scholarly journals A Comprehensive Risk Assessment Model for Ovarian Cancer Patients with Phospho-STAT3 and IL-31 as Immune Infiltration Relevant Genes

2020 ◽  
Vol Volume 13 ◽  
pp. 5617-5628
Author(s):  
Xue Wang ◽  
Fei-kai Lin ◽  
Jia-rui Li ◽  
Hu-sheng Wang
2021 ◽  
Author(s):  
Federico Nichetti ◽  
Francesca Ligorio ◽  
Giulia Montelatici ◽  
Luca Porcu ◽  
Emma Zattarin ◽  
...  

Abstract Background: Hospitalized cancer patients are at increased risk for Thromboembolic Events (TEs). As untailored thromboprophylaxis is associated with hemorrhagic complications, the definition of a risk-assessment model (RAM) in this population is needed. Objectives: INDICATE was an observational study enrolling hospitalized cancer patients, with the primary objective of assessing the Negative Predictive Value (NPV) for TEs during hospitalization and within 45 days from discharge of low-grade Khorana Score (KS=0). Secondary objectives were to assess KS Positive Predictive Value (PPV), the impact of TEs on survival and the development of a new RAM. Materials and Methods: Assuming 7% of TEs in KS=0 patients as unsatisfactory percentage and 3% of as satisfactory, 149 patients were needed to detect the favorable NPV with one-sided a= 0.10 and power=0.80. Stepwise logistic regression was adopted to identify variables included in a new RAM.Results: Among 535 enrolled patients, 153 (28.6%) had a KS=0. The primary study objective was met: 29 (5.4%) TEs were diagnosed, with 7 (4.6%) cases in the KS=0 group (NPV=95.4%, 95%CI: 90.8-98.1%; one-sided p=0.084). However, the PPV was low (5.7%, 95%CI: 1.9-12.8%); a new RAM based on albumin (OR 0.34, p=0.003), log(LDH) (OR 1.89, p=0.023) and presence of vascular compression (OR 5.32, p<.001) was developed and internally validated. Also, TEs were associated with poorer OS (median, 5.7 vs 24.8 months, p <.001).Conclusion: INDICATE showed that the KS has a good NPV but poor PPV for TEs in hospitalized cancer patients. A new RAM was developed, and deserves further assessment in external cohorts.


Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2426-2426
Author(s):  
Anna Falanga ◽  
Cinzia Giaccherini ◽  
Marina Marchetti ◽  
Giovanna Masci ◽  
Cristina Verzeroli ◽  
...  

Background. Hypercoagulability, a common finding in cancer patients, is associated with an increased risk of both thrombosis and tumor development. The HYPERCAN study (ClinicalTrials.gov, ID# NCT02622815) is an ongoing Italian prospective, multicenter, observational study, evaluating the predictive value of thrombotic markers for early cancer diagnosis in healthy subjects and for cancer prognosis and venous thromboembolism in patients with newly diagnosed malignant disease. In this analysis of a large cohort of patients with breast cancer, we evaluated whether pre-chemotherapy thrombotic biomarker levels: 1. are associated with breast cancer-specific clinicopathological features; and 2. may predict for disease recurrence (DR). Patients and Methods. D-dimer, fibrinogen, prothrombin fragment 1+2 (F1+2), and FVIIa/antithrombin complex (FVIIa/AT) levels were measured in 701 early-stage resected breast cancer patients, candidate to adjuvant chemotherapy and prospectively enrolled in the HYPERCAN study. Significant prognostic parameters for DR were identified by Cox-regression multivariate analysis and used for generating a risk assessment model. The study protocol is approved by the local Ethics Committee. Informed written consent is obtained from all study subjects. Results. Increased pre-chemotherapy D-dimer, fibrinogen, and F1+2 levels were significantly associated with a large tumor size (≥ 5 cm) and lymph node positivity. After 3.4 years follow-up, 71 patients experienced a DR. Comparison of the levels of the hypercoagulation variables of patients who experienced relapse versus patients who remained disease-free during follow-up showed that there were no statistical differences for all, but F1+2 biomarker levels, which were significantly higher in the group patients who relapsed [223 (115-618) vs 197 (115-385) pmol/l; p=0.024]. In addition, correlation analyses showed that pre-chemotherapy levels of fibrinogen were significantly and inversely associated with time to relapse (β = -0.317; p=0.012). Cox-multivariate analysis identified F1+2 (HR 2; 95% CI, 1.1-3.6; p=0.019), tumor size ≥ 5cm (HR 2.6; 95% CI, 1.4-4.6; p=0.001), and Luminal B HER2-neg or TN molecular subtypes (HR 3.9; 95% CI, 2.1-7.5; p<0.001) as independent risk factors for DR. Based on these variables, we generated a risk assessment model that significantly identified patients at low- versus high-risk of DR (cumulative incidence: 6.2 vs 20.7%; HR=3.5; p<0.001). Conclusion. Our prospective laboratory data from the HYPERCAN breast cancer subjects were essential for generating a scoring model for DR risk assessment. Future investigations addressing the role of plasma thrombotic biomarkers in breast cancer patients' management are warranted and may provide the rationale for development of new therapeutic strategies. Project funded by AIRC "5xMILLE Multiunit extension program" n. 12237 grant from the "Italian Association for Cancer Research (AIRC)". Disclosures Santoro: Bayer: Consultancy, Speakers Bureau; Amgen: Speakers Bureau; BMS: Consultancy; Sandoz: Speakers Bureau; Eisai: Consultancy, Speakers Bureau; Novartis: Speakers Bureau; Lilly: Speakers Bureau; Celgene: Speakers Bureau; Servier: Consultancy, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; AstraZeneca: Speakers Bureau; Roche: Speakers Bureau; Abb-Vie: Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; Arqule: Consultancy, Speakers Bureau; MSD: Speakers Bureau; Takeda: Speakers Bureau; BMS: Speakers Bureau.


