A multi-gene assay to predict long-term mortality in early stage lung adenocarcinoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7569-7569
Author(s):  
D. J. Raz ◽  
J. Y. Kim ◽  
M. R. Ray ◽  
D. M. Jablons
Keyword(s):  
High Risk ◽  
Lung Adenocarcinoma ◽  
Risk Group ◽  
Early Stage ◽  
Prognostic Score ◽  
Clinical Stage ◽  
Low Risk ◽  
Gene Assay ◽  
Long Term Mortality

7569 Background: The likelihood of long-term mortality for patients with early stage lung adenocarcinoma is poorly defined by clinical stage and histopathological findings. Our hypothesis was that a multigene quantitative polymerase chain reaction (PCR) assay can predict risk of mortality among patients with early stage lung adenocarcinoma. Methods: We identified 65 genes that were previously identified as prognostic for long-term mortality in early stage lung cancer in 3 published microarray studies and 2 PCR-based studies. RNA was extracted from 124 fresh-frozen tumor samples from consecutive patients with completely resected lung adenocarcinoma with at least 3 years of clinical follow-up. 80 samples were randomly assigned to a test group and the remainder assigned to a validation group. Real-time PCR of the 65 identified genes were run on the test set using Taq-man assays. A prediction model was created using a proportional hazards model of normalized gene expression levels using backwards model selection. A model score was calculated for each patient using model coefficients and individual gene expression levels. Patients were defined as high-risk if the model score was greater than the median score. Results: Adequate real-time PCR profiles were identified in all 80 patients. Eighteen genes were included in the final model. The proportion of patients identified as high-risk and low-risk was 52% and 48% percent, respectively. The Kaplan-Meier estimated five-year survival in the low-risk group was 82% and 5% in the high-risk group (P<0.001, log-rank test). Median survival was 22 months in the high-risk group and was not reached in the low-risk group. In multivariate survival analysis, the prognostic score predicted survival independent of tumor stage and size (P<0.001). Prognostic score predicted mortality better than clinical stage, based on model log-likelihood values (P<0.001). Conclusions: This multi- gene assay aids in predicting long-term mortality among patients with surgically resected early stage lung adenocarcinoma. We are currently validating this model in our test set of samples. No significant financial relationships to disclose.

P5730Do hypertensive women with coronary artery disease benefit from lowering systolic blood pressure under 130 mmHg? Long-term mortality in the INternational VErapamil SR-trandolapril STudy (INVEST)

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
R I Sava ◽  
Y Chen ◽  
Y K Taha ◽  
Y Gong ◽  
S M Smith ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Blood Pressure ◽  
Coronary Artery Disease ◽  
High Risk ◽  
Risk Group ◽  
Low Risk ◽  
High Risk Women ◽  
Artery Disease ◽  
Long Term Mortality

