肿瘤患者静脉血栓栓塞症的风险评估模型及其应用

静脉血栓栓塞症(VTE)是肿瘤患者常见的并发症和死亡原因。多项研究显示,有效的VTE风险评估模型和恰当的预防性抗凝治疗可以降低肿瘤患者的血栓发生风险。但哪些肿瘤患者需要进行预防性抗凝治疗,需要有效的VTE风险评估模型,对肿瘤患者进行VTE风险分层。对血栓高危人群,在排除抗凝禁忌证后进行预防性抗凝。但肿瘤疾病存在复杂性,不同的病理类型和分期,VTE风险和特点不同,而目前专门针对肿瘤患者的VTE风险评估模型仍然有限,本文将对肿瘤患者的VTE风险评估模型的现状及其应用进行综述。     

Venous Thromboembolism Is an Independent Predictor of Mortality Among Patients with Gastric Cancer

Background

Venous thromboembolism (VTE) is an independent predictor of death among patients with cancer. Patients with gastric cancer (GC) are at higher risk for VTE when compared to other solid tumors, and if one considers its prevalence, GC may be responsible for one of the highest incidences of cancer-associated thrombosis. The impact of VTE on mortality is not well defined among patients with GC.

Aim

The aim of this study is to measure the impact of VTE as independent predictor of GC mortality.

Methods

Chart review of patients with GC treated in the Department of Oncology at John Stroger Hospital between the years of 2010 and 2015. VTE events were objectively confirmed with imaging in all cases. Active GC was defined as biopsy-proven metastatic disease or on active chemotherapy. Along with cancer-specific data, we abstracted risk assessments tools, non-GC-specific, validated for VTE and mortality prediction cancer, including the Khorana score (KRS), platelet lymphocyte ratio (PLR), and neutrophil lymphocyte ratio (NLR). Continuous variables are expressed by the median as appropriate according to normality. Categorical variables are expressed as percentages. SPSS version 22 was used and chi-square, Mann-Whitney U, Kaplan-Meier curve, and Cox proportional hazard with forward modeling were applied.

Results

We included 112 patients in the analysis. The patients were predominantly men (66%), 58-year-old, with adenocarcinoma (84%) and advanced disease (59%). The median follow-up was 21.3 months (IQR 8.9–42.4). Cumulative incidence of VTE at 1 year was 9%. The median time from diagnosis to VTE occurrence was 59 days (IQR 36 to 258). Patients with VTE had worse OS when compared to the non-VTE group (medians 11.87 vs 29.97 months, p = 0.02). Patients stratified as high risk by the PLR had worse OS (medians 22.6 vs 42.77 months, p = 0.02). There was no statistical difference in OS among patients stratified as high risk by the KRS (medians 23.7 vs 42.5, p = 0.16) and NLR (medians 24.1 vs 42.7 months, p = 0.21). In multivariate analysis, the independent predictors of mortality were VTE (hazard ratio (HR), 2.9; 95% CI, 1.4 to 6.6; p < 0.01), adenocarcinoma (HR, 3.1; 95% CI, 1.1 to 9.0; p = 0.03), advanced disease (HR, 2.8; 95% CI, 1.4 to 5.8; p < 0.01), and PLR (HR, 2.2; 95% CI, 1.3 to 3.8; p < 0.01).

Conclusion

VTE is associated with worse survival among patients with GC along with adenocarcinoma, advanced disease, and PLR. Moreover, these findings were independent of other cancer- and treatment-specific variables. Although potentially predictive in other cancer types, NLR and KRS were not associated with worse survival in this cohort.

     

恶性肿瘤合并静脉血栓栓塞症患者的临床特点分析CSCD

目的分析恶性肿瘤合并静脉血栓栓塞症(VTE)患者的临床特点并探寻相关危险因素。方法采用回顾性病例对照研究,调查恶性肿瘤合并VTE患者的临床及生存结局信息。采用卡方检验、Log rank检验和比例风险回归模型(Cox模型)等方法进行统计分析,采用GraphPad Prism8.0绘制生存曲线,分析VTE相关影响因素。结果5年间共收治新发恶性肿瘤患者11620例,其中合并VTE患者385例(3.31%)。恶性淋巴瘤患者合并VTE的比例最大,达到4.78%,其次是结直肠癌和乳腺癌,分别为4.40%和4.08%;联合治疗的患者比单一治疗方式发生VTE的比例高;分期越晚的患者合并VTE的比例越高;随访结果显示合并VTE患者中位生存时间为17.90月(95%CI:10.21~25.59),1、3、5年生存率分别为51.89%、37.76%、18.88%;多因素分析结果显示年龄、性别、TNM分期是影响VTE患者预后的独立危险因素。结论恶性肿瘤患者容易并发VTE,临床上应对高危患者密切观察、提早预防。     

Association Between Decreased Serum Albumin With Risk of Venous Thromboembolism and Mortality in Cancer Patients

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.

