Predictive Factors of Tumor Recurrence and Survival in Patients with Hepatocellular Carcinoma treated with Transarterial Chemoembolization
Razvan Cerban1, Carmen Ester1, Speranta Iacob1, Mugur Grasu2, Liliana Pâslaru3, Radu Dumitru2, Ioana Lupescu2, Georgiana Constantin3, Adina Croitoru4, Liana Gheorghe1
1) Center for Digestive Diseases and Liver Transplantation, Fundeni Clinical Institute; Carol Davila University of Medicine and Pharmacy, Bucharest,
2) Center for Interventional Radiology and Medical Imaging, Fundeni Clinical Institute; Carol Davila University of Medicine and Pharmacy, Bucharest,
3) Department of Biochemistry, Fundeni Clinical Institute, Bucharest,
4) Department of Medical Oncology, Fundeni Clinical Institute, Bucharest, Romania
Background & Aims: To evaluate the predictive factors for recurrence of the disease and overall survival(OS) after achieving complete response (CR) in patients with hepatocellular carcinoma (HCC) treated withtransarterial chemoembolization (TACE).
Methods: From January 2013 to December 2017, 168 treatment-naïve patients diagnosed with HCCunderwent TACE as a first-line therapy and the gathered data was retrospectively reviewed. We determined the predictive factors for complete response (CR), for recurrence after CR and for survival using the Cox proportional hazard model.
Results: Median follow-up was 27.4 months (range 4-65 months). The mean patient age was 62.2±7.9 years. Eighty-three patients had an α-fetoprotein (AFP) level > 20ng/mL. The median maximal diameter of the tumors was 3.5 cm. Sixty-three patients (37.5%) achieved CR after TACE, and recurrence after CR was detected in 37 patients (58.7%). In multivariate analysis, tumor size (≤4.5 cm) and a single tumor were found to be predictive factors for CR, with hazard ratios (HRs) of 2.352 (p=0.022) and 3.964 (p<0.0001), respectively. After achieving CR the median time to recurrence was 12 months (range 6-24 months). Elevated serum AFP > 25 ng/mL and multiple tumors were demonstrated to have a significant relationship with recurrence after CR, with HRs of 1.650 (p=0.05) and 3.932 (p=0.038), respectively. Increased initial serum AFP > 22 ng/mL, tumor
size > 4.5 cm, outside Milan criteria, not receiving a liver transplant and presence of portal vein thrombosis (PVT) were correlated with poor survival.
Conclusions: In patients treated with TACE as an initial therapy, tumor size (≤4.5 cm) and single tumor were predictive factors for CR. Multiple nodules and an elevated serum AFP > 25 ng/mL were predictive factors for recurrence after CR. Outside Milan criteria tumors, elevated AFP levels and the presence of PVT were significantly correlated with decreased survival.
Key words: hepatocellular carcinoma – transarterial chemoembolization – alpha-fetoprotein – tumor recurrence – survival.
Abbreviations: AFP: alpha-fetoprotein; ALT: alanine aminotransferase; AST: aspartate aminotransferase; ART: assessment for retreatment with transarterial chemoembolization; BCLC: Barcelona Clinic Liver Cancer; CR: complete response; DEBDOX: Doxorubicin-loaded DC Bead; GGT: gammaglutamyltransferase; HCC: hepatocellular carcinoma; HBV: hepatitis B virus; HCV: hepatitis C virus; HR: hazard ratio; MELD: model for end-stage liver disease; mRECIST: modified Response Evaluation Criteria in Solid Tumors; PVT: portal vein thrombosis; RFA: radiofrequency ablation; OS: overall survival; TACE: transarterial chemoembolization.