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

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.