2592 - A Real-World Analysis of Clinical Prognostic Factors Influencing Survival in Patients with High-Grade Glioma (HGG) Receiving Radiotherapy (RT)
Presenter(s)
C. Friedes1, M. Berger1, L. C. Linkowski1, C. Hollawell1, G. Kurtz2, R. A. Lustig1, J. F. Dorsey1, A. Desai3, M. Nasrallah4, R. E. Phillips3, A. Nabavizadeh5, S. Brem6, J. Y. K. Lee6, D. O'Rourke6, N. Amankulor6, S. J. Bagley3, S. Mohan5, H. G. Hubbeling2, M. Alonso-Basanta1, and E. S. Lebow1; 1Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, 2Department of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA, 3Division of Neuro-Oncology, University of Pennsylvania, Philadelphia, PA, 4Division of Neuropathology, University of Pennsylvania, Philadelphia, PA, 5Department of Neuroradiology, University of Pennsylvania, Philadelphia, PA, 6Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA
Purpose/Objective(s): Prognostic factors for HGG are often derived from secondary analyses of clinical trials. We evaluated real-world clinicopathologic and treatment-related factors associated with survival among patients with HGG treated with adjuvant RT.
Materials/Methods: We identified patients >18 years old with biopsy-confirmed, IDH-wild type HGG at a single-institution between Jan 2014-Dec 2024. All patients underwent maximal safe resection (or biopsy if not feasible) followed by RT with protons or photons (60Gy/30fx or 40.05Gy/15fx). Subtotal (STR) or gross total resection (GTR) status was determined by post-operative MRI. Temozolomide (TMZ) was administered concurrently and adjuvantly at discretion of the treating oncologist. Complete blood counts within 120 days of RT were collected and severe lymphopenia (SL) at time of nadir was defined as G3+ toxicity (<0.5 × 109 cells/L) per CTCAE v5.0. Missing data was imputed using multiple imputation by chained equations. The primary objective was to determine clinicopathologic, treatment, and tumor-related variables associated with overall survival (OS). OS was calculated with the Kaplan-Meier method, and group comparisons made with the log-rank test. A multivariable Cox regression model assessed clinicopathologic and treatment factors associated with OS. Least absolute shrinkage and selection operator regression was used for multivariable covariate selection and models were stratified for covariates that violated proportional hazards.
Results: A total of 851 patients were included: 518 (61%) male, 461 (54%) MGMT unmethylated, 490 (58%) had STR, 616 (72%) received conventional RT, 804 (94%) received concurrent TMZ, and 478 (56%) treated with photons. There were 632 deaths with a median OS of 14.5 months (95%CI 13.5-15.5). Worse OS was observed in patients with SL (median 11.2 vs 15.9 months, p<0.001), biopsy or STR vs GTR (median 6.1 vs 12.4 vs 19.0 months, p<0.001), receipt of photon therapy (13.7 vs 15.2 months, p=0.002), and MGMT unmethylated tumors (median 12.6 vs 19.1 months, p<0.001). On multivariable modeling, OS was associated with increasing age (HR 1.03, 95%CI 1.02-1.04, p<0.001), MGMT unmethylated tumors (HR 1.69, 95%CI 1.31-2.02, p<0.001), STR (HR 1.43, 95%CI 1.20-1.71, p<0.001), proton therapy (HR 0.78, 95%CI 0.66-0.92, p=0.003), adjuvant TMZ (HR 0.53, 95%CI 0.44-0.63, p<0.001), post-RT neutrophil count (HR 1.02, 95%CI 1.01-1.03, p<0.001), and RT-induced SL (HR 1.32, 95%CI 1.11-1.58, p=0.002). In a stratified multivariable model, proton therapy was not associated with OS (HR 0.83, 95%CI 0.65-1.06, p=0.14).
Conclusion: In a real-world analysis of patients with HGG treated with adjuvant RT, survival is associated with age, methylation status, extent of resection, TMZ, and RT-induced SL. Further study is required to identify patients who may derive survival or toxicity reduction benefit from proton therapy.