Studies shed light on treatment options for catastrophic childhood brain tumors

A new study led by Washington University in St. Louis Medical School provides new guidance for the treatment of the pediatric brain tumor, medulloblastoma. Some aspects of radiation therapy may be alleviated while providing effective treatment. It shows a proton therapy plan for patients with medulloblastoma. The extra “boost” radiation dose to the back of the brain is shown in red. Green is preventive radiation therapy for the entire brain and spine.Credits: University of Washington School of Medicine

Medulloblastoma is a rare but devastating childhood brain tumor. The cancer can spread through the spinal fluid and deposit in the brain or elsewhere in the spine. Radiation therapy to the entire brain and spine is followed by additional radiation to the back of the brain to prevent this spread and become the standard of care. However, the radiation used to treat these tumors puts a lot of strain on the brain, especially in young patients who are just beginning to develop, damaging cognitive function.

Ah National survey In a study led by Washington University in St. Louis School of Medicine and St. Jude Children’s Research Hospital, children with what is called “mean risk medulloblastoma” receive a radiation “boost” to a smaller volume of the brain at the end of the age of six. — Continued radiation therapy for a week maintains the same disease control as patients receiving a wider range of radiation therapy. However, researchers also found that the dose of prophylactic radiation therapy given to the entire brain and spine in a 6-week regimen could not be reduced without reducing survival. , Showed that the patient’s cancer responds differently to treatment depending on the biology of the tumor, preparing for future clinical trials of more targeted treatment.

The 5-year survival rate for children with an average risk of medulloblastoma ranges from 75% to 90%. In contrast, the 5-year survival rate for children called “high-risk medulloblastoma” is 50% to 75%. Other factors-the age of the child and tumor Widespread — Helps determine risk categories. In this study, researchers focused on patients with average-risk medulloblastoma.

The findings will be published online on June 10. Journal of Clinical Oncology..

“Medulloblastoma is a catastrophic disease,” said Jeff M. Mikalski, lead author and responsible author of Radiation Oncology, University of Washington, Professor Carlos A. Perez. “that is Malignant brain tumor It occurs in the cerebellum, the lower posterior part of the brain, which is important for adjusting movement, speech, and balance. Radiation therapy for this tumor can also be difficult, especially for younger children with active brain development in these areas. There is a balance between effectively treating tumors without compromising children’s ability to move, think and learn. “

Children with an average risk of medulloblastoma usually have surgery to remove as many tumors as possible. They also received chemotherapy Radiation therapy This is to prevent the tumor from spreading through the cerebrospinal fluid to the brain and other parts of the spine.

“We wanted to find out if we could safely reduce the amount of radiation these patients receive, save normal parts of the brain, and reduce the side effects of children with this type of brain tumor.” Chair and director of clinical programs in the oncology department. “We found that reducing the radiation dose received during the 6-week treatment period had a negative effect on survival, but we also found that we could safely reduce the size of the volume of the brain that received the final radiation boost. We hope that such measures will help reduce the side effects of this treatment. Young patient

The researchers worked with US and international children’s hospitals to evaluate 464 patients who were treated for average-risk medulloblastoma diagnosed between the ages of 3 and 21. A standard dose (23.4 Gray) or low dose (18 Gray) of radiation is given to the head and spine areas every 30 treatments over a 6-week period. All elderly patients received standard doses because their brain development was vulnerable to radiation. In addition, all patients were randomly assigned to receive two sizes of radiation “boost” at the end of the 6-week treatment. Due to the boost, all patients received a cumulative dose of 54 Gray to the entire area of ​​the brain, called the posterior fossa, including the cerebellum, or to a smaller area of ​​the cerebellum. brain This includes the original contour of the tumor, as well as an additional margin up to about 2 centimeters away from the border of the original tumor.

“Patients with a small boost perform as well as those with an entire posterior fossa boost,” said Mikalski, who treats patients at the Sightman Kids at Washington University in St. Louis Children’s Hospital. I showed. ” “Many doctors have already adopted this small boost amount, but now there is high quality evidence that it is actually safe and effective.”

In patients who received low doses of booster immunotherapy, 82.5% survived for 5 years with no exacerbation of the cancer. And in patients who received a large boost over the entire posterior fossa, 80.5% survived for 5 years without exacerbation of the disease. These numbers were not statistically different. In a subset of tumors with a mutation in a gene called SHH, patients actually showed improved survival with less boost.

However, for younger children, reducing radiation doses over a 6-week period did not result in similar survival. Approximately 83% of patients who received standard doses of cranio-spinal radiation survived for 5 years and the cancer did not worsen. Approximately 71% of patients who received low doses survived for 5 years and their cancer did not worsen. The difference in survival rate was statistically significant.

“Young patients who received lower doses of craniospinal irradiation had higher recurrence rates and tumor growth rates,” says Michalski. “In general, in children with medulloblastoma, it is not safe to reduce the radiation dose, even though it is known that lowering the radiation dose can impair cognitive function. We are conducting research only on specific patients to see if the dose can be safely reduced. radiation Administer for them. “

Tumors were classified into four molecular subgroups based on the expected biology of gene expression. The first group of tumors have mutations in the WNT signaling pathway. The second is a mutation in the SHH gene. And the third and fourth groups of tumors each have different and more complex patterns of genetic mutations. Researchers have discovered differences in tumor response to tumor biology-based therapies that guide the design of future clinical trials.

“We have made great strides in the recognition of the molecular diversity of medulloblastoma over the last 15 years,” said Dr. Paul Northcott, Principal Author of St. Jude Children’s Research Hospital. “We performed whole exome sequencing and DNA methylation profiling to assign patients to the molecular subgroup, which is important in contextualizing this study based on the latest biology. As a step, we have shown that there are some important differences in children’s response to treatment. The results of this study play an important role in designing next-generation clinical trials for children with myeloma. Will do. ”

Patients with medulloblastoma should receive both chemotherapy and radiation therapy after surgery.

For more information:
Michalski JM et al. A pediatric oncology group phase III trial of reduced dose and volume radiation therapy with chemotherapy for newly diagnosed mean-risk medulloblastoma. Journal of Clinical Oncology. June 10, 2021.

Quote: Research reveals treatment options for catastrophic childhood brain tumors (10 June 2021) 10 June 2021 Treatment-options Obtained from -devastating-childhood-brain.html

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Studies shed light on treatment options for catastrophic childhood brain tumors

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