Diagnostic routes and time intervals for ovarian cancer in nine international jurisdictions; findings from the International Cancer Benchmarking Partnership (ICBP).

BACKGROUND: International Cancer Benchmarking Partnership Module 4 reports the first international comparison of ovarian cancer (OC) diagnosis routes and intervals (symptom onset to treatment start), which may inform previously reported variations in survival and stage. METHODS: Data were collated from 1110 newly diagnosed OC patients aged >40 surveyed between 2013 and 2015 across five countries (51-272 per jurisdiction), their primary-care physicians (PCPs) and cancer treatment specialists, supplement by treatment records or clinical databases. Diagnosis routes and time interval differences using quantile regression with reference to Denmark (largest survey response) were calculated. RESULTS: There were no significant jurisdictional differences in the proportion diagnosed with symptoms on the Goff Symptom Index (53%; P = 0.179) or National Institute for Health and Care Excellence NG12 guidelines (62%; P = 0.946). Though the main diagnosis route consistently involved primary-care presentation (63-86%; P = 0.068), onward urgent referral rates varied significantly (29-79%; P < 0.001). In most jurisdictions, diagnostic intervals were generally shorter and other intervals, in particular, treatment longer compared to Denmark. CONCLUSION: This study highlights key intervals in the diagnostic pathway where improvements could be made. It provides the opportunity to consider the systems and approaches across different jurisdictions that might allow for more timely ovarian cancer diagnosis and treatment.

Breast cancer incidence and survival in Scotland by socio-economic deprivation and tumour subtype.

BACKGROUND: Women from socio-economically deprived areas are less likely to develop and then to survive breast cancer (BC). Whether associations between deprivation and BC incidence and survival differ by tumour molecular subtypes and mode of detection in Scotland are unknown. METHODS: Data consisted of 62,378 women diagnosed with invasive BC between 2000 and 2016 in Scotland. Incidence rates and time trends were calculated for oestrogen receptor positive (ER+) and negative (ER-) tumours and stratified by the Scottish Index of Multiple Deprivation (SIMD) quintiles and screening status. SIMD is an area-based measure derived across seven domains: income, employment, education, health, access to services, crime and housing. We calculated adjusted hazard ratios (aHR [95% confidence intervals]) for BC death by immunohistochemical surrogates of molecular subtypes for the most versus the least deprived quintile. We adjusted for mode of detection and other confounders. RESULTS: In Scotland, screen-detected ER+tumour incidence increased over time, particularly in the least deprived quintile [Average Annual Percentage Change (AAPC) = 2.9% with 95% CI from 1.2 to 4.7]. No marked differences were observed for non-screen-detected ER+tumours or ER- tumours by deprivation. BC mortality was higher in the most compared to the least deprived quintile irrespective of ER status (aHR = 1.29 [1.18, 1.41] for ER+ and 1.27 [1.09, 1.47] for ER- tumours). However, deprivation was associated with significantly higher mortality for luminal A and HER2-enriched tumours (aHR = 1.46 [1.13, 1.88] and 2.10 [1.23, 3.59] respectively) but weaker associations for luminal B and TNBC tumours that were not statistically significant. CONCLUSIONS: Deprivation is associated with differential BC incidence trends for screen-detected ER+tumours and with higher mortality for select tumour subtypes. Future efforts should evaluate factors that might be associated with reduced survival in deprived populations and monitor progress stratified by tumour subtypes and mode of detection.

Patient and GP experiences of pathways to diagnosis of a second primary cancer: a qualitative study.

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.

Distinct temporal trends in breast cancer incidence from 1997 to 2016 by molecular subtypes: a population-based study of Scottish cancer registry data.

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.

Quality of life in men living with advanced and localised prostate cancer in the UK: a population-based study.

