ASTRO 2015: Pediatric Patients With Ependymoma Have Favorable Outcomes With Immediate Postsurgical Radiation Therapy
Outcomes for pediatric patients as young as 12 months old with ependymoma who are treated with immediate postoperative radiation therapy are favorable and consistent, based upon tumor surgical resection and tumor grade, according to research presented by Merchant et al (Abstract 1) on October 18, 2015, at the American Society for Radiation Oncology (ASTRO) 57th Annual Meeting.
The Children’s Oncology Group ACNS0121 trial was a prospective study for childhood ependymoma—a rare brain and spinal cord tumor. This was the largest prospective trial for childhood ependymoma ever conducted and 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.
In addition, this study is significant in that it was the first to systematically use immediate postoperative radiation therapy in children under the age of 3 with this type of brain tumor. Many children diagnosed with ependymoma are younger than 3 years old. Prior studies did not include the use of radiation therapy in front-line management for very young children with ependymoma.
Study Details
The study was conducted from 2003 to 2007 to determine the rate of tumor control in children with ependymoma who were treated with conformal radiation therapy using a 1-cm clinical target volume margin surrounding the postoperative tumor bed. The underlying goals were to reduce the volume of radiation therapy, and to decrease the risk of side effects without affecting the rate of tumor control.
The trial included 378 patients from 115 institutions. The average patient age was 5.3 years (range, 1.01–21.01 years), and each patient had been newly diagnosed. There were 216 patients with World Health Organization (WHO) grade II tumors and 140 with WHO grade III tumors. Patients were enrolled in the study within 56 days of initial surgical resection.
Researchers categorized the patients into nonoverlapping subgroups or strata. The study was designed to observe patients with WHO grade II supratentorial ependymoma after microscopically complete (GTR1) surgical 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); administer immediate postoperative conformal radiation therapy for patients with either near-total (defined as < 5 mm residual thickness) or macroscopic gross-total (GTR2) resection (stratum 3) or with WHO grade III, supratentorial or any infratentorial ependymoma (tumors in or around the fourth ventricle) after GTR1 (stratum 4).
Stratum 2 patients were treated with pre–conformal radiation therapy chemotherapy consisting of two 3-week cycles of vincristine, carboplatin, and cyclophosphamide (cycle 1) and etoposide (cycle 2); and some of the stratum 2 patients had a second surgery prior to conformal radiation therapy. Stratum 3 and stratum 4 patients received postoperative conformal radiation therapy. Radiation was administered using a 1.0-cm clinical target volume margin. The cumulative total dose was 59.4 Gy, except for patients younger than 18 months after gross total resection.
Study Findings
Progression was observed in 5 of the 11 eligible stratum 1 patients, and the 5-year event-free survival rate for patients in stratum 1 was 61.4% + 14.4%. In stratum 2, a second surgery was performed in 25 of the 64 patients, and gross total resection was achieved in 14 patients. There was no difference in event-free survival comparing the 25 patients who underwent a second surgery to the 39 patients who did not (log-rank test: P = .0790).
The event-free survival rate for stratum 2 patients was 39.2% + 7.0%. The event-free survival rate for patients in stratum 3 was 67.3% + 4.5%; and 69.5% + 3.8% for patients in stratum 4. Among the 281 patients treated on strata 3 and 4, event-free survival was 74.6% + 3.6% for those with WHO grade II tumors and 60.7% + 4.7% for those with WHO grade III tumors, according to central pathology review (log-rank test: P = .0047).
“These results indicate that radiation therapy may be safely administered to children of all ages with ependymoma, and that high rate of tumor control may be achieved for the majority of children,” said Thomas E. Merchant, DO, PhD, the Baddia J. Rashid Endowed Chair in Radiation Oncology at St. Jude Children's Research Hospital. “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.”
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