Time Trends In Survival Research Articles

Survival patterns in lung and pleural cancer in Europe 1999–2007: Results from the EUROCARE-5 study

BackgroundSurvival of patients diagnosed with lung and pleura cancer is a relevant health care indicator which is related to the availability and access to early diagnosis and treatment facilities. Aim of this paper is to update lung and pleural cancer survival patterns and time trends in Europe using the EUROCARE-5 database. MethodsData on adults diagnosed with lung and pleural cancer from 87 European cancer registries in 28 countries were analysed. Relative survival (RS) in 2000–2007 by country/region, age and gender, and over time trends in 1999–2007 were estimated. ResultsLung cancer survival is poor everywhere in Europe, with a RS of 39% and 13% at 1 and 5years since diagnosis, respectively. A geographical variability is present across European areas with a maximum regional difference of 12 and 5 percentage points in 1-year and 5-year RS respectively. Pleural cancer represents 4% of cases included in the present study with 7% 5-year RS overall in Europe. Most pleural cancers (83%) are microscopically verified mesotheliomas. Survival for both cancers decreases with advancing age at diagnosis for both cancers. Slight increasing trends are described for lung cancer. Survival over time is higher for squamous cell carcinoma and adenocarcinomas than for small and large cell carcinoma; and better among women than men. ConclusionsDespite the generalised although slight increase, survival of lung and pleural cancer patients still remains poor in European countries.Priority should be given to prevention, with tobacco control policies across Europe for lung cancer and banning asbestos exposure for pleural cancer, and in early diagnosis and better treatment. The management of mesothelioma needs a multidisciplinary team and standardised health care strategies.

Survival of male genital cancers (prostate, testis and penis) in Europe 1999–2007: Results from the EUROCARE-5 study

BackgroundWe provide updated estimates of survival and survival trends of male genital tumours (prostate, testicular and penis cancers), in Europe and across European areas. MethodsThe complete approach was used to obtain relative survival estimates for patients diagnosed in 2000–2007, and followed up through 2008 in 29 countries. Data came from 87 cancer registries (CRs) for prostate tumours and from 86 CRs for testis and penis tumours. Relative survival time trends in 1999–2007 were estimated by the period approach. Data came from 49 CRs in 25 countries. ResultsWe analysed 1,021,275 male genital cancer cases. Five-year relative survival was high and decreased with increasing age for all tumours considered. We found limited variation in survival between European regions with Eastern Europe countries having lower survival than the others. Survival for penile cancer patients did not improve from 1999 to 2007. Survival for testicular cancer patients remained stable at high levels since 1999. Survival for prostate cancer patients increased over time. ConclusionsTreatment standardisation and centralisation for very rare diseases such as penile cancers or advanced testicular tumours should be supported. The high survival of testicular cancer makes long-term monitoring of testicular cancer survivors necessary and CRs can be an important resource. Prostate cancer patients’ survival must be interpreted considering incidence and mortality data. The follow-up of the European Randomised Study of Screening for Prostate Cancer should continue to clarify the impact of screening on prostate cancer mortality together with population based studies including information on stage and treatments.

The changing trends and outcomes in renal replacement therapy: data from the ERA-EDTA Registry.

This study examines the time trends in incidence, prevalence, patient and kidney allograft survival and causes of death (COD) in patients receiving renal replacement therapy (RRT) in Europe. Eighteen national or regional renal registries providing data to the European Renal Association-European Dialysis and Transplant Association Registry between 1998 and 2011 were included. Incidence and prevalence time trends between 2001 and 2011 were studied with Joinpoint and Poisson regression. Patient and kidney allograft survival and COD between 1998 and 2011 were analysed using Kaplan-Meier and competing risk methods and Cox regression. From 2001 to 2008, the adjusted incidence of RRT rose by 1.1% (95% CI: 0.6, 1.7) annually to 131 per million population (pmp). During 2008-2011, the adjusted incidence fell by 2.2% (95% CI: -4.2, -0.2) annually to 125 pmp. This decline occurred predominantly in patients aged 45-64 years, 65-74 years and in the primary renal diseases diabetes mellitus type 1 and 2, renovascular disease and glomerulonephritis. Between 2001 and 2011, the overall adjusted prevalence increased from 724 to 1032 pmp (+3.3% annually, 95% CI: 2.8, 3.8). The adjusted 5-year patient survival on RRT improved between 1998-2002 and 2003-2007 [adjusted hazard ratio (HRa) 0.85, 95% CI: 0.84, 0.86]. Comparing these time periods, the risk of cardiovascular deaths fell by 25% (HRa 0.75, 95% CI: 0.74, 0.77). However the risk of malignant death rose by 9% (HRa 1.09, 95% CI: 1.03, 1.16) in patients ≥65 years. This European study shows a declining RRT incidence, particularly in patients aged 45-64 years, 65-74 years and secondary to diabetic nephropathy. Encouragingly, the adjusted RRT patient survival continues to improve. The risk of cardiovascular death has decreased, though the risk of death from malignancy has increased in the older population.

