Hwang WL, et al. - Whether risk stratification of patients with neuroblastoma can be improved by taking into account tumor mutational burden over and above the conventional risk factors was investigated. Given the considerable heterogeneity in outcomes seen within conventional risk groups. As per observations, for optimizing risk stratification and guiding treatment decisions, mutational burden of primary neuroblastoma may be useful in combination with conventional risk factors.

Methods

• Using three independent cohorts, researchers analyzed the somatic mutational burden of 515 primary, untreated neuroblastoma tumors.
• They performed whole-exome/genome sequencing of tumor samples vs matched blood leukocytes to determine mutations in coding regions.
• They carried out analysis of 5-year overall survival, for which the Kaplan–Meier method and log-rank test were used and for 459 patients for whom survival data were available.
• All statistical tests were two-sided.

Results

• The estimated overall somatic mutational burden (mean = 3, range = 0–56) was low but high mutational burden (>3 mutations) was seen in 107 patients.
• Unfavorable histology and age 18 months and older were linked to high mutational burden.
• Inferior 5-year overall survival (29.0%, 95% confidence interval [CI] = 17.2 to 41.8%) was seen among patients with high mutational burden vs those with three or fewer somatic mutations (76.2%, 95% CI = 71.5 to 80.3%) (log-rank P<.001); this link was sustained when limiting the analysis to genes included on a 447-gene panel commonly used in clinical practice.
• Multivariable analysis revealed prognostic significance of mutational burden, independent of age, stage, histology and MYCN status.