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Background: Cancers of Unknown Primary (CUP) are the 3-4th most common causes of cancer death and recent clinical guidelines recommend that patients should be directed to a team dedicated to their care. Our aim was to inform the care of patients diagnosed with CUP during hospital admission.Methods: Descriptive study using hospital admissions (Scottish Morbidity Record 01) linked to cancer registrations (ICD-10 C77-80) and death records from 1998 to 2011 in West of Scotland, UK (population 2.4 m). Cox proportional hazards models were used to assess effects of baseline variables on survival.Results: Seven thousand five hundred ninety nine patients were diagnosed with CUP over the study period, 54.4% female, 67.4% aged ≥ 70 years, 36.7% from the most deprived socio-economic quintile. 71% of all diagnoses were made during a hospital admission, among which 88.6% were emergency presentations and the majority (56.3%) were admitted to general medicine. Median length of stay was 15 days and median survival after admission 33 days. Non-specific morphology, emergency admission, age over 60 years, male sex and admission to geriatric medicine were all associated with poorer survival in adjusted analysis.Conclusions: Patients with a diagnosis of CUP are usually diagnosed during unplanned hospital admissions and have very poor survival. To ensure that patients with CUP are quickly identified and directed to optimal care, increased surveillance and rapid referral pathways will be required. [ABSTRACT FROM AUTHOR]

Background: Cancers of unknown primary site (CUP) pose problems for diagnosis, treatment, and accurate prediction of prognosis. However, there are limited published data describing the epidemiology of this disease entity. Our aim was to describe the epidemiology of CUP in Scotland. Methods: Anonymised data, covering the period 1961-2010, were extracted from the Scottish Cancer Registry database, based on the following ICD-10 diagnostic codes: C26.0, C26.8, C26.9, C39, and C76- C80. Age-standardised incidence rates were calculated by direct standardisation to the World Standard Population. Estimates of observed survival were calculated by the Kaplan-Meier method. Results: Between 1961 and 2010, there were 50,941 registrations of CUP, representing 3.9% of all registrations of invasive cancers. Age-standardised rates increased to a peak in the early to mid-1990s, followed by a steeper decrease in rates. During 2001-2010, age-standardised rates of CUP were higher in the most compared with the least deprived fifth of the population. Observed survival was marginally higher in patients diagnosed during 2001-2010 (median 5.6 weeks) compared with those diagnosed in the previous two decades. During the most recent decade, survival decreased with age at diagnosis, and was higher in patients with squamous cell carcinoma and with lymph node metastases. Conclusion: Patterns of CUP in Scotland are largely consistent with those reported from the few other countries that have published data. However, in comparing studies, it is important to note that there is heterogeneity in terms of definition of CUP, as well as calendar period of diagnosis or death. Variation in the definition of CUP between different epidemiological studies suggests that there would be merit in seeking international agreement on guidelines for the registration of CUP as well as a standard grouping of diagnostic codes for analysis. [ABSTRACT FROM AUTHOR]

Background: Lung and upper aero-digestive tract (UADT) cancer risk are associated with low socioeconomic circumstances and routinely measured using area socioeconomic indices. We investigated effect of country of birth, marital status, one area deprivation measure and individual socioeconomic variables (economic activity, education, occupational social class, car ownership, household tenure) on risk associated with lung, UADT and all cancer combined (excluding non melanoma skin cancer). Methods: We linked Scottish Longitudinal Study and Scottish Cancer Registry to follow 203,658 cohort members aged 15+ years from 1991–2006. Relative risks (RR) were calculated using Poisson regression models by sex offset for person-years of follow-up. Results: 21,832 first primary tumours (including 3,505 lung, 1,206 UADT) were diagnosed. Regardless of cancer, economically inactivity (versus activity) was associated with increased risk (male: RR 1.14, 95% CI 1.10–1.18; female: RR 1.06, 95% CI 1.02–1.11). For lung cancer, area deprivation remained significant after full adjustment suggesting the area deprivation cannot be fully explained by individual variables. No or non degree qualification (versus degree) was associated with increased lung risk; likewise for UADT risk (females only). Occupational social class associations were most pronounced and elevated for UADT risk. No car access (versus ownership) was associated with increased risk (excluding all cancer risk, males). Renting (versus home ownership) was associated with increased lung cancer risk, UADT cancer risk (males only) and all cancer risk (females only). Regardless of cancer group, elevated risk was associated with no education and living in deprived areas. Conclusions: Different and independent socioeconomic variables are inversely associated with different cancer risks in both sexes; no one socioeconomic variable captures all aspects of socioeconomic circumstances or life course. Association of multiple socioeconomic variables is likely to reflect the complexity and multifaceted nature of deprivation as well as the various roles of these dimensions over the life course. [ABSTRACT FROM AUTHOR]

Abstract: Aim: To assess the risk of death in patients who survive at least 5years after diagnosis of childhood, adolescent or young adult cancer. Patients and Methods: This was a population-based retrospective cohort study using linked national cancer registry and mortality records in Scotland. The study population consisted of 5229 individuals who were diagnosed with cancer before the age of 25years between 1981 and 2003, and who survived at least 5years after the date of diagnosis of their primary cancer. Indirect standardisation was used to calculate mortality ratios standardised for age and sex and absolute excess risks (AERs) compared to the general Scottish population. Results: During 58,358 person-years of follow-up, there were 359 deaths among the cohort of cancer survivors. The overall SMR was 6.1 (95% confidence interval (CI) 5.5–6.7) and AER 51 (45–58) per 10,000 person-years. Largely because of age- and sex-related differences in background mortality, SMRs were higher in patients diagnosed at 0–14years (SMR 11.0, 95% CI 9.3–12.9) than 15–24years (4.7, 4.1–5.3), and in females (9.2, 7.8–10.8) than males (4.8, 4.2–5.5). SMRs and AERs varied substantially by primary cancer and by underlying cause of death. In general, SMRs were little altered by standardisation for an area-based indicator of socio-economic deprivation. Adjusted for age and sex, the risk of death was significantly lower in five-year survivors diagnosed during 1998–2003 compared to those diagnosed during 1981–1985 (Relative hazard ratio, 0.54, 95% CI 0.36–0.81). Conclusion: Long-term survivors of cancer in childhood and young adulthood remain at higher risk of mortality than the general population, although the absolute risk of death is low and the excess risk has decreased over time. [Copyright &y& Elsevier]