Obstetric risk factors and time trends of neurodevelopmental outcome at 2years in very-low-birthweight infants: a single institution study.

To assess the time trends of neonatal survival and infant neurodevelopmental outcome in very-low-birthweight children at 24months corrected age over a 20-year period. The study cohort comprised 857 infants (439 males and 418 females) weighing less than 1500g at birth or delivered before 32weeks gestational age in the period 1989 to 2008. Neurological examination and cognitive assessment of the infants (Bayley Scales of Infant Development and Griffiths Mental Developmental Scale) were performed at 24months corrected age. The prevalence of neonatal survival with normal neurodevelopmental outcome increased from 55.3% (104/188) in 1989 to 1993, to 61.4% in 1994-1998 (116/189), 68.3% in 1999 to 2003 (138/202), and 84.5% in 2004 to 2008 (235/278) (annual increase=1%, 95% CI 2.1-4.1; p<0.001). In logistic models, the increase in the rate of normal neurodevelopmental outcome during the periods studied was consistent across the categories of birthweight (≤1000g as opposed to >1000g), gestational age (≤28wks as opposed to >28wks), and clinical characteristics (pre-eclampsia/growth restriction as opposed to spontaneous prematurity/rupture of membranes). The increased rate of normal neurodevelopmental outcome at 2years among very-low-birthweight infants is independent of obstetric risk factors.

Incidence trends in head and neck squamous cell carcinoma in Slovenia, 1983-2009: role of human papillomavirus infection.

An increase in the incidence of oropharyngeal squamous cell carcinoma (OPSCC) was observed in several population-based registries and has been attributed to human papillomavirus (HPV) infection. In the present study, we aimed to assess the contribution of HPV infection to the burden of mucosal head and neck squamous cell carcinoma (HNSCC) in Slovenia. For this purpose, data from the nationwide Cancer Registry of Slovenia for cases diagnosed between 1983 and 2009 were analyzed to determine time trends of age-adjusted incidence rates and survival in terms of annual percentage change (APC) for HNSCC in potentially HPV-related and HPV-unrelated sites. In addition, determination of p16 protein, HPV DNA and E6/E7 mRNA was performed in a cohort of OPSCC patients identified from the prospective database for the years 2007-2008. In total, 2,862 cases of HNSCC in potentially HPV-related sites and 7,006 cases in potentially HPV-unrelated sites were identified with decreased incidence observed over the time period in both groups (-0.58; 95 % CI -1.28 to -0.13 and -0.90; 95 % CI -1.23 to -0.57). Regardless of the group, incidence trends for both genders showed a significant decrease in men and increase in women. In a cohort of 99 OPSCC patients diagnosed between 2007 and 2008, 20 (20.2 %) patients had HPV positive tumors and exhibited a superior outcome compared to HPV-negative patients. In conclusion, results of the epidemiologic and histopathologic study confirmed that HPV infection had no major impact on the incidence trends in the Slovenian patients with HNSCC and, specifically, OPSCC during the studied period.

Breast cancer in Wales: time trends and geographical distribution.

Breast cancer is the second commonest malignancy in the world. In 2012, approximately 522,000 women died of breast cancer across the world. The aim of this study is to provide an up-to-date analysis of time trends in incidence, geographical distribution, survival and mortality from breast cancer in Wales. Breast cancer cases registered between 1985 and 2012 were identified from the Welsh Cancer Intelligence and Surveillance Unit (WCISU). A Poisson regression model was fitted to assess temporal trends and rate ratios (RR) and 95% confidence intervals (CI) were determined and compared in relation to age, geographical distribution and mortality across time periods. A total of 60,227 women diagnosed with breast cancer were registered with the Welsh cancer registry between 1985 and 2012. The age-standardised incidence rate of breast cancer was 113.4 per 100,000 populations over the entire study period. There has been a significant increase in the incidence of breast cancer over the study period, although a slight decline was recorded towards the end of the study. There is a considerable regional variation in incidence, with a higher incidence rate in the rural areas compared to urban areas (P<0.001). One- and five-year relative survival improved from 83.3 and 64.2 respectively in 1985-1989 to 91.1 and 78.8 respectively in 2000-2004. There has also been a considerable improvement in relative survival across all age groups. Mortality has improved over the study period with the most dramatic decline in the age groups 45-54 and 55-64 years (P<0.001). There has been a significant increase in the incidence of breast cancer in Wales over the last three decades, which is likely to be partly due to the introduction of the National Health Service Breast Screening Programme. Breast cancer incidence is higher in rural areas than urban areas and lower incidence was seen in more deprived areas. There was a considerable decline in mortality rate across almost all age groups, especially in recent years. However, women over the age of 65 years had poorer outcome throughout the study period.

