Five-year Rate Research Articles

The impact of intraocular pressure fluctuations and other factors on conversion of ocular hypertension to primary open-angle glaucoma.

To evaluate the role of intraocular pressure (IOP) fluctuations and other factors on conversion of ocular hypertension to open-angle glaucoma (OAG) within a retrospective, longitudinal cohort study. The study population included patients with ocular hypertension defined by IOP > 21mmHg with normal appearing optic discs and no visual field defect. IOP fluctuation, mean and maximum were examined in 61 eyes over a follow-up period of 36months (standard deviation (SD) 24). All patients underwent at least two 48-h IOP profiles including night-time IOP measurements in the supine position, visual field examinations, Heidelberg retina tomograph analyses (HRT) and optic disc photographs. Regression analyses were performed to demonstrate the impact of IOP parameters, myopia, sex, cup/disc ratio and visual field results on conversion to glaucoma. While IOP fluctuation and mean did not impact conversion, myopia proved to be a risk factor (HR 14.4; 95% CI: [3.9-53.0]; p ≤ 0.001). Over an average of three years, 6/61 converted to OAG. The study yielded a mean long-term IOP over all available pressure profiles of 18.1mmHg (SD 3.2) and an IOP fluctuation of 1.9mmHg (SD 1.1) within a mostly treated cohort. Conversion-free five-year rate was 59.8%. The amount of fluctuation we measured in our study sample did not result in the development of glaucoma in treated ocular hypertension patients. Myopic subjects with ocular hypertension are at a higher risk for glaucoma conversion than non-myopic ocular hypertensive subjects are.

Prognostic evaluation of patients with TNM stage I to III gastric cancer by platelet-lymphocyte ratio and neutrophil-lymphocyte ratio

Objective To compare the ability of platelet-lymphocyte ratio (PLR) and neutrophil-lymphocyte ratio (NLR) in evaluating the prognosis of patients with TNM stageⅠto Ⅲ gastric cancer. Methods From May 2001 to December 2013, the clinicopathological data of 645 patients with gastric cancer treated at Harbin Medical University Cancer Hospital were retrospectively analyzed. Chi-square test was used to analyze the differences between NLR, and PLR and clinicopathological characteristics of patients. Kaplan-Meier method and log-rank test were performed to compare the overall survival of patients. Cox proportional hazards regression model was performed to analyze the prognosis of gastric cancer patients. The ability of NLR and PLR to evaluate the prognosis of gastric cancer was compared by receiver operating characteristic curve. Results The cutoff values of PLR and NLR were 141.50 and 1.94, respectively. PLR was associated with gender, resection method, maximum diameter of tumor, whether chemotherapy, T-stage, N-stage, TNM stage, tumor location, white blood cell, hemoglobin, albumin, and whether total gastrectomy (χ2=9.224, 10.577, 28.825, 6.831, 29.059, 28.637, 30.748, 18.023, 24.320, 77.274, 9.021 and 10.745, all P<0.05). NLR were associated with resection method, maximum diameter of tumor, T-stage, N-stage and TNM stage, white blood cell, hemoglobin and albumin (χ2=14.563, 12.092, 22.697, 44.735, 34.151, 7.949, 9.611 and 7.498, all P<0.05). The results of multivariate analysis showed that resection method, whether chemotherapy, T-stage, N-stage, PLR and whether total gastrectomy were all independent risk factors for gastric cancer patients (χ2=23.653, 22.023, 16.697, 24.038, 4.110 and 22.364, all P<0.05). The five-year cumulative survival rate of the patients with PLR<141.50 was higher than that of patients with PLR≥141.50 (55.4% vs. 30.5%), and the difference was statistically significant (χ2=47.968, P<0.01). The AUC value of PLR in prognostic evaluation of gastric cancer was 0.629, which was higher than that of NLR (0.596, P<0.01). Conclusion PLR is better than NLR in the prognostic evaluation of gastric cancer patients. Key words: Stomach neoplasms; Prognosis; Platelet-lymphocyte ratio; Neutrophil-lymphocyte ratio

Accessory hepatic vein recanalization for hepatic vein-type Budd–Chiari syndrome

Purpose To explore the clinical efficacy and long-term outcomes of accessory hepatic vein (AHV) recanalization as a means of treating hepatic vein (HV)-type Budd–Chiari syndrome (BCS). Methods Between January 2011 and December 2018, a total of 46 symptomatic HV-type BCS patients were treated by AHV recanalization in our hospital. The technical and clinical success of this treatment, as well as associated long-term patient prognosis was assessed herein. Results The AHV recanalization approach was technically successful in 100% of patients, without any instances of complications associated with the operation. This procedure was 95.7% (44/46) clinically successful and resultant. AHV re-obstruction occurred in 12 patients. The cumulative primary one-, two-, and five-year patency rates were 77.3%, 71.7%, and 71.7%, respectively. The secondary cumulative one-, two-, and five-year patency rates were 97.7, 87.1, and 87.1%, respectively. The five-year patency rates did not differ significantly between patients treated with balloons and stents (p = .674). Based on Cox-regression analysis, younger age was an independent predictor of re-obstruction (p = .005). The cumulative one-, two-, and five-year survival rates were 97.7, 92.2, and 92.2%, respectively. Conclusions AHV recanalization is a safe and effective treatment for HV-type BCS.

