Prognostic value of plasma D-dimer levels in advanced non-small cell lung cancer patients treated with immune checkpoint inhibitors: a retrospective study

Abstract

Background: Plasma D-dimer is of great significance for the clinical exclusion of tumor-related thrombosis. Previous studies have shown its predictive role in non-small cell lung cancer (NSCLC) treated with chemotherapy. However, whether pretreatment D-dimer could predict the efficacy and prognosis in NSCLC patients treated with immune checkpoint inhibitors (ICIs) remains unclear.Methods: Advanced NSCLC patients treated with ICIs at the Chinese PLA General Hospital between January 2015 and March 2019 were enrolled. Patients were divided into a pretreatment normal D-dimer group (≤0.5 μg/mL) and high D-dimer group (>0.5 μg/mL). Optimization-based approach was applied to balance baseline covariates between the 2 groups, including age, sex, histological type, smoking history, stage, Eastern Cooperative Oncology Group Performance Status (ECOG PS), lines of treatment, ICI drugs, brain metastasis, treatment type, and D-dimer levels. Kaplan-Meier analysis and Cox proportional hazards model were used for analyzing survival data, including progression-free survival (PFS, the time from initial ICI treatment to PD or death), overall survival (OS, the time between initial ICI treatment and death), and hazard ratio (HR). Follow-up of all patients was performed by searching electronic medical records and counseling telephone. The follow-up cut-off date was July 6, 2020.Results: This study included 277 advanced NSCLC patients. Among the enrolled patients, 23.1% were female, 64.6% had non-squamous cell lung cancer, and 79.4% were stage IV. Univariate and multivariate analysis showed that pretreatment high D-dimer levels were independently associated with shortened PFS and OS (P<0.01). Subgroup analysis confirmed that pretreatment high D-dimer levels were associated with poor prognosis in most subsets. After balancing baseline covariates between the high D-dimer group and normal D-dimer group, the results indicated that patients with pretreatment high D-dimer levels had significantly shorter PFS [median: 6.4 vs. 11.5 months; HR, 1.70; 95% confidence ratio (CI): 1.25-2.37; P<0.001] and OS (median: 12.7 vs. 30.4 months; HR, 2.29; 95% CI: 1.54-3.41; P<0.001) than those with pretreatment normal D-dimer levels.Conclusions: Pretreatment plasma D-dimer could serve as a convenient prognostic biomarker for advanced NSCLC patients receiving ICI treatment. Patients with pretreatment high D-dimer levels may have poor PFS and OS.

Effectiveness and Safety of PD-1 Inhibitors’ Treatment for Patients with Non-Small-Cell Lung Cancer in China: A Real-World Study

“…As with other studies [44][45][46][47], we did not observe the diferences in PFS and OS between patients with nonsquamous and squamous. Pathological staging was not a prognostic factor afecting the efcacy of immunotherapy.…”

Application of a nomogram from coagulation-related biomarkers and C1q and total bile acids in distinguishing advanced and early-stage lung cancer

“…Through a meta-analysis of seven studies involving a total of 1488 LC patients and 328 control groups, Biruk et al 37 concluded that the DD value was significantly higher in LC patients (standardized mean difference) 3.10; 95% CI 2.08, 4.12; P < 0.000) when compared with the health control group. In addition, Li et al 36 found that patients with a high level of plasma DD have a worse overall survival prognosis (hazard ratio (HR) = 1.742; 95% CI 1.542, 1.969; P < 0.001; I 2 = 72.1%) compared with these patients who have a normal plasma DD; elevated plasma DD is also a risk factor of progression-free survival in LC (HR = 1.385; 95% CI 1.169, 1.641; P = 0.003; I 2 = 69.1%). Similar to our findings, Chen et al 38 showed that the level of DD was associated with tumor stage; the level of neuron-specific enolase; the presence of distant metastasis, hyponatremia, and the progression of patients.…”

“…However, increasing clinical evidence shows that the coagulation system of patients with malignant tumors is remarkably abnormal, and the level of DD is significantly elevated. 36 The mechanism may be that tumor cells or tissues around necrosis trigger the release of tissue factors, and activate coagulation factors X and XI in the external coagulation system and fibrinolysis system, resulting in the local production of plasmin to directly degrade the extracellular matrix, giving tumor cells the ability of invasion and metastasis. In this process, the released inflammatory mediators damage the vascular endothelial cells, leading to a hypercoagulable state of blood, which makes tumor cells adhere to the vascular wall.…”

Albumin-to-D-dimer ratios: A novel prognostic factor for evaluating first-line chemotherapy efficacy in advanced lung adenocarcinoma patients

“…Diminished serum albumin concentrations, emblematic of inflammatory and nutritional derangements, correspond to the grim prognosis of numerous virulent neoplasms [22,40]. Conversely, the elevation in D-dimer levels, indicative of hypercoagulable and inflammatory states, is associated with suboptimal survival across a diverse array of malignancies [41][42][43][44]. The composite measure, ADR, encompasses both albumin and D-dimer concentrations, potentially capturing a more comprehensive representation of the concomitant inflammatory, nutritional, and hemostatic perturbations in oncologic patients.…”