Defining hepatoblastoma responsiveness to induction therapy as measured by tumor volume and serum alpha-fetoprotein kinetics

Abstract

Purpose: Hepatoblastoma is commonly unresectable at presentation, necessitating induction chemotherapy before definitive resection. To refine the paradigm for timing of resection, we questioned whether a plateau in hepatoblastoma responsiveness to neoadjuvant therapy could be detected by calculating tumor volume (TV) and serum alpha-fetoprotein (sAFP) kinetics.

Methods: To calculate TV and sAFP as measures of treatment responsiveness over time, infants having initially unresectable epithelial-type hepatoblastomas were identified at a single institution (1996-2008). Effects of therapy type, therapy duration, and lobe of liver involvement on TV, sAFP, margin status, and toxicity were analyzed.

Results: Of 24 infants treated for epithelial-type hepatoblastoma during this interval, 5 were resected primarily, and 15 had complete digital films for kinetics analysis. Both TV and sAFP decreased dramatically over time (P < .0001). No statistically significant difference in mean TV or sAFP was detected after chemotherapy cycle 2. Left lobe tumors had greater presenting levels of and significantly slower decay in sAFP compared with right lobe tumors (P = .005), although no statistically significant differences in TV existed between liver lobes. Resection margins did not change with therapy duration.

Conclusions: Measuring TV and sAFP kinetics accurately reflects hepatoblastoma responsiveness to induction therapy. Treatment toxicities may be reduced by earlier resection and tailoring of chemotherapeutic regimens.

Figure 1

Graph shows number of patients having hepatoblastoma resection after each cycle of induction therapy.

Figure 2

Hepatoblastoma decay after each induction therapy cycle, as estimated by sAFP (A) and TV (B) kinetics. (C) Reduced monotonic regression curves show similar decay patterns between sAFP (red) and TV (blue) measurements.

Figure 3

Hepatoblastoma decay according to lobe of origin (left lobe, blue; right lobe, red). (A) Left lobe tumors present with higher sAFP levels and show slower decay. (B) TV changes according to lobe of origin. P-values represent mixed models ANOVA tests of lobe by time interactions.

Figure 4

Resection margins do not lengthen with increasing duration (A) or cycles (B) of induction therapy (ρ = Spearman correlation).