Tobacco Use Influences Disease Outcome and AML Potential in Myelodysplastic Syndromes,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3790-3790 ◽  
Author(s):  
Rami S. Komrokji ◽  
Dana E Rollison ◽  
Najla H Al Ali ◽  
Maria Corrales-Yepez ◽  
Pearlie K Epling-Burnette ◽  
...  
Keyword(s):  
Tobacco Use ◽  
Lower Risk ◽  
Cox Regression ◽  
Smoking History ◽  
Hypomethylating Agents ◽  
Cox Regression Analysis ◽  
Poor Risk ◽  
Baseline Characteristics ◽  
Never Smokers ◽  
Md Anderson

Abstract Abstract 3790 Background: Several epidemiologic studies suggest a linkage between smoking history and risk of myelodysplastic syndromes (MDS). Only one study addressed the potential impact of cigarette smoking on survival in lower risk MDS. We investigated the effect of smoking on disease outcome among MDS patients treated at the Moffitt Cancer Center (MCC). Methods: MDS patients were identified through the MCC database, followed by individual chart review. Tobacco use was obtained through patient self reported questionnaire. Chi square test and t-test were used to compare baseline characteristics. Kaplan Meier estimates were used to calculate overall survival (OS); log rank test was used for comparison between the different groups and Cox regression analysis was used for multivariable analysis. All analyses were conducted using SPSS version 19.0 software. Results: We identified 743 MDS patients evaluated at MCC with known tobacco smoking history (Data on tobacco use was only missing in 24 patients in the MDS database). Two hundred and fifty six patients never smoked (never-smoker group) and 487 patients were current or former smokers (ever smoker group). Tobacco use included current cigarettes smokers (n=70), former tobacco use (n=399), Cigar/pipe (n=16), Snuff/chew (n=2). The baseline characteristics compared between the 2 groups included age, WHO subtype, International Prognostic system (IPSS), MD Anderson risk model, karyotype, RBC transfusion dependence (RBC TD), serum ferritin, and treatment with hypomethylating agents. No statistically significant differences were observed between the 2 groups. (Table-1) In low and int-1 risk IPSS, a significantly greater proportion of poor risk karyotypes was observed in ever smokers (8.8%) versus never smokers (2.4%) (p=0.003). With a median duration of follow up of 55 months (95%CI 50.5–59.6), median OS for never smokers was 48 months (95%CI=36.9–59.1) compared to 35 months (95%CI =28.7–41.3) in ever smokers (p=0.01). The adverse effect of smoking was greatest in low and intermediate-1 IPSS risk groups where median OS was 69 months (95%CI= 42–96) in never smokers compared to 48 months (95%CI= 41–55) in smokers (p=0.006). The median OS was 69 mo (95%CI =42–96), 50 mo (95%CI= 43–57), and 38 mo (95%CI= 23–53) respectively in never-smoker, former-smoker, and current smoker groups in lower risk MDS (p=0.01). No difference was observed in int-2 and high risk IPSS groups with a median OS of 22 months (95%CI =11.75–32.2) in never smokers and 18 months (95%CI =14.3–21.7) in the ever smoker group. (p=0.89). An adverse impact of smoking was observed in good and intermediate risk karyotypes but not in poor risk karyotypes. Among low/int-1 risk IPSS, the rate of AML transformation was 18.2% in ever smokers compared to 9.5% in non-smokers (p=0.04) while no difference in rate of AML transformation was observed in int-2/high risk IPSS MDS between the 2 groups. In Cox regression analysis tobacco use in lower risk MDS predicted inferior OS (Hazard ratio (HR) 1.52 (95%CI 1.06–2.2) after adjustment for age >60, MD Anderson risk group, serum ferritin, RBC-TD, and use of hypomethylating agents. Conclusions: Our study confirms a negative impact of tobacco use on disease natural history and OS in a large cohort of MDS patients. The higher frequency of poor risk karyotype and AML progression among smoking, lower risk patients suggests that tobacco exposure influences disease biologic potential and behavioral modification to discontinue tobacco use may improve outcome. Disclosures: No relevant conflicts of interest to declare.

