Cox Proportional Hazards Model Analysis Research Articles

ATIM-47. NIVOLUMAB VS BEVACIZUMAB IN PATIENTS WITH RECURRENT GLIOBLASTOMA: EXPLORATORY ANALYSIS OF MGMT METHYLATION STATUS AND BASELINE CORTICOSTEROID USE

Abstract BACKGROUND Current therapies for recurrent glioblastoma provide limited survival benefit. In the open-label, phase 3 CheckMate 143 study (NCT02017717), although the primary endpoint was not met, the median overall survival (mOS) was comparable between nivolumab (anti–PD-1) and bevacizumab in the overall population of patients with glioblastoma at first recurrence after temozolomide chemoradiotherapy (Reardon et al, WFNOS 2017). Exploratory subgroup analyses were conducted to evaluate the association of O-6-methylguanine DNA methyltransferase (MGMT) promoter methylation status and corticosteroid use at baseline with mOS. METHODS Prespecified patient subgroups included MGMT promoter status (methylated vs unmethylated) and baseline corticosteroid use (yes [within 5 days of first dose] vs no). FINDINGS: Methylation status was available for 102/184 (55%) nivolumab-treated and 109/185 (59%) bevacizumab-treated patients. Using a multivariable Cox proportional hazards model analysis, no baseline corticosteroid use (HR, 0.59 [95% CI, 0.36–0.95]) and methylated MGMT status (HR, 0.47 [95% CI, 0.29–0.78]) were each associated with longer mOS among nivolumab-treated patients. Among patients with methylated MGMT and no baseline corticosteroid use, mOS was 17.0 months with nivolumab (n=31) and 10.1 months with bevacizumab (n=22; HR, 0.58 [95% CI, 0.30–1.11]). In patients with methylated tumors and baseline corticosteroids, mOS was 7.7 months with nivolumab (n=12) and 13.5 months with bevacizumab (n=17). Among patients with unmethylated tumors and no baseline corticosteroids, mOS was 8.3 months with nivolumab (n=30) and 10.3 months with bevacizumab (n=29). In patients with unmethylated tumors and baseline corticosteroids, mOS was 5.6 months with nivolumab (n=28) and 8.3 months with bevacizumab (n=28). CONCLUSION A trend toward longer mOS with nivolumab was observed in a subgroup of patients with methylated MGMT and no baseline corticosteroid use. These findings suggest that MGMT methylation status and corticosteroid use at baseline could be used to identify patients who may benefit from nivolumab and thus warrant further study.

Treatment of Intermediate-Stage Hepatocellular Carcinoma in Japan: Position of Curative Therapies

Background: Transcatheter arterial chemoembolization (TACE) is the standard therapy for intermediate-stage (IM) hepatocellular carcinoma (HCC). However, IM-HCC includes various clinical conditions, and various therapies were conducted in practice. In this study, we retrospectively analyzed the actually conducted treatments for IM-HCC and their efficacies to elucidate the treatment strategies suitable for IM-HCC. Methods: This study included 627 IM-HCC of 5,260 HCC from 9 hospitals. We examined the treatment strategies of these patients and analyzed the efficacy of each therapy with the Cox proportional hazard model and propensity score-matched analysis. Results: Liver resection, radiofrequency ablation (RFA), and TACE were performed in 165, 108, and 351 patients, respectively. Liver resection and RFA were preferably selected in cases of Barcelona Clinic Liver Cancer (BCLC)-B1/B2, and patient survival was significantly longer than in those treated with TACE (p< 0.0001). However, no beneficial effect of these active therapies was observed in cases of BCLC-B3/B4. Multivariate analysis revealed that surgical resection (hazard ratio = 0.384) and RFA (hazard ratio = 0.597) were negative risk factors for survival. Propensity score-matching analysis revealed that ­survival of RFA-treated patients was longer than that of TACE-treated patients (p = 0.036). Conclusion: RFA and surgical resection were effective for IM-HCC, particularly in BCLC-B1/B2 cases.

EP1.16-44 Survival and Prognostic Association of Non-Small Cell Lung Cancer with Brain Metastases After WBRT: A Multicentre Study

Forty percent of intracranial tumors are metastatic, arising most commonly from lung. To our knowledge, no data is available on prognosis factors of the survival of non-small cell lung cancer (NSCLC) patients with brain metastases in Bangladesh. This study aims to determine overall survival (OS) and identify prognosis factors in NSCLC patients with brain metastases after whole brain radiation therapy (WBRT). The study retrospectively investigated histologically proven NSCLC patients with brain metastases at two tertiary hospitals in Bangladesh from January, 2013 to April, 2018. A total of 62 patients were eligible who received 30 Gy (3 Gy per fraction) of WBRT. The primary end point was OS and the secondary endpoint was prognostic association with various factors including patient age and gender, tumor histology, Karnofsky performance status, pleural effusion, primary not controlled, extracranial metastases, the number of brain metastases, surgical resection and diagnosed initially with brain metastases or developed brain metastases later. RTOG Recursive Partitioning Analysis (RPA) was used to categorize the patients. Survival was calculated by Kaplan-Meier method and compared by Log-rank test. Prognostic association was evaluated with Cox proportional hazards model analysis. Mean survival of the entire cohort was 5.76 months (95% CI: 4.69 – 6.84 months). Patients with brain metastases at diagnosis or developed brain metastases later during disease progression had a statistically similar mean survival (6.18 months vs. 5.49 months; P = 0.422). Among the 62 patients, 16.1%, 30.6% and 53.2% were RPA Class I, II and III respectively. Mean survival differed significantly among the three classes (Class I: 9.10 months, Class II: 6.68 months, Class III: 3.64 months; P = 0.00). Individual prognostic factors were not found to be associated with survival difference except, single vs. multiple brain metastases (P = 0.042) and primary controlled or not (P = 0.026). The study reported survival time of NSCLC patients with brain metastases undergo WBRT, and indicated that higher RPA classes, primary not controlled and greater numbers of brain metastatic lesions are the three prognostic factors of poor survival for this cohort. Our results may help clinicians in patient counseling, treatment selection and designing future clinical trials.

