Predictors of Micrometastases in Patients with Barcelona Clinic Liver Cancer Classification B Hepatocellular Carcinoma
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Purpose: Transarterial chemoembolization (TACE) is indicated for Barcelona Clinic Liver Cancer (BCLC) B hepatocellular carcinoma(HCC). Whether TACE provides any long-term survival benefits remains unclear. We aimed to investigate micrometastases predictors with which to identify patients who would benefit from surgical resection (SR). Materials and Methods: First, we analyzed risk factors of micrometastases, microvascular invasion, and poor histologic grade in 38 patients with newly diagnosed resectable BCLC stage B HCC limited to one or two segments with well-preserved liver function and who underwent SR between January 2006 and December 2013. Second, we validated identified risk factors in 54 newly diagnosedresectable BCLC B HCC patients with well-preserved liver function who underwent TACE during the same period to determinetheir influence on survival. Results: Risk factors of micrometastases in SR patients were α-fetoprotein (AFP) ≥110 [hazard ratio (HR)=5.166; 95% confidence interval (CI), 1.031–25.897; p=0.046] and prothrombin induced by vitamin K absence-II (PIVKA-II) ≥800 (HR=5.166; 95% CI, 1.031–25.897; p=0.046). The cumulative probability of tumor recurrence (p=0.009) after SR differed according to levels of AFP and PIVKA-II. After validation of these risk factors in the TACE group, patients with SR and AFP <110 and PIVKA-II <800 had superior survival outcomes than other patients (HR=0.116; 95% CI, 0.027–0.497; p=0.004). Conclusion: AFP and PIVKA-II levels predict micrometastases and survival. Therefore, they should be considered when selecting SR for BCLC B HCC.
Abstract
Purpose: Transarterial chemoembolization (TACE) is indicated for Barcelona Clinic Liver Cancer (BCLC) B hepatocellular carcinoma(HCC). Whether TACE provides any long-term survival benefits remains unclear. We aimed to investigate micrometastases predictors with which to identify patients who would benefit from surgical resection (SR). Materials and Methods: First, we analyzed risk factors of micrometastases, microvascular invasion, and poor histologic grade in 38 patients with newly diagnosed resectable BCLC stage B HCC limited to one or two segments with well-preserved liver function and who underwent SR between January 2006 and December 2013. Second, we validated identified risk factors in 54 newly diagnosedresectable BCLC B HCC patients with well-preserved liver function who underwent TACE during the same period to determinetheir influence on survival. Results: Risk factors of micrometastases in SR patients were α-fetoprotein (AFP) ≥110 [hazard ratio (HR)=5.166; 95% confidence interval (CI), 1.031–25.897; p=0.046] and prothrombin induced by vitamin K absence-II (PIVKA-II) ≥800 (HR=5.166; 95% CI, 1.031–25.897; p=0.046). The cumulative probability of tumor recurrence (p=0.009) after SR differed according to levels of AFP and PIVKA-II. After validation of these risk factors in the TACE group, patients with SR and AFP <110 and PIVKA-II <800 had superior survival outcomes than other patients (HR=0.116; 95% CI, 0.027–0.497; p=0.004). Conclusion: AFP and PIVKA-II levels predict micrometastases and survival. Therefore, they should be considered when selecting SR for BCLC B HCC.