Background: Risk factors are often considered individually, we aimed to investigate the prevalence of combinations of multiple behavioural risk factors and their association with socioeconomic determinants.Methods: Multinomial logistic regression was used to model the associations between socioeconomic factors and multiple risk factors from data in the Scottish Health Survey 2003. Prevalence of five key risk - smoking, alcohol, diet, overweight/obesity, and physical inactivity, and their risk in relation to demographic, individual and area socioeconomic factors were assessed.Results: Full data were available on 6,574 subjects (80.7% of the survey sample). Nearly the whole adult population (97.5%) reported to have at least one behavioural risk factor; while 55% have three or more risk factors; and nearly 20% have four or all five risk factors. The most important determinants for having four or five multiple risk factors were low educational attainment which conferred over a 3-fold increased risk compared to high education; and residence in the most deprived communities (relative to least deprived) which had greater than 3-fold increased risk.Conclusions: The prevalence of multiple behavioural risk factors was high and the prevalence of absence of all risk factors very low. These behavioural patterns were strongly associated with poorer socioeconomic circumstances. Policy to address factors needs to be joined up and better consider underlying socioeconomic circumstances. [ABSTRACT FROM AUTHOR]

Study objective: To assess the risk of breast cancer in patients with a previous history of miscarriage or induced abortion. Design: Case-control study relating "exposure" to outcome by linkage of national hospital discharge and maternity records, the national cancer registry, and death records. Setting: Scotland. Participants: Miscarriage analysis-2828 women with breast cancer and 9781 matched controls; induced abortion analysis-2833 women with breast cancer and 9888 matched controls. Main results: After stratification for age at diagnosis, parity, and age at first birth, the odds ratio (95% confidence intervals) of breast cancer was 1.02(0.88 to 1.18) in women with a previous miscarriage, and 0.80 (0.72 to 0.89) in women with a previous induced abortion. Further adjustments for age at bilateral oophorectomy, socioeconomic status (based on small area of residence), and health board area of residence had only minor effects on these odds ratios. Conclusion: These data do not support the hypothesis that miscarriage or induced abortion represent substantive risk factors for the future development of breast cancer. [ABSTRACT FROM AUTHOR]

Abstract: Completeness of ascertainment of breast cancer cases by the Scottish Cancer Registry (SCR) was assessed by independent comparison with five clinical trials databases, comprising 2621 patients and spanning the total period of diagnosis 1978–2000. Overall, ascertainment was estimated to exceed 98%, although 0.3% of matched cases were misclassified as carcinoma in situ by the SCR. These results support the validity of national estimates of incidence of, and survival from, breast cancer in Scotland. [Copyright &y& Elsevier]

Background: Adjuvant chemotherapy in early stage breast cancer has been shown to reduce mortality in a large meta-analysis of over 100 randomised trials. However, these trials largely excluded patients aged 70 years and over or with higher levels of comorbidity. There is therefore uncertainty about whether the effectiveness of adjuvant chemotherapy generalises to these groups, hindering patient and clinician decision-making. This study utilises administrative healthcare data-real world data (RWD)-and econometric methods for causal analysis to estimate treatment effectiveness in these trial-underrepresented groups.Methods and Findings: Women with early breast cancer aged 70 years and over and those under 70 years with a high level of comorbidity were identified and their records extracted from Scottish Cancer Registry (2001-2015) data linked to other routine health records. A high level of comorbidity was defined as scoring 1 or more on the Charlson comorbidity index, being in the top decile of inpatient stays, and/or having 5 or more visits to specific outpatient clinics, all within the 5 years preceding breast cancer diagnosis. Propensity score matching (PSM) and instrumental variable (IV) analysis, previously identified as feasible and valid in this setting, were used in conjunction with Cox regression to estimate hazard ratios for death from breast cancer and death from all causes. The analysis adjusts for age, clinical prognostic factors, and socioeconomic deprivation; the IV method may also adjust for unmeasured confounding factors. Cohorts of 9,653 and 7,965 were identified for women aged 70 years and over and those with high comorbidity, respectively. In the ≥70/high comorbidity cohorts, median follow-up was 5.17/6.53 years and there were 1,935/740 deaths from breast cancer. For women aged 70 years and over, the PSM-estimated HR was 0.73 (95% CI 0.64-0.95), while for women with high comorbidity it was 0.67 (95% CI 0.51-0.86). This translates to a mean predicted benefit in terms of overall survival at 10 years of approximately3% (percentage points) and 4%, respectively. A limitation of this analysis is that use of observational data means uncertainty remains both from sampling uncertainty and from potential bias from residual confounding.Conclusions: The results of this study, as RWD, should be interpreted with caution and in the context of existing and emerging randomised data. The relative effectiveness of adjuvant chemotherapy in reducing mortality in patients with early stage breast cancer appears to be generalisable to the selected trial-underrepresented groups. [ABSTRACT FROM AUTHOR]

