Risk of venous thromboembolism (VTE) is elevated in cancer, but individual risk factors cannot identify a sufficiently high-risk group of outpatients for thromboprophylaxis. We developed a simple ...model for predicting chemotherapy-associated VTE using baseline clinical and laboratory variables. The association of VTE with multiple variables was characterized in a derivation cohort of 2701 cancer outpatients from a prospective observational study. A risk model was derived and validated in an independent cohort of 1365 patients from the same study. Five predictive variables were identified in a multivariate model: site of cancer (2 points for very high-risk site, 1 point for high-risk site), platelet count of 350 × 109/L or more, hemoglobin less than 100 g/L (10 g/dL) and/or use of erythropoiesis-stimulating agents, leukocyte count more than 11 × 109/L, and body mass index of 35 kg/m2 or more (1 point each). Rates of VTE in the derivation and validation cohorts, respectively, were 0.8% and 0.3% in low-risk (score = 0), 1.8% and 2% in intermediate-risk (score = 1-2), and 7.1% and 6.7% in high-risk (score ≥ 3) category over a median of 2.5 months (C-statistic = 0.7 for both cohorts). This model can identify patients with a nearly 7% short-term risk of symptomatic VTE and may be used to select cancer outpatients for studies of thromboprophylaxis.
Background
Patients with lung cancer are known to be at increased risk for venous thromboembolism (VTE). Venous thromboembolism is associated with increased risk for early mortality. However, there ...have been no studies performing a comprehensive assessment of risk factors for VTE or early mortality in lung cancer patients undergoing systemic chemotherapy in a global real‐world setting.
Materials and Methods
CANTARISK is a prospective, global, noninterventional cohort study including patients with lung cancer initiating a new cancer therapy. Clinical data were collected until 6‐month follow‐up. The impact of patient‐, disease‐, and treatment‐related factors on the occurrence of VTE and early mortality was evaluated in univariable and multivariable Cox regression analyses. A previously validated VTE risk score (VTE‐RS) was also calculated (also known as Khorana score).
Results
Of 1,980 patients with lung cancer who were enrolled from 2011 to 2012, 84% had non‐small cell lung cancer. During the first 6 months, 121 patients developed a VTE (6.1%), of which 47% had pulmonary embolism, 46% deep vein thrombosis, 3% catheter‐associated thrombosis, and 4% visceral thrombosis. Independent predictors for VTE included female sex, North America location, leg immobilization, and presence of a central venous catheter. The VTE‐RS was not significantly associated with VTE in either univariable or multivariable analysis in this population. During the study period, 472 patients died, representing 20%, 24%, 36%, and 25% with VTE‐RS 1, 2, ≥3, or unknown, respectively (p < .0001). Significant independent predictors of early mortality include older age, current/former smoking, chronic obstructive pulmonary disease, Eastern Cooperative Oncology Group performance status ≥2, no prior surgery, and metastatic disease, as well as the VTE‐RS.
Conclusion
In this global, prospective, real‐world analysis, several demographic, geographic, and clinical factors are independent risk factors for VTE and early mortality in patients with lung cancer. The VTE‐RS represents a significant independent predictor of early mortality but not for VTE in lung cancer in the era of targeted therapy.
Implications for Practice
Multiple risk factors for both venous thromboembolism (VTE) and early mortality in patients with lung cancer receiving systemic chemotherapy should guide best practice by better informing clinical evaluation and treatment decision‐making. The Khorana risk score is of value in assessing the risk of early all‐cause mortality along with other clinical parameters in patients with lung cancer receiving systemic therapy. Further study is needed to fully evaluate the validity of the risk score in predicting the risk of VTE in the modern era of lung cancer therapy.
This article provides a comprehensive assessment of patient and clinical characteristics associated with the occurrence of venous thromboembolism and early all‐cause mortality in a large, international, prospective cohort of real‐world patients with lung cancer receiving systemic cancer therapy.
Background.
Retrospective studies have suggested an association between cancer‐associated venous thromboembolism (VTE) and patient survival. We evaluated a previously validated VTE Clinical Risk ...Score in also predicting early mortality and cancer progression.
Methods.
A large, nationwide, prospective cohort study of adults with solid tumors or lymphoma initiating chemotherapy was conducted from 2002 to 2006 at 115 U.S. practice sites. Survival and cancer progression were estimated by the method of Kaplan and Meier. Multivariate analysis was based on Cox regression analysis adjusted for major prognostic factors including VTE itself.
Results.
Of 4,405 patients, 134 (3.0%) died and 330 (7.5%) experienced disease progression during the first 4 months of therapy (median follow‐up 75 days). Patients deemed high risk (n = 540, 12.3%) by the Clinical Risk Score had a 120‐day mortality rate of 12.7% (adjusted hazard ratio aHR 3.00, 95% confidence interval CI 1.4–6.3), and intermediate‐risk patients (n = 2,665, 60.5%) had a mortality rate of 5.9% (aHR 2.3, 95% CI 1.2–4.4) compared with only 1.4% for low‐risk patients (n = 1,200, 27.2%). At 120 days of follow‐up, cancer progression occurred in 27.2% of high‐risk patients (aHR 2.2, 95% CI 1.4–3.5) and 16.4% of intermediate‐risk patients (aHR 1.9, 95% CI 1.3–2.7) compared with only 8.5% of low‐risk patients (p < .0001).
