Medulloblastoma is one of the most common malignant brain tumors in children, with cases tending to surface around ages 4 or 5.

Currently, the treatment protocol is resection of as much of the tumor as can be done safely, followed by concurrent radiation therapy and chemotherapy, according to Mustafa Barbour, M.D., pediatric hematologist/oncologist at Norton Children’s Cancer Institute, affiliated with the UofL School of Medicine. Radiation is applied to the brain and spine, followed by maintenance chemotherapy.

Overall five-year survivability is about 60% to 70%, but as more patients go on to live longer lives, late mortalities from disease recurrence and malignancies are a growing concern. A 2015 study published in the Journal of Neuro-Oncology found that by age 30, about two-thirds of pediatric medulloblastoma patients had died. The most common malignancy was another brain tumor, followed by thyroid cancer.

Specialists from Norton Children’s Neuroscience Institute, affiliated with the UofL School of Medicine, and Norton Children’s Cancer Institute use a multidisciplinary approach, working together in the Brain Tumor Program and Norton Children’s Cancer Institute Neuro-oncology Clinic to diagnose, treat, and provide follow-up care for pediatric patients with malignant brain tumors.

Medulloblastoma clinical risk groups

• Standard risk – Older than 3 years with no evidence of spread and complete tumor resection. Five-year survival rate: 80%
• High risk – Older than 3 years with evidence the tumor has spread either because of metastatic disease, incomplete resection or a combination. Five-year survival rate: 50% to 65%.
• Infants and toddlers – Younger than age 3. Treatment tries to avoid radiation therapy. Five-year survival rate: about 50%.

Medulloblastoma subgroups

“We are currently not necessarily at standard of care yet using these subgroups to risk-stratify, but we are using them more,” Dr. Barbour, co-director of the Neuro-oncology Clinic, said during a recent Pediatric Grand Rounds. “We look at stage of disease, metastatic versus nonmetastatic and degree of resection. We also look at the molecular subgroup. We factor in the molecular subgroup into the risk stratification and the type of treatment that a given child will receive.”

• Wingless (WNT) – Occurs in about 10% of medulloblastoma patients. Older children and adolescents (median age 10 years) typically are affected, with an even split between genders. About 5% to 10% are metastatic at diagnosis, and the survival rate is greater than 90%. Key alterations: CTNNB1, DDX3X, SMARCA4, TP53.

“The best outcome we’ve seen in WNT. Their survival is more than 90%, and they are rarely metastatic,” Dr. Barbour said.

• Sonic Hedgehog activated (SHH) – Occurrence is about 30% of medulloblastoma patients. Age ranges run from older children and adults, with a male-to-female ratio of 1.5 to 1. About 15% to 20% are metastatic at diagnosis, and the survival rate is about 75%. Key alterations: PTCH1, SMO, SUFU, GLI2 and TP53.

“These are a slightly more aggressive tumor, but the outcome can be favorable. The key thing in these patients is the TP53 status. If the TP53 is mutated, their outcome is very poor. If the TP53 is wild type, the outcome is closer to a 75% or 80% five-year survival rate,” Dr. Barbour said.

• Group 3 – This group accounts for a quarter of medulloblastoma patients. Infants and young children typically are affected, and the male-to-female ratio is 2 to 1. At diagnosis, 40% to 45% are metastatic. The survival rate is 50%. Key alterations: MYC, OTX2, SMARCA4.

“Group 3 is the most aggressive. The five-year survival rate is only 50%, and they are commonly metastatic at presentation,” Dr. Barbour said.

• Group 4 – About 35% of medulloblastoma patients are in this group, which takes in a broad age range of children. The median age is 9 years. Males outnumber females 3 to 1, and 35% to 40% are metastatic at the time of diagnosis. Survival rate is 75%. Key alterations: KDM6A, MYCN

“Group 4 is the most common group, with a significant percentage of children presenting with metastatic disease. But they are more responsive to treatment compared with Group 3, and their outcome is better,” Dr. Barbour said.