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1.  Socioeconomic Inequalities in Lung Cancer Treatment: Systematic Review and Meta-Analysis 
PLoS Medicine  2013;10(2):e1001376.
In a systematic review and meta-analysis, Lynne Forrest and colleagues find that patients with lung cancer who are more socioeconomically deprived are less likely to receive surgical treatment, chemotherapy, or any type of treatment combined, compared with patients who are more socioeconomically well off, regardless of cancer stage or type of health care system.
Background
Intervention-generated inequalities are unintended variations in outcome that result from the organisation and delivery of health interventions. Socioeconomic inequalities in treatment may occur for some common cancers. Although the incidence and outcome of lung cancer varies with socioeconomic position (SEP), it is not known whether socioeconomic inequalities in treatment occur and how these might affect mortality. We conducted a systematic review and meta-analysis of existing research on socioeconomic inequalities in receipt of treatment for lung cancer.
Methods and Findings
MEDLINE, EMBASE, and Scopus were searched up to September 2012 for cohort studies of participants with a primary diagnosis of lung cancer (ICD10 C33 or C34), where the outcome was receipt of treatment (rates or odds of receiving treatment) and where the outcome was reported by a measure of SEP. Forty-six papers met the inclusion criteria, and 23 of these papers were included in meta-analysis. Socioeconomic inequalities in receipt of lung cancer treatment were observed. Lower SEP was associated with a reduced likelihood of receiving any treatment (odds ratio [OR] = 0.79 [95% CI 0.73 to 0.86], p<0.001), surgery (OR = 0.68 [CI 0.63 to 0.75], p<0.001) and chemotherapy (OR = 0.82 [95% CI 0.72 to 0.93], p = 0.003), but not radiotherapy (OR = 0.99 [95% CI 0.86 to 1.14], p = 0.89), for lung cancer. The association remained when stage was taken into account for receipt of surgery, and was found in both universal and non-universal health care systems.
Conclusions
Patients with lung cancer living in more socioeconomically deprived circumstances are less likely to receive any type of treatment, surgery, and chemotherapy. These inequalities cannot be accounted for by socioeconomic differences in stage at presentation or by differences in health care system. Further investigation is required to determine the patient, tumour, clinician, and system factors that may contribute to socioeconomic inequalities in receipt of lung cancer treatment.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Lung cancer is the most commonly occurring cancer worldwide and the commonest cause of cancer-related death. Like all cancers, lung cancer occurs when cells begin to grow uncontrollably because of changes in their genes. The most common trigger for these changes in lung cancer is exposure to cigarette smoke. Most cases of lung cancer are non-small cell lung cancer, the treatment for which depends on the “stage” of the disease when it is detected. Stage I tumors, which are confined to the lung, can be removed surgically. Stage II tumors, which have spread to nearby lymph nodes, are usually treated with surgery plus chemotherapy or radiotherapy. For more advanced tumors, which have spread throughout the chest (stage III) or throughout the body (stage IV), surgery generally does not help to slow tumor growth and the cancer is treated with chemotherapy and radiotherapy. Small cell lung cancer, the other main type of lung cancer, is nearly always treated with chemotherapy and radiotherapy but sometimes with surgery as well. Overall, because most lung cancers are not detected until they are quite advanced, less than 10% of people diagnosed with lung cancer survive for 5 years.
Why Was This Study Done?
As with many other cancers, socioeconomic inequalities have been reported for both the incidence of and the survival from lung cancer in several countries. It is thought that the incidence of lung cancer is higher among people of lower socioeconomic position than among wealthier people, in part because smoking rates are higher in poorer populations. Similarly, it has been suggested that survival is worse among poorer people because they tend to present with more advanced disease, which has a worse prognosis (predicted outcome) than early disease. But do socioeconomic inequalities in treatment exist for lung cancer and, if they do, could these inequalities contribute to the poor survival rates among populations of lower socioeconomic position? In this systematic review and meta-analysis, the researchers investigate the first of these questions. A systematic review uses predefined criteria to identify all the research on a given topic; a meta-analysis is a statistical approach that combines the results of several studies.
What Did the Researchers Do and Find?
The researchers identified 46 published papers that studied people with lung cancer in whom receipt of treatment was reported in terms of an indicator of socioeconomic position, such as a measure of income or deprivation. Twenty-three of these papers were suitable for inclusion in a meta-analysis. Lower socioeconomic position was associated with a reduced likelihood of receiving any treatment. Specifically, the odds ratio (chance) of people in the lowest socioeconomic group receiving any treatment was 0.79 compared to people in the highest socioeconomic group. Lower socioeconomic position was also associated with a reduced chance of receiving surgery (OR = 0.68) and chemotherapy (OR = 0.82), but not radiotherapy. The association between socioeconomic position and surgery remained after taking cancer stage into account. That is, when receipt of surgery was examined in early-stage patients only, low socioeconomic position remained associated with reduced likelihood of surgery. Notably, the association between socioeconomic position and receipt of treatment was similar in studies undertaken in countries where health care is free at the point of service for everyone (for example, the UK) and in countries with primarily private insurance health care systems (for example, the US).
What Do These Findings Mean?
These findings suggest that patients in more socioeconomically deprived circumstances are less likely to receive any type of treatment, surgery, and chemotherapy (but not radiotherapy) for lung cancer than people who are less socioeconomically deprived. Importantly, these inequalities cannot be explained by socioeconomic differences in stage at presentation or by differences in health care system. The accuracy of these findings may be affected by several factors. For example, it is possible that only studies that found an association between socioeconomic position and receipt of treatment have been published (publication bias). Moreover, the studies identified did not include information regarding patient preferences, which could help explain at least some of the differences. Nevertheless, these results do suggest that socioeconomic inequalities in receipt of treatment may exacerbate socioeconomic inequalities in the incidence of lung cancer and may contribute to the observed poorer outcomes in lower socioeconomic position groups. Further research is needed to determine the system and patient factors that contribute to socioeconomic inequalities in lung cancer treatment before clear recommendations for changes to policy and practice can be made.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001376.
The US National Cancer Institute provides information about all aspects of lung cancer for patients and health care professionals (in English and Spanish); a monograph entitled Area Socioeconomic Variations in U. S. Cancer Incidence, Mortality, Stage, Treatment, and Survival, 19751999 is available
Cancer Research UK also provides detailed information about lung cancer and links to other resources, such as a policy statement on socioeconomic inequalities in cancer and a monograph detailing cancer and health inequalities in the UK
The UK National Health Service Choices website has a page on lung cancer that includes personal stories about diagnosis and treatment
MedlinePlus provides links to other US sources of information about lung cancer (in English and Spanish)
doi:10.1371/journal.pmed.1001376
PMCID: PMC3564770  PMID: 23393428
2.  Analysing Recent Socioeconomic Trends in Coronary Heart Disease Mortality in England, 2000–2007: A Population Modelling Study 
PLoS Medicine  2012;9(6):e1001237.
A modeling study conducted by Madhavi Bajekal and colleagues estimates the extent to which specific risk factors and changes in uptake of treatment contributed to the declines in coronary heart disease mortality in England between 2000 and 2007, across and within socioeconomic groups.
Background
Coronary heart disease (CHD) mortality in England fell by approximately 6% every year between 2000 and 2007. However, rates fell differentially between social groups with inequalities actually widening. We sought to describe the extent to which this reduction in CHD mortality was attributable to changes in either levels of risk factors or treatment uptake, both across and within socioeconomic groups.
Methods and Findings
A widely used and replicated epidemiological model was used to synthesise estimates stratified by age, gender, and area deprivation quintiles for the English population aged 25 and older between 2000 and 2007. Mortality rates fell, with approximately 38,000 fewer CHD deaths in 2007. The model explained about 86% (95% uncertainty interval: 65%–107%) of this mortality fall. Decreases in major cardiovascular risk factors contributed approximately 34% (21%–47%) to the overall decline in CHD mortality: ranging from about 44% (31%–61%) in the most deprived to 29% (16%–42%) in the most affluent quintile. The biggest contribution came from a substantial fall in systolic blood pressure in the population not on hypertension medication (29%; 18%–40%); more so in deprived (37%) than in affluent (25%) areas. Other risk factor contributions were relatively modest across all social groups: total cholesterol (6%), smoking (3%), and physical activity (2%). Furthermore, these benefits were partly negated by mortality increases attributable to rises in body mass index and diabetes (−9%; −17% to −3%), particularly in more deprived quintiles. Treatments accounted for approximately 52% (40%–70%) of the mortality decline, equitably distributed across all social groups. Lipid reduction (14%), chronic angina treatment (13%), and secondary prevention (11%) made the largest medical contributions.
Conclusions
The model suggests that approximately half the recent CHD mortality fall in England was attributable to improved treatment uptake. This benefit occurred evenly across all social groups. However, opposing trends in major risk factors meant that their net contribution amounted to just over a third of the CHD deaths averted; these also varied substantially by socioeconomic group. Powerful and equitable evidence-based population-wide policy interventions exist; these should now be urgently implemented to effectively tackle persistent inequalities.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Coronary heart disease is a chronic medical condition in which the blood vessels supplying the heart muscle become narrowed or even blocked by fatty deposits on the inner linings of the blood vessels—a process known as arthrosclerosis; this restricts blood flow to the heart, and if the blood vessels completely occlude, it may cause a heart attack. Lifestyle behaviors, such as unhealthy diets high in saturated fat, smoking, and physical inactivity, are the main risk factors for coronary heart disease, so efforts to reduce this condition are directed towards these factors. Global rates of coronary heart disease are increasing and the World Health Organization estimates that by 2030, it will be the biggest cause of death worldwide. However, in high-income countries, such as England, deaths due to coronary heart disease have actually fallen substantially over the past few decades with an accelerated reduction in annual death rates since 2000.
Why Was This Study Done?
Socioeconomic factors play an important role in chronic diseases such as coronary heart disease, with mortality rates almost twice as high in deprived than affluent areas. However, the potential effect of population-wide interventions on reducing inequalities in deaths from coronary heart disease remains unclear. So in this study, the researchers investigated the role of behavioral (changing lifestyle) and medical (treatments) management of coronary heart disease that contributed to the decrease in deaths in England for the period 2000–2007, within and between socioeconomic groups.
What Did the Researchers Do and Find?