Abstract TP406: Risk of Recurrent Childhood Stroke Differs by Vasculopathy Subtype

Introduction: Head and neck vasculopathies are the most frequent identifiable cause of childhood arterial ischemic stroke, and abnormal vascular imaging is associated with higher risk of stroke recurrence. Despite this, little is known about how vasculopathy subtype impacts risk of both initial and recurrent stroke. In this single-center retrospective analysis, we analyze differences in stroke recurrence by vasculopathy subtype. Methods: Using ICD codes, we identified children treated for a head or neck vasculopathy at our tertiary care center between 2003 and 2019. Inclusion criteria included imaging-confirmed head or neck vasculopathy diagnosed between the ages of 28 days and 18 years. Retrospective chart review was carried out with attention to vasculopathy subtype and occurrence/recurrence of stroke and TIA. Results: Ninety-three patient met inclusion criteria, including 55 who experienced a stroke. Five-year stroke recurrence rates differed significantly by vasculopathy subtype (n=28, p=0.030, Fisher exact test), as patients with moyamoya disease (MMD) and sickle cell, Down syndrome, or neurofibromatosis-related vasculopathy experienced higher recurrence rates. There was a non-significant increased rate of stroke recurrence among patients with secondary versus primary MMD. Conclusions: Children with primary and secondary MMD have a higher risk of stroke recurrence than children with other vasculopathy subtypes. Further studies are needed to evaluate the effect of vasculopathy etiology and other radiographic and clinical characteristics on stroke recurrence risk so that appropriate treatment strategies can be implemented early in these high-risk patients.

Prognostic impact of SOX9 in stage II colon cancer: Results from a large nationwide cohort.

183 Background: Up-regulation of the transcription factor SOX9 has been described in colon cancer, and it has been argued that differences in the expression levels dictates cell proliferation. The aim of the present study was to analyze the prognostic impact of SOX9 in patients with stage II colon cancer. Methods: Individual patient data and formalin fixed paraffin embedded tumor tissue were collected from a large unbiased, population-based cohort, representing all patients operated for stage II colon cancer in Denmark in 2002 and 2003. The SOX9 expression was evaluated by immunohistochemistry on whole tumor sections. Patients were classified into three groups dependent on the SOX9 expression gradient in the tumor: luminal, peripheral, and uniform for comparison with the clinical data. The endpoint was disease free survival (DFS). Results: A total of 1,153 patients were included. We detected an expression-dependent relationship between SOX9 and prognosis. Patients with tumors exhibiting a luminal expression pattern (N = 267, increasing SOX9 expression towards the luminal compartment of the tumor) were characterized by a significantly better DFS compared to the uniform (N = 846) and peripheral (N = 40) patterns, p = 0.0070. The five-year DFS rates were 74%, 67%, and 56%, respectively. Multiple Cox regression analysis, confirmed an independent prognostic advantage of the luminal SOX9 expression pattern, as compared to the uniform pattern, hazard ratio (HR) 0.7211 (95% confidence interval (CI) 0.5561-0.9351), p = 0.0137, whereas the possible disadvantage of the periphery pattern could not be verified, p = 0.1405. Conclusions: The present results support a prognostic impact of SOX9 in stage II colon cancer. The consequence of an altered SOX9 expression seems to differ between intra-tumoral compartments, and we propose that a gradient-dependent evaluation should be applied to provide the most clinically relevant information about this transcription factor.