Abstract Background Hypertension (HTN) and coronary artery disease (CAD) are a prevalent combination in women, however limited data are available to guide blood pressure (BP) management. We hypothesize older women with HTN and CAD may not derive the same prognostic benefit from systolic BP (SBP) lowering <130 mmHg. Purpose To investigate the long-term mortality implications of different achieved SBP levels in hypertensive women with CAD. Methods Long-term, all-cause mortality data were analyzed for 9216 women, stratified by risk attributable to clinical severity of CAD (women with prior myocardial infarction or revascularization considered at high, all others at low risk) and by age (50 - <65 or ≥65 yo). The prognostic impact of achieving mean in-trial SBP <130 (referent group) was compared with 130 to <140 and ≥140 mmHg using Cox proportional hazards, adjusting for demographic and clinical characteristics. Results During 108,838 person-years of follow-up, 2945 deaths occurred. High risk women (n=3011) had increased long-term mortality in comparison to low risk women (n=6205) (adjusted HR 1.38, CI 1.28–1.5, p<0.001). Within risk groups, crude mortality percentages decreased according to BP values (table). As expected, high risk women were more likely to be ≥65 yo (68.68% vs. 50.51%, p<0.0001) or have SBP ≥140 mmHg (43.08% vs. 31.18%, p<0.0001). In adjusted analyses, an SBP ≥140 mmHg was associated with worse outcomes than SBP <130 mmHg in the entire cohort (HR 1.3, CI 1.2–1.5, p<0.0001) and when stratifying by risk (low risk group, HR = 1.47, CI 1.28–1.7, p<0.0001; high risk group, HR = 1.71, CI 1.01–1.35, p=0.03). In analyses stratified by age and risk, women ≥65 years and at high risk had decreased mortality in the 130 - <140 SBP category vs. <130 mmHg (HR 0.812, 95% CI 0.689–0.957, p=0.0133; figure). Women and deaths by risk and SBP group Group SBP category Women (n) Mortality (n) Mortality (%) High risk <130 773 338 44 130–<140 941 414 44 ≥140 1297 694 54 Low risk <130 2187 390 18 130–<140 2083 451 22 ≥140 1935 658 34 SBP = systolic blood pressure; n = number; % = percent per each group. Mortality adjusted HRs Conclusion In women ≥65 yo with hypertension and prior myocardial infarction and/or coronary revascularization enrolled in INVEST, a SBP between 130 to <140 mmHg was associated with lower all-cause, long-term mortality versus SBP <130 mmHg. Acknowledgement/Funding The main INVEST (International Verapamil [SR]/Trandolapril Study) was funded by grants from BASF Pharma, Ludwigshafen, Germany; Abbott Laboratories, A

Construction and validation of an eight-gene risk prediction model for stage II-IIIA lung adenocarcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e20553-e20553
Author(s):  
Jianchun Duan ◽  
Hua Bai ◽  
Yiting Sun ◽  
Fei Gai ◽  
Shenya Tian ◽  
...  
Keyword(s):  
High Risk ◽  
Prediction Model ◽  
Lung Adenocarcinoma ◽  
Risk Prediction ◽  
Risk Group ◽  
Survival Outcome ◽  
Risk Prediction Model ◽  
Low Risk ◽  
Gene Set

e20553 Background: Clinical characters cannot precisely evaluate long-term survival of patients with resectable lung adenocarcinoma. Genomics studies of lung adenocarcinoma (LUAD) have advanced our understanding of LUAD's biology. Thus, genomics-based robust models predicting survival outcome for patients with operatable LUAD needs to be investigated. Here, we aimed to identify new gene signatures to construct a risk prediction model via integrating Omics data from The Cancer Genome Atlas (TCGA) to better evaluate the long-term clinical outcome of LUAD patients. Methods: A cohort of one hundred and eighty-nine stage II-IIIA lung adenocarcinoma cases receiving tumor resection were screened out and downloaded from TCGA database. Tumor samples without survival information and genes with low or no expression were removed. Genes associated with cancer and immune were further narrowed down using a Master Panel Gene Set (Amoydx). Lasso-Cox regression analysis was used to screen gene-survival outcome, and then a risk prediction model was established. LUAD cases were divided into high-risk or low-risk groups as per the scores, to assess differential expressed genes and pathways. Results: A total of 8 most survival outcome related genes (CLEC7A, PAX5, XCR1, KRT7, PLCG1, DKK1, CLEC10A, IKZF3) were identified after Lasso-Cox regression analysis and used for model construction. The overall survival (OS), progression-free survival (PFS) and disease-free survival (DFS) from the subgroups within the high- and low-risk groups were assessed and showed significant prolonged in low-risk group, the hazard ratio (HR) of OS was 2.72 (95%CI: 2.04-3.61, P = 5.91e-12) in high-risk group. Hierarchical clustering analysis, gene ontology (GO) analysis, gene set enrichment analysis (GSEA), and gene set variation analysis (GSVA) revealed that genes involved in immune responses were significantly suppressed in high-risk group, while as genes involved in antioxidative metabolism were activated, which gave us a hint that immune-metabolism interaction might play a vital role in determining the distal survival outcome of LUAD. Conclusions: Our risk prediction model enables precise evaluation of long-term survival for patients with LUAD. Further, it provides a novel and comprehensive understanding of biological impacts on LUAD prognosis, which offers new insights for future development of precise diagnostic and therapeutic approaches.[Table: see text]

scholarly journals Identification of prognostic gene signature associated with microenvironment of lung adenocarcinoma

