Trial identifies a medulloblastoma subset that requires less aggressive therapy

May 17, 2018, St. Jude Children's Research Hospital
St. Jude Children's Research Hospital researchers have identified a subtype of the brain tumor medulloblastoma that is associated with improved survival of infants treated with less aggressive, risk-adapted therapy Credit: Peter Barta / St. Jude Children's Research Hospital

The youngest patients with the brain tumor medulloblastoma are among the most challenging because their rapidly developing brains limit treatment options. Now a team of researchers led by St. Jude Children's Research Hospital have discovered a subtype that responds to a therapy that is less likely to cause long-term cognitive problems.

The report appears today in the journal Lancet Oncology and sets the stage for screening to identify those with the subtype.

"This study has important ramifications for treatment of young children with medulloblastoma, a group whose long-term survival rates are stalled at about 50 percent and progression-free survival remains even lower," said first and corresponding author Giles Robinson, M.D., an assistant member of the St. Jude Department of Oncology. "Combination with radiation and chemotherapy has increased survival rates of older children and adolescents, but radiation toxicity has limited its use in younger patients, particularly those less than 3 years old."Now we have identified a subtype of medulloblastoma that accounts for about 25 percent of infant medulloblastoma and that can be treated successfully with reduced-intensity chemotherapy," Robinson said.

Seventy-five percent of the 21 patients in the newly identified subtype were alive five years after their diagnosis, and their disease had not worsened (progressed). The rates were even better, 91 percent, for the low-risk patients whose had been completely surgically removed and had not spread.

Medulloblastoma is the most common malignant childhood brain tumor and one of the leading causes of non-accidental death in U.S. children and adolescents. The tumor includes four main molecular subgroups—WNT, sonic hedgehog (SHH), group 3, group 4—each with different clinical and biological characteristics as well as treatment outcomes.

The tumor is diagnosed in about 400 U.S. residents annually, mostly in individuals under 16 years old. With current treatment, which includes surgery, whole-brain and spine irradiation, and chemotherapy, about 70 percent of patients are alive five years after diagnosis. However, brain and spine radiation therapy can be particularly damaging to the developing brain. But long-term survival remains about 50 percent or less when radiation therapy is omitted, reduced or delayed.

The new medulloblastoma subtype is infant SHH-II. It was discovered in a subset of patients with SHH medulloblastoma. The patients were enrolled in a St. Jude-led, 10-year, multi-center phase II clinical trial of risk-adapted therapy for treatment of medulloblastoma patients age 5 and younger. Of the 81 patients enrolled, 65, or 80 percent, were younger than age 3 and were classified as infants.

Patients were assigned to low, intermediate or high-risk therapy based on clinical factors and tumor histology (how tumors looked under the microscope). All patients were treated with chemotherapy. Radiation therapy was limited to intermediate-risk patients who received focal radiation of the tumor bed, not irradiation of the whole brain and spine. No patients received myeloablative regimens that required stem cell transplantation or intrathecal chemotherapy (chemotherapy injected into cerebrospinal fluid).

Researchers used next-generation genomic sequencing and DNA methylation patterns to analyze treatment response based on the patients' molecular subgroups. DNA methylation refers to chemical compounds called methyl groups that attach to DNA and serve as on-off switches to regulate gene expression.

Overall, researchers reported that risk-adapted therapy did not improve progression-free survival. However, analysis of the DNA methylation data revealed distinct subgroups and subtypes of medulloblastoma that were associated with distinct outcomes. First, the researchers noticed that patients with SHH medulloblastoma had higher rates of progression-free survival compared to patients with group 3 or group 4 medulloblastoma. Even more revealing was that the 42 SHH patients evenly divided between subtypes that researchers called iSHH-I and iSHH-II.

Patients with the iSHH-II subtype were less likely to have their disease worsen or return after therapy. The patients were also more likely to survive at least five years when compared to patients with iSHH-I or with group 3 or 4 medulloblastoma.

