Sequencing plays role in treating high risk pediatric brain tumors

Tests that provide molecular details on a specific tumor aren’t routinely done for pediatric brain tumors, but research suggests the extra step could change a child’s therapy.

They’re among the most ruthless opponents for pediatric oncologists: brain tumors that can’t be surgically removed or that resist standard therapies.

Doctors have limited weapons to fight them, contributing to why brain cancer is still the leading cause of cancer-related death in children.

But some institutions are re-thinking their approach.

DNA and RNA sequencing, which provide detailed molecular profiles for tumors, already play a role in personalizing therapy for patients with certain types of cancer. But the tests, which uncover a tumor’s unique combination of genetic mutations, aren’t a routine part of care and not always covered by insurance companies that don’t perceive them as critical.

But leaders in the field want to see that change.

A collaboration among several institutions, spearheaded by University of Michigan’s C.S. Mott Children’s Hospital, led to a review of four separate major studies finding evidence that molecular profiling and targeting of pediatric brain tumors could alter a child’s treatment.

Authors concluded that when it comes to children with high risk brain tumors, comprehensive sequencing should be the standard of care – everywhere. The call to action on pediatric cancer treatment was published in high profile journal Neuro-Oncology.

“It’s devastating to have to tell a family we have run out of available options for treating their child’s brain tumor,” says senior author Carl Koschmann, M.D., Mott pediatric oncologist and researcher with the Chad Carr Pediatric Brain Tumor Center at Michigan Medicine.

“Brain cancer is the leading cause of cancer death among children. We have to shift the paradigm in how we manage these cases. Younger patients with high risk or relapsed brain cancer urgently need novel effective therapies based on the unique biology of each child’s specific tumor.”

A strong foundation for sequencing

The U-M Rogel Cancer Center launched an ambitious cancer sequencing program in 2011 with a focus on adult patients whose cancer hadn’t responded to standard treatment. It was extended to pediatric patients, making Mott among the first in the country to use real-time sequencing in the care of high-risk pediatric tumors.

Genomic testing is a significant undertaking, involving taking samples of a patient’s tumor and healthy tissue and sequencing the DNA and RNA of both to compare them. This helps isolate the genetic mutations associated with the disease to help determine which mutations are driving the cancer and to match patients with treatment options that target those mutations.

At Mott, all high risk pediatric brain tumors are now routinely sequenced through the Mi-ONCOSEQ program, led by Rajen Mody, MBBS, director of pediatric oncology at Mott and Arul Chinnaiyan, M.D., Ph.D., director of the Michigan Center for Translational Pathology. Because Mi-ONCOSEQ is run as a research protocol, there’s no fee to patients.

The team has sequenced over 500 pediatric tumors since 2011 using a combination of DNA and RNA sequencing.

“Our sequencing experience suggests that glial brain tumors, along with soft tissue sarcoma and lymphoid leukemia, have the highest rate of actionable genomic alterations,” Mody says. “Hopefully these findings will lead to the development of novel, more effective therapies, including targeted biological agents and immunotherapy against high-grade pediatric brain tumors.”

A recent Mott study found that sequencing revealed a potentially actionable tumor alteration in 25 out of 40 children (63%) treated for brain cancer. Among those, 53%, or 21, resulted in an impact on treatment or change in diagnosis.

Two-thirds of patients with glial tumors (17 of 20) were also found to have a potentially actionable result, which resulted in change of therapy in 14 patients (70%).

“We have seen cases where sequencing dramatically changed our idea of what kind of tumor we thought we were looking at,” Koschmann says. “When we didn’t have a good drug or therapy for that tumor, we could get the patient into a clinical trial based on the new information we found.”

(read more at Michigan Health…)

Miklja Z et al. (2019) Molecular profiling and targeted therapy in pediatric gliomas: review and consensus recommendations. Neuro Oncol [Epub ahead of print]. [abstract]

 

Koschmann C et al. (2018) Clinically Integrated Sequencing Alters Therapy in Children and Young Adults With High-Risk Glial Brain Tumors. JCO Precision Oncology [Epub]. [abstract]

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