About medulloblastoma
What is medulloblastoma?
Medulloblastoma is the most common malignant brain tumor in children, accounting for nearly 20% of all brain tumors in this population. It originates in embryonic (fetal) tissue is usually discovered during the first 5 years of life. It affects the central nervous system and develops in the cerebellum. The cerebellum is the part of the brain responsible for coordinating muscles, balance, and movement. This tumor grows rapidly and can spread to other parts of the brain, although it rarely spreads to other parts of the body.
Medulloblastoma has an overall annual incidence of approximately 5 cases per 1 million in the pediatric population. About 75% of cases occur in children under the age of 10, with a peak incidence between 1-4 and 5-9 years of age. Sex predilection and age-specific incidence vary across groups. Medulloblastoma, as all childhood cancers, is considered a rare disease because it affects a small proportion of the population. This means that obtaining funding for research is much more difficult than for more prevalent diseases.
Symptoms
Medulloblastoma symptoms usually appear when the tumor grows or causes increased pressure in the brain and may persist even after treatment. Patients may develop:
- issues with walking, balance, and fine motor skills;
- headaches, nausea, vomiting, blurred/double vision, extreme sleepiness, confusion, seizures, and fainting;
- weakness or numbness in the arms and/or legs, change in bowel/bladder habits changes, and spinal pain;
- in the few cases where the tumor spreads to other parts of the body, coughing, chest pain and shortness of breath, enlarged lymph nodes, and bone pain may also occur.
The symptoms may vary depending on the tumor's location.
Types of medulloblastomas
Medulloblastomas are classified into four main groups based on molecular and genetic analysis of the tumor tissue, and then into further histological subgroups. This detailed classification is used to indicate the prognosis (medical opinion, based on the diagnosis, on the probable evolution and outcome of the disease) and guide treatment. The four main groups are defined according to the tumor's behavior:
WNT (wingless)
This is the least common type of medulloblastoma, accounting for only 11% of all cases. Tumors in this group are characterized by alterations in the WNT signaling pathway (an important biochemical pathway that can affect tumor growth). They affect both sexes equally and are commonly diagnosed in children aged 6 to 10 years. This type of medulloblastoma has the best prognosis, with nearly 90% of patients surviving for more than 5 years after diagnosis.
SHH (Sonic Hedgehog)
This type of medulloblastoma is common in younger patients (under 3 years of age) and those aged 16 years or older and accounts for 25% of all medulloblastomas. The SHH subgroup is associated with mutations in the Sonic Hedgehog pathway, which controls embryonic cell development and also affects tumor growth.
Group 3
Group 3 medulloblastomas are the most aggressive, with an overall survival rate of 50%, and tend to spread through the brain ventricles and spinal cord. They account for approximately 25% of all cases and are typically diagnosed in children aged 3 to 5 years.
Group 4
This is the largest and most common group, representing 35% of all medulloblastoma cases. It more frequently affects males. Tumors in this group have a good prognosis, except in case of recurrence. Group 4 childhood medulloblastoma is the focus of research supported by MBI (The Medulloblastoma Initiative), which in 2024 approved two clinical trials to test new treatments.
Diagnosis
Initially, the diagnostic process involves taking the patient’s medical history and evaluating signs and symptoms. The tests and procedures commonly used to diagnose medulloblastoma include:
- Neurological exam: This exam is used to assess vision, hearing, balance, coordination, and reflexes to identify which part of the brain might be affected by the tumor.
- Imaging tests: These tests are used to capture images of the brain to determine the size and location of the tumor. They can also reveal pressure or blockages of the cerebrospinal fluid. Computed tomography and magnetic resonance imaging are the most common imaging tests in this context.
- Tissue sampling: Although biopsies are uncommon for medulloblastoma, they may be done in certain situations. A needle is used to take a sample of the tumor, which is tested in a laboratory to determine if it is a medulloblastoma.
- Lumbar puncture: Involves inserting a needle between two bones in the lower spine to collect the cerebrospinal fluid surrounding the spinal cord. The fluid is tested in a laboratory to look for tumor cells. The lumbar puncture should only be performed after managing brain pressure or removing the tumor.
Prognosis (chance of recovery)
The prognosis, or chance of recovery, for someone with medulloblastoma depends on several factors, such as the tumor’s molecular type, stage, amount of tumor removed, the patient's age, health status at the time of diagnosis, and response to treatment. In the first few years after diagnosis, the mortality rate is close to 15%. With current treatments, the survival rate can reach 70-80% in children and 50-60% in adults. The 5-year survival rate for medulloblastoma is approximately 80.6%, but it may vary.
