On the use of flexible excess hazard regression models for describing long-term breast cancer survival: a case-study using population-based cancer registry data.

BACKGROUND: Breast cancer prognosis has dramatically improved over 40 years. There is, however, no proof of population 'cure'. This research aimed to examine the pattern of long-term excess mortality due to breast cancer and evaluate its determinants in the context of cancer registry data. METHODS: We used data from the Geneva Cancer Registry to identify women younger than 75 years diagnosed with invasive, localised and operated breast cancer between 1995 and 2002. Flexible modelling of excess mortality hazard, including time-dependent (TD) regression parameters, was used to estimate mortality related to breast cancer. We derived a single "final" model using a backward selection procedure and evaluated its stability through sensitivity analyses using a bootstrap technique. RESULTS: We analysed data from 1574 breast cancer women including 351 deaths (22.3%). The model building strategy retained age at diagnosis (TD), tumour size and grade (TD), chemotherapy and hormonal treatment (TD) as prognostic factors, while the sensitivity analysis on bootstrap samples identified nodes involvement and hormone receptors (TD) as additional long-term prognostic factors but did not identify chemotherapy and hormonal treatment as important prognostic factors. CONCLUSIONS: Two main issues were observed when describing the determinants of long-term survival. First, the modelling strategy presented a lack of robustness, probably due to the limited number of events observed in our study. The second was the misspecification of the model, probably due to confounding by indication. Our results highlight the need for more detailed data and the use of causal inference methods.

Which patients are not included in the English Cancer Waiting Times monitoring dataset, 2009-2013? Implications for use of the data in research.

BACKGROUND: Cancer waiting time targets are routinely monitored in England, but the Cancer Waiting Times monitoring dataset (CWT) does not include all eligible patients, introducing scope for bias. METHODS: Data from adults diagnosed in England (2009-2013) with colorectal, lung, or ovarian cancer were linked from CWT to cancer registry, mortality, and Hospital Episode Statistics data. We present demographic characteristics and net survival for patients who were and were not included in CWT. RESULTS: A CWT record was found for 82% of colorectal, 76% of lung, and 77% of ovarian cancer patients. Patients not recorded in CWT were more likely to be in the youngest or oldest age groups, have more comorbidities, have been diagnosed through emergency presentation, have late or missing stage, and have much poorer survival. CONCLUSIONS: Researchers and policy-makers should be aware of the limitations in the completeness and representativeness of CWT, and draw conclusions with appropriate caution.

Persistent inequalities in 90-day colon cancer mortality: an English cohort study.

BACKGROUND: Variation in colon cancer mortality occurring shortly after diagnosis is widely reported between socio-economic status (SES) groups: we investigated the role of different prognostic factors in explaining variation in 90-day mortality. METHODS: National cancer registry data were linked with national clinical audit data and Hospital Episode Statistics records for 69 769 adults diagnosed with colon cancer in England between January 2010 and March 2013. By gender, logistic regression was used to estimate the effects of SES, age and stage at diagnosis, comorbidity and surgical treatment on probability of death within 90 days from diagnosis. Multiple imputations accounted for missing stage. We predicted conditional probabilities by prognostic factor patterns and estimated the effect of SES (deprivation) from the difference between deprivation-specific average predicted probabilities. RESULTS: Ninety-day probability of death rose with increasing deprivation, even after accounting for the main prognostic factors. When setting the deprivation level to the least deprived group for all patients and keeping all other prognostic factors as observed, the differences between deprivation-specific averaged predicted probabilities of death were greatly reduced but persisted. Additional analysis suggested stage and treatment as potential contributors towards some of these inequalities. CONCLUSIONS: Further examination of delayed diagnosis, access to treatment and post-operative care by deprivation group may provide additional insights into understanding deprivation disparities in mortality.

Do pre-diagnosis primary care consultation patterns explain deprivation-specific differences in net survival among women with breast cancer? An examination of individually-linked data from the UK West Midlands cancer registry, national screening programme and Clinical Practice Research Datalink.

