Induction Chemotherapy Learn more about standard induction chemotherapy for high-risk neuroblastoma in the UK. Expand The main aim of induction chemotherapy is to reduce the size of the primary tumour to make it easier to remove as much of it as possible during surgery. Chemotherapy uses drugs to kill cancer cells. It's delivered through a central line - a tube that feeds into one of the large veins in the chest. This will be fitted under general anaesthetic to minimise the distress caused by intravenous injections. There are different chemotherapy regimens used in the induction phase but the most common in the UK are: Rapid COJEC This is a combination of five agents (cisplatin, vincristine, carboplatin, etoposide and cyclophosphamide) that is delivered directly into your child’s bloodstream through their central line This therapy is administered in eight cycles, separated by intervals of ten days and is completed within 70 days of the first treatment In high-risk patients, the use of Rapid COJEC is to give high doses of chemotherapy over a shorter time which may improve survival. Modified N7 Modified N7 uses the drugs cyclophosphamide, doxorubicin, vincristine, cisplatin and etoposide. One cycle lasts three-four days every three weeks, and there are five cycles. Your child will also be given a 'growth factor' known as G-CSF as an injection, given daily between chemotherapy cycles to reduce the risk of infection. During induction chemotherapy, your child will have some of their 'peripheral haematopoietic stem cells' taken from their blood. These are cells that can develop into any of the different types of blood cells and so are very important for carrying oxygen, fighting infection, and preventing bleeding. During chemotherapy, these cells can get damaged and this can limit the amount of therapy your child can have as it takes some time for the blood to recover and for blood counts to improve. Taking some cells while they are healthy (known as stem cell harvest) and storing them during the induction phase means that these cells can be replaced later, therefore improving your child’s ability to make new blood cells. Side-effects Chemotherapy damages cancer cells that divide often with the aim of destroying them. But other types of cells also divide, like skin, hair and nail cells. Damaged other cells can repair and recover. Some side-effects of chemotherapy are: Tiredness/weakness Sore mouth Hair loss Feeling sick/being sick Diarrhoea Loss of appetite- in some cases your child may need a nasogastric (NG) tube to provide nutrition directly to the stomach if they are unable to eat. Increased chance of infection These problems are temporary and steps can be taken to manage them as best as possible with support from your healthcare provider. Following induction chemotherapy, your child is likely to have surgery. Read more about neuroblastoma surgery.
Surgery Learn more about surgery as treatment for neuroblastoma in the UK. Expand Usually, after induction chemotherapy, surgery will be performed to remove as much of the primary tumour as possible. At this point, the hope is that the tumour will have reduced in size since diagnosis so that the surgery will be as successful as it can be. The surgeon will remove the tumour along with a margin of healthy cells while trying to cause little disruption to surrounding structures and organs. The tumour that has been removed is then sent for further testing in the laboratory. This can provide a clearer picture of the genetic makeup of that tumour as well as identifying how much or how little of the tumour remains active tissue. Following surgery, a child with high-risk neuroblastoma will have high-dose chemotherapy to clear any remaining cancer cells. Read more about high-dose chemotherapy.
High-Dose Chemotherapy Learn more about high-dose chemotherapy used as standard treatment for high-risk neuroblastoma in the UK. Expand Also known as consolidation therapy, high-dose chemotherapy aims to ‘mop-up’ any remaining cancer cells that might be left over following induction chemotherapy and surgery. This chemotherapy is known as 'myeloablative' and is high-dose. The term 'myeloablative' refers to the depletion of the blood-producing cells in the bone marrow as a side-effect. The drugs used in this process are called busulfan and melphalan. Stem cell treatment Giving higher doses of chemotherapy might be more effective in treating neuroblastoma but it causes severe damage to the bone marrow (where new blood cells are made). Doctors help children by replacing bone marrow cells - this is called stem cell transplant. Isolation Your child will be kept in isolation until they are no longer at risk of infection. They are at a high risk of infection because of their low white blood cell count. This does not mean that they will be alone during this treatment- in fact it is most likely that a family member will need to be with the child 24 hours a day. To help lower the risk of infection, your child will stay in a special hospital room and care is taken when you and family members visit. Side-effects High-dose chemotherapy can have severe life-threatening toxicities, occurring in 4% of patients. Because the treatment requires several weeks in isolation while blood counts recover, the child is at risk of infection, and usually suffers from mouth sores and mucositis throughout the gastrointestinal tract. Children receive antibiotics, anti-fungal medications, and blood products. Often they are on nutritional support due to inability to eat. Other adverse events include general condition, infection, stomatitis and veno-occlusive disease (VOD). Studies continue to assess long term effects.