Conclusion.
The Clinical Risk Score, originally developed to predict the occurrence of VTE, is also predictive of early mortality and cancer progression during the first four cycles of outpatient chemotherapy, independent from other major prognostic factors including VTE itself. Ongoing and future studies will help determine the impact of VTE prophylaxis on survival.
Implications for Practice:
The risk of venous thromboembolism (VTE) is increased in patients receiving cancer chemotherapy. In this article, the authors demonstrate that a popular risk score for VTE in patients with cancer is also associated with the risk of early mortality in this setting. It is important that clinicians evaluate the risk of VTE in patients receiving cancer treatment and discuss the risk and associated symptoms of VTE with patients. Individuals at increased risk should be advised that VTE is a medical emergency and should be urgently diagnosed and appropriately treated to reduce the risk of serious and life‐threatening complications.
The authors applied the previously validated venous thromboembolism Clinical Risk Score to 4,405 adults with solid tumors or lymphoma initiating chemotherapy. Risk scores were predictive of early mortality and cancer progression during the first four cycles of outpatient chemotherapy. High‐risk patients had 120‐day mortality rates of 12.7% and cancer progression rates of 27.2%; intermediate‐risk patients, 5.9% and 16.4%, respectively; and low‐risk patients, 1.4% and 8.5%.
Frailty is associated with an increased risk of chemotherapy toxicity. Cellular markers of inflammation can help identify patients with frailty characteristics. However, the role of cellular markers ...of inflammation in identifying patients at risk of developing chemotherapy-induced frailty and their clinical utility are not fully understood.
This study was a secondary analysis of a large nationwide cohort study of women with stage I-IIIC breast cancer (n = 581, mean age 53.4; range 22-81). Measures were completed pre-chemotherapy (T1), post-chemotherapy (T2), and 6 months post-chemotherapy (T3). Frailty was assessed at all three time points using a modified Fried score consisting of four self-reported measures (weakness, exhaustion, physical activity, and walking speed; 0-4, 1 point for each). Immune cell counts as well as neutrophil to lymphocyte ratio (NLR) and lymphocyte to monocyte ratio (LMR) were obtained at T1 and T2 time points. Separate linear regressions were used to evaluate the associations of (1) cell counts at T1 with frailty at T1, T2, and T3 and (2) change in cell counts (T2-T1) with frailty at T2 and T3. We controlled for relevant covariates and frailty at the T1 time point.
From T1 to T2, the mean frailty score increased (1.3 vs 2.0; p < 0.01) and returned to T1 levels by the T3 time point (1.3 vs 1.3; p = 0.85). At the T1 time point, there was a positive association between cellular markers of inflammation and frailty: WBC (β = 0.04; p < 0.05), neutrophils (β = 0.04; p < 0.05), and NLR (β = 0.04; p < 0.01). From T1 to T2, a greater increase in cellular markers of inflammation was associated with frailty at T2 (WBC: β = 0.02, p < 0.05; neutrophils: β = 0.03, p < 0.05; NLR: β = 0.03; p < 0.01). These associations remained significant after controlling for the receipt of growth factors with chemotherapy and the time between when laboratory data was provided and the start or end of chemotherapy.
In patients with breast cancer undergoing chemotherapy, cellular markers of inflammation are associated with frailty. Immune cell counts may help clinicians identify patients at risk of frailty during chemotherapy.
ClinicalTrials.gov , NCT01382082.
Purpose
Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting side effect of taxane and platinum chemotherapy for breast cancer. Clinicians cannot accurately predict CIPN ...severity partly because its pathophysiology is poorly understood. Although inflammation may play a role in CIPN, there are limited human studies. Here, we identified the strongest predictors of CIPN using variables measured before taxane- or platinum-based chemotherapy, including serum inflammatory markers.
Methods
116 sedentary women with breast cancer (mean age 55 years) rated (1) numbness and tingling and (2) hot/coldness in hands/feet on 0–10 scales before and after 6 weeks of taxane- or platinum-based chemotherapy. A sub-study was added to collect cytokine data in the final 55 patients. We examined all linear models to predict CIPN severity at 6 weeks using pre-chemotherapy assessments of inflammatory, behavioral, clinical, and psychosocial factors. The final model was selected via goodness of fit.
Results
The strongest pre-chemotherapy predictors of numbness and tingling were worse fatigue/anxiety/depression (explaining 27% of variance), older age (9%), and baseline neuropathy (5%). The strongest predictors of hot/coldness in hands/feet were worse baseline neuropathy (11%) and fatigue/anxiety/depression (6%). Inflammation was a risk for CIPN, per more pro-inflammatory IFN-γ (12%) and IL-1β (6%) and less anti-inflammatory IL-10 (6%) predicting numbness/tingling and more IFN-γ (17%) and less IL-10 (9%) predicting hot/coldness in hands/feet.
Conclusions
The strongest pre-chemotherapy predictors of CIPN included worse fatigue/anxiety/depression and baseline neuropathy. A pro-inflammatory state also predicted CIPN. Because this is an exploratory study, these results suggest specific outcomes (e.g., IL-1β) and effect size estimates for designing replication and extension studies.
Clinical trial registration
: NCT00924651.
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