The researchers used a well-known, tried and tested epidemiological model (IMPACT) but adapted it to include socioeconomic inequalities to analyze the total population of England aged 25 and older in 2000 and in 2007. The researchers included all the major risk factors for coronary heart disease plus 45 current medical and surgical treatments in their model. They used the Index of Multiple Deprivation 2007 as a proxy indicator of socioeconomic circumstances of residents in neighborhoods. Using the postal code of residence, the researchers matched deaths from, and patients treated for, coronary heart disease to the corresponding deprivation category (quintile). Changes in risk factor levels in each quintile were also calculated using the Health Survey for England. Using their model, the researchers calculated the total number of deaths prevented or postponed for each deprivation quintile by measuring the difference between observed deaths in 2007 and expected deaths based on 2000 data, if age, sex, and deprivation quintile death rates had remained the same.
The researchers found that between 2000 and 2007, death rates from coronary heart disease fell from 229 to 147 deaths per 100,000—a decrease of 36%. Both death rates and the number of deaths were lowest in the most affluent quintile and the pace of fall was also faster, decreasing by 6.7% per year compared to just 4.9% in the most deprived quintile. Furthermore, the researchers found that overall, about half of the decrease in death rates was attributable to improvements in uptake of medical and surgical treatments. The contribution of medical treatments to the deaths averted was very similar across all quintiles, ranging from 50% in the most affluent quintile to 53% in the most deprived. Risk factor changes accounted for approximately a third fewer deaths in 2007 than occurred in 2000, but were responsible for a smaller proportion of deaths prevented in the most affluent quintile compared with the most deprived (approximately 29% versus 44%, respectively). However, the benefits of improvements in blood pressure, cholesterol, smoking, and physical activity were partly negated by rises in body mass index and diabetes, particularly in more deprived quintiles.
What Do These Findings Mean?
These findings suggest that approximately half the recent substantial fall in deaths from coronary heart disease in England was attributable to improved treatment uptake across all social groups; this is consistent with equitable service delivery across the UK's National Health Service. However, opposing trends in major risk factors, which varied substantially by socioeconomic group, meant that their net contribution accounted for just a third of deaths averted. Other countries have implemented effective, evidence-based interventions to tackle lifestyle risk factors; the most powerful measures involve legislation, regulation, taxation, or subsidies, all of which tend to be equitable. Such measures should be urgently implemented in England to effectively tackle persistent inequalities in deaths due to coronary heart disease.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001237.
The World Health Organization has information about the global statistics of coronary heart disease
The National Heart Lung and Blood Institute provides a patient-friendly description of coronary heart disease
The National Heart Forum is the leading UK organization facilitating the prevention of coronary heart disease and other chronic diseases
The British Heart Foundation supports research and promotes preventative activity
Heart of Mersey is the UK's largest regional organization promoting the prevention of coronary heart disease and other chronic diseases
More information about the social determinants of health is available from WHO
doi:10.1371/journal.pmed.1001237
PMCID: PMC3373639  PMID: 22719232
3.  Variation in incidence of breast, lung and cervical cancer and malignant melanoma of skin by socioeconomic group in England 
BMC Cancer  2008;8:271.
Background
Cancer incidence varies by socioeconomic group and these variations have been linked with environmental and lifestyle factors, differences in access to health care and health seeking behaviour. Socioeconomic variations in cancer incidence by region and age are less clearly understood but they are crucial for targeting prevention measures and health care commissioning.
Methods
Data were obtained from all eight English cancer registries for patients diagnosed between 1998 and 2003, for all invasive cases of female breast cancer (ICD-10 code C50), lung cancer (ICD-10 codes C33-C34), cervical cancer (ICD-10 code C53), and malignant melanoma of the skin (ICD-10 code C43). Socioeconomic status was assigned to each patient based on their postcode of residence at diagnosis, using the income domain of the Index of Multiple Deprivation 2004. We analysed the socioeconomic variations in the incidence of breast, lung and cervical cancer and malignant melanoma of the skin for England, and regionally and by age.
Results
Incidence was highest for the most deprived patients for lung cancer and cervical cancer, whilst the opposite was observed for malignant melanoma and breast cancer. The difference in incidence between the most and the least deprived groups was higher for lung cancer patients aged under 65 at diagnosis than those over 65 at diagnosis, which may indicate a cohort effect. There were regional differences in the socioeconomic gradients with the gap being widest for lung and cervical cancer in the North (North East, North West and Yorkshire and Humberside) and for malignant melanoma in the East and South West. There were only modest variations in breast cancer incidence by region. If the incidence of lung and cervical cancer were decreased to that of the least deprived group it would prevent 36% of lung cancer cases in men, 38% of lung cancer cases in women and 28% of cervical cancer cases. Incidence of breast cancer and melanoma was highest in the least deprived group, therefore if all socioeconomic groups had incidence rates similar to the least deprived group it is estimated that the number of cases would increase by 7% for breast cancer, 27% for melanoma in men and 29% for melanoma in women.
Conclusion
National comparison of socioeconomic variations in cancer incidence by region and age can provide an unbiased basis for public health prevention and health commissioning. Decreasing inequalities in incidence requires the integration of information on risk factors, incidence and projected incidence but targeted public health interventions could help to reduce regional inequalities in incidence and reduce the future cancer burden.
doi:10.1186/1471-2407-8-271
PMCID: PMC2577116  PMID: 18822122
4.  Emergency presentation of cancer and short-term mortality 
British Journal of Cancer  2013;109(8):2027-2034.
Background:
The short-term survival following a cancer diagnosis in England is lower than that in comparable countries, with the difference in excess mortality primarily occurring in the months immediately after diagnosis. We assess the impact of emergency presentation (EP) on the excess mortality in England over the course of the year following diagnosis.
Methods:
All colorectal and cervical cancers presenting in England and all breast, lung, and prostate cancers in the East of England in 2006–2008 are included. The variation in the likelihood of EP with age, stage, sex, co-morbidity, and income deprivation is modelled. The excess mortality over 0–1, 1–3, 3–6, and 6–12 months after diagnosis and its dependence on these case-mix factors and presentation route is then examined.
Results:
More advanced stage and older age are predictive of EP, as to a lesser extent are co-morbidity, higher income deprivation, and female sex. In the first month after diagnosis, we observe case-mix-adjusted excess mortality rate ratios of 7.5 (cervical), 5.9 (colorectal), 11.7 (breast ), 4.0 (lung), and 20.8 (prostate) for EP compared with non-EP.
Conclusion:
Individuals who present as an emergency experience high short-term mortality in all cancer types examined compared with non-EPs. This is partly a case-mix effect but EP remains predictive of short-term mortality even when age, stage, and co-morbidity are accounted for.
doi:10.1038/bjc.2013.569
PMCID: PMC3798965  PMID: 24045658
diagnosis; pathways; referral; survival; emergency; route
5.  The impact of age at diagnosis on socioeconomic inequalities in adult cancer survival in England 
Cancer Epidemiology  2015;39(4):641-649.
Highlights
•Socioeconomic inequalities in survival persist for the majority of adult cancers.•Socioeconomic inequalities have not been observed for childhood cancers.•We studied the effect of age on socioeconomic differences in survival for breast, lung and colon cancer patients.•Substantial age-specific socioeconomic inequalities in survival from cancers of the breast, lung and colon.•Policy makers should ensure that young and old, from affluent and deprived areas, seek and obtain timely access to care.
Background
Understanding the age at which persistent socioeconomic inequalities in cancer survival become apparent may help motivate and support targeting of cancer site-specific interventions, and tailoring guidelines to patients at higher risk.
Patients and methods
We analysed data on more than 40,000 patients diagnosed in England with one of three common cancers in men and women, breast, colon and lung, 2001–2005 with follow-up to the end of 2011. We estimated net survival for each of the five deprivation categories (affluent, 2, 3, 4, deprived), cancer site, sex and age group (15–44, 45–54, 55–64, and 65–74 and 75–99 years).
Results
The magnitude and pattern of the age specific socioeconomic inequalities in survival was different for breast, colon and lung. For breast cancer the deprivation gap in 1-year survival widened with increasing age at diagnosis, whereas the opposite was true for lung cancer, with colon cancer having an intermediate pattern. The ‘deprivation gap’ in 1-year breast cancer survival widened steadily from −0.8% for women diagnosed at 15–44 years to −4.8% for women diagnosed at 75–99 years, and was the widest for women diagnosed at 65−74 years for 5- and 10-year survival. For colon cancer in men, the gap was widest in patients diagnosed aged 55–64 for 1-, 5- and 10-year survival. For lung cancer, the ‘deprivation gap’ in survival in patients diagnoses aged 15–44 years was more than 10% for 1-year survival in men and for 1- and 5-year survival in women.
Conclusion
Our findings suggest that reduction of socioeconomic inequalities in survival will require updating of current guidelines to ensure the availability of optimal treatment and appropriate management of lung cancer patients in all age groups and older patients in deprived groups with breast or colon cancer.
doi:10.1016/j.canep.2015.05.006
PMCID: PMC4542220  PMID: 26143284
Breast cancer; Colon cancer; Lung cancer; Net survival; Deprivation; Socioeconomic inequalities; Survival
6.  Impact of deprivation on breast cancer survival among women eligible for mammographic screening in the West Midlands (UK) and New South Wales (Australia): Women diagnosed 1997–2006 
International Journal of Cancer  2016;138(10):2396-2403.
Women diagnosed with breast cancer in the UK display marked differences in survival between categories defined by socio‐economic deprivation. Timeliness of diagnosis is one of the possible explanations for these patterns. Women whose cancer is screen‐detected are more likely to be diagnosed at an earlier stage. We examined deprivation and screening‐specific survival in order to evaluate the role of early diagnosis upon deprivation‐specific survival differences in the West Midlands (UK) and New South Wales (Australia). We estimated net survival for women aged 50–65 years at diagnosis and whom had been continuously eligible for screening from the age of 50. Records for 5,628 women in West Midlands (98.5% of those eligible, mean age at diagnosis 53.7 years) and 6,396 women in New South Wales (99.9% of those eligible, mean age at diagnosis 53.8 years). In New South Wales, survival was similar amongst affluent and deprived women, regardless of whether their cancer was screen‐detected or not. In the West Midlands, there were large and persistent differences in survival between affluent and deprived women. Deprivation differences were similar between the screen‐detected and non‐screen detected groups. These differences are unlikely to be solely explained by artefact, or by patient or tumour factors. Further investigations into the timeliness and appropriateness of the treatments received by women with breast cancer across the social spectrum in the UK are warranted.
What's new?
In the UK, affluent women are known to have higher breast cancer survival than deprived women, regardless of access to screening. In this study, the authors examined net survival by socioeconomic status in the West Midlands (UK) and New South Wales (Australia). They found a persistent ‘deprivation gap’ in survival in the former, but not in the latter region. Further investigation into the treatment and follow‐up received by women with breast cancer across the social spectrum in the UK is warranted.
doi:10.1002/ijc.29983
PMCID: PMC4833186  PMID: 26756181
breast cancer; net survival; New South Wales; West Midlands; England; Australia; deprivation; socioeconomic; cancer screening
7.  Social and geographical factors affecting access to treatment of colorectal cancer: a cancer registry study 
BMJ Open  2012;2(2):e000410.
