Cumulative Incidence Of Death Research Articles

Heart failure mortality according to acute variations in N-terminal pro B-type natriuretic peptide and cystatin C levels

Changes in N-terminal pro B-type natriuretic peptide (NT-proBNP) levels and cystatin C (CysC) are predictors of adverse outcomes in acute heart failure. This study assess whether NT-proBNP variations might provide independent information in addition to that obtained from CysC levels. NT-proBNP levels were assessed in patients admitted due to acute heart failure using an observational study. Patients were classified as follows: group 1, those with a decrease in NT-proBNP levels of at least 30% from admission to 4 weeks after discharge; group 2, those with no significant changes in levels; and group 3, those who showed an increase in NT-proBNP of 30%. A multivariable Cox regression model and c-statistics were used. The primary end-point was all-cause mortality at 1-year follow-up. A total of 195 patients completed the follow-up. The mortality rate reached 20.5% (40 patients); 14 out of the 32 in group 3. The cumulative incidence of death, according to the change in NT-proBNP and Kaplan-Meier analysis, showed a significant increase in group 3 (log-rank P = 0.004). In the multivariable analysis, NT-proBNP variation for group 3 (hazard ratio 4.27; P <0.001) and for group 2 (hazard ratio 2.19; P = 0.043) in comparison with group 1 were independently associated with all-cause mortality, as well as anemia, hyponatremia, and admission CysC levels. Patients in group 3, and those with levels of serum CysC above the median, were also associated with slight increase in mortality. An increase of at least 30% in NT-proBNP levels after hospitalization is related to all-cause mortality in patients with acute heart failure and provides supplementary prognostic information in patients with high levels of CysC. A decrease in NT-proBNP of at least 30% is a desirable target to achieve.

Sirolimus-eluting stent implantation for ostial right coronary artery lesions: five-year outcomes from the j-Cypher registry

Ostial right coronary artery (RCA) lesions are associated with a high restenosis rate after bare-metal stent implantation. However, long-term outcomes after drug-eluting stent (DES) implantation for ostial RCA lesions have not been adequately evaluated. Among 12824 patients enrolled in the j-Cypher registry, 5-year outcomes were compared between 397 patients with ostial RCA lesions, and 3716 patients with non-ostial RCA lesions treated with sirolimus-eluting stents (SES). Through 5-year follow-up, patients with ostial RCA lesions had a significantly higher cumulative incidence of target lesion revascularization (TLR) (28.2 versus 13.7%, P<0.0001) than those with non-ostial RCA lesions. After adjusting for confounders, excess TLR risk of the ostial group relative to the non-ostial group was significant for both early TLR within 1-year and late TLR beyond 1-year (HR 2.14 [95% CI 1.59-2.84], P<0.0001, and HR 1.58 [95% CI 1.06-2.26], P=0.02, respectively). Although the cumulative incidence of death was also significantly higher in the ostial group than in the non-ostial group (25.7 versus 14.4%, P<0.0001), the excess risk of the ostial group relative to the non-ostial group was no longer significant after adjusting for confounders (HR 1.25 [95% CI 0.99-1.57], P=0.07). SES implantation for ostial RCA lesions was associated with higher risk for TLR as compared with that for non-ostial RCA lesions. Restenosis, both early and late, remains an issue in coronary DES implantation for ostial RCA lesions.

Acquired Factor VIII Inhibitor: A Single Institution Experience With 62 Patients

BackgroundAcquired Factor VIII inhibitor or autoimmune hemophilia A (AHA), has an estimated incidence of up to 1.5 cases per million/year and may result in severe hemorrhagic complications and death. Approximately 50% of cases have an underlying condition such as malignancies, autoimmune disorders and post-partum state. AHA should be suspected in any patient presenting with unexplained bleeding and an inhibited aPTT. Management consists of maintaining hemostasis and elimination of the inhibitor, however management is not standardized. We present 62 cases of AHA managed at Mayo Clinic Rochester, over the course of 36 years. We also analyzed whether aPTT at presentation correlated with the strength of inhibition measured by Bethesda Titer. MethodsAfter IRB approval, medical records of patients with AHA were reviewed and all clinical data collected. Cumulative incidence of death was estimated by Kaplan-Meier analysis. Spearman correlation was used to calculate relation of APTT to Bethesda titer. ResultsBetween 1976 and 2012, we identified 62 patients (male: 35), with a median age at diagnosis of AHA 69 years (mean 64, range 20-86). Clinical presentation consisted of extensive ecchymoses (n=40, 64%) in majority of cases. 29/62 (47%) patients had at least 1 identifiable predisposing condition with 12/62 (19%) patients with an underlying malignancy and 16/62 (26%) with underlying autoimmune conditions. Median Bethesda titer was 29 (range 1 to 1178). Bethesda titer was not related to the number or duration of hospitalizations. Most (69%) patients had at least one hospitalization and 12 (19%) had more than one hospitalization for bleeding complication. Inpatient therapy for bleeding consisted most commonly of FEIBA in 21 pts (34%) and rFVIIa in 6 pts (10%). Prednisone was the most common immunosuppressant used in 54 (87%) patients while Rituximab was used in 11 (18%) patients. Of 32 patients with available follow up labs most (69%) achieved remission. There was no difference in remission rates between patients treated or not treated with Rituximab (p=0.1735). ConclusionAcquired Hemophilia A is a rare condition with very heterogenous presentation. It affects mostly older male patients who present with ecchymoses and elevated APTT. The degree of APTT prolongation at the time of diagnosis does not correlate with the strength of the Bethesda titer and should not guide choice of therapy in a patient presenting with an acute bleed. Rituximab use in the 11 patients treated at Mayo did not seem to influence remission rates or survival. Disclosures:No relevant conflicts of interest to declare.