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e8128 ◽  
Author(s):  
Cheng Yue ◽  
Hongtao Ma ◽  
Yubai Zhou
Keyword(s):  
High Risk ◽  
Lung Adenocarcinoma ◽  
Prognostic Model ◽  
Cox Regression ◽  
Risk Group ◽  
Expression Profiles ◽  
Gene Signature ◽  
Low Risk ◽  
Differentially Expressed ◽  
Lasso Regression

Background Lung cancer has the highest morbidity and mortality worldwide, and lung adenocarcinoma (LADC) is the most common pathological subtype. Accumulating evidence suggests the tumor microenvironment (TME) is correlated with the tumor progress and the patient’s outcome. As the major components of TME, the tumor-infiltrated immune cells and stromal cells have attracted more and more attention. In this study, differentially expressed immune and stromal signature genes were used to construct a TME-related prognostic model for predicting the outcomes of LADC patients. Methods The expression profiles of LADC samples with clinical information were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). The differentially expressed genes (DEGs) related to the TME of LADC were identified using TCGA dataset by Wilcoxon rank sum test. The prognostic effects of TME-related DEGs were analyzed using univariate Cox regression. Then, the least absolute shrinkage and selection operator (LASSO) regression was performed to reduce the overfit and the number of genes for further analysis. Next, the prognostic model was constructed by step multivariate Cox regression and risk score of each sample was calculated. Then, survival and Receiver Operating Characteristic (ROC) analyses were conducted to validate the model using TCGA and GEO datasets, respectively. The Kyoto Encyclopedia of Genes and Genomes analysis of gene signature was performed using Gene Set Enrichment Analysis (GSEA). Finally, the overall immune status, tumor purity and the expression profiles of HLA genes of high- and low-risk samples was further analyzed to reveal the potential mechanisms of prognostic effects of the model. Results A total of 93 TME-related DEGs were identified, of which 23 DEGs were up-regulated and 70 DEGs were down-regulated. The univariate cox analysis indicated that 23 DEGs has the prognostic effects, the hazard ratio ranged from 0.65 to 1.25 (p < 0.05). Then, seven genes were screened out from the 23 DEGs by LASSO regression method and were further analyzed by step multivariate Cox regression. Finally, a three-gene (ADAM12, Bruton Tyrosine Kinase (BTK), ERG) signature was constructed, and ADAM12, BTK can be used as independent prognostic factors. The three-gene signature well stratified the LADC patients in both training (TCGA) and testing (GEO) datasets as high-risk and low-risk groups, the 3-year area under curve (AUC) of ROC curves of three GEO sets were 0.718 (GSE3141), 0.646 (GSE30219) and 0.643 (GSE50081). The GSEA analysis indicated that highly expressed ADAM12, BTK, ERG mainly correlated with the activation of pathways involving in focal adhesion, immune regulation. The immune analysis indicated that the low-risk group has more immune activities and higher expression of HLA genes than that of the high-risk group. In sum, we identified and constructed a three TME-related DEGs signature, which could be used to predict the prognosis of LADC patients.

Abstract TP387: Abcd 2 Score Predicts The Long-term Risk Of Stroke After Transient Ischemic Attack: Fukuoka Stroke Registry

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Yasuhiro Kumai ◽  
Takuya Kiyohara ◽  
Masahiro Kamouchi ◽  
Sohei Yoshimura ◽  
Hiroshi Sugimori ◽  
...  
Keyword(s):  
High Risk ◽  
Transient Ischemic Attack ◽  
Risk Group ◽  
High Risk Group ◽  
Low Risk ◽  
Rank Test ◽  
Moderate Risk ◽  
Stroke Registry ◽  
Ischemic Attack

