Driver Genes Associated With the Incidence of Venous Thromboembolism in Patients With Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis

Qian, Xiaohan; Fu, Mengjiao; Zheng, Jing; Zhou, Jianya

doi:10.3389/fonc.2021.680191

Cited by 17 publications

(12 citation statements)

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“…Currently, there is a growing interest in exploring the potential correlation between driver genes and VTE risk in lung cancer ( 49 – 51 ). Clearly, there is a critical need to incorporating positive driver genes into a risk assessment model for lung cancer to improve performance.…”

Section: Discussionmentioning

confidence: 99%

Derivation, validation and assessment of a novel nomogram-based risk assessment model for venous thromboembolism in hospitalized patients with lung cancer: A retrospective case control study

Tian

Niu

et al. 2022

Front. Oncol.

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PurposeThis study aimed to develop and validate a specific risk-stratification nomogram model for the prediction of venous thromboembolism(VTE) in hospitalized patients with lung cancer using readily obtainable demographic, clinical and therapeutic characteristics, thus guiding the individualized decision-making on thromboprophylaxis on the basis of VTE risk levels.MethodsWe performed a retrospective case–control study among newly diagnosed lung cancer patients hospitalized between January 2016 and December 2021. Included in the cohort were 234 patients who developed PTE and 936 non-VTE patients. The patients were randomly divided into the derivation group (70%, 165 VTE patients and 654 non-VTE patients) and the validation group (30%, 69 VTE patients and 282 non-VTE patients). Cut off values were established using a Youden´s Index. Univariate and multivariate regression analyses were used to determine independent risk factors associated with VTE. Variance Inflation Factor(VIF) was used for collinearity diagnosis of the covariates in the model. The model was validated by the consistency index (C-index), receiver operating characteristic curves(ROC) and the calibration plot with the Hosmer-Lemeshow goodness-of-fit test. The clinical utility of the model was assessed through decision curve analysis(DCA). Further, the comparison of nomogram model with current models(Khorana, Caprini, Padua and COMPASS-CAT) was performed by comparing ROC curves using the DeLong’s test.ResultsThe predictive nomogram modle comprised eleven variables: overweight(24-28) defined by body mass index (BMI): [odds ratio (OR): 1.90, 95% confidence interval (CI): 1.19-3.07], adenocarcinoma(OR:3.00, 95% CI: 1.88-4.87), stageIII-IV(OR:2.75, 95%CI: 1.58-4.96), Central venous catheters(CVCs) (OR:4.64, 95%CI: 2.86-7.62), D-dimer levels≥2.06mg/L(OR:5.58, 95%CI:3.54-8.94), PT levels≥11.45sec(OR:2.15, 95% CI:1.32-3.54), Fbg levels≥3.33 g/L(OR:1.76, 95%CI:1.12-2.78), TG levels≥1.37mmol/L (OR:1.88, 95%CI:1.19-2.99), ROS1 rearrangement(OR:2.87, 95%CI:1.74-4.75), chemotherapy history(OR:1.66, 95%CI:1.01-2.70) and radiotherapy history(OR:1.96, 95%CI:1.17-3.29). Collinearity analysis with demonstrated no collinearity among the variables. The resulting model showed good predictive performance in the derivation group (AUC 0.865, 95% CI: 0.832-0.897) and in the validation group(AUC 0.904,95%CI:0.869-0.939). The calibration curve and DCA showed that the risk-stratification nomogram had good consistency and clinical utility. Futher, the area under the ROC curve for the specific VTE risk-stratification nomogram model (0.904; 95% CI:0.869-0.939) was significantly higher than those of the KRS, Caprini, Padua and COMPASS-CAT models(Z=12.087, 11.851, 9.442, 5.340, all P<0.001, respectively).ConclusionA high-performance nomogram model incorporated available clinical parameters, genetic and therapeutic factors was established, which can accurately predict the risk of VTE in hospitalized patients with lung cancer and to guide individualized decision-making on thromboprophylaxis. Notably, the novel nomogram model was significantly more effective than the existing well-accepted models in routine clinical practice in stratifying the risk of VTE in those patients. Future community-based prospective studies and studies from multiple clinical centers are required for external validation.

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Section: Discussionmentioning

confidence: 99%

Derivation, validation and assessment of a novel nomogram-based risk assessment model for venous thromboembolism in hospitalized patients with lung cancer: A retrospective case control study

Tian

Niu

et al. 2022

Front. Oncol.