Implications for Practice:

Cancer patients are at increased risk of venous thromboembolism (VTE). In this prospective cohort study of 1,070 cancer patients, decreased serum albumin was a marker for risk of VTE and mortality, independent of kidney or liver function and inflammation markers. The study identified a group of patients with high risk of cancer-associated VTE and a reduced prognosis who may benefit from supportive therapy such as primary VTE prophylaxis.     

Novel High-Sensitive D-Dimer Determination Predicts Chemotherapy-Associated Venous Thromboembolism in Intermediate Risk Lung Cancer Patients

IntroductionWe hypothesized that the use of a novel high sensitivity (HS) assay for D-dimer determination might ameliorate venous thromboembolism (VTE) risk prediction in intermediate risk lung cancer patients in whom chemotherapy could act as a trigger for VTE onset.Patients and MethodsPretreatment HS D-dimer levels were retrospectively evaluated in 108 lung cancer outpatients using a novel automated latex enhanced turbidimetric immunoassay. All patients were at the start of a new platinum-based chemotherapy regimen and were classified as intermediate risk according to Khorana's assessment model. Patients were followed-up for a median period of 6.9 months.ResultsReceiver operating characteristic (ROC) curves and corresponding Bayesian analysis showed that the best performance was obtained at a cutoff level of 1500 ng/mL, which resulted in a sensitivity of 81%, a specificity of 69%, a positive predictive value (PPV) of 31%, a negative predictive value (NPV) of 96%, and an accuracy of 70%. Patients with HS D-dimer levels above the cutoff had a worse VTE-free survival (60%) compared with those with levels below the cutoff (95%; P = .0001). Multivariate Cox proportional hazards survival analysis confirmed that pretreatment HS D-dimer levels were able to significantly predict VTE with a hazard ratio of 11 (95% confidence interval, 2.62-46.2; P = .001), independently of classic VTE risk factors.ConclusionsThe use of HS D-dimer determination prior to chemotherapy might allow for VTE risk stratification of intermediate risk cancer patients, helping in identifying those individuals who could benefit from thromboprophylaxis.     

Venous Thromboembolism Risk in Patients With Locoregional Urothelial Tract Tumors

Background

Venous thromboembolism (VTE) is common in cancer patients, but there is limited data on patients with urothelial tract tumors (UTT). We previously identified several associative factors for increased VTE rates in patients with metastatic UTT. In this study, we assessed the frequency, associative factors, and impact on survival of VTE in patients with locoregional UTT.

Venous Thromboembolism Risk in Patients With Cancer Receiving Chemotherapy: A Real‐World Analysis

Introduction.

The occurrence of malignant disease increases the risk for venous thromboembolism (VTE). Here we evaluate the risk for VTE in a large unselected cohort of patients with cancer receiving chemotherapy.

Methods.

The United States IMPACT health care claims database was retrospectively analyzed to identify patients with a range of solid tumors who started chemotherapy from January 2005 through December 2008. International Classification of Diseases, 9th revision, Clinical Modification Codes were used to identify cancer location, presence of VTE 3.5 months and 12 months after starting chemotherapy, and incidence of major bleeding complications. Health care costs were assessed one year before initiation of chemotherapy and one year after initiation of chemotherapy.

Results.

The overall incidence of VTE 3.5 months after starting chemotherapy was 7.3% (range 4.6%–11.6% across cancer locations) rising to 13.5% at 12 months (range 9.8%–21.3%). The highest VTE risk was identified in patients with pancreatic, stomach, and lung cancer. Patients in whom VTE developed had a higher risk for major bleeding at 3.5 months and at 12 months (11.0% and 19.8% vs. 3.8% and 9.6%, respectively). Health care costs were significantly higher in patients in whom VTE developed.

Conclusion.

Those undergoing chemotherapy as outpatients are at increased risk for VTE and for major bleeding complications. Thromboprophylaxis may be considered for such patients after carefully assessing the risks and benefits of treatment.     