Objective
Cancer outcomes vary between and within countries with patients from deprived backgrounds known to have inferior survival. The authors set out to explore the effect of deprivation in relation to the accessibility of hospitals offering diagnostic and therapeutic services on stage at presentation and receipt of treatment.
Design
Analysis of a Cancer Registry Database. Data included stage and treatment details from the first 6 months. The socioeconomic status of the immediate area of residence and the travel time from home to hospital was derived from the postcode.
Setting
Population-based study of patients resident in a large area in the north of England.
Participants
39 619 patients with colorectal cancer diagnosed between 1994 and 2002.
Outcomes measured
Stage of diagnosis and receipt of treatment in relation to deprivation and distance from hospital.
Results
Patients in the most deprived quartile were significantly more likely to be diagnosed at stage 4 for rectal cancer (OR 1.516, p<0.05) but less so for colonic cancer. There was a trend for both sites for patients in the most deprived quartile to be less likely to receive chemotherapy for stage 4 disease. Patients with colonic cancer were very significantly less likely to receive any treatment if they came from any but the most affluent area (ORs 0.639, 0.603 and 0.544 in increasingly deprived quartiles), this may have been exacerbated if the hospital was distant from their residence (OR for forth quartile for both travel and deprivation 0.731, not significant). The effect was less for rectal cancer and no effect of distance was seen.
Conclusions
Residing in a deprived area is associated with tendencies to higher stage at diagnosis and especially in the case of colonic cancer to reduced receipt of treatment. These observations are consistent with other findings and indicate that access to diagnosis requires further investigation.
Article summary
Article focus
There is evidence that the poorer survival of British patients' with bowel cancer is related to more advanced stage than in similar countries.
Is this related to the environment in which people live?
Are there differences in this regard between colonic and rectal cancer?
Key messages
Residing in a deprived area is associated with:
tendencies to higher stage at diagnosis.
especially in the case of colonic cancer with reduced receipt of treatment.
Strengths and limitations of this study
A cancer registry study looks at the whole population of a defined area and so does not depend on access to specific institutions.
A large number of patients have been studied.
The patients analysed were diagnosed some years ago.
Deprivation indices relate to area of residence rather than to individuals.
This is a cross-sectional study so inferences of causality must be cautious.
doi:10.1136/bmjopen-2011-000410
PMCID: PMC3341592  PMID: 22535788
8.  Evidence for Community Transmission of Community-Associated but Not Health-Care-Associated Methicillin-Resistant Staphylococcus Aureus Strains Linked to Social and Material Deprivation: Spatial Analysis of Cross-sectional Data 
PLoS Medicine  2016;13(1):e1001944.
Background
Identifying and tackling the social determinants of infectious diseases has become a public health priority following the recognition that individuals with lower socioeconomic status are disproportionately affected by infectious diseases. In many parts of the world, epidemiologically and genotypically defined community-associated (CA) methicillin-resistant Staphylococcus aureus (MRSA) strains have emerged to become frequent causes of hospital infection. The aim of this study was to use spatial models with adjustment for area-level hospital attendance to determine the transmission niche of genotypically defined CA- and health-care-associated (HA)-MRSA strains across a diverse region of South East London and to explore a potential link between MRSA carriage and markers of social and material deprivation.
Methods and Findings
This study involved spatial analysis of cross-sectional data linked with all MRSA isolates identified by three National Health Service (NHS) microbiology laboratories between 1 November 2011 and 29 February 2012. The cohort of hospital-based NHS microbiology diagnostic services serves 867,254 usual residents in the Lambeth, Southwark, and Lewisham boroughs in South East London, United Kingdom (UK). Isolates were classified as HA- or CA-MRSA based on whole genome sequencing. All MRSA cases identified over 4 mo within the three-borough catchment area (n = 471) were mapped to small geographies and linked to area-level aggregated socioeconomic and demographic data. Disease mapping and ecological regression models were used to infer the most likely transmission niches for each MRSA genetic classification and to describe the spatial epidemiology of MRSA in relation to social determinants. Specifically, we aimed to identify demographic and socioeconomic population traits that explain cross-area extra variation in HA- and CA-MRSA relative risks following adjustment for hospital attendance data. We explored the potential for associations with the English Indices of Deprivation 2010 (including the Index of Multiple Deprivation and several deprivation domains and subdomains) and the 2011 England and Wales census demographic and socioeconomic indicators (including numbers of households by deprivation dimension) and indicators of population health. Both CA-and HA-MRSA were associated with household deprivation (CA-MRSA relative risk [RR]: 1.72 [1.03–2.94]; HA-MRSA RR: 1.57 [1.06–2.33]), which was correlated with hospital attendance (Pearson correlation coefficient [PCC] = 0.76). HA-MRSA was also associated with poor health (RR: 1.10 [1.01–1.19]) and residence in communal care homes (RR: 1.24 [1.12–1.37]), whereas CA-MRSA was linked with household overcrowding (RR: 1.58 [1.04–2.41]) and wider barriers, which represent a combined score for household overcrowding, low income, and homelessness (RR: 1.76 [1.16–2.70]). CA-MRSA was also associated with recent immigration to the UK (RR: 1.77 [1.19–2.66]). For the area-level variation in RR for CA-MRSA, 28.67% was attributable to the spatial arrangement of target geographies, compared with only 0.09% for HA-MRSA. An advantage to our study is that it provided a representative sample of usual residents receiving care in the catchment areas. A limitation is that relationships apparent in aggregated data analyses cannot be assumed to operate at the individual level.
Conclusions
There was no evidence of community transmission of HA-MRSA strains, implying that HA-MRSA cases identified in the community originate from the hospital reservoir and are maintained by frequent attendance at health care facilities. In contrast, there was a high risk of CA-MRSA in deprived areas linked with overcrowding, homelessness, low income, and recent immigration to the UK, which was not explainable by health care exposure. Furthermore, areas adjacent to these deprived areas were themselves at greater risk of CA-MRSA, indicating community transmission of CA-MRSA. This ongoing community transmission could lead to CA-MRSA becoming the dominant strain types carried by patients admitted to hospital, particularly if successful hospital-based MRSA infection control programmes are maintained. These results suggest that community infection control programmes targeting transmission of CA-MRSA will be required to control MRSA in both the community and hospital. These epidemiological changes will also have implications for effectiveness of risk-factor-based hospital admission MRSA screening programmes.
Community associated MRSA variants, rather than hospital associated ones, are more readily transmitted and this is where control programs should focus to limit both hospital and community infections.
Editors' Summary
Background
Addressing health inequality requires understanding the social determinants of poor health. Previous studies have suggested a link between deprived living conditions and infections with methicillin-resistant Staphylococcus aureus (MRSA), that is, strains of the common bacterium S. aureus that have acquired antibiotic resistance and are therefore more difficult to treat. MRSA was first identified in the 1960s and for years thought of as a dangerous health-care-associated (HA-) pathogen that infects hospital patients who are predominantly older, sick, or undergoing invasive procedures. In the late 1990s, however, community-associated MRSA (CA-MRSA) emerged as pathogen infecting healthy individuals of all ages and without recent hospital contact. Most CA-MRSA cases are contagious skin infections, and numerous outbreaks have been reported in different communities. The traditional distinction between HA-MRSA and CA-MRSA based on where transmission occurred has become problematic in recent years, because CA-MRSA transmission has also been reported in health care settings. However, as HA- and CA-MRSA strains are genetically distinct, cases can be classified by DNA sequencing regardless of where a patient got infected.
Why Was This Study Done?
With hospitals historically considered the only place of MRSA transmission, prevention efforts remain focused on health care settings. Given the changing patterns of MRSA infections, however, the need to consider HA and CA transmission settings together has been recognized. This study was designed to take a closer look at the relationship between both HA- and CA-MRSA and socioeconomic deprivation, with the ultimate aim to inform prevention efforts. The researchers selected three boroughs in South East London with a highly diverse population of approximately 850,000 residents for whom socioeconomic and demographic data were available at a high level of spatial resolution. They also had data on hospital attendance for the residents and were therefore able to account for this factor in their analysis. The study addressed the following questions: is there a link between socioeconomic deprivation and both HA- and CA-MRSA cases among the residents? What social determinants are associated with HA- and CA-MRSA cases? What are the transmission settings (i.e., community versus health care) for HA- and CA-MRSA?
What Did the Researchers Do and Find?
They analyzed data on all MRSA samples collected over 4 consecutive mo in late 2011 and early 2012 by microbiology laboratories that serve the three boroughs. Of 471 MRSA cases that occurred in residents, 392 could be classified based on genome sequencing. Of these, approximately 72% were HA-MRSA, and 26% were CA-MRSA. Approximately 2% of residents carried both HA- and CA-MRSA. All MRSA cases were mapped to 513 smaller areas (called Lower Layer Super Output Areas, or LSOAs) in the three boroughs for which extensive socioeconomic and demographic data existed. The former included data on income, employment, health, and education, the latter data on number individuals per household, their ages and gender, and length of residence in the UK. MRSA cases were detected in just over half of the LSOAs in the study area. The researchers then used mathematical models to determine the most likely transmission settings for each MRSA genetic classification. They also described the spatial distributions of the two in relation to socioeconomic and demographic determinants. Both CA-and HA-MRSA were associated with household deprivation, which was itself correlated with hospital attendance. HA-MRSA was also associated with poor health and with living in communal care homes, whereas CA-MRSA was linked with household overcrowding and a combination of household overcrowding, low income, and homelessness. CA-MRSA was also associated with recent immigration to the UK. Around 27% of local variation in CA-MRSA could be explained by the spatial arrangement of LSOAs, meaning areas of high risk tended to cluster. No such clustering was observed for HA-MRSA.
What Do these Findings Mean?
