Key Points: Brain tumor patients have a very high risk of VTE. Podoplanin expression by primary brain tumors induces platelet aggregation and is associated with hypercoagulability and a high risk of VTE.

Background: Biomarkers for predicting response to immune checkpoint inhibitors (ICI) are scarce and often lack external validation. This study provides a comprehensive investigation of pretreatment C-reactive protein (CRP) levels as well as its longitudinal trajectories as a marker of treatment response and disease outcome in patients with advanced non-small cell lung cancer (NSCLC) undergoing immunotherapy with anti PD-1 or anti PD-L1 agents. Methods: We performed a retrospective bi-center study to assess the association between baseline CRP levels and anti PD-(L)1 treatment outcomes in the discovery cohort (n = 90), confirm these findings in an external validation cohort (n = 101) and explore the longitudinal evolution of CRP during anti PD-(L)1 treatment and the potential impact of dynamic CRP changes on treatment response and disease outcome in the discovery cohort. Joint models were implemented to evaluate the association of longitudinal CRP trajectories and progression risk. Primary treatment outcomes were progression-free survival (PFS) and overall survival (OS), while the objective response rate (ORR) was a secondary outcome, respectively. Results: In the discovery cohort, elevated pretreatment CRP levels emerged as independent predictors of worse PFS (HR per doubling of baseline CRP = 1.37, 95% CI: 1.16–1.63, p < 0.0001), worse OS (HR per doubling of baseline CRP = 1.42, 95% CI: 1.18–1.71, p < 0.0001) and a lower ORR ((odds ratio (OR) of ORR per doubling of baseline CRP = 0.68, 95% CI: 0.51–0.92, p = 0.013)). In the validation cohort, pretreatment CRP could be fully confirmed as a predictor of PFS and OS, but not ORR. Elevated trajectories of CRP during anti PD-(L)1 treatment (adjusted HR per 10 mg/L increase in CRP = 1.22, 95% CI: 1.15–1.30, p < 0.0001), as well as a faster increases of CRP over time (HR per 10 mg/L/month faster increase in CRP levels = 13.26, 95% CI: 1.14–154.54, p = 0.039) were strong predictors of an elevated progression risk, whereas an early decline of CRP was significantly associated with a reduction in PFS risk (HR = 0.91, 95% CI: 0.83–0.99, p = 0.036), respectively. Conclusion: These findings support the concept that CRP should be further explored by future prospective studies as a simple non-invasive biomarker for assessing treatment benefit during anti PD-(L)1 treatment in advanced NSCLC.

Background.: In cancer patients, reduced serum albumin has been described as a marker for global declining health and poor prognosis. Our aim was to investigate the association of albumin concentrations with the occurrence of venous thromboembolism (VTE) and mortality in patients with cancer. Methods.: This investigation was performed in the framework of the Vienna Cancer and Thrombosis Study (CATS), a prospective observational cohort study. We included 1,070 patients with active cancer and assayed serum albumin from venous blood taken at study inclusion. Risk for occurrence of VTE was calculated in a proportional subdistribution hazard regression model with respect to competing risk of death and adjusted for cancer site, leukocyte count, estimated glomerular filtration rate, and cholinesterase. Results.: Patients (630 males [58.9%] and 440 females [41.1%]) were observed for a median of 723 days. During follow-up, 90 VTE events (8.4%) and 396 deaths (37.0%) occurred. The median albumin was 41.3 g/L (25th–75th percentile, 37.6–44.2). Patients with albumin levels below the 75th percentile had a 2.2-fold increased risk of VTE (95% confidence interval [CI] 1.09–4.32), as well as a 2.3-fold increased risk of death (95% CI 1.68–3.20) compared with patients with albumin above the 75th percentile. Conclusion.: Decreased serum albumin levels in cancer patients were significantly associated with increased risk of VTE and mortality. Serum albumin, a marker of a cancer patient’s overall prognosis, could be considered for risk assessment of important clinical outcomes such as VTE and mortality.

Unplanned excisions (UE) of soft tissue sarcomas (STS) carry a high risk for local recurrence (LR) due to marginal/intralesional resections. However, there

Atrial fibrillation (AF) adds significant risk of stroke and thromboembolism in patients on hemodialysis (HD). The aim of this study was to investigate the prevalence of AF in a population-based cohort of HD patients and practice patterns of antithrombotic therapy for stroke prevention in AF. The Vienna InVestigation of AtriaL fibrillation and thromboembolism in patients on hemodialysis (VIVALDI), an ongoing prospective observational cohort study, investigates the prevalence of AF and the risk of thromboembolic events in HD patients in Vienna, Austria. We analyzed cross-sectional data of 626 patients (63.4% men, median age 66 years, approx. 73% of HD patients in Vienna), who provided informed consent. A structured interview with each patient was performed, recent and archived ECGs were viewed and medical histories were verified with electronic records. The overall prevalence of AF was 26.5% (166 patients, 71.1% men, median age 72 years) of which 57.8% had paroxysmal AF, 3.0% persistent AF, 32.5% permanent AF, and 6.6% of patients had newly diagnosed AF. The median CHA₂DS₂-VASc Score was 4 [25^th-75^th percentile 3–5]. In multivariable analysis, AF was independently associated with age (odds ratio: 1.05 per year increase, 95% confidence interval: 1.03–1.07), male sex (1.7, 1.1–2.6), history of venous thromboembolism (2.0, 1.1–3.6), congestive heart failure (1.7, 1.1–2.5), history of or active cancer (1.5, 1.0–2.4) and time on HD (1.08 per year on HD, 1.03–1.13). Antithrombotic treatment was applied in 84.4% of AF patients (anticoagulant agents in 29.5%, antiplatelet agents in 33.7%, and both in 21.1%). In AF patients, vitamin-K-antagonists were used more often than low-molecular-weight heparins (30.1% and 19.9%). The prevalence of AF is high amongst HD patients and is associated with age, sex, and distinct comorbidities. Practice patterns of antithrombotic treatment indicate a lack of consensus for stroke prevention in HD patients with AF.