Short- Versus Long-Term Duration of Dual Antiplatelet Therapy in Patients Treated for In-Stent Restenosis: A PRODIGY Trial Substudy (Prolonging Dual Antiplatelet Treatment After Grading Stent-Induced Intimal Hyperplasia)

This study sought to investigate the clinical outcome of patients treated with percutaneous coronary intervention (PCI) for in-stent restenosis (ISR) randomized to short (6 months) versus long (24 months) dual antiplatelet therapy (DAPT) regimen. It is still unclear if patients treated for ISR may benefit from a long DAPT regimen. For the present purpose, we selected 224 patients undergoing the PCI procedure for ISR enrolled in the PRODIGY (Prolonging Dual Antiplatelet Treatment After Grading Stent-Induced Intimal Hyperplasia) trial and randomized to short (6 months) versus long (24 months) DAPT regimen. The primary objective was the cumulative incidence of death, nonfatal myocardial infarction (MI), or cerebrovascular accident at 24 months. Safety endpoints were moderate and major bleeding complications. Overall, 114 patients were allocated to short DAPT regimen, whereas 110 patients were allocated to long DAPT regimen. Twenty-seven patients reached the primary endpoint (19 in short DAPT regimen vs. 8 in long DAPT regimen; p= 0.02). The cumulative incidence of the primary endpoint at 24 months was 16.7% in the short DAPT regimen group compared with 7.3% in the long DAPT regimen group (p= 0.034). This is principally due to a lower occurrence of death and MI in the long DAPT regimen group as compared to the short DAPT regimen group (6.5%vs.15.5%; p= 0.03). There was no difference in the occurrence of bleeding complications between long and short DAPT regimen. Our study offers preliminary evidence that patients receiving a new PCI procedure for ISR may benefit from long-term administration of aspirin plus clopidogrel. (Synergy Between Stent and Drugs to Avoid Ischemic Recurrences After Percutaneous Coronary Intervention [PRODIGY]; NCT00611286).

Ceppellini Lecture 2012: collateral damage from HLA mismatching in kidney transplantation.

Inclusion of human leukocyte antigen (HLA) matching in donor kidney allocation schemes has been based solely on its association with graft survival. Other long-term effects associated with HLA incompatibility are largely unexplored. Data from deceased donor kidney transplants reported to the Collaborative Transplant Study have been analyzed to assess the relation between HLA mismatching and clinical events to 3 years post-transplant, and an overview of these analyses is presented. A significant correlation was observed between the number of mismatches and the need for anti-rejection therapy during the first year post-transplant, which was maintained for HLA-DR and HLA-A + B mismatching separately and at years 2 and 3 post-transplant. The number of HLA-DR mismatches and the number of HLA-A + B mismatches as well as rejection treatment showed significant associations with the dose of maintenance steroids. The cumulative incidences of death with a functioning graft from infection or cardiovascular causes, but not from cancer, were also significantly associated with HLA mismatching. The number of HLA-DR mismatches showed a significant association with the incidence of non-Hodgkin lymphoma and hip fractures. These findings show that the adverse consequences of HLA mismatching on kidney transplants extend beyond an effect on graft survival, and include an increased risk of death with a functioning graft, non-Hodgkin lymphoma and hip fracture.

Competing mortality (CM) risk in patients with resected stage I and II non-small cell lung cancer (NSCLC): A Surveillance, Epidemiology, and End Results (SEER) analysis.

