Neuroblastoma - ENEA | European Neuroblastoma Association ONLUS
What is neuroblastoma?
Neuroblastoma is a rare cancer that most commonly affects young children, and rarely occurs in older children and adults.
Neuroblastoma is the most common childhood cancer aside from brain tumours: it is a progressive disorder, with good prognosis when detected at an early stage or in very young patients (~90% 5-year survival) and bad prognosis when detected at a later stage in older patients (~40% 5-year survival). Overall, neuroblastoma causes over 15% of all childhood cancer-related deaths.
Neuroblastoma is a cancer of the sympathetic nervous system (SNS). It typically develops in the adrenal glands, but can start anywhere along the SNS (neck, chest, pelvis). During development, both nerve cells and cells of the adrenal medulla (inner part of the adrenal gland) develop from neuroblasts in the foetus. Neuroblastoma develops from these neuroblast cells. It occurs because the normal foetal neuroblasts fail to become mature nerve cells, or adrenal medulla cells. Instead, these cells continue to grow and divide at an uncontrolled rate, which is a hallmark of cancer.
During metastasis, neuroblastoma spreads via the lymphatic system or blood, most commonly to the bones, liver and skin.
Neuroblastoma is related to ganglioneuroblastoma and ganglioneuroma. These tumours are less aggressive and are composed of more mature neural cells (more schwann cells in the tumour and fewer neuroblastic cells). About 1 in 100 neuroblastoma patients have a family history of neuroblastoma.
Surprisingly few recurrent gene alterations have been identified in neuroblastoma. Aggressive / late stage tumours commonly have ATRX deletions, MYCN amplifications, ALK activation and/or TERT overexpression. MYCN amplification is observed in 20-25% of all neuroblastomas and is associated with a poor prognosis. Often MYCN amplification co-occurs with deletion of the distal short arm of chromosome 1, and outcome also negatively correlates with 11q deletion.
Neuroblastoma disproportionally co-occurs with Opsoclonus myoclonus syndrome (2-3% compared to 0.0000001% in the general population).
Patient outlook: only 67% of patients survive to five years, making neuroblastoma one of the lowest survival rate cancers affecting children. An unusual observation in NB is that girls appear to do better than boys.
The very young fair better than older patients at diagnosis.
The correct stratification of neuroblastoma patients within risk groups (low, intermediate, high and ultra-high) is critical for the adequate treatment of the patient.
Subtypes/stages: there isn't yet a single classification scheme for NBs. Tumours are classified based on the age of the patient at the time of discovery, tumour phenotype, and genetic aberrations.
Morphologically, neuroblastomas can be divided into three subcategories: undifferentiated, poorly differentiated and differentiating neuroblastomas. Differentiation has been strongly correlated with a better overall prognosis.
NB typing bases up on cytogenetic observations
- 1. NB with whole chromosome 17 gain
- 2. NB with 17q gain with 1p loss
- 3. NB with 17q gain without 1p loss
- 4. NB with 17q gain with 11q loss
- 5. NB with 17q gain without 11q loss
- 6. MYCN-amplified NBs
NB staging and prognostication:
Stage 1 - localized tumour, complete surgical resection - good
Stage 2A - localized tumour, incomplete surgical resection - good prognosis
Stage 2B - tumour metastasis to the ipsilateral lymph nodes - good prognosis
Stage3 - unresectable, metastases - bad prognosis
Stage4 - metastasis to distant lymph nodes and/or other organs (except those for 4s) - bad prognosis
Stage 4s - metastasis limited to the skin, liver or bone marrow, differentiated tumours - good prognosis, many regress
Symptoms: Neuroblastoma belongs to the neuroblastic group of tumours that also include ganglioneuroblastoma and ganglioneuroma. Children often present with: lumps in the abdomen, swelling in the neck, fever, sweats, weight loss.
Drugs and treatments: combination treatment is typically used for neuroblastoma.
The correct stratification of neuroblastoma patients within risk groups (low, intermediate, high and ultra-high) is critical for the adequate treatment of the patients.
Low risk NBs
For children with low risk NBs, e.g. <1-year-old or with small easily accessible tumours, surgery or careful follow-up may be enough - sometimes tumours disappear on their own
Intermediate risk NBs
Patients with large tumours but no spreading, or metastases, but no
MYCN amplification may be treated with surgery + 4-8 months chemotherapy
High risk NBs (e.g. with MYCN amplification)
Multiple treatment therapies are used for high risk neuroblastoma management:
- 1. Chemotherapy
Main chemotherapy compounds used include (usually given in combination):
- Cyclophosphamide or ifosfamide
- Cisplatin or carboplatin
- Doxorubicin (Adriamycin)
- Actinomycin D (dactinomycin)
- Etoposide (not effective against fast growing tumours)
- Busulfan and melphalan (sometimes used during stem cell transplant)
The most common combination of drugs includes carboplatin (or cisplatin), cyclophosphamide, doxorubicin, and etoposide, but others may be used.
- Vincristine, cyclophosphamide, and doxorubicin
- Carboplatin and etoposide
- Cisplatin and etoposide
- Ifosfamide and etoposide
- Cyclophosphamide and topotecan
- Consolidation regimens may additionally include:
Carboplatin and etoposide with melphalan or cyclophosphamide
Thiotepa and cyclophosphamide
Melphalan and total body irradiation
- 2. Surgery
- 3. High dose chemotherapy with stem cell rescue
- 4. Radiotherapy
- 5. Immunotherapy