Billiat intra-operative stents in orthotopic liver transplantation

Presenter: Mohammed Aldamry | McGill University Background: Biliary complications can affect 40% of patients after orthotopic liver transplantation (OLTx). Endoscopic management has a high success rate but involves multiple sessions and up to 21% complications. Biliary plastic stents placed manually during OLTx can splint a choledocho-choledochal anastomosis, possibly reducing biliary strictures and leaks. This study evaluates the feasibility and clinical outcomes of “prophylactic” intraoperative stenting at a single center, using a propensity-matched analysis. Methods: All consecutive OLTx patients over a 10-year period are included except for patients with hepaticojejunostomy, fulminant hepatic failure, redo grafts and combined organ transplants. The primary outcome is the incidence of biliary complications (leaks and strictures). Secondary outcomes include: stent morbidity, number of biliary interventions, cholangitis, acute renal failure, graft and patient survival. Propensity scoring was used to diminish selection bias. Outcomes were analyzed for a minimum of 5 years. Results: 265 OLTx patients were included between 2002-2011. 95 patients (36%) received intraoperative stents whereas 170 did not. Age, Gender, and medical comorbidities were similar between groups. Total biliary complications (44.2% Vs 44.7%, P=0.94) and biliary stricture rates (45.3%Vs 43.5%, P= 0.79) were similar between groups. However biliary leaks were significantly less frequent in the stented group (2%) vs. non-stented (10%), (P=0.02). Five-year rates of cholangitis, choledocholithiasis, and acute renal failure were similar between both groups. A propensity score model based on multiple covariates including surgeon, year of transplantation and Charlson comorbidity score was used to match 95 patients in each group. The rate of biliary leaks remained significantly lower in the stented group, OR= 0.19 (95%CI= 0.04; 0.86). Conclusion: Intraoperative use of biliary stents at OLTx is feasible and safe, resulting in less biliary leaks without significantly greater adverse events. 5-year biliary stricture rates appear similar. This study suggests a stenting strategy is feasible and that a randomized trial is worthwhile.

Mitral Valve Surgery in Neonates, Infants, and Children: Surgical Approach, Outcomes, and Predictors

The surgical treatment of mitral disease in pediatrics is challenging. Managing diversity in patient anatomy, growth, and the need for long-term anticoagulation requires trade-offs between imperfect solutions. We sought to assess our approach to pediatric mitral valve surgery and identify predictors associated with mortality and recurrent mitral disease. The medical records, echocardiograms, and operative reports of all patients who underwent surgical intervention on the mitral valve from January 2000 to April 2016 were reviewed. A total of 143 patients underwent mitral valve surgery, 64 of which were neonates or infants (ages 10-355 days) and 79 of which were children (ages 1-17.8 years). Neonates and infants had a higher preoperative New York Heart Association heart failure classification in comparison to children (P < 0.001) with a less severe degree of mitral valve insufficiency (P = 0.007). Postoperative outcomes for primary repair patients (n = 133) demonstrated significant differences in recurrence of mitral valve disease, with 38% of neonates/infants and 21% of children affected (P = 0.028). Five-year rates of mortality or transplant were 22% (8%, 33%) in neonates and infants compared to 4% (0%, 10%) in children, P = 0.013. Mitral valve surgery in neonates and infants is particularly high risk and is associated with higher rate of recurrence and reintervention early. However, if successful early, mitral valve repair in neonates and infants can result in a durable freedom from reintervention that parallels freedom from reintervention in older children undergoing repair. Further understanding of mechanisms of failure and better matching of anatomic substrate to strategy is needed.

Relative survival after diagnosis with a primary brain or other central nervous system tumor in the National Program of Cancer Registries, 2004 to 2014.

The majority of reported cancer survival statistics in the United States are generated using the National Cancer Institute's publicly available Surveillance, Epidemiology, and End Results (SEER) data, which prior to 2019 represented 28% of the US population (now 37%). In the case of rare cancers or special subpopulations, data sets based on a larger portion of the US population may contribute new insights into these low-incidence cancers. The purpose of this study is to characterize the histology-specific survival patterns for all primary malignant and nonmalignant primary brain tumors in the United States using the Centers for Disease Control and Prevention's National Program of Cancer Registries (NPCR). Survival data were obtained from the NPCR (includes data from 39 state cancer registries, representing 81% of the US population). Relative survival rates (RS) with 95% CI were generated using SEER*Stat 8.3.5 from 2004 to 2014 by behavior, histology, sex, race/ethnicity, and age at diagnosis. Overall, there were 488 314 cases from 2004 to 2014. Overall 5-year RS was 69.8% (95% CI = 69.6%-69.9%). Five-year RS was 35.9% (95% CI = 35.6%-36.1%) for malignant and 90.2% (95% CI = 90.1%-90.4%) for nonmalignant tumors. Pilocytic astrocytoma had the longest 5-year RS (94.2%, 95% CI = 93.6%-94.6%) of all glioma subtypes, whereas glioblastoma had the shortest 5-year RS (6.1%, 95% CI = 6.0%-6.3%). Nonmalignant nerve sheath tumors had the longest 5-year RS (99.3%, 95% CI = 99.1%-99.4%). Younger age and female sex were associated with increased survival for many histologies. Survival after diagnosis with primary brain tumor varies by behavior, histology, and age. Using such a database that includes more than 80% of the US population may represent national survival patterns.