7563 Background: CM risk has been identified as a potential confounder in the interpretation of treatment effects in head and neck cancer (Rose et al. J Clin Oncol. 2011). Lung cancer patients (pts) are at considerable risk for CM due to their advanced age at diagnosis and smoking related chronic diseases. We plan to identify risk factors for CM in pts with early stage NSCLC and develop a statistical model to estimate the effect of CM on power calculation for lung cancer clinical trials. Methods: Using SEER registry we identified 32104 pts who had undergone surgical resection with or without radiation for stage I and II NSCLC between 1994 and 2006. The data set was split into two groups: training set (75%) and testing set (25%). Risk factors for lung cancer-specific mortality (LCSM) and CM were identified using training data by Gray’s sub-distribution regression of competing risk. Pts from the testing data were then stratified according to CM risk and the impact of this risk on power loss was evaluated. Results: The 5-year cumulative incidence of death from lung cancer, other causes and overall mortality was 32.7%, 14.2% and 46.9% respectively. Risk factors for CM were: age (hazard ratio [HR] 1.05), male gender (HR 1.43), divorced (HR 1.30), widowed (HR 1.23) or single (HR 1.29) marital status, squamous (HR 1.40) or not-otherwise-specified (HR 1.22) histology, stage I NSCLC (HR 1.27) and sublobar resection (HR 1.23). The 5-year cumulative incidence of CM in low, mid and high-risk tertiles was 7%, 14% and 21% respectively. Sample size calculations based on all-cause mortality (ACM) result in over-estimation of power as the risk for CM increases. In order to restore the underestimated power in LCSM, 19% and 35% more pts are required in the mid and high CM risk groups respectively (Table). Conclusions: Our findings indicate that conventional sample size calculation methods can result in significant loss of power and incorporating CM risk models in power estimation should be considered for clinical trials involving early stage NSCLC pts. [Table: see text]

Development of a nomogram to predict for all-cause and cancer-specific mortality in high-risk prostate cancer treated by external beam radiotherapy and androgen deprivation.

e16004 Background: Men receiving high dose external beam radiotherapy (EBRT) and androgen deprivation therapy (ADT) for high risk prostate cancer (HRPC) have other competing causes of mortality, however predictive schema do not account for patient-related co-morbidities. We aim to create nomograms estimating all-cause mortality (ACM) and prostate cancer-specific mortality (PCSM) in this population. Methods: 660 patients with HRPC defined by NCCN guidelines were treated with EBRT ≥74 Gy and ADT from 1996-2009. The probabilities of death from prostate cancer and other causes were estimated by cumulative incidence function. Multivariable Cox proportional hazards regression and competing risks regression analyses were used for modeling ACM and PCSM respectively. Deaths from other causes were treated as competing risks for PCSM. Missing values in the predictors were multiply imputed before conducting multivariable regression analysis. Variables investigated were age, clinical T stage, prostate specific antigen (PSA), Gleason score, race, family history, duration of ADT, body mass index (BMI), Charlson co-morbidity index score, coronary artery disease, and smoking pack-years. The stepdown method was used to make parsimonious models based on the rank of the predictive ability of each variable with respect to each endpoint. The final nomograms were internally validated by assessing the discrimination and calibration with bootstrap resamples. Results: At last follow up, there were 199 deaths. The 10-year cumulative incidence of death from prostate cancer was 14% and from other causes was 26%. The variables that predicted for 10-year ACM included age, PSA, BMI, Charlson score, and smoking pack-years. The ACM nomogram achieved a concordance index of 0.672. The variables that predicted for PCSM included Gleason score, PSA, race, and duration of ADT. The nomogram concordance index for PCSM was 0.673. The calibrations for both ACM and PCSM appear reasonable. Conclusions: We have developed nomograms that predict for ACM and PCSM in men with aggressive prostate cancer and competing risks of death. External validation may be useful.

996 NATION-WIDE ANALYSIS OF SURVIVAL AFTER RADICAL PROSTATECTOMY FOR CLINICALLY LOCALIZED PROSTATE CANCER IN DENMARK 1995-2011

INTRODUCTION AND OBJECTIVES: PSA-screening for prostate cancer (PCa) has never been recommended in Denmark. Radical prostatectomy (RP) for clinically localized PCa was introduced in 1995. The objective of study was to describe survival after RP in a nationwide cohort of Danish PCa patients. METHODS: Prospective observational study of 6489 men with localized PCa treated with RP at 6 different hospitals in Denmark between 1995 and 2011. Survival was described using Kaplan-Meier estimates. Causes of death were obtained in national registry and cross-checked with patient files. Cumulative incidence of death; any cause and PCa-specific was described using Nelson-Aalen estimates. Risk for PCa death was analyzed in a Cox multivariate regression model using covariates age, cT-category, PSA and biopsy Gleason score (GS). RESULTS: Median follow-up was 4 years. During follow-up, 328 patients died, 109 (33.2%) of PCa and 219 (66.8%) of other causes. Six patients (0.09%) died within 30 days of surgery. In multivariate analysis, cT-category was a predictor of PCa death (p .001). Compared to T1 disease, both cT2c (HR 2.2) and cT3 (HR 7.2) significantly increased the risk of PCa death. For every doubling of PSA the risk of PCa death was increased by 34.8% (p 0.001). Biopsy GS 4 3 and 8 were associated with an increased risk of PCa death compared to biopsy GS 6 of 2.3 and 2.7 (p 0.003), respectively. The cumulative incidence of any-cause mortality after 10 years was 15.4% (95% CI:13.2-17.7) and 6.6% (95% CI:4.9-8.2) for PCa mortality. CONCLUSIONS: Our results seem comparable to high-volume, single institution, single surgeon series u even in a country where PCa are primarily clinically detected and patients are managed by small volume, multi-surgeon institutions. The true benefit of RP in localized PCa compared other treatment strategies remains controversial.