Decade-long Trends in Atrial Fibrillation Incidence and Survival: A Community Study

BackgroundContemporary data on temporal trends in incidence and survival after atrial fibrillation are scarce. MethodsResidents of Olmsted County, Minn., with a first-ever atrial fibrillation or atrial flutter event between 2000 and 2010 were identified. Age- and sex-adjusted incidence rates were standardized to the 2010 US population, and the relative risk of atrial fibrillation in 2010 versus 2000 was calculated using Poisson regression. Standardized mortality ratios of observed versus expected survival were calculated, and time trends in survival were examined using Cox regression. ResultsWe identified 3344 patients with incident atrial fibrillation/atrial flutter events (52% were male, mean age 72.6 years, 95.7% were white). Incidence did not change over time (age- and sex-adjusted rate ratio, 1.01; 95% confidence interval [CI], 0.91-1.13 for 2010 vs 2000). Within the first 90 days, the risk of all-cause mortality was greatly elevated compared with individuals of a similar age and sex distribution in the general population (standardized mortality ratios 19.4 [95% CI, 17.3-21.7] and 4.2 [95% CI, 3.5-5.0] for the first 30 days and 31 to 90 days after diagnosis, respectively). Survival within the first 90 days did not improve over the study period (adjusted hazard ratio, 0.96; 95% CI, 0.71-1.32 for 2010 vs 2000); likewise, no difference in mortality between 2010 and 2000 was observed among 90-day survivors (hazard ratio, 1.05; 95% CI, 0.85-1.31). ConclusionsIn the community, atrial fibrillation incidence and survival have remained constant over the last decade. A dramatic and persistent excess risk of death was observed in the 90 days after atrial fibrillation diagnosis, underscoring the importance of early risk stratification.

Survival for haematological malignancies in Europe between 1997 and 2008 by region and age: results of EUROCARE-5, a population-based study

More effective treatments have become available for haematological malignancies from the early 2000s, but few large-scale population-based studies have investigated their effect on survival. Using EUROCARE data, and HAEMACARE morphological groupings, we aimed to estimate time trends in population-based survival for 11 lymphoid and myeloid malignancies in 20 European countries, by region and age. In this retrospective observational study, we included patients (aged 15 years and older) diagnosed with haematological malignancies, diagnosed up to Dec 31, 2007, and followed up to Dec 31, 2008. We used data from the 30 cancer registries (across 20 countries) that provided continuous incidence and good quality data from 1992 to 2007. We used a hybrid approach to estimate age-standardised and age-specific 5-year relative survival, for each malignancy, overall and for five regions (UK, and northern, central, southern, and eastern Europe), and four 3-year periods (1997-99, 2000-02, 2003-05, 2006-08). For each malignancy, we also estimated the relative excess risk of death during the 5 years after diagnosis, by period, age, and region. We analysed 560 444 cases. From 1997-99 to 2006-08 survival increased for most malignancies: the largest increases were for diffuse large B-cell lymphoma (42·0% [95% CI 40·7-43·4] to 55·4% [54·6-56·2], p<0·0001), follicular lymphoma (58·9% [57·3-60·6] to 74·3% [72·9-75·5], p<0·0001), chronic myeloid leukaemia (32·3% [30·6-33·9] to 54·4% [52·5-56·2], p<0·0001), and acute promyelocytic leukaemia (50·1% [43·7-56·2] to 61·9% [57·0-66·4], p=0·0038, estimate not age-standardised). Other survival increases were seen for Hodgkin's lymphoma (75·1% [74·1-76·0] to 79·3% [78·4-80·1], p<0·0001), chronic lymphocytic leukaemia/small lymphocytic lymphoma (66·1% [65·1-67·1] to 69·0% [68·1-69·8], p<0·0001), multiple myeloma/plasmacytoma (29·8% [29·0-30·6] to 39·6% [38·8-40·3], p<0·0001), precursor lymphoblastic leukaemia/lymphoma (29·8% [27·7-32·0] to 41·1% [39·0-43·1], p<0·0001), acute myeloid leukaemia (excluding acute promyelocytic leukaemia, 12·6% [11·9-13·3] to 14·8% [14·2-15·4], p<0·0001), and other myeloproliferative neoplasms (excluding chronic myeloid leukaemia, 70·3% [68·7-71·8] to 74·9% [73·8-75·9], p<0·0001). Survival increased slightly in southern Europe, more in the UK, and conspicuously in northern, central, and eastern Europe. However, eastern European survival was lower than that for other regions. Survival decreased with advancing age, and increased with time only slightly in patients aged 75 years or older, although a 10% increase in survival occurred in elderly patients with follicular lymphoma, diffuse large B-cell lymphoma, and chronic myeloid leukaemia. These trends are encouraging. Widespread use of new and more effective treatment probably explains much of the increased survival. However, the persistent differences in survival across Europe suggest variations in the quality of care and availability of the new treatments. High-resolution studies that collect data about stage at diagnosis and treatments for representative samples of cases could provide further evidence of treatment effectiveness and explain geographic variations in survival. Compagnia di San Paolo, Fondazione Cariplo, European Commission, and Italian Ministry of Health.

