Cancer Mortality In People Research Articles

Solid cancer mortality risk in the cohort of Urals population exposed to radiation for up the age of 20

The objective of the current study is the direct assessment of the excess relative risk of solid cancer mortality in people affected by low dose-rate chronic exposure mainly in low-to medium dose range (up to 1 Gy) at the age of <20. The study cohort consists of the population exposed at the age of <20 as a result of two large radiation accidents at the “Mayak” Production Association. The size of the cohort is 32,762 persons, follow-up period – 71 years (from 1950 through 2020), the number of person-years at risk is – 1 218 855. For this cohort the mortality catchment area includes Chelyabinsk and Kurgan Oblasts. Over a 71-year follow-up period 1,788 solid cancer deaths were registered in the cohort. Mean dose accumulated in the stomach walls over the whole follow-up period was 0.04 Gy, maximum dose was 1.1 Gy. Statistical processing of data was performed using Amfit and Datab software packages (Epicure statistics software package). Solid cancer mortality risk was analyzed with the Poisson regression using simple parametric excess relative risk model. Statistical significance of the results was estimated using the maximum likelihood method with 95% probability. For the first time the direct assessments of the excess relative risk of solid cancer mortality have been obtained in the Urals Cohort of population exposed at age <20 for a 71-year period (Excess Relative Risk was 0.84/Gy, 95% confidence interval: 0.24-1.55 for 10-years minimal latency period and 0.83 (0.24-1.55) for 5-year minimal latency period). Statistically significant estimates of the excess relative risk have been obtained for specific groups within the cohort selected according to the sex, age at the onset of exposure, and Oblast of residence at the time of exposure.

Abstract P192: Association Between Time-Restricted Eating and All-Cause and Cause-Specific Mortality

Introduction: Time-restricted eating (TRE) has gained popularity as a dietary intervention that limits daily food consumption to a 4- to 12-hour window. Most short-term randomized controlled trials reported that TRE improved cardiometabolic risk profiles. However, whether TRE is associated with long-term hard endpoints remains unknown. Hypothesis: We assessed the hypothesis that TRE is associated with a reduced risk of all-cause and cause-specific mortality. Methods: Participants aged at least 20 years who completed two valid 24-hour dietary recalls and reported usual intake in both recalls were included from the National Health and Nutrition Examination Survey in 2003-2018. Mortality status as of December 2019 was obtained through linkage to the National Death Index. An eating occasion required consuming more than 5 kcal of foods or beverages. Eating duration between the last and first eating occasion was calculated for each day. The average duration of two recall days defined typical eating duration which was then categorized as <8, 8-<10, 10-<12, 12-16 (reference group; mean duration in US adults), and >16 hours. Multivariable Cox proportional hazards models were employed to estimate the association of eating duration with all-cause and cause-specific mortality in the overall sample and among adults with cardiovascular disease or cancer. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were derived. Results: Among 20,078 adults included, the weighted mean (SE) age was 48.5 (0.3) years, 50.0% were men, and 73.3% were non-Hispanic White. During a median follow-up of 8.0 years (IQR, 4.2-11.8), 2797 all-cause deaths occurred, including 840 cardiovascular deaths and 643 cancer deaths. Compared with eating duration of 12-16 hours, eating duration <8 hours was significantly associated with an increased risk of cardiovascular mortality (HR, 1.96 [95% CI, 1.23-3.13]); this association was also observed in adults with cardiovascular disease (HR, 2.06 [95% CI, 1.12-3.81]) and adults with cancer (HR, 2.72 [95% CI, 1.28-5.80]). Other eating durations were not associated with cardiovascular mortality, except for eating duration of 8-<10 hours in people with cardiovascular disease (HR, 1.64 [95% CI, 1.02-2.63]). No significant associations were found between eating duration and all-cause or cancer mortality in the overall sample and diseased subsamples, except that eating duration >16 hours was associated with a lower risk of cancer mortality in people with cancer (HR, 0.46; [95% CI, 0.22-0.95]). Conclusions: In US adults, TRE with eating duration <8 hours was significantly associated with a higher risk of cardiovascular mortality in the general population as well as in people with cardiovascular disease or cancer. These findings do not support long-term use of 16:8 TRE for preventing cardiovascular death.