"While we've understood for some time that medulloblastoma is not a single disease, the results of this molecular analysis are a humbling reminder of differences within medulloblastoma subgroups that influence treatment response," Robinson said. "That is important to keep in mind as the next generation of molecularly driven therapies are designed."

Explore further: Genetic counseling and testing proposed for patients with the brain tumor medulloblastoma

More information: Giles W Robinson et al, Risk-adapted therapy for young children with medulloblastoma (SJYC07): therapeutic and molecular outcomes from a multicentre, phase 2 trial, The Lancet Oncology (2018). DOI: 10.1016/S1470-2045(18)30204-3

Related Stories

Genetic counseling and testing proposed for patients with the brain tumor medulloblastoma

May 9, 2018
Researchers have identified six genes that predispose carriers to develop the brain tumor medulloblastoma and have used the discovery to craft genetic counseling and screening guidelines. The study appears today in the journal ...

Medulloblastoma patients should receive both chemotherapy and radiation post-surgery

September 26, 2016
In a recent study, a Yale Cancer Center team revealed that the addition of chemotherapy to postoperative treatment for adults with medulloblastoma improves survival. The benefit of chemotherapy, in addition to craniospinal ...

Targeted therapy shows effectiveness against a subtype of the brain tumor medulloblastoma

July 29, 2015
A targeted therapy already used to treat advanced skin cancer is also effective against the most common subtype of the brain tumor medulloblastoma in adults and should be considered for treatment of newly diagnosed patients, ...

New pathway identified as a target for precision medicine against a common brain tumor

November 2, 2017
St. Jude Children's Research Hospital scientists have discovered a promising target for precision medicines to block a mechanism that drives several cancers, including about 30 percent of cases of the brain tumor called medulloblastoma. ...

Study helps explain launch switch for most common malignant pediatric brain tumor

March 29, 2018
A delicate balance during brain development could have profound implications for understanding and treating medulloblastoma, the most common malignant brain tumor affecting children.

Adult cancer drugs show promise against an aggressive childhood brain tumor

March 27, 2014
The quest to improve survival of children with a high-risk brain tumor has led St. Jude Children's Research Hospital investigators to two drugs already used to treat adults with breast, pancreatic, lung and other cancers. ...

Recommended for you

MR spectroscopy imaging reveals effects of targeted treatment of mutant IDH1 gliomas

May 18, 2018
Using a novel imaging method, a Massachusetts General Hospital (MGH) research team is investigating the mechanisms behind a potential targeted treatment for a subtype of the deadly brains tumors called gliomas. In their report ...

Particle shows promise to prevent the spread of triple-negative breast cancer

May 18, 2018
USC researchers have pinpointed a remedy to prevent the spread of triple-negative breast cancer. Metastatic breast cancer is a leading cause of death for women. The findings appear today in Nature Communications.

Dilemma for cancer patients as life-saving meds are tied to vision loss

May 18, 2018
(HealthDay)—A newer type of cancer treatment may offer the chance of longer survival, but the drugs could also trigger new side effects, such as vision problems.

Polygenic scores to classify cancer risk

May 18, 2018
Polygenic risk scores could be useful to stratify the risk of several cancers among patients in medical centers, allowing for the potential discovery of new associations between genes, disease and secondary effects, according ...

A way to prevent pancreatic cancer from spreading post-surgery?

May 17, 2018
Scientists at Cold Spring Harbor Laboratory (CSHL) have solved a mystery about how pancreatic cancer spreads following surgery in patients whose tumor is successfully removed. After surgery, patients' typically experience ...

Erectile dysfunction drugs and flu vaccine may work together to help immune system fight cancer after surgery

May 17, 2018
A new study suggests that a common treatment for erectile dysfunction combined with the flu vaccine may be able to help the immune system mop up cancer cells left behind after surgery. The study, published in OncoImmunology, ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.