Why do lifespan variability trends for the young and old diverge? A perturbation analysis.

BACKGROUNDVariation in lifespan has followed strikingly different trends for the young and old: while total lifespan variability has decreased as life expectancy at birth has risen, the variability conditional on survival to older ages has increased. These diverging trends reflect changes in the underlying demographic parameters determining age-specific mortality.OBJECTIVEWe ask why the variation in the ages at death after survival to adult ages has followed a different trend than the variation at younger ages, and aim to explain the divergence in terms of the age pattern of historical mortality changes.METHODSUsing simulations, we show that the empirical trends in lifespan variation are well characterized using the Siler model, which describes the mortality trajectory using functions representing early-life, later-life, and background mortality. We then obtain maximum likelihood estimates of the Siler parameters for Swedish females from 1900 to 2010. We express mortality in terms of a Markov chain model, and apply matrix calculus to compute the sensitivity of age-specific variance trends to the changes in Siler model parameters.RESULTSOur analysis quantifies the influence of changing demographic parameters on lifespan variability at all ages, highlighting the influence of declining childhood mortality on the reduction of lifespan variability, and the influence of subsequent improvements in adult survival on the rising variability of lifespans at older ages.CONCLUSIONSThese findings provide insight into the dynamic relationship between the age pattern of survival improvements and time trends in lifespan variability.

Incidence and survival of children with central nervous system primitive tumors in the French National Registry of Childhood Solid Tumors

Central nervous system (CNS) tumors are the second most common childhood malignancy. The French National Registry of Childhood Solid Tumors (NRCST) makes it possible to describe this variety of distinct tumor types and to provide incidence and survival data in France on a nationwide basis. All children aged 0-14 years, who were registered with a primary CNS tumor in the NRCST of France between 2000 and 2008, were identified. Tumors were classified according to the International Classification of Childhood Cancer, third edition. Approximately 57% of pediatric CNS tumors were gliomas, with astrocytomas of the pilocytic type predominating. Distributions of subtypes by age showed that primitive neuroectodermal tumors and ependymomas mainly occurred in children aged <5 years. The mean annual incidence rate of CNS tumors was 39 per million. No statistically significant change in time trends of incidence rate was observed during 2000-2008. For all tumors combined, overall survival was 84.8% (95% CI, 83.7%-85.9%) at 1 year and 72.9% (95% CI, 71.5%-74.3%) at 5 years. Survival time trends were studied in a multivariate analysis observing a reduction in the risk of death in periods of diagnosis 2003-2005 (HR = 0.8; 95% CI, 0.7–0.9) and 2006-2008 (HR = 0.7; 95% CI, 0.6-0.9) compared with 2000-2002. The stable incidence rates during the last 10 years could indicate that major changes in environmental risk factors are unlikely, but the ongoing need for population-based surveillance remains relevant. Results indicate a positive trend in the survival probability still persistent in the 2000s.

