The efficacy of treatment schedules according to Barcelona Clinic Liver Cancer staging for hepatocellular carcinoma - Survival analysis of 3892 patients

The Barcelona Clinic Liver Cancer (BCLC) staging offers prognostic stratification and treatment allocation for hepatocellular carcinoma (HCC). We conducted this retrospective study to assess the efficacy of different treatment options for patients with initial HCC diagnosis. Survival rate and median survival times associated with different treatment options in each stage of BCLC classification were compared using the Kaplan–Meier method and log-rank test. A total of 3892 patients were enrolled. Overall survival rates were 46.2% at 1 year and 16.6% at 5 years. The median survival times decreased from 57.7 months in very early stage to 1.6 months in terminal stage. Surgical resection offered the best survival benefit for patients in very early, early and even intermediate stages. Transarterial embolisation and conformal radiotherapy offered survival benefits for selected patients in advanced and terminal stages. In conclusion, following the treatment schedules allocated by BCLC staging had survival benefits for HCC patients.     

Radiofrequency ablation versus surgical resection for hepatocellular carcinoma within the Milan criteria: A study of 281 Western patients

Abstract

Objectives: The aim of this study was to compare survival between radiofrequency ablation (RFA) and surgical resection (SR) in patients with hepatocellular carcinoma (HCC) within Milan criteria. Methods: From January 2004 to December 2013 we consecutively and retrospectively included all patients with first occurrence of HCC within Milan criteria receiving SR or RFA as first-line treatment. The cumulative overall survival (OS) and disease-free survival (DFS) were compared after inverse probability weighting (including confounding factor). Results: A total of 281 patients (RFA 178, SR 103) were enrolled. In multivariate Cox regression RFA and SR were not independent predictors of survival or recurrence. The respective weighted 5 years OS and DFS for patients with propensity scores between 0.1–0.9 in the SR and RFA groups were 54–33% and 60–16.9%, P?=?0.695 and P?=?0.426, respectively. Local tumour progression rate did not differ according to treatment (P?=?0.523). Major complication rate was higher in the SR group, P?=?0.001. Hospitalisation duration was lower in the RFA group (mean 2.19 days, range 2–7) than in the SR group (mean 10.2 days, range 3–30), P?<?0.001. Conclusion: This large Western study has shown that OS and DFS did not differ after RFA (using mainly multipolar devices) and SR, for HCC within the Milan criteria in a European population, with a shorter hospitalisation time and a lower complication rate for RFA.     

Minimally invasive surgery versus percutaneous radiofrequency ablation for early-stage hepatocellular carcinoma: Results from a high-volume liver surgery center in East Asia

Background & aimsThe outcomes of minimally invasive surgery (MIS) vs. percutaneous radiofrequency ablation (RFA) in treating early-stage hepatocellular carcinoma (HCC) remain inconclusive. This study thus aimed to compare the outcomes of both treatments for early-stage HCCs.MethodsThis retrospective study consecutively enrolled patients with newly diagnosed early-stage HCCs treated with MIS or percutaneous RFA between 2011 and 2018. Outcomes were compared between the MIS and RFA groups both before and after 1:1 propensity score matching (PSM).ResultsA total of 119 and 481 patients underwent MIS and percutaneous RFA, respectively. Patients undergoing percutaneous RFA exhibited older age (p = 0.007) and higher rates of Child–Pugh class B (p < 0.001) and multifocal disease (p < 0.001). The median overall survival (OS) was 73.7 months in the MIS group, which was significantly higher than that for the RFA group of 65.1 months (p = 0.003). 50% HCC recurrence after MIS was not reached. The mean recurrence-free survival (RFS) was 49.6 months for the MIS group, which was significantly higher than the RFA group of 41.3 months (p < 0.001). On multivariate analysis, age ≥65 (HR: 1.61; 95% CI: 1.13–2.31, p = 0.009), RFA (HR: 2.21; 95% CI: 1.14–4.29, p = 0.019), and Child–Pugh class B (HR: 2.03; 95% CI: 1.29–3.21, p = 0.002) remained risk factors for OS, and RFA (HR: 2.18; 95% CI: 1.42–3.35; p < 0.001) remained a risk factor for RFS. After PSM, 103 patients were included in each group. No significant difference in OS was identified (p = 0.198), but RFS was higher in the MIS group than the RFA group (p = 0.003). Severe postoperative complications occurred at the same rate (1%) in both groups (p > 0.99).ConclusionAfter PSM, severe postoperative complication and OS rates were found to be comparable between the MIS and RFA groups, but RFS was higher in the MIS group than the RFA group, suggesting that MIS may have better outcomes for patients with early-stage HCC.     