Survival after radical prostatectomy for clinically localised prostate cancer: a population‐based study

To describe survival and cause of death in a nationwide cohort of Danish patients with prostate cancer undergoing radical prostatectomy (RP). To describe risk factors associated with prostate cancer mortality. Observational study of 6489 men with localised prostate cancer treated with RP at six different hospitals in Denmark between 1995 and 2011. Survival was described using Kaplan-Meier estimates. Causes of death were obtained from the national registry and cross-checked with patient files. Cumulative incidence of death, any cause and prostate cancer-specific, was described using Nelson-Aalen estimates. Risk for prostate cancer death was analysed in a Cox multivariate regression model using the covariates: age, cT-category, PSA level and biopsy Gleason score. The median follow-up was 4 years. During follow-up, 328 patients died, 109 (33.2%) from prostate cancer and 219 (66.8%) from other causes. Six patients (0.09%) died ≤30 days of RP. In multivariate analysis, cT-category was a predictor of prostate cancer death (P < 0.001). Compared with T1 disease, both cT2c (hazard ratio [HR] 2.2) and cT3 (HR 7.2) significantly increased the risk of prostate cancer death. For every doubling of PSA level the risk of prostate cancer death was increased by 34.8% (P < 0.001). Biopsy Gleason score 4 + 3 and ≥8 were associated with an increased risk of prostate cancer death compared with biopsy Gleason score ≤ 6 of 2.3 and 2.7 (P = 0.003), respectively. The cumulative hazard of all-cause and prostate cancer-specific mortality after 10 years was 15.4% (95% confide3nce interval [CI] 13.2-17.7) and 6.6% (95% CI 4.9-8.2) respectively. We present the first survival analysis of a complete, nationwide cohort of men undergoing RP for localised prostate cancer. The main limitation of the study was the relatively short follow-up. Interestingly, our national results are comparable to high-volume, single institution, single surgeon series.

The inferior prognosis of adolescents with acute lymphoblastic leukaemia (ALL) is caused by a higher rate of treatment‐related mortality and not an increased relapse rate – a population‐based analysis of 25 years of the Austrian ALL‐BFM (Berlin‐Frankfurt‐Münster) Study Group

Adolescents aged 15-18 years with acute lymphoblastic leukaemia (ALL) have been historically reported to have a poorer prognosis than younger children. We retrospectively analysed the characteristics and outcome of 67 adolescents included in a population-based series of 1125 non-infant cases that were enrolled into four Austrian ALL-BFM (Berlin-Frankfurt-Münster) multicentre trials at paediatric institutions within a 25-year period. Five-year event-free survival (EFS) and overall survival (OS) were 66 ± 6% and 76 ± 5% respectively, and thus lower than in younger children (83 ± 1%, 91 ± 1%; P < 0·001). This was not due to an increased cumulative incidence of relapse (CIR) (5-year CIR: 19 ± 5% vs. 13 ± 1%; P = 0·284), but due to an increased incidence of treatment-related death [5-year cumulative incidence of death (CID): 15 ± 4% vs. 3 ± 0%; P < 0·001] as a first event. Furthermore, while 44/67 (66%) non-high-risk adolescents had favourable 5-year EFS and OS rates (76 ± 7%, 89 ± 5%), 18/67 (27%) high-risk adolescents had an inferior outcome (5-year EFS: 56 ± 12%, OS 61 ± 11%, P < 0·05). Among the latter patients the CID was significantly higher than in younger high-risk children (22 ± 10% vs. 6 ± 2%; P = 0·020). Given that adolescent age is an independent risk factor for death as a first event, this specific age group may need particular vigilance when receiving intense BFM-type chemotherapy, as relapse-free survival is similar to younger children.

Recurrence of hepatocellular carcinoma after liver transplantation: Comparison between superselective and non-superselective chemoembolization.

