Predictors of differential outcomes according to response to induction chemotherapy in high-risk neuroblastoma.

Abstract

10032 Background: Response to induction chemotherapy has been shown to predict outcome in patients with high risk neuroblastoma, with those achieving a complete response (CR) having superior outcomes. Little is known about what factors impact survival within groups of patients with favorable and unfavorable end-induction response. We evaluated whether conventional prognostic factors remain prognostic in subsets of patients defined by response to induction. Methods: Patients from four COG high risk trials (A3973, ANBL02P1, ANBL0532, and ANBL12P1) were included. End-induction response was determined according to the 1993 International Neuroblastoma Response Criteria (INRC). Patients were categorized as having end-induction responses of CR, partial response (PR) or better, less than PR without progressive disease (PD), and PD. Univariate Cox models calculated OS hazard ratios for clinical and biological variables in subsets defined by response category. Results: 1,244 patients were included. Among all patients, age >5 years, INSS stage 4 disease, adrenal primary site and unfavorable histology by INPC were associated with inferior OS (see Table). Among patients who achieved a CR, stage 4 disease was the only factor that remained significantly associated with worse OS. Among those who achieved PR or better, age >5 years, stage 4 disease and unfavorable histology remained significantly associated with inferior OS. For those with less than PR but without PD, adrenal primary site, MYCN amplification and 1p LOH were significantly associated with inferior OS. For those with PD, MYCN amplification and 1p LOH were associated with worse OS, but older age was associated with better OS. Conclusions: Specific prognostic factors in neuroblastoma are associated with differential survival in groups defined by response to induction. Age, stage, and histology appear to be associated with OS for patients with more favorable response to induction, whereas MYCN and 1p LOH play a greater role in patients with unfavorable response to induction. These data can help to further define prognosis for patients with variable responses to induction. [Table: see text]