Pediatric brain tumors (PBTs) are the second most common cancer of childhood, with an incidence of 4.3 per 100,000 people in the United States and children between the ages of three and seven years being the most commonly affected age group [1]. Medulloblastoma is the most common type of brain tumor in children, accounting for 20 percent of all children with pediatric brain tumors.
Typical signs of brain tumors in children are:
- Headaches that may be worse in the morning and get better during the day.
- Nausea or vomiting in the morning.
- Problems with motor skills, such as clumsiness or poor handwriting.
- Tiredness.
- Tilting of the head to one side.
- Walking difficulty and balance problems.
Treatment of pediatric brain tumors has improved drastically over the last decade, which has led to a significant improvement in the outcome for children with medulloblastoma.
Ideally, doctors will try to conduct a total resection or removal of the tumor as that has the best long-term outcome. However, if the tumor is located at a sensitive location or a previously resected tumor has returned, then chemotherapy will be the recommended option [2].
Chemotherapy refers to the use of anti-tumor drugs that are generally administered either intravenously or orally. Most of these drugs enter the bloodstream and are able to reach almost all parts of the body, with the exception of the brain due to the presence of the blood-brain barrier. Therefore, with most brain tumors, the drugs have to be administered either through the cerebrospinal fluid, directly into the brain or into the spinal canal. In order to aid with the delivery, a small hole is drilled into the skull and then a small tube can be inserted during surgery [3].
Physicians like to avoid chemotherapy for the treatment of brain tumors in children as it can lead to long-term neurocognitive deficiencies. However, for some tumors, including medulloblastoma, chemotherapy can be very effective at eradicating cancer. In fact, in some cases chemotherapy is used as a first-line therapy, or primary therapy, because it can help stop tumor growth without exposing the patient to radiation, which also comes with severe long-term effects [4].
Depending on the type of tumor and severity of the patient’s condition, these drugs might either be administered alone or in different combinations. Since chemotherapy takes a major toll on patient’s bodies, they are generally administered in cycles with one cycle lasting between 3-4 weeks and then a period of rest for the body.
Generally, a specific treatment protocol for children with pediatric brain tumors is developed by the oncologist, which includes the amount or concentration of drug, interval of each cycle and the number of cycles [5]. The ideal outcome of treating with chemotherapy is a significant regression of the tumor. However, often the goal is reduced to simply achieving stability in the growth of the tumor. This is often done in smaller children because if the tumor regrows, which it does 20-50 percent of the time, the child will be able to withstand the effects of radiation more easily [6].
While each chemotherapy regimen is specific to the child being treated, one of the more common regimens and the most aggressive is one referred to as the “8 drugs in 1 day protocol”, which employs the use of carmustine, cisplatin, procarbazine cytarabine, Prednisone, cyclophosphamide hydroxyurea and vincristine in one day.
The Children’s Cancer Group (CCG) demonstrated a higher 5-year survival for a protocol that utilized only vincristine, lomustine and Prednisone, also known as the VCP protocol with a survival rate of 63%, as compared to the “8 drugs in 1 day protocol”, which has a survival rate of 45%. The Pediatric Oncology Group conducted a similar trial with the chemotherapies vincristine, cyclophosphamide, etoposide and cisplatin and obtained similar results at the CCG group [8].
The greatest benefit to be obtained from chemotherapy occurs in patients that are at a severe stage of cancer. Newer research is experimenting and looking at conducting chemotherapy prior to radiation as that will allow the tumor to become more sensitive to radiation. Some studies are looking at the use of chemotherapy to treat patients prior to surgery as that can cause a regression of the tumor. As mentioned above, the use of chemotherapy can lead to long-term neurocognitive and neuroendocrine effects. Furthermore, it can also lead to more immediate adverse effects such as kidney toxicity, liver toxicity, fibrosis in lungs and gastrointestinal issues, but these are most often reversed when the drug stops being administered [9].
Brain tumors in children are one of the most difficult tumors to treat due to the presence of the blood-brain barrier which stops the entry of chemotherapeutic drugs. Furthermore, even with the administration of chemotherapy, the short and long-term side effects can be debilitating for the patient, and therefore, doctors try to avoid chemotherapy administration.
For other less common tumors, while chemotherapy may be utilized, the exact benefits of this therapy remain unknown. Furthermore, in the situation of less common tumors, the use of these drugs is uneducated as most doctors do not know which drugs will work and which ones won’t. Therefore, while effective in some cases, further research needs to be conducted on the the use of chemotherapies to treat brain tumors in children.
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