Treatment with conformal radiation therapy immediately following surgery in children with ependymoma may greatly improve survival. The findings were published by Merchant et al in the Journal of Clinical Oncology.
“Historically, children under the age of 3 with ependymoma have a worse prognosis than older children,” said Thomas E. Merchant, DO, PhD, principal investigator of the study and Chair of the St. Jude Children’s Research Hospital Department of Radiation Oncology. “However, results from this clinical trial show that even in young children, survival can be improved when radiation is administered immediately after surgery.”
The phase II clinical trial was sponsored by Children’s Oncology Group. This was the first cooperative group study to give immediate postoperative radiation to children under age 3 with ependymoma. The clinical trial was open at more than 100 locations and enrolled 356 patients.
The study included both patients with infratentorial ependymomas, as well as patients with rarer supratentorial ependymomas. These ependymomas occured either above or below the cerebellar tentorium, an extension of the dura mater that separates the cerebellum from the inferior portion of the occipital lobes. Patients with classic supratentorial ependymoma were observed after gross total resection. Those undergoing subtotal resection received chemotherapy, second surgery, and conformal radiation therapy. The remaining patients received immediate postoperative conformal radiation therapy after near-total resection or gross total resection.
The cumulative total radiation dose was 59.4 Gray (Gy), except in patients who either underwent gross total resection or were younger than 18 months—they received 54 Gy. Participants ranged in age from 1 year to 21 years old and were observed for 5 years after treatment to evaluate long-term effects of care.
The primary goal of the clinical trial was to evaluate the effectiveness of postoperative radiation for children with ependymoma. However, the researchers also conducted molecular analyses to study the underlying biology of this disease and determine the significance of certain biologic markers regarding patient outcomes.
The 5-year event-free survival rates were 61.4%, 37.2%, and 68.5% for observation, subtotal resection, and near-total resection/gross total resection groups given immediate postoperative conformal radiotherapy, respectively.
In patients with supratentorial ependymomas, a chromosomal abnormality called a RELA fusion was previously linked to high-risk disease. However, this clinical trial showed that when radiation is given immediately after surgery, RELA fusion status is not a significant indicator of outcome.
The researchers also investigated the molecular biology of infratentorial ependymomas. For this subtype, patients are classified as posterior fossa group A (PFA) or posterior fossa group B (PFB). These classifications reflect how genes are regulated within the tumor. It was previously held that the PFA subtype, which occurs in very young children, predicted worse outcomes than the PFB subtype. Like the RELA fusion findings, the results of this study suggest that regardless of PFA or PFB classification, patients can do equally well with surgery followed immediately by radiation.
Molecular analyses revealed that gaining chromosome 1q increases the risk of tumor progression, solidifying the gain of 1q as a poor prognostic biomarker for ependymoma.
“This study is a huge leap forward, as it is the first study to incorporate biology into the outcome of children with ependymoma,” said senior study author Vijay Ramaswamy, MD, PhD, staff neuro-oncologist at The Hospital for Sick Children and Assistant Professor at the University of Toronto. “These are important findings, because [if] new clinical trials [are designed] using molecular features to stratify patients according to outcome, you have to understand what those biomarkers mean in the context of currently used therapies.”
“These data show that surgery and radiation therapy are the backbone of ependymoma treatment,” Dr. Merchant said. “Now we can move on to testing new agents and finding other treatments in addition to radiation therapy to further improve outcomes for these children.”
Disclosure: The research was funded in part by the Children’s Oncology Group; the Ontario Institute for Cancer Research through the Government of Ontario, Ministry of Research, Innovation, and Science; and ALSAC. The study authors' full disclosures can be found at jco.ascopubs.org.
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