Neuroblastoma Treatment Protocol
The treatment of neuroblastoma should follow a risk-stratified approach based on the International Neuroblastoma Risk Group (INRG) classification system, with therapy tailored according to low-risk, intermediate-risk, or high-risk disease categories. 1
Risk Classification and Initial Assessment
Risk classification is essential before initiating treatment and depends on several key factors:
- Age at diagnosis: Important prognostic factor (better outcomes in children <18 months)
- INRG stage: L1 (localized without image-defined risk factors), L2 (localized with image-defined risk factors), M (metastatic), or MS (metastatic special - children <18 months with metastases limited to skin, liver, and/or bone marrow)
- MYCN status: Amplification indicates high-risk disease regardless of other factors
- Tumor histology: Favorable vs. unfavorable based on International Neuroblastoma Pathology Classification
- DNA ploidy: Diploid vs. hyperdiploid
- Segmental chromosomal aberrations (SCAs): Presence indicates higher risk
Essential diagnostic workup includes:
- Cross-sectional imaging (MRI preferred) of primary tumor site
- 123I-MIBG scan for metastatic evaluation (90% sensitivity)
- Laboratory tests including CBC, comprehensive metabolic panel, urinary catecholamines
- Adequate tissue sampling for histology and molecular studies
Treatment Protocols by Risk Group
Low-Risk Disease
- Primary approach: Surgical resection or observation
- For infants <6 months with adrenal masses ≤3.1 cm (solid) or ≤5 cm (≥25% cystic): Observation without biopsy 1, 2
- For L1 tumors: Complete surgical resection if feasible with minimal morbidity
- For asymptomatic MS disease with favorable biology: Observation
- Five-year survival rates exceed 95% 1
Intermediate-Risk Disease
- Primary approach: Chemotherapy (2-8 cycles) followed by surgery
- Number of cycles depends on:
- Disease stage
- Age
- Tumor biology (favorable features include favorable histology, hyperdiploid DNA, no SCAs)
- For infants with MS disease who are too unstable for biopsy: Start chemotherapy, then obtain biopsy when stable
- Response assessment guides further therapy
- Five-year survival rates approximately 90-95% 1
High-Risk Disease
Multi-modal therapy in three phases:
Dinutuximab specifically indicated for high-risk neuroblastoma patients who achieve at least partial response to prior first-line multimodality therapy 3
Immunotherapy has demonstrated improved event-free survival and overall survival compared to standard therapy 3
Special Considerations
Emergent Situations
- For symptomatic infants with MS disease (especially with hepatomegaly causing respiratory compromise):
Response Assessment
- Regular imaging to evaluate treatment response
- Primary tumor response assessed by tumor volume reduction or RECIST criteria
- For non-high-risk disease: 50-90% reduction in primary tumor volume may be targeted depending on biology 1
Long-term Follow-up
- Audiologic, thyroid, cardiac, pulmonary, renal, bone, and reproductive health screening
- Fertility preservation discussion before starting chemotherapy, especially for high-risk patients 2
- Monitor for second malignancies
Common Pitfalls to Avoid
- Inadequate tissue sampling leading to incomplete molecular characterization
- Overtreatment of small, localized tumors in young infants that may spontaneously regress
- Failure to recognize atypical presentations
- Delaying therapy for unstable patients while awaiting complete workup
- Not recognizing differences between COG risk classification and criteria used outside North America 1
By following this risk-stratified approach, treatment can be optimized to maximize cure rates while minimizing unnecessary toxicity, particularly for patients with favorable biology.