Background and Purpose— ABCD 2 score has been developed to predict the early risk of stroke after transient ischemic attack (TIA). The aim of this study was to clarify whether ABCD 2 score predicts the occurrence of stroke in the long term after TIA. Methods— Fukuoka Stroke Registry (FSR) is a multicenter epidemiological study database on acute stoke. From June 2007 to June 2011, 496 (305 males, 70 ± 13 years of age) patients who had suffered from TIA and were hospitalized in the 7 stroke centers within 7 days after the onset of TIA were enrolled in this study. The patients were divided into three groups according to the risk: low-risk (ABCD 2 score 0-3; n=72), moderate-risk (4-5; n=229) and high-risk group (6-7; n=195). They were followed up prospectively for up to 3 years. Cox proportional hazard regression model was used to elucidate whether ABCD 2 score was a predictor for stroke after TIA after adjusting for confounding factors. Results— Among three groups, there were significant differences in age, hypertension, diabetes mellitus and the decrease in estimated glomerular filtration rate (P<0.01, significantly). During a mean follow-up of 1.3 years, Kaplan-Meier analysis demonstrated that the stroke rate in TIA patients was significantly lower in low-risk group than in moderate-risk or high-risk group (log rank test, p<0.001). The adjusted hazard ratios for stroke in patients with TIA increased with moderate-risk group (Hazard ratio [HR]: 3.47, 95% CI: 1.03-21.66, P<0.05) and high-risk group (HR: 4.46, 95% CI: 1.31-27.85, P<0.05), compared to low-risk group. Conclusions— The ABCD 2 score is able to predict the long-term risk of stroke after TIA.

Long-term outcomes of endovascular aneurysm repair for challenging aortic necks using the Talent endograft

Vascular ◽  
2011 ◽  
Vol 19 (3) ◽  
pp. 132-140 ◽  
Author(s):  
Jeffrey Jim ◽  
Brian G Rubin ◽  
Patrick J Geraghty ◽  
Luis A Sanchez
Keyword(s):  
High Risk ◽  
Risk Group ◽  
Endovascular Aneurysm Repair ◽  
High Risk Group ◽  
Low Risk ◽  
Long Term Results ◽  
Long Term Outcomes ◽  
Aneurysm Repair ◽  
Related Mortality

The aim of the present paper is to evaluate the long-term outcomes of endovascular aneurysm repair (EVAR) for challenging aortic necks. Subgroup analyses were performed on 156 patients from the prospective multicenter Talent eLPS (enhanced Low Profile Stent Graft System) trial. Patients with high-risk aortic necks (length < 15 mm or diameter ≥28 mm) were compared with the remaining patients. Patients with high-risk ( n = 86) and low-risk necks ( n = 70) had similar age and gender distribution. Despite similar prevalences of co-morbidities, the high-risk group had higher Society for Vascular Surgery scores. The high-risk group also had larger maximum aneurysm diameters (56.6 versus 53.0 mm, P < 0.02). There were lower freedoms from major adverse events (MAEs) for the high-risk group at 30 days (84.9 versus 95.7%; P < 0.04) and 365 days (73.4 versus 89.2%; P = 0.02). Effectiveness endpoints at 12 m showed no significant differences. Freedom from all-cause mortality at 30 days (96.5 versus 100%) and aneurysm-related mortality at 365 days (96.0 versus 100%) were similar. At five years, there were no differences in endoleaks or change in aneurysm diameter. All migrations occurred in the high-risk group. The five-year freedom from aneurysm-related mortality for the high- and low-risk groups was 93.2 and 100%, respectively. In conclusion, despite a higher rate of MAEs within the first year and higher migration rates at five years, EVAR in aneurysms with challenging aortic necks can be treated with acceptable long-term results.