238 Background: To compare post-transplant recurrence rates of hepatocellular carcinoma (HCC) and differences in percent tumor necrosis in patients with pre-operative superselective chemoembolization (CE) vs. non-superselective CE. Methods: Retrospective review of 147 patients with liver transplant (LT) for HCC treated with pre-operative CE. Those transplanted less than 24 hours after CE and those who had other concomitant treatments were excluded. The angiographic studies and written reports were reviewed to categorize patients into superselective and non-superselective groups. CE was done with an emulsion of lipiodol, cisplatin, doxorubicin, mitomycin C, and contrast, with or without embolization particles. Superselective CE was defined as treatment directly into the vessel(s) feeding the tumor. Treatment from more proximal vessels was considered non-superselective. Data gathered included age, gender, date of CE, date of LT, tumor size and number, tumor stage, MELD score, Child-Pugh class, alpha fetoprotein, percent tumor necrosis at explant, date of recurrence, date and cause of death, and date of last follow-up. Patient and disease characteristics and percent tumor necrosis were analyzed with a Wilcoxon rank sum test or Fisher’s exact test. The Kaplan-Meier method was used to estimate the cumulative incidences of death due to recurrent disease after LT. Results: 99 patients were included, 53 had superselective CE and 46 non-superselective. HCC recurrence rates at 1, 3, 5, and 8 years were all significantly less for superselective CE compared to non-superselective CE (p = 0.039 single, p = 0.011 multivariable). Using multivariable analysis, superselective CE had a lower risk of death due to recurrent HCC at 1, 3, 5, and 8 years (p = 0.046). There was a trend toward more percent tumor necrosis after superselective CE, but it did not reach significance (p = 0.057). Conclusions: This study provides evidence that HCC recurrence after LT and death due to recurrent HCC is lower after pre-LT superselective CE versus non-superselective CE. The strong trend for greater percent tumor necrosis with superselective CE may explain the differences in recurrence rate.

Risks of Death and Graft Failure After Surgical Versus Percutaneous Coronary Revascularization in Renal Transplant Patients

BackgroundReliable data regarding absolute and relative risks of death and graft failure after coronary artery bypass graft surgery (CABG) and percutaneous coronary intervention (PCI) in renal transplant patients are unavailable.Methods and ResultsRenal transplant patients undergoing inpatient CABG (n=1400) or PCI (n=4097) were identified from United States Renal Data System data. Cumulative incidence of nonfatal graft failure and death was reported for observed events. A Cox model with the Fine–Gray method was used to account for competing risks in assessing relative hazards. Age and race were similarly distributed; patients who underwent CABG were more likely to have acute arrhythmia and congestive heart failure but less likely to have acute myocardial infarction on index admission. In‐hospital death was more frequent after CABG (5.6% versus 3.0%, P<0.001). Cumulative incidence of death, graft failure, and the combined outcome at 3 years were 23.1%, 15.4%, and 38.5% after CABG and 22.9%, 13.3%, and 36.1% after PCI, respectively. In adjusted analyses, CABG was not associated with increased risk of graft failure versus PCI during the first 6 months (hazard ratio 1.06, 95% CI 0.79 to 1.43) or from 6 to 36 months (0.98, 0.78 to 1.22). Risk of death increased after CABG during the first 3 months (1.37, 1.08 to 1.73), but decreased from 6 months on (0.76, 0.63 to 0.93).ConclusionsCABG does not appear to be associated with a difference in risk of graft failure compared with PCI in renal transplant patients. Compared with PCI, adjusted risk of early death is higher after CABG; however, mortality from 6 months on is lower.

Very Long‐Term (15 to 23 Years) Outcomes of Successful Balloon Angioplasty Compared With Bare Metal Coronary Stenting

BackgroundTarget lesion revascularization (TLR) continues to occur beyond 4 years after bare metal stent (BMS) implantation. However, long-term outcomes after balloon angioplasty (BA) compared with BMS are currently unknown.Methods and ResultsFrom 1989 to 1990, 659 patients (748 lesions) underwent successful BA with final balloon ≥3.0 mm excluding patients with acute myocardial infarction and were compared with 405 patients (424 lesions) with BMS implantation from June 1990 to 1993. Cumulative incidences of death and target lesion thrombosis (>1 year) were similar between the BA group and the BMS group (44.4% versus 45.4%, P=0.60; and 1.5% versus 0.7%, P=0.99; respectively). Cumulative incidence of TLR during overall follow-up was significantly higher after BA than after BMS implantation (44.6% versus 36.0%, P<0.001), whereas cumulative incidence of late TLR (>4 years) tended to be lower in the BA group than in the BMS group (16.3% versus 21.4%, P=0.16). Cumulative incidence of late TLR after BA was significantly lower in patients with small percent diameter stenosis (%DS) at early follow-up angiography compared with large %DS (14.5% versus 28.0%, P=0.02). In lesions with serial angiography, late lumen loss from early (6 to 14 months) to long-term (4 to 10 years) follow-up angiography was significantly smaller in the BA group (n=42) than in the BMS group (n=55) (−0.08±0.45 mm versus 0.11±0.46 mm, P=0.047).ConclusionsCompared with BMS implantation, BA was associated with a trend for less late TLR beyond 4 years and with significantly smaller late lumen loss from early to long-term follow-up angiography.