BACKGROUND: Little is known about the health-related quality of life (HRQOL) of men living with advanced prostate cancer. We report population-wide functional outcomes and HRQOL in men with all stages of prostate cancer and identify implications for health-care delivery. METHODS: For this population-based study, men in the UK living 18-42 months after diagnosis of prostate cancer were identified through cancer registration data. A postal survey was administered, which contained validated measures to assess functional outcomes (urinary incontinence, urinary irritation and obstruction, bowel, sexual, and vitality and hormonal function), measured with the Expanded Prostate Cancer Index Composite short form (EPIC-26), plus questions about use of interventions for sexual dysfunction) and generic HRQOL (assessed with the 5-level EuroQol five dimensions questionnaire [EQ-5D-5L] measuring mobility, self-care, usual activities, pain or discomfort, and anxiety or depression, plus a rating of self-assessed health). Log-linear and binary logistic regression models were used to compare functional outcomes and HRQOL across diagnostic stages and self-reported treatment groups. Each model included adjustment for age, socioeconomic deprivation, and number of other long-term conditions. FINDINGS: 35 823 (60·8%) of 58 930 men responded to the survey. Disease stage was known for 30 733 (85·8%) of 35 823 men; 19 599 (63·8%) had stage I or II, 7209 (23·4%) stage III, and 3925 (12·8%) stage IV disease. Mean adjusted EPIC-26 domain scores were high, indicating good function, except for sexual function, for which scores were much lower. Compared with men who did not receive androgen deprivation therapy, more men who received the therapy reported moderate to big problems with hot flushes (30·7% [95% CI 29·8-31·6] vs 5·4% [5·0-5·8]), low energy (29·4% [95% CI 28·6-30·3] vs 14·7% [14·2-15·3]), and weight gain (22·5%, 21·7-23·3) vs 6·9% [6·5-7·3]). Poor sexual function was common (81·0%; 95% CI 80·6-81·5), regardless of stage, and more than half of men (n=18 782 [55·8%]) were not offered any intervention to help with this condition. Overall, self-assessed health was similar in men with stage I-III disease, and although slightly reduced in those with stage IV cancer, 23·5% of men with metastatic disease reported no problems on any EQ-5D dimension. INTERPRETATION: Men diagnosed with advanced disease do not report substantially different HRQOL outcomes to those diagnosed with localised disease, although considerable problems with hormonal function and fatigue are reported in men treated with androgen deprivation therapy. Sexual dysfunction is common and most men are not offered helpful intervention or support. Service improvements around sexual rehabilitation and measures to reduce the effects of androgen deprivation therapy are required. FUNDING: The Movember Foundation, in partnership with Prostate Cancer UK.

Chemotherapy effectiveness in trial-underrepresented groups with early breast cancer: A retrospective cohort study.

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.

Occult blood in faeces is associated with all-cause and non-colorectal cancer mortality.

OBJECTIVE: An association between detectable faecal haemoglobin (f-Hb) and both the risk of death from colorectal cancer (CRC) and all-cause mortality has been reported. We set out to confirm or refute this observation in a UK population and to explore the association between f-Hb, as indicated by a positive guaiac faecal occult blood test (gFOBT) result, and different causes of death. DESIGN: All individuals (134 192) who participated in gFOBT screening in Tayside, Scotland between 29/03/2000 and 29/03/2016 were studied by linking their test result (positive or negative) with mortality data from the National Records of Scotland database and following to 30/03/2016. RESULTS: Those with a positive test result (n=2714) had a higher risk of dying than those with a negative result, from CRC: HR 7.79 (95% CI 6.13 to 9.89), p<0.0001, (adjusted for, gender, age, deprivation quintile and medication that can cause bleeding) and all non-CRC causes: HR 1.58 (95% CI 1.45 to 1.73), p<0·0001.· In addition, f-Hb detectable by gFOBT was significantly associated with increased risk of dying from circulatory disease, respiratory disease, digestive diseases (excluding CRC), neuropsychological disease, blood and endocrine disease and non-CRC. CONCLUSION: The presence of detectable f-Hb is associated with increased risk of death from a wide range of causes.

Independent validation of the PREDICT breast cancer prognosis prediction tool in 45,789 patients using Scottish Cancer Registry data.

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.

Investigation of the international comparability of population-based routine hospital data set derived comorbidity scores for patients with lung cancer.