Long-Term Outcome of Iron-Induced Cardiac Disease in Patients with Thalassemia Major Treated with Combined DFP/DFO or DFO Alone.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1764-1764
Author(s):  
Maria Eliana Lai ◽  
Stefania Vacquer ◽  
Alessia Pepe ◽  
Aurelio Maggio ◽  
Maria P. Carta ◽  
...  
Keyword(s):  
High Risk ◽  
Cardiac Disease ◽  
Risk Group ◽  
Thalassemia Major ◽  
Left Ventricular ◽  
Low Risk ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction

Abstract We conducted a 4-yr prospective trial to evaluate the long-term effects of combined deferiprone (DFP)/deferoxamine (DFO) on reversal of cardiac complications in thalassemia major compared to those of DFO alone. Twenty-eight patients (pts) with cardiac disease requiring medication were stratified according to their risk for cardiac death. Fourteen pts were high risk, serum ferritin (SF) > 2500 ug/L on two-thirds of occasions since the onset of cardiac disease. Of those with a SF < 2500 ug/L (low risk), six had progressive decrements of left ventricular ejection fraction (LVEF). Nine high-risk pts and six low-risk pts were placed on DFP/DFO (DFP, 75 mg/kg/d divided t.i.d.; DFO, 40 – 50 mg/kg over 8 – 12 h at night 5 – 7 d/wk. The others infused DFO alone. If SF fell below 500 ug/L, DFO infusions were reduced to 2 d/wk. Cardiac follow-up (including blood work and ECG) was done at 4-m intervals. M-mode and two-dimensional echocardiograms were done at 4- to 6-m intervals. Cardiac T2* was not available at the beginning of the study. All but eight patients (3 death, 1 refusal, 2 claustrophobic, 2 pacemaker) subsequently had at least one T2* assessment. Routine lab tests were done at 1- to 6-m intervals. Blood counts were done at 7- to 10-d intervals for those taking DFP. Mean follow-up was approximately 40 m. Compliance with DFO was significantly better among low-risk pts in both treatment groups (DFP/DFO, 82% vs 61%; DFO alone, 83% vs 52%) as was that with DFP (94% vs 76%). At baseline, no statistically significant differences were observed between the SF levels, LVEFs or left ventricular shortening fractions (LVSFs) of pts on DFP/DFO or DFO alone in either risk group except for the LVEFs of the low-risk group (DFP/DFO, 56.5% +/− 5.5%; DFO alone, 65.4% +/− 5.0%; p = 0.032). In the high-risk group, four cardiac events (3 deaths, 1 worsening of CHF) occurred in the group getting DFO alone vs none in the DFP/DFO-treated group. The latter pts showed a decrease in SF and an increase in both LVEF and LVSF at the end of study (EOS). The three pts who died (at 17 to 35 m) had increased SFs. These pts were not rescued by IV DFO (98 +/− 12 mg/kg/d). The two DFO-treated pts who survived had marginally improved T2*s (1.5 to 3.0 ms and 7.6 to 8.8 ms) over the year prior to EOS. Only one of the seven evaluable pts on DFP/DFO had a T2* < 10 ms, the others averaging 19.4 +/− 6.7 ms. Among the low-risk pts, those on DFP/DFO showed a reduction in SF and an improvement in both LVEF and LVSF. Those on DFO alone had increased SF but essentially no change in LVEFs or LVSFs. Five pts on DFP/DFO had T2* evaluations. In two pts, T2* rose from 9.0 to 37 ms (38 m) and from 9.3 to 11.8 ms (17 m). The remaining three had T2* values > 20 ms at EOS. Similar results were seen in low-risk pts on DFO alone. These finding clearly support the notion that DFP/DFO has a beneficial effect upon the heart, even in well established disease. Moreover, our finding of low T2* values associated with low SF levels indicates the importance of tailoring treatment to each individual.

Influence of Race and Nutritional Status on the Long Term Event Free Survival in Childhood Acute Lymphoblastic Leukemia (ALL): A 14-year Follow-up with a Reduced BFM-Based Treatment Protocol (GBTLI ALL-93)

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 13-13
Author(s):  
Silvia Regina Brandalise ◽  
Maria Pombo-de-Oliveira ◽  
Vitoria Régia Pereira Pinheiro ◽  
Maria Jose Mastellaro ◽  
Waldir Veiga Pereira ◽  
...  
Keyword(s):  
High Risk ◽  
Complete Remission ◽  
Nutritional Status ◽  
Risk Group ◽  
Treatment Protocol ◽  
Low Risk ◽  
Event Free Survival ◽  
Free Survival ◽  
All Treatment