Microscopic Extracapsular Extension in Sentinel Lymph Nodes Does Not Mandate Axillary Dissection in Z0011-Eligible Patients

In the ACOSOG (American College of Surgeons Oncology Group) Z0011 trial and the AMAROS (After Mapping of the Axilla: Radiotherapy or Surgery?) trial, matted nodes with gross extracapsular extension (ECE), a risk factor for locoregional recurrence, were an indication for axillary lymph node dissection (ALND), but the effect of microscopic ECE (mECE) in the sentinel lymph nodes (SLNs) on recurrence was not examined. Between 2010 and 2017, 811 patients with cT1-2N0 breast cancer and SLN metastasis were prospectively managed according to Z0011 criteria, with ALND for those with more than two positive SLNs or gross ECE. Management of mECE was not specified. In this study, we compare outcomes of patients with one to two positive SLNs with and without mECE, treated with SLN biopsy alone (n = 685). Median patient age was 58years, and median tumor size was 1.7cm. mECE was identified in 210 (31%) patients. Patients with mECE were older, had larger tumors, and were more likely to be hormone receptor positive and HER2 negative, have two positive SLNs, and receive nodal radiation. At a median follow-up of 41months, no isolated axillary failures were observed. There were 11 nodal recurrences; two supraclavicular ± axillary, four synchronous with breast, and five with distant failure. The five-year rate of any nodal recurrence was 1.6% and did not differ by mECE (2.3% vs. 1.3%; p = 0.84). No differences were observed in local (p = 0.08) or distant (p = 0.31) recurrence rates by mECE status. In Z0011-eligible patients, nodal recurrence rates in patients with mECE are low after treatment with SLN biopsy alone, even in the absence of routine nodal radiation. The presence of mECE should not be considered a routine indication for ALND.

Limited value of NT-proBNP as a prognostic marker of all-cause mortality in patients with heart failure with preserved and mid-range ejection fraction in primary care: A report from the swedish heart failure register

Aim: The prognostic value of natriuretic peptides in the management of heart failure (HF) patients with ejection fraction (EF) <40% is well established, but is less known for those with EF ≥40% managed in primary care (PC). Therefore, the aim of this study is to describe the prognostic significance of plasma NT-proBNP in such patients managed in PC.Subjects: We included 924 HF patients (48% women) with EF ≥40% and NT-proBNP registered in the Swedish Heart Failure Registry. Follow-up was 1100 ± 687 days.Results: One-, three- and five-year mortality rates were 8.1%, 23.9% and 44.7% in patients with EF 40–50% (HFmrEF) and 7.3%, 23.6% and 37.2% in patients with EF ≥50% (HFpEF) (p = 0.26). Patients with the highest mean values of NT-proBNP had the highest all-cause mortality but wide standard deviations (SDs). In univariate regression analysis, there was an association only between NT-proBNP quartiles and all-cause mortality. In HFmrEF patients, hazard ratio (HR) was 1.96 (95% CI 1.60–2.39) p < 0.0001) and in HFpEF patients, HR was 1.72 (95% CI 1.49–1.98) p < 0.0001). In a multivariate Cox proportional hazard regression analysis, adjusted for age, NYHA class, atrial fibrillation and GFR class, this association remained regarding NT-proBNP quartiles [HR 1.83 (95% CI 1.38–2.44), p < 0.0001] and [HR 1.48 (95% CI 1.16–1.90), p = 0.0001], HFmrEF and HFpEF, respectively.Conclusion: NT-proBNP has a prognostic value in patients with HF and EF ≥40% managed in PC. However, its clinical utility is limited due to high SDs and the fact that it is not independent in this population which is characterized by high age and much comorbidity.Key pointsIt is uncertain whether NT-proBNP predicts risk in heart failure with preserved ejection fraction (EF > 40%, HFpEF) managed in primary care.We show that high NT-proBNP predicts increased all-cause mortality in HFpEF-patients managed in primary care.The clinical use is however limited due to large standard deviations, many co-morbidities and high age.Many of these co-morbidities contribute to all-cause mortality and management of these patients should also focus on these co-morbidities.

P2241Patients examined with coronary computed tomography angiography have comparable five-year outcomes to age- and sex-matched population controls