PCN8 Primary Androgen Deprivation Therapy Versus Radical Prostatectomy in Seer-Medicare Dataset: A Comparative Effectiveness Analysis of Retrospective Cohorts

To examine the comparative effectiveness of primary androgen deprivation therapy (PADT) and radical prostatectomy (RP). Male patients with localized prostate cancer (T1-T2, N0, M0) were identified in the SEER-Medicare database from January 1998 to December 2007. Patients were 66-74 years old, without other documented cancers, and had PADT initiation or RP within 6 months after the first recorded diagnosis of prostate cancer in the dataset. PADT-treated patients were 1:1 matched to the RP-treated patients via propensity score (PS) matching. The overall survival from diagnosis to death was analyzed using Cox proportional hazard models; prostate cancer specific survival examined using Fine and Gray competing risk modeling. The independent regression variables included age at diagnosis, race, marital status, census regions, urban residence, clinical cancer stage, Gleason score, prostate specific antigen level, Charlson comorbidity index, calendar year at diagnosis, and hospitalization (yes or no), surgery (yes or no) and outpatient visit (yes or no) during one year baseline period. The PS-matched sample size was 3432 with mean age of 66.0 years. The baseline characteristics were comparable between the two cohorts (all p-values>0.05). During median follow-up of 2.95 years, the cumulative incidence of death was 304 (17.72%) among 1716 PADT patients and 94 (5.48%) among 1716 RP patients; 66 (3.85%) and 2 (0.12%) for prostate cancer specific deaths, respectively. The PADT group had nearly 4 times higher overall mortality risk compared to those using RP (odds ratio (OR)=3.534, 95% confidence interval (CI)=2.801-4.464, p<0.001). Furthermore, patients who received PADT had significantly higher prostate cancer specific mortality compared to those using RP (OR=30.875, 95% CI=7.535-126.506, p<0.001). Overall mortality and prostate cancer specific mortality following PADT were significantly higher compared to those following RP among localized prostate cancer patients. These data do not support the use of PADT in men with clinically localized prostate cancer.

Monotherapy of androgen deprivation therapy versus radical prostatectomy among veterans with localized prostate cancer: comparative effectiveness analysis of retrospective cohorts

Correspondence: Jinan Liu Tulane University, School of Public Health and Tropical Medicine, Tulane University, 1440 Canal Street, Suite 1900, New Orleans, LA 70112, USA Tel +1 504 810 7282 Fax +1 504 988 3783 Email jliu4@tulane.edu Background: This retrospective cohort study aimed to examine the comparative effectiveness of monotherapy of primary androgen deprivation therapy or radical prostatectomy. Methods: Male patients with localized prostate cancer (T1-T2, N0, M0) were identified in the Veterans Affairs Veterans Integrated Service Network 16 data warehouse (January 2003 to June 2006), with one-year baseline and at least three-year follow-up data (until June 2009). Patients were required to be 18–75 years old and without other recorded cancer history. The initiation of primary androgen deprivation therapy or monotherapy of radical prostatectomy within six months after the first diagnosis of prostate cancer was used as the index date. Primary androgen deprivation therapy patients were matched to the radical prostatectomy patients via propensity score, which was predicted from a logistic regression of treatment selection (primary androgen deprivation therapy versus radical prostatectomy) on age, race, marital status, insurance type, cancer stage, Charlson comorbidity index, and alcohol and tobacco use. The overall survival from initiation of index treatment was then analyzed using the Kaplan–Meier and Cox proportional hazards model. Results: The two cohorts were well matched at baseline (all P . 0.05). During a median follow-up of 4.3 years, the cumulative incidence of death was 13 (10.57%) among 123 primary androgen deprivation therapy patients and four (3.25%) among 123 radical prostatectomy patients (P , 0.05). The overall three-year survival rate was 92.68% for primary androgen deprivation therapy and 98.37% for radical prostatectomy (P , 0.05). Patients who received primary androgen deprivation therapy had almost three times as high a mortality risk as those using radical prostatectomy (hazards ratio 3.388, 95% confidence interval 1.094–10.492, P = 0.034). Conclusion: After propensity score matching, overall three-year survival rate following radical prostatectomy among patients with localized prostate cancer was significantly higher than that after primary androgen deprivation therapy.

Survival in Daily Home Hemodialysis and Matched Thrice-Weekly In-Center Hemodialysis Patients