BACKGROUND: In England and Wales breast cancer survival is higher among more affluent women. Our aim was to investigate the potential of pre-diagnostic factors for explaining deprivation-related differences in survival. METHODS: Individually-linked data from women aged 50-70 in the West Midlands region of England, diagnosed with breast cancer 1989-2006 and continuously eligible for screening, was retrieved from the cancer registry, screening service and Clinical Practice Research Datalink. Follow-up was to the end of July 2012. Deprivation was measured at small area level, based on the quintiles of the income domain of the English indices of deprivation. Consultation rates per woman per week, time from last breast-related GP consultation to diagnosis, and from diagnosis to first surgery were calculated. We estimated net survival using the non-parametric Pohar-Perme estimator. RESULTS: The rate of primary care consultations was similar during the 18 months prior to diagnosis in each deprivation group for breast and non-breast symptoms. Survival was lower for more deprived women from 4 years after diagnosis. Lower net survival was associated with more advanced extent of disease and being non-screen-detected. There was a persistent trend of lower net survival for more deprived women, irrespective of the woman's obesity, alcohol, smoking or comorbidity status. There was no significant variation in time from last breast symptom to diagnosis by deprivation. However, women in more deprived categories experienced significantly longer periods between cancer diagnosis and first surgery (mean = 21.5 vs. 28.4 days, p = 0.03). Those whose surgery occurred more than 12 weeks following their cancer diagnosis had substantially lower net survival. CONCLUSIONS: Our data suggest that although more deprived women with breast cancer display lifestyle factors associated with poorer outcomes, their consultation frequency, comorbidities and the breast cancer symptoms they present with are similar. We found weak evidence of extended times to surgical treatment among most deprived women who were not screen-detected but who presented with symptoms in primary care, which suggests that treatment delay may play a role. Further investigation of interrelationships between these variables within a larger dataset is warranted.

Deriving stage at diagnosis from multiple population-based sources: colorectal and lung cancer in England.

BACKGROUND: Stage at diagnosis is a strong predictor of cancer survival. Differences in stage distributions and stage-specific management help explain geographic differences in cancer outcomes. Stage information is thus essential to improve policies for cancer control. Despite recent progress, stage information is often incomplete. Data collection methods and definition of stage categories are rarely reported. These inconsistencies may result in assigning conflicting stage for single tumours and confound the interpretation of international comparisons and temporal trends of stage-specific cancer outcomes. We propose an algorithm that uses multiple routine, population-based data sources to obtain the most complete and reliable stage information possible. METHODS: Our hierarchical approach derives a single stage category per tumour prioritising information deemed of best quality from multiple data sets and various individual components of tumour stage. It incorporates rules from the Union for International Cancer Control TNM classification of malignant tumours. The algorithm is illustrated for colorectal and lung cancer in England. We linked the cancer-specific Clinical Audit data (collected from clinical multi-disciplinary teams) to national cancer registry data. We prioritise stage variables from the Clinical Audit and added information from the registry when needed. We compared stage distribution and stage-specific net survival using two sets of definitions of summary stage with contrasting levels of assumptions for dealing with missing individual TNM components. This exercise extends a previous algorithm we developed for international comparisons of stage-specific survival. RESULTS: Between 2008 and 2012, 163 915 primary colorectal cancer cases and 168 158 primary lung cancer cases were diagnosed in adults in England. Using the most restrictive definition of summary stage (valid information on all individual TNM components), colorectal cancer stage completeness was 56.6% (from 33.8% in 2008 to 85.2% in 2012). Lung cancer stage completeness was 76.6% (from 57.3% in 2008 to 91.4% in 2012). Stage distribution differed between strategies to define summary stage. Stage-specific survival was consistent with published reports. CONCLUSIONS: We offer a robust strategy to harmonise the derivation of stage that can be adapted for other cancers and data sources in different countries. The general approach of prioritising good-quality information, reporting sources of individual TNM variables, and reporting of assumptions for dealing with missing data is applicable to any population-based cancer research using stage. Moreover, our research highlights the need for further transparency in the way stage categories are defined and reported, acknowledging the limitations, and potential discrepancies of using readily available stage variables.

Do colorectal cancer patients diagnosed as an emergency differ from non-emergency patients in their consultation patterns and symptoms? A longitudinal data-linkage study in England.