P4770Antithrombotic challenge in the clinical dilemma of high-risk patients with atrial fibrillation: one-year result from ChiOTEAF Registry

Abstract Background The antithrombotic treatment is the main goal of management on atrial fibrillation (AF). However, the optimal thrombophylaxis still remains the problem in the “high-risk” population, such as the elderly, with renal/liver dysfunction, malignancy, stent implantation, etc. Objectives The present study aims to explore the optimal antithrombotic strategy in a “high-risk” population with multiple comorbidities. Methods The ChiOTEAF (Ethic approval number of Central Medical Ethic Committee of General PLA Hospital: S2014–065–01) is a prospectively, multi-center (44 research centers), real-world registry across China. The protocol was seen in BMJ Open (Guo Y, et al. 2018). A Cox proportional hazard model analysis was performed for the outcome of antithrombotic therapy among this high-risk population. Results 6148 patients with AF (mean age 74 years old, female 39.4%), were enrolled into ChiOTEAF study between Oct 2014 to Dec 2018. The use of non-vitamin K antagonist oral anticoagulants (NOACs), warfarin, and antiplatelet were 1444 (23.5%), 1300 (21.1%), and 2521 (41.0%), respectively, in this high-risk AF population. During one-year follow-up, there were 186 (3.0%) all-cause death. In this AF cohort, the patients with chronic kidney disease (CKD)/liver disease were 878 (14.3%), with malignancy were 555 (9.0%), with prior thromboembolism (TE) were 1538 (25%), with prior haemorrhage were 348 (5.7%), and current anemia were 859 (14.0%), respectively. Stent implantation (coronary artery, aortic or peripheral artery) were 671 (10.9%). CHA2DS2-VASc and HAD-BLED scores (mean±standard deviation) were 3.8±1.7, and 2.0±1.1, respectively. Among the above “clinical dilemma”, the antiplatelet use was common in patients with CKD/Liver disease and stent implantation (43.5%, 56.9%, respectively, p&lt;0.05), the oral anticoagulants (OACs) combined with antiplatelet was most seen in patients with stent implantation (15.4%, p&lt;0.05), OACs alone were highest in patients with prior TE (38.1%, p&lt;0.05), while patients with malignancy and prior bleeding far less received any antithrombotic drugs (41.8%, 31.3%, respectively, p&lt;0.05) (Figure 1). However, after adjusting baseline characteristics, OACs reduced the risk for all-cause death (hazard ratio, HR, 95% confidential interval, CI) for the patients with CKD/liver disease (HR, 95% CI, 0.28, 0.11–0.69, p=0.006), and for patients with prior TE (HR, 95% CI, 0.43, 0.21–0.91, p=0.028), respectively. Conclusion Although suboptimal anticoagulants were common in the “high-risk” AF patients, OACs demonstrated the benefit for AF patients with CKD/liver disease, etc., while more evidences would be needed to optimise the antithrombotic strategy in different complex clinical settings. Acknowledgement/Funding The study was supported by Beijing Natural Science Foundation (Z1411ehz745.11462114050) and National Natural Science Foundation of China (H2501)

EP1.16-21 Frequencies and Prognosis of Non-Small Cell Lung Cancers Complicated with Synchronous/Metachronous Multiple Primary Cancers