Frequent hemodialysis improves cardiovascular surrogates and quality-of-life indicators, but its effect on survival remains unclear. We used a matched-cohort design to assess relative mortality in daily home hemodialysis and thrice-weekly in-center hemodialysis patients between 2005 and 2008. We matched 1873 home hemodialysis patients with 9365 in-center patients (i.e., 1:5 ratio) selected from the prevalent population in the US Renal Data System database. Matching variables included first date of follow-up, demographic characteristics, and measures of disease severity. The cumulative incidence of death was 19.2% and 21.7% in the home hemodialysis and in-center patients, respectively. In the intention-to-treat analysis, home hemodialysis associated with a 13% lower risk for all-cause mortality than in-center hemodialysis (hazard ratio [HR], 0.87; 95% confidence interval [95% CI], 0.78-0.97). Cause-specific mortality HRs were 0.92 (95% CI, 0.78-1.09) for cardiovascular disease, 1.13 (95% CI, 0.84-1.53) for infection, 0.63 (95% CI, 0.41-0.95) for cachexia/dialysis withdrawal, 1.06 (95% CI, 0.81-1.37) for other specified cause, and 0.59 (95% CI, 0.44-0.79) for unknown cause. Findings were similar using as-treated analyses. We did not detect statistically significant evidence of heterogeneity of treatment effects in subgroup analyses. In summary, these data suggest that relative to thrice-weekly in-center hemodialysis, daily home hemodialysis associates with modest improvements in survival. Continued surveillance should strengthen inference about causes of mortality and determine whether treatment effects are homogeneous throughout the dialysis population.

Abstract B39: Time trends in cause of death among men with prostate cancer in Sweden and the U.S.

Abstract Purpose: Due to increased diagnostic intensity and widespread PSA testing, the number of prostate cancer patients that are diagnosed with early stage, low risk disease has increased dramatically over the past decades. Because the majority of these men have a very good prognosis, most newly diagnosed patients are likely to die from causes other than prostate cancer. Temporal trends in cause of death among prostate cancer patients have, however, not been well described. Methods: We analyzed the distribution of causes of death among all incident prostate cancers recorded in the nation-wide Swedish Cancer Register (1961-2008; n = 209,946) and in the US Surveillance, Epidemiology and End Results Program (1973-2008; n = 490,341) with follow-up for mortality through 2008 in both studies. The cumulative incidence of death due to seven selected causes – prostate cancer, ischemic heart disease, cerebrovascular disease, non-prostate cancers, diabetes mellitus, chronic obstructive pulmonary disease, and external causes – was calculated. Trends in cumulative incidence were analyzed by follow-up time, calendar period, and age at diagnosis. Results: Prostate cancer accounted for 52% of the 143,027 deaths in Sweden and 30% of the 259,021 deaths in the US among men with prostate cancer during the study period. The cumulative incidence of prostate cancer death was 35% among the Swedish prostate cancer patients and 16% in the US. In both populations, ischemic heart disease was the second most common cause of death followed by death from cancers other than prostate. The cumulative incidence of death from prostate cancer declined over time, while ischemic heart disease and cerebrovascular disease remained constant. In contrast, the cumulative incidence of death from non-prostate cancers and from other causes increased at similar levels over time in both populations. Among men diagnosed at older ages (≥75) in both populations, the cumulative incidence of death from other causes (44% in Sweden, 55% in US) was higher than that of prostate cancer (38% in Sweden, 21% in US). In contrast, the cumulative incidence of death from prostate cancer (28%) was higher among Swedish men diagnosed at younger ages (≤60) compared to other causes (15%). However, in the US, the cumulative incidence of death from other causes (12%) remained higher than that of prostate cancer (10%) among men diagnosed at age 60 or younger. We also saw trends by calendar time, with a lower cumulative incidence of death due to prostate cancer among men diagnosed in the PSA era, compared to the pre-PSA era (1991 in US, 1994 in Sweden) in both populations; these trends persisted both with ≥5 and ≥10 years of follow-up time. Conclusion: Among patients with prostate cancer, other causes of death have become increasingly common over the past decades. In fact, among men diagnosed in recent years, the majority will die of causes other than prostate cancer. Because many of these causes are preventable, lifestyle intervention should become integrated in the management of patients with prostate cancer. Such interventions might indeed prevent more deaths than prevailing curative treatments for prostate cancer. Citation Format: Mara Meyer Epstein, Gustaf Edgren, Jennifer R. Rider, Lorelei A. Mucci, Hans-Olov Adami. Time trends in cause of death among men with prostate cancer in Sweden and the U.S [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr B39.

Outcomes of Antiretroviral Treatment Programs in Rural Southern Africa

Data on outcomes of antiretroviral treatment (ART) programs in rural sub-Saharan African are scarce. We describe early losses and long-term outcomes in 6 rural programs in Southern Africa with limited access to viral load monitoring and second-line ART. Patients aged ≥16 years starting ART in 2 programs each in Zimbabwe, Mozambique, and Lesotho were included. We evaluated risk factors for no follow-up after starting ART and mortality and loss to follow-up (LTFU) over 3 years of ART, using logistic regression and competing risk models. Odds ratios and subdistribution hazard ratios, adjusted for gender, age category, CD4 category, and World Health Organization stage at start of ART are reported. Among 7725 patients, 449 (5.8%) did not return after initiation of ART. During 9575 person-years, 698 (9.6%) of those with at least 1 follow-up visit died, and 1319 (18.1%) were LTFU. At 3 years, the cumulative incidence of death and LTFU were 12.5% (11.5%-13.5%) and 25.4% (24.0%-26.9%), respectively, with important differences between countries as follows: in Zimbabwe 75.1% (72.8%-77.3%) were alive and on ART at 3 years compared with 55.4% (52.8%-58.0%) in Lesotho and 51.6% (48.0%-55.2%) in Mozambique. In all settings, young age and male gender predicted LTFU, whereas advanced clinical stage and low baseline CD4 counts predicted death. In African ART programs with limited access to second-line treatment, mortality, and LTFU are high in the first 3 years of ART. Low retention in care is a major threat to the sustainability of ART delivery in Southern Africa, particularly in rural sites.