The results show that residents in the most deprived areas are at greater risk for MRSA. The absence of spatial clusters of HA-MRSA suggests that transmission of genetically determined HA-MRSA occurs in hospitals, with little or no transmission in the community. The most important risk factor for acquiring HA-MRSA is therefore likely to be hospital attendance as a result of deprivation. In contrast, genetically determined CA-MRSA both affects deprived areas disproportionately, and—as the clusters imply—spreads from such areas in the community. This suggests that living in deprived conditions itself is a risk factor for acquiring CA-MRSA, as is living near deprived neighbors. Some of the CA-MRSA cases are also likely imported by recent immigrants. Whereas transmission of CA-MRSA in health care settings has been reported in a number of other studies, data from this study cannot answer whether or to what extent this is the case here. However, because of ongoing transmission in the community, and because deprived residents are both more likely to have CA-MRSA and to attend a hospital, importation of CA-MRSA strains into hospitals is an obvious concern. While the researchers intentionally located the study in an area with a very diverse population, it is not clear how generalizable the findings are to other communities, either in the UK or in other countries. Nonetheless, the results justify special focus on deprived populations in the control of MRSA and are useful for the design of specific strategies for HA-MRSA and CA-MRSA.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001944.
Online information on MRSA from the UK National Health Service: http://www.nhs.uk/conditions/MRSA/Pages/Introduction.aspx
MRSA webpage from the US Centers of Disease Control and Prevention: http://www.cdc.gov/mrsa/
MRSA page from the San Francisco Department of Public Health: http://www.sfcdcp.org/mrsa.html
MedlinePlus provides links to information about MRSA, including sources in languages other than English: https://www.nlm.nih.gov/medlineplus/mrsa.html
doi:10.1371/journal.pmed.1001944
PMCID: PMC4727805  PMID: 26812054
9.  Deprivation and survival from breast cancer. 
British Journal of Cancer  1995;72(3):738-743.
We studied the association between deprivation and survival from breast cancer in 29,676 women aged 30 and over who were diagnosed during the period 1980-89 in the area covered by the South Thames Regional Health Authority. The measure of deprivation was the Carstairs Index of the census enumeration district of each woman's residence at diagnosis. We studied the impact of stage at diagnosis, morphology and type of treatment on this association, with the relative survival rate and the hazard ratio as measures of outcome. There was a clear gradient in survival, with better survival for women from more affluent areas. At all ages, women in the most deprived category had a 35% greater hazard of death than women from the most affluent areas after adjustment for stage at diagnosis, morphological type and type of treatment. In younger women (30-64 years), the survival gradient by deprivation category cannot be explained by these prognostic factors. In older women (65-99 years), part of the unadjusted gradient in survival can be explained by differences in the stage of disease: older women in the most deprived category were more often diagnosed with advanced disease. Other factors, so far unidentified, are responsible for the gradient in breast cancer survival by deprivation category. The potential effect on breast cancer mortality of eliminating the gradient in survival by deprivation category is substantial (7.4%). In women aged 30-64 years, 10% of all deaths within 5 years might be avoidable, while in older women this figure is 5.8%.
PMCID: PMC2033898  PMID: 7669587
10.  Variation in advanced stage at diagnosis of lung and female breast cancer in an English region 2006–2009 
British Journal of Cancer  2012;106(6):1068-1075.
Background:
Understanding variation in stage at diagnosis can inform interventions to improve the timeliness of diagnosis for patients with different cancers and characteristics.
Methods:
We analysed population-based data on 17 836 and 13 286 East of England residents diagnosed with (female) breast and lung cancer during 2006–2009, with stage information on 16 460 (92%) and 10 435 (79%) patients, respectively. Odds ratios (ORs) of advanced stage at diagnosis adjusted for patient and tumour characteristics were derived using logistic regression.
Results:
We present adjusted ORs of diagnosis in stages III/IV compared with diagnosis in stages I/II. For breast cancer, the frequency of advanced stage at diagnosis increased stepwise among old women (ORs: 1.21, 1.46, 1.68 and 1.78 for women aged 70–74, 75–79, 80–84 and ⩾85, respectively, compared with those aged 65–69 , P<0.001). In contrast, for lung cancer advanced stage at diagnosis was less frequent in old patients (ORs: 0.82, 0.74, 0.73 and 0.66, P<0.001). Advanced stage at diagnosis was more frequent in more deprived women with breast cancer (OR: 1.23 for most compared with least deprived, P=0.002), and in men with lung cancer (OR: 1.14, P=0.011). The observed patterns were robust to sensitivity analyses approaches for handling missing stage data under different assumptions.
Conclusion:
Interventions to help improve the timeliness of diagnosis of different cancers should be targeted at specific age groups.
doi:10.1038/bjc.2012.30
PMCID: PMC3304409  PMID: 22382691
stage; diagnosis; advanced; age; multiple; imputation
11.  Nuclear Receptor Expression Defines a Set of Prognostic Biomarkers for Lung Cancer 
PLoS Medicine  2010;7(12):e1000378.
David Mangelsdorf and colleagues show that nuclear receptor expression is strongly associated with clinical outcomes of lung cancer patients, and this expression profile is a potential prognostic signature for lung cancer patient survival time, particularly for individuals with early stage disease.
Background
The identification of prognostic tumor biomarkers that also would have potential as therapeutic targets, particularly in patients with early stage disease, has been a long sought-after goal in the management and treatment of lung cancer. The nuclear receptor (NR) superfamily, which is composed of 48 transcription factors that govern complex physiologic and pathophysiologic processes, could represent a unique subset of these biomarkers. In fact, many members of this family are the targets of already identified selective receptor modulators, providing a direct link between individual tumor NR quantitation and selection of therapy. The goal of this study, which begins this overall strategy, was to investigate the association between mRNA expression of the NR superfamily and the clinical outcome for patients with lung cancer, and to test whether a tumor NR gene signature provided useful information (over available clinical data) for patients with lung cancer.
Methods and Findings
Using quantitative real-time PCR to study NR expression in 30 microdissected non-small-cell lung cancers (NSCLCs) and their pair-matched normal lung epithelium, we found great variability in NR expression among patients' tumor and non-involved lung epithelium, found a strong association between NR expression and clinical outcome, and identified an NR gene signature from both normal and tumor tissues that predicted patient survival time and disease recurrence. The NR signature derived from the initial 30 NSCLC samples was validated in two independent microarray datasets derived from 442 and 117 resected lung adenocarcinomas. The NR gene signature was also validated in 130 squamous cell carcinomas. The prognostic signature in tumors could be distilled to expression of two NRs, short heterodimer partner and progesterone receptor, as single gene predictors of NSCLC patient survival time, including for patients with stage I disease. Of equal interest, the studies of microdissected histologically normal epithelium and matched tumors identified expression in normal (but not tumor) epithelium of NGFIB3 and mineralocorticoid receptor as single gene predictors of good prognosis.
Conclusions
NR expression is strongly associated with clinical outcomes for patients with lung cancer, and this expression profile provides a unique prognostic signature for lung cancer patient survival time, particularly for those with early stage disease. This study highlights the potential use of NRs as a rational set of therapeutically tractable genes as theragnostic biomarkers, and specifically identifies short heterodimer partner and progesterone receptor in tumors, and NGFIB3 and MR in non-neoplastic lung epithelium, for future detailed translational study in lung cancer.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Lung cancer, the most common cause of cancer-related death, kills 1.3 million people annually. Most lung cancers are “non-small-cell lung cancers” (NSCLCs), and most are caused by smoking. Exposure to chemicals in smoke causes changes in the genes of the cells lining the lungs that allow the cells to grow uncontrollably and to move around the body. How NSCLC is treated and responds to treatment depends on its “stage.” Stage I tumors, which are small and confined to the lung, are removed surgically, although chemotherapy is also sometimes given. Stage II tumors have spread to nearby lymph nodes and are treated with surgery and chemotherapy, as are some stage III tumors. However, because cancer cells in stage III tumors can be present throughout the chest, surgery is not always possible. For such cases, and for stage IV NSCLC, where the tumor has spread around the body, patients are treated with chemotherapy alone. About 70% of patients with stage I and II NSCLC but only 2% of patients with stage IV NSCLC survive for five years after diagnosis; more than 50% of patients have stage IV NSCLC at diagnosis.
Why Was This Study Done?
Patient responses to treatment vary considerably. Oncologists (doctors who treat cancer) would like to know which patients have a good prognosis (are likely to do well) to help them individualize their treatment. Consequently, the search is on for “prognostic tumor biomarkers,” molecules made by cancer cells that can be used to predict likely clinical outcomes. Such biomarkers, which may also be potential therapeutic targets, can be identified by analyzing the overall pattern of gene expression in a panel of tumors using a technique called microarray analysis and looking for associations between the expression of sets of genes and clinical outcomes. In this study, the researchers take a more directed approach to identifying prognostic biomarkers by investigating the association between the expression of the genes encoding nuclear receptors (NRs) and clinical outcome in patients with lung cancer. The NR superfamily contains 48 transcription factors (proteins that control the expression of other genes) that respond to several hormones and to diet-derived fats. NRs control many biological processes and are targets for several successful drugs, including some used to treat cancer.
What Did the Researchers Do and Find?
The researchers analyzed the expression of NR mRNAs using “quantitative real-time PCR” in 30 microdissected NSCLCs and in matched normal lung tissue samples (mRNA is the blueprint for protein production). They then used an approach called standard classification and regression tree analysis to build a prognostic model for NSCLC based on the expression data. This model predicted both survival time and disease recurrence among the patients from whom the tumors had been taken. The researchers validated their prognostic model in two large independent lung adenocarcinoma microarray datasets and in a squamous cell carcinoma dataset (adenocarcinomas and squamous cell carcinomas are two major NSCLC subtypes). Finally, they explored the roles of specific NRs in the prediction model. This analysis revealed that the ability of the NR signature in tumors to predict outcomes was mainly due to the expression of two NRs—the short heterodimer partner (SHP) and the progesterone receptor (PR). Expression of either gene could be used as a single gene predictor of the survival time of patients, including those with stage I disease. Similarly, the expression of either nerve growth factor induced gene B3 (NGFIB3) or mineralocorticoid receptor (MR) in normal tissue was a single gene predictor of a good prognosis.
What Do These Findings Mean?
These findings indicate that the expression of NR mRNA is strongly associated with clinical outcomes in patients with NSCLC. Furthermore, they identify a prognostic NR expression signature that provides information on the survival time of patients, including those with early stage disease. The signature needs to be confirmed in more patients before it can be used clinically, and researchers would like to establish whether changes in mRNA expression are reflected in changes in protein expression if NRs are to be targeted therapeutically. Nevertheless, these findings highlight the potential use of NRs as prognostic tumor biomarkers. Furthermore, they identify SHP and PR in tumors and two NRs in normal lung tissue as molecules that might provide new targets for the treatment of lung cancer and new insights into the early diagnosis, pathogenesis, and chemoprevention of lung cancer.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000378.