2021 ◽  
Vol 200 ◽  
pp. S63
Author(s):  
F. Nichetti ◽  
G. Montelatici ◽  
L. Provenzano ◽  
A. Franza ◽  
L. Porcu ◽  
...  

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1181-1181 ◽  
Author(s):  
Dana E. Angelini ◽  
M. Todd Greene ◽  
Julie N Wietzke ◽  
Scott A Flanders ◽  
Suman L. Sood

Abstract Background Current guidelines recommend all cancer inpatients receive pharmacologic VTE prophylaxis in the absence of contraindications. This is extrapolated from trials showing the benefit of VTE prophylaxis in general medical inpatients and the known increased risk of VTE in cancer patients. However, given the increased risk of bleeding in cancer patients on anticoagulation (AC), it is vital to better define a subpopulation of cancer inpatients who most benefit from VTE prophylaxis. Current inpatient VTE risk models, including Padua, Caprini and IMPROVE, contain cancer as a variable and thus are not discriminative among cancer patients. Although the Khorana score (KS) stratifies VTE risk by cancer type, it was originally derived for cancer outpatients, and has yet to be validated for inpatients. Using a large multi-center cohort, we developed a novel VTE risk assessment model (RAM) specific to cancer inpatients, the CANclot score. Methods The Michigan Hospital Medicine Safety Consortium, a 49 hospital collaborative, established a multicenter retrospective cohort of medical inpatients > 18 years of age. Exclusion criteria include surgical patients, pregnancy, admission to the ICU or for palliative care, therapeutic AC, diagnosis of acute VTE, history of VTE within 6 months, and length of stay < 2 days. Patient demographics, clinical characteristics, and VTE events (both hospital associated and 90 day post discharge) were recorded. The CANclot risk assessment model was derived from logistic regression analyses of an apriori list of risk factors. Significant risk factors included in the CANclot scale were weighted based on the respective odds ratio estimates and an optimal cut-off was chosen. Model discrimination of the CANclot score was compared with other published risk models. Results Between 7/2012-7/2015, 18,956 cancer admissions were included. 2,464 (13%) had a pre-defined contraindication to prophylaxis (active bleed within 3 months, coagulopathy, or high risk brain metastasis). Of all admissions, 52.8% received VTE prophylaxis. A total of 327 (1.7%) VTE events were observed; 51/327 (15.6%) VTE events occurred during admission and 276/327 (84.4%) within 90 day f/u. When comparing AUC's of different risk models, CANclot ≥ 3 was superior to Padua ≥ 4 (p=0.01), Caprini ≥ 5 (p=0.01) and IMPROVE ≥ 2 (p=0.02). In our dataset 4,695 (25%) of patients had a CANclot score ≥ 3. Conclusion: The CANclot score is a novel VTE risk assessment tool derived specifically for cancer inpatients. Compared to other published risk prediction tools used in the general population, CANclot ≥ 3 shows an improved predictive ability for VTE and good yield, applying to 25% of the population. Improving VTE prediction in hospitalized cancer patients is crucial because targeting only those at highest risk may spare low risk patients from untoward bleeding complications from AC. Additionally, we found the majority of VTE events occurred during the 90 day followup period which calls for further attention to the possible need for extended prophylaxis in this population. Limitations to our study include a low overall rate of VTE, lack of some cancer specific variables, and that risk score values have not yet been corrected for optimism. The CANclot VTE risk score is a promising new tool for cancer inpatients that warrants further validation. 1 Patell R et al. JCO 34, 2016 (suppl; abstr 6598) Disclosures Flanders: Blue Cross Blue Shield: Research Funding; Wiley Publishing: Patents & Royalties. Sood:Bayer: Research Funding.


