Release time：2024-09-13 Source：Xurui Biotechnology
D-dimer is a product of the degradation of cross-linked fibrin by plasmin, and its production requires the synergistic action of thrombin, activator IIIa, and plasmin. At present, the commonly used cutoff value for D-dimer is 500 μ g/L. Due to different detection methods, the cutoff value may vary to some extent.
D-dimer plays an important role in coagulation and fibrinolysis activity. The coagulation and fibrinolysis system of cancer patients is activated to form a hypercoagulable state, which becomes a key factor driving cancer progression. Current research suggests that cancer cells directly participate in coagulation, induce platelet aggregation, or regulate endothelial cells and inflammatory processes, thereby promoting bidirectional regulation of coagulation function and cancer progression, leading to thrombosis or bleeding while promoting tumor growth, invasion, stromal formation, and metastasis. D-dimer detection has important clinical significance for assessing coagulation function in cancer patients.
Evaluation of therapeutic efficacy and prognosis of PD-1/PD-L1 inhibitors in patients with esophageal squamous cell carcinoma at the level of 01 D-dimer
PD-1 and PD-L1 are the most targeted checkpoints in immune checkpoint inhibitor (ICIs) therapy. The efficacy of anti-PD-1/PD-L1 therapy varies, with most patients having poor response and only a few benefiting, and acquired resistance may develop over time. Given the narrow time window and high cost of ICIs treatment, it is crucial to identify reliable biomarkers to predict treatment efficacy and prognosis. At present, there is a lack of simple and effective ideal biomarkers to evaluate the efficacy and prognosis of PD-1/PD-L1 inhibitor therapy.
As is well known, platelets, fibrinogen, and D-dimer are basic blood markers that reflect the coagulation and fibrinolysis status of the patient's physiological system in clinical practice, and are easy to measure with low cost. The value of some coagulation fibrinolysis related biomarkers in predicting the outcome of esophageal squamous cell carcinoma (ESCC) patients has been confirmed. However, there are limited reports on the biomarker value of efficacy evaluation and prognosis in patients with esophageal squamous cell carcinoma treated with PD-1/PD-L1 inhibitors.
Based on this, a study published in The International Journal of Biological Markers retrospectively analyzed ESCC patients treated with PD-1/PD-L1 inhibitors, aiming to explore the value of D-dimer levels in predicting efficacy and prognosis.
This study collected clinical data from 233 patients with advanced or metastatic ESCC who received PD-1/PD-L1 inhibitor treatment at Zhejiang Cancer Hospital from July 2017 to May 2021, and conducted a retrospective analysis. This study analyzed indicators such as platelets, fibrinogen, and D-dimer in patients to evaluate the relationship between these biomarkers and the therapeutic effect of PD-1/PD-L1 inhibitors.
The main research content and results are as follows:
1. Determine the optimal cutoff values for platelets, fibrinogen, and D-dimer. The optimal critical values for platelets, fibrinogen, and D-dimer were determined to be 243 × 10 ^ 9/L, 3.9 g/L, and 236 ng/mL, respectively, using the maximum selection rank statistic method. Using these established cutoff value grouping analyses, it was found that there were significant differences (P<0.05) in overall survival (OS) between the high and low groups of platelets, fibrinogen, and D-dimer.
2. The clinical data of 233 patients with esophageal squamous cell carcinoma and their relationship with D-dimer levels were studied. The results showed that among patients receiving PD-1/PD-L1 inhibitor treatment, third line therapy, non concurrent radiotherapy and/or chemotherapy, lower primary site, higher fibrinogen levels, and higher D-dimer levels (>236 ng/mL) were associated with shorter progression free survival (PFS). In addition, ESCC patients with higher levels of D-dimer who receive PD-1/PD-L1 inhibitor treatment have poorer PFS and OS compared to ESCC patients with lower levels of D-dimer.
3. Subgroup analysis was conducted at different levels of fibrinogen. The results showed that in patients with low fibrinogen levels (≤ 3.90 g/L), those with high D-dimer levels (>236 ng/mL) had significantly shorter progression free survival and overall survival. In patients with high levels of fibrinogen (>3.90 g/L), D-dimer levels were not significantly correlated with progression free survival and overall survival.