Abstract Background: Different event-free survival rates (EFS) of childhood ALL treatment regarding race, were published in the literature. However, a better consensus exists considering the bad prognosis of undernutrition. Taking into account the social economic reality of a low-income country such as Brazil, the systematic evaluation of these variables is of utmost importance, while inserted in a modern ALL treatment protocol. Objective: To compare, prospectively, the long-term EFS rates of previously untreated children with ALL, according to race and nutritional status at diagnosis. Methods: Patients were classified as Low Risk and High Risk according to NCI Criteria. Treatment schedule: Low Risk group: Remission induction therapy with DEXA 6mg/m2/d × 28 days, VCR 1.5 mg/m2/wk × 4, Daunomycin 25 mg/m2/wk × 4, L-ASP 10.000 U/m2/dose × 8, Ara-C 75mg/m2/dose × 8 and TIT therapy (day 0,28 and 42). Intensification therapy with MTX 2g/m2/wk × 4, 24 h continuous infusion with LCV rescue 15mg/m2/dose × 4, 6MP-50mg/m2 d × 21days and TIT therapy (x 4). Re-induction therapy: Dexa 6mg/m2 d × 21days, VCR 1.5mg/m2/wk × 4, L-ASP 10.000 U/m2/d × 4, 6-MP 50mg/m2/d × 14days, Ara-C 75 mg/m2/d × 4 and TIT therapy (x3). Central randomization was done for maintenance therapy duration (130 vs 103 wk). Maintenance: 6-MP 50mg/m2/d, MTX 25mg/m2/wk and TIT therapy every 8 weeks during all treatment. No CNS radiation was done. For High Risk patients, an induction intensification with intermediate dose of AraC (750 mg/m2/d × 6) was introduced, as well as, a rotational maintenance therapy with different pair of drugs were proposed (AraC 750mg/m2 × 4/Asp 6 000 U; Dexa/VCR/wk × 3 and 6-MP 75 mg/m2/d × 21 days/MTX 40 mg/m2/wk × 3). Prophylatic CNS radiation(18Gy) was done at wks 19–21 of therapy. Statistical analysis: EFS is defined as the time from diagnosis till any failure, relapse, death, or the development of a second malignancy. Continuous complete remission duration (CCR) is defined as EFS, contingent upon induction of a complete remission. EFS and CCR rates have been estimated by Kaplan and Meier’s method. Results: From October 1993 to September 1999, 867 patients were consecutively enrolled in the protocol GBTLI ALL-93. Fourteen pts were excluded (1.5%), due to wrong diagnosis or previous corticosteroid treatment. 853 pts were evaluated in this study. 447 pts were classified as Low Risk group (52%) and 406(48%) as High Risk. According to race, 226 pts (26.5%)were classified as black and 627 (73.5%) as white. Overall undernutrition was diagnosed among 7.0 % of the patients. In the black population 10.4% were undernourished, comparing with 5.7% in the white group. The 14yrs-EFS for all the study patients is 80% ± 2% and 55% ± 2.5% for the Low Risk and High Risk pts, respectively. Concerning race, the 14yrs-EFS is of 71.7% ± 4.5% for the black children, comparatively to 83% ± 2.1% for the white ones (p=0.01). According to the nutritional status, the EFS is of 70.2%± 1.7% and 53.0%± 6.8% for the nourished and undernourished children, respectively. Malnutrition had the worst desfavorable impact among the High Risk pts, with a 14yrs-EFS of 40.1% ± 8.7%, compared to those without malnutrition of 57.8% ± 2.7% (p = 0.05). Social and economical issues directly involved with treatment, were provided by means of free medical attention and drugs supplies. Treatment abandon was &lt; 1%. Conclusion: The black race and undernutrition had significant adverse effect on the long-term EFS among the patients of this study.