BACKGROUND: More than 20% of colorectal cancers are diagnosed following an emergency presentation. We aimed to examine pre-diagnostic primary-care consultations and related symptoms comparing patients diagnosed as emergencies with those diagnosed through non-emergency routes. METHODS: Cohort study of colorectal cancers diagnosed in England 2005 and 2006 using cancer registration data individually linked to primary-care data (CPRD/GPRD), allowing a detailed analysis of clinical information referring to the 5-year pre-diagnostic period. RESULTS: Emergency diagnosis occurred in 35% and 15% of the 1029 colon and 577 rectal cancers. 'Background' primary-care consultations (2-5 years before diagnosis) were similar for either group. In the year before diagnosis, >95% of emergency and non-emergency presenters had consulted their doctor, but emergency presenters had less frequently relevant symptoms (colon cancer: 48% vs 71% (P<0.001); rectal cancer: 49% vs 61% (P=0.043)). 'Alarm' symptoms were recorded less frequently in emergency presenters (e.g., rectal bleeding: 9 vs 24% (P=0.002)). However, about 1/5 of emergency presenters (18 and 23% for colon and rectal cancers) had 'alarm' symptoms the year before diagnosis. CONCLUSIONS: Emergency presenters have similar 'background' consultation history as non-emergency presenters. Their tumours seem associated with less typical symptoms, however opportunities for earlier diagnosis might be present in a fifth of them.

No 'cure' within 12 years of diagnosis among breast cancer patients who are diagnosed via mammographic screening: women diagnosed in the West Midlands region of England 1989-2011.

BACKGROUND: We have previously reported that there is little evidence of population 'cure' among two populations of women diagnosed with invasive breast cancer. 'Cure' has not yet been examined in the context of screen-detection. PATIENTS AND METHODS: We examined cancer registry data on 19 800 women aged 50-70, diagnosed with a primary, invasive, non-metastatic breast cancer between 1 April 1989 and 31 March 2011 in the West Midlands region of England, linked to Hospital Episode Statistics (HES) and the National Breast Screening Service (NBSS). Follow-up was complete on all women up to 31 July 2012. Analyses were stratified by screening status, age, tumour stage, deprivation and ethnicity. We estimated net survival for the whole cohort and each subgroup. Population 'cure' was evaluated by fitting flexible parametric log-cumulative excess hazard regression models in which the excess hazard of breast cancer death was assumed to be equal to zero after a given follow-up time. RESULTS: There was an overall lack of evidence for 'cure'. Across all subgroups examined, the general pattern was that of a continuous decrease in net survival over time, with no obvious asymptotic tendency within 12 years of follow-up. Model-based analyses confirmed this observation. CONCLUSIONS: Despite dramatic improvements in survival over past decades, diagnosis with breast cancer remains associated with a small but persistent increased risk of death for all groups of women, including those whose cancer is detected asymptomatically. These findings are unlikely to be due to methodological inadequacies. Communication of these long-term consequences of breast cancer among women recently diagnosed and to those considering undergoing screening should take due consideration of these patterns.

Cancer survival differences between South Asians and non-South Asians of England in 1986-2004, accounting for age at diagnosis and deprivation.

BACKGROUND: South Asian migrants show lower cancer incidence than their host population in England for most major cancers. We seek to study the ethnic differences in survival from cancer. METHODS: We described and modelled the effect of ethnicity, time, age and deprivation on survival for the five most incident cancers in each sex in South Asians in England between 1986 and 2004 using national cancer registry data. South Asian ethnicity was flagged using the validated name-recognition algorithm SANGRA (South Asian Names and Group Recognition Algorithm). RESULTS: We observed survival advantage in South Asians in earlier periods. This ethnic gap either remained constant or narrowed over time. By 2004, age-standardised net survival was comparable for all cancers except three in men, where South Asians had higher survival 5 years after diagnosis: colorectal (58.9% vs 53.6%), liver (15.0% vs 9.4%) and lung (15.9% vs 9.3%). Compared with non-South Asians, South Asians experienced a slower increase in breast and prostate cancer survival, both cancers associated with either a screening programme or an early diagnosis test. We did not find differential patterns in survival by deprivation between both ethnicities. CONCLUSIONS: Considering recent survival trends, appropriate action is required to avoid deficits in cancer survival among South Asians in the near future.

