How is it treated and managed?
Most children will have surgery for their brain tumour as this is the most effective treatment to relieve selected symptoms at short notice and is a significant prognostic factor in the management of several tumours. Surgery, with the aim to remove the entire visible tumour may not be possible due to the location and proximity to functionally important or vital areas of the brain (e.g. pons - responsible for breathing or motor strip in the fronto-parietal lobes of dominant hemisphere). In these cases, either a biopsy or partial ‘debulking’ will be performed and adjuvant (follow-up) therapy with either radiotherapy, chemotherapy or a combination of both may be used. For some tumour types (e.g. low grade astrocytoma or other benign tumours) complete surgical resection is the only treatment necessary. However, for malignant brain tumours (e.g. medulloblastoma, malignant glioma) and some lower grade tumours (e.g. ependymoma) adjuvant therapy will be recommended for the majority of cases even if a complete resection is achieved because of concerns about residual microscopic disease.
In young children (under 3 years of age) the management depends not only on the tumour type, location and stage but also possible late effects of treatment, particularly radiotherapy induced effects on brain development. The immature developing brain is very sensitive to radiotherapy and this can result in significant and severe ongoing learning difficulties, growth problems and endocrine deficits. The younger the child is, the worse the outcome. The functional effects are manifested over a prolonged period (years) as the child’s ability to learn is reduced compared to their peers, which means that the gap in their abilities compared to the norm widens over time. This means that children under 3 who have received radiotherapy have a significantly lower IQ after treatment and frequently have impaired fine motor, visuo-motor and visuo-spatial skills and memory difficulties. This is not restricted to those below 3 years of age but it is more pronounced in the younger age group. Over time radiotherapy treated children are likely to require special help at school because of their cognitive impairments. Young children, therefore often have more chemotherapy based adjuvant therapy to either, avoid, delay or reduce the need for radiotherapy.
Surgery
Craniotomy
This is the main operation used for most brain tumours - a large incision is made and a flap of bone lifted from the skull to gain access to the brain underneath. It is performed under general anaesthesia in children. Initial recovery takes place in hospital with the hospital stay ranging from 5-14 days. The scars tend to be behind the hairline and do not affect appearance in the longer term. Return to normal function after this type of surgery depends on several factors:
- Level of function before surgery
- Whether further damage was caused by surgery
- Whether neurorehabilitation (medical processes to aid recovery from nervous system injury and to compensate for functional alterations) is required
- Whether further treatment such as radiotherapy or chemotherapy is required.
Common problems after surgery include:
- Headaches – these normally resolve within two weeks but may persist for months.
- Lack of concentration and memory problems – can gradually improve over several months.
- Tiredness – likely to be severe for the first 2 weeks and then improve but does not always completely resolve and is made worse by adjuvant treatment.
A child who was well prior to their surgery and who does not need any neurorehabilitation or any further adjuvant treatment may be well enough to return to school 6 -12 weeks after surgery.
A child with a neurological deficit such as weakness, clumsiness, memory problems or difficulty with speech should have access to neurorehabilitation. For mild problems this can be offered as an outpatient with regular therapy sessions including Physiotherapy, Occupational therapy and Speech and Language therapy. This may be at a local hospital or via community teams and therapists. For more severe deficits this may involve a period as an inpatient on a neurorehabilitation ward.
Neurological deficits are likely to improve quickly for a few months and then improve much more slowly, usually improving for up to 2 years. This can vary and can be assessed by therapists who can monitor patients’ recovery at key stages of their pathway and offer appropriate intervention. Needs will decrease as improvement occurs. Some neurological deficits will not improve with rehabilitation and for some children a neurological deficit may persist. Part of the rehabilitation process will include learning compensatory and coping skills to overcome disabling effects of both physical and cognitive impairment and to optimise function. This may include the use of adaptive devices or equipment to enable activities of daily living. A stable condition is likely to be reached in two years.
Other types of surgery:
Shunts - thin flexible plastic tubes are implanted in to the body to redirect cerebrospinal fluid (CSF) when a blockage has occurred – they relieve raised intracranial pressure and its symptoms. Shunts may be temporary or permanent. Recovery from this type of surgery takes up to a few weeks; it is not associated with any permanent neurological deficits but can be complicated by shunt blockage and infection requiring further treatment and possible revision of the original shunt.
Neuroendoscopy - this technique uses an endoscope to operate through, this means only one or two small ‘burr’ holes have to be made in the skull and recovery is quicker. Unfortunately, at the moment, it can only be used for a small proportion of brain tumours. A ‘third ventriculostomy’ is an endoscopic operation to relieve raised intracranial pressure avoiding a plastic shunt.
Transphenoidal surgery - this means an operation performed via the nose so there are no external scars. This type of surgery is virtually exclusively used for pituitary gland tumours as the pituitary gland is located behind the nose. There are no external scars after this type of surgery – recovery time is up to 6 weeks.
Radiosurgery - this is not surgery at all but highly focused and targeted radiotherapy treatment.
Radiotherapy
Radiotherapy is a commonly used treatment for brain tumours, it is used as:
- primary treatment for tumours that cannot be removed by surgery
- adjuvant treatment for tumours that have been either completely removed or 'debulked' by surgery either after a time of observation (less aggressive tumours) or at first diagnosis of a malignant tumour, or for treatment of recurrent disease.
Radiotherapy treatments are usually given daily (Monday to Friday) over 6 weeks. Side effects occur during treatment but are not usually severe. In young children (less than 5 years old) daily general anaesthesia may be needed to deliver the radiotherapy. Long term side effects are significant in children especially if they are under 3. If possible radiotherapy treatment is delayed until the child is older.