The Nuclear Receptor Signaling Atlas (NURSA) is consortium of scientists sponsored by the US National Institutes of Health that provides scientific reagents, datasets, and educational material on nuclear receptors and their co-regulators to the scientific community through a Web-based portal
The Cancer Prevention and Research Institute of Texas (CPRIT) provides information and resources to anyone interested in the prevention and treatment of lung and other cancers
The US National Cancer Institute provides detailed information for patients and professionals about all aspects of lung cancer, including information on non-small-cell carcinoma and on tumor markers (in English and Spanish)
Cancer Research UK also provides information about lung cancer and information on how cancer starts
MedlinePlus has links to other resources about lung cancer (in English and Spanish)
Wikipedia has a page on nuclear receptors (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
doi:10.1371/journal.pmed.1000378
PMCID: PMC3001894  PMID: 21179495
12.  Impact of mammographic screening on ethnic and socioeconomic inequities in breast cancer stage at diagnosis and survival in New Zealand: a cohort study 
BMC Public Health  2015;15:46.
Background
Indigenous Māori women experience a 60% higher breast cancer mortality rate compared with European women in New Zealand. We explored the impact of differences in rates of screen detected breast cancer on inequities in cancer stage at diagnosis and survival between Māori and NZ European women.
Methods
All primary breast cancers diagnosed in screening age women (as defined by the New Zealand National Breast Cancer Screening Programme) during 1999–2012 in the Waikato area (n = 1846) were identified from the Waikato Breast Cancer Register and the National Screening Database. Stage at diagnosis and survival were compared for screen detected (n = 1106) and non-screen detected (n = 740) breast cancer by ethnicity and socioeconomic status.
Results
Indigenous Māori women were significantly more likely to be diagnosed with more advanced cancer compared with NZ European women (OR = 1.51), and approximately a half of this difference was explained by lower rate of screen detected cancer for Māori women. For non-screen detected cancer, Māori had significantly lower 10-year breast cancer survival compared with NZ European (46.5% vs. 73.2%) as did most deprived compared with most affluent socioeconomic quintiles (64.8% vs. 81.1%). No significant survival differences were observed for screen detected cancer by ethnicity or socioeconomic deprivation.
Conclusions
The lower rate of screen detected breast cancer appears to be a key contributor towards the higher rate of advanced cancer at diagnosis and lower breast cancer survival for Māori compared with NZ European women. Among women with screen-detected breast cancer, Māori women do just as well as NZ European women, demonstrating the success of breast screening for Māori women who are able to access screening. Increasing breast cancer screening rates has the potential to improve survival for Māori women and reduce breast cancer survival inequity between Māori and NZ European women.
doi:10.1186/s12889-015-1383-4
PMCID: PMC4314740  PMID: 25637343
Breast cancer; Screening, Ethnicity, Deprivation, Inequity
13.  Inequalities in survival from colorectal cancer: a comparison of the impact of deprivation, treatment, and host factors on observed and cause specific survival 
Objective: To investigate whether socioeconomic deprivation is associated with cause specific and all cause survival for colorectal cancer and to what extent this is independent of significant prognostic factors.
Design: Prospective cohort.
Setting: The former Wessex Health Region, South West England.
Participants: All patients resident in Wessex registered with a diagnosis of colorectal cancer over three years (n=5176). Survival analysis was carried out on those patients with compete data for all factors and a positive survival time (n=4419).
Outcomes: Death from colorectal cancer and all cause over five year follow up from initial diagnosis.
Main results: Deprivation was significantly associated with survival for both outcomes in univariate analysis; the unadjusted hazard ratio for dying from colorectal cancer (most deprived compared with most affluent) was 1.12 (95% CI 1.00 to 1.25) and for all cause was 1.18 (1.07 to 1.30). Significant prognostic factors for both outcomes were age, specialisation of surgeon, Dukes's stage, and emergency compared with elective surgery. Comorbidity and gender were only associated with all cause survival. After adjustment for prognostic factors, the effect of deprivation on both cause specific and all cause mortality was reduced, and it was non-significant for colorectal cancer. However, the most deprived group had consistently worse survival than the most affluent.
Conclusions: Factors associated with survival with colorectal cancer depend on the outcome measure. Socioeconomic deprivation is adversely associated with survival in patients with colorectal cancer. This is strongest for non-colorectal cancer death, partly reflecting higher comorbidity, but it is there for colorectal cancer though not statistically significant. Conclusive evidence of the inequalities by socioeconomic status and underlying reasons needs to come from studies using individual based measures of socioeconomic status and more detail on treatment and host related factors.
doi:10.1136/jech.57.4.301
PMCID: PMC1732424  PMID: 12646548
14.  Estimating the potential survival gains by eliminating socioeconomic and sex inequalities in stage at diagnosis of melanoma 
British Journal of Cancer  2015;112(Suppl 1):S116-S123.
Background:
Although inequalities in cancer survival are thought to reflect inequalities in stage at diagnosis, little evidence exists about the size of potential survival gains from eliminating inequalities in stage at diagnosis.
Methods:
We used data on patients diagnosed with malignant melanoma in the East of England (2006–2010) to estimate the number of deaths that could be postponed by completely eliminating socioeconomic and sex differences in stage at diagnosis after fitting a flexible parametric excess mortality model.
Results:
Stage was a strong predictor of survival. There were pronounced socioeconomic and sex inequalities in the proportion of patients diagnosed at stages III–IV (12 and 8% for least deprived men and women and 25 and 18% for most deprived men and women, respectively). For an annual cohort of 1025 incident cases in the East of England, eliminating sex and deprivation differences in stage at diagnosis would postpone approximately 24 deaths to beyond 5 years from diagnosis. Using appropriate weighting, the equivalent estimate for England would be around 215 deaths, representing 11% of all deaths observed within 5 years from diagnosis in this population.
Conclusions:
Reducing socioeconomic and sex inequalities in stage at diagnosis would result in substantial reductions in deaths within 5 years of a melanoma diagnosis.
doi:10.1038/bjc.2015.50
PMCID: PMC4385984  PMID: 25734390
avoidable deaths; socioeconomic inequalities; sex inequalities; excess mortality models
15.  Socio-demographic inequalities in stage of cancer diagnosis: evidence from patients with female breast, lung, colon, rectal, prostate, renal, bladder, melanoma, ovarian and endometrial cancer 
Annals of Oncology  2012;24(3):843-850.
Background
Understanding socio-demographic inequalities in stage at diagnosis can inform priorities for cancer control.
Patients and methods
We analysed data on the stage at diagnosis of East of England patients diagnosed with any of 10 common cancers, 2006–2010. Stage information was available on 88 657 of 98 942 tumours (89.6%).
Results
Substantial socio-demographic inequalities in advanced stage at diagnosis (i.e. stage III/IV) existed for seven cancers, but their magnitude and direction varied greatly by cancer: advanced stage at diagnosis was more likely for older patients with melanoma but less likely for older patients with lung cancer [odds ratios for 75–79 versus 65–69 1.60 (1.38–1.86) and 0.83 (0.77–0.89), respectively]. Deprived patients were more likely to be diagnosed in advanced stage for melanoma, prostate, endometrial and (female) breast cancer: odds ratios (most versus least deprived quintile) from 2.24 (1.66–3.03) for melanoma to 1.31 (1.15–1.49) for breast cancer. In England, elimination of socio-demographic inequalities in stage at diagnosis could decrease the number of patients with cancer diagnosed in advanced stage by ∼5600 annually.
Conclusions
There are substantial socio-demographic inequalities in stage at diagnosis for most cancers. Earlier detection interventions and policies can be targeted on patients at higher risk of advanced stage diagnosis.
doi:10.1093/annonc/mds526
PMCID: PMC3574550  PMID: 23149571
cancer; demographic; diagnosis; inequalities; socio-economic; stage
16.  Deprivation and emergency admissions for cancers of colorectum, lung, and breast in south east England: ecological study 
BMJ : British Medical Journal  1998;317(7153):245-252.
Objectives: To examine the relation between deprivation and acute emergency admissions for cancers of the colon, rectum, lung, and breast in south east England.
Design: Ecological analysis with data from hospital episode statistics and 1991 census.
Setting: North and South Thames Regional Health Authorities (population about 14 million), divided into 10 aggregations of 31 470 census enumeration districts (median population 462).
Subjects: 146 639 admissions relating to 76 552 patients aged <100 years on admission, resident in the Thames regions, admitted between 1 April 1992 and 31 March 1995.
Results: Residents living in deprived areas were more likely to be admitted as emergencies and has ordinary inpatient admissions and less likely to be admitted as day cases. Adjusted odds of ordinary admissions from the most deprived tenth occurring as emergencies (relative to admissions from the most affluent tenth) were 2.29 (95% confidence interval 2.09 to 2.52) for colorectal cancer, 2.20 (1.99 to 2.43) for lung cancer, and 2.41 (2.17 to 2.67) for female breast cancer; adjusted odds of admissions as day cases were 0.70 (0.64 to 0.76), 0.50 (0.44 to 0.56), and 0.56 (0.50 to 0.62), respectively. Patients from deprived areas with lung or breast cancers were less likely to be recorded as having surgical interventions. Adjusted odds of patients from the most deprived tenth receiving surgery were 0.88 (0.78 to 1.00), 0.58 (0.48 to 0.70), and 0.63 (0.56 to 0.71), respectively. Admissions for colorectal cancer from the most deprived areas were less likely to be to hospitals admitting 100 or more new patients a year; the opposite held true for breast cancer admissions. No association was found for lung cancer admissions.
Conclusions: Earlier diagnostic and referral procedures in primary care in deprived areas are required if there are to be significant reductions in mortality from these cancers. A national information strategy is required to ensure the continued availability of population based data on NHS patients and to mandate standardised datasets from the private sector. Rationalisation of acute services, hospital mergers, and plans for bed closures must take into account the increased healthcare needs and inequities in access to treatment and care of residents in areas with high levels of deprivation. Health authorities and primary care groups should re-examine their purchasing intentions, service reviews, and monitoring arrangements in the light of these findings.