Obesity Is Poor Prognostic Factor in Lower Risk Myelodysplastic Syndrome

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5018-5018
Author(s):  
Asmita Mishra ◽  
Dana E Rollison ◽  
Najla H Al Ali ◽  
Maria Corrales-Yepez ◽  
Pearlie K Epling-Burnette ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factor ◽  
Myelodysplastic Syndrome ◽  
Lower Risk ◽  
Cox Regression ◽  
Cancer Center ◽  
Kaplan Meier ◽  
Baseline Characteristics ◽  
Md Anderson ◽  
The Impact

Abstract Abstract 5018 Background: Obesity was associated with a more than 2-fold greater risk of myelodysplastic syndrome (MDS) in a recent epidemiological study (Ma et al, Am J Epidemiol. 2009 June 15; 169(12): 1492–1499). The impact of obesity on outcome of disease in patients with an established diagnosis of MDS has not been studied. We examined the prognostic value of obesity in a large cohort of lower risk MDS patients treated at the Moffitt Cancer Center (MCC). Methods: Data were collected retrospectively from the Moffitt Cancer Center (MCC) MDS database and individual charts reviewed. The primary objective was to evaluate the impact of obesity on overall survival (OS) in lower risk patients with MDS. Patients with low or intermediate-1 (int-1) risk disease by International Prognostic Scoring System (IPSS) were included. Obesity was defined as a body mass index (BMI) ≥ 30 (Standard definition) measured at time of referral to MDS program at MCC. Patients were divided into two groups according to BMI ≥ 30 or BMI < 30. All analyses were conducted using SPSS version 19.0. Chi square and independent t-test were used to compare baseline characteristics between the 2 groups for categorical and continuous variables, respectively. The Kaplan–Meier method was used to estimate median overall survival. Log rank test was used to compare Kaplan–Meier survival estimates between two groups. Cox regression was used for multivariable analysis. Results: Between January 2001 and December 2009, 479 low/int-1 IPSS risk MDS patients were included. Among those, 132 (27.6%) had BMI ≥ 30 and 325 (67.8%) had BMI <30; BMI was missing in 22 patients (4.6%). The baseline characteristics between the two groups were comparable. No difference was noted in mean age, WHO subtype, karyotype, MD Anderson risk model group, red blood cell transfusion dependency (RBC-TD), or serum ferritin (Table-1). The median OS was 59 mo (95%CI 48–70) in patients with BMI <30 compared to 44 (95%CI 38–50) in patients with BMI ≥ 30. (p=0.03). There was no difference in rate of AML transformation according to BMI, 12.9% and 15.7% respectively for BMI ≥ 30 and BMI <30. (P=0.3). In Cox regression analysis obesity predicted inferior OS (Hazard ratio (HR) 1.7 (95%CI 1.15–2.4) (P=0.007) after adjustment for age, MD Anderson risk group, serum ferritin, RBC-TD, use of hypomethylating agents and tobacco use. Conclusion: Our data suggest that obesity is an independent adverse prognostic factor for OS in patients with lower risk MDS. Obesity may be associated with other comorbidities and metabolic dearrangements that contribute to the pathogenesis of the underlying disease. Disclosures: No relevant conflicts of interest to declare.

MO757COMPARISON OF ANTI-COAGULATION AND NO ANTI-COAGULATION IN DIALYSIS PATIENTS WITH ATRIAL FIBRILLATION: A SINGLE CENTER RETROSPECTIVE STUDY

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Jun Young Lee ◽  
Jae Won Yang ◽  
Jae Seok Kim ◽  
Seong Ok Choi ◽  
Byoung Geun Han
Keyword(s):  
Atrial Fibrillation ◽  
Cox Regression ◽  
Dialysis Patients ◽  
Dialysis Therapy ◽  
Cox Regression Analysis ◽  
Significant Difference ◽  
Baseline Characteristics ◽  
Stage Renal Disease ◽  
End Stage ◽  
Risk And Benefit