Recently, opportunities to diagnose multiple primary cancers have been increasing due to the progress of diagnostic technology, resulting in the difficulty in treatment decisions. Therefore, we examined the frequencies, background, and prognosis of non-small cell lung cancers (NSCLC) complicated with synchronous/metachronous multiple primary cancers. Between 2013 and 2017, we retrospectively examined the medical charts in patients with NSCLC who had never experienced cancers before. We classified such NSCLC patients into the following three groups: (1) single primary NSCLC group (SPN), showing no other cancers during the follow-up period, (2) synchronous NSCLC group (SN), showing other cancers diagnosed within 2 months from the first NSCLC diagnosis, and (3) metachronous NSCLC group (MN), showing other cancers diagnosed after 3 months or more from the first NSCLC diagnosis. Among 1350 cases enrolled, the frequencies of SPN, SN, and MN groups were 88.6% (1196 cases), 8.3% (112 cases), and 3.1% (42 cases), respectively. Background factors such as age, sex, performance status, smoking history, clinical stage, EGFR mutation, EML4-ALK fusion gene, ROS-1 gene, PD-L1 expression, and the number of affected cancers were adjusted using Cox proportional hazards model analysis. In SN group, NSCLC (32 cases), colon cancer (20 cases), and gastric cancer (12 cases) were commonly observed. Similarly, in MN group, NSCLC (17 cases), colon cancer (4 cases), and gastric cancer (4 cases) were commonly observed. The median survival times of SPN, SN, and MN groups were 24.0 months, 42.1 months, and not reached, respectively (p <0.001). Regarding the prognostic factors, the hazard ratios [HR] of SN and MN groups toward SPN group were 0.98 (95% confidence interval [CI]; 0.71 to 1.36, p = 0.91) and 0.38 (95% CI; 0.22 to 0.66, p <0.001), respectively. The other prognostic factors were 75 years old or older (HR; 1.46, 95% CI; 1.24 to 1.72, p <0.001), male (HR; 1.56, 95% CI; 1.26 to 1.94, p <0.001), performance status 3-4 (HR; 3.88, 95% CI; 3.09-4.82, p <0.001), smoking history (HR; 1.44, 95% CI; 1.12 to 1.84, p = 0.01), and clinical stage IIIB-IV NSCLC (HR; 4.37, 95% CI; 3.62 to 5.30, p <0.001). In patients with NSCLC who had never experienced cancers before, synchronous/metachronous multiple primary cancers could be often observed. However, their coexistence might not adversely affect the prognosis of firstly diagnosed NSCLC.

P5447Prognostic significance of carboxy-terminal telopeptide (ICTP) and Caspase-3 in patients with non-ischemic dilated cardiomyopathy

Abstract Background Non-ischemic dilated cardiomyopathy (niDCM) is a common debilitating disease leading to heart failure and poor prognosis. Therefore, a reliable diagnosis of niDCM and search of prognostic biomarkers is a task of paramount importance preventing final destruction of myocardium and improving the outcomes of the disease. The aim of the study was to evaluate the prognostic value of carboxy-terminal telopeptide (ICTP), a marker of myocardial collagen I degradation, and Caspase-3, a marker of apoptosis, in serum and endomyocardium biopsies (EMBs) of patients with niDCM. Methods 34 consecutive patients (male 25 (78%); 43.83±12.17 years) with niDCM (average of left ventricle (LV) end-diastolic diameter 6.94±0.78 cm, LV ejection fraction 24.97±6.93%, mean pulmonary capillary wedge pressure 32.9±8.7 mmHg) were enrolled in the study. The levels of ICTP and Caspase-3 in patients' serum and EMBs were measured by ELISA. After a follow-up period of 5 years, 18 patients (53%) have reached the primary composite end-point of heart failure: 6 patients (17.6%) died, 6 patients (17.6%) had heart transplantation and 6 patients (17.6%) underwent left ventricle assist device implantation. Results Univariate Cox proportional hazard model and ROC curve analysis identified levels of ICTP and Caspase-3 in serum as predictors of composite end-point (Table 1). However, the levels of ICTP and Caspase-3 in EMBs had no prognostic value. The cut-off values of serum biomarkers for prediction of the outcome were 13.43 pg/mg protein (sensitivity 67%; specificity 81%) for ICTP and 10.21 pg/mg protein (sensitivity 53%; specificity 87%) for Caspase-3. Univariate Cox regression analysis revealed that patients with higher levels of ICTP and Caspase-3 than cut-off values in serum had higher risk of reaching the composite end-point compared to the patients with lower cut-off values (HR 4.4 (95% CI: 1.6–12.1) and 3.15 (95% CI: 1.2–8.29), respectively). Kaplan-Meier survival analysis demonstrated that patients with serum Caspase-3 and ICTP levels above cut-off values had significantly worse outcome (p=0.01 and p=0.002, respectively). Table 1 Biomarkers (pg/mg protein) Mean ± SD HR (95% CI) p-value AUC (95% CI) ICTP in serum 15.26±10.59 1.052 (1.013–1.093) 0.009 0.71 (0.53–0.89) ICTP in EMB 132±295 0.999 (0.998–1.001) 0.56 0.45 (0.28–0.61) Caspase-3 in serum 7.78±9.86 1.047 (1.002–1.093) 0.04 0.69 (0.51–0.87) Caspase-3 in EMB 283±282 1 (0.998–1.002) 0.92 0.50 (0.28–0.72) Conclusion The findings show that increased serum levels of Caspase-3 and ICTP are significantly associated with poor outcome in patients with niDCM. Acknowledgement/Funding the Research Council of Lithuania (Grants nos. MIP-086/2012 and MIP-011/2014), the European Union, EU-FP7, SARCOSI Project (no. 291834)

Association between esophagogastric varices in hepatocellular carcinoma and poor prognosis after transarterial chemoembolization: A propensity score matching analysis

