ID #294 Patterns of Failure after Treatment for Pediatric Ependymoma: Findings from Children’s Oncology Group (COG) Clinical Trial ACNS0831
Thomas Merchant, Andrew Chang, Erika Krzeminski, Shelly Lensing, Kathyrn Karolczuk, Janaki Moni, Thomas Fitzgerald, David Ellison, Jeffery Bennett, Arzu Onar-Thomas, Sarah Leary, Maryam Fouladi, Amy SmithAbstract
Purpose
To compare patterns of failure for pediatric ependymoma patients treated with maintenance chemotherapy after radiation therapy (RT) versus RT alone. This study also examined outcomes by adherence to RT guidelines, RT modality (proton vs. photon), and prescribed dose (54Gy vs. 59.4Gy).
Methods
In the Children’s Oncology Group ACNS0831 clinical trial, 179 patients with molecularly defined posterior fossa (PF) tumors received RT after gross/near-total resection (GTR/NTR) including 72 patients who received maintenance chemotherapy. The protocol prescribed 59.4 Gy to the post-operative tumor bed with a 0.5 cm margin; for patients under 18 months, 54 Gy was permitted. Volume reductions after 54 Gy minimized exposure to critical structures. Minor deviations occurred when doses were between 54 and 59.4 Gy. Central review assessed dose, uniformity, target coverage, and tissue constraints. Tumor progression imaging was matched with dosimetry to classify failures as local or distant, and statistical analyses correlated outcomes with clinical, molecular, and treatment variables.
Results
Performance evaluation was not associated with progression-free survival, RT modality, or the number of patients treated by facility. In patients with PF tumors who underwent GTR/NTR, distant progression correlated with higher tumor grade (P = 0.01), 1q gain (P < 0.001), and 6q alteration (P < 0.001). Local progression was linked to higher tumor grade (P = 0.030) and lower radiation dose (P = 0.008), but not to 1q gain or 6q alteration. After adjusting for high-risk features, distant progression rates did not differ significantly for patients treated with RT alone and those who also received maintenance chemotherapy (P = 0.072). Patients receiving 59.4 Gy had significantly better local control compared to those treated with 54 Gy (HR = 0.376; 95% CI: 0.166–0.85; P = 0.018), after adjusting for high-risk features.
Conclusions
Reduced margin RT is feasible in a cooperative group trial. Chemotherapy after radiation does not lower distant tumor progression, while higher radiation dose increases local control.