Abstract C057: Methylome-wide profiling of early-onset colorectal cancer in underrepresented populations

Abstract Colorectal cancer (CRC) is the third leading cause of death from cancer in both men and women in the United States. Late onset colorectal cancer (LOCRC) or CRC diagnosed in older adults >50 years old has continued to decline while early onset colorectal cancer (EOCRC) or colorectal cancer in patients under the age of 50 continues to rise at an alarming rate since the mid-1990s. In fact, EOCRC is now the second most common cancer and the third leading cause of cancer mortality in people <50 years of age in the USA. The incidence of EOCRC has been on the rise over the past four decades and is expected to increase by >140% by 2030. Notably, Blacks and Hispanics are disproportionately affected with the EOCRC diagnosis. Despite this, minority patients remain underrepresented in clinical trials and translational research. It has been proposed that environmental exposures including westernized diet, metabolic factors, and the microbiome might be responsible for the rise in incidence of EOCRC. Epigenetic modifications are well-known mechanisms by which the environment can modulate gene expression without changing the DNA sequence. One such modification is DNA methylation, which controls DNA accessibility, chromatin formation, and gene transcriptional activity. Unfortunately, however, little is known about the role of DNA methylation in EOCRC and much less is understood of EOCRC in minority populations. Therefore, we identified a unique cohort of 11 EOCRC patients within the Baylor College of Medicine/Harris Health System which is comprised of majority minority EOCRC population (7- Hispanic, 2 Non-Hispanic (NH) Black, and 1 NH-White EOCRC patients). Using whole-genome bisulfite sequencing, we comprehensively characterized the DNA methylome at single-base resolution in our 11 EOCRC patient samples. Our analyses revealed distinct EOCRC methylation patterns including both global hypomethylation and promoter-specific hypermethylation, which were not previously captured in The Cancer Genome Atlas (TCGA) Analyses. Among the differentially methylated regions (DMRs), we discovered that DNA and RNA transcription pathways were enriched in EOCRCs at advanced stage. Furthermore, we identify differential DMRs patterns among ethnicities. Taken together, our work supports a pathogenic role for DNA methylation in EOCRC. We are the first group to take this comprehensive unbiased approach to analyze the methylome in an underrepresented EOCRC cohort of patients. Citation Format: Karen Riggins, Jason Sheng Li, Benjamin Musher, Li Yang, Patricia Castro, Wedad Alfarkh, Neda Zarrin-Kamah, Michael Scheurer, Chad Creighton, Wei Li, Lanlan Shen. Methylome-wide profiling of early-onset colorectal cancer in underrepresented populations [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C057.

Breast cancer treatment disparities in patients with severe mental illness: A systematic review and meta-analysis.

The incidence and mortality rates of breast cancer in individuals with pre-existing severe mental illness (SMI), such as schizophrenia, bipolar disorder, and major depression, are higher than in the general population. Reduced screening is one factor but there is less information on possible barriers to subsequent treatment following diagnosis. We undertook a systematic review and meta-analysis on access to guideline-appropriate care following a diagnosis of breast cancer in people with SMI including the receipt of surgery, endocrine, chemo- or radiotherapy. We searched for full-text articles indexed by PubMed, EMBASE, PsycInfo and CINAHL that compared breast cancer treatment in those with and without pre-existing SMI. Study designs included population-based cohort or case-control studies. There were 13 studies included in the review, of which 4 contributed adjusted outcomes to the meta-analyses. People with SMI had a reduced likelihood of guideline-appropriate care (RR=0.83, 95% CI=0.77-0.90). Meta-analyses were not possible for the other outcomes but in adjusted results from a single study, people with SMI had longer wait-times to receiving guideline-appropriate care. The results for specific outcomes such as surgery, hormone, radio- or chemotherapy were mixed, possibly because results were largely unadjusted for age, comorbidities, or cancer stage. People with SMI receive less and/or delayed guideline-appropriate care for breast cancer than the general population. The reasons for this disparity warrant further investigation, as does the extent to which differences in treatment access or quality contribute to excess breast cancer mortality in people with SMI.