Whether esophagogastric varices (EGV) can determine the outcome of patients with hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE) remains unknown. This study aimed to assess the impact of EGV on the prognosis of HCC patients after TACE. From 2007 to 2012, we retrospectively enrolled 251 treatment-naïve HCC patients who underwent TACE and received esophagogastroduodenoscopy when HCC was diagnosed. The prognostic factors were analyzed using a Cox proportional hazards model and propensity score-matching analysis. There were 120 (47.8%) patients with EGV. Compared to those without EGV, patients with EGV had worse liver functional reserve. After a median follow-up of 14.7 months (25th-75th percentiles, 6.4-35.6 months), 152 patients died. The cumulative 5-year overall survival (OS) rates were 11.2% and 38.8% in patients with and without EGV, respectively (p<0.001). Multivariate analysis showed that presence of EGV, presence of ascites, tumor size >5cm, serum alpha-fetoprotein >20ng/mL, progressive disease by modified Response Evaluation Criteria in Solid Tumors, Assessment for Retreatment with TACE score ≥2.5, and higher albumin-bilirubin grades were the independent predictors of poor OS. Subgroup analysis also demonstrated that EGV was associated with poor OS in most of the subgroups. After propensity score matching, the EGV group still had a lower OS rate than their counterparts (p=0.004). HCC patients with EGV had worse liver functional reserve compared to those without EGV. Moreover, EGV was an independent risk factor to predict poor prognosis in patients with HCC after TACE.

Hepatobiliary phase hypointense nodule without arterial phase hyperenhancement as a risk factor for late recurrence (>1 year) of hepatocellular carcinoma after surgery

To evaluate the value of magnetic resonance imaging (MRI) features, including liver stiffness measured by magnetic resonance elastography (MRE) and the presence of hepatobiliary phase (HBP) hypointense nodule without arterial phase hyperenhancement (APHE), for predicting late recurrence (>1 year) after surgery for hepatocellular carcinoma (HCC). This retrospective study included 124 consecutive patients who had undergone surgery for HCC and preoperative MRI. After excluding patients with early recurrence within 1 year after surgery, 89 patients were analysed. Preoperative MRI images were reviewed by a radiologist to record imaging findings, including (1) liver stiffness by MRE, (2) size of the HCCs, (3) number of HCCs, and (4) presence of HBP hypointense nodule without APHE. Pathological findings included tumour grade, vascular/biliary/capsule invasion, and fibrosis stage of the liver. Considering imaging/pathological findings and patients' characteristics as dependent variables, Cox proportional hazards model analysis was performed to identify independent factors associated with late recurrence after surgery. The median follow-up period was 37.3 months. During follow-up, 29 patients (32.5%) developed late recurrence after surgery. In multivariate analysis, underlying liver disease (viral hepatitis) and presence of HBP hypointense nodules without APHE (p=0.010 and 0.033, respectively) were independently associated with disease-free survival (DFS). Kaplan-Meier analysis revealed that patients with HBP hypointense nodules without APHE had a significantly lower DFS rate than those without the nodule (39.2% versus 74.1% at 3 years after surgery, p=0.008). The presence of HBP hypointense nodules without APHE was an indicator of late recurrence after surgery for HCC.

Wedge resection is equal to segmental resection for pulmonary typical carcinoid patients at localized stage: a population-based analysis.

BackgroundMedical institutions worldwide have not reached a consensus on what surgery is the most advisable for pulmonary typical carcinoid (TC) patients at the localized stage. This research focuses on exploring whether wedge resection or segmental resection is the superior option.MethodsThe demographic and clinical information of 1,887 TC patients diagnosed at the localized stage from 2004 to 2015 was collected from the Surveillance, Epidemiology, and End Results (SEER) Program. Patient prognosis was evaluated by KM curves. The chi-square test was used to examine the variation between different groups that would be eliminated by propensity score matching (PSM). Univariate and multivariate Cox proportional hazard model analyses were used to evaluate prognostic values of relative factors.ResultsThe prognosis of TC was the most favorable for patients suffering from pulmonary squamous cell carcinoma (SCC), adenocarcinoma (ADC), and pulmonary carcinoids (PCs). The choice to have surgery, not the type of surgery chosen, was the most significant independent prognostic factor correlated with overall survival (OS) and lung cancer-special survival (LCSS). The prognostic result of the comparison between wedge resection and segmental resection was not statistically significant before or after PSM. In subgroup analysis, the inference still held.

