Segmental chromosome aberrations and clinical response impact outcome of inss stage III patients ≥18 months with unfavorable histology and without MYCN amplification: A Children’s Oncology Group (COG) report

• Published in: Journal of clinical oncology Vol. 38; no. 15_suppl; p. 10502
• Main Authors: Pinto, Navin R., Naranjo, Arlene, Hibbitts, Emily, Ding, Xiangming, Tibbetts, Rachelle, Kennedy, Rebekah, Pfau, Ruthann, Hogarty, Michael D., Kreissman, Susan G., Irwin, Meredith, Park, Julie R., Asgharzadeh, Shahab
• Format: Journal Article
• Language: English
• Published: 20.05.2020
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2020.38.15_suppl.10502

Abstract only 10502 Background: Patients with INSS stage III neuroblastoma represent a heterogeneous population with respect to disease presentation and prognosis and controversy exists regarding the most effective treatment algorithms. Patients ≥18 months of age with INSS Stage 3 tumors that are unfavorable histology (UH) and MYCN-non-amplified ( MYCN-NA) represent a small cohort of patients with an outcome intermediate of those with favorable histology tumors and MYCN amplified tumors. The presence of Segmental Chromosome Aberrations (SCA) may predict outcome; however, their impact specifically in this cohort of patients has not been reported. Methods: Eligible patients enrolled on therapeutic protocols A3973 (n=34), ANBL0532 (n=27), and biology protocol ANBL00B1 (n=101 with 29 treated on A3973/ANBL0532) with stage III disease, MYCN–NA, UH and age ≥18 months at diagnosis were analyzed. Copy number alterations and loss of heterozygosity (LOH) for relevant loci were scored for gains/losses by two independent reviewers. Results: The 5-year EFS/OS for children ≥18 months with stage III, MYCN–NA, UH disease treated on A3973 and ANBL0532 was 73.0±8.1%/87.9±5.9% and 61.4±10.2%/ 73.0±9.2%, respectively, with no statistical differences in EFS or OS between the two cohorts (p=0.1286 and p=0.2180, respectively). In the combined cohort of patients enrolled on A3973 and ANBL0532, statistically significant differences were found (p(s) <0.0001) in patients with CR/VGPR (n=39) and PR (n=13) having better outcomes than <PR (n=5) (5-year EFS: 74.0±7.6% vs. 75.0±12.5% vs. 0%; 5-year OS: 84.4±6.2% vs. 100% vs. 20.0±17.9%). Subjects with chromosome 11q loss/LOH had an inferior outcome in comparison to those without 11q loss/LOH (10-year EFS: 44.4+/-24.1% vs. 78.1+/-9.4%, p=0.01; 10-year OS: 62.4+/-15.9% vs. 85.9+/-7.8%, p=0.02)). Patients with 1p loss/LOH and 2p gain also showed trend towards worse event-free survival (p=0.086 and p=0.088, not statistically significant) but not in overall survival. Conclusions: High-risk therapy that included single myeloablative therapy led to an 81.6±5.3%5-year OS in patients ≥18 months with UH and MYCN–NA stage III neuroblastoma. Response to therapy is a powerful predictor of survival and the presence of chromosome 11q loss/LOH is also associated with inferior outcomes. These patients should continue to be treated on high-risk clinical trials.