170 - Reduced-Dose Radiation Therapy for High-Risk Neuroblastoma: Results from a Prospective Clinical Trial

C. B. Jackson¹, S. Modak¹, M. P. LaQuaglia², B. Kushner¹, J. T. Gerstle³, E. Basu¹, N. K. Cheung¹, F. Iglesias-Cardenas¹, and S. L. Wolden¹; ¹Memorial Sloan Kettering Cancer Center, New York, NY, ²Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, ³Memorial Sloan Kettering Center, New York, NY

Purpose/Objective(s): After receiving dose-intensive chemotherapy and gross total resection (GTR), patients with high-risk neuroblastoma (HR-NB) are treated with adjuvant radiation therapy (RT) to the primary site, typically to a dose of approximately 21 Gy. This regimen is associated with excellent local control. However, in these young children, late toxicities to bone, pancreas, and other organs as well as second cancer risk are a major concern. After favorable results in a pilot trial using 18 Gy in 25 patients, we sought to prospectively evaluate local control with a further dose reduction to 15 Gy. Materials/

Methods: Eligible patients included those with HR-NB (as defined by the Children’s Oncology Group risk stratification schema) who have achieved a GTR of the primary site of disease after induction systemic therapy. Any patients with macroscopic residual disease at the primary site after surgery were excluded. Following surgery, patients were treated with 15 Gy to the primary site in 1.5 Gy fractions twice daily. The primary outcome of the trial was to assess the local failure (LF) rate, as determined by radiographic imaging. Gray’s test was used to compare the incidence of LF across MYCN status. Secondary outcomes included an assessment of event-free survival (EFS), overall survival (OS), and both acute (<6 months) and late (=6 months) toxicity, as assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
Results: A total of 53 patients were enrolled between 2018-2023 at a single institution. Median follow up from time of RT was 22 months (range 4-65 months). Median age at the time of RT was 3.5 years (range 0.8-10.9 years). Primary site was abdominal in 50 patients (94%) and mediastinal in 3 (6%). Forty-four patients (83%) received proton RT. Four patients experienced LF at the primary site of disease (crude risk 7.5%). These failures occurred 1, 3, 8, and 16 months after RT (median 5.5 months). The estimated risk of LF 2 years after RT was 8.4% (95% confidence interval 2.6%-19%). The risk of LF was not significantly different between patients with MYCN-amplified disease (n=28) versus those who had non-MYCN-amplified disease (n=25) (p>0.9). Six of the 53 patients died (11%); the median OS was not reached. There were 19 instances of any neuroblastoma progression (36%); median EFS was not reached. Of the 53 patients, 16 patients experienced acute toxicity, which included grade 1-2 fatigue, nausea, decreased appetite, diarrhea, and dermatitis. There were no toxicities above grade 2. There were no late toxicities of any grade observed in the cohort of patients, with current dates of follow up.
Conclusion: For patients with HR-NB who have a GTR of the primary site, reduced-dose RT of 15 Gy is associated with a 2-year LF rate of 8.4%, in line with published data after 21 Gy. The treatment was well-tolerated, with only grade 1-2 acute toxicities and no late toxicities. These data support continued use of 15 Gy for HR-NB. More follow-up is needed to verify a reduction in late effects.