LSD1、MGMT和Ki-67在高级别胶质瘤中的表达及对预后的影响

Objective To investigate the expressions of histone lysine-specific demethylase 1 (LSD1), O6-methylguanine DNA methyltransferase (MGMT) and cell proliferation-associated antigen Ki-67 in high-grade glioma and their influences on prognosis. Methods Sixty-five cases of grade Ⅲ and Ⅳ glioma confirmed by pathology from January 2011 to June 2017 in the First Affiliated Hospital of Xinjiang Medical University were selected. Immunohistochemistry (SP method) was used to detect the expressions of LSD1, MGMT and Ki-67 in pathological specimens. The therapeutic effect was evaluated by long-term follow-up. The relationships between the three markers and pathological grade, progression-free survival (PFS) and overall survival (OS) were analyzed. Results The overall positive rates of LSD1, MGMT and Ki-67 in the 65 high-grade glioma specimens were 70.8% (46/65), 60.0% (39/65) and 100.0% (65/65), respectively. There were no significant differences in the expressions of LSD1 and MGMT in grade Ⅲ and Ⅳ glioma (χ2=1.588, P=0.208, χ2=0.013, P=0.908). Ki-67 expression (+ ), (+ + ), (+ + + ) in grade Ⅳ glioma were observed in 18, 19 and 11 cases, respectively. Ki-67 expression (+ ), (+ + ) in grade Ⅲ glioma were observed in 11, 5 cases, and 1 case was (+ + + ), and the difference in expression intensity between the two groups was statistically significant (Z=-2.083, P=0.037). Log-rank test showed that the positive expressions of LSD1, MGMT and Ki-67 were negatively correlated with the PFS of patients with high-grade glioma (χ2=12.217, P=0.007; χ2=4.446, P=0.035; χ2=12.536, P=0.002), also were negatively correlated with OS (χ2=11.708, P=0.008; χ2=6.637, P=0.010; χ2=11.807, P=0.003). Grade Ⅳ patients were more likely to have relapse progression than grade Ⅲ patients (χ2=6.573, P=0.010), and OS was shorter (χ2=3.974, P=0.046). Cox proportional hazards model analysis showed that the expressions of LSD1 (HR=1.361, 95%CI: 1.094-1.694, P=0.006; HR=1.406, 95%CI: 1.117-1.771, P=0.004) and Ki-67 (HR=1.703, 95%CI: 1.175-2.468, P=0.005; HR=1.778, 95%CI: 1.209-2.616, P=0.003) were the independent prognostic risk factors for PFS and OS of patients with high-grade glioma. Correlation analysis results showed that the expression of MGMT was positively correlated with the expression of LSD1 (r=0.406, P=0.001). Conclusion LSD1, MGMT and Ki-67 have higher positive expression rates in high-grade glioma. MGMT is a prognostic factor for high-grade glioma, and LSD1 and Ki-67 can be used as independent predictors of prognosis for high-grade gliomas. Key words: Glioma; O(6)-methylguanine-DNA methyltransferase; Ki-67 antigen; Prognosis; Lysine specific demethylase 1

Abstract P2066: The Difference of With or Without Blood Pressure Adjustment for Pulse Wave Velocity as a Risk Factor for Cardiovascular Disease

Background: Arterial stiffness, assessed by pulse wave velocity (PWV), is an independent predictor of future cardiovascular (CV) events. While blood pressure (BP) functionally increases the value of PWV, the significance of this increase as a risk for CV disease (CVD) has not been fully clarified. The stiffness-index beta has been used as a less BP-influenced marker to assess arterial stiffness. Then, the present study examined whether BP-adjusted value of the PWV improve or attenuate the predictive value for the development of the hypertension, retinopathy, and renal dysfunction, or of future CV events as compared to brachial-ankle PWV (baPWV). Methods and Results: Study 1: In the 7-year prospective observation conducted in 3274 Japanese men without hypertension at the baseline for the development of hypertension and also in 3490 Japanese men for the development of organ damage, baPWV, BP, estimated glomerular filtration rate (eGFR), and fundus findings were measured at baseline and end of study period. During the study period, 474 subjects developed to hypertension, 29 subjects had renal dysfunction, and 91 subjects had the development of retinopathy. The area under the curve (AUC), in the receiver operator characteristic curve analysis, of baPWV was higher than that of BP-adjusted baPWV for the development of hypertension (0.73 vs. 0.59; p&lt;0.01), for eGFR &lt;60 mL/min/1.73m 2 and for the development of retinopathy. The baPWV rather than BP-adjusted baPWV showed a significant odds ratio for the development of hypertension (1.84 per standard deviation increase, p&lt;0.01) and that of retinopathy (1.25 per standard deviation increase, p&lt;0.01). Study 2: During the 3-year observation period in 511 patients with coronary artery disease, 72 CV events were confirmed. While the AUCs of both markers for the development of CV events were similar, the Cox proportional hazards model analysis revealed that baPWV rather than BP-adjusted baPWV showed a significant hazard ratio (1.38, P&lt;0.01) for the development of CV events. Conclusions: The BP adjustment, based on the concept of stiffness-index beta, may attenuate the significance of baPWV as a risk marker for the development of CVD, especially in its development related pathophysiological abnormalities in male subjects.

Type 2 Diabetes Mellitus non-surgical remission: A possible mission

BackgroundRemission of Type 2 Diabetes Mellitus (DM) has been observed throughout the last few years, yet factors associated with remission through non-surgical approaches are still unclear. So, the factors associated with type 2 DM remission were investigated. MethodsOut 670 patients, 63 patients gained non-surgical remission of type 2 DM (defined according to ADA criteria), and 396 patients served as control matched for age, sex, and BMI. The records of patients who attended Alexandria University Students Hospital between the years 2015 and 2018 were reviewed retrospectively. The collected data at first visit and 1 year after remission were history, examination, HbA1c %, oral glucose tolerance test & fasting blood glucose and lipid profile and type of treatment. Results75% of patients were females with mean age 51.5 ± 11.34 years. The mean duration of treatment till remission was 26.4 ± 33.1 months. One year after remission HbA1c & BMI were significantly decreased (P = 0.001, 0.03; respectively). However, cox proportional hazards model & ROC curve analysis showed that age < 50 years, female sex, short duration of diabetes < 5.2 years, intial HbA1c < 8.5%, HDL > 45.6 mg/dl, and initial intervention with lifestyle modification, 2000 mg metformin and 100 mg vildagliptin are the factors associated with remission. ConclusionOur mission in type 2 DM female patients < 50 years with short duration of disease < 5.2 years, initial HbA1c < 8.5% and HDL > 45.6 mg/dl, is to achieve diabetes remission by intensive life style modification with daily metformin and vildagliptin.

