2566 - Clinical and Dosimetric Predictors of Severe Radiation-Induced Lymphopenia in Patients with Newly Diagnosed IDH-Wildtype High Grade Glioma Undergoing Adjuvant Radiotherapy
Presenter(s)
M. Berger1, C. Friedes1, L. C. Linkowski1, C. Hollawell1, H. G. Hubbeling2, R. A. Lustig1, G. Kurtz2, J. F. Dorsey1, A. Desai3, R. E. Phillips3, M. Nasrallah4, A. Nabavizadeh5, S. Brem6, J. Y. K. Lee6, D. O'Rourke6, N. Amankulor6, S. J. Bagley3, S. Mohan5, 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): Severe radiation-induced lymphopenia (sRIL) is associated with poor prognosis among patients with IDH-wildtype (IDH-WT) high grade glioma (HGG) receiving adjuvant radiotherapy (RT). We evaluated baseline patient and treatment characteristics associated with sRIL.
Materials/Methods: We identified 922 patients > 18 years old with biopsy-confirmed IDH-WT HGG at a single-institution between Jan 2014 and Dec 2024 who received RT. Complete blood counts within 30 days of RT start and 120 days of RT end were collected. Lymphopenia at nadir values were graded according to the CTCAE v5.0 where sRIL was defined as G3 or higher toxicity (<0.5 × 109 cells/L). Target and organ-at-risk dosimetry (whole brain V5-V45Gy) were abstracted. Missing laboratory and dosimetry data was imputed using multiple imputation by chained equations and predictive mean matching. A multivariable logistic regression model was used to assess clinical, treatment, and dosimetric factors associated with sRIL.
Results: A total of 922 patients were included: 60% male, 54% MGMT unmethylated, 95% received concurrent temozolomide (TMZ) with RT, 54% treated with photon therapy, 73% received conventionally fractionated RT prescribed to 60 Gy (30 fractions), and 27% received hypofractionated RT to 40.05 Gy (15 fractions). There were 278 (30%) patients who developed sRIL: 225 (24%) and 53 (6%) events of G3 and G4 sRIL, respectively. Patients with sRIL had larger target volumes and higher whole brain radiation doses, including V35Gy (p=0.002), V40Gy (p=0.004), and V45Gy (p=0.009). There was no significant difference between conventional vs hypofractionation (p=0.50), receipt of TMZ (p>0.99), or radiation modality (p=0.85) and odds of sRIL. On multivariable modeling, female sex (OR 1.83, 95%CI 1.25-2.69, p=0.002) and whole brain V35Gy (OR 1.33, 95% CI 1.14-1.56, p<0.001) were associated with higher odds of sRIL, while receipt of proton therapy (OR 0.63, 95% CI 0.39-1.00, p=0.049) and higher pretreatment lymphocyte count (OR 0.95, 95% CI 0.93-0.96) were associated with lower odds of sRIL.
Conclusion: In a multivariate model of patients with IDH-WT HGG treated with adjuvant RT, sRIL is associated with female sex and whole brain radiation dose; receipt of proton RT is associated with lower odds of sRIL. Given the negative prognostic significance of sRIL, further efforts should focus on identifying high-risk patients and mitigating modifiable risk factors.