Key messages A major reorganisation of cancer services is under way in England and Wales with the aim of improving access to and quality of treatment Residents with cancers of the bowel, lung, or breast in deprived areas in the Thames region were more likely to be admitted as emergencies and ordinary inpatients than their counterparts from more affluent areas, and patients with lung or breast cancers from deprived areas were less likely to receive surgical treatment Patients with colorectal cancer from the most deprived areas were less likely to be seen at hospitals with a large caseload than were patients from affluent areas; the opposite held true for patients with breast cancer, but no association was found for admissions for lung cancer More effective early diagnostic and referral procedures in primary care in deprived areas are required if reductions in mortality are to be achieved Hospital mergers and plans for service reconfiguration and bed closures must take into account inequities in access to treatment among residents in deprived areas
PMCID: PMC28615  PMID: 9677214
17.  Survival among women with cancer of the uterine cervix: influence of marital status and social class. 
STUDY OBJECTIVE--The aim was to investigate whether the survival of women with cancer of the uterine cervix is associated with their marital status and social class. DESIGN--The study was a survey of survival up to 5 years from diagnosis of women with cancer of the cervix registered in the South Thames Cancer Registry, using Cox regression to adjust for marital status, social class, age, and stage at registration. Because of deficiencies in social class data held by the Registry (social class was assigned in only 51% of cases, as opposed to 93% for marital status), the findings were compared with survival data from the OPCS Longitudinal Study. SETTING--During the period of study (1977-81) the South Thames Cancer Registry covered a female population of about 3.5 million in the south east of England. PATIENTS--Data on 1728 women were analysed. MEASUREMENTS AND AND MAIN RESULTS--Apparent differences in crude survival by marital status and social class were examined. These were found to be accounted for by adjustment for age and stage. The better survival of those whose social class was unknown was found to be an artefact of the way in which cancer registries assign social class, but this did not appear to bias registry based studies of social class survival seriously. CONCLUSIONS--(1) After adjusting for age, factors affecting survival in women with cancer of the cervix, such as stage at presentation or host resistance, appear to be similarly distributed in the different marital status and social class groups; (2) for cervical cancer, the marked social class gradient and unusual marital status distribution found in cross sectional mortality data reflect the incidence of the disease, not differences in survival; (3) explanations for these patterns in incidence and mortality data are to be found in the aetiology of the disease.
PMCID: PMC1060672  PMID: 2277250
18.  Socioeconomic inequalities in cancer survival in England after the NHS cancer plan 
British Journal of Cancer  2010;103(4):446-453.
Background:
Socioeconomic inequalities in survival were observed for many cancers in England during 1981–1999. The NHS Cancer Plan (2000) aimed to improve survival and reduce these inequalities. This study examines trends in the deprivation gap in cancer survival after implementation of the Plan.
Materials and method:
We examined relative survival among adults diagnosed with 1 of 21 common cancers in England during 1996–2006, followed up to 31 December 2007. Three periods were defined: 1996–2000 (before the Cancer Plan), 2001–2003 (initialisation) and 2004–2006 (implementation). We estimated the difference in survival between the most deprived and most affluent groups (deprivation gap) at 1 and 3 years after diagnosis, and the change in the deprivation gap both within and between these periods.
Results:
Survival improved for most cancers, but inequalities in survival were still wide for many cancers in 2006. Only the deprivation gap in 1-year survival narrowed slightly over time. A majority of the socioeconomic disparities in survival occurred soon after a cancer diagnosis, regardless of the cancer prognosis.
Conclusion:
The recently observed reduction in the deprivation gap was minor and limited to 1-year survival, suggesting that, so far, the Cancer Plan has little effect on those inequalities. Our findings highlight that earlier diagnosis and rapid access to optimal treatment should be ensured for all socioeconomic groups.
doi:10.1038/sj.bjc.6605752
PMCID: PMC2939774  PMID: 20588275
relative survival; deprivation; socioeconomic inequalities; health policy
19.  Breast cancer incidence, stage, treatment and survival in ethnic groups in South East England 
British Journal of Cancer  2009;100(3):545-550.
Studies from the US have shown variations in breast cancer incidence, stage distribution, treatment and survival between ethnic groups. Data on 35 631 women diagnosed with breast cancer in South East England between 1998 and 2003 with self-assigned ethnicity information available were analysed. Results are reported for White, Indian, Pakistani, Bangladeshi, Black Caribbean, Black African and Chinese women. Age-standardised breast cancer incidence rate ratios, patterns of stage of disease at diagnosis, treatment, overall and breast cancer-specific survival were examined. All ethnic groups studied had lower age-standardised breast cancer incidence rates than White women, with Bangladeshi women having the lowest rate ratio (0.23, 95% CI: 0.20–0.26). White women were the most likely to have a stage recorded at diagnosis (adjusted proportion 75%), and least likely to be diagnosed with metastatic disease (7%). Black African women were the least likely to have a record of cancer surgery (63%) or hormone therapy (32%), and most likely to receive chemotherapy (38%). After fully adjusting for age, socioeconomic deprivation, stage of disease and treatment received, there was no significant variation in breast cancer-specific survival. However, Black African women had significantly worse overall survival (hazard ratio 1.24, P=0.025). These findings suggest that a strategy of earlier detection should be pursued in Black and South Asian women.
doi:10.1038/sj.bjc.6604852
PMCID: PMC2658548  PMID: 19127253
ethnicity; breast cancer; incidence; stage; treatment; survival
20.  Extracorporeal Lung Support Technologies – Bridge to Recovery and Bridge to Lung Transplantation in Adult Patients 
Executive Summary
For cases of acute respiratory distress syndrome (ARDS) and progressive chronic respiratory failure, the first choice or treatment is mechanical ventilation. For decades, this method has been used to support critically ill patients in respiratory failure. Despite its life-saving potential, however, several experimental and clinical studies have suggested that ventilator-induced lung injury can adversely affect the lungs and patient outcomes. Current opinion is that by reducing the pressure and volume of gas delivered to the lungs during mechanical ventilation, the stress applied to the lungs is eased, enabling them to rest and recover. In addition, mechanical ventilation may fail to provide adequate gas exchange, thus patients may suffer from severe hypoxia and hypercapnea. For these reasons, extracorporeal lung support technologies may play an important role in the clinical management of patients with lung failure, allowing not only the transfer of oxygen and carbon dioxide (CO2) but also buying the lungs the time needed to rest and heal.
Objective
The objective of this analysis was to assess the effectiveness, safety, and cost-effectiveness of extracorporeal lung support technologies in the improvement of pulmonary gas exchange and the survival of adult patients with acute pulmonary failure and those with end-stage chronic progressive lung disease as a bridge to lung transplantation (LTx). The application of these technologies in primary graft dysfunction (PGD) after LTx is beyond the scope of this review and is not discussed.
Clinical Applications of Extracorporeal Lung Support
Extracorporeal lung support technologies [i.e., Interventional Lung Assist (ILA) and extracorporeal membrane oxygenation (ECMO)] have been advocated for use in the treatment of patients with respiratory failure. These techniques do not treat the underlying lung condition; rather, they improve gas exchange while enabling the implantation of a protective ventilation strategy to prevent further damage to the lung tissues imposed by the ventilator. As such, extracorporeal lung support technologies have been used in three major lung failure case types:
As a bridge to recovery in acute lung failure – for patients with injured or diseased lungs to give their lungs time to heal and regain normal physiologic function.
As a bridge to LTx – for patients with irreversible end stage lung disease requiring LTx.
As a bridge to recovery after LTx – used as lung support for patients with PGD or severe hypoxemia.
Ex-Vivo Lung Perfusion and Assessment
Recently, the evaluation and reconditioning of donor lungs ex-vivo has been introduced into clinical practice as a method of improving the rate of donor lung utilization. Generally, about 15% to 20% of donor lungs are suitable for LTx, but these figures may increase with the use of ex-vivo lung perfusion. The ex-vivo evaluation and reconditioning of donor lungs is currently performed at the Toronto General Hospital (TGH) and preliminary results have been encouraging (Personal communication, clinical expert, December 17, 2009). If its effectiveness is confirmed, the use of the technique could lead to further expansion of donor organ pools and improvements in post-LTx outcomes.
Extracorporeal Lung support Technologies
ECMO
The ECMO system consists of a centrifugal pump, a membrane oxygenator, inlet and outlet cannulas, and tubing. The exchange of oxygen and CO2 then takes place in the oxygenator, which delivers the reoxygenated blood back into one of the patient’s veins or arteries. Additional ports may be added for haemodialysis or ultrafiltration.
Two different techniques may be used to introduce ECMO: venoarterial and venovenous. In the venoarterial technique, cannulation is through either the femoral artery and the femoral vein, or through the carotid artery and the internal jugular vein. In the venovenous technique cannulation is through both femoral veins or a femoral vein and internal jugular vein; one cannula acts as inflow or arterial line, and the other as an outflow or venous line. Venovenous ECMO will not provide adequate support if a patient has pulmonary hypertension or right heart failure. Problems associated with cannulation during the procedure include bleeding around the cannulation site and limb ischemia distal to the cannulation site.
ILA
Interventional Lung Assist (ILA) is used to remove excess CO2 from the blood of patients in respiratory failure. The system is characterized by a novel, low-resistance gas exchange device with a diffusion membrane composed of polymethylpentene (PMP) fibres. These fibres are woven into a complex configuration that maximizes the exchange of oxygen and CO2 by simple diffusion. The system is also designed to operate without the help of an external pump, though one can be added if higher blood flow is required. The device is then applied across an arteriovenous shunt between the femoral artery and femoral vein. Depending on the size of the arterial cannula used and the mean systemic arterial pressure, a blood flow of up to 2.5 L/min can be achieved (up to 5.5 L/min with an external pump). The cannulation is performed after intravenous administration of heparin.
Recently, the first commercially available extracorporeal membrane ventilator (NovaLung GmbH, Hechingen, Germany) was approved for clinical use by Health Canada for patients in respiratory failure. The system has been used in more than 2,000 patients with various indications in Europe, and was used for the first time in North America at the Toronto General Hospital in 2006.
Evidence-Based Analysis
The research questions addressed in this report are:
Does ILA/ECMO facilitate gas exchange in the lungs of patients with severe respiratory failure?
Does ILA/ECMO improve the survival rate of patients with respiratory failure caused by a range of underlying conditions including patients awaiting LTx?
What are the possible serious adverse events associated with ILA/ECMO therapy?
To address these questions, a systematic literature search was performed on September 28, 2009 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, the Cumulative Index to Nursing & Allied Health Literature (CINAHL), the Cochrane Library, and the International Agency for Health Technology Assessment (INAHTA) for studies published from January 1, 2005 to September 28, 2008. Abstracts were reviewed by a single reviewer and, for those studies meeting the eligibility criteria, full-text articles were obtained. Reference lists were also examined for any additional relevant studies not identified through the search. Articles with an unknown eligibility were reviewed with a second clinical epidemiologist and then a group of epidemiologists until consensus was established.
