Definition and Overview

Neuroblastoma is the third most common children cancer following leukemia and brain cancer. It affects about 1 in every 7,000 children and accounts for 15% of cancer deaths in patients younger than five years old.

The disease starts in the early form of nerve cells (neuroblasts) that make up the nervous system, which consists of the spinal cord and brain and is essential for movement, sensation, and thinking. A part of this system, called autonomic nervous system, is responsible for a number of body functions such as digestion, heart rate, breathing, and blood pressure. A part of the autonomic nervous system is the sympathetic nervous system that is composed of nerve fibres that line the sides of the spinal cord, nerve-like cells in the centre of the adrenal glands, and clusters of cells found along the path of nerve fibres. When neuroblasts in the sympathetic nervous system fail to mature properly, neuroblastoma develops. Most of these malignant tumours are found in the adrenal glands while others develop in the sympathetic nerve ganglia in the abdomen, pelvis or near the spine.

Neuroblastoma cancer can grow and spread at different rates; while some are very aggressive, others grow very slowly. In some cases, cancer cells die or go away without treatment. In others, they grow rapidly, leaving patients with poor chances of long-term survival despite aggressive treatment.

Causes of Condition

The exact cause of the disease is not fully understood. Various studies on neuroblastoma in children focus on factors that prevent neuroblasts from maturing properly during gestation and conception. Previous research has ruled out environmental factors such as smoking, use of medicinal drugs during pregnancy, and exposure to specific chemicals as possible causes of the condition. Other studies that examined its possible link with the use of fertility drugs and exposure to infection early in life are inconclusive.

However, scientists agree that gene mutations and congenital syndromes may play a part in the development of the disease. About 2% of patients have close family members with neuroblastoma. Familial neuroblastoma can be caused by mutations in the anaplastic lymphoma kinase, KIF1B, and PHOX2A genes. Also, a number of neuroblastoma patients have been diagnosed with congenital central hypoventilation syndrome, a breathing control disorder.

Key Symptoms

Neuroblastoma produces a wide range of symptoms depending on the tumour’s size and location, the patient’s age, the stage of cancer, and whether cancer cells have invaded nearby and distant organs (metastasis). Many symptoms of the disease manifest when the malignant mass starts to compress surrounding organs or structures. Neuroblastoma in the abdomen, which is the most common form, results in a swollen belly, constipation, abdominal pain, and a lump under the skin. If found in the chest, the malignant tumour can cause persistent coughing, difficulty breathing, and chest pain.

Other common neuroblastoma symptoms include:

  • Difficulty walking, crawling or standing, if the tumour presses on the spinal cord

  • Eyes bulging out, if cancer has spread to the bones around the eyes

  • Pain and limping, if cancer spreads to the bones

  • Anemia, if cancer spreads to the bone marrow

  • Spinal cord compression, which may lead to paralysis

  • Treatment-resistant diarrhoea

  • Hypertension

  • Fever

  • Unexplained weight loss

The said symptoms commonly appear when cancer has already spread to other parts of the body. Up to 60% of patients present with metastases when diagnosed, which makes treatment more challenging.

If neuroblastoma cells secrete certain chemicals, patients will experience signs of paraneoplastic syndromes such as difficulty in coordination and rapid eye movements.

Who to See and Types of Treatments Available

There are various medical tests and procedures to diagnose neuroblastoma. Doctors usually start with a thorough physical exam and non-invasive tests such as urine and blood tests, which may indicate the cause of the patient’s symptoms. If doctors are unable to make a diagnosis or require additional information, imaging tests are performed. These tests, which may include ultrasound, X-ray, magnetic resonance imaging (MRI), computerised tomography (CT) scan, and metaiodobenzylguanidine (MIBG) are highly effective in finding tumours in any part of the body.

If a neuroblastoma tumour is found, doctors will order a biopsy, in which a small tissue sample from the mass is obtained and analysed under a microscope. This test reveals the type of cells that have formed the tumour, allowing doctors to confirm a neuroblastoma diagnosis.

Neuroblastoma treatment largely depends on the stage of cancer. Neuroblastoma staging involves the use of imaging tests mentioned above.

  • Stage I - A localised tumour that can be completely and safely removed with surgery. In the majority of cases, patients with stage I neuroblastoma do not require additional treatment following surgery.

  • Stage II neuroblastoma – Localised tumour that cannot be easily removed (some are connected to vital organs) through surgery. Lymph nodes connected to the tumour may or may not contain cancer cells.

  • Stage III – Advanced stage of neuroblastoma characterised by a larger tumour and nearby lymph nodes that may contain cancer cells.

  • Stage IV – Neuroblastoma stage 4 is cancer that has spread to other parts of the body

  • Stage IVS – A special category of neuroblastoma that is exclusively used in patients younger than one year old. Although this stage means that cancer has spread to the skin, liver, and bone marrow, there had been cases when it resolves on its own.

Other than the stage of cancer, other factors that are being considered when planning the best course of treatment include the patient’s age, symptoms of neuroblastoma, the type of cells involved, and whether there are any abnormalities in the patient’s chromosomes or genes. Combining all these factors, doctors categorise the disease as low, intermediate or high risk.

In patients with low-risk neuroblastoma, surgery is the main and most often, the only required treatment. For those with tumours that are too risky to remove, such as those attached to nearby vital organs like the spinal cord and lungs, surgeons still perform surgery to remove as much of the malignant mass as possible. Other treatments used to kill any remaining cancer cells are radiation and chemotherapy.

Patients with stage 4 neuroblastoma often receive high doses of chemotherapy to shrink the tumour so it can be removed entirely during surgery. In some cases, stem cell transplant is performed prior to chemotherapy wherein stem cells are harvested from the patient’s body and stored for later use. Following chemotherapy, the harvested stem cells are injected back into the patient’s body where they form new healthy blood cells.

Another common treatment is radiation therapy, which uses high-energy beams to destroy cancer cells. It is often useful in children with low- to intermediate-risk neuroblastoma. It is also often recommended for patients with high-risk tumours with the goal to prevent recurrences. This procedure is sometimes supplemented with immunotherapy, which strengthens the patient’s immune system to fight cancer cells.

Neuroblastoma prognosis is better in patients with low-risk tumours that can be removed entirely by surgery. Up to 50% of high-risk neuroblastomas do not respond well to high-dose chemotherapy and relapse following a successful treatment is very common. Meanwhile, those who survive the condition may suffer from long-term effects of treatment including hearing loss, learning difficulties, thyroid function disorder, and growth reduction. They also have an increased risk of secondary cancers.

References:

  • Olshan, Andrew F.; Smith, Joanna; Cook, Michael N.; Grufferman, Seymour; Pollock, Brad H.; Stram, Daniel O.; Seeger, Robert C.; Look, A. Thomas; Cohn, Susan L.; Castleberry, Robert P.; Bondy, Melissa L. (1999). "Hormone and Fertility Drug Use and the Risk of Neuroblastoma: A Report from the Children's Cancer Group and the Pediatric Oncology Group". American Journal of Epidemiology. 150 (9): 930–8. doi:10.1093/oxfordjournals.aje.a010101. PMID 10547138.

  • Wilson JS, et al. A systematic review of 131I-meta iodobenzylguanidine molecular radiotherapy for neuroblastoma. European Journal of Cancer. 2014;50:801.

  • Radiation therapy for neuroblastoma. American Cancer Society. http://www.cancer.org/cancer/neuroblastoma/detailedguide/neuroblastoma-treating-radiation-therapy. Accessed Nov. 11, 2015.

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