Survival Predictability Between the American Joint Committee on Cancer 8th Edition Staging System and the Barcelona Clinic Liver Cancer Classification in Patients with Hepatocellular Carcinoma

This study compared the prognostic significance of staging between the American Joint Committee on Cancer 8th edition Tumor, Node, Metastasis (TNM) staging system and the Barcelona Clinic Liver Cancer (BCLC) classification in patients with hepatocellular carcinoma (HCC). The study population comprised patients with liver cancer registered in the Taiwan Cancer Database from 2007 to 2013 and was followed up until December 31, 2016. The study included patients with HCC, with known staging in both TNM and BCLC systems, and with follow‐up >1 month. Primary endpoint was overall survival. Univariate and multivariate Cox proportional hazards model were constructed to investigate the significance of staging by two systems. Goodness‐of‐fit of model was evaluated via Akaike''s information criterion (AIC), the lower the better. Among 73,136 patients with newly diagnosed liver cancer, a total of 37,062 patients with HCC (25.6% underwent surgery) were eligible. The mean age and overall survival of this cohort were 63.9 years and 27.2%, respectively. Overall survivals for stages I, II, III, and IV (the TNM system) were 54.5%, 34.9%, 10.3%, and 6.4%, respectively. Overall survivals for stages A, B, C, and D (the BCLC classification) were 54.5%, 29.2%, 9.8%, and 4.0%, respectively. The median follow‐up time was 59.4 months. Multivariate Cox proportional hazards model revealed that both systems predicted overall survival, cancer‐specific survival, disease‐free survival, and local recurrence‐free rate well. Values of ΔAIC of the BCLC classification and the TNM system were lower for the surgery group and nonsurgery group, respectively. The TNM system (8th edition) predicted long‐term outcome better than the BCLC classification in patients with HCC. But in patients treated initially with surgery, the BCLC classification outperformed the 8th edition of the TNM system.Implications for PracticeThis work demonstrates that the Tumor, Node, Metastasis (TNM) system (8th edition) and the Barcelona Clinic Liver Cancer (BCLC) classification both predict long‐term outcome significantly in patients with hepatocellular carcinoma but that the TNM system (8th edition) predicts long‐term outcome better than the BCLC classification. For patients treated initially with surgery, BCLC classification outperforms in 8th edition TNM system in predicting long‐term outcome.     

肝切除治疗原发性肝癌自发性破裂

目的 探讨肝切除治疗原发性肝癌自发性破裂(简称肝癌破裂)的作用。方法 分析我院1973年以来采用肝切除术治疗肝癌破裂12例的临床资料。结果 本组男10例，女2例。平均年龄42(22—65)岁。11例为急症肝切除术，1例为2期肝切除，包括肝左外叶切除6例，左内叶切除1例，左半肝切除1例，右肝部分切除2例，肿瘤局部切除2例。本组中Child-Paugh肝功能分级A组的11例中无死亡；B组者1例术后死于肝衰，手术死亡率为8．3％。术后生存的1例均获随访，平均生存时间为16．5个月，1，3，5年生存率分别为72．7，18．2％，9．1％。其中1例已无瘤生存25年9个月。结论 肝切除是治疗肝癌破裂的最好方法，当有可能时应争取施行。肝切除治疗肝癌破裂可能使患者获行长时间生存。     

Treatment Efficacy and Prognostic Factors for Huge HCC Based on Barcelona Clinic Liver Cancer Staging

