Background
Dose-escalation/secondary analysis within COG ANBL0532. Evaluated the impact of RT dose and local control in high-risk neuroblastoma patients enrolled on ANBL0532. Specifically examined whether the delivered RT dose to the primary site (21.6 Gy) was adequate for local tumor control and whether dose escalation might be warranted for bulky primary disease.
Interventions and follow up
Arm A: Involved-field RT 21.6 Gy to primary site post-HDCT (as per ANBL0532 protocol)
Primary endpoint: Local failure rate, local PFS
mFollow up: 3.0 year
Primary endpoint: Local failure rate, local PFS
mFollow up: 3.0 year
Results
Arm B (comparison): Institutional variation in RT practice — higher dose, different volumes, or timing variations
Local control at 3 yr: 77% overall in ANBL0532 per-protocol RT patients
Local failure as first event: ~12% of patients
Dose-response: No significant benefit of doses >21.6 Gy in unselected patients
Local control at 3 yr: 77% overall in ANBL0532 per-protocol RT patients
Local failure as first event: ~12% of patients
Dose-response: No significant benefit of doses >21.6 Gy in unselected patients
Adverse events
Main adverse events: Hepatotoxicity and nephrotoxicity with large-volume abdominal RT. GI toxicity. Gonadal dose minimization critical in young children. Vertebral body RT associated with scoliosis risk; attempts to spare vertebral body using IMRT are ongoing.
Conclusions
Local RT 21.6 Gy to the primary site provides acceptable local control in high-risk neuroblastoma. Dose escalation above 21.6 Gy does not appear to improve local control in unselected patients. IMRT/proton techniques can reduce dose to adjacent normal structures.
Key Limitations
Key Limitations: Secondary/exploratory analysis with inherent selection bias and small subgroup numbers. Institutional variation in RT technique confounds dose-response analysis. Prospective dose-escalation data are lacking.
Clinical Context
Standard RT dose for neuroblastoma primary site remains 21.6 Gy involved-field post-HDCT. IMRT and proton therapy are increasingly used to reduce dose to the liver, kidney, spinal cord, and gonads, particularly in young children. Boost doses for partial responders are explored on subsequent COG trials.
References
References: Park JR et al, JCO 2019 (ANBL0532)