Cancer symptom awareness and barriers to symptomatic presentation in England--are we clear on cancer?

BACKGROUND: Low cancer awareness may contribute to delayed diagnosis and poor cancer survival. We aimed to quantify socio-demographic differences in cancer symptom awareness and barriers to symptomatic presentation in the English population. METHODS: Using a uniquely large data set (n=49 270), we examined the association of cancer symptom awareness and barriers to presentation with age, gender, marital status and socio-economic position (SEP), using logistic regression models to control for confounders. RESULTS: The youngest and oldest, the single and participants with the lowest SEP recognised the fewest cancer symptoms, and reported most barriers to presentation. Recognition of nine common cancer symptoms was significantly lower, and embarrassment, fear and difficulties in arranging transport to the doctor's surgery were significantly more common in participants living in the most deprived areas than in the most affluent areas. Women were significantly more likely than men to both recognise common cancer symptoms and to report barriers. Women were much more likely compared with men to report that fear would put them off from going to the doctor. CONCLUSIONS: Large and robust socio-demographic differences in recognition of some cancer symptoms, and perception of some barriers to presentation, highlight the need for targeted campaigns to encourage early presentation and improve cancer outcomes.

Ethnicity, deprivation and screening: survival from breast cancer among screening-eligible women in the West Midlands diagnosed from 1989 to 2011.

BACKGROUND: Social inequalities in breast cancer survival are smaller when the cancer is screen-detected. We examined survival from screen-detected and non screen-detected breast cancer by ethnicity and deprivation. METHODS: Cancer registry data for 20 283 women aged 50-70 years, diagnosed between 1989-2011 and invited for screening, were linked with screening and ethnicity data. We examined Asian, Black and White groups, less deprived and middle/more deprived women. Net survival was estimated using ethnic- and deprivation-specific life tables. Estimates were corrected for lead-time bias and over-diagnosis. RESULTS: Net survival varied by screening history. No significant differences in survival were found by ethnicity. Five-year net survival was 90.0% (95% CI, 89.3-90.8%) in less deprived groups and 86.7% (85.9-87.4%) among middle/more deprived women. Screening benefitted all ethnic and both deprivation groups. Whether screen-detected or not, more deprived women had significantly poorer outcomes: 5-year net survival was 78.0% (76.7-79.2%) for deprived women who were not screen-detected compared with 94.0% (93.1-95.1%) for less deprived women who were screen-detected. CONCLUSIONS: The three ethnic groups differed little in their breast cancer survival. Although screening confers a survival benefit to all, there are still wide disparities in survival by deprivation. More needs to be done to determine what underlies these differences and tackle them.

The impact of life tables adjusted for smoking on the socio-economic difference in net survival for laryngeal and lung cancer.

BACKGROUND: Net survival is a key measure in cancer control, but estimates for cancers that are strongly associated with smoking may be biased. General population life tables represent background mortality in net survival, but may not adequately reflect the higher mortality experienced by smokers. METHODS: Life tables adjusted for smoking were developed, and their impact on net survival and inequalities in net survival for laryngeal and lung cancers was examined. RESULTS: The 5-year net survival estimated with smoking-adjusted life tables was consistently higher than the survival estimated with unadjusted life tables: 7% higher for laryngeal cancer and 1.5% higher for lung cancer. The impact of using smoking-adjusted life tables was more pronounced in affluent patients; the deprivation gap in 5-year net survival for laryngeal cancer widened by 3%, from 11% to 14%. CONCLUSIONS: Using smoking-adjusted life tables to estimate net survival has only a small impact on the deprivation gap in survival, even when inequalities are substantial. Adjusting for the higher, smoking-related background mortality did increase the estimates of net survival for all deprivation groups, and may be more important when measuring the public health impact of differences or changes in survival, such as avoidable deaths or crude probabilities of death.

No socioeconomic inequalities in ovarian cancer survival within two randomised clinical trials.

