TY - JOUR
T1 - Evaluating hematologic parameters in newly diagnosed and recurrent glioblastoma
T2 - Prognostic utility and clinical trial implications of myelosuppression
AU - Deng, Davy
AU - Hammoudeh, Lubna
AU - Youssef, Gilbert
AU - Chen, Yu Hui
AU - Shin, Kee Young
AU - Lim-Fat, Mary Jane
AU - McFaline-Figueroa, Jose Ricardo
AU - Chukwueke, Ugonma N.
AU - Tanguturi, Shyam
AU - Reardon, David A.
AU - Lee, Eudocia Q.
AU - Nayak, Lakshmi
AU - Bi, Wenya Linda
AU - Arnaout, Omar
AU - Ligon, Keith L.
AU - Wen, Patrick Y.
AU - Rahman, Rifaquat
N1 - Publisher Copyright:
© 2023 The Author(s). Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.
PY - 2023/1/1
Y1 - 2023/1/1
N2 - 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.
AB - 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.
KW - Glioblastoma
KW - blood-based biomarkers
KW - clinical trial design
KW - lymphopenia
KW - neutrophil-To-lymphocyte ratio (NLR)
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U2 - 10.1093/noajnl/vdad083
DO - 10.1093/noajnl/vdad083
M3 - Article
AN - SCOPUS:85168573734
SN - 2632-2498
VL - 5
JO - Neuro-Oncology Advances
JF - Neuro-Oncology Advances
IS - 1
M1 - vdad083
ER -