Zosia Chustecka

October 20, 2015

SAN ANTONIO — The largest trial so far conducted in children with ependymoma, a type of brain tumor, and the first study to include very young infants, show that targeted radiotherapy given immediately after surgery is beneficial and improves survival rates compared with what has been seen historically.

Both event-free survival (EFS) and overall survival (OS) were doubled with adjuvant radiation therapy when compared with results seen in the 1990s, when surgery and chemotherapy was used, lead author Thomas Merchant, DO, PhD, chairman of the Department of Radiation Oncology at St Jude Children's Research Hospital, Memphis, Tennessee, told Medscape Medical News. Some of his patients are now 20 years out from their radiotherapy, and a number are attending college, he said.

The Children's Oncology Group ACNS0121 trial was the first cooperative group trial for ependymoma to target the postoperative tumor bed and to use three-dimensional conformal radiation therapy and intensity-modulated radiation therapy. The results show that "radiation therapy may be safely administered to children of all ages with ependymoma and a high rate of tumor control may be achieved for the majority of children," Dr Merchant concluded. He was speaking here at the American Society for Radiation Oncology (ASTRO) 57th Annual Meeting.

Often Diagnosed in Very Young Infants

Ependymomas arise from the ependymal cells that line the ventricles of the brain, and in children they are often located in the lower back part of the skull (posterior fossa). This is the third most common pediatric brain tumor and is somewhat similar to glioma, with the same aggressiveness and lethality, Dr Merchant said.

The malignancy is often diagnosed in very young children, between 3 and 5 years old, but previously radiotherapy was used only in children older than age 3 years, he explained. In the current trial, more than 100 infants under the age of 3 years were included, and more than 200 were younger than age 6 years. In total, the trial included 378 patients (at 115 institutions), with a median age of 5.3 years (range, 1.01 to 21.01 years).

Patients were newly diagnosed with ependymoma and enrolled into the study within 56 days of surgery. "Enrollment and compliance were outstanding," Dr Merchant said.

Patients were divided into three groups, depending on tumor grade and success of surgery. The median follow-up was 6 to 7 years.

The first group of patients was small (n = 11) and included patients with grade 2 tumors who had gross total resection (GTR) and were followed by observation alone. In this group, 5 of the 11 patients progressed, and the 5-year EFS was 61%.

The second group of patients (n = 64) had grade 2 or 3 tumors, underwent subtotal resection, and were given chemotherapy (vincristine, carboplatin, and cyclophosphamide for one cycle, followed by etoposide). They then underwent a second surgery if that was possible, and all received radiotherapy. The 5-year EFS was 39% for the group overall, but there was a striking difference between patients who underwent a second surgery and those who did not (5-year EFS, 50% vs 27%). Dr Merchant noted that 39% of patients were able to undergo a second surgery, and 59% of these had GTR.

The third and largest group was composed of two cohorts of patients (n = 281) who had grade 2 or 3 tumors, had undergone GTR or near-total resection, and received radiotherapy. The 5-year EFS in these two cohorts was 67% and 70%.

Dr Merchant commented that now the results of this study are out, pediatric patients with ependymomas should not be followed with observation but should receive radiotherapy.

The results also demonstrate the important of surgery, he said.

This is one of the important messages to come out of this study, said Sammer Keole, MD, assistant professor of radiation oncology at the Mayo Clinic, Phoenix, Arizona, who was approached for comment on the study. "Gross total resection is the cornerstone of treatment, as this doubles your chance of cure," he told Medscape Medical News. "The message to radiation oncologists is that if you are presented with a patient that is not completely resected, before starting radiotherapy, go back to the neurosurgeon to see if they can do a repeat surgery to remove remaining tumor," he said.

Dr Keole said that another key point of this study was that very young infants were treated with radiotherapy — which is unprecedented and demonstrates feasibility. He noted that the radiotherapy dose in the youngest infants was a little lower than in older children, but the survival rates were similar. (Five-year OS was 87.4% in infants under age 3 years and 85.8% in those age 3 years and older, while the 5-year EFS was 62.9% and 70.5%, respectively.)

The other point Dr Keole highlighted was that this study demonstrates the effectiveness of acute target delineation (by MRI) and highly conformal radiation. In this study, the radiotherapy was directed within a 1-cm margin of the tumor, whereas previously a 2-cm margin had been used. The efficacy was just as good as has been seen previously, and the advantage is that less of the normal brain tissue is affected, which would be assumed to result in fewer adverse events.

A further step forward, Dr Keole said, is the use of proton therapy, which has similar control rates but even fewer adverse events. He has used proton therapy to treat over 30 children with ependymoma, he told Medscape Medical News.

Dr Merchant commented that his team has established that highly conformal radiotherapy, given immediately after surgery, is beneficial in young patients with ependymoma. Now that radiation is established as a treatment, attention is turning to newer techniques of delivering radiotherapy, and this includes proton beam therapy. He also said that other treatments, in addition to surgery and radiotherapy, should be explored, and he mentioned that an ongoing trial is investigating the addition of chemotherapy, which is considered experimental at this stage.

"All children with ependymoma should receive expert care, and treatment teams should follow protocol guidelines similar to those used in this study, with consideration given to the importance of gross-total tumor resection and advances in radiation therapy methods," Dr Merchant said in a statement.

American Society for Radiation Oncology (ASTRO) 57th Annual Meeting. Abstract 1. Presented October 19, 2015.

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