Evaluating hematologic parameters in newly diagnosed and recurrent glioblastoma: Prognostic utility and clinical trial implications of myelosuppression

Davy Deng; Lubna Hammoudeh; Gilbert Youssef; Yu-Hui Chen; Kee-Young Shin; Mary Jane Lim-Fat; Jose Ricardo McFaline-Figueroa; Ugonma N Chukwueke; Shyam Tanguturi; David A Reardon; Eudocia Q Lee; Lakshmi Nayak; Wenya Linda Bi; Omar Arnaout; Keith L Ligon; Patrick Y Wen; Rifaquat Rahman

doi:10.1093/noajnl/vdad083

Evaluating hematologic parameters in newly diagnosed and recurrent glioblastoma: Prognostic utility and clinical trial implications of myelosuppression

Neurooncol Adv. 2023 Jul 8;5(1):vdad083. doi: 10.1093/noajnl/vdad083. eCollection 2023 Jan-Dec.

Authors

Davy Deng¹, Lubna Hammoudeh^{2

3}, Gilbert Youssef⁴, Yu-Hui Chen^{2

5}, Kee-Young Shin², Mary Jane Lim-Fat⁶, Jose Ricardo McFaline-Figueroa⁴, Ugonma N Chukwueke⁴, Shyam Tanguturi², David A Reardon⁴, Eudocia Q Lee⁴, Lakshmi Nayak⁴, Wenya Linda Bi⁷, Omar Arnaout⁷, Keith L Ligon⁸, Patrick Y Wen⁴, Rifaquat Rahman²

Affiliations

¹ Massachusetts Institute of Technology, Harvard University, Boston, Massachusetts, USA.
² Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts, USA.
³ Department of Radiation Medicine, Oregon Health and Science University, Portland, Oregon, USA.
⁴ Center of Neuro-Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts¸ USA.
⁵ Department of Data Sciences, Dana-Farber Cancer Institute, Boston, Massachusetts¸USA.
⁶ Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
⁷ Department of Neurosurgery, Brigham and Women's Hospital, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts, USA.
⁸ Department of Pathology, Brigham and Women's Hospital, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts, USA.

Abstract

Background: Glioblastoma (GBM) patients are treated with radiation therapy, chemotherapy, and corticosteroids, which can cause myelosuppression. To understand the relative prognostic utility of blood-based biomarkers in GBM and its implications for clinical trial design, we examined the incidence, predictors, and prognostic value of lymphopenia, neutrophil-to-lymphocyte ratio (NLR), and platelet count during chemoradiation (CRT) and recurrence.

Methods: This cohort study included 764 newly diagnosed glioblastoma patients treated from 2005 to 2019 with blood counts prior to surgery, within 6 weeks of CRT, and at first recurrence available for automatic extraction from the medical record. Logistic regression was used to evaluate exposures and Kaplan-Meier was used to evaluate outcomes.

Results: Among the cohort, median age was 60.3 years; 87% had Karnofsky performance status ≥ 70, 37.5% had gross total resection, and 90% received temozolomide (TMZ). During CRT, 37.8% (248/656) of patients developed grade 3 or higher lymphopenia. On multivariable analysis (MVA), high NLR during CRT remained an independent predictor for inferior survival (Adjusted Hazard Ratio [AHR] = 1.57, 95% CI = 1.14-2.15) and shorter progression-free survival (AHR = 1.42, 95% CI = 1.05-1.90). Steroid use was associated with lymphopenia (OR = 2.66,1.20-6.00) and high NLR (OR = 3.54,2.08-6.11). Female sex was associated with lymphopenia (OR = 2.33,1.03-5.33). At first recurrence, 28% of patients exhibited grade 3 or higher lymphopenia. High NLR at recurrence was associated with worse subsequent survival on MVA (AHR = 1.69, 95% CI = 1.25-2.27).

Conclusions: High NLR is associated with worse outcomes in newly diagnosed and recurrent glioblastoma. Appropriate eligibility criteria and accounting and reporting of blood-based biomarkers are important in the design and interpretation of newly diagnosed and recurrent glioblastoma trials.

Keywords: Glioblastoma; blood-based biomarkers; clinical trial design; lymphopenia; neutrophil-to-lymphocyte ratio (NLR).