Background Melanomas are initially excised in primary care, and rates vary internationally. Until now, there has been no strong evidence one way or the other that excising melanomas in primary care is safe or unsafe. European guidelines make no recommendations, and the United Kingdom (UK) melanoma guidelines require all suspicious skin lesions to be initially treated in secondary care based on an expert consensus, which lacks supporting evidence, that primary care excision represents substandard care. Despite this, studies have found that up to 20% of melanomas in the UK are excised by general practitioners (GPs). Patients receiving primary care melanoma excision may fear that their care is substandard and their long-term survival threatened, neither of which may be justified. Methods Scottish cancer registry data from 9367 people diagnosed with melanoma in Scotland between 2005 and 2013 were linked to pathology records, hospital data and death records. A Cox proportional hazards regression analysis, adjusting for key confounders, explored the association between morbidity and mortality and setting of primary melanoma excision (primary versus secondary care). A pooled estimate of the relative hazard of death of having a melanoma excised in primary versus secondary care including 7116 patients from a similar Irish study was also performed. Results The adjusted hazard ratio (95% CI) of death from melanoma for those having primary care excision was 0.82 (0.61–1.10). Those receiving primary care excision had a median (IQR) of 8 (3–14) out-patient attendances compared to 10 (4–17) for the secondary care group with an adjusted relative risk (RR) (95% CI) of 0.98 (0.96–1.01). Both groups had a median of 1 (0–2) hospital admissions with an adjusted rate ratio of 1.05 (0.98–1.13). In the meta-analysis, with primary care as the reference, the pooled adjusted hazard ratio (HR, 95% CI) was 1.26 (1.07–1.50) indicating a significantly higher all-cause mortality among those with excision in secondary care. Conclusions The results of the Scottish and pooled analyses suggest that those receiving an initial excision for melanoma in primary care do not have poorer survival or increased morbidity compared to those being initially treated in secondary care. A randomised controlled trial to inform a greater role for GPs in the initial excision of melanoma is justified in the light of these results. [ABSTRACT FROM AUTHOR]

Background: Worldwide, the incidence of cutaneous melanoma has been reported to be highest in the summer and lowest in the winter. Northern Irish data suggested seasonal variation for women only, especially those with thinner melanomas, sited on limbs. We interrogated two larger UK cancer registries for temporal differences in melanoma diagnosis and associated patient characteristics. Methods: Melanomas diagnosed from 2006 to 2010 in the Eastern England and Scottish cancer registries (n = 11,611) were analysed by month of diagnosis, patient demographics and melanoma characteristics, using descriptive and multivariate modelling methods. Results: More patients with melanoma were diagnosed in the summer months (June 9.9%, July 9.7%, August 9.8%) than the winter months (December 7.2%, January 7.2%, February 7.1%) and this pattern was consistent in both regions. There was evidence that the seasonal patterns varied by sex (p = 0.015), melanoma thickness (p = 0.002), body site (p = 0.006), and type (superficial spreading melanomas p = 0.005). The seasonal variation was greatest for diagnosis of melanomas occurring on the limbs. Conclusion: This study has confirmed seasonal variation in melanoma diagnosis in Eastern England and Scotland across almost all population demographics and melanoma characteristics studied, with higher numbers diagnosed in the summer months, particularly on the limbs. Seasonal patterns in skin awareness and related help-seeking are likely to be implicated. Targeted patient interventions to increase sun awareness and encourage year-long skin inspection are warranted. [ABSTRACT FROM AUTHOR]

Objectives This study describes changes in the survival of patients with hepatocellular carcinoma (HCC) registered with the Scottish Cancer Registry between 1985 and 2008. Methods Data on patients diagnosed with HCC were extracted from the Scottish Cancer Registry, along with linked data on treatment and risk factors for liver disease. One-, 3- and 5-year relative survival rates were calculated for each time period and a Cox regression model was used to assess the impact of prior admissions on survival. Results The incidence of HCC increased between 1985 and 2008. The proportion of patients with prior alcohol-related admissions rose over the time period studied from 16.0% to 27.1%. Five-year relative survival increased in women between 1985-1989 and 2005-2007 from 0.5% [95% confidence interval (CI) 0.0-3.7] to 10.6% (95% CI 5.2-18.1). In men, 5-year relative survival increased from 0.4% (95% CI 0.2-2.2) to 4.4% (95% CI 1.5-9.9). Regression analysis showed that older age, history of alcohol-related admissions and deprivation were associated with lower survival, and hospitalization for viral hepatitis was associated with higher survival. Conclusions Against the background of an increasing incidence of HCC in Scotland, survival times have increased substantially. [ABSTRACT FROM AUTHOR]

Many countries report a decline in breast cancer incidence among peri- and post-menopausal women following a decline in HRT prescribing. To investigate recent Scottish incidence trends, European age-standardised incidence rates from 1997 to 2005 were stratified by method of first detection, ER status and age group. We developed change point models of the annual age-specific cases for the peri- and post-menopausal age groups and ER status using Poisson regression. In Scotland all HRT categories together show a 32.4% increase in the number of items dispensed in 1993–2000 followed by a striking 61.8% decline by 2007. The incidence rates of screen-detected tumours increased gradually in the 50–64 and 65–74 age groups. For the older age group this increase accelerated after 2003 corresponding to an extension of the age range of screening. For ER positive tumours in the 50–64 age group, age-standardised rates increased 31.5% from 1997 to 2000, followed by a statistically significant decrease of 11.2% by 2005 (change in slope=−0.0943, P <0.0001). We conclude that an overall incidence in the 50–64 age group declined since 2000 reflecting the sudden fall in HRT dispensed items and is largely accounted for by the decrease in ER positive tumour incidence. A longer term decline in ER negative tumours for this age group was pre-existing and is unaffected by the collapse in HRT prescribing. [Copyright &y& Elsevier]

