Peds - Neuroblastoma

About this video

• Video Title: Peds - Neuroblastoma
• Channel: Rad Onc Talks
• Speakers: Ria Craft
• Duration: 52:12

Overview

This video provides a comprehensive overview of neuroblastoma, a common and aggressive pediatric solid tumor. It covers the tumor's origins, characteristics, staging systems (INSS and INRG), risk stratification, diagnostic workup, and treatment paradigms, with a particular focus on the role and technical aspects of radiation therapy in high-risk cases.

Key takeaways

• Neuroblastoma is a common, aggressive pediatric solid tumor primarily affecting infants, originating from neural crest cells.
• It is differentiated from Wilms tumor based on origin, appearance, epidemiological factors, and metastatic patterns.
• Diagnosis involves history, physical exam, labs (urine catecholamines), imaging (ultrasound, CT, MRI, MIBG scan), and pathology (bone marrow biopsy, incisional biopsy).
• Staging is categorized using the INRG system (L1, L2, M, MS), which informs risk stratification into low, intermediate, and high-risk groups.
• Radiation therapy is primarily indicated for high-risk neuroblastoma, delivered to the primary tumor and metastatic sites at a dose of 21.6 Gray in 12 fractions.
• Treatment for high-risk neuroblastoma is multimodal, including induction chemotherapy, surgery, consolidation chemotherapy with immunotherapy, stem cell transplant, radiation, and post-consolidation therapy.

Neuroblastoma typically presents as a more aggressive, heterogeneous abdominal mass that often crosses the midline and is associated with systemic symptoms like fever, malaise, and weight loss, due to elevated catecholamines. Imaging may show calcifications and displacement but not distortion of renal architecture.

Wilms tumor, on the other hand, usually presents as a more well-defined, circumscribed, painless abdominal mass. Patients may have fever, hematuria, or anemia, but generally appear less acutely ill than neuroblastoma patients. Imaging reveals a mass that disrupts renal architecture, often with a characteristic "claw sign." Metastases from Wilms tumor are more commonly to the lungs, whereas neuroblastoma is less likely to spread to the lungs and more likely to spread to lymph nodes, bone marrow, liver, and skin.

According to the NCCN risk stratification, neuroblastoma is considered high-risk if any of the following criteria are met:

• Incomplete resection: If the primary tumor cannot be completely removed surgically.
• Presence of MYCN amplification: This is a critical genetic marker associated with aggressive disease.
• Certain image-defined risk factors: These indicate tumor invasion into vital structures, such as encasing major vessels, compressing the trachea, or infiltrating specific anatomical regions.
• Unfavorable histology: This includes undifferentiated or poorly differentiated neuroblastoma according to the INPC system.
• Chromosomal abnormalities: Such as a DNA index of one (diploid) or segmental chromosomal alterations (e.g., 1p deletion, 17q gain, 11q loss of heterozygosity).
• Metastatic disease: Patients with L2, M, or MS stage disease (as defined by the INRG staging system) are considered high-risk, especially if other unfavorable factors are present.

According to the NCCN risk stratification, neuroblastoma is considered high-risk if any of the following criteria are met:

• Incomplete resection: If the primary tumor cannot be completely removed surgically.
• Presence of MYCN amplification: This is a critical genetic marker associated with aggressive disease.
• Certain image-defined risk factors: These indicate tumor invasion into vital structures, such as encasing major vessels, compressing the trachea, or infiltrating specific anatomical regions.
• Unfavorable histology: This includes undifferentiated or poorly differentiated neuroblastoma according to the INPC system.
• Chromosomal abnormalities: Such as a DNA index of one (diploid) or segmental chromosomal alterations (e.g., 1p deletion, 17q gain, 11q loss of heterozygosity).
• Metastatic disease: Patients with L2, M, or MS stage disease (as defined by the INRG staging system) are considered high-risk, especially if other unfavorable factors are present.

The treatment paradigm for high-risk neuroblastoma is intensive and multimodal, typically involving the following phases:

1. Induction Chemotherapy: This is the initial treatment, consisting of multi-agent chemotherapy regimens. A common regimen mentioned is the "cape" regimen (cyclophosphamide, adriamycin, cisplatin, and etoposide). This phase aims to reduce tumor burden before surgery.

2. Surgery: Following induction chemotherapy, patients undergo surgery to resect the primary tumor and any associated local regional disease (lymph nodes).

3. Consolidation Therapy: This phase is critical and involves:

   • Chemoimmunotherapy: This includes agents like dinutuximab (an anti-GD2 antibody) which targets neuroblastoma cells.
   • Stem Cell Transplant: Myeloablative chemotherapy is administered, followed by an autologous stem cell transplant. Tandem transplants (two transplants) have shown improved event-free survival compared to single transplants.
   • Radiation Therapy: Radiotherapy is delivered during this consolidation phase, typically 28 to 42 days post-transplant.
     • Role: Radiation is given to the primary tumor site and any persistent sites of metastatic disease. It is not generally used for low or intermediate-risk disease unless there are urgent life- or organ-threatening concerns.
     • Dose and Fractions: The standard dose is 21.6 Gray (Gy) in 12 fractions, delivered daily. This dose is given to the pre-operative gross tumor volume (GTV) identified after induction chemotherapy.
     • Treatment Volume: The target volume includes the post-chemo GTV, with a 1 cm margin for the clinical target volume (CTV) and an additional 3-5 mm for the planning target volume (PTV).
     • Boost: The ANBL0532 study indicated no benefit from a radiotherapy boost to gross residual disease, meaning the 21.6 Gy dose is typically sufficient.

4. Post-Consolidation Therapy (Maintenance Therapy): This phase aims to maintain remission and includes:

   • Immunotherapy: Continued treatment with an anti-GD2 monoclonal antibody (like dinutuximab).
   • Isotretinoin: Adjuvant 13-cis-retinoic acid is administered.

In summary, for high-risk neuroblastoma, radiation therapy is a crucial component of the consolidation phase, delivered after stem cell transplant, at a dose of 21.6 Gy to the primary tumor bed and any persistent metastatic sites.

Here are some topics and tags to explore this video in detail:

Topic	Tags
Neuroblastoma Basics	Pediatric cancer, childhood tumors, oncology, small round blue cell tumor
Differential Diagnosis	Wilms tumor, nephroblastoma, abdominal masses in children
Genetics and Risk Factors	MYCN amplification, chromosomal abnormalities, genetic markers
Staging and Risk Stratification	INRG staging, NCCN risk stratification, low risk, intermediate risk, high risk
Diagnostic Workup	Urine catecholamines, MIBG scan, bone marrow biopsy, imaging
Treatment Modalities	Chemotherapy, surgery, immunotherapy, stem cell transplant, radiation therapy
Radiation Therapy Specifics	Pediatric radiation oncology, dose fractionation, treatment volume, GTV, CTV, PTV
Clinical Trials and Evidence	ANBL0532 study, treatment outcomes, survival rates
Prognosis and Outcomes	Survival rates by risk group, pediatric oncology prognosis
Specific Syndromes/Signs	Raccoon eyes, blueberry muffin sign, Horner's syndrome, Opsoclonus-myoclonus syndrome