Abstract Background and Aims Atrial fibrillation (AF) is common arrhythmia in end stage renal disease patients. Although, the need of anticoagulation to prevent stroke and thromboembolism is increasing, the efficacy of anticoagulation is not proven in most of study. We retrospectively analyzed the risk and benefit of anticoagulation in dialysis patients with AF. Method By using medical record, we retrospectively analyzed all data of 99 patients who received dialysis therapy and diagnosed AF. Results Among 99 patients who diagnosed AF with dialysis 36 patients received anticoagulation (17 coumadin, 19 apixaban 2.5mg bid), 63 patients received no anticoagulation. There was no significant difference of baseline characteristics between anticoagulation, and no anticoagulation patients. Although no anticoagulation group experienced more all-cause (39.7% vs 32.4%, p=0.572) and cardiovascular mortality (17.6% vs 10.8%, p=0.197) than anticoagulation group it was not statistically significant. Compared to apixaban 2.5mg bid patients, coumadin anticoagulation patients experienced more frequent mfig ajor adverse cardiovascular events (35.3% vs 15.8%, p=0.109) but it was not statistically significant in multi variate Cox regression analysis (Hazard ratio 1.143, 95% Confidence Interval 0.503-2.597). Conclusion Apixaban 2.5mg bid was not inferior than coumadin considering risk and benefit of anticoagulation in dialysis patients.

Abstract 16587: More Than Five Years After FDA Approval, There Remains Very Limited Adoption of New Evidence-Based, Highly Effective Medications for the Treatment of Patients With Heart Failure, Especially Among Those on Medicare

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Joseph B Muhlestein ◽  
Heidi T May ◽  
Tami L Bair ◽  
Stacey Knight ◽  
Kirk U Knowlton ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cox Regression ◽  
Sglt2 Inhibitor ◽  
Clinical Effectiveness ◽  
Major Adverse Cardiovascular Events ◽  
Evidence Based ◽  
Cox Regression Analysis ◽  
Reduced Ejection Fraction ◽  
Highly Effective ◽  
Baseline Characteristics

Background: Over the past decade, the FDA has approved several new medications that are highly effective when added to existing standard therapy in the treatment of heart failure with reduced ejection fraction (HFrEF). It is possible that, despite the presence of substantial evidence regarding the clinical effectiveness of these new medications, their high cost and the complex medical reimbursement system in America may prevent their routine adoption. Methods: We analyzed 5,824 Intermountain Healthcare patients, age ≥18 years with a new clinical diagnosis of HFrEF (LVEF ≤35%), from 1/1/2015 onward, for the use of newly-approved sacubitril/valsartan or any sodium-glucose cotransporter-2 inhibitor (SGLT2-I). We collected baseline characteristics and medication utilization data. We followed the patients for 1.7±1.4 years for future major adverse cardiovascular events (MACE), including death, myocardial infarction (MI), stroke, and heart failure hospitalization (HFH). We identified differences between groups by multivariable Cox regression analysis. Results: Baseline characteristics and incidence of MACE, according to insurance status and the use of common HFrEF medications, are shown in the Table. Overall, only 344 (5.9%) and 169 (2.9%) of patients ever received a prescription for sacubitril/valsartan or an SGLT2 inhibitor, respectively. The figures show survival curves for MACE of patients receiving or not receiving the newly-approved medications. Conclusion: In this large, modern, real-world HFrEF population, the adoption of newly-approved evidence-based HFrEF medications is minimal in all patients and especially in Medicare patients. This lack of adoption is associated with a significant worsening in patient outcomes. These findings demonstrate a critical need to resolve our present healthcare financial crisis, which is almost certainly the reason for these findings.

Plasma GH as a diagnostic and prognostic biomarker in HCC without cirrhosis.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 227-227
Author(s):  
Roberto Carmagnani Pestana ◽  
Manal Hassan ◽  
Reham Abdel-Wahab ◽  
Yehia I. Abugabal ◽  
Lauren Girard ◽  
...  
Keyword(s):  
Cox Regression ◽  
Early Stage ◽  
Tnm Staging ◽  
Cancer Center ◽  
Limited Information ◽  
Cox Regression Analysis ◽  
Diagnostic Role ◽  
Md Anderson ◽  
Plasma Gh