Analysis of clinical characteristics and medium-term prognosis of advanced elderly patients with mild ischemic stroke

Objective To investigate clinical characteristics and medium-term prognosis of the advanced elderly patients with mild ischemic stroke, and to evaluate the risk factors for poor clinical outcome. Methods The 574 elderly patients with mild acute ischemic stroke admitted in neurology department of our hospital were retrospectively studied from January 2016 to December 2017.All cases were divided into the advanced elderly group(n=276, ≥80 years old)and elderly patient group(n=298, 60-79 years old). Clinical characteristics were analyzed.After 12-month follow-up, the mid-term prognosis and risk factors for poor clinical outcome(mRS≥3)were analyzed in the two groups. Results Compared with the elderly patients, the advanced elderly patients were more often complicated with history of atrial fibrillation, diabetes and stroke(P 0.05). After an average follow-up of(11.3±1.5)months, the proportions of poor clinical outcome and mortality were higher in the advanced elderly patients than in the elderly patients(63.4% or 175/276 vs.48.0% or 143/298, 25.7% or 71/276 vs.16.1% or 48/298, P<0.05). Cox proportional hazard model analysis showed that age, baseline NIHSS score and mRS score, diabetes and stroke history were the risk factors for poor clinical outcome in elderly patients with mild ischemic stroke(all P<0.05). Conclusions The advanced elderly patients with mild ischemic stroke have a severe clinical condition, higher rates of atrial fibrillation, diabetes and stroke history, and poor mid-term prognosis.Age, baseline scores of NIHSS and mRS, diabetes and stroke history are the risk factors for poor clinical outcome in elderly patients with mild ischemic stroke. Key words: Aged, 80 and over; Brain ischemic; Prognosis; Risk factors

Use of Survival Analysis to Predict Attrition Among Women Participating in Longitudinal Community-Based Nutrition Research

ObjectiveTo identify participant characteristics and study methodology that influenced the completion of a 15-month community-based longitudinal study evaluating the impact of the Supplemental Nutrition Assistance Program Education and Expanded Food and Nutrition Education Program. DesignObservational longitudinal 15-month study across 12 data collection timepoints. Sociodemographic characteristics were collected with a paper-based survey at baseline. SettingFive counties across central and southern Illinois. ParticipantsWomen, aged 18 to 65 years (n = 297), recruited at sites likely to serve families eligible for the Supplemental Nutrition Assistance Program Education and Expanded Food and Nutrition Education Program (housing departments, child care centers, etc). Main Outcome MeasuresPredictors of participant attrition during the study duration. AnalysisCox proportional hazard models. ResultsNinety-seven participants were retained across the full study. In unadjusted models, greater income and education levels were significantly related to lower attrition; however, this relationship did not persist in a multivariate model. When adjusted for other characteristics, larger household size was the only measured variable significantly related to greater odds of attrition (odds ratio = 1.09; 95% confidence interval = 1.02, 1.17). Conclusions and ImplicationsSeveral characteristics predicting attrition in other settings were not significant in this study. Future attrition analyses that evaluate social support, transportation capacity, and type of phone in longitudinal nutrition education studies are warranted.

Snoring and incident chronic kidney disease: a community-based prospective cohort study

ObjectivesPrevious studies have shown that symptoms of sleep-disordered breathing are associated with metabolic derangements and vascular disease development. However, the relationship between snoring and renal function is not well investigated....

SUN-042 C3 GLOMERULOPATHY AND IMMUNE COMPLEX MEDIATED MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS: COMPARING DIALYSIS AND TRANSPLANT OUTCOMES