Abstract: To explore possible causes of the poor survival of Scottish lung cancer patients, a retrospective registry-based audit was conducted comparing demography, treatment and survival of 3833 Scottish patients and 2073 from British Columbia (BC). Patients from Scotland were older, had a lower rate of pathological confirmation (74% vs 89%, p <0.001), but more squamous (51% vs 31%, p <0.001) or small cell (SCLC) (18% vs 15%, p =0.005) cancers. Fewer Scottish patients received any treatment (57% vs 66%, p <0.001) or treatment aimed at cure (14% vs 26%, p <0.001). Survival was lower in Scotland (median 3.6 months vs 7.3 months; 5% vs 10% 5-year overall survival, p <0.001), irrespective of treatment intent (potentially curative treatment median survival 20.9 months vs 34.0 months, 5-year overall survival 29% vs 34%, p <0.001; palliative treatment 5.0 months vs 6.3 months (p <0.001) and no treatment 1.4 months vs 2.5 months (p <0.001)). With treatment intent included in a multivariate analysis, the hazard ratio for death for lung cancer patients in Scotland compared to British Columbia was 1.5. Relative survival was higher in BC (38% at 1 year and 12% at 5 years vs 22% and 6%, p <0.001), indicating that life expectancy differences between the two countries was not the explanation. Reduced levels of treatment could only partially explain survival differences and other unknown factors related to lifestyle differences such as diet and smoking, co-morbid diseases, population genetics or cancer biology, may be important and warrant further exploration. [Copyright &y& Elsevier]

Abstract: Background: Lung and upper aero-digestive tract (UADT) cancer risk is associated with socioeconomic inequality (SEI) but the degree of socioeconomic burden by age, tumour subtype, and sex is not known. Methods: We reviewed 216,305 cases excluding non melanoma skin cancer (All Cancer) comprising 37,274 lung; 8216 head and neck; and 6534 oesophageal cancers from 2000 to 2007 classified into anatomical or morphology subtypes. Deprivation was measured using the Scottish Index of Multiple Deprivation and SEI was measured using the Slope Index of Inequality and the Relative Index of Inequality (RII). Analyses were partitioned by 5-year age group and sex. RII was adapted to rank tumour type contribution to All Cancer SEI and to examine subtype by age and sex simultaneously. Rank was defined as proportion of All Cancer SEI. Results: All Cancer SEI was greater for males (RII=0.366; female RII=0.279); the combination of lung and UADT SEI contributed 91% and 81% respectively to All Cancer SEI. For both sexes lung and UADT subtypes showed significant SEI (P <0.001) except oesophageal adenocarcinoma in males (P =0.193); for females, SEI was borderline significant (P =0.048). Although RII rank differed by sex, all lung and larynx subtypes contributed most to All Cancer SEI with RII rank for oral cavity, oesophagus-squamous cell, and oropharynx following. For males 40–44 years, SEI increased abruptly peaking at 55–59 years. For females, SEI gradually peaked 10 years later. In both sexes, the SEI peak preceded peak incidence. Conclusion: SEI in lung and UADT cancers vary greatly by age, tumour subtype and sex; these variations are likely to largely reflect differences between the sexes in risk behaviours which vary by birth cohort and are socioeconomically patterned. [Copyright &y& Elsevier]

Background: More people are surviving a first primary cancer and experiencing a second, different cancer. However, little is known about the diagnostic journeys of patients with second primary cancer (SPC). This study explores the views of patients and general practitioners (GPs) on their experiences of pathways to diagnosis of SPC, including the influence of a previous diagnosis of cancer on symptom appraisal, help-seeking and referral decisions., Methods: Qualitative interviews with patients with a SPC diagnosis and case-linked GP interviews in a Scottish primary care setting. In-depth face to face or telephone interviews were conducted, underpinned by a social constructionist approach. Interviews were transcribed and Braun and Clarke's thematic analysis undertaken. Three analysts from the research team read transcripts and developed the coding framework using QSR NVivo version 10, with input from a fourth researcher. Themes were developed from refined codes and interpreted in the context of existing literature and theory., Results: Interviews were conducted with 23 patients (aged 43-84 years) with a SPC diagnosis, and 7 GPs. Five patient themes were identified: Awareness of SPC, symptom appraisal and help-seeking, pathways to diagnosis, navigating the healthcare system, and impact of SPC. GPs interviews identified: experience and knowledge of SPC and referrals and decision-making., Conclusions: Insights into the pathway to diagnosis of SPC highlights the need for increased awareness of and vigilance for SPC among patients and healthcare providers (HCPs), and emotional support to manage the psychosocial burden.