BACKGROUND: Ovarian cancer is the leading cause of death among cancers of the female genital tract, with poor outcomes despite chemotherapy. There was a persistent socioeconomic gradient in 1-year survival in England and Wales for more than 3 decades (1971-2001). Inequalities in 5-year survival persisted for more than 20 years but have been smaller for women diagnosed around 2000. We explored one possible explanation. METHODS: We analysed data on 1406 women diagnosed with ovarian cancer during 1991-1998 and recruited to one of two randomised clinical trials. In the second International Collaborative Ovarian Neoplasm (ICON2) trial, women diagnosed between 1991 and 1996 were randomised to receive either the three-drug combination cyclophosphamide, doxorubicin and cisplatin (CAP) or single-agent carboplatin given at optimal dose. In the ICON3 trial, women diagnosed during 1995-1998 were randomised to receive either the same treatments as ICON2, or paclitaxel plus carboplatin.Relative survival at 1, 5 and 10 years was estimated for women in five categories of socioeconomic deprivation. The excess hazard of death over and above background mortality was estimated by fitting multivariable regression models with Poisson error structure and a dedicated link function in a generalised linear model framework, adjusting for the duration of follow-up and the confounding effects of age, Federation of Gynecology and Obstetrics (FIGO) stage and calendar period. RESULTS: Unlike women with ovarian cancer in the general population, no statistically significant socioeconomic gradient was seen for women with ovarian cancer treated in the two randomised controlled trials. The deprivation gap in 1-year relative survival in the general population was statistically significant at -6.7% (95% CI (-8.1, -5.3)), compared with -3.6% (95% CI (-10.4, +3.2)) in the trial population. CONCLUSIONS: Although ovarian cancer survival is significantly lower among poor women than rich women in England and Wales, there was no evidence of an association between socioeconomic deprivation and survival among women with ovarian cancer who were treated and followed up consistently in two well-conducted randomised controlled trials. We conclude that the persistent socioeconomic gradient in survival among women with ovarian cancer, at least for 1-year survival, may be due to differences in access to treatment and standards of care.

Funnel plots for population-based cancer survival: principles, methods and applications.

Funnel plots are graphical tools designed to detect excessive variation in performance indicators by simple visual inspection of the data. Their main use in the biomedical domain so far has been to detect publication bias in meta-analyses, but they have also been recommended as the most appropriate way to display performance indicators for a vast range of health-related outcomes. Here, we extend the use of funnel plots to population-based cancer survival and several related measures. We present three applications to familiarise the reader with their interpretation. We propose funnel plots for various cancer survival measures, as well as age-standardised survival, trends in survival and excess hazard ratios. We describe the components of a funnel plot and the formulae for the construction of the control limits for each of these survival measures. We include three transformations to construct the control limits for the survival function: complementary log-log, logit and logarithmic transformations. We present applications of funnel plots to explore the following: (i) small-area and temporal variation in cancer survival; (ii) racial and geographical variation in cancer survival; and (iii) geographical variation in the excess hazard of death. Funnel plots provide a simple and informative graphical tool to display geographical variation and trend in a range of cancer survival measures. We recommend their use as a routine instrument for cancer survival comparisons, to inform health policy makers in planning and assessing cancer policies. We advocate the use of the complementary log-log or logit transformation to construct the control limits for the survival function.

Management of colorectal cancer explains differences in 1-year relative survival between France and England for patients diagnosed 1997-2004.

BACKGROUND: Few international population-based studies have provided information on potential determinants of international disparities in cancer survival. This population-based study was undertaken to identify the principal differences in disease characteristics and management that accounted for previously observed poorer survival in English compared with French patients with colorectal cancer. METHODS: The study population comprised all cases of colorectal cancer diagnosed between 1997 and 2004 in the areas covered by three population-based cancer registries in France and one in England (N=40 613). To investigate the influence of clinical and treatment variables on survival, we applied multivariable excess hazard modelling based on generalised linear models with Poisson error. RESULTS: Poorer survival for English patients was primarily due to a larger proportion dying within the first year after diagnosis. After controlling for inter-country differences in the use of chemotherapy and surgical resection with curative intent, country of residence was no-longer associated with 1-year survival for advanced colon cancer patients (excess hazard ratio (EHR)=0.99 (0.92-1.01), P=0.095)). Longer term (2-5 years) excess hazards of death for colon and rectal cancer patients did not differ between France and England. CONCLUSION: This study suggests that difference in management close to diagnosis of colon and rectum cancer is related to differences in survival observed between France and England. All efforts (collection and standardisation of additional variables such as co-morbidity) to investigate the reasons for these disparities in management between these two countries, and more generally across Europe, should be encouraged.