Membranoproliferative glomerulonephritis (MPGN) is a rare cause of end stage kidney disease (ESKD) that is comprised of two separate pathogenic entities: C3 glomerulopathy (C3GN) and immune complex mediated MPGN (ICMPGN). Whether these conditions have different clinical outcomes is currently unknown. We used the Australian and New Zealand Dialysis and Transplant (ANZDATA) Registry to compare the characteristics and outcomes of patients with ESKD secondary to C3GN and ICMPGN. All patients with ESKD secondary to MPGN who commenced dialysis or kidney transplantation in Australia and New Zealand between 1996 and 2016 were included. Patients with ESKD secondary to C3GN were compared to those with ESKD secondary to ICMPGN. Dialysis patient survival, transplant patient survival and death-censored graft survival were evaluated by Kaplan-Meier and multivariable Cox proportional hazards model analyses. Competing risks regression was performed as a sensitivity analysis. Competing events were transplantation and renal recovery for dialysis patient survival, allograft failure for transplant patient survival and patient death for death-censored allograft survival. Of the total ESKD population of 53,729 patients, 76 had C3GN (mean age 52 ± 20 years, 36% female) and 380 had ICMPGN (mean age 50 ± 18 years, 39% female). Baseline demographic and clinical characteristics were comparable between the two groups. Patients with C3GN had lower 5-year dialysis survival rates compared to those with ICMPGN (42% vs. 62%, p=0.05; Cox-adjusted hazard ratio [HR] 1.40, 95% CI 0.94-2.08; competing risks HR 1.34, 95% CI 1.01-1.8). Renal recovery following dialysis commencement was significantly less common with C3GN compared to ICMPGN (0% vs. 4%, p<0.01). 37 patients with C3GN and 171 patients with ICMPGN proceeded to kidney transplantation. Death-censored graft survival was similar between C3GN and ICMPGN (5 year survival 68% vs. 74%, p=0.42; Cox-adjusted HR 1.47, 95% CI 0.74-2.89; competing risk HR 1.47, 95% CI 0.84-2.55). Graft loss due to disease relapse was a common cause of graft loss in both groups occurring in 16% of patients with C3GN and 9% of those with ICMPGN (p=0.35). Transplant patient survival was comparable between the two groups (5 year survival 96% vs. 92%, p=0.35; Cox-adjusted HR 0.39, 95% CI 0.05-2.97; competing risk HR 0.35, 95% CI 0.06-1.85). Compared to patients with ESKD due to ICMPGN, those with C3GN had poorer survival on dialysis, lower rates of dialysis-independent renal recovery and comparable kidney transplant outcomes. Both groups had high rates of disease relapse causing graft loss. These findings support the notion that ICMPGN and C3GN are different clinical entities.

Abstract 462: Results from multiple datasets including the TCGA reveal limited clinical significance of molecular subtypes in bladder cancer

Abstract INTRODUCTION AND OBJECTIVE: Molecular subtypes have been suggested to predict outcome in patients with muscle invasive bladder cancer (MIBC). The major subtypes reported have been “luminal” and “basal”; however, there is little consensus regarding subtype-signatures and the clinical parameters used to evaluate outcome. The objective of this study was to examine using multiple datasets, if molecular subtypes are distinct entities within MIBC and whether they predict clinical outcome. METHODS: We analyzed transcriptome data from all 402 MIBC samples in The Cancer Genome Atlas (TCGA) and 151 high-grade MIBC samples from three datasets in Oncomine™. Transcript levels were also measured in 52 bladder tumor specimens with clinical follow-up (cohort-1). Samples were subtype-scored using gene panels (GP-11, GP-30, BASQ) consisting only of those genes common among published studies. Correlation of subtypes to recurrence/progression-free survival (R/PFS), metastasis, cancer-specific survival (CSS) and overall-survival (OS) was examined by logistic regression, Cox proportional Hazards model and Kaplan-Meier analyses. RESULTS: Based on GP-11 subtype-scoring, &amp;gt;75% of the MIBC TCGA-dataset samples were mixed, i.e. neither pure-luminal nor pure-basal. When tumors were categorized as pure-luminal, pure-basal, or mixed, the subtypes could not predict OS or R/PFS. Consistent with published studies, when tumors were categorized as luminal or basal the subtypes predicted OS (P=0.051); sensitivity: 53.9%; specificity: 62%. Subtypes also correlated with tumor-grade (P=0.0005); most low-grade MIBC cases (16/21) in the TCGA-dataset were luminal. However, MIBC is rarely low-grade and subtypes could not predict OS (P=0.131) when only high-grade cases were included. Subtypes were not significant prognosticators in multivariate analyses. GP-30 and BASQ panels validated these results. In the Oncomine-dataset and cohort-1, subtypes could not predict metastasis, CSS, or OS. CONCULUSIONS: Our study of multiple datasets reveals that molecular subtypes may reflect tumor-heterogeneity but are likely not distinct entities within MIBC. Furthermore, molecular subtypes have limited prognostic capability for MIBC patients. Although there is a need to individualize patient care, further examination into the molecular subtypes of MIBC is needed before their incorporation into clinical practice. Citation Format: Sarrah S. Lahorewala, Daley S. Morera, Jiaojiao Wang, Vinata B. Lokeshwar. Results from multiple datasets including the TCGA reveal limited clinical significance of molecular subtypes in bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 462.