Objective: To explore the most appropriate treatment for patients with hepatocellular cancer (HCC) >10 cmby using the Barcelona Clinic Liver Cancer (BCLC) classification. Materials and Methods: A total of 124 HCCpatients undergoing surgery were selected. Disease-free survival (DFS), overall survival (OS) and prognosticfactors were respectively assessed. Results: This study showed that the cumulative 1-, 3-, 5-year survival rateswere 79.7%, 59.8% and 41.6% in BCLC-A patients, 76.2%, 9.5% and 0% in BCLC-B patients and 44.9%, 0%and 0% in BCLC-C patients, respectively. The 1-, 3-, 5-year DFS rates were 49%, 24.5% and 9.1% in BCLC-Apatients, 7.5%, 0% and 0% in BCLC-B patients, respectively. No BCLC-C patients survived 1 year after surgery.Multivariate analysis indicated that hepatitis B surface antigen (HBsAg), vascular invasion, intra-hepaticmetastasis, curative resection, tumor rupture and pathologic differentiation were independent prognostic factors.Conclusions: Surgery is effective and safe for patients with HCC >10 cm with sufficient hepatic reserve.     

Liver resection for hepatocellular carcinoma in patients who have undergone prior renal transplantation

BACKGROUND AND OBJECTIVES: Because renal transplantation recipients require immunosuppressive drugs, they have a higher incidence of subsequent malignancies. Among them, hepatocellular carcinoma (HCC) is common. Although liver resection remains an option for curing HCC, the role of liver resection in renal transplantation recipients remains unclear. METHODS: A retrospective review of liver resection for newly diagnosed HCC in 680 patients was conducted. Among them, 18 patients had undergone prior renal transplantation (RT group). The patient background, tumor characteristics, early and long-term results after liver resection were compared with the other 662 patients who had not previously undergone renal transplantation (non-RT group). RESULTS: The patient's background characteristics were comparable between RT and non-RT group. The tumor characteristics, postoperative morbidity, and mortality were not significantly different between the two groups. The 5-year disease-free survival rates in RT and non-RT groups were 18.8% and 41.2%, respectively (P = 0.242), whereas 5-year actuarial survival rates in RT and non-RT groups were 59.1% and 58.3%, respectively (P = 0.738). Two patients lost their graft kidney 3 and 8 years after liver resection. CONCLUSION: With careful protection of the graft kidney, liver resection is still a justified treatment option for HCC in patients who have undergone renal transplantation.     

Imaging of hepatocellular carcinoma recurrence post liver resection: A pictorial essay

This pictorial essay presents and discusses the imaging findings of patients with hepatocellular carcinoma recurrence post liver resection. A broad range of recurrence patterns is reviewed including intrahepatic and extrahepatic recurrences.     

Liver resection in the treatment of hepatocellular carcinoma

Hepatocellular carcinoma is a leading cause of cancer death worldwide. Liver resection and liver transplantation remain the only options for cure. Since the indications for orthotopic liver transplantation are limited, partial liver resection is the more common treatment. Recently, indications for liver resection have been expanded and there have been advances in the associated surgical techniques. This review describes the state-of-the-art of liver resection for hepatocellular carcinoma. Topics covered include: new indications, such as treatment of large tumors, bilobar tumors and those associated with vascular invasion; preoperative assessment of liver function; and surgical strategies. An overview of the most common staging systems, which are useful in predicting prognosis after liver resection for hepatocellular carcinoma, is given.     

Liver resection for hepatocellular carcinoma in patients with end-stage renal failure.

BACKGROUND AND OBJECTIVES: Surgical resection remains the main option for curing hepatocellular carcinoma (HCC). However, liver resection in patients with end-stage renal disease (ESRD) is risky. The aim of this study is to clarify the role of liver resection for treating HCC in patients with ESRD. METHODS: A retrospective review was carried out on 468 patients who underwent liver resection for HCC between 1989 and 1999. The clinicopathological characteristics and operative results of 12 patients who had ESRD (ESRD group) were compared with those of the other 456 patients who did not have ESRD (non-ESRD group). In the ESRD group, heparin-free hemodialysis using the periodic saline-rinse method was performed during the perioperative period. RESULTS: The ESRD group had lower hemoglobin and a higher serum creatinine levels. Other patient background and tumor pathological characteristics were comparable between the two groups as well. The operative morbidity and mortality between the two groups were also similar. The 5-year disease-free survival rates for ESRD and non-ESRD groups were 35.0 and 34.2% (P = 0.31), respectively, while the 5-year actuarial survival rates were 67.8 and 53.3% (P = 0.54), respectively. CONCLUSION: With improving techniques and knowledge of dialysis, liver resection for HCC is justified in selected patients with ESRD.     