Antioxidant Small-spotted Catshark Burgers

Event Abstract Back to Event Antioxidant Small-spotted Catshark Burgers Joana Patriarca1*, Maria J. Rodrigues1 and Rui Pedrosa1 1 Polytechnic Institute of Leiria - Marine Resources Research Group (GIRM), Portugal Tons of fish are rejected daily, not only on board, but also on shore during the industrial processing (INE, 2012). In order to reuse these wastes, restructured seafood products must be developed. On the other hand, in western countries a trend in the increase of the number of cancer cases is observed, especially among the youngsters (Steliarova-Foucher et al, 2004). A healthy and high quality nutrition plays an important role on cancer prevention (Davis et al, 2010; Kuno et al, 2012). Many authors found several phytochemical compounds naturally present in foods with powerful antioxidant properties. These have the ability to stop or delay the development of the tumors, by inducing apoptosis and prevent angiogenesis or metastasis (Kou et al, 2013). In the present work, it was developed a restructured functional food based on rejected small-spotted catshark. The functional capacity of this food is attained by the addition of ingredients with proven antioxidant ability. Studies have been made to optimize the antioxidant extraction process from the fish burger through different combinations of solvent extraction. Furthermore, the antioxidant activity of the restructured product was characterized in terms of total phenolic content (TPC), 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity and oxygen radical absorbance capacity (ORAC). Apparently, a higher level of antioxidants is detected when methanol is used for extraction during twelve hours at room temperature. The results also showed the functional fish product presents a higher capacity for DPPH reduction and increased values for ORAC by comparison with small-spotted catshark only. Acknowledgements The idea of the present project was granted with the National University Award Lotaçor 2011-2012. References Davis, C.D., Emenaker, N.J., Milner, J.A. (2010). Angiogenesis: Molecular Targets for Nutritional Preemption of Cancer. Seminars in Oncology, 37(3):243-257. INE (2012). Estatística da Pesca 2011. Instituto Nacional de Estatística, I.P., Direcção-Geral de Recursos Naturais, Segurança e Serviços Marítimos, Lisboa, Portugal Kou, X., Kirberger, M., Yang, Y., Chen, N. (2013). Natural products for cancer prevention associated with Nrf2–ARE pathway. Food Science and Human Wellness, 2:22-28. Kuno, T., Tsukamto, T., Hara, A., Tanaka, T. (2012). Cancer chemoprevention through the induction of apoptosis by natural compounds. Journal of Biophysical Chemistry, 3(2):156-173. Steliarova-Foucher, E., Stiller, C., Kaatsch P., Berrino, F., Coebergh, J.W., Lacour, B., Perkin, M. (2004). Geographical patterns and time trends of cancer incidence and survival among children and adolescents in Europe since the 1970s (the ACCIS project): an epidemiological study. The Lancet, 364(9451):2097-2105. Keywords: DPPH, Fish burger, ORAC, polyphenol content, small-spotted catshark Conference: IMMR | International Meeting on Marine Research 2014, Peniche, Portugal, 10 Jul - 11 Jul, 2014. Presentation Type: Poster Presentation Topic: SEAFOOD TECHNOLOGY Citation: Patriarca J, Rodrigues MJ and Pedrosa R (2014). Antioxidant Small-spotted Catshark Burgers. Front. Mar. Sci. Conference Abstract: IMMR | International Meeting on Marine Research 2014. doi: 10.3389/conf.fmars.2014.02.00179 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 05 May 2014; Published Online: 18 Jul 2014. * Correspondence: Miss. Joana Patriarca, Polytechnic Institute of Leiria - Marine Resources Research Group (GIRM), Peniche, Portugal, joanapatriarca22@gmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Joana Patriarca Maria J Rodrigues Rui Pedrosa Google Joana Patriarca Maria J Rodrigues Rui Pedrosa Google Scholar Joana Patriarca Maria J Rodrigues Rui Pedrosa PubMed Joana Patriarca Maria J Rodrigues Rui Pedrosa Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Progress against laryngeal cancer in The Netherlands between 1989 and 2010

Cancer of the larynx is a frequently occurring head and neck cancer in The Netherlands. The main risk factors are smoking and excessive alcohol consumption. The aim of our study was to evaluate the progress against laryngeal cancer by studying trends in incidence, mortality and survival in The Netherlands. All patients in The Netherlands Cancer Registry diagnosed with invasive primary squamous cell carcinoma of the larynx during the period 1989-2010 were included for analysis. Time trends in incidence, mortality, treatment and survival were described for the total group and stratified by sex and subsite: glottis, supraglottis and subglottis. The most frequently affected subsite for men was the glottis (69%) and for women the supraglottis (55%). Glottic cancer was diagnosed at lower stages than supraglottic cancer. Incidence and mortality rates decreased for males with -2.5 and -2.8% per year, respectively, but remained stable for women, except for an increasing mortality rate in older women (EAPC: +2.5%). Five-year relative survival rates were stable for glottic (85%) and supraglottic (50%) cancer, whereas patients with high-staged cancers more often received radiotherapy. Multivariable analysis showed lower relative excess risks of dying for women, younger patients (<75 years), glottic cancer, lower stage cancer and those undergoing surgery. Changes in incidence and mortality rates are in line with changing smoking habits in The Netherlands. Declining incidence with stable survival rates gives rise to hope and worry at the same time.

Trends In Incidence, Presentation, and Outcomes Of Chronic Graft-Versus-Host Disease In Allogeneic Transplantation- Report From The Center For International Blood and Marrow Transplant Research