Oncotype DX DCIS use and clinical utility: A SEER population-based study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12046-e12046 ◽  
Author(s):  
Yao Yuan ◽  
Alison Len Van Dyke ◽  
Allison W. Kurian ◽  
Serban Negoita ◽  
Valentina I. Petkov
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Risk Group ◽  
Low Risk ◽  
Cancer Data ◽  
Gene Assay ◽  
Risk Patients ◽  
To Receive ◽  
In Situ Breast Cancer

e12046 Background: OncotypeDX DCIS is a 12-gene assay designed to predict the 10-year risk of local recurrence and to guide treatment decisions, specifically the benefit of radiation therapy in breast ductal carcinoma in situ (DCIS). The test became available in December 2011 and is not currently recommended by guidelines. The Surveillance, Epidemiology and End Results (SEER) program captures cancer data at the population-level and has been conducting annual linkages with Genomic Health Clinical Laboratory, the only lab performing the test, to identify patients receiving the test. Methods: SEER cases diagnosed with in situ breast cancer (DCIS or papillary in situ) between 2011-2015 were included in the analysis. SEER data on patient demographics, tumor characteristics, and treatments were combined with linkage variables for OncotypeDX DCIS tests reported by Genomic Health. Logistic regression was used to identify which patient related factors were associated with having received the test and to evaluate the relationship between test generated risk categories and treatments. Results: Of the 68,826 in situ breast cancer cases, 2,155 were linked to DCIS test data. Test utilization increased from < 1% to 5.3% for patients diagnosed in 2011 vs. 2015. Patients were less likely to receive the test if they had larger and higher-grade tumors, were divorced, had Medicaid insurance, and were in the lowest socioeconomic status tertile. The majority of patients (68%) were at low risk, 17% intermediate, and 15% in the high risk group. Patients at intermediate or high risk were more likely to receive radiation (OR = 2.4, 95% CI: 1.8-3.2 and OR = 3, 95% CI: 2.3,4.1, respectively) than the low risk group. High risk patients were more likely than low risk patients to receive chemotherapy (OR = 4.3, 95% CI: 1.2, 14.4) and to undergo mastectomy than lumpectomy (OR = 1.47, 95% CI: 1.12-1.93). Conclusions: Clinical adoption of the OncotypeDX DCIS test has been slow. The association between multiple demographic factors and receiving the test indicated disparities in the US population. Clinical factors also influenced whether patients received the test. OncotypeDX DCIS results appeared to guide clinical decisions.

scholarly journals A genetic risk score predicts recurrent events after myocardial infarction in young patients with a low level of traditional risk factors

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
F Mendonca ◽  
M I Mendonca ◽  
M Temtem ◽  
M Santos ◽  
J A Sousa ◽  
...  
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Genetic Risk ◽  
Risk Group ◽  
Low Risk ◽  
Low Level ◽  
Coronary Syndrome ◽  
C Statistic ◽  
Traditional Risk Factors