227 Background: The association between the GH/IGF-1 axis and HCC was reported in patients (pt) with underlying cirrhosis. However, there is limited information among HCC pt without (w/o) cirrhosis. We herein investigated the role of GH as a circulating biomarker for HCC diagnosis and prognosis in pt w/o cirrhosis. Methods: Under IRB approval, we prospectively enrolled 1267 newly-diagnosed HCC pt in a case control study at the MD Anderson Cancer Center (2000-2015). Controls were healthy individuals (n = 1104). Plasma GH and AFP were measured 274 HCC pt w/o cirrhosis 200 healthy controls. IGF-1 was measured in 133 and 82 pt, respectively. We classified HCC pt into higher and lower GH values (cutoff for women, 3.7 µg/L; men, > 0.9 µg/L). Results: Most pt (74%) were male, with advanced BCLC staging (C-D, 74%) and 61% were older than 60y. Baseline GH was higher in HCC w/o cirrhosis (mean 3.3 µg/L) than controls (mean 0.4 µg/) (p < .001). ROC curve was plotted to assess diagnostic role. The AUC for AFP was 82.9 (p < .001); for GH 78.2 (p < .001). When only non-cirrhotic HCC pt with early stage (CLIP 0-2) and AFP < 20 ng/m were compared to controls, the GH/IGF-1 ratio had high prediction of early stage HCC - AUC 83 (95% CI 78-89%) (p < .0001). At a specificity of 90%, sensitivity of GH/IGF ratio was 67%. In addition, among HCC w/o cirrhosis, higher GH levels correlated with presence of vascular invasion (p < .001) and thrombosis (p = .004), tumor involvement of > 50% liver (p = .003), and more advanced BCLC (p < .001) and TNM staging (p < .001). Median overall survival (months) of HCC pt w/o cirrhosis with high GH levels was 13.1 (10.8-15.4) compared to 37.4 (19.8-55.1) of pt with lower plasma GH (p < .001). Multivariate cox-regression analysis identified high GH as an independent risk factor for mortality (HR = 1.8; 95% CI, 1.3-2.4; p < .001). Conclusions: Our study demonstrates the diagnostic and prognostic role of plasma GH in non-cirrhotic HCC and identifies the GH/IGF-1 ratio as a promising diagnostic marker for early stage HCC w/o cirrhosis and low AFP; this analysis excludes the confounding effect hepatocyte impaired function by presence of cirrhosis. Further studies are warranted to assess the causes of the observed differences.

scholarly journals Impact of malignancy on outcomes in European patients with atrial fibrillation: a report from the ESC-EHRA EURObservational Research Programme in Atrial Fibrillation General Long-Term Registry

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
V L Malavasi ◽  
M Vitolo ◽  
M Proietti ◽  
L Fauchier ◽  
F Marin ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Regression Analysis ◽  
Lower Risk ◽  
Cox Regression ◽  
Cumulative Risk ◽  
Research Programme ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Prior Malignancy

Abstract Background Management of patients with atrial fibrillation (AF) and malignancy is a clinical challenge given the paucity of evidence supporting the appropriate clinical management. Purpose To evaluate the outcomes of patients with active or prior malignancy in a large contemporary cohort of European AF patients. Methods We analyzed patients enrolled in the ESC-EHRA EORP-AF General Long-Term Registry. We stratified the population into three categories (i) No Malignancy (NoM) (ii) Prior Malignancy (PriorM) and (iii) Active Malignancy (ActM). The primary outcome for this analysis was all-cause death among the three groups. The association between anticoagulant treatment, all-cause death and haemorrhagic events was also evaluated. Results Among the original 11 096 AF patients enrolled, 10 383 were included in this analysis (median age 71 years (interquartile range [IQR] 63–77, males 59.7%). Of these, 9 597 (92.4%) were NoM patients, 577 (5.6%) PriorM and 209 (2%) ActM. Patients with malignancy (prior or active) had a higher median age, median CHA2DS2-VASc and HAS-BLED scores, compared to patients without malignancy (p&lt;0.001). Lack of anticoagulation (AC) prescription occurred more commonly in ActM (21.5%) as compared with the other groups (PriorM 10.1% vs NoM 12.8%, p&lt;0.001). In case of AC treatment, patients with ActM were treated more frequently with heparins (ActM 8.1% vs PriorM 2.4% vs NoM 2%, p&lt;0.001). After a median follow-up of 730 days [IQR 692–749], 982 (9.5%) patients died. Among all deaths, the proportion of cardiovascular death was different according to the three groups (40.0% in NoM, 26.0% in PrioM and 22.2% in ActM, p=0.002). For all cause-death, Kaplan-Meier analysis showed a progressively higher cumulative risk in the PriorM and ActM groups compared to NoM patients (Figure 1). On multivariable Cox regression analysis, adjusted for CHA2DS2-VASc score, use of AC, type of AF and chronic kidney disease, ActM group was independently associated with a higher risk for all cause death (hazard ratio [HR] 2.90, 95% confidence interval [CI] 2.23–3.76) while PriorM group was not. Among PriorM and NoM patients, multivariable adjusted Cox regression analysis found that the use of any AC was independently associated with a lower risk for all-cause death (HR 0.36, 95% CI 0.19–0.66; HR 0.66, 95% CI 0.54–0.81). No significant association between AC and all-cause death was found for ActM patients. Conclusions In a large contemporary cohort of European AF patients, active malignancy was found to be independently associated with all-cause death. Use of any AC was associated with a lower risk for all-cause death in patients with no malignancies and with prior malignancies, but with no significant association amongst patients with active malignancies. FUNDunding Acknowledgement Type of funding sources: Other. Main funding source(s): Since the start of EORP, the following companies have supported the programme: Abbott Vascular Int. (2011–2021), Amgen Cardiovascular (2009–2018), AstraZeneca (2014–2021), Bayer (2009–2018), Boehringer Ingelheim (2009–2019), Boston Scientific (2009–2012), The Bristol Myers Squibb and Pfizer Alliance (2011–2016), The Alliance Daiichi Sankyo Europe GmbH and Eli Lilly and Company (2011–2017), Edwards (2016–2019), Gedeon Richter Plc. (2014–2017), Menarini Int. Op. (2009–2012), MSD-Merck & Co. (2011–2014), Novartis Pharma AG (2014–2020), ResMed (2014–2016), Sanofi (2009–2011), SERVIER (2010–2021), and Vifor (2019–2022). Figure 1. Kaplan-Meier for all-cause death

