Neuroblastoma is a rare form of childhood cancer. The condition arises when a tumour occurs within particular nerve cells which run in a chain-like fashion from the back of a child’s abdomen and chest along the spinal cord into the skull. The solid tumours will take the form of a lump or mass beginning as nerve tissues in the neck, chest, abdomen, pelvis or, most commonly, the adrenal gland (situated above the kidney) and, sometimes, spreading to other areas of the body such as the lymph nodes or bone marrow.
Symptoms
The first symptoms of neuroblastoma are often vague and can include fatigue and loss of appetite. As the disease progresses, the symptoms that the child experiences are dependent upon the location of the tumour:
Many of these symptoms are similar to those of other more common illnesses and unless a parent or doctor discovers a lump, a diagnosis of neuroblastoma may not be initially considered. As a result, more than half of all neuroblastomas have spread to other parts of the body by the time a diagnosis of neuroblastoma has been made.
The average age for diagnosis of children affected by neuroblastoma is two years old.
Staging
Doctors recognise several categories of neuroblastoma which determine the stage of the disease. Stage is a term that refers to the location and extent of the cancer tumour, or cells. The stages of neuroblastoma differ widely in form of treatment, as each stage carries with it different risks. Below is a brief summary of the International Neuroblastoma Staging System (INSS) which has been a widely used method to categorise neuroblastoma.
Stage 1 Tumour confined to where it arose and can be completely removed by surgery
Stage 2 The tumour is confined to a specific area in which it grows, but cannot be completely removed by surgery, or, neuroblastoma cells are present in the lymph nodes adjacent to the tumour.
Stage 3 The tumour has spread from one side of the body to the other and may have also spread to nearby lymph nodes; the tumour remains confined to the area in which it grows, but neuroblastoma cells have spread to the lymph nodes on the other side of the body; or the tumour remains confined to the middle of the body and neuroblastoma cells have spread to lymph nodes on both sides of the body.
Stage 4 The primary tumour may be of any size, but some of the neuroblastoma cells have broken away and spread to other organs of the body, most commonly bones, bone marrow or the liver.
Stage 4S This stage is applicable only to children who are younger than one year. The tumour is confined to the area in which it arose, as in stages 1 and 2, but some cells have spread to the liver, skin, or bone marrow.
Low-risk and intermediate-risk neuroblastoma
Low risk neuroblastoma includes all cases classified in stage 1 or stage 2 and most cases classified as 4S. The treatment of low risk neuroblastoma has sought to avoid both chemotherapy and radiation therapy for patients.
Intermediate-risk groups include stage 3, stage 4 in babies (less than 18 months old), and the more severe cases of stage 4S, together with some patients with large tumours that have not spread. Around 80 - 95% of these intermediate-risk neuroblastomas are curable, with the exception of 10 - 15% of stage 3 cases, which may not respond well to chemotherapy. The treatment of intermediate-risk neuroblastoma relies upon chemotherapy and radiation therapy cautiously with treatment tailored to the individual patient’s condition.
High-risk neuroblastoma
Stage 4 neuroblastoma diagnosed in children over 18 months old is considered ‘high risk’. In addition, tumours with the genetic characteristic known as ‘MYCN amplification’, irrespective of age or stage, are generally regarded as high risk.
High-risk neuroblastoma is the most difficult stage of the disease to treat and requires use of a combination of treatment approaches including chemotherapy, radiotherapy, surgery and immunotherapy. These treatments are conducted in phases and usually take about two and half years to complete.
Approximately 40% of high risk stage 4 patients relapse, usually within the first two to three years of diagnosis. Although some of these patients (following the current protocol of intensive chemotherapy, surgery, radiotherapy and cis-retonic acid) can be brought back to near remission, currently statistics in Europe suggest that fewer than 20% of these patients are expected to survive for longer than five years.
Given the difficulty in achieving long term remission in cases of relapse, heavy emphasis is placed on the prevention of relapse during treatment. The major cause for relapse in patients, previously declared to be in remission, is minimal residual disease (MRD). MRD refers to the presence of neuroblastoma cells which are too small and too dispersed throughout the body to be detected by standard testing. Research is being undertaken to develop wholly sensitive methods to detect and monitor MRD because once left unchecked MRD will progress to detectable relapse, i.e. the reoccurrence of the tumour and spread of neuroblastoma cells.
In a meeting in June 2009 the North American Children’s Oncology Group presented early results from a randomised clinical trial. In this trial one group received immunotherapy and chemotherapy and the other received chemotherapy with no immunotherapy. The children who received the immunotherapy had a better chance of surviving without a recurrence of their neuroblastoma two years later.