition,BCLC-B HCC patients with N + S ≤ 10 had overall survival(OS)、recurrence-to-death survival(RTDS)and recurrence patterns similar to those in BCLC-A MNHCC patients.Among 823 patients who underwent LR for single HCC,patients undergoing AR and NAR had similar prognosis.However,in single HCC patients with preoperative NLR ≥ 2.81,those patients who underwent AR had a worse 5-year OS.Among 188 patients undergoing LR for single HCC with MVI,patients receiving postoperative adjuvant programmed cell death receptor-1(PD-1)inhibitor therapy had a better 1-year recurrence-free survival(RFS)than patients without adjuvant therapy,but there was no statistical difference in 1-year RFS between patients receiving postoperative adjuvant transarterial chemoembolization(TACE)therapy and patients without adjuvant therapy.Conclusions: N + S can well predict the prognosis of BCLC-B HCC patients undergoing LR,and could be used to select BCLC-B HCC patients who are more suitable for LR.Preoperative NLR level is helpful to guide the selection of AR or NAR for single HCC patients,and adjuvant PD-1 inhibitor therapy can be used as postoperative adjuvant therapy for single HCC patients with MVI.Part Ⅰ: Prognostic Prediction of Barcelona Clinic Liver Cancer Stage B Hepatocellular Carcinoma Patients After Hepatectomy by the Sum of Tumor Number and Maximum Tumor SizeObjective: To investigate the prognostic value of N + S in BCLC-B HCC patients.Methods: including patients undergoing curative LR for BCLC stage A or B MNHCC and stratified BCLC-B patients by N + S.OS、RFS、RTDS、recurrence patterns,and treatments after recurrence in BCLC-B patients in each subgroup were compared with those in BCLCA patients.Results: In total,143 patients who underwent curative LR for MNHCC with BCLC-A(n = 25)or BCLC-B(n = 118)were retrospectively analyzed.According to the N + S,patients with BCLC-B HCC were divided into two subgroups: BCLC-B1(N + S ≤ 10,n = 83)and BCLC-B2(N + S > 10,n = 35).Compared with BCLC-B2 patients,those with BCLC-B1 had a better OS(5-year OS rate: 67.4% vs 33.6%;P < 0.001),which was comparable to that in BCLC-A patients(5-year OS rate: 67.4% vs 74.1%;P = 0.250),and a better RFS(median RFS: 19 mo vs 7 mo;P < 0.001),which was worse than that in BCLC-A patients(median RFS: 19 mo vs 48 mo;P = 0.022).Further analysis of patients who developed recurrence showed that both BCLC-B1 and BCLC-A patients had better RTDS(median RTDS: Not reached vs 49 mo;P = 0.599),while the RTDS in BCLC-B2 patients was worse(median RTDS: 16 mo vs not reached,P < 0.001;16 mo vs 49 mo,P = 0.042).The recurrence patterns were similar between BCLC-B1 and BCLC-A patients,but BCLC-B2 patients had a shorter recurrence time and a higher proportion of patients had recurrence with macrovascular invasion or extrahepatic metastasis,both of which were independent risk factors for RTDS.Conclusions: BCLC-B HCC patients undergoing hepatectomy with N + S ≤ 10 had good OS,RTDS and mild recurrence patterns similar to those in BCLC-A MNHCC patients,and LR could be considered in these patients.Part Ⅱ: Prognostic Prediction of Single Hepatocellular Carcinoma Patients Undergoing Anatomical Resection or Non-anatomical Resection by Preoperative Neutrophil-to-lymphocyte RatioObjective: To investigate the value of preoperative NLR in the selection of AR or NAR for single HCC patients.Methods: Patients with single HCC undergoing curative LR were included and stratified according to preoperative NLR levels.The outcomes of patients treated with AR and NAR were compared in patients with high and low preoperative NLR,respectively.Results: In total,823 patients who underwent curative AR(n = 