참고문헌 (29)
- Zhong JH, "Comparison of long-term survival of patients with BCLC stage B hepatocellular carcinoma after liver resection or transarterial chemoembolization", PLoS One, 8, pp.e68193~ (2013)
- Bosetti C, "Trends in mortality from hepatocellular carcinoma in Europe, 1980-2004", Hepatology, 48, pp.137~145 (2008)
- Zhong JH, "Hepatic resection associated with good survival for selected patients with intermediate and advanced-stage hepatocellular carcinoma", Ann Surg, 260, pp.329~340 (2014)
- Bruix J, "Management of hepatocellular carcinoma: an update", Hepatology, 53, pp.1020~1022 (2011)
- Okuda K, "Natural history of hepatocellular carcinoma and prognosis in relation to treatment. Study of 850 patients", Cancer, 56, pp.918~928 (1985)
- "A new prognostic system for hepatocellular carcinoma: a retrospective study of 435 patients: the Cancer of the Liver Italian Program (CLIP) investigators", Hepatology, 28, pp.751~755 (1998)
- Chevret S, "A new prognostic classification for predicting survival in patients with hepatocellular carcinoma. Groupe d’Etude et de Traitement du Carcinome Hépatocellulaire", J Hepatol, 31, pp.133~141 (1999)
- European Association For The Study Of The Liver, "EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma", J Hepatol, 56, pp.908~943 (2012)
- Livraghi T, "Is it time to reconsider the BCLC", AASLD therapeutic flow-chart?, 2010, pp.102, 868~876
- Cabibbo G, "A meta-analysis of survival rates of untreated patients in randomized clinical trials of hepatocellular carcinoma", Hepatology, 51, pp.1274~1283 (2010)
- Cillo U, "Prospective validation of the Barcelona Clinic Liver Cancer staging system", J Hepatol, 44, pp.723~731 (2006)
- Llovet JM, "Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival", Hepatology, 37, pp.429~442 (2003)
- Jianyong L, "Barcelona clinic liver cancer stage B hepatocellular carcinoma:transarterial chemoembolization or hepatic resection?", Medicine (Baltimore), 93, pp.e180~ (2014)
- Yu SJ, "A concise review of updated guidelines regarding the management of hepatocellular carcinoma around the world: 2010-2016", Clin Mol Hepatol, 22, pp.7~17 (2016)
- Sasaki A, "Microsatellite distribution and indication for locoregional therapy in small hepatocellular carcinoma", Cancer, 103, pp.299~306 (2005)
- Okusaka T, "Satellite lesions in patients with small hepatocellular carcinoma with reference to clinicopathologic features", Cancer, 95, pp.1931~1937 (2002)
- Bruix J, "Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver", J Hepatol, 35, pp.421~430 (2001)
- Sala M, "Prognostic prediction in patients with hepatocellular carcinoma", Semin Liver Dis, 25, pp.171~180 (2005)
- Delis SG, "Hepatic resection for hepatocellular carcinoma exceeding Milan criteria", Surg Oncol, 19, pp.200~207 (2010)
- Yang T, "Surgical resection for advanced hepatocellular carcinoma according to Barcelona Clinic Liver Cancer (BCLC) staging", J Cancer Res Clin Oncol, 138, pp.1121~1129 (2012)
- Torzilli G, "A snapshot of the effective indications and results of surgery for hepatocellular carcinoma in tertiary referral centers: is it adherent to the EASL", AASLD recommendations?: an observational study of the HCC East-West study group, 2013, pp.257, 929~937
- Chan SL, "New utility of an old marker: serial alpha-fetoprotein measurement in predicting radiologic response and survival of patients with hepatocellular carcinoma undergoing systemic chemotherapy", J Clin Oncol, 27, pp.446~452 (2009)
- Liu W, "Hepatic resection improved the long-term survival of patients with BCLC stage B hepatocellular carcinoma in Asia: a systematic review and meta-analysis", J Gastrointest Surg, 19, pp.1271~1280 (2015)
- Weinmann A, "Survival analysis of proposed BCLC-B subgroups in hepatocellular carcinoma patients", Liver Int, 35, pp.591~600 (2015)
- Plessier A, "Underestimation of the influence of satellite nodules as a risk factor for post-transplantation recurrence in patients with small hepatocellular carcinoma", Liver Transpl, 10(2 Suppl 1), pp.S86~S90 (2004)
- Ishii M, "Simultaneous measurements of serum alpha-fetoprotein and protein induced by vitamin K absence for detecting hepatocellular carcinoma. South Tohoku District Study Group", Am J Gastroenterol, 95, pp.1036~1040 (2000)
- Kang SH, "Clinical characteristics and prognosis of hepatocellular carcinoma with different sets of serum AFP and PIVKA-II levels", Eur J Gastroenterol Hepatol, 24, pp.849~856 (2012)
- Fujiyama S, "Tumor markers in early diagnosis, follow-up and management of patients with hepatocellular carcinoma", Oncology, 62(Suppl 1), pp.57~63 (2002)
- Toyoda H, "Prognostic significance of simultaneous measurement of three tumor markers in patients with hepatocellular carcinoma", Clin Gastroenterol Hepatol, 4, pp.111~117 (2006)