Rapid decrease of serum alpha-fetoprotein and tumor volume predicts outcome in children with hepatoblastoma treated with neoadjuvant chemotherapy

Abstract

Background

Neoadjuvant chemotherapy is given to children with unresectable hepatoblastoma to increase the rate and safety of curative complete surgical resection. Elevated levels of serum alpha-fetoprotein (sAFP) decline with tumor shrinkage. In this single-institution retrospective study, we determined early dynamic changes of sAFP levels and tumor volume in children during therapy for unresectable hepatoblastoma.

Methods

We correlated early dynamic changes of sAFP levels and tumor volume and the sum of the longest primary tumor and measurable metastatic disease diameters as per RECIST 1.1 criteria with patient outcome.

Results

There were 34 patients, 7 of whom died of disease. Patients with ≥ 90% (≥ 1 log₁₀) decrease in sAFP levels after two chemotherapy courses had a better event-free survival (P = 0.039) and overall survival (OS; P = 0.045) than those with < 90% decrease. During this treatment interval, average tumor volume decreased from 481 mL (± 254 mL) to 268 mL (± 258 mL; P < 0.001) which was associated with OS (P = 0.029). Relative change in sAFP levels or tumor volume in between course 2 and pre-surgery or response as per RECIST 1.1 was not associated with OS.

Conclusion

Early decline of sAFP levels and tumor volume, but not response as per RECIST 1.1 may predict survival in children with unresectable hepatoblastoma. This finding could be useful to identify therapy non-responders for whom alternative interventions may be required for cure. Confirmation of the finding using larger patient cohorts will be necessary before this strategy is incorporated into prospective trials.

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