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.
The first symptoms of neuroblastoma are often vague (in fact, many children have little in the way of symptoms) 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:
- Tumours situated in the abdomen may cause a swollen belly, stomach pain, constipation, or diarrhoea
- a tumour in the chest may cause breathing problems, often similar, at the stage, to a chest infection
- a tumour resting on the spinal cord may cause weakness or difficulty walking
- some children experience bone pain, some may have unexplained “black eyes” or bulging eyes
Many of these symptoms are similar to those of other more common illnesses and unless a parent or a doctor discovers a lump, a diagnosis of neuroblastoma may not be initially considered. Furthermore, neuroblastoma is a rare condition affecting approximately 80-90 children in the UK per year and is unlikely to be suspected if ambiguous symptoms are present. As a result, more than half of all neuroblastomas have spread to other parts of the body by the time that a diagnosis has been made.
The average age for diagnosis of children affected by neuroblastoma is two years old.
Doctors recognise several special 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.
Tumour confined to where it arose and can be completely removed by surgery
The tumour is confined to the area which it grows, but cannot be completely removed by surgery, or neuroblastoma cells are present in the lymph nodes adjacent to the tumour.
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.
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 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% to 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 patients’ condition.
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, radiation 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 can be brought back to near remission, 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.
Even following the current protocol of intensive chemotherapy, surgery, radiotherapy and cis-retonic acid, children with high-risk neuroblastoma currently have a two year survival rate of approximately 20% in the UK.
There is a poor prognosis for those diagnosed with neuroblastoma and, in particular, a low survival rate for those patients diagnosed with high-risk neuroblastoma. Many children respond initially to conventional treatments such as chemotherapy and radiotherapy but unfortunately, often relapse.
Immunotherapy is a new innovative therapy under clinical trial at the Sloan-Kettering Hospital in New York State which is designed to train the body’s immune system to detect and destroy neuroblastoma cells that have survived chemotherapy and radiation therapy. This involves the injection of monoclonal antibodies into the bloodstream which seek out and attach to neuroblastoma cells and signal for the immune system to destroy them.
The Sloan-Kettering’s ability to conduct immunotherapy trials is largely thanks to its being the grateful recipient of a $20 million grant for cancer research from the Ludwig Fund. Such funds are not available to hospitals operating within the UK and this has meant that those children suffering from neuroblastoma must travel to the US in order to receive immunotherapy treatment which seeks to treat neuroblastoma cells which have become resistant to chemotherapy and radiotherapy and to minimise the likelihood of relapse through the elimination of MRD.