Identification of potential key genes and pathways predicting pathogenesis and prognosis for triple-negative breast cancer

BackgroundTriple negative breast cancer (TNBC) is a specific subtype of breast cancer with a poor prognosis due to its aggressive biological behaviour and lack of therapeutic targets. We aimed to explore some novel genes and pathways related to TNBC prognosis through bioinformatics methods as well as potential initiation and progression mechanisms.MethodsBreast cancer mRNA data were obtained from The Cancer Genome Atlas database (TCGA). Differential expression analysis of cancer and adjacent cancer, as well as, triple negative breast cancer and non-triple negative breast cancer were performed using R software. The key genes related to the pathogenesis were identified by functional and pathway enrichment analysis and protein–protein interaction network analysis. Based on univariate and multivariate Cox proportional hazards model analyses, a gene signature was established to predict overall survival. Receiver operating characteristic curve was used to evaluate the prognostic performance of our model.ResultsBased on mRNA expression profiling of breast cancer patients from the TCGA database, 755 differentially expressed overlapping mRNAs were detected between TNBC/non-TNBC samples and normal tissue. We found eight hub genes associated with the cell cycle pathway highly expressed in TNBC. Additionally, a novel six-gene (TMEM252, PRB2, SMCO1, IVL, SMR3B and COL9A3) signature from the 755 differentially expressed mRNAs was constructed and significantly associated with prognosis as an independent prognostic signature. TNBC patients with high-risk scores based on the expression of the 6-mRNAs had significantly shorter survival times compared to patients with low-risk scores (P < 0.0001).ConclusionsThe eight hub genes we identified might be tightly correlated with TNBC pathogenesis. The 6-mRNA signature established might act as an independent biomarker with a potentially good performance in predicting overall survival.

PD-L1 expression on circulating tumor cells and prognosis of breast cancer patients.

e14028 Background: Nowadays programmed cell death (ligand) 1 (PD1/PD-L1) inhibitors in the clinic show benefit for appropriate patient. There are clinical trials for specific breast cancer patients. We all know that the prognosis of breast cancer is associated with CTC. However, PD-L1 expression on circulating tumor cells (CTC) is lack of research. It is crucial for the prediction and supervision of molecular-targeted therapy, while the predictive biomarker response to PD(-L)1 checkpoint inhibitors is lacking. So we tried to explore the relationship between overexpression of PD-L1 on CTCs and prognosis and clinicopathological features of breast cancer patients. Methods: We analyzed CTC and PD-L1 mRNA expression on CTC in 20 primary breast cancer patients, through mRNA probe hybridization. The relationship between clinicopathological features and PD-L1 expression on CTC was analyzed by chi square test. Kaplan-Meier and univariate Cox proportional hazards model analyses were used to compare the survival of patients with high PD-L1 expression and patients with low PD-L1 expression. Results: The median follow-up time was 40 months (range, 36-43 months). Of the 20 patients, 15 had more than 1 CTC in 7.5ml peripheral blood. Among the 15 patients, each one has at least 1 CTC showing PD-L1. The expression of PD-L1 on CTC was divided into low expression, medium expression and high expression, then we gave 1 score for low expression, 2 score for medium expression and 3 score for high expression. PD-L1 high expression was total score≥3, while PD-L1 low expression was total score ＜ 3. We found PD-L1 expression on CTC is related to the tumor size(P = 0.012) lymph node status (P = 0.001) and PR status (P = 0.037). There was significant difference between T2 and T3 in large tumor group(P = 0.003), while in node status group statistical difference can be found in N1 vs N3(P = 0.000) and N2 vs N3(P = 0.015). Our data indicated that patients with high PD-L1 expression on CTC had poor overall survival(P = 0.004) compared to low PD-L1 expression on CTC (Table). Univariate Cox proportional hazards model analysis showed that high PD-L1 expression on CTC was an independent prognostic factor. Conclusions: PD-L1 on CTC is indeed associated with some poor clinicopathological features. High expression of PD-L1 on CTC is an independent prognostic factor for shorter survival. [Table: see text]

Expression of MiR-148b-3p in Lung Adenocarcinoma and Its Correlation with Prognosis

背景与目的MiR-148b-3p是一种重要的微小RNA，已经被报道与多种癌症密切相关，但其在肺腺癌中的作用仍不清楚。本研究的目的是检测miR-148b-3p在肺腺癌中的表达水平，并分析其与临床病理特征及患者预后的相关性。方法收集2011年1月-2012年12月在本科室经手术切除的肺腺癌患者的肿瘤标本123例，利用实时荧光定量PCR方法检测miR-148b-3p的表达量，分析其与患者临床病理特征的相关性。利用多因素Cox比例风险模型分析影响患者总生存的独立预测因子。利用Kaplan-Meier生存分析方法估计miR-148b-3p高表达组和低表达组患者的总生存期，并使用Log-rank检验方法进行显著性检验。结果在123例肺腺癌患者中，有71例高表达miR-148b-3p，52例低表达。miR-148b-3p与肿瘤的分化程度（P=0.001）、肿瘤大小（P=0.007）显著相关，而与年龄、性别、吸烟史、饮酒史、脉管癌栓、胸膜侵犯、淋巴结转移、远处转移和术后治疗不存在统计学显著的相关性。多因素Cox比例风险模型分析显示肿瘤大小（P=0.032）、淋巴结转移（P=0.005）和miR-148b-3p表达量（P=0.047）是影响患者总生存的独立预测因子。Kaplan-Meier生存分析显示miR-148b-3p高表达组患者的总生存显著优于miR-148b-3p低表达组患者（P=0.010）。结论MiR-148b-3p在肺腺癌中与肿瘤的分化程度、肿瘤大小显著相关，并且是影响患者总生存的独立预测因子。MiR-148b-3p高表达组患者的总生存显著优于低表达组患者。因此，miR-148b-3p可能成为新的肺腺癌治疗靶标或预后生物标志物。