Objective: Cancer screening should be equitably accessed by all populations. Uptake of colorectal cancer screening was examined using the Scottish Health and Ethnicity Linkage Study that links the Scottish Census 2001 to health data by individual-level self-reported ethnicity and religion., Setting: Data on 1.7 million individuals in two rounds of the Scottish Bowel Cancer Screening Programme (2007-2013) were linked to the 2001 Census using the Scottish Community Health Index number., Main Outcome Measure: Uptake of colorectal cancer screening, reported as age-adjusted risk ratios (RRs) by ethnic group and religion were calculated for men and women with 95% CI., Results: In the first, incidence screening round, compared with white Scottish men, Other White British (RR 109.6, 95% CI 108.8 to 110.3) and Chinese (107.2, 95% CI 102.8 to 111.8) men had higher uptake. In contrast, men of all South Asian groups had lower uptake (Indian RR 80.5, 95% CI 76.1 to 85.1; Pakistani RR 65.9, 95% CI 62.7 to 69.3; Bangladeshi RR 76.6, 95% CI 63.9 to 91.9; Other South Asian RR 88.6, 95% CI 81.8 to 96.1). Comparable patterns were seen among women in all ethnic groups, for example, Pakistani (RR 55.5, 95% CI 52.5 to 58.8). Variation in uptake was also observed by religion, with lower rates among Hindu (RR (95%CI): 78.4 (71.8 to 85.6)), Muslim (69.5 (66.7 to 72.3)) and Sikh (73.4 (67.1 to 80.3)) men compared with the reference population (Church of Scotland), with similar variation among women: lower rates were also seen among those who reported being Jewish, Roman Catholic or with no religion., Conclusions: There are important variations in uptake of bowel cancer screening by ethnic group and religion in Scotland, for both sexes, that require further research and targeted interventions., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Background: We describe temporal trends in breast cancer incidence by molecular subtypes in Scotland because public health prevention programmes, diagnostic and therapeutic services are shaped by differences in tumour biology., Methods: Population-based cancer registry data on 72,217 women diagnosed with incident primary breast cancer from 1997 to 2016 were analysed. Age-standardised rates (ASR) and age-specific incidence were estimated by tumour subtype after imputing the 8% of missing oestrogen receptor (ER) status. Joinpoint regression and age-period-cohort models were used to assess whether significant differences were observed in incidence trends by ER status., Results: Overall, ER-positive tumour incidence increased by 0.4%/year (95% confidence interval (CI): -0.1, 1.0). Among routinely screened women aged 50-69 years, we observed an increase in ASR from 1997 to 2011 (1.6%/year, 95% CI: 1.2-2.1). ER-negative tumour incidence decreased among all ages by 2.5%/year (95% CI: -3.9 to -1.1%) over the study period. Compared with the 1941-1959 birth cohort, women born in 1912-1940 had lower incidence rate ratios (IRR) for ER+ tumours and women born in 1960-1986 had lower IRR for ER- tumours., Conclusions: Future incidence and survival reporting should be monitored by molecular subtypes to inform clinical planning and cancer control programmes.

Aim: The prevalence of hysterectomy is decreasing worldwide. It is not clear whether changes in the population at risk (women with intact uteruses) have contributed to an increased uterine cancer incidence. This study aims to assess the effect of changing trends in hysterectomy prevalence on uterine cancer incidence in Scotland., Methods: The population of women aged ≥25 years with intact uteri was estimated using the estimated hysterectomy prevalence in 1995 and the number of procedures performed in Scotland (1996-2015). Age-standardized uterine cancer incidence was estimated using uncorrected (total) or corrected (adjusted for hysterectomy prevalence) populations as denominators and the number of incident cancers as numerators. Annual percentage change in uterine cancer was estimated., Results: Hysterectomy prevalence fell from 13% to 10% between 1996-2000 and 2011-2015, with the most marked decline (from 20% to 6%) in the 50-54-year age group. After correction for hysterectomy prevalence, age-standardized incidence of uterine cancer increased by 20-22%. Annual percentage change in incidence of uterine cancer remained stable through the study period and was 2.2% (95%CI 1.8-2.7) and 2.1% (95%CI 1.7-2.6) for uncorrected and corrected estimates, respectively., Conclusion: Uterine cancer incidence in Scotland corrected for hysterectomy prevalence is higher than estimates using a total female population as denominator. The annual percentage increase in uterine cancer incidence was stable in both uncorrected and corrected populations despite a declining hysterectomy prevalence. The rise in uterine cancer incidence may thus be driven by other factors, including an ageing population, changing reproductive choices, and obesity., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: PREDICT is a widely used online prognostication and treatment benefit tool for patients with early stage breast cancer. The aim of this study was to conduct an independent validation exercise of the most up-to-date version of the PREDICT algorithm (version 2) using real-world outcomes from the Scottish population of women with breast cancer., Methods: Patient data were obtained for all Scottish Cancer Registry (SCR) records with a diagnosis of primary invasive breast cancer diagnosed in the period between January 2001 and December 2015. Prognostic scores were calculated using the PREDICT version 2 algorithm. External validity was assessed by statistical analysis of discrimination and calibration. Discrimination was assessed by area under the receiver-operator curve (AUC). Calibration was assessed by comparing the predicted number of deaths to the observed number of deaths across relevant sub-groups., Results: A total of 45,789 eligible cases were selected from 61,437 individual records. AUC statistics ranged from 0.74 to 0.77. Calibration results showed relatively close agreement between predicted and observed deaths. The 5-year complete follow-up sample reported some overestimation (11.5%), while the 10-year complete follow-up sample displayed more limited overestimation (1.7%)., Conclusions: Validation results suggest that the PREDICT tool remains essentially relevant for contemporary patients with early stage breast cancer.

Background: Those living in rural areas have poorer cancer outcomes, but current evidence on how rurality impacts melanoma care and survival is contradictory., Aim: To investigate the impact of rurality on setting of melanoma excision and mortality in a whole-nation cohort., Design and Setting: Analysis of linked routine healthcare data comprising every individual in Scotland diagnosed with melanoma, January 2005-December 2013, in primary and secondary care., Method: Multivariate binary logistic regression was used to explore the relationship between rurality and setting of melanoma excision; Cox proportional hazards regression between rurality and mortality was used, with adjustments for key confounders., Results: In total 9519 patients were included (54.3% [ n = 5167] female, mean age 60.2 years [SD 17.5]). Of melanomas where setting of excision was known, 90.3% ( n = 8598) were in secondary care and 8.1% ( n = 771) in primary care. Odds of primary care excision increased with increasing rurality/remoteness. Compared with those in urban areas, those in the most remote rural locations had almost twice the odds of melanoma excision in primary care (adjusted odds ratio [aOR] 1.92; 95% confidence interval [CI] = 1.33 to 2.77). No significant association was found between urban or rural residency and all-cause mortality. Melanoma-specific mortality was significantly lower in individuals residing in accessible small towns than in large urban areas (adjusted hazards ratio [HR] 0.53; 95% CI = 0.33 to 0.87) with no trend towards poorer survival with increasing rurality., Conclusion: Patients in Scottish rural locations were more likely to have a melanoma excised in primary care. However, those in rural areas did not have significantly increased mortality from melanoma. Together these findings suggest that current UK melanoma management guidelines could be revised to be more realistic by recognising the role of primary care in the prompt diagnosis and treatment of those in rural locations., (© British Journal of General Practice 2018.)