Inclusion Criteria
Studies in which ILA/ECMO was used as a bridge to recovery or bridge to LTx
Studies containing information relevant to the effectiveness and safety of the procedure
Studies including at least five patients
Exclusion Criteria
Studies reporting the use of ILA/ECMO for inter-hospital transfers of critically ill patients
Studies reporting the use of ILA/ECMO in patients during or after LTx
Animal or laboratory studies
Case reports
Outcomes of Interest
Reduction in partial pressure of CO2
Correction of respiratory acidosis
Improvement in partial pressure of oxygen
Improvement in patient survival
Frequency and severity of adverse events
The search yielded 107 citations in Medline and 107 citations in EMBASE. After reviewing the information provided in the titles and abstracts, eight citations were found to meet the study inclusion criteria. One study was then excluded because of an overlap in the study population with a previous study. Reference checking did not produce any additional studies for inclusion. Seven case series studies, all conducted in Germany, were thus included in this review (see Table 1).
Also included is the recently published CESAR trial, a multicentre RCT in the UK in which ECMO was compared with conventional intensive care management. The results of the CESAR trial were published when this review was initiated. In the absence of any other recent RCT on ECMO, the results of this trial were considered for this assessment and no further searches were conducted. A literature search was then conducted for application of ECMO as bridge to LTx patients (January, 1, 2005 to current). A total of 127 citations on this topic were identified and reviewed but none were found to have examined the use of ECMO as bridge to LTx.
Quality of Evidence
To grade the quality of evidence, the grading system formulated by the GRADE working group and adopted by MAS was applied. The GRADE system classifies the quality of a body of evidence as high, moderate, low, or very low according to four key elements: study design, study quality, consistency across studies, and directness.
Results
Trials on ILA
Of the seven studies identified, six involved patients with ARDS caused by a range of underlying conditions; the seventh included only patients awaiting LTx. All studies reported the rate of gas exchange and respiratory mechanics before ILA and for up to 7 days of ILA therapy. Four studies reported the means and standard deviations of blood gas transfer and arterial blood pH, which were used for meta-analysis.
Fischer et al. reported their first experience on the use of ILA as a bridge to LTx. In their study, 12 patients at high urgency status for LTx, who also had severe ventilation refractory hypercapnea and respiratory acidosis, were connected to ILA prior to LTx. Seven patients had a systemic infection or sepsis prior to ILA insertion. Six hours after initiation of ILA, the partial pressure of CO2 in arterial blood significantly decreased (P < .05) and arterial blood pH significantly improved (P < .05) and remained stable for one week (last time point reported). The partial pressure of oxygen in arterial blood improved from 71 mmHg to 83 mmHg 6 hours after insertion of ILA. The ratio of PaO2/FiO2 improved from 135 at baseline to 168 at 24 hours after insertion of ILA but returned to baseline values in the following week.
Trials on ECMO
The UK-based CESAR trial was conducted to assess the effectiveness and cost of ECMO therapy for severe, acute respiratory failure. The trial protocol were published in 2006 and details of the methods used for the economic evaluation were published in 2008. The study itself was a pragmatic trial (similar to a UK trial of neonatal ECMO), in which best standard practice was compared with an ECMO protocol. The trial involved 180 patients with acute but potentially reversible respiratory failure, with each also having a Murray score of ≥ 3.0 or uncompensated hypercapnea at a pH of < 7.2. Enrolled patients were randomized in a 1:1 ratio to receive either conventional ventilation treatment or ECMO while on ventilator. Conventional management included intermittent positive pressure ventilation, high frequency oscillatory ventilation, or both. As a pragmatic trial, a specific management protocol was not followed; rather the treatment centres were advised to follow a low volume low pressure ventilation strategy. A tidal volume of 4 to 8 mL/kg body weight and a plateau pressure of < 30 cm H2O were recommended.
Conclusions
ILA
Bridge to recovery
No RCTs or observational studies compared ILA to other treatment modalities.
Case series have shown that ILA therapy results in significant CO2 removal from arterial blood and correction of respiratory acidosis, as well as an improvement in oxygen transfer.
ILA therapy enabled a lowering of respiratory settings to protect the lungs without causing a negative impact on arterial blood CO2 and arterial blood pH.
The impact of ILA on patient long-term survival cannot be determined through the studies reviewed.
In-hospital mortality across studies ranged from 20% to 65%.
Ischemic complications were the most frequent adverse events following ILA therapy.
Leg amputation is a rare but possible outcome of ILA therapy, having occurred in about 0.9% of patients in these case series. New techniques involving the insertion of additional cannula into the femoral artery to perfuse the leg may lower this rate.
Bridge to LTx
The results of one case series (n=12) showed that ILA effectively removes CO2 from arterial blood and corrects respiratory acidosis in patients with ventilation refractory hypercapnea awaiting a LTx
Eight of the 12 patients (67%) awaiting a LTx were successfully transplanted and one-year survival for those transplanted was 80%
Since all studies are case series, the grade of the evidence for these observations is classified as “LOW”.
ECMO
Bridge to recovery
Based on the results of a pragmatic trial and an intention to treat analysis, referral of patient to an ECMO based centre significantly improves patient survival without disability compared to conventional ventilation. The results of CESAR trial showed that:
For patients with information about disability, survival without severe disability was significantly higher in ECMO arm
Assuming that the three patients in the conventional ventilation arm who did not have information about severe disability were all disabled, the results were also significant.
Assuming that none of these patients were disabled, the results were at borderline significance
A greater, though not statistically significant, proportion of patients in ECMO arm survived.
The rate of serious adverse events was higher among patients in ECMO group
The grade of evidence for the above observations is classified as “HIGH”.
Bridge to LTx
No studies fitting the inclusion criteria were identified.
There is no accurate data on the use of ECMO in patients awaiting LTx.
Economic Analysis
The objective of the economic analysis was to determine the costs associated with extracorporeal lung support technologies for bridge to LTx in adults. A literature search was conducted for which the target population was adults eligible for extracorporeal lung support. The primary analytic perspective was that of the Ministry of Health and Long-Term Care (MOHLTC). Articles published in English and fitting the following inclusion criteria were reviewed:
Full economic evaluations including cost-effectiveness analyses (CEA), cost-utility analyses (CUA), cost-benefit analyses (CBA);
Economic evaluations reporting incremental cost-effectiveness ratios (ICER) i.e. cost per quality adjusted life year (QALY), life years gained (LYG), or cost per event avoided; and
Studies in patients eligible for lung support technologies for to lung transplantation.
The search yielded no articles reporting comparative economic analyses.
Resource Use and Costs
Costs associated with both ILA and ECMO (outlined in Table ES-1) were obtained from the University Health Network (UHN) case costing initiative (personal communication, UHN, January 2010). Consultation with a clinical expert in the field was also conducted to verify resource utilization. The consultant was situated at the UHN in Toronto. The UHN has one ECMO machine, which cost approximately $100,000. The system is 18 years old and is used an average of 3 to 4 times a year with 35 procedures being performed over the last 9 years. The disposable cost per patient associated with ECMO is, on average, $2,200. There is a maintenance cost associated with the machine (not reported by the UHN), which is currently absorbed by the hospital’s biomedical engineering department.
The average capital cost of an ILA device is $7,100 per device, per patient, while the average cost of the reusable pump $65,000. The UHN has performed 16 of these procedures over the last 2.5 years. Similarly, there is a maintenance cost not that was reported by UHN but is absorbed by the hospital’s biomedical engineering department.
Resources Associated with Extracorporeal Lung Support Technologies
Hospital costs associated with ILA were based on the average cost incurred by the hospital for 11 cases performed in the FY 07/08 (personal communication, UHN, January 2010). The resources incurred with this hospital procedure included:
Device and disposables
OR transplant
Surgical ICU
Laboratory work
Medical imaging
Pharmacy
Clinical nutrition
Physiotherapy
Occupational therapy
Speech and language pathology
Social work
The average length of stay in hospital was 61 days for ILA (range: 5 to 164 days) and the average direct cost was $186,000 per case (range: $19,000 to $552,000). This procedure has a high staffing requirement to monitor patients in hospital, driving up the average cost per case.
PMCID: PMC3415698  PMID: 23074408
21.  Deriving stage at diagnosis from multiple population-based sources: colorectal and lung cancer in England 
British Journal of Cancer  2016;115(3):391-400.
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.
doi:10.1038/bjc.2016.177
PMCID: PMC4973150  PMID: 27328310
cancer; stage; TNM; routine data; survival; population-based
22.  Breast cancer survival in South Asian women in England and Wales 
Study objectives: To estimate ethnic and socioeconomic differences in breast cancer incidence and survival between South Asians and non-South Asians in England and Wales, and to provide a baseline for surveillance of cancer survival in South Asians, the largest ethnic minority.
Setting: 115 712 women diagnosed with first primary invasive breast cancer in England and Wales during 1986–90 and followed up to 1995.
Methods/design: Ethnic group was ascribed by a computer algorithm on the basis of the name. Incidence rates were derived from 1991 census population denominators for each ethnic group. One and five year relative survival rates were estimated by age, quintile of material deprivation, and ethnic group, using national mortality rates to estimate expected survival.
Main results: Age standardised incidence was 29% lower among South Asian women (40.5 per 100 000 per year) than among all other women (57.4 per 100 000). Five year age standardised relative survival was 70.3% (95%CI 65.2 to 75.4) for South Asian women and 66.7% (66.4 to 67.0) for other women. For both ethnic groups, survival was 8%–9% higher for women in the most affluent group than those in the most deprived group. In each deprivation category, however, survival was 3%–8% higher for South Asian women than other women.
Conclusions: This national study confirms that breast cancer incidence is substantially lower in South Asians than other women in England and Wales. It also provides some evidence that South Asian women diagnosed up to 1990 had higher breast cancer survival than other women in England and Wales, both overall and in each category of deprivation.
doi:10.1136/jech.2004.030965
PMCID: PMC1733081  PMID: 15831690
23.  A Gene Expression Signature Predicts Survival of Patients with Stage I Non-Small Cell Lung Cancer 
PLoS Medicine  2006;3(12):e467.
Background
Lung cancer is the leading cause of cancer-related death in the United States. Nearly 50% of patients with stages I and II non-small cell lung cancer (NSCLC) will die from recurrent disease despite surgical resection. No reliable clinical or molecular predictors are currently available for identifying those at high risk for developing recurrent disease. As a consequence, it is not possible to select those high-risk patients for more aggressive therapies and assign less aggressive treatments to patients at low risk for recurrence.
Methods and Findings
In this study, we applied a meta-analysis of datasets from seven different microarray studies on NSCLC for differentially expressed genes related to survival time (under 2 y and over 5 y). A consensus set of 4,905 genes from these studies was selected, and systematic bias adjustment in the datasets was performed by distance-weighted discrimination (DWD). We identified a gene expression signature consisting of 64 genes that is highly predictive of which stage I lung cancer patients may benefit from more aggressive therapy. Kaplan-Meier analysis of the overall survival of stage I NSCLC patients with the 64-gene expression signature demonstrated that the high- and low-risk groups are significantly different in their overall survival. Of the 64 genes, 11 are related to cancer metastasis (APC, CDH8, IL8RB, LY6D, PCDHGA12, DSP, NID, ENPP2, CCR2, CASP8, and CASP10) and eight are involved in apoptosis (CASP8, CASP10, PIK3R1, BCL2, SON, INHA, PSEN1, and BIK).