There have been considerable changes in the practice of allogeneic transplantation over the last several years. In this study, we evaluate the impact of these changes on chronic graft-versus-host disease (cGVHD), the most important long-term complication. Our study utilized the central database of the CIBMTR to describe time trends for cGVHD incidence, presentation, nonrelapse mortality and overall survival from 1995-2007. The 12-year period was divided into three time periods- 1995-1999, 2000-2003, 2004-2007 to allow for the systematic analysis and description of trends. The trends of cGVHD severity (mild, moderate, severe), type of onset (progressive, interrupted, de novo), and major organ involved over the past years were analyzed using chi-square tests. Cumulative incidence was used to estimate cGVHD incidence and nonrelapse mortality. Death/ 2nd transplant/donor cell infusion/relapse were treated as competing risks for estimation of cumulative incidence of cGVHD. A test of trend was used to estimate HR across time periods. Multivariate logistic regression analysis was used to determine clinical variables affecting the incidence of cGVHD, including the time period of transplant. The study included 26,563 patients with acute leukemia (AML= 10,737, ALL= 6756), chronic myeloid leukemia (n=6341) and myelodysplastic syndrome (n=2729). In the univariate analysis, the incidence of cGVHD was significantly increased in the recent time periods (HR= 1.14, p for test of trend <0.0001). This trend persisted when the incidence was evaluated by donor type (HLA identical sibling-HR=1.17; unrelated donor-HR=1.07; cord blood-HR=1.24, all p < 0.01), graft type (PBSC-HR=1.19; cord blood-HR=1.24, p < 0.01), or conditioning intensity (myeloablative-HR=1.13; reduced intensity-HR=1.16, p< 0.01). In mismatched-related donors (HR=1.08, p=0.24) and bone marrow grafts (HR=1.01,p=0.54) there was no significant change in the incidence of cGVHD. Progressive cGVHD was found to be less frequently diagnosed over time, possibly from the recognition of the late acute classification introduced in 2005. Extensive, moderate and severe categories of cGVHD were more frequent in the two most recent time periods (2000-2003 and 2004-2007), as compared to the earliest time period (1995-1999). Skin was more frequently involved in the recent time period (2004-2007), with greater association of skin involvement at maximum severity reported in peripheral blood (33%), compared with bone marrow (25%), thus graft type appears to have impacted cGVHD presentation. In multivariate analysis, the recent time period (2004-2007) was associated with higher risk of cGVHD when compared to the two earlier time periods (2004-2007 versus 1995-1999, OR 1.19, p<0.0001; 2004-2007 versus 2000-2003, OR 1.13, p=0.002). Use of bone marrow with an unrelated donor (matched or mismatched), and peripheral blood graft with all categories of donor group were associated with higher risk of cGVHD, as compared to the use of bone marrow with a matched sibling donor. The risk of cGVHD was similar between marrow with a matched sibling donor and cord blood (matched or mismatched). In conclusion, this analysis of cGVHD trends over time demonstrates an increased cGVHD incidence in recent years despite controlling for factors in the donor, the graft and the conditioning that are associated with that trend, and serves as a useful reference for future research in the management of cGVHD. Disclosures:No relevant conflicts of interest to declare.

Time trends in population-based breast cancer survival in Estonia: Analysis by age and stage

Background. Survival from breast cancer (BC) in Estonia has been consistently among the lowest in Europe. The aim of this study was to examine most recent trends in BC survival in Estonia by age and stage. The trends in overall BC incidence and mortality are also shown in the paper. Material and methods. Estonian Cancer Registry data on all cases of BC, diagnosed in women in Estonia during 1995–2007 (n = 7424) and followed up for vital status through 2009, were used to estimate relative survival ratios (RSR). Period hybrid approach was used to obtain the most recent estimates (2005–2009). Stage was classified as localized, local/regional spread or distant. Results. BC incidence continued to rise throughout the study period, but mortality has been in steady decline since 2000. The distribution of patients shifted towards older age and earlier stage at diagnosis. Overall age-standardized five-year RSR increased from 63% in 1995–1999 to 74% in 2005–2009. Younger age groups experienced a more rapid improvement compared to women over 60. Significant survival increase was observed for both localized and locally/regionally spread BC with five-year RSRs reaching 96% and 70% in 2005–2009, respectively; the latest five-year RSR for distant BC was 11%. Survival for T4 tumors was poor and large age difference was seen for locally/regionally spread BC. Conclusions. Considerable improvement in BC survival was observed over the study period. Women under 60 benefited most from both earlier diagnosis and treatment advances of locally/regionally spread cancers. However, the survival gap with more developed countries persists. Further increase in survival, but also decline in BC mortality in Estonia could be achieved by facilitating early diagnosis in all age groups, but particularly among women over 60. Investigations should continue to clarify the underlying mechanisms of the stage-specific survival deficit in Estonia.