Study Question: What is the impact of cancer in females aged ≤39 years on subsequent chance of pregnancy?, Summary Answer: Cancer survivors achieved fewer pregnancies across all cancer types, and the chance of achieving a first pregnancy was also lower., What Is Known Already: The diagnosis and treatment of cancer in young females may be associated with reduced fertility but the true pregnancy deficit in a population is unknown., Study Design, Size, Duration: We performed a retrospective cohort study relating first incident cancer diagnosed between 1981 and 2012 to subsequent pregnancy in all female patients in Scotland aged 39 years or less at cancer diagnosis (n = 23 201). Pregnancies were included up to end of 2014. Females from the exposed group not pregnant before cancer diagnosis (n = 10 271) were compared with general population controls matched for age, deprivation quintile and year of diagnosis., Participants/materials, Setting, Methods: Scottish Cancer Registry records were linked to hospital discharge records to calculate standardized incidence ratios (SIR) for pregnancy, standardized for age and year of diagnosis. Linkage to death records was also performed. We also selected women from the exposed group who had not been pregnant prior to their cancer diagnosis who were compared with a matched control group from the general population. Additional analyses were performed for breast cancer, Hodgkin lymphoma, leukaemia, cervical cancer and brain/CNS cancers., Main Results and the Role of Chance: Cancer survivors achieved fewer pregnancies: SIR 0.62 (95% CI: 0.60, 0.63). Reduced SIR was observed for all cancer types. The chance of achieving a first pregnancy was also lower, adjusted hazard ratio = 0.57 (95% CI: 0.53, 0.61) for women >5 years after diagnosis, with marked reductions in women with breast, cervical and brain/CNS tumours, and leukaemia. The effect was reduced with more recent treatment period overall and in cervical cancer, breast cancer and Hodgkin lymphoma, but was unchanged for leukaemia or brain/CNS cancers. The proportion of pregnancies that ended in termination was lower after a cancer diagnosis, and the proportion ending in live birth was higher (78.7 vs 75.6%, CI of difference: 1.1, 5.0)., Limitations, Reasons for Caution: Details of treatments received were not available, so the impact of specific treatment regimens on fertility could not be assessed. Limited duration of follow-up was available for women diagnosed in the most recent time period., Wider Implications of the Findings: This analysis provides population-based quantification by cancer type of the effect of cancer and its treatment on subsequent pregnancy across the reproductive age range, and how this has changed in recent decades. The demonstration of a reduced chance of pregnancy across all cancer types and the changing impact in some but not other common cancers highlights the need for appropriate fertility counselling of all females of reproductive age at diagnosis., Study Funding/competing Interest(s): This study was funded by NHS Lothian Cancer and Leukaemia Endowments Fund. Part of this work was undertaken in the MRC Centre for Reproductive Health which is funded by the MRC Centre grant MR/N022556/1. RAA has participated in Advisory Boards and/or received speaker's fees from Beckman Coulter, IBSA, Merck and Roche Diagnostics. He has received research support from Roche Diagnostics, Ansh labs and Ferring. The other authors have no conflicts to declare.

Background: Place of cancer death varies ethnically and internationally. Palliative care reviews highlight limited ability to demonstrate equal access due to incomplete or unreliable ethnicity data., Aim: To establish place of cancer death by ethnicity and describe patient characteristics., Design: We linked census, hospital episode and mortality data for 117 467 persons dying of cancer, 2001-2009. With White Scottish population as reference, prevalence ratios (PR), 95% CIs and p values of death in hospital, home or hospice adjusted for sex and age were calculated by ethnic group., Results: White Scottish group and minority ethnic groups combined constituted 91% and 0.4% of cancer deaths, respectively. South Asian, Chinese and African Origin patients were youngest at death (66, 66 and 65.9 years). Compared with the Scottish White reference, the White Irish (1.15 (1.10 to 1.22), p<0.0001) and Other White British (1.07 (1.02 to 1.12), p=0.003) groups were more likely to die at home. Generally, affluent Scottish White patients were less likely to die in hospital and more likely to die at home or in a hospice regardless of socioeconomic indicator used., Conclusions: Cancer deaths occur most often in hospital (52.3%) for all ethnic groups. Regardless of the socioeconomic indicator used, more affluent Scottish White patients were less likely to die in hospital; existing socioeconomic indicators detected no clear trend for the non-White population. Regardless of ethnic group, significant work is required to achieve more people dying at home or the setting of their choice., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Objective: Colorectal cancer (CRC) has a substantial heritable component. Common genetic variation has been shown to contribute to CRC risk. A study was conducted in a large multi-population study to assess the feasibility of CRC risk prediction using common genetic variant data combined with other risk factors. A risk prediction model was built and applied to the Scottish population using available data., Design: Nine populations of European descent were studied to develop and validate CRC risk prediction models. Binary logistic regression was used to assess the combined effect of age, gender, family history (FH) and genotypes at 10 susceptibility loci that individually only modestly influence CRC risk. Risk models were generated from case-control data incorporating genotypes alone (n=39,266) and in combination with gender, age and FH (n=11,324). Model discriminatory performance was assessed using 10-fold internal cross-validation and externally using 4187 independent samples. The 10-year absolute risk was estimated by modelling genotype and FH with age- and gender-specific population risks., Results: The median number of risk alleles was greater in cases than controls (10 vs 9, p<2.2 × 10(-16)), confirmed in external validation sets (Sweden p=1.2 × 10(-6), Finland p=2 × 10(-5)). The mean per-allele increase in risk was 9% (OR 1.09; 95% CI 1.05 to 1.13). Discriminative performance was poor across the risk spectrum (area under curve for genotypes alone 0.57; area under curve for genotype/age/gender/FH 0.59). However, modelling genotype data, FH, age and gender with Scottish population data shows the practicalities of identifying a subgroup with >5% predicted 10-year absolute risk., Conclusion: Genotype data provide additional information that complements age, gender and FH as risk factors, but individualised genetic risk prediction is not currently feasible. Nonetheless, the modelling exercise suggests public health potential since it is possible to stratify the population into CRC risk categories, thereby informing targeted prevention and surveillance., Competing Interests: The authors report no conflicts of interest with respect to the work presented in this paper.