Cancer Mortality in People Receiving Dialysis for Kidney Failure: An Australian and New Zealand Cohort Study, 1980-2013

Cancer is a significant cause of morbidity in the population with kidney failure; however, cancer mortality in people undergoing dialysis has not been well described. We sought to compare cancer mortality in people on dialysis for kidney failure with cancer mortality in the general population. A retrospective cohort study using linked health-administrative and dialysis registry data. All people receiving dialysis represented in the Australian and New Zealand Dialysis and Transplantation Registry, 1980-2013. Dialysis; hemodialysis (HD) and peritoneal dialysis (PD). Death and underlying cause of death ascertained using health administrative data and classified using International Classification of Diseases, Tenth Revision, Australian Modification (ICD-10-AM) codes. Indirect standardization on age at death, sex, year, and country to estimate standardized mortality ratios (SMR). Over 269,598 person years of observation, 34,100 deaths occurred among 59,648 people on dialysis, including 3,677 cancer deaths. The relative risk of all-site cancer death in dialysis was twice (SMR, 2.4 [95% CI, 2.33-2.49]) that of the general population and highest for oral and pharynx cancers (SMR, 24.3 [95% CI, 18.0-31.5]) and multiple myeloma (SMR, 22.5 [95% CI, 20.3-23.9]). Women on dialysis had a significantly higher risk of all-site cancer mortality (SMR, 2.7 [95% CI, 2.59-2.89]) compared with men (SMR, 2.3 [95% CI, 2.17-2.36]) (P< 0.001). People on HD (SMR, 2.2 [95% CI, 2.11-2.30]) experienced greater excess deaths from all-site cancer compared with people on PD (SMR, 1.3 [95% CI, 1.23-1.44]). Excess deaths have gradually decreased over time for all-site, multiple myeloma, and kidney cancers (P< 0.001) but have not kept up with improvements in the general population. By contrast, among people receiving dialysis, excess deaths increased for colorectal and lung cancers (P< 0.001). Confirmation of cancer diagnoses and population incidence data were not available; inability to exclude pre-existing cancers. People on dialysis experience excess all-site and site-specific cancer mortality compared with the general population. Mortality differs by modality type, age, and sex. Understanding the role of kidney failure and other morbidities in the treatment of cancer is important for shared decision-making regarding cancer treatments and identifying potential approaches to improve outcomes.

323Breast and cervical cancer screening and outcomes in NSW mental health service consumers

Abstract Focus of Presentation This presentation describes methods and findings from the NSW Mental Health Living Longer (MHLL) Program. MHLL involves population-wide data linkage that combines records from nine NSW data collections. Our collection includes over 120 million records for more than nine million people. This presentation focuses on the use of linked data to develop indicators to support reporting on premature cancer mortality for people living with mental illness. We will use these indicators to identify variation in care, assess areas for targeted intervention, and evaluate the effectiveness of research translation into safer and more effective care. Findings This work will be finalised by August 2020. We will use regression techniques to examine predictors of participation in breast and cervical cancer screening for women who use mental health services in NSW. These results will be used to assess geographical variation in risk-adjusted screening participation rates. We will also present methods and results for measuring incidence and stage at presentation, as well as 12 month and 5 year survival for women who use mental health services compared to other women in NSW. Conclusions/Implications If cancer survival is a key measure of the effectiveness of healthcare systems, then reduced survival in people with mental health problems reflects less effective health care. Improving screening and treatment services is likely to be the most important strategy for reducing the cancer mortality gap for people with mental illness. Key messages Health systems must move from recognition to action if we are to reduce premature cancer mortality in people living with mental illness.

