Hemoglobin Levels and Red Blood Cells Distribution Width Highlights Glioblastoma Patients Subgroup With Improved Median Overall Survival

Abstract

Glioblastoma multiforme (GBM) is known for its dismal prognosis, though its dependence on patients' readily available RBCs parameters is not fully established. In this work, 170 GBM patients, diagnosed and treated in Soroka University Medical Center (SUMC) over the last 12 years were retrospectively inspected for their survival dependency on pre-operative RBCs parameters. Besides KPS and tumor resection supplemented by oncological treatment, age under 70 (HR = 0.4, 95% CI 0.24-0.65, p = 0.00073), low hemoglobin level (HR = 1.79, 95% CI 1.06-2.99, p = 0.031), and Red Cell Distribution Width (RDW) < 14% (HR = 0.57, 95% CI 0.37-0.88, p = 0.018) were found to be prognostic of patients' overall survival in multivariate analysis, accounting for a false discovery rate of < 5% due to multiple hypothesis testing. According to these results, a stratification tree was made, from which a favorable route highlighted a subgroup of nearly 30% of the cohorts' patients whose median overall survival was 21.1 months (95% CI 16.2-27.2)-higher than the established chemo-radiation standard first-line treatment regimen overall median survival average of about 15 months. The beneficial or detrimental effect of RBCs parameters on GBM prognosis and its possible causes is discussed.

Keywords: RDW (red cell distribution width); glioblastoma multiforme (GBM); hemoglobin; overall survival; prognostic factors.

Figure 1

Primary stratification tree which presents cohorts' prognosis. Each colored box represents a specified subgroup with a number of patients (N), median overall survival in months (S), and 95% confidence interval (in brackets). The entire cohort was first divided into treated vs. partial/non-treated groups, which demonstrates a 4-fold increase in overall survival of the treated group compared to the partial/non-treated group. Notably, age under 70 is an independent favorable prognostic factor in both groups. Further stratification of treated patients whose age is under 70 revealed that normal hemoglobin level in those patients enhanced their overall survival to 18 months (95% CI 13–23.3) and RDW categorization to RDW < 14% highlighted a subgroup of 52 patients that survived for 21 months (95% CI 16.2–27.2). Hence, this cohort favorable prognosis group is characterized by the following four parameters: patients that underwent tumor resection supplemented with oncological treatment, age under 70, normal hemoglobin level, and RDW < 14%. Abbreviations: Hb, hemoglobin; RDW, red blood cell distribution width.

Figure 2

Kaplan-Meir overall survival curve of the treated group. Patients whose age was over 70 and patients whose age was under 70 but with low hemoglobin level demonstrated the worst prognosis of the entire treated cohort. According to the data analysis, these patients did not survive past the first year following GBM diagnosis. Patients whose age was under 70 with a normal hemoglobin level but with RDW > 14% showed a slight trend toward improved overall survival, though not statistically significant. Patients whose age was under 70, with normal hemoglobin level and RDW < 14%, exhibited the best cohort overall survival, with long-term survival patterns demonstrated. Hb, hemoglobin; RDW, red blood cell distribution width.