Time trends in overall survival (OS) gain in advanced non-small-cell lung cancer (NSCLC).

e19144 Background: There is an ongoing debate about the adequacy of OS as primary endpoint (PEP) in phase III trials in various tumor types, including NSCLC (Soria Ann Oncol 2010). Moreover, median OS and post-progression survival are increasing in NSCLC (Hotta PLoS One 2011 and Hayashi Ann Oncol 2012). We assessed the frequency and time trends in OS gain in recent trials. Methods: We searched PubMed for phase III trials in advanced NSCLC published between January 1998 and December 2011 in 13 leading journals. The PEP was the endpoint stated explicitly, used for N calculation, or listed first. Gain in OS was ascertained when there were significant differences in any pairwise comparison on OS following the original authors’ definitions. Results: We retrieved 148 trials that enrolled a total of 70,716 patients in 325 trial arms. The median number of patients per arm was larger for the 2005-2011 period than for the 1998-2004 period (207 vs 150; P&lt;0.01). OS was used as PEP alone in 99 trials, and as one of the co-primary endpoints in 3 trials (the PEP could not be ascertained for one trial). There was no trend regarding the use of OS as PEP in the two periods compared, either overall (P=0.44) or in first line (P=0.41). Gain in OS according to trial features is shown in the Table. Conclusions: Significant gains in OS appear to decrease along the years, despite the growth in size of NSCLC trials and the continued use of OS as PEP. [Table: see text]

Abstract P003: Survival after Incident Atrial Fibrillation: A Community-Based Study

Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice, causes substantial morbidity, and is associated with an excess risk of mortality. However, information on contemporary time trends in survival after AF is lacking. Thus, we aimed to determine whether survival after incident AF has changed over the last decade in a community-based cohort of 3413 individuals with incident AF between 2000 and 2010. Methods: Olmsted County, MN residents 18 years of age and older with a first-ever AF or atrial flutter event between 2000 and 2010 were identified using inpatient and outpatient diagnostic codes and electrocardiograms. Deaths from any cause were ascertained through August 31, 2012 and time trends in survival after AF were examined using Kaplan-Meier curves and Cox proportional hazards regression. Results: Among 3413 individuals with incident AF (52% men, age range 18-104) between 2000 and 2010, 1561 deaths were observed over a median follow-up of 3.4 years. Survival did not differ by year of AF diagnosis (figure). In addition, the proportion of cardiovascular disease-related deaths compared to non-cardiovascular deaths did not differ over time. After adjustment for age, sex, and Charlson comorbidity index, the hazard ratios for all-cause mortality were 1.09 (95% CI 0.97-1.23) for those diagnosed with AF in 2004-2007 vs. 2000-2003 and 1.04 (95% CI 0.90-1.12) for 2008-2010 vs. 2000-2003. Furthermore, the risk of death did not differ by sex after adjustment for age and comorbidity (HR 1.00, 95% CI 0.90-1.11 for men vs. women). Conclusions: In the community, survival after AF has remained constant over the last decade despite substantial changes in the recommendations for treatment of AF. This underscores the importance of identification of prognostic factors and continued surveillance of outcomes in AF, as well as a better understanding of how to optimize the management of AF to improve outcomes in these patients.

Time trends in survival from cancer of unknown primary: Small steps forward

BackgroundCancer of unknown primary (CUP) is a fatal cancer for which incidence trends have changed but detailed survival trends remain unexplored. These could point out successful diagnostic and therapeutic approaches. We investigate survival trends in CUP according to histology, locations of metastases and site-specific causes of death. Patients and methodsA total of 20,523 CUP patients with nodal and extranodal metastases were identified from the Swedish Cancer Registry. Hazard ratios (HRs) were estimated, comparing three different time periods (1987–1993, 1994–2000 and 2001–2008) with respect to histological subtype, CUP location and the cause of death. ResultsSurvival for patients with CUP increased over the study period (HR=0.91 [95% confidence interval (CI): 0.78–0.84], p<0.001 for trend). Adenocarcinoma was the only histology associated with increased survival (0.78 [0.74–0.82], p<0.001 for trend). Survival was improved most clearly for CUP of the pelvis (0.55 [0.36–0.83]), peritoneum (0.58 [0.53–0.65]) and nervous system (0.46 [0.29–0.72]). Survival improved substantially in patients with ovarian (0.57 [0.46–0.70]), peritoneal (0.39 [0.24–0.65]) and biliary system cancers (0.67 [0.52–0.87]). Kaplan–Meier curves showed significant survival gains for all CUP and adenocarcinoma patients (p<0.001). ConclusionsOver time, survival for patients with CUP increased for adenocarcinoma and for CUP of the pelvis, peritoneum and nervous system. Survival trends in CUP may be related to (1) similar trends in other common metastatic tumours, particularly pancreatic and hepatobiliary cancers, which are common ‘hidden’ primaries for CUP, (2) earlier detection and (3) advances in the management of metastatic cancers. The improvement in survival at specific locations suggests true therapeutic gains.