Abstract Background According to Danish national guidelines, coronary computed tomography angiography (CCTA) is the preferred frontline test in patients without known coronary artery disease (CAD) and stable symptoms indicative of CAD. Over the last decade in Denmark, we have seen a steadily and considerable increase in CCTA use. Data on long-term cardiovascular risk following CCTA remains limited, in particular in comparison to background population controls. Purpose To study individual and composite five-year outcomes of mortality, myocardial infarction (MI) and revascularization in CCTA-examined patients compared to background population controls. Methods Nationwide registry-based study including 58,176 patients with an incident CCTA examination during 2007–2014 in Denmark versus 116,352 age- and sex-matched population controls. Despite no detailed information on CCTA results were available, a landmark analysis including patients and corresponding controls alive six months post-CCTA enabled us to study five patient categories: 1) 19,135 patients with no relevant medical therapy (nitrates, cholesterol-lowering, antiplatelet and/or anticoagulant drugs) before or 180 days post-CCTA; 2) 6,073 patients on relevant medical therapy prior to but not 180 days post-CCTA; 3) 5,086 patients who initiated relevant medical therapy during 180 days post-CCTA; 4) 19,809 patients on relevant medical therapy both before and during 180 days post-CCTA; and 5) 8,073 patients with myocardial infarction (MI) or treated with percutaneous intervention (PCI) or coronary artery bypass surgery (CABG) within 180 days post-CCTA. Within each CCTA patient group, two controls matched on age and sex were identified for each CCTA patient. Neither CCTA-patients nor controls had prior ischemic heart disease. Results Outcomes of MI for CCTA patient groups 1)-5) versus controls were: 0.3%, 0.6%, 0.8%, 0.7%, and 11.4% versus 0.7%, 1.1%, 1.0%, 1.1%, and 1.5%. Corresponding figures for all-cause mortality were: 2.2%, 2.0%, 4.1%, 4.9%, and 6.8%, versus 2.1%, 2.8%, 4.2%, 4.3%, and 6.4%. For composite endpoint of MI, PCI or CABG, results for CCTA patients versus controls were: 0.3%, 0.6%, 0.8%, 0.7%, and 18.2% versus 0.9%, 1.3%, 1.2%, 1.4%, and 1.9%. Lastly, for composite endpoint of MI, PCI, CABG or death, results for CCTA patients versus controls were: 2.5%, 2.6%, 4.8%, 4.9%, and 24.2% versus 3.0%, 3.9%, 5.3%, 6.1%, and 8.0%. Conclusions Only the CCTA group treated with PCI or CABG or diagnosed with MI during the first 180 days post-CCTA had substantially higher five-year MI event rates and composite endpoints of MI, PCI or CABG and MI, PCI, CABG or death. In addition, no difference in five-year all-cause mortality was seen for all CCTA patient groups when compared to their respective controls. Altogether, the majority of CCTA-examined patients were event-free at five-year follow-up suggesting a potential overutilization of CCTA and a need for refinement of CCTA referral criteria.

LBA18 - Clinical outcomes by chemotherapy regimen in patients with RS 26-100 in TAILORx

BackgroundThe recurrence score (RS) based on the 21-gene breast cancer assay predicts chemotherapy benefit if it is high and a low risk of recurrence in the absence of chemotherapy if it is low. There is little information from prospective clinical trials, however, regarding outcomes for patients with a high RS treated with chemotherapy regimens including taxanes and/or anthracyclines. MethodsWomen with hormone-receptor-positive, HER2-negative, axillary-node-negative breast cancer and a high RS of 26-100 were assigned to receive endocrine therapy plus a chemotherapy regimen selected by the treating physician. ResultsAmong the 9719 eligible women, 1389 (14%) had a RS of 26-100.The most common chemotherapy regimens included docetaxel/cyclophosphamide in 589 (42%), an anthracycline without a taxane in 334 (24%), an anthracycline and taxane in 244 (18%), cyclophosphamide/methotrexate/5-FU in 52 (4%), other regimens in 81 (6%), and no chemotherapy in 89 (6%). The estimated rates of freedom from recurrence of breast cancer at a distant site were 93.0% (standard error [SE]+0.8%) at 5 years and 86.8% (SE+1.7%) at 9 years. In contrast, the projected rates of freedom from distant recurrence in this population if treated with endocrine therapy alone was estimated to be 78.8% (SE±14.0%) at 5 years and 65.4% (SE±10.4%) at 9 years when estimating outcomes based on the treatment effect of chemotherapy noted in the HER2-negative cohort of the B20 trial. Five-year rates of freedom from distant recurrence ranged from 92.3% to 95.5% for all chemotherapy regimens with the exception of CMF (88.5%). ConclusionsThe estimated rate of freedom from distant recurrence in women with a RS of 26-100 treated with a variety of adjuvant taxane and/or anthracycline-containing chemotherapy regimens plus endocrine therapy in the prospective TAILORx trial was 93% at 5 years, an outcome better than expected with endocrine therapy alone in this population. Clinical trial identificationNCT00310180. Legal entity responsible for the studyECOG-ACRIN Cancer Research Group. FundingUSA National Cancer Institute, Genomic Health. DisclosureAll authors have declared no conflicts of interest.

