Long-term follow-up of patients with intermediate-risk neuroblastoma treated with response- and biology-based therapy: A report from the Children's Oncology Group study ANBL0531

Abstract

Background: We previously reported excellent three-year overall survival (OS) for patients with newly diagnosed intermediate-risk neuroblastoma treated with a biology- and response-based algorithm on the Children's Oncology Group study ANBL0531. We now present the long-term follow-up results.

Methods: All patients who met the age, stage, and tumor biology criteria for intermediate-risk neuroblastoma were eligible. Treatment was based on prognostic biomarkers and overall response. Event-free survival (EFS) and OS were estimated by the Kaplan-Meier method.

Results: The 10-year EFS and OS for the entire study cohort (n = 404) were 82.0% (95% confidence interval (CI), 77.2%-86.9%) and 94.7% (95% CI, 91.8%-97.5%), respectively. International Neuroblastoma Staging System stage 4 patients (n = 133) had inferior OS compared with non-stage 4 patients (n = 271; 10-year OS: 90.8% [95% CI, 84.5%-97.0%] vs 96.6% [95% CI, 93.9%-99.4%], p = .02). Infants with stage 4 tumors with ≥1 unfavorable biological feature (n = 47) had inferior EFS compared with those with favorable biology (n = 61; 10-year EFS: 66.8% [95% CI, 50.4%-83.3%] vs 86.9% [95% CI, 76.0%-97.8%], p = .02); OS did not differ (10-year OS: 84.4% [95% CI, 71.8%-97.0%] vs 95.0% [95% CI, 87.7%-100.0%], p = .08). Inferior EFS but not OS was observed among patients with tumors with (n = 26) versus without (n = 314) 11q loss of heterozygosity (10-year EFS: 68.4% [95% CI, 44.5%-92.2%] vs 83.9% [95% CI, 78.7%-89.2%], p = .03; 10-year OS: 88.0% [95% CI, 72.0%-100.0%] vs 95.7% [95% CI, 92.8%-98.6%], p = .09).

Conclusions: The ANBL0531 trial treatment algorithm resulted in excellent long-term survival. More effective treatments are needed for subsets of patients with unfavorable biology tumors.

Keywords: Intermediate risk; long‐term follow‐up; neuroblastoma; outcomes.

FIGURE 1

(A) ANBL0531 treatment overview. (B) Group patient numbers including completion of protocol, discontinuation from protocol and deaths (created with BioRender.com).

FIGURE 2

(A) Event-free survival (EFS) and overall survival (OS) for intermediate risk (IR) patients (n=404). (B) EFS for IR patients according to initial treatment assignment (n=404; P=0.002). (C) OS for IR patients according to initial treatment assignment (n=404; P<0.001). (D) EFS for evaluable, intermediate risk patient according to 1p loss of heterozygosity (LOH) status (n=341; P=0.64). (E) OS for evaluable, intermediate risk patient according to 1p LOH status (n=341; P=0.44). (F) EFS for evaluable, intermediate risk patient according to 11q LOH status (n=340; P=0.03). (G) OS for evaluable, intermediate risk patient according to 11q LOH status (n=340; P=0.09). Life tables data is available in Supplemental Table S6.

FIGURE 3

(A) Event-free survival (EFS) and overall survival (OS) for evaluable infants with stage 4 disease younger than 365 days (n=125). (B) EFS for evaluable infants with stage 4 disease younger than 365 days of age according to tumor biology* (n=108; P=0.0154). (C) OS for evaluable infants with stage 4 disease younger than 365 days of age according to tumor biology* (n=108; P=0.08). Life tables data is available in Supplemental Table S6. * Favorable biology constituted hyperdiploid tumors with favorable histology and normal 1p and 11q alleles. Unfavorable biology tumors had at least one unfavorable feature (diploidy, unfavorable histology, 1p loss of heterozygosity, or 11q loss of heterozygosity)