2089 - Treatment Related Lymphopenia and Associated Outcomes in a Large Cohort Treated with Radiation/TMZ Incorporating Brain Dosimetric Analysis
Presenter(s)
A. Ho1, K. E. Fink2, P. Yadav1, and S. Sachdev1; 1Department of Radiation Oncology, Northwestern University, Chicago, IL, 2Northwestern University Feinberg School of Medicine, Chicago, IL
Purpose/Objective(s): Standard-of-care for glioblastoma (GBM) includes maximal resection followed by radiotherapy (RT) with temozolomide (TMZ). Lymphopenia during chemoradiation is associated with poorer outcomes, and brain RT may contribute via low-dose exposure. We evaluated the relationship between absolute lymphocyte count (ALC) kinetics, survival, and brain dose–volume metrics in IDH-wild type (IDH-WT) GBM treated per the Stupp protocol.
Materials/Methods: In a retrospective cohort at a high-volume academic center, adults with IDH-WT GBM receiving conventionally fractionated RT with concurrent TMZ were included; exclusions: hypofractionated RT, concurrent investigational agents, IDH-mutant glioma, or no concurrent TMZ. Hematologic data included weekly ALCs during chemoradiation and up to three months after. RT metrics (when fully available) included prescribed dose, fractionation, and whole-brain V5–V75 Gy (5-Gy increments).
Results: Among 347 patients (median age 60; 139 [40%] MGMT+), median RT dose was 60 Gy (range 54–61.2). Median DFS was 11.7 months (MGMT+ 20.9 vs MGMT- 9.7; p<0.001). Median OS was 20 months (MGMT+ 34 vs MGMT- 16; p<0.001). Gross-total resection (GTR) improved OS (24 vs 17 months; p<0.001). Median baseline ALC was 1.5; median nadir 0.6, reached at median 6.3 weeks. After adjustment of major prognostic factors (MGMT status, gross total resection, age), nadir ALC <0.6 independently predicted worse DFS (10.9m vs 14.3m, p=0.049) and OS (23m vs 18m, p=0.02) In a subset with fully available dosimetric data (n=99), while accounting for baseline ALC, greater low-dose brain exposure correlated with severe lymphopenia (ALC nadir): V5Gy% (p=0.02), V10Gy% (p=0.005), and V15Gy% (p=0.02); higher-dose metrics were not significant.
Conclusion: In IDH-WT GBM treated with standard RT/TMZ, treatment-related lymphopenia is independently associated with inferior DFS and OS beyond known prognostic factors (MGMT status, age, and extent of resection). Low-dose brain exposure (V5–V15 Gy) correlates with severe lymphopenia, supporting RT planning strategies that minimize low-dose spread when feasible. Prospective validation and development of low-dose constraints are warranted.