Incidence of healthcare-associated infections in a tertiary hospital in Beijing, China: results from a real-time surveillance system

BackgroundTo quantify the five year incidence trend of all healthcare-associated infections (HAI) using a real-time HAI electronic surveillance system in a tertiary hospital in Beijing, China.MethodsThe real-time surveillance system scans the hospital’s electronic databases related to HAI (e.g. microbiological reports and antibiotics administration) to identify HAI cases. We conducted retrospective secondary analyses of the data exported from the surveillance system for inpatients with all types of HAIs from January 1st 2013 to December 31st 2017. Incidence of HAI is defined as the number of HAIs per 1000 patient-days. We modeled the incidence data using negative binomial regression.ResultsIn total, 23361 HAI cases were identified from 633990 patients, spanning 6242375 patient-days during the 5-year period. Overall, the adjusted five-year HAI incidence rate had a marginal reduction from 2013 (4.10 per 1000 patient days) to 2017 (3.62 per 1000 patient days). The incidence of respiratory tract infection decreased significantly. However, the incidence rate of bloodstream infections and surgical site infection increased significantly. Respiratory tract infection (43.80%) accounted for the most substantial proportion of HAIs, followed by bloodstream infections (15.74%), and urinary tract infection (12.69%). A summer peak in HAIs was detected among adult and elderly patients.ConclusionsThis study shows how continuous electronic incidence surveillance based on existing hospital electronic databases can provide a practical means of measuring hospital-wide HAI incidence. The estimated incidence trends demonstrate the necessity for improved infection control measures related to bloodstream infections, ventilator-associated pneumonia, non-intensive care patients, and non-device-associated HAIs, especially during summer months.

645-P: QTc Prolongation as a Risk Factor for Five-Year Survival after Above-Ankle Amputation in Patients with Type 2 Diabetes

Patients with diabetic foot ulcers (DFU) are considered high-risk individuals for increased cardiovascular disease and mortality. After a major amputation the mortality risk is even higher, with five-year mortality rates exceeding 70%. QTc interval prolongation is a potential indicator of increased cardiovascular risk in the general population as well as in patients with diabetes. The aim of this study was to evaluate the impact of QTc prolongation on 5-years survival after above ankle amputation in patients with type 2 diabetes. We retrospectively enrolled all patients (n=97) with type 2 diabetes, not older than 85 years without a pacemaker, who underwent a major amputation at two hospitals with multidisciplinary DFU teams. Patients were grouped according to QTc time ≤ or &amp;gt;440 ms. Mortality data after 5 years was obtained from the Swedish National Death Registry. Non-parametric statistics were used when assessing differences and survival was analyzed with Kaplan-Meier estimates with log-rank test. As shown in the Figure, QTc prolongation was significantly associated with worse survival (82 vs. 57% 5-year mortality). Presence of ischemic heart disease, age and diabetes duration did not differ between groups. In conclusion, we have demonstrated that routinely ECG screening with QT interval analysis in a DFU-population, provides important information regarding long-term survival. Disclosure S. Puvaneswaralingam: None. K. Fagher: Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp &amp; Dohme Corp., Novo Nordisk A/S, Sanofi. M. Londahl: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk A/S, Sanofi. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk A/S, Sanofi. Funding Craaford Foundation; Krapperyp Foundation; County of Skåne Foundation; Diabetes Foundation

Is neratinib following trastuzumab in early-stage HER2-positive breast cancer cost-effective?

6625 Background: Neratinib after adjuvant trastuzumab significantly improves disease-free survival (DFS) in human epidermal growth factor receptor 2-postiive (HER2+) breast cancer, but the median absolute DFS gain is only 1.3 months. There has been much controversy in the clinical and lay media as to whether the substantial cost of neratinib is justified by its effects, including a prominent ASCO Post article from Dr. Vogl about a year ago. We performed a cost-utility analysis to formally assess the value of adding neratinib based on Phase III ExteNET trial results. Methods: We developed a Markov state-transition model to assess the value of neratinib in Stage I-III HER2+ breast cancer. Five-year recurrence rates were derived from ExteNet. Mortality and recurrence rates after 5 years were derived from the HERceptin Adjuvant (HERA) trial. Costs were derived from wholesale acquisition costs and peer-reviewed literature. Health state utilities were derived from ExteNET and prior publications. Outcomes included life years (LY), quality-adjusted life years (QALYs), direct medical expenditures, and cost per QALY gained. The analysis took a payer perspective over a lifetime horizon and results were discounted at 3% per year. One-way and probabilistic analyses were conducted to evaluate uncertainty. As neratinib conferred more clinical benefit in hormone receptor-positive (HR+) disease, we also assessed value in that specific subgroup. Results: Base case results are presented in Table. At typical U.S. willingness to pay thresholds of $100,000 and $150,000 per QALY gained, neratinib had 16.7% and 27.2%, probabilities of cost-effectiveness, respectively. In the HR+ subgroup, neratinib had a cost of $275,311 per QALY gained (19.9% &amp; 31.2% probability of cost-effectiveness at $100,000 &amp; $150,000 per QALY). Conclusions: In the first independent assessment of the value of neratinib after adjuvant trastuzumab, neratinib is not projected to be cost-effective, even among patients who derived the most clinical benefit. Future analyses should reassess the cost-effectiveness of neratinib treatment as trial data mature. Base case results. [Table: see text]

