Optimal time point of response assessment for predicting survival is associated with tumor burden in hepatocellular carcinoma receiving repeated transarterial chemoembolization

Objectives Objective response rate (ORR) under mRECIST criteria after transarterial chemoembolization (TACE) is a well-perceived surrogate endpoint of overall survival (OS). However, its optimal time point remains controversial and may be influenced by tumor burden. We aim to investigate the surrogacy of initial/best ORR in relation to tumor burden. Methods A total of 1549 eligible treatment-naive patients with unresectable hepatocellular carcinoma (HCC), Child-Pugh score <= 7, and performance status score <= 1 undergoing TACE between January 2010 and May 2016 from 17 academic hospitals were retrospectively analyzed. Based on six-and-twelve criteria, tumor burden was graded as low, intermediate, and high if the sum of the maximum tumor diameter and tumor number was <= 6, > 6 but <= 12, and > 12, respectively. Results Both initial and best ORRs interacted with tumor burden. Initial and best ORRs could equivalently predict and correlate with OS in low (adjusted HR, 2.55 and 2.95, respectively, both p < 0.001; R = 0.84, p = 0.035, and R = 0.97, p = 0.002, respectively) and intermediate strata (adjusted HR, 1.81 and 2.22, respectively, both p < 0.001; R = 0.74, p = 0.023, and R = 0.9, p = 0.002, respectively). For high strata, only best ORR exhibited qualified surrogacy (adjusted HR, 2.61, p < 0.001; R = 0.70, p = 0.035), whereas initial ORR was not significant (adjusted HR, 1.08, p = 0.357; R = 0.22, p = 0.54). Conclusions ORR as surrogacy of OS is associated with tumor burden. For patients with low/intermediate tumor burden, initial ORR should be preferred in its early availability upon similar sensitivity, whereas for patients with high tumor burden, best ORR has optimal sensitivity. Timing of OR assessment should be tailored according to tumor burden.

Automated summary

The relationship between initial/best objective response rate (ORR) and tumor burden was investigated in patients with unresectable hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE). The results showed that both initial and best ORR were associated with tumor burden and could predict overall survival (OS) in patients with low/intermediate tumor burden. However, only best ORR exhibited qualified surrogacy in patients with high tumor burden.