Background: Lymphopenia may lead to worse outcomes for glioblastoma patients. This study is a secondary analysis of the CCTG CE.6 trial evaluating the impact of chemotherapy and radiation on lymphopenia, and effects of lymphopenia on overall survival (OS).
Methods: CCTG CE.6 randomized elderly glioblastoma patients (≥ 65 years) to short-course radiation alone (RT) or short-course radiation with temozolomide (RT + TMZ). Lymphopenia (mild-moderate: grade 1-2; severe: grade 3-4) was defined per CTCAE v3.0, and measured at baseline, 1 week and 4 weeks post-RT. Preselected key factors for analysis included age, sex, ECOG, resection extent, MGMT methylation, Mini-Mental State Examination, and steroid use. Multinomial logistic regression and multivariable Cox regression models were used to identify lymphopenia-associated factors and association with survival.
Results: Five hundred and sixty-two patients were analyzed (281 RT vs 281 RT+TMZ). At baseline, both arms had similar rates of mild-moderate (21.4% vs 21.4%) and severe (3.2% vs 2.9%) lymphopenia. However, at 4 weeks post-RT, RT+TMZ was more likely to develop lymphopenia (mild-moderate: 27.9% vs 18.2%; severe: 9.3% vs 1.8%; pP < .001). Baseline lymphopenia (hazard ratio [HR] 1.3) was associated with worse OS (HR: 1.30, 95% confidence interval [CI] 1.05-1.62; P = .02), regardless of MGMT status.
Conclusions: Development of post-RT lymphopenia is associated with addition of TMZ and baseline lymphopenia and not with RT alone in patients treated with short-course radiation. However, regardless of MGMT status, only baseline lymphopenia is associated with worse OS, which may be considered as a prognostic biomarker for elderly glioblastoma patients.
Song, Andrew; Ding, Keyue; Alnahhas, Iyad; Laperriere, Normand J; Perry, James; Mason, Warren P; Winch, Chad; O'Callaghan, Chris J; Menten, Johan J; Brandes, Alba A; Phillips, Claire; Fay, Michael F; Nishikawa, Ryo; Osoba, David; Cairncross, J Gregory; Roa, Wilson; Wick, Wolfgang; and Shi, Wenyin, "Impact of lymphopenia on survival for elderly patients with glioblastoma: A secondary analysis of the CCTG CE.6 (EORTC 26062-22061, TROG03.01) randomized clinical trial" (2021). Department of Radiation Oncology Faculty Papers. Paper 163.
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