Population-Wide Data Linkage to Reduce Premature Mortality in Women Who Use Mental Health Services In NSW

IntroductionCancer deaths are a major contributor to premature mortality in people with mental health conditions. Some cancers occur more often in people with mental health conditions because of increased risk factors. However, most premature cancer mortality in people with mental health conditions arises from increased cancer case fatality rates due to health care related factors. While there is substantial evidence that a problem exists, further evidence is needed to support effective action and the translation of research findings into better policy, services and care.&#x0D; Objectives and ApproachThe NSW Mental Health Living Longer program involves population-wide data linkage that combines records from nine NSW data collections. Our collection includes over 120 million records for more than nine million people. This presentation focuses on the use of linked data to develop indicators to support reporting on premature breast and cervical cancer mortality for women living with mental illness. These indicators will be used to identify variation in care, assess areas for targeted intervention, and evaluate the effectiveness of research translation into more effective care.&#x0D; ResultsThis work is ongoing and will be finalised by August 2020. We will use regression techniques to examine predictors of participation in breast and cervical cancer screening for women who use mental health services in NSW. These results will be used to assess geographical variation in risk-adjusted screening participation rates. We will also present methods and results for measuring incidence and stage at presentation, as well as 5 year survival for women who use mental health services in NSW.&#x0D; Conclusion / ImplicationsIf cancer survival is a key measure of the effectiveness of healthcare systems, then reduced survival in people with mental health problems reflects less effective health care. Improving screening and treatment services is likely to be the most important strategy for reducing the cancer mortality gap for women with mental illness.

Clinical impact and cost-effectiveness of integrating smoking cessation into lung cancer screening: a microsimulation model.

Low-dose computed tomography (CT) screening can reduce lung cancer mortality in people at high risk; adding a smoking cessation intervention to screening could further improve screening program outcomes. This study aimed to assess the impact of adding a smoking cessation intervention to lung cancer screening on clinical outcomes, costs and cost-effectiveness. Using the OncoSim-Lung mathematical microsimulation model, we compared the projected lifetime impact of a smoking cessation intervention (nicotine replacement therapy, varenicline and 12 wk of counselling) in the context of annual low-dose CT screening for lung cancer in people at high risk to lung cancer screening without a cessation intervention in Canada. The simulated population consisted of Canadians born in 1940-1974; lung cancer screening was offered to eligible people in 2020. In the base-case scenario, we assumed that the intervention would be offered to smokers up to 10 times; each intervention would achieve a 2.5% permanent quit rate. Sensitivity analyses varied key model inputs. We calculated incremental cost-effectiveness ratios with a lifetime horizon from the health system's perspective, discounted at 1.5% per year. Costs are in 2019 Canadian dollars. Offering a smoking cessation intervention in the context of lung cancer screening could lead to an additional 13% of smokers quitting smoking. It could potentially prevent 12 more lung cancers and save 200 more life-years for every 1000 smokers screened, at a cost of $22 000 per quality-adjusted life-year (QALY) gained. The results were most sensitive to quit rate. The intervention would cost over $50 000 per QALY gained with a permanent quit rate of less than 1.25% per attempt. Adding a smoking cessation intervention to lung cancer screening is likely cost-effective. To optimize the benefits of lung cancer screening, health care providers should encourage participants who still smoke to quit smoking.

1550-P: Trends in Cancer Mortality among U.S. Adults With and Without Diabetes, 1988-2015