P1650HIGH-DENSITY LIPOPROTEIN PARTICLES AND THEIR RELATIONSHIP TO POSTTRANSPLANTATION DIABETES IN RENAL TRANSPLANT RECIPIENTS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Sara Sokooti Oskooei ◽  
Tamas Szili-Torok ◽  
Jose L Flores-Guerrero ◽  
Maryse C.J. Osté ◽  
António W Gomes-Neto ◽  
...  
Keyword(s):  
Renal Transplant ◽  
Lower Risk ◽  
Cox Regression ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Cox Proportional Hazards ◽  
Relative Mass ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Cox Regression Analysis

Abstract Background and Aims It is established that high concentrations of High-Density Lipoprotein (HDL) are associated with low risk of type 2 diabetes and posttransplantation diabetes mellitus (PTDM). However, HDL particles vary by size, density, and biological action. The aim of our study was to determine the association between different HDL particles with the development of PTDM in renal transplant recipients (RTRs). Method We included 351 stable outpatient adult RTR with a functioning graft ≥1 year from the Tranplantlines Food and Nutrition Study(NCT02811835). HDL particle concentration and size were measured by 1H-NMR spectroscopy using a Vantera® NMR Clinical Analyzer (LabCorp, Raleigh, NC). HDL size was weighted averages derived from the sum of the diameter of each subclass multiplied by its relative mass percentage. Estimated ranges of HDL diameter for the HDL subclasses were as follows: large HDL particles, 9.6–13 nm; medium HDL particles, 8.1–9.5 nm; and small HDL particles, 7.4–8.0 nm. PTDM was defined according the American Diabetes Association’s diagnostic criteria for diabetes. Multivariable-adjusted Cox proportional-hazards regression analyses were performed to assess the prospective association of HDL particles with PTDM. Results During 5.2 (IQR, 4.1–5.8) years of follow-up, 39 (11%) RTR developed PTDM. In a multivariable Cox regression analysis, higher HDL cholesterol was associated with a lower risk of PTDM development, after adjustment for age, sex and BMI (hazard ratio[HR] 0.55, 95% CI 0.36-0.83 per 1SD mg/dL; P=0.005). Moreover, among different HDL indices; HDL size, and large HDL were inversely associated with PTDM, after adjustment for age, sex, and BMI ([ HR 0.48, 95% CI 0.31-0.76 per 1SD nm; P=0.002], and [HR 0.63, 95% CI 0.47-0.84 per 1SD µmol/L; P=0.002], respectively ). However medium HDL and small HDL were not associated with risk of developing PTDM ([ HR 0.88, 95% CI 0.64-1.23 per 1SD µmol/L; P=0.48], and [HR 1.14, 95% CI 0.85-1.52 per µmol/L; P=0.37], respectively ). In additional models, the association remained significant for HDL cholesterol, HDL size, and large HDL after adjustment for other confounders including, the lifestyle, use of medication, kidney function and transplantation-specific parameters. In the last model after adjustment for age, sex, BMI, triglycerides, systolic blood pressure, and fasting plasma glucose, association were similar for HDL cholesterol, HDL size, and large HDL ([ HR 0.61, 95% CI 0.40-0.94 per 1SD mg/dL; P=0.024], [HR 0.58, 95% CI 0.36-0.93 per 1SD nm; P=0.025], and [HR 0.68, 95% CI 0.50-0.93 per 1SD µmol/L; P=0.017]. Conclusion In this study, we found that higher concentrations of HDL cholesterol, large HDL, and higher HDL size were associated with a lower risk of developing PTDM in RTRs, independent of established risk factors for PTDM development.