Kaplan Meier survival curves of ESCC patients with different levels of D-dimer
In summary, the results of this study suggest that platelets, fibrinogen, and D-dimer may serve as important indicators for predicting treatment response and survival rate in patients with esophageal squamous cell carcinoma. Especially for patients with low levels of fibrinogen, the level of D-dimer may have a significant impact on their prognosis.
02 Albumin to D-dimer ratio: a novel prognostic factor for evaluating first-line chemotherapy efficacy in patients with advanced lung adenocarcinoma
In recent years, the incidence rate of lung adenocarcinoma (LUAD) has increased significantly, and it has become the most common subtype of all lung cancers. Platinum based chemotherapy remains the preferred option for most advanced LUAD patients. Given the inherent differences in chemotherapy efficacy, identifying prognostic markers associated with chemotherapy response is crucial for early optimization of treatment plans, thereby improving the prognosis of late stage LUAD patients.
Previous studies have shown that the use of albumin and D-dimer alone can predict the survival of patients with malignant tumors; However, for advanced lung adenocarcinoma patients receiving first-line platinum based chemotherapy, the albumin to D-dimer ratio (ADR) as a predictive indicator has not been studied.
A study published in the journal Neoplasma retrospectively analyzed data from 313 patients with advanced lung adenocarcinoma, aiming to explore the value of ADR as an indicator for predicting the efficacy and survival prognosis of first-line platinum based chemotherapy in patients with advanced lung adenocarcinoma.
This study collected data from 313 patients with advanced LUAD admitted to the Fifth People's Hospital of Shenyang from January 2017 to January 2021, and conducted a retrospective analysis of their serum biomarkers (such as albumin, fibrinogen, D-dimer, etc.), tumor staging, chemotherapy response, and survival rate.
The main research content and results are as follows:
Firstly, the AUC values of different biomarkers were determined through ROC curves, with the highest AUC value being the albumin/D-dimer ratio (ADR), with an AUC of 0.805.
2. Then, the Youden index was used to determine the optimal cutoff value for ADR, which was 16.608, and it was used to divide patients into high-risk group (ADR<16.608) and low-risk group (ADR>16.608).
Subsequently, the clinical characteristics and chemotherapy outcomes of the two groups of patients were compared, and it was found that the high ADR group had significantly increased disease control rate (DCR) and overall response rate (ORR) after chemotherapy. Finally, prognostic factors were determined through multivariate analysis, including ADR, gender, body mass index, red blood cell count, platelet count, alkaline phosphatase, and sodium ion levels. In addition, among the PFS beneficiaries identified by multivariate analysis, the median progression free survival (PFS) of the high ADR group was significantly longer than that of the low ADR group (254 vs. 142 days, p < 0.0001）。
Kaplan Meier survival curves of progression free survival based on different ADR thresholds
Overall, the research results confirm that ADR can serve as a novel and promising prognostic indicator for patients with advanced lung adenocarcinoma, with higher accuracy than using albumin or D-dimer alone, as well as the albumin to fibrinogen ratio. ADR can be used to evaluate the efficacy of first-line chemotherapy and PFS in patients with advanced lung adenocarcinoma, while also helping doctors develop more effective treatment plans.
references：1.Wu Y, Liu X, Li H, et al. D-dimer levels predict the treatment efficacy and prognosis of esophageal squamous cell carcinoma treated with PD-1/PD-L1 inhibitors. The International Journal of Biological Markers. 2024;0(0). doi:10.1177/039361552412620452.Zhang L, Li X, Wang Z, Zhang Z, Zhang L, Liu Z, Zhang L, Wang S, Khorobrykh TV, He M, Xiao J. Albumin-to-D-dimer ratios: A novel prognostic factor for evaluating first-line chemotherapy efficacy in advanced lung adenocarcinoma patients. Neoplasma. 2024 Feb;71(1):77-87. doi: 10.4149/neo_2024_230413N205. PMID: 38506032.
