What is the management and treatment approach for a suspected case of neuroblastoma?

Management and Treatment Approach for Suspected Neuroblastoma

The management of suspected neuroblastoma requires a systematic diagnostic workup followed by risk-stratified treatment, with surgical resection considered for localized disease without image-defined risk factors and minimally invasive biopsy preferred for disease with risk factors. 1

Diagnostic Workup

Initial Evaluation

• Complete history and physical examination with special attention to:
  • Abdominal examination for masses and organomegaly
  • Thorough neurologic examination
  • Assessment for common symptoms: abdominal distension, loss of appetite, weight loss, irritability, constipation, fever, hypertension, anemia, paralysis, bruising/swelling around eyes, bone pain 1
  • Evaluation for opsoclonus-myoclonus-ataxia syndrome (OMAS) - characterized by rapid eye movements, ataxia, irritability, sleep disturbance 1
• Family history assessment for neuroblastoma or other childhood cancers 1

Laboratory Tests

• Essential tests:
  • Complete blood count with differential
  • Comprehensive metabolic panel
  • Urinary catecholamine metabolites (homovanillic acid [HVA] and vanillylmandelic acid [VMA])
  • Lactate dehydrogenase (LDH) and ferritin levels (in select cases) 1, 2

Imaging Studies

• Cross-sectional imaging:
  • MRI with/without contrast (preferred) or CT with contrast of the primary tumor site 2
  • Chest radiograph or CT
  • Abdominal/pelvic CT or MRI
• Functional imaging:
  • 123I-MIBG scan (high specificity and sensitivity in up to 90% of neuroblastoma tumors)
  • SPECT or SPECT/CT if available for better anatomic localization 2
  • 18F-FDG PET/CT if MIBG scan is negative 3

Tissue Diagnosis

Approach to Tissue Sampling

• For localized disease without image-defined risk factors (IDRFs):
  • Consider surgical resection 1, 2
• For disease with IDRFs:
  • Perform minimally invasive biopsy 1
  • Multiple core biopsies (at least 10 cores, ideally 20-30 mm in length using a 16-gauge needle) 2
  • Open biopsy may be preferred if adequate tissue cannot be obtained by less invasive means 1
• Ensure adequate tissue for:
  • Histologic evaluation
  • Molecular characterization (MYCN amplification, segmental chromosomal aberrations, ALK gene status, DNA ploidy) 1, 2

Special Considerations

• Infants <6 months with L1 adrenal tumors ≤3.1 cm if solid or ≤5 cm if at least 25% cystic may not require initial biopsy or resection 1, 2
• Infants <2 months with hepatomegaly should not undergo biopsy until after initiation of therapy and clinical stabilization 1, 2
• Bilateral bone marrow aspirates and trephine biopsies can be used for diagnostic purposes when marrow is the only source of tumor material 1

Risk Classification and Staging

After completing the diagnostic workup, use the International Neuroblastoma Risk Group (INRG) Staging System to determine stage and risk classification, which guides treatment decisions 1, 2:

• Low-risk: Minimal intervention
• Intermediate-risk: Moderate intervention
• High-risk: Intensive multimodality treatment

Treatment Approach Based on Risk Classification

High-Risk Neuroblastoma Treatment

High-risk neuroblastoma requires intensive multimodal therapy divided into three phases 4:

1. Induction Phase:

   • Multiagent chemotherapy
   • Surgical resection of primary tumor

2. Consolidation Phase:

   • Myeloablative chemotherapy
   • Autologous stem cell transplantation
   • Radiation therapy to residual disease sites

3. Maintenance Phase:

   • Immunotherapy with dinutuximab (anti-GD2 antibody) in combination with GM-CSF, IL-2, and 13-cis-retinoic acid 5
   • Dinutuximab dosage: 17.5 mg/m²/day as intravenous infusion over 10-20 hours for 4 consecutive days for maximum of 5 cycles 5

Important Considerations for Dinutuximab Administration

• Premedication requirements:
  • IV hydration (0.9% Sodium Chloride 10 mL/kg over 1 hour)
  • Analgesics (morphine sulfate 50 mcg/kg IV prior to infusion, then 20-50 mcg/kg/hour during and 2 hours after)
  • Antihistamines (diphenhydramine 0.5-1 mg/kg IV)
  • Antipyretics (acetaminophen 10-15 mg/kg) 5
• Monitor for serious adverse reactions:
  • Infusion reactions (26% of patients)
  • Neurotoxicity including severe neuropathic pain
  • Peripheral sensory and motor neuropathy 5

Special Considerations

Age-Specific Approaches

• Infants and young children have better prognosis than older children 6
• Spontaneous regression can occur in some cases, particularly in infants 3

Monitoring for Late Effects

• Audiologic assessment for patients treated with platinum-based chemotherapy
• Thyroid, cardiac, pulmonary, renal, bone, and reproductive health screening
• Monitoring for second malignant neoplasms 1

Fertility Considerations

• Refer to fertility specialists for discussion of preservation options before starting chemotherapy, especially for high-risk disease patients 1, 5

Potential Pitfalls

• Inadequate tissue sampling leading to insufficient material for complete molecular testing
• Delaying emergent therapy when needed
• Failure to recognize atypical presentations
• Over-treatment of small, localized tumors in young infants that may spontaneously regress 2
• Underestimating the severity of pain during immunotherapy with dinutuximab 5

By following this systematic approach to diagnosis and treatment, outcomes for patients with neuroblastoma can be optimized based on their individual risk classification.