Short term side effects include:
- Tiredness and sleepiness – if severe, towards the end of treatment the child having radiotherapy may do little other than sleep. In medical evidence this may be referred to as ‘somnolence syndrome’. This can occur after the radiotherapy has been completed and persist up to 12 weeks after treatment has finished but usually improves without intervention.
- Sickness – may require treatment with anti-emetic drugs.
- Worsening neurological deficit – problems caused by the tumour, such as clumsiness or speech difficulty, may get worse during treatment because of swelling within the treatment area. Steroid drugs are often used to treat this. Deficits associated with swelling should improve once treatment is complete.
- Hair loss and skin changes – hair in the treated area is likely to fall out and this may be permanent depending on dose and the individual. There may be skin changes similar to mild sunburn - the skin may become very sore, red and dry.
- Disturbed hearing – hearing may be affected during treatment due to local inflammation, which may persist if the cochlea is within the radiotherapy field.
- Difficulty concentrating and remembering – in children under 7 the IQ is reduced after radiotherapy treatment, the younger the child the greater the reduction. This is rare in the short term setting and usually manifests 6 months or later after treatment.
In the long term mild-moderate problems with concentration and memory are common in children who have had radiotherapy treatment to the head (depends on age, dose and volume of brain irradiated), they are not necessarily disabling but they may mean that a child does not fulfil their intellectual potential.
Conformal radiotherapy is a technique for giving radiotherapy that reduces the dose of radiotherapy to normal tissues so reducing associated damage and long term side effects. It not used very often in children.
Proton therapy
Proton treatment is a highly specialised means of delivering radiotherapy dose to a target volume. The particular characteristic of proton beams means that comparatively little radiation is given to normal tissues. This is especially useful for children with certain types of brain and spinal cord tumours. This is a new technique and long term outcomes are still limited. There are currently no Proton facilities in the UK capable of treating brain tumours. In May 2007, the final report of the National Radiotherapy Advisory Group (NRAG) contained a recommendation that the Department of Health facilitated the setting up of panel to review high priority clinical cases on behalf of Primary Care Trusts (PCTs). Since April 2008, suitable cases have been funded for treatment abroad by a service nationally commissioned by the National Commissioning Group (NCG.) A Proton Therapy Clinical Reference Panel (PTCRP) has been set up, which manages the referral pathway and has the necessary knowledge of proton therapy to approve cases for consideration for treatment abroad. Local clinicians following discussions with patients and their families may choose to refer to the panel for consideration of Proton therapy rather than conventional radiotherapy.
For further details of see - Proton Beam Therapy
Steroid drugs
Steroid drugs are commonly used in short courses to reduce brain swelling related to the tumour itself or its treatment, particularly with surgery or radiotherapy – both of which cause tissue inflammation and swelling. Prolonged use of steroid drugs will have side effects; they cause weight gain, osteoporosis, muscle weakness, behavioural changes and growth retardation.
Anticonvulsants
Epileptic fits are common symptoms of brain tumours but they may also occur as a result of treatment such as radiotherapy or surgery. These drugs are commonly used prophylactically to prevent fits in children undergoing treatment whether they have had a fit because of their tumour or not. Children who have had fits may need to take anticonvulsants permanently to control epilepsy. Disabling effects of epilepsy relate to frequency and type of fits – refer to epilepsy guidance.
Chemotherapy
Chemotherapy, unlike in adults with CNS tumours, may be the primary treatment of choice for some patients e.g. unresectable low grade astrocytoma (glioma- NB. this term is often used if no histological diagnosis), and malignant tumours in young children. It is also frequently used in combination with radiotherapy.
Chemotherapy can occasionally be delivered directly into the tumour by placing a drug impregnated implant or wafer into the tumour bed at the time of surgery. This has only been used in clinical trials in 2010. Conventionally it is given in cycles using oral or intravenous combinations of chemotherapy drugs. Most chemotherapy for brain tumours is given either intravenously or by mouth (orally). Drugs likely to be used include:
- Cisplatin.
- Carboplatin.
- Cyclophosphamide.
- Etoposide.
- Vincristine.
- Methotrexate.
- Temozolomide.
- Nitrosoureas.
In young children to avoid radiotherapy or in poor prognostic tumours ‘high dose chemotherapy’ may also be used. Trials are underway testing the outcome of high dose chemotherapy with stem cell transplant in children under 4 and for high risk PNET (Primitive Neuroectodermal Tumour). This treatment involves high dose chemotherapy followed by peripheral blood stem cell transplant (PBSCT).
Peripheral Blood Stem Cell Transplant (PBSCT) or Bone Marrow Transplant
Biological therapy
There are multiple options most of which will be used in the context of clinical trials. They include monoclonal antibodies (e.g.Avastin™), dendritic cell vaccination, tyrosine kinase inhibitors e.g. Glivec (Imatinib), gene therapy and oncolytic viruses. Side effects of these are generally milder compared to the effects of conventional chemotherapy but targeted therapies affecting developmental pathways may possibly result in side effects that could only be seen in children e.g. growth effects.
Treatment of recurrent brain tumours
Often recurrent brain tumours cannot be cured but they can be controlled for a period of time, depending on the tumour type and location of the recurrence. Children may be offered additional chemotherapy, (radiotherapy if not already received), enrolment onto a clinical trial for a new treatment or symptomatic palliative care.
