Study Lowers the Age Bar for Radiation in Children With Ependymoma


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Thomas E. Merchant, DO, PhD

Postoperative Radiotherapy in Young Children With Ependymoma

This is the first study to include immediate postoperative radiation therapy in children under the age of 3 years. This trial is a success and will be a benchmark for others to consider in designing future trials.

—Thomas E. Merchant, DO, PhD

The good news is that children as young as 1 year old with the aggressive brain tumor ependymoma can be treated safely and effectively with immediate postoperative radiation therapy, according to the results of a trial presented at the 2015 ASTRO Annual Meeting.1

“Ependymoma is the third most common brain tumor, and affects hundreds of children each year in the United States,” explained Thomas E. Merchant, DO, PhD, Chairman of the Department of Radiation Oncology, St. Jude Children’s Research Hospital, Memphis. “Many children who develop ependymoma are under the age of 3 years.”

“This is the first study to include children under the age of 3. Outcomes were favorable whether children were under or over the age of 3,” Dr. Merchant said. “This trial was a success and will be a benchmark for others to consider in designing future trials.”

“The previous standard was surgery and chemotherapy, but results were poor,” he added. “Children over age 3 were also treated with radiation therapy in the past, but there was room for improvement. The advent of conformal and intensity-modulated radiation therapy allowed more focused radiation to the tumor bed. St. Jude Children’s Research Hospital showed early positive outcomes including cognitive preservation. The Children’s Oncology Group designed a new study that included conformal radiation therapy and included children aged 12 months to 21 years.”

Study Details and Results

The study included 378 patients with newly diagnosed intracranial ependymoma from 115 institutions. About one-third of patients were younger than age 2; more than 200 patients were younger than age 6. The median age was 5.3 years old. Children were enrolled within 56 days of surgery.

The Children’s Oncology Group ACNS0121 trial was designed to observe patients with WHO grade II, supratentorial ependymoma after microscopically complete resection (stratum 1); administer chemotherapy with optional second surgery prior to conformal radiation therapy for patients with subtotal resection at the time of protocol enrollment (stratum 2); provide immediate postoperative conformal radiation therapy for patients after near-total resection (defined as < 5 mm residual thickness) or macroscopic gross-total resection (stratum 3); and provide immediate postoperative conformal radiation therapy for patients with WHO grade III, supratentorial, or any grade, infratentorial, ependymoma after microscopically complete resection (stratum 4).

At a median follow-up of 7 years, 5-year event-free survival was 61% for stratum 1. “Now we would not recommend observation alone for this group outside of a clinical trial,” Dr. Merchant stated.

For those in stratum 2, 5-year event-free survival was 39%. However, 39% of this group underwent a second surgery (59% of those were able to achieve gross-total resection), and 5-year event-free survival was 50% in those who had a second surgery and 27% in those who did not. “We were able to [nearly] double the event-free survival for the group that had second surgery,” he added.

Strata 3 and 4 had 5-year event-free survival rates of 67% and 70%, respectively. “This represents an excellent outcome for this very aggressive tumor,” Dr. Merchant remarked.

When analyzed according to age, outcomes were not statistically different. In children under the age of 3, 5-year event-free survival was 63%, and 5-year overall survival was 87%.

In all children aged 3 or older, 5-year event-free survival was 71%, and 5-year overall survival was 86%.

Tumor grade influenced outcome, with patients who had differentiated tumors having a more favorable outcome than those with anaplastic tumors. Five-year event-free survival was 74.6% for those with grade 2 tumors and 60.7% for those with grade 3 tumors (P = .0047).

“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. Other treatments, in addition to surgery and radiation therapy, should be investigated to further increase the rate of tumor control,” Dr. Merchant stated. ■

Disclosure: Dr. Merchant reported no potential conflicts of interest.

Reference

1. Merchant TE, Bendel AE, Sabin N, et al: A phase II trial of conformal radiation therapy for pediatric patients with local ependymoma, chemotherapy prior to second surgery for incompletely resected ependymoma and observation for completely resected, differentiated, supratentorial ependymoma. 2015 ASTRO Annual Meeting. Abstract 1. Presented October 18, 2015.

 


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Expert Point of View: Anita Mahajan, MD

This study pushes the envelope of how to use our therapies to give the most benefit to patients we otherwise wouldn’t be treating: in this case, children under the age of 3. This age group has historically been a ‘no man’s land.’ Now we see we can treat children as young as 1 year,” said Anita...


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