Objective: To assess the risk of skin cancer in persons treated with neonatal phototherapy (NNPT) for jaundice., Design: Retrospective cohort study., Setting: Grampian Region, Scotland, UK., Data Source: Aberdeen Maternity and Neonatal Databank. NNPT exposure was abstracted from paper records spanning 1976-1990. Follow-up to 31 December 2006 by linkage to cancer registration and mortality records., Main Outcome Measures: Incidence ratios, standardised for age, sex, calendar period and socio-economic position., Results: After excluding neonatal deaths (n=435), the cohort comprised 77,518 persons. 5868 Received NNPT, providing 138,000 person-years at risk (median follow-up, 24 years). Two cases of melanoma occurred in persons exposed to NNPT versus 16 cases in unexposed persons, yielding a standardised incidence ratio of 1.40 (95% CI, 0.17 to 5.04; p=0.834). No cases of squamous cell or basal cell carcinoma of skin were observed in exposed persons., Conclusions: Although there is no statistically significant evidence of an excess risk of skin cancer following NNPT, limited statistical power and follow-up duration mean it is not possible categorically to rule out an effect. However, taken in conjunction with the results of the only other study to investigate risk of melanoma following NNPT, evidence available so far does not suggest a major cause for concern.

The aim of this study was to present detailed population-based survival estimates for patients with a rectal adenocarcinoma, using cancer register data supplemented with clinical data. Based on cancer register data, differences in rectal cancer survival have been reported between countries in Europe. Variation in the distribution of stage at diagnosis, initial therapy including surgical technique, and comorbidity are possible explanatory factors. Adenocarcinomas in the rectum, diagnosed in 1997 and identified in the national cancer registries in the Nordic countries and Scotland were included. Age standardized 5-year relative survival and multiplicative regression models for the relative excess mortality were calculated. 3888 patients were included in the survival study. Men in Denmark, Finland and Iceland had lower 5-year relative survival and poorer stage distribution compared to Norway, Sweden and Scotland. Danish men had the highest rate of excess deaths in the first six months after diagnosis. Stage adjusted, the elevated relative excess mortality decreased and after six months the excess mortality rates were the same in all countries. The poor 5-year relative survival in Danish men was mainly due to a high excess rate of death during the first six months after diagnosis. The low survival in Finland and Iceland was not in accordance with other periods. For both countries this may be explained by random variation due to small numbers. The study emphasizes the need for high quality and detailed data in order to understand international survival differences, and cautions comparisons between large national samples and those of smaller areas.

Introduction: Lung cancer survival in Scotland has historically been poor but many changes to the lung cancer services have been introduced and this study was conducted to investigate the impact of these changes on treatment and survival., Methods: Data obtained from the Scottish Cancer Registry, South-East Scotland Cancer Network audit and Edinburgh Cancer Centre database were used to conduct a comparison of the management and outcomes of lung cancer patients from South-East Scotland diagnosed in 1995 and in 2002., Results: Data on 971 patients diagnosed in 2002 and 927 in 1995 were analyzed and demonstrated that though the use of treatment overall had not changed (62% in 2002 versus 63% in 1995) the use of potentially curative radiotherapy (15 versus 5% chi p < 0.001) and chemotherapy for non-small cell lung cancer (18 versus 7% chi p < 0.001) had increased, but not resection rates (11 versus 10%). The use of palliative radiotherapy declined (38% versus 31% chi p < 0.001). Patients diagnosed in 2002 had an adjusted hazard of death of 0.7 (95% confidence interval, 0.6-0.8) compared with 1995, with median survival from date of diagnosis of 5.2 versus 4.1 month and 2 year overall survival 15 versus 11% (log rank p = 0.004). Localized disease and younger age were also associated with a reduced hazard of death., Conclusions: Patients diagnosed with lung cancer in Scotland in 2002 had a reduced hazard of death and improved survival compared with 1995. It is hypothesized that this was due in part to improvements in service organization and increased use of treatments likely to increase survival.

To investigate the laterality of cutaneous melanoma (ICD-10 C43), we obtained data spanning the period of diagnosis 1998-2003 from six population-based cancer registries: New South Wales, Australia; England; Finland; The Netherlands; Scotland; and the Surveillance Epidemiology and End Results (SEER) Program of the United States of America (restricted to 'White' race category only). For cases with laterality recorded, the overall ratios of left- to right-sided tumours were calculated. We found that left to right ratios were consistently greater than 1.00, ranging from 1.08 (New South Wales, Australia and US SEER 'White') to 1.18 (Scotland), with an overall ratio for all registries combined of 1.10 (95% confidence interval 1.08-1.11). There were no statistically significant differences by sex or age group for all sub-sites combined, or for upper limb or lower limb melanomas. The excess of left-sided tumours seems unlikely to be explained by chance or recording bias. The most likely explanations would appear to be either differences in sun exposure and/or asymmetry of melanocyte distribution or characteristics arising at the time of embryological development.

