Pre-operative mean platelet volume is associated with overall survival in patients with IDH-wildtype glioblastoma undergoing maximal safe resection

Glioblastoma (GBM) is the most common, fast-growing, and aggressive malignant primary CNS tumor, with a survival time of ~15 months despite the use of surgery and adjuvant treatments. In recent years, there has been a growing interest in exploring the potential contribution of hemostasis and platelet activation in GBM biology. The present study assessed the association between the pre-operative coagulation profile [as indicated by prothrombin time (PT) ratio and activated partial thromboplastin time (aPTT) ratio], overall platelets (PLT) count and the mean platelet volume (MPV) with tumoral characteristics and overall survival in patients with isocitrate dehydrogenase-wildtype (IDH-wt) GBM. A total of 167 adult patients undergoing maximal safe resection of newly diagnosed World Health Organization grade 4 IDH-wt glioblastoma were included. The variables of interest (MPV, PT ratio, and aPTT ratio) were dichotomized at the median, while the overall PLT count was split using the central distribution (10th to 90th percentile). Correlation analyses of markers with tumoral and demographic characteristics, Kaplan Meier survival analysis, and Cox multivariate regression analysis were conducted to assess the single contributions of these parameters in building a predictive model of overall survival (OS) in these patients. The mean baseline MPV correlated with increasing age (r=0.18, P=0.01), the overall fluid-attenuated inversion recovery tumoral volume (r=0.17, P=0.02), and lesion T1-weighted post-contrast sequence (T1-CE) volume (r=0.19, P=0.01). The median OS in the whole cohort of patients with GBM was 14.4 months (95% CI 12.9-17.6). Patients with MPV >10.3x10-15 l had a median OS of 13.4 months (95% CI 10.6-17.6) compared with 14.5 months (95% CI 13.4-20.6) in patients with MPV ≤10.3x10-15 l (P=0.028). Similarly, shorter OS was recorded in patients with PT ratio >1.01 (12.3 months, 95% CI 10.2-15.1 vs. 17.6 months, 95% CI 13.4-20.6; P=0.006) and PLT count out-of-range 165-300x109/l (11.5 months, 95% CI 8.8-16.3 vs. 14.7 months, 95% CI 13.4-19.1; P=0.026). A subgroup analysis of patients >65 years of age confirmed baseline MPV >10.3 10-15 l was associated with shorter OS (9.4 months, 95% CI 8.1-13.4) compared with 13.3 months (95% CI 11.3-32.3, P=0.028) for those with MPV ≤10.3x10-15 l. Baseline-increased MPV showed an independent predictive role for poor survival (HR, 1.56; 95% CI 1.13-2.16; P=0.006) in multivariate analysis accounting for age, gender, performance status, extent or resection, adjuvant therapies, and tumoral molecular and radiological characteristics, whereas PLT count within the central range predicted longer OS (HR, 0.26; 95% CI 0.13-0.54; P<0.001). The present study indicates a possible association between tumoral burden and systemic hemostasis activation in patients with IDH-wt GBM. Increased MPV and deranged PLT outside the central range demonstrated an independent role in predicting shorter OS, which was even more prominent among older patients. These findings require additional studies to further validate these results and specifically characterize GBM pathological features of aggressiveness related to hemostasis activation, neo-angiogenesis, the tumor immune microenvironment, and their effect on response to treatments and OS.