Gefitinib combined biologic therapy for advanced lung adenocarcinoma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19098-e19098
Author(s):  
Baoping Li ◽  
Lei Zhang
Keyword(s):  
Quality Of Life ◽  
Genetic Testing ◽  
Lung Adenocarcinoma ◽  
Response Rate ◽  
Cox Regression ◽  
Immune Therapy ◽  
Fluid Pressure ◽  
Smoking History ◽  
Cox Regression Analysis

e19098 Background: Gefitinib is an effective treatment for non-small cell lung cancer patients with epidermal growth factor receptor (EGFR) mutations. However, due to the limited genetic testing methods and other constraints, a large proportion of patients did not benefit from it. In order to overcome the limitation of genetic testing and other constraints, we use gefitinib with the immune-biotherapy to treatment advanced lung adenocarcinoma. Methods: From February 2011 to December 2012, we use gefitinib combined with immune-therapy to treat 59 cases with advanced lung adenocarcinoma. These patients completes at least one cycle of therapy. The efficacy and quality of life were investigated. The prognostic factors were analyzed using Cox regression model. Results: CRF0, PR:46, SD:13, the PD:0. The overall response rate = 77.97%. FACT-L: 100%. The response rate and scores of quality of life are higher than the reported data. COX regression analysis showed that the complete remission after the treatment is significant factor(P <0.01), but the factors such as the disease control status, gender, tumor stage, smoking history were not significant. Conclusions: Gefitinib and biological therapy combined, can significantly improve short-term effect of advanced lung adenocarcinoma. Its possible mechanism of gefitinib to reduce interstitial fluid pressure may increase immunocompetent cells into the tumor tissues, thereby enhancing efficacy.

Checkpoint inhibitors in metastatic renal cell carcinoma patients including elderly subgroups: Results from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4580-4580
Author(s):  
Steven Yip ◽  
Connor Wells ◽  
Raphael Brandao Moreira ◽  
Alex Wong ◽  
Sandy Srinivas ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Real World ◽  
Renal Cell ◽  
Cox Regression ◽  
Cell Cancer ◽  
Second Line ◽  
Cox Regression Analysis ◽  
Poor Risk

4580 Background: Immuno-oncology (IO) checkpoint inhibitor treatment outcomes are poorly characterized in the real world metastatic renal cell cancer (mRCC) patient population, including geriatric patients. Methods: Using the IMDC database, a retrospective analysis was performed on mRCC patients treated with IO, as listed below. Patients received one or more lines of IO therapy, with or without a targeted agent. Duration of treatment (DOT) and overall response rates (ORR) were calculated. Cox regression analysis was performed to examine the association between age as a continuous variable and DOT. Results: 312 mRCC patients treated with IO were included. In patients who were evaluable, ORR to IO therapy was 29% (32% first-, 22% second-, 33% third-, and 32% fourth-line treatment (Tx)). Patients treated with second-line IO therapy were divided into favorable, intermediate, and poor risk using IMDC criteria; the corresponding median DOT rates were not reached (NR), 8.6 mo, and 1.9 mo, respectively (p<0.0001). Based upon age, hazard ratios were calculated in the first- through fourth-line therapy setting, ranging from 1.03 to 0.97. Conclusions: The ORR to IO appears to remain consistent, regardless of line of therapy. In the second-line, IMDC criteria appear to appropriately stratify patients into favorable, intermediate, and poor risk groups for DOT. Premature OS data will be updated. In contrast to clinical trial data, longer DOT is observed in real world practice. Age may not be a factor influencing DOT. [Table: see text]

