Risk Score For Venous Thromboembolism (VTE) In Ambulatory Patients: Impact Of Cancer Type and Risk Score On VTE Incidence, Early Mortality and Progression-Free Survival

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3597-3597
Author(s):  
Nicole M. Kuderer ◽  
Alok A. Khorana ◽  
Charles Francis ◽  
Eva Culakova ◽  
Gary H. Lyman

Abstract Background While ambulatory patients receiving cancer chemotherapy are at increased risk for venous thromboembolism (VTE), current guidelines do not recommend routine thromboprophylaxis with a few notable exceptions (Lyman, Khorana et al, J Clin Oncol 2013). A previously validated VTE risk score for cancer outpatients stratifies patients into low (0), intermediate (1-2), or high (>=3) risk categories (Khorana, Kuderer et al, Blood 2008). Understanding cancer types at greatest risk for VTE as well as early mortality and progression based on the risk score provides key clinical understanding. Methods A prospective cohort study was conducted of consenting solid tumor and lymphoma patients initiating a new chemotherapy regimen at 115 randomly selected US oncology practices between 2002 – 2006 by the ANC Study Group. VTE incidence, progression-free survival (PFS), and all-cause mortality over the first 120 days (early mortality) of ambulatory chemotherapy were estimated based on the method of Kaplan and Meier. Results Among 4,458 patients initiating a new chemotherapy regimen, 93 (2.1%) developed a symptomatic VTE within 120 days of chemotherapy. The risk of VTE across cancer types increased from 0.6%, to 1.8% to 6.6% in low-, intermediate- and high-risk categories, respectively. The risk of VTE among low risk patients was 1% or less across all cancer types. However, the risk of VTE was highest among intermediate- and high-risk categories in patients with breast, colorectal, and lung cancer, reaching 16% for high risk breast cancer patients. Early all-cause mortality occurred in 136 patients (3.1%) and also increased with increasing risk score from 0.8% to 3.4% to 6.4% in low-, intermediate- and high-risk categories, respectively. The risk of early mortality was 2.1% or less in low risk patients across all cancer types. However, the risk of early mortality was highest among high-risk category patients, reaching 23% and 14% in colorectal cancer patients and pancreatic or gastric cancer patients, respectively. PFS decreased from 92% to 82% to 72% across the three risk categories, with lowest rates of PFS among colorectal (52%) and lung cancer (52%) patients. Conclusions VTE incidence and all-cause mortality increase and PFS correspondingly decreases with increasing VTE risk score across major solid tumors. Interestingly, while breast cancer is not considered a high risk tumor for VTE, breast cancer patients with a risk score of >=3 had the highest VTE incidence compared to other major solid tumor types. Among patients with a risk score of >=3, gastrointestinal cancer patients had the greatest risk of early mortality and correspondingly, the lowest PFS compared to other major solid tumors. These findings also suggest that both the mortality risk as well as the VTE risk are only partially influenced by tumor type. Funding: 1KM1-CA156687-01 (NK), ASCO Young Investigator Award (NK), NHLBI-1R01HL095109 (all), ANC Study Group (GL), and K23 CA120587 (AK). Disclosures: No relevant conflicts of interest to declare.

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xuan Li ◽  
Hefen Sun ◽  
Qiqi Liu ◽  
Yang Liu ◽  
Yifeng Hou ◽  
...  

Abstract Background Distance metastasis is the leading cause of death for breast cancer patients, and circulating tumor cells (CTCs) play a key role in cancer metastasis. There have been few studies on CTCs at the molecular level due to their rarity, and the heterogeneity of CTCs may provide special information for solid tumor analysis. Methods In this study, we used the gene expression and clinical information of single-cell RNA-seq data of CTCs of breast cancer and discovered a cluster of epithelial cells that had more aggressive characteristics. The differentially expressed genes (DEGs) between the identified epithelial cells cluster and others from single-CTCs were selected for further analysis in bulk sequence data of solid breast cancers. Results Eighteen genes closely related to the specific CTC epithelial phenotype and breast cancer patient prognosis were identified. Among these 18 genes, we selected the GARS gene, which has not been studied in breast cancer, for functional research and confirmed that it may be a potential oncogene in breast cancer. A risk score was established by the 18 genes, and a high-risk score was strongly associated with a high metastasis rate and poor survival prognosis in breast cancer. The high-risk score group was related to a defective immune infiltration environment in breast cancer, and the immune checkpoint therapy response rate was lower in this group. The drug-sensitive analysis shows that the high-risk score patients may be more sensitive to AKT-mTOR and the cyclin-dependent kinase (CDK) pathways drugs than low-risk score patients. Conclusions Our 18-gene risk score shows good prognostic and predictive values and might be a personalized prognostic marker or therapy guide marker in breast cancer patients.


Author(s):  
Menha Swellam ◽  
Hekmat M EL Magdoub ◽  
May A Shawki ◽  
Marwa Adel ◽  
Mona M Hefny ◽  
...  

1996 ◽  
Vol 32 (1) ◽  
pp. 41-46 ◽  
Author(s):  
F. Perrone ◽  
C. Carlomagno ◽  
R. Lauria ◽  
M. De Laurentiis ◽  
A. Morabito ◽  
...  

2021 ◽  
Vol 12 ◽  
Author(s):  
Mengdi Chen ◽  
Deyue Liu ◽  
Weilin Chen ◽  
Weiguo Chen ◽  
Kunwei Shen ◽  
...  

BackgroundThe 21-gene assay recurrence score (RS) provides additional information on recurrence risk of breast cancer patients and prediction of chemotherapy benefit. Previous studies that examined the contribution of the individual genes and gene modules of RS were conducted mostly in postmenopausal patients. We aimed to evaluate the gene modules of RS in patients of different ages.MethodsA total of 1,078 estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients diagnosed between January 2009 and March 2017 from Shanghai Jiao Tong University Breast Cancer Data Base were included. All patients were divided into three subgroups: Group A, ≤40 years and premenopausal (n = 97); Group B, >40 years and premenopausal (n = 284); Group C, postmenopausal (n = 697). The estrogen, proliferation, invasion, and HER2 module scores from RS were used to characterize the respective molecular features. Spearman correlation and analysis of the variance tests were conducted for RS and its constituent modules.ResultsIn patients >40 years, RS had a strong negative correlation with its estrogen module (ρ = −0.76 and −0.79 in Groups B and C) and a weak positive correlation with its invasion module (ρ = 0.29 and 0.25 in Groups B and C). The proliferation module mostly contributed to the variance in young patients (37.3%) while the ER module contributed most in old patients (54.1% and 53.4% in Groups B and C). In the genetic high-risk (RS >25) group, the proliferation module was the leading driver in all patients (ρ = 0.38, 0.53, and 0.52 in Groups A, B, and C) while the estrogen module had a weaker correlation with RS. The impact of ER module on RS was stronger in clinical low-risk patients while the effect of the proliferation module was stronger in clinical high-risk patients. The association between the RS and estrogen module was weaker among younger patients, especially in genetic low-risk patients.ConclusionsRS was primarily driven by the estrogen module regardless of age, but the proliferation module had a stronger impact on RS in younger patients. The impact of modules varied in patients with different genetic and clinical risks.


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