Stereotactic Radiosurgery as First-Line Treatment for Childhood Low-Grade Brain Tumors

When Erin Murphy, MD, completed her fellowship in pediatric radiation oncology at St. Jude Children’s Research Hospital in 2011, fractionated treatment was the standard radiation approach for pediatric low-grade glioma.

It still is.

When radiation is required, children with brain tumors receive low doses five days a week for up to six weeks. Low doses allow healthy tissue bordering the tumor to recover between treatments.

“Standard fractionated treatment has the most data on safety and long-term effectiveness,” says Dr. Murphy, now Director of Pediatric Radiation Oncology at Cleveland Clinic Children’s. “It provides good results, but there can be some short- and long-term side effects. However, there has not been much of a push to challenge this radiation approach.”

Until now.

Today Dr. Murphy is an advocate for stereotactic radiosurgery (SRS), used most often for adult brain tumors.

Instead of radiation applied in low doses over 30-or-so treatments (fractions), SRS applies powerful doses in one to five fractions, precisely pinpointing the target so adjacent normal tissue isn’t affected. Multiple low-power beams, coming from various directions, combine into a high-powered dose when they intersect inside a tumor.

“SRS has been used infrequently in children — mostly for recurrent disease or small residual tumors,” says Dr. Murphy. “It’s not usually considered for first-line treatment. Indications and toxicity are not well understood, but there are so many reasons SRS could be a good tool for children.”

Benefits of SRS over other radiation therapy

Proton and photon radiation therapy, the types most commonly used on pediatric brain tumors, are certainly targeted, but still expose normal brain tissue to excess low-dose radiotherapy. Radiation oncologists plan proton and photon treatments with MRI, explains Dr. Murphy. They typically add a 1- to 2-centimeter margin around the tumor to ensure treatment of any microscopic cancer cells.

“This type of treatment is well-suited for glioblastoma and other aggressive brain cancers that tend to invade surrounding tissue,” she says. “But benign or metastatic tumors tend to push away from normal tissue. They have well-defined edges. That’s when the pinpoint precision of SRS can offer an advantage.”

With the help of sophisticated 3-D guidance and high-definition imaging, SRS sends radiation beams “tight to the target.” That means SRS can apply higher, more ablative doses of radiation more quickly, usually only requiring one to five treatments total.

Because less healthy tissue is affected, patients can have fewer side effects during and after treatment, such as headaches, fatigue, nausea, decreased appetite, hair loss and progressive neurological symptoms. There is also potential for reduced late effects, including neurocognitive impact, endocrine deficits, craniofacial growth changes, hearing loss and secondary malignancy. Prospective studies need to be done to validate these findings, notes Dr. Murphy.

“Patients have a better quality of life with SRS while still receiving effective treatment,” she says.

One catch: SRS requires immobilization of the treatment area. Head frames are standard, but masks that attach to treatment tables are a newer alternative that can be more comfortable for children.

Promising results in pilocytic astrocytoma

Because studies on SRS in children tend to be small, Dr. Murphy sees a need for larger, multicenter studies. Her most recent research was an international multicenter study on the use of SRS for pilocytic astrocytoma.

“Pilocytic astrocytoma is a grade I glioma more common in younger patients,” she says. “It doesn’t tend to invade surrounding tissues. The primary treatment is surgical resection, but depending on tumor location, resection isn’t always possible. That’s why SRS could be an ideal first-line therapy — more precise than a proton or photon approach.”

Nine medical centers from the International Gamma Knife Research Foundation provided data on 141 patients (ages 2 to 84) with pilocytic astrocytoma. All patients were treated with Gamma Knife radiosurgery, a type of SRS. For patients under age 18, rates of progression-free survival were excellent.

*Includes patients of all ages who had Gamma Knife radiosurgery as primary treatment

These results are comparable to photon radiotherapy, which has a 10-year overall survival of 96 percent.

“Physicians should consider SRS, such as Gamma Knife radiosurgery, a useful tool for treating pilocytic astrocytoma, especially in younger patients,” says Dr. Murphy.

She will present full results of the study in July at the International Symposium on Pediatric Neuro-Oncology in Denver.

More research to come

Next Dr. Murphy is pursuing a prospective study on treating recurrent and metastatic disease brain tumors with SRS or, for areas outside the brain, stereotactic body radiation therapy (SBRT).

Retrospective studies show good local control and imaging response, yet not without toxicity, such as radiation necrosis. Prospective studies are needed to help determine guidelines for use in children and to reduce toxicity.

“A good portion of kids with metastatic disease can have extended survival, so it makes sense to use a definitive approach rather than a palliative one,” she says. “We can treat them in a shorter period of time and with a better quality of life with SRS or SBRT.”