A Sensitive Risk Score for Directing Treatment in Younger Patients with AML.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 18-18 ◽  
Author(s):  
Alan K. Burnett ◽  
Robert K. Hills ◽  
Keith Wheatley ◽  
Anthony H. Goldstone ◽  
Archie G. Prentice ◽  
...  
Keyword(s):  
Risk Score ◽  
Cox Regression ◽  
Risk Group ◽  
Experimental Therapy ◽  
Intermediate Risk ◽  
Total Risk ◽  
Younger Patients ◽  
Cox Regression Analysis ◽  
Poor Risk ◽  
Secondary Disease

Abstract Treatment strategies for younger patients (<60 years) with AML who enter complete remission (CR) are frequently decided on a risk assessment based on cytogenetic characterisation. Most collaborative groups have devised prognostic cytogenetic groupings of favourable, intermediate or poor risk which have relapse risks of 25–35%, 50–60%, and 80–85% respectively. The precise lesions in each group might vary by study group, but the overall discrimination is consistent. Favourable and possibly intermediate risk cases may not receive transplantation, whereas poor risk cases will. Outcomes for poor risk cases have failed to improve over the years, and if not transplanted these patients are candidates for experimental therapy. There is concern that cytogenetic segregation may not on its own be sufficiently sensitive on an individual patient level, and the inclusion of other factors may better customise risk. We performed a Cox regression analysis on 1937 non-APL cases with complete data who entered CR in the MRC AML10 and 12 trials. Increasing age, cytogenetic risk group higher WBC, male sex, secondary disease, and incomplete response to course 1 were all identified as significantly (p= 0.05) associated with poorer survival. These respectively contributed 0.013 per year, 0.651 per cytogenetic group, 0.002 per WBC unit (/nl), 0.170 for males, 0.221 for secondary disease, and 0.195 for PR/ 0.390 for resistant disease following course 1 to an individual’s total risk score. The groups were separated into scores of <2.00 (good risk), 2.00–2.667 (standard) and >2.667 (poor risk) which gave excellent discrimination for survival from CR at 5 years of 63%, 47% and 24% (p<0.00001). The score was prospectively validated in 897 patients who entered the MRC AML15 trial and was confirmed to be predictive with survivals from CR of 69%, 61% and 42% (p<0.00001). The value of the new score was to move patients out of the old cytogenetic category. The major effect was to move 274 patients from intermediate risk to poor risk and 42 poor risk patients to intermediate risk (table). This score has implications for treatment approach since, relatively, 60% more patients were identified as high risk and are therefore candidates for experimental therapy, or may, from Mantel-Byar analysis, benefit from transplantation. MRC Risk Group Total Good Standard Poor Crosstabulation of old and new risk group classification New Risk Classification Good 309 28 0 337 (14%) Standard 51 1288 42 1381 (59%) Poor 2 274 353 629 (27%) Total 362 (15%) 1590 (68%) 395 (17%) 2347

Prognostic Value of “Monosomal Karyotype” in Comparison to “Complex Aberrant Karyotype” in AML: A Study on 824 Cases with Aberrant Karyotype

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 418-418
Author(s):  
Claudia Haferlach ◽  
Tamara Alpermann ◽  
Susanne Schnittger ◽  
Wolfgang Kern ◽  
Torsten Haferlach
Keyword(s):  
Cox Regression ◽  
Complex Karyotype ◽  
Employment Equity ◽  
Cytogenetic Abnormalities ◽  
Cox Regression Analysis ◽  
Poor Risk ◽  
Risk Patients ◽  
Equity Ownership ◽  
The Impact ◽  
Monosomal Karyotype