INTRODUCTION: The International Cancer Benchmarking Partnership (ICBP) identified significant international differences in lung cancer survival. Differing levels of comorbid disease across ICBP countries has been suggested as a potential explanation of this variation but, to date, no studies have quantified its impact. This study investigated whether comparable, robust comorbidity scores can be derived from the different routine population-based cancer data sets available in the ICBP jurisdictions and, if so, use them to quantify international variation in comorbidity and determine its influence on outcome. METHODS: Linked population-based lung cancer registry and hospital discharge data sets were acquired from nine ICBP jurisdictions in Australia, Canada, Norway and the UK providing a study population of 233 981 individuals. For each person in this cohort Charlson, Elixhauser and inpatient bed day Comorbidity Scores were derived relating to the 4-36 months prior to their lung cancer diagnosis. The scores were then compared to assess their validity and feasibility of use in international survival comparisons. RESULTS: It was feasible to generate the three comorbidity scores for each jurisdiction, which were found to have good content, face and concurrent validity. Predictive validity was limited and there was evidence that the reliability was questionable. CONCLUSION: The results presented here indicate that interjurisdictional comparability of recorded comorbidity was limited due to probable differences in coding and hospital admission practices in each area. Before the contribution of comorbidity on international differences in cancer survival can be investigated an internationally harmonised comorbidity index is required.

The impact of cancer on subsequent chance of pregnancy: a population-based analysis.

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.

Urinary, bowel and sexual health in older men from Northern Ireland.

OBJECTIVES: To provide data on the prevalence of urinary, bowel and sexual dysfunction in Northern Ireland (NI), to act as a baseline for studies of prostate cancer outcomes and to aid service provision within the general population. SUBJECTS AND METHODS: A cross-sectional postal survey of 10 000 men aged ≥40 years in NI was conducted and age-matched to the distribution of men living with prostate cancer. The EuroQoL five Dimensions five Levels (EQ-5D-5L) and 26-item Expanded Prostate Cancer Composite (EPIC-26) instruments were used to enable comparisons with prostate cancer outcome studies. Whilst representative of the prostate cancer survivor population, the age-distribution of the sample differs from the general population, thus data were generalised to the NI population by excluding those aged 40-59 years and applying survey weights. Results are presented as proportions reporting problems along with mean composite scores, with differences by respondent characteristics assessed using chi-squared tests, analysis of variance, and multivariable log-linear regression. RESULTS: Amongst men aged ≥60 years, 32.8% reported sexual dysfunction, 9.3% urinary dysfunction, and 6.5% bowel dysfunction. In all, 38.1% reported at least one problem and 2.1% all three. Worse outcome was associated with increasing number of long-term conditions, low physical activity, and higher body mass index (BMI). Urinary incontinence, urinary irritation/obstruction, and sexual dysfunction increased with age; whilst urinary incontinence, bowel, and sexual dysfunction were more common among the unemployed. CONCLUSION: These data provide an insight into sensitive issues seldom reported by elderly men, which result in poor general health, but could be addressed given adequate service provision. The relationship between these problems, raised BMI and low physical activity offers the prospect of additional health gain by addressing public health issues such as obesity. The results provide essential contemporary population data against which outcomes for those living with prostate cancer can be compared. They will facilitate greater understanding of the true impact of specific treatments such as surgical interventions, pelvic radiation or androgen-deprivation therapy.

A cancer geography paradox? Poorer cancer outcomes with longer travelling times to healthcare facilities despite prompter diagnosis and treatment: a data-linkage study.

BACKGROUND: Rurality and distance from cancer treatment centres have been shown to negatively impact cancer outcomes, but the mechanisms remain obscure. METHODS: We analysed the impact of travel time to key healthcare facilities and mainland/island residency on the cancer diagnostic pathway (treatment within 62 days of referral, and within 31 days of diagnosis) and 1-year mortality using a data-linkage study with 12 339 patients. RESULTS: After controlling for important confounders, mainland patients with more than 60 min of travelling time to their cancer treatment centre ((OR 1.42; 95% CI 1.25-1.61) and island dwellers (OR 1.32; 95% CI 1.09-1.59) were more likely to commence cancer treatment within 62 days of general practitioner (GP) referral and within 31 days of their cancer diagnosis compared with those living within 15 min. Island-dweller patients were more likely to have their diagnosis and treatment started on the same or next day (OR 1.72; 95% CI 1.31-2.25). Increased travelling time to a cancer treatment centre was associated with increased mortality to 1 year (30-59 min (HR 1.21; 95% CI 1.05-1.41), >60 min (HR 1.18; 95% CI 1.03-1.36), island dweller (HR 1.17; 95% CI 0.97-1.41). CONCLUSIONS: Island dwelling and greater mainland travel burden was associated with more rapid cancer diagnosis and treatment following GP referral even after adjustment for advanced disease; however, these patients also experienced a survival disadvantage compared with those living nearer. Cancer services may need to be better configured to suit the different needs of dispersed populations.