2010 ◽  
Vol 151 (34) ◽  
pp. 1365-1374 ◽  
Author(s):  
Marianna Dávid ◽  
Hajna Losonczy ◽  
Miklós Udvardy ◽  
Zoltán Boda ◽  
György Blaskó ◽  
...  

A kórházban kezelt sebészeti és belgyógyászati betegekben jelentős a vénásthromboembolia-rizikó. Profilaxis nélkül, a műtét típusától függően, a sebészeti beavatkozások kapcsán a betegek 15–60%-ában alakul ki mélyvénás trombózis vagy tüdőembólia, és az utóbbi ma is vezető kórházi halálok. Bár a vénás thromboemboliát leggyakrabban a közelmúltban végzett műtéttel vagy traumával hozzák kapcsolatba, a szimptómás thromboemboliás események 50–70%-a és a fatális tüdőembóliák 70–80%-a nem a sebészeti betegekben alakul ki. Nemzetközi és hazai felmérések alapján a nagy kockázattal rendelkező sebészeti betegek többsége megkapja a szükséges trombózisprofilaxist. Azonban profilaxis nélkül marad a rizikóval rendelkező belgyógyászati betegek jelentős része, a konszenzuson alapuló nemzetközi és hazai irányelvi ajánlások ellenére. A belgyógyászati betegek körében növelni kell a profilaxisban részesülők arányát és el kell érni, hogy trombózisrizikó esetén a betegek megkapják a hatásos megelőzést. A beteg trombóziskockázatának felmérése fontos eszköze a vénás thromboembolia által veszélyeztetett betegek felderítésének, megkönnyíti a döntést a profilaxis elrendeléséről és javítja az irányelvi ajánlások betartását. A trombózisveszély megállapításakor, ha nem ellenjavallt, profilaxist kell alkalmazni. „A thromboemboliák kockázatának csökkentése és kezelése” című, 4. magyar antithromboticus irányelv felhívja a figyelmet a vénástrombózis-rizikó felmérésének szükségességére, és elsőként tartalmazza a kórházban fekvő belgyógyászati és sebészeti betegek kockázati kérdőívét. Ismertetjük a kockázatbecslő kérdőíveket és áttekintjük a kérdőívekben szereplő rizikófaktorokra vonatkozó bizonyítékokon alapuló adatokat.


Author(s):  
C.K. Lakshminarayan ◽  
S. Pabbisetty ◽  
O. Adams ◽  
F. Pires ◽  
M. Thomas ◽  
...  

Abstract This paper deals with the basic concepts of Signature Analysis and the application of statistical models for its implementation. It develops a scheme for computing sample sizes when the failures are random. It also introduces statistical models that comprehend correlations among failures that fail due to the same failure mechanism. The idea of correlation is important because semiconductor chips are processed in batches. Also any risk assessment model should comprehend correlations over time. The statistical models developed will provide the required sample sizes for the Failure Analysis lab to state "We are A% confident that B% of future parts will fail due to the same signature." The paper provides tables and graphs for the evaluation of such a risk assessment. The implementation of Signature Analysis will achieve the dual objective of improved customer satisfaction and reduced cycle time. This paper will also highlight it's applicability as well as the essential elements that need to be in place for it to be effective. Different examples have been illustrated of how the concept is being used by Failure Analysis Operations (FA) and Customer Quality and Reliability Engineering groups.


2013 ◽  
Vol 19 (3) ◽  
pp. 521-527 ◽  
Author(s):  
Song YANG ◽  
Shuqin WU ◽  
Ningqiu LI ◽  
Cunbin SHI ◽  
Guocheng DENG ◽  
...  

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