Long-term follow-up of HCV-infected hematopoietic SCT patients and effects of antiviral therapy

This prospective study was initiated in 1993 with the aim to study late effects and responses to antiviral therapy in a cohort of hepatitis C virus (HCV)-infected patients. A total of 195 patients were included from 12 centers. In all, 134 patients had undergone allogeneic and 61 autologous hematopoietic SCT (HSCT). The median follow-up from HSCT is currently 16.8 years and the maximum 27.2 years. Overall 33 of 195 patients have died of which 6 died from liver complications. The survival probability was 81.6% and the cumulative incidence for death in liver complications was 6.1% at 20 years after HSCT. The cumulative incidence of severe liver complications (death from liver failure, cirrhosis and liver transplantation) was 11.7% at 20 years after HSCT. In all, 85 patients have been treated with IFN; 42 in combination with ribavirin. The sustained response rate was 40%. The rates of severe side effects were comparable to other patient populations and no patient developed significant exacerbations of GVHD. Patients receiving antiviral therapy had a trend toward a decreased risk of severe liver complications (odds ratio=0.33; P=0.058). HCV infection is associated with morbidity and mortality in long-term survivors after HSCT. Antiviral therapy can be given safely and might reduce the risk for severe complications.

Imatinib Long-Term Effects Study: Global Independent Assessment of Imatinib in Chronic Myeloid Leukemia: Results At 8 Years,

Abstract 3766The independent, multicenter Imatinib Long Term Effects (ILTE) study assessed overall survival, loss of complete cytogenetic remission (CCyR), attainment of negative Philadelphia chromosome hematopoiesis assessed with quantitative polymerase chain reaction (PCR), serious adverse events (SAE), and toxicities not qualifying as SAE (NSAE) but judged by treating physicians as substantially affecting quality of life. The ILTE study also investigated the development of second tumours after at least two years of treatment. Consecutive CML patients, who started imatinib before 2005 and who were in CCyR after two years, were eligible. Overall survival, incidence of the first adverse events, and loss of CCyR were estimated according to the Kaplan-Meier method and compared with the standard log-rank test. Cumulative incidence of death was broken down into incidence related or unrelated to CML, accounting for competing risks. Standardized incidence ratio were calculated based on population rates specific for gender and age classes.The results at December 31st 2008 were published in J Natl Cancer Inst 2011; 103: 553–561. Here we report the results updated at December 31st, 2009, where a total of 832 patients were enrolled with a median treatment duration of 6.7 years. A comparison of the observed mortality rate in CML patients with the rate in the general Italian population showed no excess mortality. Thirty-three deaths were observed (8 CML-related), with a mortality incidence rate of 0.8 per 100 person-years (standardized incidence ratio = 0.85; 95% CI = 0.58 to 1.19). Similar results were obtained when this analysis was restricted to Italian patients. The CML-related death rate was 0.12 per 100 person-years. There were 139 recorded SAE, of which 19.4% were probably related to imatinib. Among the 830 NSAEs (which developed in 57.8% of patients and were possibly related to imatinib in 68.2% of the 830 events), the most frequent ones were muscle cramps, asthenia (observed in 4.9% of patients), edema, skin fragility, diarrhea, conjunctival hemorrhages, osteoarticular pain and tendon or ligament lesions. Nineteen patients (2.3%) discontinued imatinib because of drug-related toxicities. Fifty-three patients lost CCyR, corresponding to a rate of 1.4 per 100 person years (1.1% in patients who received imatinib as first line treatment). Durable (greater than 1 year) Philadelphia negative hematopoiesis, as evaluated by PCR was attained by 125 patients (15%).The onset of second tumours was also evaluated: 34 patients developed second cancers. The overall rate was not significantly different from that of the general population (SIR = 0.9, 95% CI = 0.63 to 1.26), with the exception of prostate cancer (SIR = 2.86; 95% CI = 1.48 to 4.99).In conclusion, CML-related deaths are uncommon in CML patients who are in CCyR two years after starting imatinib. Survival is not statistically significantly different from that of the general population. Side effects are present but generally not serious. A higher incidence of prostate cancer, to be confirmed and further analyzed, was observed. Disclosures:No relevant conflicts of interest to declare.