Breast cancer survival and stage at diagnosis in Australia, Canada, Denmark, Norway, Sweden and the UK, 2000-2007: a population-based study.

BACKGROUND: We investigate whether differences in breast cancer survival in six high-income countries can be explained by differences in stage at diagnosis using routine data from population-based cancer registries. METHODS: We analysed the data on 257,362 women diagnosed with breast cancer during 2000-7 and registered in 13 population-based cancer registries in Australia, Canada, Denmark, Norway, Sweden and the UK. Flexible parametric hazard models were used to estimate net survival and the excess hazard of dying from breast cancer up to 3 years after diagnosis. RESULTS: Age-standardised 3-year net survival was 87-89% in the UK and Denmark, and 91-94% in the other four countries. Stage at diagnosis was relatively advanced in Denmark: only 30% of women had Tumour, Nodes, Metastasis (TNM) stage I disease, compared with 42-45% elsewhere. Women in the UK had low survival for TNM stage III-IV disease compared with other countries. CONCLUSION: International differences in breast cancer survival are partly explained by differences in stage at diagnosis, and partly by differences in stage-specific survival. Low overall survival arises if the stage distribution is adverse (e.g. Denmark) but stage-specific survival is normal; or if the stage distribution is typical but stage-specific survival is low (e.g. UK). International differences in staging diagnostics and stage-specific cancer therapies should be investigated.

Cancer survival in Australia, Canada, Denmark, Norway, Sweden, and the UK, 1995-2007 (the International Cancer Benchmarking Partnership): an analysis of population-based cancer registry data.

BACKGROUND: Cancer survival is a key measure of the effectiveness of health-care systems. Persistent regional and international differences in survival represent many avoidable deaths. Differences in survival have prompted or guided cancer control strategies. This is the first study in a programme to investigate international survival disparities, with the aim of informing health policy to raise standards and reduce inequalities in survival. METHODS: Data from population-based cancer registries in 12 jurisdictions in six countries were provided for 2·4 million adults diagnosed with primary colorectal, lung, breast (women), or ovarian cancer during 1995-2007, with follow-up to Dec 31, 2007. Data quality control and analyses were done centrally with a common protocol, overseen by external experts. We estimated 1-year and 5-year relative survival, constructing 252 complete life tables to control for background mortality by age, sex, and calendar year. We report age-specific and age-standardised relative survival at 1 and 5 years, and 5-year survival conditional on survival to the first anniversary of diagnosis. We also examined incidence and mortality trends during 1985-2005. FINDINGS: Relative survival improved during 1995-2007 for all four cancers in all jurisdictions. Survival was persistently higher in Australia, Canada, and Sweden, intermediate in Norway, and lower in Denmark, England, Northern Ireland, and Wales, particularly in the first year after diagnosis and for patients aged 65 years and older. International differences narrowed at all ages for breast cancer, from about 9% to 5% at 1 year and from about 14% to 8% at 5 years, but less or not at all for the other cancers. For colorectal cancer, the international range narrowed only for patients aged 65 years and older, by 2-6% at 1 year and by 2-3% at 5 years. INTERPRETATION: Up-to-date survival trends show increases but persistent differences between countries. Trends in cancer incidence and mortality are broadly consistent with these trends in survival. Data quality and changes in classification are not likely explanations. The patterns are consistent with later diagnosis or differences in treatment, particularly in Denmark and the UK, and in patients aged 65 years and older. FUNDING: Department of Health, England; and Cancer Research UK.

Cardiovascular diseases among diffuse large B-cell lymphoma long-term survivors in Asia: a multistate model study.

