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By Dr Stergios Zacharoulis,
Paediatric Oncology Consultant at the Royal Marsden Hospital and The Harley Street Clinic
Article Last Updated: October 29, 2009
Overview
Approximately 1 to 2 children per 10,000 are diagnosed with cancer each year. Clearly this is a very serious diagnosis and only a few decades ago only a small percentage of these children would have survived. However, things have improved rapidly and these days the good news is that most children can be cured. The cause of cancer in children is mostly unknown and only a very small percentage can be explained by genetic syndromes and conditions.
Treatment options include the use of surgery, radiation therapy and chemotherapy depending on the type of tumour. This article describes the different types of brain cancer in children and the latest recommended treatment options.
Chemotherapy in children
Chemotherapy involves the administration of medications that specifically affect all those cells that divide and grow rapidly, which is the predominant feature of most cancer cells. Most of these medications are given through the vein, less commonly by mouth or with injections under the skin. In order to avoid frequent painful venous puncture a permanent catheter is inserted (under anaesthesia by surgeons) which can be under the skin (port-a-cath) or externally, outside the chest (Hickman catheter).These catheters are removed after the end of therapy.
Side effects
The side effects of chemotherapy can be variable and are due to the fact that these medicines affect other cells in the body. Very commonly children feel nausea and vomit but several medicines are used that can prevent or control these symptoms.
Hair loss is also very common but this is a transient side effect and the hair re-grows within a few weeks after the treatment is over. Loss of appetite, diarrhoea or constipation, mouth sores, and loss of weight are also common. A lot of children require nutritional support during treatment using feeding tubes which are not painful and several medicines are used to ease these side effects.
Fever, the need for transfusions and infections are also relatively common side effects. Basic hygiene, hand washing, avoidance of prolonged exposure to sick contacts and balanced diet are some ways to prevent infections but unfortunately most of the time they cannot be avoided.
Depending on the type of chemotherapy medicines used hearing loss, jaw pain and the sensation of “pins and needles” can also occur. Very rarely some of the medicines can cause heart, kidney, nerve, liver or lung damage.
Long term side effects are in general rare but depending on the medicines used can include infertility or second cancers such as leukaemia. Details of the side effects, the method of administration and potential long term risks are always discussed prior to treatment for each individual medicine and patients are monitored very closely with blood or other tests during and following the end of therapy.
Brain tumours
There are a number of different brain tumours that can affect children and I will explain each one in turn.
High Grade Glioma
Glioma is a type of brain tumour and the vast majority of high grade gliomas originate from cells known as astrocytes. They are called “high grade” because these are fast dividing tumours, they are aggressive and therefore doctors are generally wary about the prognosis. The two main types of high grade gliomas are called “Anaplastic Astrocytoma” (Grade III) and “Glioblastoma” (Grade IV) .These tumours require surgical removal followed by radiation therapy and chemotherapy, typically this is one medicine which is taken by mouth, (Temozolomide).
The radiation therapy to treat this form of cancer requires about 6 weeks to be completed and is given on an outpatient basis. Following the completion of radiotherapy patients continue to receive chemotherapy at home for a minimum of 6 months followed with MRIs, physical examinations and blood tests. The chemotherapy in general is very well tolerated. Unfortunately most but not all patients experience relapse (when the tumour grows back). In these circumstances, we will try the new innovative, experimental medicines. Most of these therapies are administered in the context of a clinical trial or novel combinations can be offered. All of these approaches are based on the most up to date, published information that is available.
Diffuse Pontine Glioma
These are tumours, typically of the glioma variety that infiltrate the most important part of the brain. Due to their location and infiltrative nature they cannot be removed (resected) surgically. Biopsy in general is relatively safe, but is performed only for research purposes. The current standard of care is radiation therapy which at its best provides some improvement of the symptoms which last typically for a few months. Currently several other drugs are being investigated and offered in order to overcome what is otherwise an extremely poor prognosis.
Low Grade Glioma
The vast majority of low grade gliomas also originate from the astrocyte cells in the nervous tissue. They are called “low grade” because they are tumours that divide slowly, they only spread gradually (indolent) and in general have a very good to excellent prognosis. After the surgeon has completely removed all the tumour material there is no need for any other therapy (chemotherapy or radiation therapy) unless the tumour comes back, which can happen on rare occasions. In cases where it has been too difficult to completely remove all of the tumour material we can follow any progression of the cancer by MRI. A further course of treatment will begin if or when the tumour starts growing. An alternative option is an immediate treatment period with chemotherapy or radiation. Choice of approach will depend on age, the location of the tumour and the symptoms of the child. Progressive low grade gliomas require either chemotherapy or irradiation.