The specific type of medulloblastoma also impacts prognosis. WNT-activated tumors have a better prognosis than those activated by the SHH pathway or Group 3 and 4 tumors. In cases of recurrence, the 5-year survival rate drops to less than 40%.
Treatment
Current treatments for medulloblastoma, which were largely introduced in the 1980s and mostly remain unchanged, rely heavily on cytotoxic and nontargeted methods – such as conventional X-ray radiotherapy, which applies radiation to all tissue surrounding the tumor. Despite advancements, mortality rates for medulloblastoma remain high, and many survivors experience long-term side effects from radiation and cytotoxic chemotherapy, as well as cognitive difficulties, psychological and social problems, and even hormonal deficiencies. These effects may require ongoing support to enhance the quality of life of patients, especially children, who are much more sensitive to the effects of radiotherapy, as their bodies are still growing and developing.
Treatment for medulloblastoma generally involves a combination of surgery, radiotherapy, and chemotherapy. Initial treatment involves surgical removal of the tumor, followed by radiation therapy and chemotherapy, depending on the tumor’s type, location, and extent of spread. Proton therapy (a type of radiotherapy that is more precise than conventional X-ray treatment and specifically targets the tumor) for medulloblastoma may be recommended to minimize damage to surrounding organs. Currently available treatments are described in detail below.
- Surgery to relieve fluid buildup in the brain: Medulloblastomas may grow and block the flow of cerebrospinal fluid, causing a buildup that puts pressure on the brain. To relieve this pressure, a surgeon can create a pathway for the fluid to drain out of the brain. This procedure can be combined with surgical removal of the tumor.
- Surrey to remove the tumorThe goal of surgery is to remove the entire tumor. However, if it is located close to important instructors in the brain, this may not be possible. Most people with medulloblastoma will require additional treatment after surgery to kill remaining cancer cells.
- Radiotherapy: Radiotherapy uses powerful energy beams to kill cancer cells. This energy may come from X-rays, protons, or other sources. During radiotherapy, a machine directs energy beams to specific areas of the body. It is usually performed after surgery.
- Chemotherapy: Chemotherapy uses medications to kill cancer cells. Typically, children and adults with medulloblastoma receive these medications through intravenous injections. Chemotherapy may be given after surgery or radiotherapy and, in some cases, may be administered simultaneously with radiotherapy.
Future prospects
Clinical trials with new medications may also be an option for some patients. Clinical trials enroll eligible participants to study new treatments, such as immunotherapy, or new ways of using existing treatments, such as different combinations or durations of radiotherapy and chemotherapy. These studies offer patients the opportunity to try the most recent treatment options, although the risks of side effects may not be fully known.
Since its creation in 2021, the MBI has been raising resources to find a cure for Group 4 medulloblastomas. MBI has successfully secured financial support for a consortium of 14 laboratories in the United States, Germany, and Canada (the Cure Group 4 Consortium), led by Dr. Roger Packer from Children’s National Hospital. The group has already made a significant discovery about the likely mechanism of development for the cells that give rise to medulloblastoma.
In addition, in under 3 years, two clinical trials have also already been approved by the U.S. Food and Drug Administration (FDA) to test two new treatments:
Study 1
Also called MATCHPOINT – it will attack the tumor in two ways: 1) by training the patient’s own cells to identify and destroy cancer cells, and 2) by using an additional drug to disrupt the tumor's defense system.
Study 2
It will test an mRNA vaccine, similar to the COVID-19 vaccine, but more personalized, as it uses the patient’s own cells. Nanotechnology is used to create the vaccine. Once injected, the vaccine generates a targeted immune response to destroy the tumors.
Three more clinical trials will be submitted between 2024 and 2025. This effort supported by philanthropy is expected to find a cure for Group 4 medulloblastomas.
References
https://www.mayoclinic.org/diseases-conditions/medulloblastoma/cdc-20363524/
https://mbinitiative.org/pt/clinical-trails-approved/
https://www.ncbi.nlm.nih.gov/books/NBK431069/
https://www.cancer.gov/rare-brain-spine-tumor/tumors/medulloblastoma
https://ascopubs.org/doi/10.1200/JCO.2017.72.7842
https://medulloblastoma.org/medulloblastoma-statistics/
https://www.sciencedirect.com/science/article/pii/S1878747923014630
https://www.infopedia.pt/dicionarios/lingua-portuguesa/progn%C3%B3stico
https://mbinitiative.org/wp-content/uploads/2024/09/MBI-Report-September-2024-EN.pdf
https://mbinitiative.org/wp-content/uploads/2024/04/Report-MBI-Abril-2024-PT.pdf