BACKGROUND: We modeled the clinical course of a cohort of diffuse large B-cell lymphoma (DLBCL) patients with no prior cardiovascular diseases (CVDs) using a multistate modeling framework. PATIENTS AND METHODS: Data on 2600 patients with DLBCL diagnosed between 2000 and 2018 and had received chemotherapy with or without radiotherapy were obtained from a population-wide electronic health database of Hong Kong. We used the Markov illness-death model to quantify the impact of doxorubicin and various risk factors (therapeutic exposure, demographic, comorbidities, cardiovascular risk factors, and lifestyle factors which included smoking) on the clinical course of DLBCL (transitions into incident CVD, lymphoma death, and other causes of death). RESULTS: A total of 613 (23.6%) and 230 (8.8%) of 2600 subjects died of lymphoma and developed incident CVD, respectively. Median follow-up was 7.0 years (interquartile range 3.8-10.8 years). Older ages [hazard ratio (HR) for >75 versus ≤60 years 1.88; 95% confidence interval (CI) 1.25-2.82 and HR for 61-75 versus ≤60 years 1.60; 95% CI 1.12-2.30], hypertension (HR 4.92; 95% CI 2.61-9.26), diabetes (HR 1.43; 95% CI 1.09-1.87), and baseline use of aspirin (HR 5.30; 95% CI 3.93-7.16) were associated with an increased risk of incident CVD. In a subgroup of anticipated higher-risk patients (aged 61-75 years, smoked, had diabetes, and received doxorubicin), we found that they remained on average 7.9 (95% CI 7.2-8.8) years in the DLBCL state and 0.1 (95% CI 0.0-0.4) years in the CVD state, if they could be followed up for 10 years. The brief time in the CVD state is consistent with the high chance of death in patients who developed CVD. Other causes of death have overtaken DLBCL-related death after about 5 years. CONCLUSIONS: In this Asian population-based cohort, we found that incident CVDs can occur soon after DLBCL treatment and continued to occur throughout survivorship. Clinicians are advised to balance the risks and benefits of treatment choices to minimize the risk of CVD.

Changes over time in socioeconomic inequalities in breast and rectal cancer survival in England and Wales during a 32-year period (1973-2004): the potential role of health care.

BACKGROUND: Socioeconomic inequalities in cancer survival are well documented but they vary for different cancers and over time. Reasons for these differences are poorly understood. PATIENTS AND METHODS: For England and Wales, we examined trends in socioeconomic survival inequalities for breast cancer in women and rectal cancer in men during the 32-year period 1973-2004. We used a theoretical framework based on Victora's 'inverse equity' law, under which survival inequalities could change with the advent of successive new treatments, of varying effectiveness, which are disseminated with different speed among patients of different socioeconomic groups. We estimated 5-year relative survival for patients of different deprivation quintiles and examined trends in survival inequalities in light of major treatment innovations. RESULTS: Inequalities in breast cancer survival (921,611 cases) narrowed steadily during the study (from -10% to -6%). In contrast, inequalities in rectal cancer survival (187,104 cases) widened overall (form -5% to -11%) with fluctuating periods of narrowing inequality. CONCLUSIONS: Trends in socioeconomic differences in tumour or patient factors are unlikely explanations of observed changes over time in survival inequalities. The sequential introduction into clinical practice of new treatments of progressively smaller incremental benefit may partly explain the reduction in inequality in breast cancer survival.

Cancer mortality in ethnic South Asian migrants in England and Wales (1993-2003): patterns in the overall population and in first and subsequent generations.

BACKGROUND: Cancer mortality has been examined among ethnic South Asian migrants in England and Wales, but not by generation of migration. METHODS: Using South Asian mortality records, identified by a name-recognition algorithm, and census information, age-standardised rates among South Asians, and South Asian vs non-South Asian rate ratios, were calculated. RESULTS AND CONCLUSIONS: All-cancer rates in ethnic South Asians were half of those in non-South Asians in first-generation (all-cancer-standardised mortality ratio (SMR) in males 0.51 and in females 0.56) and subsequent-generation South Asians (SMR in males 0.43 and in females 0.36). The higher mortality in first-generation South Asians for liver (both sexes), oral cavity and gallbladder cancer (females), particularly marked among Bangladeshis, was reduced in subsequent generations.