As reported in the Journal of Clinical Oncology by Irwin et al, the Children’s Oncology Group (COG) has developed a new neuroblastoma risk classification (COG version 2) that uses the International Neuroblastoma Risk Group Staging System (INRGSS) and incorporates segmental chromosome aberrations as an additional biomarker. As noted by the investigators, the most recent COG risk classification system (version 1) used tumor stage as defined by the International Neuroblastoma Staging System (INSS).
Study Details
The study involved data from 4,832 newly diagnosed patients enrolled in the COG neuroblastoma biology study ANBL00B1 between 2007 and 2017 with known age, INSS stage, and INRGSS stage. Central testing was performed for tumor MYCN status, ploidy, segmental chromosome aberration status (1p and 11q), and International Neuroblastoma Pathology Classification (INPC) histology.
Key Findings
Most patients with locoregional tumors had excellent outcomes. Exceptions were patients with image-defined risk factors (INRGSS L2) with MYCN amplification, who had 5-year event-free and overall survival rates of 76.3% and 79.9%, and patients aged ≥ 18 months with L2 MYCN nonamplified tumors with unfavorable INPC histology, who had 5-year event-free and overall survival rates of 72.7% and 82.4%. These categories included the majority of L2 patients with segmental chromosome aberrations.
Among patients with stage M (metastatic) and MS (metastatic, special) disease, genomic biomarkers that affected risk assignment were MYCN status for those up to 12 months of age as well as MYCN status, histology, ploidy, and segmental chromosome aberration status for those between the ages of 12 to 18 months.
In COG version 2, high-risk groups include INRGSS L2 patients:
- With MYCN amplification, any segmental chromosome aberration, any ploidy, and any INPC histology
- Aged 18 months to 5 years with no MYCN amplification, any segmental chromosome aberration, any ploidy, and unfavorable histology
- Aged ≥ 5 years with no MYCN amplification, any segmental chromosome aberration, any ploidy, and unfavorable histology.
COG version 2 intermediate-risk groups include INRGSS L2 patients:
- Aged < 18 months with no MYCN amplification, no segmental chromosome aberration, ploidy = DNA index > 1, and favorable histology
- Aged < 18 months with no MYCN amplification and any segmental chromosome aberration, ploidy, or histology
- Aged 18 months to 5 years with no MYCN amplification, any segmental chromosome aberration, any ploidy, and favorable histology
- Aged ≥ 5 years with no MYCN amplification, any segmental chromosome aberration, any ploidy, and unfavorable histology.
COG version 2 low-risk groups include all INRGSS L1 patients.
Among 2,466 non–high-risk patients on COG version 1, 85 (3.4%) were reassigned as high risk on COG version 2, whereas reassignments involving other risk groups were more common. For example, in a COG version 2 low-risk group with 1,383 patients, 18.6% were intermediate risk and 2.9% were high risk on COG version 1. In a COG version 2 intermediate-risk group with 427 patients, 17.8% were low risk and 0.2% were high risk on version 1. In a version 2 high-risk group with 94 patients, 17.0% were low risk and 9.6% were intermediate risk on version 1.
On COG version 1, the 5-year event-free and overall survival rates were 89.4% and 97.9% for low-risk patients, 86.1% and 84.9% for intermediate-risk patients, and 50.8% and 61.9% for high-risk patients. On COG version 2, the 5-year event-free and overall survival rates were 90.7% and 97.9% for low-risk patients, 85.1% and 95.8% for intermediate-risk patients, and 51.2% and 62.5% for high-risk patients.
The investigators concluded: “A revised 2021 COG neuroblastoma risk classifier (version 2) that uses the INRGSS and incorporates segmental chromosome aberrations has been adopted to prospectively define COG clinical trial eligibility and treatment assignment.”
Michael D. Hogarty, MD, of Children’s Hospital of Philadelphia and Perelman School of Medicine, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was supported by National Cancer Institute grants and St. Baldrick’s Foundation. For full disclosures of the study authors, visit ascopubs.org.