Abstract Introduction Coronary Heart Disease (CAD) is a multifactorial disease, including environmental and genetic risk factors. Current smoking, dyslipidemia and diabetes have a significant impact in long- term mortality and morbidity. However, several genetic variants associated with CAD but not with traditional risk factors (TRFs) has been reported to improve prediction of events and extended mortality, in younger CAD people. Aim To evaluate the clinical utility of a GRS composed by variants from GWAS associated to CAD but not with TRF to predict life-long residual risk in patients under 55 years old and a low level of TRFs. Methods We conducted a prospective study with 573 consecutive patients aged &lt;55 years presenting with AMI and a low level of TRFs (without diabetes and with LDL cholesterol &gt;150 mg/ml). We analysed several biochemical markers and performed a GRS with variants not associated with TRFs (TCF21 rs12190287, CDKN2B-AS1 rs1333049, CDKN2B rs4977574, PHACTR1 rs1332844, MIA3 rs17465637, ADAMTS7 rs3825807, ZC3HC1 rs11556924, SMAD3 rs17228212 and GJA4 rs618675). We studied the GRS association with a primary composite endpoint of all-cause vascular morbidity and mortality including recurrent acute coronary syndrome (myocardial infarct and unstable angina), coronary revascularization (coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI), re-hospitalization for heart failure, ischemic stroke and cardiovascular dead. Results A total of 573 patients were studied and followed up for a mean of 4.7±4.0 years. There were 169 recurrent cardiovascular events. The GRS was sub-divided into terciles, verifying that patients in the third tercile (high risk) had a higher number of risk alleles. Compared with the low-risk GRS tercile, the multivariate-adjusted HR for recurrences was 1.520 (95% CI 1.011–2.286); p=0.044 for the intermediate-risk group and was 2.051 (95% CI 1.382–3.044); p&lt;0.0001 for the high-risk group. Inclusion of the GRS in the model with TRFs alone (low risk) improved the C-statistic analysis (C-statistic = 0.030; p=0.004), cNRI (continuous net reclassification improvement) (30.8%), and the IDI (integrated discrimination improvement index) (0.022). Conclusions A multilocus GRS may identify young coronary disease patients with a low level of TRFs but at significant risk of long-term events recurrence. The genetic information may improve prediction discrimination, and reclassification over the conventional risk factors alone, providing better cost-effective therapeutic strategies. FUNDunding Acknowledgement Type of funding sources: None. Figure 1

scholarly journals Evaluation of clinical efficacy of Chemotherapy for Rhabdomyosarcoma in children

2020 ◽  
Vol 36 (5) ◽  
Author(s):  
Zhaohui Ning ◽  
Xiping Liu ◽  
Guang Qin ◽  
Lei Wei ◽  
Xia Li ◽  
...  
Keyword(s):  
High Risk ◽  
Clinical Efficacy ◽  
Clinical Characteristics ◽  
Risk Group ◽  
Clinical Stage ◽  
Combined Treatment ◽  
Low Risk ◽  
Alveolar Type ◽  
Urogenital System ◽  
Curative Effect

Objective: To investigate the clinical characteristics and treatment methods of rhabdomyosarcoma in children and the efficacy of the methods. Methods: The clinical data of 30 children with rhabdomyosarcoma who were admitted to our hospital from August 2013 to August 2017 were retrospectively analyzed. The clinical characteristics were summarized, and the curative effect and prognosis were evaluated. Results: Among all the children (N=30), there were 20 males and 10 females, with a median age of 3.5 years. As to the primary site, there were 13 cases of head and neck, 11 cases of trunk, three cases of urogenital system and three cases of limbs. There were 25 cases of embryonic type, 4 cases of alveolar type and one case of polymorphic type. As to the clinical stage, there were one case of stage I, 9 cases of stage II, 13 cases of stage III and 7 cases of stage IV. There were one case of low risk, 19 cases of medium risk and 10 cases of high risk. Eight cases received surgery alone, 22 cases received combined treatment of surgery and chemotherapy (the chemotherapeutics followed three schemes, low-risk group (VAC+VA), moderate risk group (VAC) and high risk group (alternating use of VDC and IE). Among all the cases (N=30), there were 14 cases of complete remission (CR), five cases of partial remission (PR), four cases of stable disease (SD), and 7 cases of progressive disease (PD). The CR rate was (N=14, 46.7%). The three-year overall survival (OS) rate was (N=19, 63.3%). The clinical efficacy and prognosis of children receiving surgery and chemotherapy were better than those of children receiving surgery alone, and the difference was statistically significant (P<0.05). Conclusion: Rhabdomyosarcoma in children frequently happens in the head, neck and trunk. Embryonic type is the main pathological type of rhabdomyosarcoma. Comprehensive and standardized treatment based on surgery and chemotherapy is an important way to improve the curative effect in the treatment of rhabdomyosarcoma in children. doi: https://doi.org/10.12669/pjms.36.5.1829 How to cite this:Ning Z, Liu X, Qin G, Wei L, Li X, Shen J. Evaluation of clinical efficacy of Chemotherapy for Rhabdomyosarcoma in children. Pak J Med Sci. 2020;36(5):1069-1074. doi: https://doi.org/10.12669/pjms.36.5.1829 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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