晚期肿瘤患者深静脉血栓形成的危险因素分析

[目的]探讨晚期肿瘤患者发生深静脉血栓的危险因素.[方法]采用回顾性分析方法,对2005年1月至2010年12月期间发生深静脉血栓的78例晚期肿瘤患者的临床资料进行分析,同时随机选择同期不伴有血栓性疾病的78例恶性肿瘤患者为对照,分析晚期肿瘤患者深静脉血栓形成的危险因素.[结果]多因素分析显示,并发感染(OR=3.249,P=0.038)、输血(OR=1.460,P=0.041)及远处转移(OR=7.376,P＜0.001)是晚期肿瘤患者发生深静脉血栓的独立危险因素,病例组1年生存率明显低于对照组(41.0％ vs 52.6％,x2=4.991,P=0.025).[结论]远处转移、并发感染、输血治疗是晚期肿瘤患者发生深静脉血栓的危险因素,发生深静脉血栓者预后较差.     

住院肿瘤患者中心静脉导管相关血流感染监测结果的分析与研究简

目的：了解肿瘤患者住院期间中心静脉导管相关血流感染（CRBSI）的发病特点,为做好CRBSI预防和控制的临床护理决策提供依据.方法：对2011年5月至2011年12月入院且符合纳入排除标准的506例中心静脉置管患者进行前瞻性调查,自患者入院时动态监测患者中心静脉导管使用情况及CRBSI发病特点.结果：本研究中共检出6例CRBSI患者,CRBSI感染率为0.62例次/1 000个导管日,其中PICC感染率为0.42例次/1 000个导管日,CVC感染率为0.81例次/1 000个导管日.病原菌包括金黄色葡萄球菌、肺炎克雷伯杆菌、大肠埃希氏菌和念珠菌.结论：住院肿瘤患者中心静脉导管相关血流感染发病率较低,病原菌均为临床常见致病菌,但CRBSI感染患者均为研究报道的CRBSI易感人群,临床护士应加强中心静脉置管患者特别是CRBSI易感患者的监测管理.     

居民防癌健康素养优化策略研究

[目的]了解居民对浙江省肿瘤医院开展的肿瘤筛查等工作及防癌科普知识的知晓水平并分析影响因素,为更好开展肿瘤筛查和制定科学传播策略提供依据。[方法]以浙江省肿瘤医院部分在院患者为抽样调查对象,设计调查问卷,共发放问卷300份,收集人口学信息、健康状况、对癌症科普、义诊、筛查行动的看法及满意度等情况。采用量化分析的方式,利用方差、斯皮尔曼系数等分析变量之间的相关性。[结果]共238份问卷有效。“对这些癌症科普、义诊、筛查行动的感受”分值平均数为4.66（总分5分）。“是否了解防癌筛查车的功能”与“是否觉得防癌筛查对你有帮助”呈正相关关系（r=0.005,P=0.001）。“是否知道有这方面的健康问题”与“我喜欢医院安排的这些癌症科普、义诊、筛查行动”呈正相关关系（r=0.141,P=0.041）。“在不同的地方见到防癌筛查车”与“是否觉得防癌筛查对你有帮助”呈正相关关系（r=0.650,P=0.003）。[结论]通过提高知晓率、说服群众主动参与、制定群众容易接受的干预策略并提高满意度,可以提高居民防癌健康素养。     

肿瘤患者中心静脉导管相关性血栓的危险因素研究进展

摘 要：肿瘤患者中心静脉导管相关性血栓的发生率高,且可能导致一系列严重的后果,将相关危险因素进行分层,可能有助于早期诊断及早期预防,而目前缺乏与此相关的特异性的评估方法。全文主要从置管、肿瘤患者特点及抗肿瘤治疗三个方面来总结肿瘤患者并发导管相关性血栓的主要危险因素。     

Prevalence and Clinical Significance of Incidental and Clinically Suspected Venous Thromboembolism in Lung Cancer Patients

