Risk stratification in pediatric low-grade glioma and glioneuronal tumor treated with radiation therapy: An integrated clinicopathologic and molecular analysis

Acharya, Sahaja; Liu, Jo-Fen; Tatevossian, Ruth G.; Chiang, Jason; Qaddoumi, Ibrahim; Gajjar, Amar; Walker, David; Harreld, Julie; Merchant, Thomas E.; Ellison, David W.

Abstract

Background
Management of unresectable pediatric low-grade glioma and glioneuronal tumor (LGG/LGGNT) is controversial. There are no validated prognostic features to guide use of radiation therapy (RT). Our study aimed to identify negative prognostic features in patients treated with RT using clinicopathologic and molecular data and validate these findings in an external dataset.

Methods
Children with non-metastatic, biopsy-proven unresectable LGG/LGGNT treated with RT at a single institution between 1997 and 2017 were identified. Recursive partitioning analysis (RPA) was used to stratify patients into low- and high-risk prognostic groups based on overall survival (OS). CNS9702 data were used for validation.

Results
One hundred and fifty patients met inclusion criteria. Median follow-up was 11.4 years. RPA yielded low- and high-risk groups with 10-year OS of 95.6% versus 76.4% (95% CI: 88.7%–98.4% vs 59.3%–87.1%, P = 0.003), respectively. These risk groups were validated using CNS9702 dataset (n = 48) (4-year OS: low-risk vs high-risk: 100% vs 64%, P < 0.001). High-risk tumors included diffuse astrocytoma or location within thalamus/midbrain. Low-risk tumors included pilocytic astrocytoma/ganglioglioma located outside of the thalamus/midbrain. In the subgroup with known BRAF status (n = 49), risk stratification remained prognostic independently of BRAF alteration (V600E or fusion). Within the high-risk group, delayed RT, defined as RT after at least one line of chemotherapy, was associated with a further decrement in overall survival (P = 0.021).

Conclusion
A high-risk subgroup of patients, defined by diffuse astrocytoma histology or midbrain/thalamus tumor location, have suboptimal long-term survival and might benefit from timely use of RT. These results require validation.

Citation

Acharya, S., Liu, J.-F., Tatevossian, R. G., Chiang, J., Qaddoumi, I., Gajjar, A., …Ellison, D. W. (2020). Risk stratification in pediatric low-grade glioma and glioneuronal tumor treated with radiation therapy: An integrated clinicopathologic and molecular analysis. Neuro-Oncology, 22(8), 1203–1213. https://doi.org/10.1093/neuonc/noaa031

• Journal Article Type: Article
• Acceptance Date: Feb 3, 2020
• Online Publication Date: Feb 13, 2020
• Publication Date: 2020-08
• Deposit Date: Mar 10, 2020
• Publicly Available Date: Feb 14, 2021
• Journal: Neuro-Oncology
• Print ISSN: 1522-8517
• Electronic ISSN: 1523-5866
• Publisher: Oxford University Press
• Peer Reviewed: Peer Reviewed
• Volume: 22
• Issue: 8
• Pages: 1203–1213
• DOI: https://doi.org/10.1093/neuonc/noaa031
• Keywords: Cancer Research; Oncology; Clinical Neurology
• Public URL: https://nottingham-repository.worktribe.com/output/4121103
• Publisher URL: https://academic.oup.com/neuro-oncology/advance-article/doi/10.1093/neuonc/noaa031/5734990