Cancer-related mortality is higher among people with diabetes (DM) than people without DM. However, it is not known if this excess risk has changed over time. To estimate rates of cancer mortality in people with and without self-reported DM, we used data from adults aged ≥18 years who participated in the 1985-2012 National Health Interview Survey. Participants were linked to the National Death Index to determine vital status through the end of 2015. Cancer deaths were classified according to underlying cause of death. Death rates for five time periods (1988-1994, 1995-1999, 2000-2004, 2005-2009, 2010-2012) were estimated by survival analysis using Poisson regression models adjusted for age, sex and race/ethnicity with p for trend reported. Among people with DM, overall cancer mortality (per 1,000 person-years) declined 34.1% from 4.1 (95% CI: 3.0-5.3) in 1988-1994 to 2.7 (2.3-3.2) in 2010-2015, ptrend&amp;lt;0.01. Among people without DM, overall cancer mortality declined 26.7% from 3.0 (2.8-3.2) to 2.2 (2.0-2.3), respectively for the 1988-1994 and 2010-2015 periods, ptrend&amp;lt;0.01. The excess rate of cancer mortality in people with vs. without DM did not change over time (from rate ratio 1.4 (1.0-1.8) in 1988-1994, to 1.3 (1.2-1.4) in 2010-2015). In this nationally representative study, cancer mortality rates declined in people with and without DM but cancer mortality rates remain 30% higher in people with DM. Future research could identify risk factors and prevention strategies for this excess risk. Disclosure J.L. Harding: None. L.J. Andes: None. Y.J. Cheng: None. K.M. Bullard: None. E. Gregg: None. H.K. Weir: None. N. Burrows: None. G. Imperatore: None.

Risk of Advanced Adenoma, Colorectal Cancer, and Colorectal Cancer Mortality in People With Low-Risk Adenomas at Baseline Colonoscopy: A Systematic Review and Meta-Analysis.

We conducted a systematic review and meta-analysis of the risk of advanced adenomas (AAs), colorectal cancer (CRC), and/or CRC-related death among individuals with low-risk adenomas (LRAs). We searched PubMed and Embase for studies published between January 2006 and July 2015. Quality and strength of the evidence were rated using the Newcastle-Ottawa Scale (NOS) and the GRADE framework, respectively. Eleven observational studies (n=64,317) were included. A meta-analysis of eight cohort studies (n=10,139, 3 to 10 years' follow-up) showed a small but statistically significant increase in the incidence of AAs in individuals with LRAs compared with those with a normal baseline colonoscopy (RR 1.55 (95% CI 1.24-1.94); P=0.0001; I2=0%). The pooled 5-year cumulative incidence of AA was 3.28% (95% CI: 1.85-5.10%), 4.9% (95% CI: 3.18-6.97%), and 17.13% (95% CI: 11.97-23.0%) for the no adenoma, LRA, and AA baseline groups, respectively. Two studies, which could not be pooled, showed a reduction in the risk of CRC in individuals with LRAs compared with the general population (standardized incidence ratio 0.68 (95% CI 0.44-0.99) at a median follow-up of 7.7 years and OR 0.4 (95% CI 0.2-0.6) at 3-5 years). One large retrospective cohort study found a 25% reduction in CRC mortality in individuals with LRAs compared with the general population (SMR 0.75 (95% CI 0.63-0.88) at a median follow-up of 7.7 years). We observed a small but significant increase in the risk of AAs in people with LRAs compared with those with a normal baseline colonoscopy, but compared with the general population, people with LRAs have significantly lower risks of CRC and of CRC-related mortality.

Cancer Mortality in People Treated with Antidepressants before Cancer Diagnosis: A Population Based Cohort Study.

BackgroundDepression is common after a cancer diagnosis and is associated with an increased mortality, but it is unclear whether depression occurring before the cancer diagnosis affects cancer mortality. We aimed to study cancer mortality of people treated with antidepressants before cancer diagnosis.Methods and FindingsWe conducted a population based cohort study of all adults diagnosed with cancer between January 2003 and December 2010 in Denmark (N = 201,662). We obtained information on cancer from the Danish Cancer Registry, on the day of death from the Danish Civil Registry, and on redeemed antidepressants from the Danish National Prescription Registry. Current users of antidepressants were defined as those who redeemed the latest prescription of antidepressant 0–4 months before cancer diagnosis (irrespective of earlier prescriptions), and former users as those who redeemed the latest prescription five or more months before cancer diagnosis. We estimated an all-cause one-year mortality rate ratio (MRR) and a conditional five-year MRR for patients who survived the first year after cancer diagnosis and confidence interval (CI) using a Cox proportional hazards regression model. Overall, 33,111 (16.4%) patients redeemed at least one antidepressant prescription in the three years before cancer diagnosis of whom 21,851 (10.8%) were current users at the time of cancer diagnosis. Current antidepressant users had a 32% higher one-year mortality (MRR = 1.32, 95% CI: 1.29–1.35) and a 22% higher conditional five-year mortality (MRR = 1.22, 95% CI: 1.17–1.26) if patients survived the first year after the cancer diagnosis than patients not redeeming antidepressants. The one-year mortality was particularly high for patients who initiated antidepressant treatment within four months before cancer diagnosis (MRR = 1.54, 95% CI: 1.47–1.61). Former users had no increased cancer mortality.ConclusionsInitiation of antidepressive treatment prior to cancer diagnosis is common and is associated with an increased mortality.