Several chemotherapy regimens (the latest drugs include Temozolomide, Carboplatin and Vincristine, Vinblastine, TPCV) can be used for these tumours with reasonable success in controlling the disease. Generally, chemotherapy is well tolerated by the patient. However, the duration of chemotherapy is long (more than a year). The primary aim is to delay the need for any radiation therapy for as long as possible. Radiation therapy has the potential to cause learning difficulties, affect IQ and memory loss (neuro-cognitive problems) in very young children and is generally to be avoided until the child is older (around 10 years).
Some low grade gliomas arise in a part of the brain situated behind the eyes known as the hypothalamus. These hyptothalamic gliomas are more difficult to cure and we therefore increasingly turn to the more novel and latest therapies.
Medulloblastoma/PNET
These are malignant tumours, arising from undeveloped stem cells either in the portion of the brain that controls voluntary movement, the cerebellum (medullobalstoma) or elsewhere within the brain (Primitive Neuroectodermal Tumour, PNET). They can spread to other parts of the brain and to the spinal cord.
Treatment of these tumours involves maximum possible surgical removal of the tumour by a highly experienced neurosurgeon. Following surgery and within a few weeks following recovery the next phase of treatment will begin. Choice of treatment depends on the following factors:
- the child’s age,
- the location of the tumour,
- whether or not there is any residual tumour following surgery,
- the presence of other areas of disease (disseminated disease)
Treatment can include higher or lower doses of radiation therapy to the brain and spine. This can be combined with several cycles of intensive chemotherapy involving drugs such as Cisplatin, Cyclophosphamide, Vincristine, CCNU and retinoic acid for approximately one year.
Radiation therapy to the brain and spine is avoided if possible in young children due to the potential of neuro-cognitive damage (memory, IQ, concentration,etc).Overall the prognosis is good for medulloblastoma and fair for PNET.
Patients who experience relapse (re-growth of their tumour) unfortunately have a poor prognosis. Treatment options will depend on the type of previous therapy and will include relapse surgery, irradiation, high doses of chemotherapy, novel chemotherapy combinations and enrolment on clinical trials with experimental drugs.
Ependymoma
Ependymomas are a rare brain tumour of the glioma type. They develop within the ependymal cells lining the brain's ventricles (a series of fluid filled cavities in the brain).These tumours have the capacity to metastasize to other parts of the brain and spine (approximately 10%). The treatment involves maximum possible surgical tumour removal followed by radiation therapy or chemotherapy (Cyclophoshamide, Cisplatin, Methotrexate, Etoposide, Vincristive, Carboplatin) for very young children. The extent of surgical removal of the tumour is the most important prognostic factor. In the case of any residual tumour remaining following the first operation, a second surgical procedure is always considered following a few cycles of chemotherapy.
The prognosis is fair. For patients who experience any re-growth of the tumour, depending on the precise location of the tumour, they can be offered surgery, radiation and / or the promising novel therapies that are still under trial.
Neuroblastoma
The part of the nervous system that is responsible for controlling the automatic (involuntary) activities of the body such as glands and organs is known as the sympathetic nervous system. Neuroblastoma is a rare cancer of the sympathetic nervous system. It affects usually young children, and is the most common cancer among infants. These cancers are typically found in the adrenal glands (the organs sitting on the top of the kidneys), but they may begin in other nerve tissues in the neck, chest, abdomen or pelvis. They may also spread to other areas of the body, including bone and bone marrow, lymph nodes and liver.
Treatment for neuroblastoma differs depending on many factors, particularly the stage of the disease, the age of the patient and the biologic factors that can be determined following a biopsy and a report from the pathology laboratory. These factors include the following:
- How much the cancer cells appear like normal tissue (Degree of differentiation)
- How aggressive the cancer is (n-myc oncogene status)
and- The presence of any chromosome abnormalities
Some neuroblastomas will go away without any treatment (especially in very young infants), and others can be cured by surgery alone (especially if in the early stages). Large tumours that have not spread to other parts of the body (metastases),and tumours that are found not to be “aggressive” biologically, can be highly curable with only 4-8 cycles of chemotherapy and surgery.
Approximately half of all neuroblastomas will already have spread to the bone and bone marrow by the time they are found, and these tumours require more complex treatment. This usually includes a phase of intensive chemotherapy followed by surgery, radiation therapy, high dose chemotherapy with autologous bone marrow transplant, retinoic acid and anti-GD2 monoclonal antibody.