Prognostic impact of SOX9 in stage II colon cancer: Results from a large nationwide cohort.

e15165 Background: Up-regulation of the transcription factor SOX9 has been described in colon cancer, and it has been argued that differences in the expression levels dictates cell proliferation. The aim of the present study was to analyze the prognostic impact of SOX9 in stage II colon cancer. Methods: Individual patient data and formalin fixed paraffin embedded tumor tissue were collected from a large unbiased, population-based cohort, representing all patients operated for stage II colon cancer in Denmark in 2002 and 2003. The SOX9 expression was evaluated by immunohistochemistry on whole tumor sections. Patients were classified into three groups dependent on the SOX9 expression gradient in the tumor: luminal, peripheral, and uniform for comparison with the clinical data. The endpoint was disease free survival (DFS). Results: A total of 1,153 patients were included. We detected an expression-dependent relationship between SOX9 and prognoses. Patients with tumors exhibiting a luminal expression pattern (N = 267, increasing SOX9 expression towards the luminal compartment of the tumor) were characterized by a significantly better DFS compared to the uniform (N = 846) and peripheral (N = 40) patterns, p = 0.0070. The five-year DFS rates were 74%, 67%, and 56%, respectively. Multiple Cox regression analysis, adjusted for all standard high risk factors, confirmed an independent prognostic advantage of the luminal SOX9 expression pattern, as compared to the uniform pattern, hazard ratio (HR) 0.7211 (95% confidence interval (CI) 0.5561-0.9351), p = 0.0137, whereas the possible disadvantage of the periphery pattern could not be verified, HR 1.4393 (95% CI 0.8869-2.3660), p = 0.1405. Conclusions: The present results support a prognostic impact of SOX9 in stage II colon cancer. The consequence of an altered SOX9 expression seems to differ between intra-tumoral compartments, and we propose that a gradient-dependent evaluation should be applied to provide the most clinically relevant information about this transcription factor.

Correlation analysis of radiotherapy and prognosis of elderly patients with hormone receptor-positive breast cancer in different immunohistochemical subtyping.

e12061 Background: Our study aimed to assess the effect of radiotherapy on the recurrence and survival in elderly patients with hormone-receptor-positive early breast cancer. Methods: We performed a retrospective analysis of 327 breast cancer patients who were 65 years or older with stage I-II, hormone-receptor-positive, after breast-conserving surgery and who received endocrine therapy(ET) or radiotherapy plus endocrine therapy(ET+RT). ET group was subgroup analyzed according to luminal A type and luminal B type, the same as ET+RT group. Evaluation Criterias were five-year local relapse rate(LRR),distant metastasis rate(DMR), disease-free survival rate (DFS) and overall survival rate (OS). Results: There were significant differences in five-year LRR (HR 3.33, 95% CI 1.51-7.34, P=0.0028) and DFS (HR 1.59, 95% CI 1.15-2.19, P=0.0045), but there were no significant differences in DMR and OS between the two groups. In luminal A type, there was no significant difference in five-year LRR, DMR,DFS, and OS between the ET group and the ET + RT group. In luminal B type, the difference was statistically significant in five-years LRR(HR 5.447, 95% CI 1.65-17.98, P=0.0054), DFS (HR 2.188, 95% CI 1.37-3.49, P=0.0010) and OS (HR 1.752, 95% CI 1.01-3.054, P=0.0478). In ET group, there were significant differences between luminal A type and luminal B type in five-years DFS (HR 1.841, 95% CI 1.23-2.75, P=0.0028) and OS (HR 1.763, 95% CI 1.07-2.91, P=0.0264). Conclusions: After breast-conserving surgery, radiotherapy can reduce the LRR and improve the DFS and OS of luminal B type elderly early patients, but luminal A type elderly early patients can not benefit from radiotherapy. Without radiotherapy, luminal A type patients have a better OS and DFS than luminal B.