Worldwide Inverse Association between Gastric Cancer and Esophageal Adenocarcinoma Suggesting a Common Environmental Factor Exerting Opposing Effects.

OBJECTIVES: The incidence of esophageal adenocarcinoma (EAC) is increasing while adenocarcinoma of the stomach is decreasing. We have investigated whether the incidences of these two cancers and their time trends might be inversely related pointing to a common environmental factor exerting opposite effects on these cancers. METHODS: For cross-sectional analyses data were abstracted from "Cancer Incidence in Five Continents" (CI5) Volume X and GLOBOCAN 2012. Relevant ICD-10 codes were used to locate esophageal and gastric cancers anatomically, and ICD-O codes for the histological diagnosis of EAC. For longitudinal analyses, age standardized rates (ASRs) of EAC and total gastric cancer (TGC) were extracted from CI5C-Plus. RESULTS: Estimated (2012) ASRs were available for 51 countries and these showed significant negative correlations between EAC and both TGC (males: correlation coefficient (CC)=-0.38, P=0.006, females: CC=-0.41, P=0.003) and non-cardia gastric cancer rates (males: CC=-0.41, P=0.003 and females: CC=-0.43, P=0.005). Annual incidence trends were analyzed for 38 populations through 1989-2007 and showed significant decreases for TGC in 89% and increases for EAC in 66% of these, with no population showing a fall in the latter. Significant negative correlation between the incidence trends of the two cancers was observed in 27 of the 38 populations over the 19-50 years of available paired data. Super-imposition of the longitudinal and cross-sectional data indicated that populations with a current high incidence of EAC and low incidence of gastric cancer had previously resembled countries with a high incidence of gastric cancer and low incidence of EAC. CONCLUSIONS: The negative association between gastric cancer and EAC in both current incidences and time trends is consistent with a common environmental factor predisposing to one and protecting from the other.

Cumulative impact of common genetic variants and other risk factors on colorectal cancer risk in 42,103 individuals.

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.

Increasing survival of hepatocellular carcinoma patients in Scotland: a review of national cancer registry data.

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.

Second primary malignancies among women with uterine sarcoma.

OBJECTIVE: Uterine sarcomas (US) are rare malignancies with unclear aetiology. Studies on uterine sarcomas in the setting of second primary malignant tumours can provide clues to aetiology and identify side effects of different treatments. METHODS: A cohort of 8606 cases of US was extracted from the data from 13 cancer registries and followed for second primary cancers within the period 1943-2000. Standardized incidence ratios (SIRs) were calculated, and Poisson regression analyses were performed. RESULTS: There were 499 cancer cases observed after a first diagnosis of US (SIR 1.26, 95%CI 1.16-1.38). SIRs were elevated for cancers of the mouth and pharynx (2.16, 95%CI 1.15-3.69), colorectum (1.60, 95%CI 1.28-1.98), lung (1.73, 95%CI 1.27-2.29), breast (1.25, 95%CI 1.05-1.49), urinary bladder (1.74, 95%CI 1.02-2.79), kidney (2.00, 95%CI 1. 24-3.06), thyroid gland (2.74, 95%CI 1.42-4.79), and soft tissue sarcoma (5.23, 95%CI 2.51-9.62). The risk of breast cancer increased along with increasing age of US diagnosis (p trend 0.040). The risk of kidney cancer increased along with decreasing age of US diagnosis (p trend 0.004) and short time since the US diagnosis (p trend 0.018). CONCLUSIONS: Our study demonstrated increased risk of certain cancers following a diagnosis of US. The elevated risk for breast cancer may indicate shared hormonal aetiology, while the increased risk of colorectal and bladder cancers after US may be caused by radiation therapy of US. The clustering of smoking-related cancers after US is worth exploring in the future.

Cardiovascular disease and air pollution in Scotland: no association or insufficient data and study design?