Bladder Cancer Mortality after Spinal Cord Injury over 4 Decades

We estimate bladder cancer mortality in people with spinal cord injury compared to the general population. Data and statistics were retrieved from the National Spinal Cord Injury Statistical Center and the National Center for Health Statistics. The mortality experience of the 45,486 patients with traumatic spinal cord injury treated at a Spinal Cord Injury Model System or Shriners Hospital was compared to the general population using a standardized mortality ratio. The standardized mortality ratio data were further stratified by age, gender, race, time since injury and injury severity. Our study included 566,532 person-years of followup between 1960 and 2009, identified 10,575 deaths and categorized 99 deaths from bladder cancer. The expected number of deaths from bladder cancer would have been 14.8 if patients with spinal cord injury had the same bladder cancer mortality as the general population. Thus, the standardized mortality ratio is 6.7 (95% CI 5.4-8.1). Increased mortality risk from bladder cancer was observed for various ages, races and genders, as well as for those injured for 10 or more years and with motor complete injuries. Bladder cancer mortality was not significantly increased for ventilator users, those with motor incomplete injuries or those injured less than 10 years. Individuals with a spinal cord injury can potentially live healthier and longer by reducing the incidence and mortality of bladder cancer. Study findings highlight the need to identify at risk groups and contributing factors for bladder cancer death, leading to the development of prevention, screening and management strategies.

Glycated Hemoglobin Predicts All-Cause, Cardiovascular, and Cancer Mortality in People Without a History of Diabetes Undergoing Coronary Angiography

OBJECTIVEGlycated hemoglobin has been suggested to be superior to fasting glucose for the prediction of vascular disease and death from any cause. The aim of the present work was to analyze and compare the predictive value of glycated hemoglobin and fasting glucose on all-cause and cause-specific mortality in subjects who underwent coronary angiography.RESEARCH DESIGN AND METHODSWe studied 2,686 participants of the Ludwigshafen Risk and Cardiovascular health study without a history of diabetes. The majority of this cohort had coronary artery disease. Glycated hemoglobin was measured at the baseline examination. The mean (± SD) duration of the follow-up for all-cause, cardiovascular, and cancer mortality was 7.54 ± 2.1 years.RESULTSA total of 508 deaths occurred during the follow-up. Of those, 299 were accounted for by cardiovascular diseases and 79 by cancer. Baseline glycated hemoglobin was predictive of all-cause, cardiovascular, and cancer mortality. The multivariable-adjusted hazard ratios (HR) (95% CI) for glycated hemoglobin values of <5.0, 5.0–5.4, 5.5–5.9, 6.0–6.4, 6.5–7.4, and ≥7.5% for all-cause mortality were 1.36 (0.85–2.18), 1.00 (0.76–1.32), 1.00 (reference), 1.11 (0.88–1.41), 1.39 (1.07–1.82), and 2.15 (1.32–3.53), respectively. Similar J-shaped relationships were found between glycated hemoglobin and cardiovascular and cancer mortality. The associations of glycated hemoglobin with all-cause and cardiovascular mortality remained significant after inclusion of fasting glucose as a covariate. However, fasting glucose was not significantly related to mortality when adjusting for glycated hemoglobin.CONCLUSIONSGlycated hemoglobin significantly and independently of fasting glucose predicts all-cause and cardiovascular mortality in whites at intermediate to high cardiovascular risk.