Abstract Abstract 418 Background: Several classifications based on cytogenetics have been proposed in AML. Typically 3 major categories for prognostication are defined: favorable, intermediate and unfavorable. The assignment to the unfavorable group shows minor differences between the different cytogenetic classifications currently used, however certain cytogenetic subgroups are assigned to the unfavorable subgroup concordantly: −5/5q−, 7q−/−7, −17/abn17p, inv(3)(q21q26)/t(3;3)(q21;q26) and complex karyotype (CK). With respect to CK 3 definitions are used: ≥3, ≥4 or ≥5 unrelated abnormalities. Recently, a so-called “monosomal karyotype” (MSK) defined as a karyotype showing “two or more distinct autosomal chromosome monosomies or one single autosomal monosomy in the presence of structural abnormalities” was introduced (Breems et al. JCO 2008). It was suggested that patients with MSK have a poor outcome being even inferior to CK. Aim: We here evaluated the prognostic power of differently defined cytogenetic subsets in order to identify the best definition for the prognostically most unfavorable subgroup. Patients: From our initial cohort of newly diagnosed AML (n=1,959) patients with t(15;17), t(8;21) or inv(16) (n=170) and AML with normal karyotype (n=965) were excluded. Thus, 824 patients with cytogenetic abnormalities remained for further investigation. Results: 428/824 (51.9%) patients showed an intermediate risk karyotype according to revised MRC criteria (MRC-I) (Grimwade et al. Blood 2010), while the remaining 396/824 (48.1%) cases belonged to the unfavorable MRC group (MRC-U). 162/824 cases (19.7%) fulfilled the criteria of MSK. According to MRC, 4 of these 162 cases with MSK were classified MRC-I while 158 were classified MRC-U. The overlap in classification between CK and MRC-U differed depending on the number of aberrations used to define CK. As such, the number of cases with CK was 272 (33.0%; MRC-I: 17, MRC-U: 255) using ≥3 clonal aberrations, and decreased to 222 (26.9%; all MRC-U) patients using ≥4 clonal aberrations or 196 (23.8%; all MRC-U) cases when applying the criterion of ≥5 clonal aberrations, respectively. Univariate Cox regression analysis revealed that unfavorable cytogenetics as defined by MRC-U, MSK, CK defined as ≥3, ≥4 or ≥5 unrelated abnormalities were all significantly associated with inferior OS as compared to the respective remaining intermediate group (for all p<0.001). Hazard ratios were 1.61, 1.93, 1.68, 1.94, and 1.92, respectively. Median OS in the respective categories was 8.5, 5.7, 6.3, 5.7, and 5.7 months, respectively. We then performed further analyses within the unfavorable risk group defined according to MRC and tested the impact of the 4 definitions for unfavorable subsets. In each comparison the median OS was significantly shorter for the subset with MSK, or CK defined as ≥3, '4 or ≥5 unrelated abnormalities as compared to the remaining MRC-U cases (5.7 vs 11.7 mo p=0.005; 6.3 vs 10.6 mo, p=0.031; 5.7 vs 11.0 mo, p=0.003; 5.7 vs 10.9 mo, p=0.006). Furthermore OS of patients within MRC-U excluding cases with MSK, or CK with ≥3, ≥4 or ≥5 unrelated abnormalities did not differ from patients with cytogenetic abnormalities assigned to MRC-I (median OS 11.7, 10.6, 11.0 and 10.9 mo, respectively vs 21.1 mo, p=0.072, p=0.16, p=0.28, and p=0.11, respectively). Within the MRC-U cohort only 124 cases fulfilled both criteria: MSK and CK≥4 (median OS 5.3 mo), 97 were CK≥4 only (median OS 6.3 mo) and 35 MSK only (median OS 6.7 mo). OS did not differ between these 3 subgroups but was significantly shorter for all comparisons to patients included in none of these subgroups (p<0.001, p=0.009, p=0.012, respectively). On the other hand OS of the 33 cases with 3 unrelated abnormalities did not differ from MRC-U cases with 1 or 2 abnormalities (18.9 vs 10.6, p=0.48). Conclusions: All definitions of very poor risk AML patients allow to identify a subset within MRC-U that shows significantly shorter OS than the remaining MRC-U cases. However, “complex karyotype defined as ≥4 unrelated abnormalities” is the best parameter as it identifies the largest proportion of very poor risk patients. Even more important, the application of the monosomal karyotype for prognostication and clinical guidance in AML misses 24.5% of the very poor risk patients identified based on CK ≥4. This may lead to suboptimal treatment decisions in this clinically proven very high risk patients. Disclosures: Haferlach: MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Alpermann:MLL Munich Leukemia Laboratory: Employment. Schnittger:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Kern:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership.

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