In‐hospital mortality from liver resection for hepatocellular carcinoma

BACKGROUND:

There is a wide spectrum of disease burden in hepatocellular carcinoma accompanied by several options for surgical management. However, the associated mortality of such procedures is not well defined. Accurate predictions of patients' perioperative risk would be helpful to guide decision making.

METHODS:

The Nationwide Inpatient Sample was queried for data from 1998 to 2005. A cohort of patients who were discharged for hepatic procedures with a diagnosis of primary liver neoplasm was assembled. Procedures were categorized as hepatic lobectomy, wedge resection, or enucleation/ablation. Logistic regression and bootstrap methods were used to create an integer risk score for estimating the risk of in‐hospital mortality using procedure type, patient demographics, comorbidities, and hospital type. A randomly selected sample of 80% of the cohort (n = 2263) was used to create the score with validation conducted in the remaining 20% (n = 571).

RESULTS:

In total, 2834 patient discharges were identified. Overall in‐hospital mortality was 6.52%. Factors that were included in the final model were age, sex, Charlson comorbidity score, procedure type, and teaching hospital status. Integer values were assigned to these characteristics and were used to calculate an additive score. Four clinically relevant score groups were assembled to stratify the risk of in‐hospital mortality, with a 19‐fold gradient of mortality that ranged from 1.5% to 28.3%. In the derivation set, as in the validation set, the score discriminated well with c‐statistics of 0.75 and 0.73, respectively.

CONCLUSIONS:

The current results indicated that an integer‐based risk score can be used to predict in‐hospital mortality after surgery for hepatocellular carcinoma, and it may be useful for preoperative risk stratification and patient counseling. Cancer 2010. © 2010 American Cancer Society.     

Hepatectomy for ruptured hepatocellular carcinoma classified as Barcelona Clinic Liver Cancer stage 0/A: The optimal treatment

Background and aimsRuptured hepatocellular carcinoma (rHCC) generally has a very poor prognosis and is currently classified as T4 in the tumor–node–metastasis (TNM) staging system. In this study, we aimed to demonstrate the actual impact of rHCC, as well as the positive effect of hepatectomy in patients with Barcelona Clinic Liver Cancer (BCLC) stage 0/A rHCC.MethodsWe enrolled 86 patients with rHCC after surgery and 526 patients with non-rHCC after surgery or transcatheter arterial chemoembolization (TACE). Survival curves were plotted using the Kaplan–Meier method to compare the postoperative prognosis of patients with rHCC with that of patients with non-rHCC. Univariate and multivariate Cox regression analyses were used to identify the risk factors affecting patient survival.ResultsBCLC stage 0/A rHCC treated with surgery had a worse prognosis than BCLC stage 0/A non-rHCC treated with surgery (overall survival [OS]: hazard ratio [HR] = 3.12 [2.24–4.34], P < 0.001; recurrence-free survival [RFS]: HR = 2.26 [1.65–3.09], P < 0.001). Rupture was an independent prognostic factor in patients with BCLC stage 0/A rHCC (OS: HR = 1.685 [1.416–2.006], P < 0.001; RFS: HR = 1.484 [1.267–1.737], P < 0.001), and patients with BCLC stage 0/A rHCC who underwent surgery had a comparable prognosis to patients with BCLC stage B HCC who underwent surgery or TACE (OS: P = 0.78).ConclusionsPatients classified as having BCLC stage 0/A rHCC can achieve comparable outcomes to patients with BCLC stage B HCC after hepatectomy. However, not all patients with rHCC should be classified as T4 in the TNM staging system.     

