New Test Aims to Spare Children With Medulloblastoma From Toughest Treatments

Children's Hospital Los Angeles (CHLA) this week launched a new test to help doctors make better treatment decisions for children with medulloblastoma, one of the most common types of brain tumors in children. Although the survival rate for medulloblastoma is higher now than it was 30 years ago, the treatments for it are intense and can leave children with severe life-long problems.

“The standard treatment for medulloblastoma includes radiation to the whole brain and spine, as well as surgery and chemotherapy,” says Shahab Asgharzadeh, M.D., a pediatric oncologist at CHLA and the researcher who led the development of the new test. “Unfortunately, radiation to the brain has significant long-term side effects in children. These side effects range from mild learning disabilities to severe mental retardation – and the brain-damaging effects are most severe in young children.”

This is why Asgharzadeh designed a test that doctors could use to determine which children will benefit most from – or absolutely need – radiation.

Dr. Shahab Asgharzadeh in his office

“Recent studies have shown that some (but not all) children can be cured of medulloblastoma using only surgery and chemotherapy,” says Asgharzadeh. “If we are able to identify ahead of time patients whose medulloblastoma was curable with chemotherapy alone, we could spare many children the devastating effects of radiation, which is the current standard of therapy.”

Asgharzadeh’s test can pinpoint which of 4 subtypes of medulloblastoma a child has, which is information that can help a doctor decide whether and how much radiation is necessary. Using a tissue sample from the medulloblastoma, the test looks for particular genetic markers and can tell with a high degree of accuracy which subtype of medulloblastoma the child has.

Asgharzadeh and colleagues will soon be launching the Head Start 4 clinical trial program that will use the new test to assign children different therapies based on their molecular subgroup. The trial will be headquartered at Nationwide Children’s Hospital and CHLA, with another 30 institutions participating.

For children who do not get enrolled in the clinical trial, their doctors can still send samples to be tested at CHLA’s Department of Pathology. In these cases, the doctor can use the results of the test at their discretion to help make treatment decisions.

“Any doctor in the world with a patient who has medulloblastoma can now send a tissue sample to CHLA to be analyzed using the MBL31 assay [test] and receive a full pathology report stating which molecular group this sample belongs to,” says Asgharzadeh. “This is the first clinically available test that can tell apart medulloblastoma subgroups.”

Asgharzadeh’s research and work to develop the new test was funded in part by a grant from the American Cancer Society. “I got my American Cancer Society grant 4 years ago and it was the predominant grant I used to do all of this work; if I had not had this funding I would not be where I am right now with the test,” says Asgharzadeh.

Next Up: A Faster, Easier Test That Could Determine Cancer Subtype Without Surgery

The new test requires a tissue sample, meaning the child still needs to have surgery to remove the tumor from the brain before the doctor can find out what subtype of medulloblastoma the child has. The current standard of care is to remove the entire tumor, if possible, and then follow up with radiation and chemotherapy.

Asgharzadeh is now working on another type of test that would allow doctors to know upfront what subtype of medulloblastoma a child has so that, if appropriate, they can give chemotherapy first to shrink the tumor before doing surgery. In general, the smaller the tumor, the less risky the surgery.

His new research, published August 7 in the journal Neuro-Oncology, shows that an existing and widely used imaging test called magnetic resonance spectroscopy (MRS) may be effective in determining subgroups of medulloblastoma in a non-invasive manner.

“What we are trying to do now is figure out if there is another test we could use that would even more rapidly tell apart the medulloblastoma subgroups,” says Asghazadeh.

“I am working to develop the test with Dr. Stefan Blüml, a physicist who is an expert in MRS. MRS technology is widely available as part of MRI imaging and may be able to tell apart the important subtypes of medulloblastoma without having tissue on hand.”

Asghazadeh hopes that the results from a child’s MRI could give doctors clues ahead of time, before deciding on a treatment strategy. These clues may lead a doctor to do a less risky surgery first to remove just a piece of the tumor for more testing (a biopsy) or could help neurosurgeons decide how aggressive they need to be.

“The goal is to combine MRS with less invasive techniques or take only a small part of the tumor out for testing, based on what the MRS tells you. If MRS informs you the tumor is among the higher risk subgroups, then at this point you have no choice but to remove it. But if it is a lower risk subgroup, you could maybe reduce the risks associated with surgery by using neoadjuvant therapy, treatments given ahead of surgery to shrink a tumor to a manageable size for surgery. Of course, these ideas first need to be tested in a clinical research setting.”

Asghazadeh says the MRI test for telling apart medulloblastoma subtypes is still experimental. He will be expanding his study to confirm the test will work.

Long-Term Hopes: Develop Better Treatments for Children With Medulloblastoma

Asghazadeh also has other plans to expand his work. He hopes to use what he is learning about how medulloblastomas function on the molecular level and how they interact with the immune system to develop more effective and less toxic treatments. “Our long-term goal is to use the information about the genetic makeup of different subtypes of medulloblastoma and the role of the immune system to develop innovative targeted and immunotherapies to treat patients without use of radiation.”

“We have gotten better at curing children with a lot of therapies, but our goal now is to cure children while also allowing them to become healthy adults, meaning we need to make sure we don’t use toxic therapies when we don’t need to.”

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