Unfortunately a significant number of patients with advanced disease at diagnosis experience re-growth of their tumour which is associated with a very poor prognosis. Patients with relapsed neuroblastoma are usually enrolled in available clinical trials or treated with novel chemotherapeutic/biological combination therapies.
Paediatric Sarcomas
Sarcomas represent approximately one tenth of all childhood tumours. These are cancers originating from the muscle (rhabdomyosarcoma) or the bone (osteosarcoma, Ewing’s). Biopsy is always performed first to confirm the diagnosis. Because sarcomas can spread to other parts of the body, “staging” procedures (CT scan of the chest, bone marrow biopsies, bone scan and PET scan) are performed prior to treatment.
Depending on several factors (age, location, size, type of the tumour) patients with rhabdomyosarcoma receive tailored-based therapy according to their risk (low, intermediate , high ,very high). In general the treatment involves chemotherapy (Ifosfamide, Cyclophosphamide, Actinomycin-D, Vincristine, Doxorubicin) maximum possible surgery and/or radiation therapy. Their prognosis is usually very good.
Patients with osteosarcoma receive initial chemotherapy (Cisplatin, Doxorubicin, Methotrexate,) followed by surgical resection, and depending on the findings, the duration and type of chemotherapy following surgery is tailored accordingly. Patients with osteosarcoma do not routinely receive radiation therapy. Their prognosis, if not metastatic (spread to other parts) is very good.
Patients with Ewing’s sarcoma also receive several cycles of chemotherapy (Ifosfamide, Etoposide, Vincristine, Doxorubicin) followed by surgical resection of the tumour and/or radiation therapy. Further chemotherapy is administered after the surgical removal of the tumour for approximately 8 months.
Other types of sarcomas require individualized treatment depending on the type and size with surgery only, surgery and radiation therapy, surgery and chemotherapy (most commonly Ifosfamide/ Doxorubicin) and radiation therapy.
Patients who experience relapse (re-growth of their tumour) have unfortunately poor prognosis and their treatment is individualized. Patients usually receive novel drugs alone or in combination typically enrolled in clinical trials or offered novel combinations based on the most up to date published information.
Wilms Tumour
Wilms tumour is the most common kidney cancer in children. Most of the time this tumour is confined (localized) in just one kidney. However, it can sometimes spread to other parts of the body including the lungs. In rare cases it can involve both kidneys at the same time. The treatment involves biopsy, CT scan of the chest to look for any tumour spread, administration of chemotherapy for approximately a month (Vincristine, Actinomycin-D, sometimes Doxorubicin), surgery and depending on the findings and the stage of tumour further chemotherapy (Vincristine, Actinomycin-D, sometimes Doxorubicin, Carboplatin,Cyclophosphamide) with or without radiation therapy.
The prognosis is excellent. For the patients who experience re-growth of their tumour depending on the initial therapy further surgery, chemotherapy, and radiotherapy can be offered with fair prognosis.
Germ Cell Tumours
There are two main types of Germ cell tumours of the brain: Germinomas and Non-Germinomatous Germ cell tumours. Germinomas are highly curable tumours with radiation therapy administered in the tumour and surrounding area or in order to decrease the dose of the radiation a few cycles of chemotherapy can be included.
Non-Germinomatous Germ cell tumours include a wide variety of tissue types (histologies) such as teratoma (mature and immature), choriocarcinoma, embryonal carcinoma, yolk sac tumour and mixed germ cell tumour. Their treatment includes biopsy of the tumour, measurement of the tumour markers in the blood and cerebrospinal fluid (spinal tap) chemotherapy for 4-6 cycles, surgical resection of the tumour and radiation therapy. Their prognosis is inferior to germinoma.
For germ cell tumours outside the brain, surgery is the fundamental treatment approach. This is followed up with blood tests to measure the level of the relevant tumour markers. Chemotherapy might have to be used for inoperable tumours or patients whose tumour markers do not show any decline following surgery.
Repeat surgery, radiation therapy and/or a high dose of chemotherapy with autologous bone marrow transplant are offered to those patients who relapse and experience re-growth of their tumour. The choice of treatment will mostly depend on the pattern of relapse.
Conclusion
The treatment methods available for children with brain tumours have improved substantially over recent years. There are also a number of new and exciting treatment modalities currently undergoing clinical trials and these treatments will be made available when it is deemed appropriate. Clearly, the diagnosis of a childhood brain tumour is a shocking scenario for both the patient and their family, but with the latest treatment options it is now possible for there to be a good prognosis. Most children can now be cured.
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