Time-trends in survival in young women with breast cancer in a SEER population-based study

Mortality improvements in young women with breast cancer (BC) may be attributable to treatment advances; screening likely plays a less significant role as mammography is not recommended <40. We examined time-trends in outcome in a cohort of young women. Our goal was to determine the contributions of treatment and screening to mortality improvements and evaluate whether differential outcomes by ER status exist. Using SEER, patients (73,447) were divided into three categories by diagnosis year (1990-1994, 1995-1999, 2000-2004) and also categorized as <40 or 40-50 years. Multivariate analysis was done to investigate the association of survival with time period for both age groups by ER status. Hazard ratios (HR) for mortality in women 40-50 with ER positive BC declined over time. With 1990-1994 as referent, the HR in 1995-1999 was 0.77 (0.69-0.86) and 0.65 (0.59-0.71) in 2000-2004 (p < 0.001). Women <40 with ER positive BC also had improvements over time. In ER negative patients, the degree of improvements over time was less than that seen in ER positive women. We report a survival disparity over time in young women by ER status. Patients with ER negative disease have not had the degree of improvements over time as seen in ER positive disease. Therefore, mortality improvements in young women with ER positive BC may be attributed to treatment advances with endocrine agents.

Abstract P3-07-02: Time-trends in survival in young women with breast cancer in a SEER population-based study

Abstract Background: As mammography is not generally recommended to women under 40, it is reasonable to conclude that documented outcome improvements over time are attributable to treatment advances with screening playing a less important role. In order to determine the contribution of screening and treatment to improvements, we evaluated the odds of presenting with more advanced disease by time-period and examined the time-trends in outcome in a population-based cohort ≤50. We evaluated whether any outcomes differentials existed by ER status. Methods: Patients in SEER diagnosed with breast cancer (BC) were divided into 4 by year of diagnosis (1990–1994, 1995–1999, 2000–2004, 2005–2008). Patients were also categorized into 2 age-groups: &amp;lt;40 and 40–50 years. Odds ratios for presenting with more advanced disease over the 4 time-periods were calculated for the 2 age-groups. Multivariate analysis was done to investigate the association of survival with time-period for the 2 age-groups by ER status. Results: 110,629 patient records were included. Multivariate adjusted hazard ratio for mortality in women aged 40–50 with ER positive BC declined over time. Comparing all time periods to 1990–1994, the HR for mortality in 1995–1999 was 0.83 (0.77–0.89), 0.61 (0.57–0.65) in 2000–2004, and 0.35 (0.30–0.40) in 2005–2008 (p &amp;lt;.001). Those &amp;lt;40 years with ER positive BC also had mortality improvements over time (HR 0.86, 0.63, 0.26 for 1995–1999, 2000–2004, and 2005–2008 respectively). On the contrary, no mortality improvements were seen in women with ER negative disease. Trends in progressively worsening mortality over time were observed in this cohort. A 1.3-fold increase in the odds of presenting with stage I BC was seen in women 40–50 years comparing the 3 latter time periods with 1990–1994. Similarly, in the same age group, there was a 2.12-fold likelihood of presenting with a tumor ≤1cm in 2005–2008 versus 1990–1994. In women &amp;lt;40 years at diagnosis, the probability of presenting with stage I disease was lower in the 3 latter time periods than in 1990–1994; and a 2.84-fold higher probability of presenting with stage III/IV disease was seen in 2005–2008 compared with 1990–1994. Conclusions: Patients who are ER positive and between 40–50 years have had time-trend changes with improvements in breast cancer outcome and smaller tumors likely attributable to both screening and hormonal therapies. Patients who are &amp;lt;40 years and/or ER negative have not had improvements in breast cancer outcome. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-07-02.

Time trends in chemotherapy (administration and costs) and relative survival in stage III colon cancer patients – a large population-based study from 1990 to 2008

Background. Use of adjuvant chemotherapy for stage III colon cancer has increased since several trials have shown the beneficial effect on survival. In this population-based study we show time trends in the administration and costs of chemotherapy and relative survival of patients with stage III colon cancer. Methods. All patients surgically treated for adenocarcinoma of the colon stage III between 1990 and 2008 in The Netherlands were included. Relative survival (using period analyses) and Relative Excess Risks of death (RER) were calculated. The costs of chemotherapy were estimated. Results. A total of 24 111 colon cancer patients with stage III were included in the cohort. The administration (from 9.5% in 1990 to 61.8% in 2008; p < 0.001) and costs of chemotherapy (from €38 467 in 1990 to €3 876 150 in 2008) increased during the study period. Multivariable relative survival improved for patients receiving adjuvant chemotherapy (RER 0.93; 95% CI 0.92–0.94; p < 0.001). In contrast, relative survival remained stable for patients, younger than 80 years, who did not receive chemotherapy (RER 1.00; 95% CI 1.00–1.01; p = 0.3). Patients aged 80 years and older without chemotherapy, relative survival increased during the study period (RER 0.98; 95% CI 0.97–0.99; p < 0.001). Conclusions. The administration, the costs of chemotherapy and the survival of patients with stage III colon cancer increased over time. Whereas the costs and administration of chemotherapy increased extensively, relative survival increased to a lesser extent. For patients treated with adjuvant chemotherapy relative survival increased equally in all age groups.