Perioperative and Follow-up Results of Carotid Artery Stenting and Carotid Endarterectomy in Patients with Carotid Near-Occlusion

The aim was to compare perioperative and follow-up results of carotid artery stenting (CAS) and carotid endarterectomy (CEA) in patients with carotid near-occlusion (NO). A retrospective analysis was conducted from January 2012 to June 2017 on consecutive patients with NO in our center. Perioperative complications, recurrence rate of ischemic stroke, restenosis rate, and mortality in follow-up were compared between the CAS group and CEA group. 92 patients (CAS group, 54 and CEA group, 38) were identified. Perioperative (30-day) results were as follows: the rate of new lesions on diffusion-weighted imaging (DWI) was higher in the CAS group (n=31, 57.4%) than in the CEA group (n=13, 34.2%) (P=0.03); no differences were found in ischemic stroke, transient ischemic attack (TIA), cardiac infarction, and death rate between the two groups. Results from follow-up with a mean period of 28.3 (range from 3 to 60) months were as follows: the restenosis rate was lower in the CAS group (n=1, 1.8%) than the CEA group (n=4, 10.5%) (P=0.04); no differences were found in ischemic stroke, TIA, and the death rate between the two groups. Kaplan-Meier survival curves showed that the five-year survival rate was 85.8% of the CAS group and 82.7% of the CEA group (P=0.61); the five-year rate of freedom from target-lesion restenosis was 93.3% of the CAS group and 80.4% of the CEA group (P=0.02). Both CAS and CEA can be used for carotid NO with the same rate of TIA/stroke and long-term survival. The rate of new lesions on DWI after CAS was higher than that in CEA in the perioperative period. CAS had a lower restenosis rate than CEA in follow-up, which might be more beneficial for remodeling of the distal internal carotid artery.

Conservative management of low-risk prostate cancer among young versus older men in the United States: Trends and outcomes from a novel national database.

12 Background: The optimal management for men age ≤55 with low-risk prostate cancer (PCa) is debated given quality of life implications with definitive treatment versus potential missed opportunity for cure with conservative management. We sought to define rates of conservative management for low-risk PCa and associated short-term outcomes in young versus older men in the United States (U.S.). Methods: The Surveillance, Epidemiology, and End Results (SEER) Prostate with Active Surveillance/Watchful Waiting (AS/WW) Database identified 50,302 men diagnosed with low-risk PCa from 2010-2015. AS/WW rates in the U.S. were stratified by age (≤55 versus ≥56). Prostate cancer-specific mortality (PCSM)and overall mortality were defined by initial management type (AS/WW versus definitive treatment [referent]) and age. This non-public data was released by the SEER custom data group. Results: AS/WW utilization increased from 8.61% in 2010 to 34.56% in 2015 among men age ≤55 (Ptrend&lt; 0.001) and from 15.99% to 43.81% among men age ≥56 (Ptrend&lt; 0.001). Among patients with ≤2 positive biopsy cores, AS/WW rates increased from 12.90% to 48.78% for men age ≤55 and from 21.85% to 58.01% for men age ≥56. Among patients with ≥3 positive biopsy cores, AS/WW rates increased from 3.89% to 22.45% for men age ≤55 and from 10.05% to 28.49% for men age ≥56 (all Ptrend&lt; 0.001). Five-year PCSM rates were below 0.30% across age and initial management type subgroups. Conclusions: AS/WW rates quadrupled for patients age ≤55 from 2010-2015, with favorable short-term outcomes. These findings demonstrate the short-term safety and increasing acceptance of AS/WW for both younger and older patients. However, there are still higher absolute rates of AS/WW in older patients (P &lt; 0.001), suggesting some national ambivalence toward AS/WW in younger patients.

The effect of the timing of biochemical failure after external beam radiotherapy or low-dose-rate brachytherapy for definitive prostate cancer treatment.

28 Background: To assess the effect of the timing of biochemical failure (bF) after definitive radiotherapy with external beam (EBRT) or low dose-rate brachytherapy (LDR) on clinical failure (cF) and prostate cancer-specific mortality (PCSM). Methods: From 1996 to 2009, 4478 patients were treated and by 2010, 456 patients were noted to have a bF. They were categorized as early (&lt; 5 years post-therapy) or late (≥ 5 years post-therapy) failures. Factors thought to influence cF and PCSM were scored. Cox regression was used to assess the timing of bF on cF and Fine and Gray regression was used to assess the timing of bF on PCSM. Results: There were 330 (72.4 %) patients categorized as early and 126 (27.6 %) as late failures. The median PSA follow-up post-radiotherapy for the early bF group is 82 months vs. 155 months for the late bF group, and the median PSA follow-up post-bF is 54 months for the early bF group vs. 69 months for the late bF group. The early failures were more likely to be high-risk (p = 0.0080), have a higher Gleason score (p = 0.0008), and use ADT (p = 0.0325). The five-year rate of cF post early bF is 61% vs 43% post late bF (p &lt;0.0001). The five-year rate of PCSM post early bF is 27% vs 9% post late bF (p &lt;0.0001). The multivariable analyses assessing the cF and PCSM are shown in Table. Conclusions: Early bF is associated with higher rates of cF and PCSM. Patients treated with LDR have a lower risk of PCSM. [Table: see text]