BackgroundIt is unclear what proportion of VTE events in lung cancer patients are incidentally discovered and whether incidental events affect mortality.Patients and MethodsWe conducted a retrospective cohort study of lung cancer patients seen at the University of Rochester between January 1, 2006 and December 31, 2008 with the goal of quantifying and characterizing VTE events. Multiple clinical variables and mortality outcomes were compared using Kaplan-Meier survival analysis and multivariate Cox proportional hazards.ResultsThe study population consisted of 207 subjects with lung cancer. The median age was 66 years and 55% were female (n = 115). Thirty-one patients (14.9%) experienced at least 1 VTE event with 32.2% (10/31) of these incidentally discovered. Incidental events comprised 29.4% (n = 5) of pulmonary embolisms, 11.1% (n = 2) of deep vein thrombosis, and 100% (n = 3) of visceral events. The median survival for patients with incidental VTE was 23.4 months (95% confidence interval [CI], 4.8-32.1) compared with 45.8 months (95% CI, 34.1-56.8) in patients without VTE (HR 2.4; 95% CI, 1.2-4.9; P = .01), but in a subgroup analysis of stage IV patients overall survival was not significantly different (HR, 0.94; P = .33). Patients with clinically suspected VTE had the lowest median survival at 13.1 months (95% CI, 6.4-18.9) which was significantly lower than patients without VTE (HR, 2.7; 95% CI, 1.6-4.5; P = .002), but not significantly different from patients with incidental VTE (HR, 1.2; 95% CI, 0.4-2.0; P = .7). In multivariate analysis, occurrence of VTE (HR, 2.3; 95% CI, 1.3-3.8; P = .002) was significantly associated with mortality when adjusting for age, stage, and histology.ConclusionsOne-third of VTE events in lung cancer patients are incidentally discovered and VTE has negative clinical effect in lung cancer patients.     

导致肺癌化疗患者发生静脉血栓栓塞症的相关因素及其治疗

目的探讨导致肺癌化疗患者发生静脉血栓栓塞症的相关因素及其治疗。方法回顾性分析106例伴有静脉血栓栓塞症的肺癌化疗患者(观察组)和120例未伴有静脉血栓栓塞症肺癌化疗患者(对照组)的临床症状。对可能导致2组患者发生不同病症的相关影响因素,如:性别、年龄、既往病史(高脂血症、肥胖、高血压、吸烟史、糖尿病)、病理类型与分期、血小板计数、血黏稠度、D-二聚体进行统计分析。对106例患者中5例实施了尿激酶溶栓治疗,其余101例患者采用低分子肝素-华法林序贯抗凝治疗方法。结果单因素方差分析结果显示2组患者的年龄、吸烟史、病理分期、血黏稠度和D-二聚体之间的差异具有统计学意义(P<0.05),性别、高脂血症、肥胖、高血压、糖尿病、病理分型、血小板计数之间的差异无统计学意义(P>0.05)。对筛选出的影响因素进行多因素Logistic回归分析,结果显示年龄≥60岁、有吸烟史、晚期、血黏稠度上升(男士>4.66 c P/女士>3.93 c P)、D-二聚体上升(>500μg/L)是肺癌化疗患者发生静脉血栓栓塞症的危险因素。经积极治疗后58例治愈,11例好转,有效率为65.09%。结论年龄≥60岁、有吸烟史、晚期、血黏稠度上升、D-二聚体上升是肺癌化疗患者发生静脉血栓栓塞症的危险因素,在治疗时应及时评估其致病的相关危险因素,尽早实施抗凝治疗,提高疗效,减少并发症的发生。     

肺癌围术期患者静脉血栓栓塞症的预防与护理现状调查分析

背景与目的 了解我国医院肺癌围术期患者静脉血栓栓塞症(venous thromboembolism, VTE)的预防与护理现状.方法 采用自行设计的调查问卷,在第一届胸科加速康复外科(enhanced recovery after surgery, ERAS)华西论坛上,对全国108名胸外科护士长进行调查.结果 ①评估工具与预防规范:97.22%的医院已采用不同评估工具对肺癌围术期患者进行VTE风险分级,其中67.59%的医院已形成VTE预防护理规范.②筛查、预防与随访:56.48%的医院对肺癌患者进行了VTE术前筛查,90.74%的医院对住院患者进行了VTE预防,52.78%的医院对出院患者继续进行了VTE预防,仅有17.59%医院对出院患者VTE的发生情况进行了随访.③不同类型医院肺癌围术期患者VTE预防现状相比,差异无统计学意义(P>0.05),但在VTE风险评估、住院患者VTE预防方面专科医院所有患者已全面实现(100.00%).结论 肺癌围术期VTE预防工作已受到广泛重视,但尚缺乏有效的VTE风险评估工具和标准化的VTE预防护理指南.