What are the treatment options for neuroblastoma?

Indian Articles in Neuroblastoma

I was unable to identify any Indian-specific articles or guidelines in the provided evidence. The evidence base consists entirely of international guidelines and research, primarily from:

• North American sources: NCCN (National Comprehensive Cancer Network) guidelines 1 and COG (Children's Oncology Group) protocols 2, 3, 4
• European sources: SIOPEN protocols 1 and JASTRO/JSPHO guidelines from Japan 1
• Historical research: Studies from Joint Center for Radiation Therapy/Dana-Farber Cancer Institute/Children's Hospital 5, 6
• General reviews: Contemporary management reviews 7, 8, 9

Treatment Options for Neuroblastoma (Based on Available Evidence)

Since no Indian-specific evidence was provided, I will outline the current international standard treatment approaches that would be applicable globally, including in India:

Risk-Stratified Treatment Approach

Low-Risk Disease:

• Surgical resection alone is the primary treatment, with observation appropriate for select infants <6 months with small adrenal masses (≤3.1 cm if solid, ≤5 cm if ≥25% cystic) 4
• No chemotherapy or radiation required for most patients, with 5-year survival exceeding 95% 4

Intermediate-Risk Disease:

• Requires 2-8 cycles of cyclophosphamide-based chemotherapy to achieve 50-90% tumor volume reduction before surgical resection 4
• Number of cycles determined by disease stage, age, and biologic features 4
• No radiation routinely indicated, with 5-year survival of 90-95% 4

High-Risk Disease:

Induction Phase:

• The NCCN recommends 5-cycle ANBL12P1 or ANBL1531 protocols combining topotecan, cyclophosphamide, cisplatin, etoposide, and doxorubicin 2, 3
• Approximately 80% of patients achieve partial response or better 2
• Surgical resection after several cycles of cytoreductive chemotherapy, aiming for gross total resection (>90% resection) 1

Consolidation Phase:

• Tandem transplantation with two consecutive rounds of high-dose chemotherapy with autologous stem cell rescue is the standard approach for patients responding adequately to induction 2, 3
• First transplant uses thiotepa/cyclophosphamide, followed 6-10 weeks later by reduced-dose carboplatin/etoposide/melphalan (CEM) 1, 2
• This approach achieves 3-year EFS of 61.6% versus 48.4% with single transplant 1, 2
• Alternative: Busulfan/melphalan (BuMel) is preferred in European protocols with superior EFS but higher risk of sinusoidal obstruction syndrome 1, 2

Radiation Therapy:

• 21.6 Gy to the primary tumor site is the standard dose, administered after recovery from high-dose chemotherapy 1
• NCCN recommends radiation to sites of residual metastatic disease remaining on 123I-MIBG or FDG-PET at end-induction evaluation 1
• Dose escalation beyond 21.6 Gy or field extension to uninvolved nodes is NOT recommended based on COG trials showing no benefit 1

Postconsolidation/Maintenance Therapy:

• Anti-GD2 antibody (dinutuximab) combined with sargramostim and isotretinoin is the category 1 recommendation for patients without disease progression after consolidation 1
• This regimen improved 2-year EFS from 46% (isotretinoin alone) to 66% (immunotherapy regimen) in the ANBL0032 trial 1
• Interleukin-2 is no longer included based on SIOPEN HR-NBL1 trial showing no benefit and increased toxicity 1

Critical Management Caveats

• MYCN amplification overrides all other prognostic factors and automatically assigns high-risk status, except for completely resected L1 tumors 4
• All patients ≥18 months with stage M disease are high-risk regardless of other features 4
• Patients with progressive disease during induction are not candidates for consolidation and should receive non-myeloablative chemoimmunotherapy or clinical trial enrollment 1

Long-Term Monitoring

Surveillance Imaging:

• 123I-MIBG scan with SPECT (or FDG-PET if MIBG nonavid) every 3-6 months in year 1, every 6 months in year 2, annually in year 3 1
• CT or MRI of primary site with similar frequency 1

Late Effects Monitoring:

• High-risk patients are at particularly high risk for hearing impairment, endocrine deficiencies, growth retardation, chronic kidney disease, impaired fertility, cardiotoxicity, neurocognitive impairment, and second malignancies 1, 3
• Echocardiogram every 2-5 years depending on anthracycline dose and cardiac radiation exposure 1
• Thyroid studies (TSH, free T4 if abnormal) every 6 months for years 1-2, then annually 1
• A personalized survivorship care plan should be developed for each patient 1

Special Considerations for Resource-Limited Settings

While not specifically addressed in the provided evidence, clinicians in India and other resource-limited settings may need to adapt these protocols based on:

• Availability of anti-GD2 antibodies and stem cell transplant facilities
• Access to 123I-MIBG imaging and therapy
• Supportive care capabilities for intensive chemotherapy regimens

The fundamental principles of risk stratification, multimodality therapy for high-risk disease, and long-term survivorship monitoring remain applicable regardless of geographic location.