术前抗病毒治疗对HBV-DNA 阴性肝细胞癌患者术后病毒再激活及肝功能的影响*

目的:评估术前抗病毒治疗对术后乙肝病毒再激活以及肝功能的影响。方法:2012年7 月至2016年3 月将广西医科大学附属肿瘤医院肝胆胰脾外科乙肝病毒DNA 阴性的HCC 患者分成抗病毒组（66例）及对照组（108 例）,抗病毒组术前给予恩替卡韦分散片抗病毒治疗,对照组未给予抗病毒治疗。统计分析术后HBV 再激活及肝功能指标变化情况。结果:抗病毒组HBV 激活率为3%（2/ 66）,对照组为27.8%（30/ 108）。 多因素分析显示小部分肝切术（HR= 4.695;95%CI:1.257- 17.537,P = 0.021）及术前未抗病毒治疗（HR= 8.164;95%CI:1.831- 36.397,P = 0.006）是术后HBV 再激活的危险因素。抗病毒组与未抗病毒组,激活组与未激活组术后7 天内肝功能指标差异无统计学意义（P > 0.05）,术后30天比较,ALT 及ALB 差异有统计学意义（P < 0.05）。 结论:对于DNA阴性的HCC 患者,肝切除术可导致HBV 再激活,术前抗病毒治疗能有效降低HBV 再激活风险及保护肝功能。      

Long‐term outcomes of proton beam therapy in patients with previously untreated hepatocellular carcinoma

Long‐term efficacy of proton beam therapy (PBT) remains unclear for patients with previously untreated hepatocellular carcinoma (HCC). We aimed to study the long‐term outcomes of PBT according to Barcelona Clinic Liver Cancer (BCLC) staging classifications in patients with previously untreated HCC. The major eligibility criteria of this observational study were an Eastern Cooperative Oncology Group performance status (PS) 0–2, Child–Pugh grade A or B, previously untreated HCC covered within an irradiation field, and no massive ascites. A total of 66.0–77.0 GyE was administered in 10–35 fractions. Local tumor control (LTC), defined as no progression in the irradiated field, progression‐free survival (PFS), and overall survival (OS) were assessed according to BCLC staging. From 2002 to 2009 at our institution, 129 patients were eligible. The 5‐year LTC, PFS, and OS rates were 94%, 28%, and 69% for patients with 0/A stage disease (n = 9/21), 87%, 23%, and 66% for patients with B stage disease (n = 34), and 75%, 9%, and 25% for patients with C stage disease (n = 65), respectively. The 5‐year LTC and OS rates of 15 patients with tumor thrombi in major vessels were 90% and 34%, respectively. Multivariate analyses revealed that PS (0 versus 1–2) was a significant prognostic factor for OS. No grade 3 or higher adverse effects were observed. PBT showed favorable long‐term efficacies with mild adverse effects in BCLC stage 0 to C, and can be an alternative treatment for localized HCC especially when accompanied with tumor thrombi. This study was registered with UMIN Clinical Trials Registry (UMIN000025342).     

Efficacy and Safety of CalliSpheres^® Drug-Eluting Beads Transarterial Chemoembolization in Barcelona Clinic Liver Cancer Stage C Patients

This study aimed to investigate the efficacy and safety of drug-eluting beads transarterial chemoembolization (DEB-TACE) treatment in Barcelona Clinic Liver Cancer (BCLC) stage C liver cancer patients. In 39 patients with BCLC stage C liver cancer, after the first cycle of DEB-TACE, 2 (5.1%) and 24 (61.5%) patients achieved complete response (CR) and partial response (PR) to give an overall objective response rate (ORR) of 66.7%. With respect to the second cycle of therapy, the ORR was higher in patients receiving DEB-TACE compared with those receiving cTACE (57.1% vs. 11.1%). After the first cycle of DEB-TACE treatment, the percentages of abnormal albumin (ALB), total protein (TP), total bilirubin (TBIL), and alanine aminotransferase (ALT) worsened at 1 week and recovered at 1 month. The number of patients with abnormal aspartate aminotransferase (AST) did not increase at 1 week but elevated at 1 month. After the second cycle of DEB-TACE or cTACE treatment, no difference was observed between cTACE and DEB-TACE in terms of all adverse events (AEs) at all visits, and most of the AEs did not change after the second cycle in both groups. The most common AEs after the first and second treatment cycles were pain, fever, and nausea/vomiting. These results demonstrate that DEB-TACE offers patients with BCLC stage C liver cancer a clinically active short-term treatment that is safe and relatively well tolerated.