Stem Cell Transplant Stem cell transplant is used to repair the immune system following high-dose chemotherapy for neuroblastoma. Expand High-dose chemotherapy is used in cases where the neuroblastoma has spread to several parts of the body, and aims to wipe out any remaining neuroblastoma cells. Due to its toxicity, it will also wipe out the body’s bone marrow where stem cells are made, so the stem cells that were taken from your child and frozen during induction chemotherapy will be replaced in a stem cell transplant. This process aims to restore the blood-producing cells in the bone marrow using your child’s own cells, meaning that there is no risk of rejection as there could be with donor stem cells. The stem cells are thawed and given by a drip back into the body after any high-dose treatment has destroyed the cells in the body. Usually, within a couple of weeks, the stem cells will begin making new white blood cells. This is followed by new platelet production and new red blood cell production. Until this happens your child is at risk of infection and stays in a special hospital room in isolation. Once this is complete and dependant on the risk group, your child may undergo radiotherapy on the area around their primary tumour site. Again, this is to try to ensure any cancer cells left after other treatments are killed off.
Radiotherapy Learn more about radiotherapy as standard treatment for neuroblastoma in the UK. Expand Your child may have radiotherapy in the location of the original (primary) tumour to ensure any cancer cells remaining from induction chemotherapy, surgery and high-dose chemotherapy are killed off. The goal is to reduce the chances of the cancer coming back in that area. In some cases your child may have to have radiotherapy whilst under general anaesthetic as they will need to be very still for the treatment to be administered effectively. It uses high energy x-rays to kill the cancer cells in daily fractions over the course of three to five weeks. It's administered using a radiotherapy machine and your child won't feel anything during treatment. There are some short-term side-effects like possible skin reactions, nausea/diarrhoea and tiredness. As your child is being exposed to significant levels of radiation, there may be precautions that need to be in place when coming into contact with others. This will depend on the type of radiation being given, and you can find out more about this from your healthcare provider.
Immunotherapy Immunotherapy is used to avoid relapse after neuroblastoma has been successfully treated. Learn more about the protocol in the UK. Expand The aim of immunotherapy - also commonly referred to as antibody therapy - (as with any maintenance therapy) is to keep your child in remission and keep the cancer away. It helps the body’s own defences to turn against the neuroblastoma cells using antibodies. This should hopefully stop the cancer from returning as the body will learn to recognise and kill the cells. After immunotherapy, some families look towards clinical trials for further prevention therapies. Immunotherapy is given into the bloodstream and lasts for six months. Anti-GD2 Anti-GD2 therapy is a type of immunotherapy which targets a molecule on the surface of neuroblastoma cells called GD2. It is present in high amounts on cancer cells but not on normal cells. The standard anti-GD2 therapy used for neuroblastoma is call dinutuximab beta. Solving Kids’ Cancer worked alongside a range of other charities to push for the outcome of NICE recommending the life-saving drug for NHS use in England and Wales. Read our statement here. Dinutuximab beta is a monoclonal antibody, meaning it is a manmade version of naturally occurring antibodies. It binds to the surface of neuroblastoma cells and marks them as target for the patient’s own immune cells to destroy. It is usually given in 5 consecutive treatment cycles, each one lasting 35 days. The dinutuximab beta will be administered as a continuous infusion over the first 10 days of the cycle (240hrs continuous infusion). As with many treatments for neuroblastoma, there are side effects which your child may or may not experience, these include: Pain Fever Nerve problems, such as numbness of tingling in the limbs Low blood pressure Vomiting and diarrhoea Capillary leak syndrome, where proteins leak from small blood vessels in the body causing swelling and low blood pressure Your child may experience other side effects, and you can speak with your treatment team about the best way to manage these. Retinoic Acid Alongside anti-GD2 immunotherapy, your child may also be treated with a retinoid called 1,3-cis-retinoic acid (isoretinoin). This can reduce the risk of the cancer coming back after high-dose chemotherapy and stem cell transplant, by helping cancer cells to differentiate into normal cells. It is normally taken as a capsule, twice a day for 2 weeks, followed by a 2-week break. It is often recommended to be taken for around 6 months, but this will depend on your child’s circumstances and your treatment team will carry the best advice for this.