182)or NAR(n = 641)for single HCC without macrovascular invasion or extrahepatic spread were retrospectively analyzed.Among 823 patients with single HCC,patients undergoing NAR and AR had similar 5-year RFS(48.4% vs 44.9%,P = 0.220),5-year OS(74.4% vs 67.5%,P = 0.081),and 2-year RFS(65.5% vs 59.3%,P = 0.056).Preoperative NLR levels were stratified with a cut-off value of 2.81.Multivariate analysis showed that preoperative NLR ≥ 2.81 was an independent risk factor for 5-year OS,5-year RFS,and 2-year RFS in 823 patients undergoing LR for single HCC.Among 667 patients with preoperative NLR < 2.81,patients undergoing NAR(n = 535)and AR(n = 132)had similar 5-year RFS(50.9% vs 49.1%,P = 0.535),5-year OS(76.8% vs 75.5%,P = 0.852),and 2-year RFS(67.3% vs 63.6%,P = 0.296).In 156 patients with preoperative NLR ≥ 2.81,patients undergoing NAR(n = 106)and AR(n = 50)had similar 5-year RFS(35.3% vs 34.4%,P = 0.599)and 2-year RFS(56.6% vs 48%,P = 0.224),but patients in the NAR group had better 5-year OS(62.1% vs 47%,P = 0.048).A comparison of the clinicopathologic features of patients with preoperative NLR ≥ 2.81 between those treated with NAR and those treated with AR showed that patients undergoing AR had a higher incidence of postoperative ascites,which was an independent risk factor for 5-year OS in 823 single HCC patients undergoing LR.Conclusions: In single HCC patients with preoperative NLR ≥ 2.81,NAR surgery deserves higher priority than AR surgery.Part Ⅲ: Effect of Postoperative Adjuvant Therapy on Early Recurrence of Single Hepatocellular Carcinoma with Microvascular Invasion After HepatectomyObjective: To investigate the effect of postoperative adjuvant therapy on early recurrence of single HCC with MVI after LR.Methods: Patients undergoing curative LR for single HCC with MVI were retrospectively analyzed.The 1-year RFS of patients who received no postoperative adjuvant therapy,postoperative adjuvant TACE therapy,and postoperative adjuvant PD-1 inhibitor therapy were compared.Results: In total,188 patients who underwent curative LR for MVI-positive single HCC without macrovascular invasion or extrahepatic spread were retrospectively analyzed.Among the 188 patients,103 patients received no adjuvant therapy after LR,37 patients received adjuvant TACE,and 48 patients received adjuvant PD-1 inhibitors.Patients treated with adjuvant PD-1 inhibitor therapy after LR had better 1-year RFS than those treated without adjuvant therapy(79.2% vs 57.3%,P = 0.011).However,there was no statistical difference in 1-year RFS between patients who received adjuvant TACE and those who without adjuvant therapy(59.5% vs 57.3%,P = 0.836).Multivariate analysis showed that postoperative adjuvant PD-1 inhibitor therapy could reduce the risk of tumor recurrence in MVI-positive single HCC patients within 1 year after hepatectomy(HR 0.467,0.239~0.914;P = 0.026).Of the 48 patients receiving adjuvant PD-1 inhibitors,31 had controllable treatment-related adverse events,and none discontinued therapy due to adverse events.In addition,among 127 MVI-positive single HCC patients with tumor diameter > 5 cm,patients receiving adjuvant PD-1 inhibitors had better 1-year RFS than patients without adjuvant therapy(72.7% vs 52.3%,P = 0.046),while there was still no statistical difference in 1-year RFS between patients receiving adjuvant TACE and those without adjuvant therapy(51.7% vs 52.3%,P = 0.875).Conclusions: Postoperative adjuvant PD-1 inhibitor therapy can improve the 1-year RFS of patients undergoing LR for single HCC with MVI,and can be used as postoperative adjuvant therapy for these patients. |
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