Study sheds light on treatment options for devastating childhood brain cancer

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

Medulloblastoma is a rare but devastating childhood brain tumor. The cancer can spread through the cerebrospinal fluid and deposit elsewhere in the brain and spine. Radiation therapy to the entire brain and spine followed by additional radiation doses to the back of the brain prevent this spread and become standard treatment. However, the radiation used to treat such tumors strains the brain and damages cognitive function, especially in young patients whose brain is just beginning to develop.

Ah National survey Leading by the Washington University School of Medicine and St. Jude Children’s Research Hospital in St. Louis suggests that children with so-called “mean risk medulloblastoma” can receive a small amount of radiation “boost” to the brain at the end of 6. Masu-A one-week course of radiation therapy that maintains the same disease control as patients who irradiate a larger area. However, researchers also found that the dose of prophylactic radiation therapy given to the entire brain and spine in a 6-week regimen cannot be reduced without reducing survival. In addition, researchers have shown that patients’ cancers respond differently to treatment depending on the biology of the tumor, preparing for future clinical trials of more targeted treatment.

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

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

“Medulloblastoma is a catastrophic disease,” said Jeff M. Michalski, a prominent professor of radiation oncology at the University of Washington, the first corresponding author. “that is Malignant brain tumor It occurs in the cerebellum, the lower lower part of the brain, which is important for adjusting movement, speech, and balance. Radiation therapy for this tumor can be difficult, especially in infants with active brain development in these areas. There is a balance in effectively treating tumors without compromising children’s ability to move, think and learn. “

Children with medulloblastoma at average risk usually undergo surgery to remove as much of the tumor as possible. They also received chemotherapy Radiation therapy To prevent the tumor from spreading to the brain and other parts of the spine through the cerebrospinal fluid.

“We wanted to investigate whether these patients could safely reduce the amount of radiation they receive-saving normal parts of the brain and reducing side effects in children with this type of brain tumor-at the same time. “Maintaining effective treatment,” said Michalski, chair and director of the clinical program of the Department of Radiation Oncology. “We found that reducing the radiation dose received during the 6-week treatment process had a negative impact 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 especially help reduce the side effects of this treatment. Young patient

The researchers worked with pediatric hospitals in the United States and internationally to evaluate 464 patients treated for mean-risk medulloblastoma diagnosed between the ages of 3 and 21. Young patients aged 3 to 7 years, a key period of brain development, were randomly assigned to receive either to the head and spine areas in each of the 30 treatments given over a 6-week period. Standard dose (23.4 grey) or low dose (18 grey) radiation. All older patients received standard doses because their brain development was less susceptible to radiation. In addition, all patients were randomly assigned to receive two different sizes of radiation “boost” at the end of 6 weeks of treatment. Due to the boost, all patients received a cumulative radiation dose of 54 Gray, either in the entire area of ​​the brain, called the posterior fossa, including the cerebellum, or in a smaller area of ​​the cerebellum. brain This includes the original contour of the tumor, as well as an additional margin of up to about 2 centimeters beyond the boundaries of the original tumor.

“Patients who received a smaller boost did the same as those who received a boost for the entire posterior fossa,” said Michalski, who is treating patients at the University of Washington School of Medicine and Sightman Kids at Washington University in St. Louis. Said. “Many doctors have already adopted this small boost volume, but now there is high quality evidence that it is really safe and effective.”

In patients with low boosts, 82.5% survived for 5 years and the cancer did not worsen. Also, in patients who received a greater boost over the entire posterior fossa, 80.5% survived for 5 years and the disease did not worsen. These numbers did not differ statistically. In a subset of tumors with a mutation in a gene called SHH, patients actually showed better survival with lower boosts.

However, for younger children, low doses of radiation over 6 weeks did not result in similar survival numbers. Approximately 83% of patients who received standard doses of craniospinal radiation survived for 5 years and the cancer did not worsen. Approximately 71% of the patients who received the low dose survived for 5 years and the cancer did not worsen. The difference in survival rate was statistically significant.

“Young patients who received low doses of craniospinal radiation had a higher recurrence rate and tumor spread,” Michalski said. “In general, lowering the radiation dose in children with medulloblastoma is not safe, even if it is known that it can reduce cognitive function, but in certain subgroups of patients (mutated into a gene called WNT). (Patients with) worked well. Because of the lower doses, we are currently conducting studies only on these specific patients and safely radiation Dose 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 a more complex pattern of different genetic mutations. Researchers have discovered differences in tumor response to tumor biology-based therapies that can guide the design of future clinical trials.

Dr. Paul Northcott, Senior Author of St. Jude Children’s Research Hospital, said: “We performed whole exome sequencing and DNA methylation profiling to assign patients to the molecular subgroup. This is an important step in contextualizing this study based on the latest biology. They have shown some important differences in the way children respond to treatment otherwise. The results of this study help design next-generation clinical trials in children with myelblastoma. It plays an important role. ”

Patients with medulloblastoma should receive both postoperative chemotherapy and radiation therapy

For more information:
Michalski JM et al. Pediatric Oncology Group Phase III trial of weight loss and volume radiation therapy with chemotherapy for newly diagnosed mean-risk medulloblastoma. Journal of Clinical Oncology. June 10, 2021.

Quote: The study was a catastrophic childhood brain tumor obtained on June 10, 2021 from https: // (June 2021) 10 days) shed light on treatment options

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Study sheds light on treatment options for devastating childhood brain cancer Source link Study sheds light on treatment options for devastating childhood brain cancer

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