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“… 1 Nonetheless, many details of risk factors for VTE developing during the clinical course of lung cancer remain unclear, including whether the presence or absence of a driver gene mutation is a risk factor. 9 Therefore, there are no clear screening guidelines for identifying the risk of VTE in patients with lung cancer.…”

Section: Introductionmentioning

confidence: 99%

Incidence of venous thromboembolism in advanced lung cancer and efficacy and safety of direct oral anticoagulants: a multicenter, prospective, observational study (Rising-VTE/NEJ037 study)

et al. 2022

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Background: Venous thromboembolism (VTE) is a well-known type of cancer-associated thrombosis and a common complication of malignancy. However, the incidence of VTE associated with lung cancer and the effectiveness of direct oral anticoagulants remain unclear. This study aimed to identify the incidence of VTE associated with lung cancer at the time of diagnosis or during treatment, the efficacy and safety of edoxaban, and associated risk factors. Methods: The Rising-VTE/NEJ037 study was a multicenter prospective observational study. Altogether, 1021 patients with lung cancer who were unsuitable for radical resection or radiation were enrolled and followed up for 2 years. Patients with VTE at the time of lung cancer diagnosis started treatment with edoxaban. The primary endpoint of this trial was the rate of newly diagnosed VTE after enrollment or recurrence rate 6 months after treatment initiation. Results: Data were available for 1008 patients. The median age was 70 years (range: 30–94 years), and 70.8% were men. Sixty-two patients had VTE at the time of lung cancer diagnosis, and 38 (9.9%) developed VTE at follow-up. No cases of VTE recurrence were recorded 6 months after treatment initiation with edoxaban. Major and clinically relevant non-major bleeding events occurred in 4.9% of patients and increased to 22.7% in the edoxaban treatment group. Conclusions: VTE occurrence should be monitored during lung cancer treatment. Although treatment with edoxaban was highly effective in preventing VTE recurrence, its administration should be cautiously considered because of the high bleeding rate. Trial registration: jRCTs061180025.

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“…Furthermore, a prospective cohort study involving 341 patients with lung cancer, including 26 positive for ALK fusion gene, indicated a higher cumulative VTE incidence rate of 26.9% in ALK fusion gene-positive patients (9.2% in ALK fusion gene-negative patients) [ 28 ]. In assessing other gene mutations ( EGFR and KRAS ), a meta-analysis of 25 studies suggested that neither EGFR nor KRAS gene mutations is risk factors for VTE development [ 29 ]. We only studied whether EGFR gene mutation and ALK fusion gene are risk factors for VTE and found that neither was a risk factor.…”

Section: Discussionmentioning

confidence: 99%

Identification of risk factors for venous thromboembolism and validation of the Khorana score in patients with advanced lung cancer: based on the multicenter, prospective Rising-VTE/NEJ037 study data

et al. 2022

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Background Management of cancer-associated venous thromboembolism (VTE) is essential in cancer treatment selection and prognosis. However, currently, no method exists for assessing VTE risk associated with advanced lung cancer. Therefore, we assessed VTE risk, including driver gene mutation, in advanced lung cancer and performed a Khorana score validation. Methods The Rising-VTE/NEJ037 study was a multicenter prospective observational study that included patients with advanced lung cancer. In the Rising-VTE/NEJ037 study, the Khorana score was calculated for enrolled patients with available data on all Khorana score components. The modified Khorana score was based on the body mass index of ≥ 25 kg/m2, according to the Japanese obesity standard. A multivariate logistic regression analysis, including patient background characteristics, was performed to evaluate the presence of VTE 2 years after the lung cancer diagnosis. Results This study included 1008 patients with lung cancer, of whom 100 (9.9%) developed VTE. From the receiver operating characteristic curve analysis, VTE risk could not be determined because both the Khorana score (0.518) and modified Khorana score (0.516) showed very low areas under the curve. The risk factors for VTE in the multivariate analysis included female sex, adenocarcinoma, performance status, N factor, lymphocyte count, platelet count, prothrombin fragment 1 + 2 and diastolic blood pressure. Conclusion The Khorana score, which is widely used in cancer-VTE risk assessment, was less useful for Japanese patients with advanced lung cancer. Prothrombin fragment 1 + 2, a serum marker involved in coagulation, was more suitable for risk identification. Clinical trial information jRCTs061180025.

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Driver Genes Associated With the Incidence of Venous Thromboembolism in Patients With Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis

Cited by 17 publications

References 73 publications

Derivation, validation and assessment of a novel nomogram-based risk assessment model for venous thromboembolism in hospitalized patients with lung cancer: A retrospective case control study

Derivation, validation and assessment of a novel nomogram-based risk assessment model for venous thromboembolism in hospitalized patients with lung cancer: A retrospective case control study

Incidence of venous thromboembolism in advanced lung cancer and efficacy and safety of direct oral anticoagulants: a multicenter, prospective, observational study (Rising-VTE/NEJ037 study)

Identification of risk factors for venous thromboembolism and validation of the Khorana score in patients with advanced lung cancer: based on the multicenter, prospective Rising-VTE/NEJ037 study data

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