Conclusions
Our results indicate that gene expression signatures from several datasets can be reconciled. The resulting signature is useful in predicting survival of stage I NSCLC and might be useful in informing treatment decisions.
Meta-analysis of several lung cancer gene expression studies yields a set of 64 genes whose expression profile is useful in predicting survival of patients with early-stage lung cancer and possibly informing treatment decisions.
Editors' Summary
Background.
Lung cancer is the commonest cause of cancer-related death worldwide. Most cases are of a type called non-small cell lung cancer (NSCLC) and are mainly caused by smoking. Like other cancers, how NSCLC is treated depends on the “stage” at which it is detected. Stage IA NSCLCs are small and confined to the lung and can be removed surgically; patients with slightly larger stage IB tumors often receive chemotherapy after surgery. In stage II NSCLC, cancer cells may be present in lymph nodes near the tumor. Surgery plus chemotherapy is the usual treatment for this stage and for some stage III NSCLCs. However, in this stage, the tumor can be present throughout the chest and surgery is not always possible. For such cases and in stage IV NSCLC, where the tumor has spread throughout the body, patients are treated with chemotherapy alone. The stage at which NSCLC is detected also determines how well patients respond to treatment. Those who can be treated surgically do much better than those who can't. So, whereas only 2% of patients with stage IV lung cancer survive for 5 years after diagnosis, about 70% of patients with stage I or II lung cancer live at least this long.
Why Was This Study Done?
Even stage I and II lung cancers often recur and there is no accurate way to identify the patients in which this will happen. If there was, these patients could be given aggressive chemotherapy, so the search is on for a “molecular signature” to help identify which NSCLCs are likely to recur. Unlike normal cells, cancer cells divide uncontrollably and can move around the body. These behavioral differences are caused by changes in their genetic material that alter their patterns of RNA transcription and protein expression. In this study, the researchers have investigated whether data from several microarray studies (a technique used to catalog the genes expressed in cells) can be pooled to construct a gene expression signature that predicts the survival of patients with stage I NSCLC.
What Did the Researchers Do and Find?
The researchers took the data from seven independent microarray studies (including a new study of their own) that recorded gene expression profiles related to survival time (less than 2 years and greater than 5 years) for stage I NSCLC. Because these studies had been done in different places with slightly different techniques, the researchers applied a statistical tool called distance-weighted discrimination to smooth out any systematic differences among the studies before identifying 64 genes whose expression was associated with survival. Most of these genes are involved in cell adhesion, cell motility, cell proliferation, and cell death, all processes that are altered in cancer cells. The researchers then developed a statistical model that allowed them to use the gene expression and survival data to calculate risk scores for nearly 200 patients in five of the datasets. When they separated the patients into high and low risk groups on the basis of these scores, the two groups were significantly different in terms of survival time. Indeed, the gene expression signature was better at predicting outcome than routine staging. Finally, the researchers validated the gene expression signature by showing that it predicted survival with more than 85% accuracy in two independent datasets.
What Do These Findings Mean?
The 64 gene expression signature identified here could help clinicians prepare treatment plans for patients with stage I NSCLC. Because it accurately predicts survival in patients with adenocarcinoma or squamous cell cancer (the two major subtypes of NSCLC), it potentially indicates which of these patients should receive aggressive chemotherapy and which can be spared this unpleasant treatment. Previous attempts to establish gene expression signatures to predict outcome have used data from small groups of patients and have failed when tested in additional patients. In contrast, this new signature seems to be generalizable. Nevertheless, its ability to predict outcomes must be confirmed in further studies before it is routinely adopted by oncologists for treatment planning.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030467.
US National Cancer Institute information on lung cancer for patients and health professionals.
MedlinePlus encyclopedia entries on small-cell and non-small-cell lung cancer.
Cancer Research UK, information on patients about all aspects of lung cancer.
Wikipedia pages on DNA microarrays and expression profiling (note that Wikipedia is a free online encyclopedia that anyone can edit).
doi:10.1371/journal.pmed.0030467
PMCID: PMC1716187  PMID: 17194181
24.  Lung cancer incidence and survival in different ethnic groups in South East England 
British Journal of Cancer  2011;105(7):1049-1053.
Background:
This study aimed to examine the incidence and survival of lung cancer patients from several different ethnic groups in a large ethnically diverse population in the United Kingdom.
Methods:
Data on residents of South East England diagnosed with lung cancer between 1998 and 2003 were extracted from the Thames Cancer Registry database. Age- and socioeconomic deprivation-standardised incidence rate ratios were calculated for males and females in each ethnic group. Overall survival was examined using Cox regression, adjusted for age, socioeconomic deprivation, stage of disease and treatment. Results are presented for White, Indian, Pakistani, Bangladeshi, Black Caribbean, Black African and Chinese patients, apart from female survival results where only the White, South Asian and Black ethnic groups were analysed.
Results:
Compared with other ethnic groups of the same sex, Bangladeshi men, White men and White women had the highest incidence rates. Bangladeshi men had consistently higher survival estimates compared with White men (fully adjusted hazard ratio 0.46; P<0.001). Indian (0.84; P=0.048), Black Caribbean (0.87; P=0.47) and Black African (0.68; P=0.007) men also had higher survival estimates. South Asian (0.73; P=0.006) and Black (0.74; P=0.004) women had higher survival than White women.
Conclusion:
Smoking prevention messages need to be targeted for different ethnic groups to ensure no groups are excluded. The apparent better survival of South Asian and Black patients is surprising, and more detailed follow-up studies are needed to verify these results.
doi:10.1038/bjc.2011.282
PMCID: PMC3185928  PMID: 21863024
ethnicity; lung cancer; incidence; survival
25.  Predicting Survival within the Lung Cancer Histopathological Hierarchy Using a Multi-Scale Genomic Model of Development 
PLoS Medicine  2006;3(7):e232.
Background
The histopathologic heterogeneity of lung cancer remains a significant confounding factor in its diagnosis and prognosis—spurring numerous recent efforts to find a molecular classification of the disease that has clinical relevance.
Methods and Findings
Molecular profiles of tumors from 186 patients representing four different lung cancer subtypes (and 17 normal lung tissue samples) were compared with a mouse lung development model using principal component analysis in both temporal and genomic domains. An algorithm for the classification of lung cancers using a multi-scale developmental framework was developed. Kaplan–Meier survival analysis was conducted for lung adenocarcinoma patient subgroups identified via their developmental association. We found multi-scale genomic similarities between four human lung cancer subtypes and the developing mouse lung that are prognostically meaningful. Significant association was observed between the localization of human lung cancer cases along the principal mouse lung development trajectory and the corresponding patient survival rate at three distinct levels of classical histopathologic resolution: among different lung cancer subtypes, among patients within the adenocarcinoma subtype, and within the stage I adenocarcinoma subclass. The earlier the genomic association between a human tumor profile and the mouse lung development sequence, the poorer the patient's prognosis. Furthermore, decomposing this principal lung development trajectory identified a gene set that was significantly enriched for pyrimidine metabolism and cell-adhesion functions specific to lung development and oncogenesis.
Conclusions
From a multi-scale disease modeling perspective, the molecular dynamics of murine lung development provide an effective framework that is not only data driven but also informed by the biology of development for elucidating the mechanisms of human lung cancer biology and its clinical outcome.
Editors' Summary
Background.
Lung cancer causes the most deaths from cancer worldwide—around a quarter of all cancer deaths—and the number of deaths is rising each year. There are a number of different types of the disease, whose names come from early descriptions of the cancer cells when seen under the microscope: carcinoid, small cell, and non–small cell, which make up 2%, 13%, and 86% of lung cancers, respectively. To make things more complicated, each of these cancer types can be subdivided further. It is important to distinguish the different types of cancer because they differ in their rates of growth and how they respond to treatment; for example, small cell lung cancer is the most rapidly progressing type of lung cancer. But although these current classifications of cancers are useful, researchers believe that if the underlying molecular changes in these cancers could be discovered then a more accurate way of classifying cancers, and hence predicting outcome and response to treatment, might be possible.
Why Was This Study Done?
Previous work has suggested that some cancers come from very immature cells, that is, cells that are present in the early stages of an animal's development from an embryo in the womb to an adult animal. Many animals have been closely studied so as to understand how they develop; the best studied model that is also relevant to human disease is the mouse, and researchers have previously studied lung development in mice in detail. This group of researchers wanted to see if there was any relation between the activity (known as expression) of mouse genes during the development of the lung and the expression of genes in human lung cancers, particularly whether they could use gene expression to try to predict the outcome of lung cancer in patients.
What Did the Researchers Do and Find?
They compared the gene expression in lung cancer samples from 186 patients with four different types of lung cancer (and in 17 normal lung tissue samples) to the gene expression found in normal mice during development. They found similarities between expression patterns in the lung cancer subtypes and the developing mouse lung, and that these similarities explain some of the different outcomes for the patients. In general, they found that when the gene expression in the human cancer was similar to that of very immature mouse lung cells, patients had a poor prognosis. When the gene expression in the human cancer was more similar to mature mouse lung cells, the prognosis was better. However, the researchers found that carcinoid tumors had rather different expression profiles compared to the other tumors.
  The researchers were also able to discover some specific gene types that seemed to have particularly strong associations between mouse development and the human cancers. Two of these gene types were ones that are involved in building and breaking down DNA itself, and ones involved in how cells stick together. This latter group of genes is thought to be involved in how cancers spread.
What Do These Findings Mean?
These results provide a new way of thinking about how to classify lung cancers, and also point to a few groups of genes that may be particularly important in the development of the tumor. However, before these results are used in any clinical assessment, further work will need to be done to work out whether they are true for other groups of patients.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030232.
•  MedlinePlus has information from the United States National Library of Medicine and other government agencies and health-related organizations [MedlinePlus]
•  National Institute on Aging is also a good place to start looking for information [National Institute for Aging]
•  [The National Cancer Institute] and Lung Cancer Online [ Lung Cancer Online] have a wide range of information on lung cancer
Comparison of gene expression patterns in patients with lung cancer and in mouse lung development showed that those tumors associated with earlier mouse lung development had a poorer prognosis.
doi:10.1371/journal.pmed.0030232
PMCID: PMC1483910  PMID: 16800721

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