Objective: The incidence of thyroid cancer is increasing in several countries. The aim was to investigate trends in the incidence and mortality of thyroid cancer in Scotland, where thyroid cancer is relatively uncommon, between 1960 and 2002., Design: Descriptive epidemiological study., Methods: Thyroid cancer registrations between 1960 and 2000 were obtained from the Scottish Cancer Registry. Mortality data (1960-2002) and population estimates were supplied by the Registrar General for Scotland. Incidence and mortality data are expressed as age-specific rates and European age-standardized rates (EASRs)., Results: Thyroid cancer was three times more common in females than in males and was more common in older than younger age groups. Between 1960 and 2000, the annual EASR of thyroid cancer increased from 1.76 to 3.54 per 100,000 for females (P < 0.001) and from 0.83 to 1.25 per 100,000 in males (P < 0.001). The overall thyroid cancer increase between 1975 and 2000 was primarily caused by an increase in papillary thyroid cancer, particularly over the most recent decade. The incidence of follicular thyroid cancer also increased while the incidence of anaplastic and medullary thyroid cancer did not change significantly. Mortality from thyroid cancer fell progressively between 1960 and 2002. EASR for females decreased from 1.05 to 0.28 (P < 0.001) and in males from 0.73 to 0.34 (P < 0.001). For both sexes, in general, survival at 1-, 5- and 10-year follow-up intervals from diagnosis improved steadily over the study period. In both females and males, survival from thyroid cancer was better if the diagnosis was made under the age of 50 years., Conclusions: Thyroid cancer incidence has increased in Scotland over the past 40 years. This is accompanied by a change in the distribution of histological type with a particular increase in papillary carcinoma. The reasons for this may relate partly to changes in clinical practice and histological criteria. Falling mortality in the face of increasing incidence reflects improvements in survival, which should improve further with the introduction and implementation of standardized treatment protocols.

In collaboration with the network of genetics clinics in Scotland, a brief questionnaire was designed to gather data prospectively about the impact of information arising from pedigree research provided by Scottish Cancer Registry personnel. Pedigree research in Scotland is facilitated by access to public records of births, deaths, marriages, and historic census returns up to 1901, and enables the construction of accurate and extensive family pedigrees encompassing generations beyond the detailed knowledge of the proband. Subject to existing confidentiality guidelines, linkage of these pedigrees to cancer registration records results in a more comprehensive family history including the age at diagnosis of any cancer, multiple primary cancers, and cancers unreported from death certificates. Of 454 requests for pedigree research completed between 1 April 2002 and 31 March 2003, questionnaires were returned for 425 (94%). The information fed back to genetics clinics led to changes in family history, risk categorisation, and management in 41%, 30%, and 23% of cases, respectively. Management advice altered in both directions, that is, to institute active follow-up and surveillance of clinic attendees and their relatives where none was previously envisaged, and viceversa. The interests of current and future generations of patients concerned about their familial risk of cancer will be served by measures which enable cancer registries to collect data that are as accurate and complete as possible.

Objective: To quantify risks for cause-specific mortality among hospitalized patients with rheumatoid arthritis (RA), juvenile chronic arthritis (JCA), and 4 other rheumatic conditions in a nationwide, population based cohort over a 20 year period., Methods: All subjects were identified from Scottish hospital inpatient records from 1981 to 2000 and were followed up by computer linkage to the national registry of deaths. Expected mortality was calculated from national mortality rates and was related to the observed incidence by the standardized mortality ratio (SMR) and the corresponding 95% confidence interval (95% CI)., Results: Overall mortality was elevated in each of the 6 rheumatic conditions examined, most notably in JCA (males: SMR 3.4, 95% CI 2.0,5.5; females: SMR 5.1, 95% CI 3.2,7.8). Among patients with RA, there was an increased risk for death in all International Classification of Disease chapters other than those relating to mental disorders. Specific causes of death with an increased risk for subjects with RA included lung cancer [males: 1.4 (1.2,1.5); females: 1.6 (1.5,1.8)], hematopoietic malignancies [M: 1.8 (1.4,2.3); F: 2.0 (1.7,2.3)], coronary artery disease (CAD) [M: 1.6 (1.5,1.7); F: 1.95 (1.9,2.0)], respiratory infections [M: 1.9 (1.7,2.2); F: 2.4 (2.3,2.6)], chronic obstructive pulmonary disease [M: 1.8 (1.6,2.0); F: 2.1 (1.9,2.3)], and renal failure [M: 3.1 (2.5,3.9); F: 3.5 (3.0,4.0)]. Conversely, RA subjects were less likely to die from gastrointestinal tract malignancies [M: 0.82 (0.7,1.0); F: 0.8 (0.7,0.9)]., Conclusion: Population studies for primary data collection are required to extend our knowledge about the underlying mechanisms of early mortality in patients with rheumatic conditions.

Lung cancer is a major public health concern worldwide. Our study aims to examine trends in incidence of lung cancer in Scotland during 1959-97 and by histologic type for 1975-97. In Scotland, lung cancer is the most commonly diagnosed cancer in men and is the second most commonly diagnosed cancer in women. Due to poor survival rates, trends in incidence and mortality display similar patterns. Within the United States and many parts of Europe, falls in the incidence of squamous cell carcinoma have occurred whilst the incidence of adenocarcinoma has increased. Data were extracted from the Scottish Cancer Registry. Trends in incidence were examined by standardising rates to the World Standard Population. Age-specific rates were examined by year of diagnosis and mid year of birth. In Scotland the incidence of lung cancer in men has fallen since the late 1970s, whereas incidence in women has continued to increase. Incidence rates of adenocarcinoma have increased over time but squamous cell carcinoma remains the predominant type of lung cancer in Scotland. The quality of lung cancer registration data has improved over time, although a large proportion of lung cancers (>20%) are not microscopically verified. Changes in histologic types are unlikely to be solely due to diagnostic advances. Rates of adenocarcinoma have increased steadily over time, and this may be due to changes in cigarette design during the 1950s., (Copyright 2002 Wiley-Liss, Inc.)