BACKGROUND: Coronary heart disease and stroke are leading causes of mortality and ill health in Scotland, and clear associations have been found in previous studies between air pollution and cardiovascular disease. This study aimed to use routinely available data to examine whether there is any evidence of an association between short-term exposure to particulate matter (measured as PM10, particles less than 10 micrograms per cubic metre) and hospital admissions due to cardiovascular disease, in the two largest cities in Scotland during the years 2000 to 2006. METHODS: The study utilised an ecological time series design, and the analysis was based on overdispersed Poisson log-linear models. RESULTS: No consistent associations were found between PM10 concentrations and cardiovascular hospital admissions in either of the cities studied, as all of the estimated relative risks were close to one, and all but one of the associated 95% confidence intervals contained the null risk of one. CONCLUSIONS: This study suggests that in small cities, where air quality is relatively good, then either PM10 concentrations have no effect on cardiovascular ill health, or that the routinely available data and the corresponding study design are not sufficient to detect an association.

Second malignancies after childhood noncentral nervous system solid cancer: Results from 13 cancer registries.

Children diagnosed with noncentral nervous system solid cancers (NCNSSC) experience several adverse late effects, including second malignant neoplasm. The aim of our study was to assess the risk of specific second malignancies after a childhood NCNSSC. Diagnosis and follow-up data on 10,988 cases of NCNSSC in children (0-14 years) were obtained from 13 registries. Standardized incidence ratios (SIRs) with 95% confidence intervals (CI) and cumulative incidence of second malignancies were computed. We observed 175 second malignant neoplasms, yielding a SIR of 4.6, 95% CI: 3.9-5.3. When considering second cancers with at least 10 occurrences, highest relative risks were found for second malignant bone tumors (SIR = 26.4, 16.6-40.0), soft tissue sarcomas (SIR = 14.1, 6.7-25.8) and myeloid leukemia (SIR = 12.7, 6.3-22.8). Significant increased risks for all malignancies combined were observed after sympathetic nervous system tumors (SIR = 11.4, 5.2-21.6), retinoblastomas (SIR = 7.3, 5.4-9.8), renal tumors (SIR = 5.7, 3.8-8.0), malignant bone tumors (SIR = 5.6, 3.7-8.2), soft tissue sarcomas (SIR = 4.7, 3.2-6.8), germ-cell, trophoblastic and other gonadal neoplasms (SIR = 2.5, 1.1-4.9), carcinomas and other malignant epithelial neoplasms (SIR = 2.2, 1.4-3.3). The highest risk of a second malignancy of any type occurred 5 to 9 years after NCNSSC (SIR = 9.9, 6.8-13.9). The cumulative incidence of second malignancies 10 years after the first neoplasm was eight times higher among NCNSSC survivors than in the general population, with the absolute difference between observed and expected cumulative incidence still increasing after 50 years of follow-up. Children who survived a NCNSSC experience a large increased risk of developing a new malignancy, even many years after their initial diagnosis.

High constant incidence rates of second primary cancers of the head and neck: a pooled analysis of 13 cancer registries.

Scanty data are available on the incidence (i.e., the absolute risk) of second cancers of the head and neck (HN) and its pattern with age. We investigated this issue using data from a multicentric study of 13 population-based cancer registries from Europe, Canada, Australia and Singapore for the years 1943-2000. A total of 99,257 patients had a first primary HN cancer (15,985 tongue, 22,378 mouth, 20,758 pharyngeal, and 40,190 laryngeal cancer), contributing to 489,855 person-years of follow-up. A total of 1,294 of the patients (1.3%) were diagnosed with second HN cancers (342 tongue, 345 mouth, 418 pharynx and 189 larynx). Male incidence rates of first HN cancer steeply increased from 0.68/100,000 at age 30-34 to 46.2/100,000 at age 70-74, and leveled off at older age; female incidence increased from 0.50/100,000 at age 30-34 to 16.5/100,000 at age 80-84. However, age-specific incidence of second HN cancers after a first HN cancer in men was around 200-300/100,000 between age 40-44 and age 70-74 and tended to decline at subsequent ages (150/100,000 at age 80-84); in women, incidence of second HN cancers was around 200-300/100,000 between age 45-49 and 80-84. The patterns of age-specific incidence were consistent for different subsites of second HN cancer and sexes; moreover, they were similar for age-specific incidence of first primary HN cancer in patients who subsequently developed a second HN cancer. The incidence of second HN cancers does not increase with age, but remains constant, or if anything, decreases with advancing age.