Relative Risk of Cardiovascular and Cancer Mortality in People With Severe Mental Illness From the United Kingdom's General Practice Research Database

Relative Risk of Cardiovascular and Cancer Mortality in People With Severe Mental Illness From the United Kingdom's General Practice Research Database

Severe mental illness increases the risk of death from coronary heart disease or stroke

Are people with severe mental health illness at increased risk of death from coronary heart disease, stroke or cancer? Osborn DPJ, Levy G, Nazareth I, et al . Relative risk...

Error in Table in: Relative Risk of Cardiovascular and Cancer Mortality in People With Severe Mental Illness From the United Kingdom's General Practice Research Database

Error in Table in: Relative Risk of Cardiovascular and Cancer Mortality in People With Severe Mental Illness From the United Kingdom's General Practice Research Database

Relative Risk of Cardiovascular and Cancer Mortality in People With Severe Mental Illness From the United Kingdom's General Practice Research Database

People with severe mental illness (SMI) appear to have an elevated risk of death from cardiovascular disease, but results regarding cancer mortality are conflicting. To estimate this excess mortality and the contribution of antipsychotic medication, smoking, and social deprivation. Retrospective cohort study. United Kingdom's General Practice Research Database. Patients Two cohorts were compared: people with SMI diagnoses and people without such diagnoses. Main Outcome Measure Mortality rates for coronary heart disease (CHD), stroke, and the 7 most common cancers in the United Kingdom. A total of 46 136 people with SMI and 300 426 without SMI were selected for the study. Hazard ratios (HRs) for CHD mortality in people with SMI compared with controls were 3.22 (95% confidence interval [CI], 1.99-5.21) for people 18 through 49 years old, 1.86 (95% CI, 1.63-2.12) for those 50 through 75 years old, and 1.05 (95% CI, 0.92-1.19) for those older than 75 years. For stroke deaths, the HRs were 2.53 (95% CI, 0.99-6.47) for those younger than 50 years, 1.89 (95% CI, 1.50-2.38) for those 50 through 75 years old, and 1.34 (95% CI, 1.17-1.54) for those older than 75 years. The only significant result for cancer deaths was an unadjusted HR for respiratory tumors of 1.32 (95% CI, 1.04-1.68) for those 50 to 75 years old, which lost statistical significance after controlling for smoking and social deprivation. Increased HRs for CHD mortality occurred irrespective of sex, SMI diagnosis, or prescription of antipsychotic medication during follow-up. However, a higher prescribed dose of antipsychotics predicted greater risk of mortality from CHD and stroke. This large community sample demonstrates that people with SMI have an increased risk of death from CHD and stroke that is not wholly explained by antipsychotic medication, smoking, or social deprivation scores. Rates of nonrespiratory cancer mortality were not raised. Further research is required concerning prevention of this mortality, including cardiovascular risk assessment, monitoring of antipsychotic medication, and attention to diet and exercise.

SU-FF-T-382: Planning Non-Uniform Dose Distributions for Brain Tumor

Purpose: Inhomogeneous radiobiology exists within tumor volume of malignant gliomas as shown by biological imaging. The purpose of this project is to plan non-uniform dose distributions to account for inhomogeneous radiosensitivity using IMRT. Method and Materials: Sample tumor volumes were divided into several sub-regions of different radiosensitivity that may be considered to correspond to different tumor grade. A pooled clinical and in-vitro data for gliomas were analyzed to determine radiosensitivity parameters for different tumor grades. LQ model and equivalent uniform dose (EUD) were used to calculate the required radiation dose to account for different tumor grade in different sub-region. While the required dose in each sub-region is uniform, the dose distribution within the entire tumor volume is non-uniform. The Xio/CMS IMRT planning system was used to plan the required non-uniform dose distributions and also the conventional 60Gy uniform dose. The EUDs for both uniform and non-uniform distributions were compared. Results: Using the parameters determined from clinical data the required dose (EUD in 2Gy fractions) was found to be >55Gy for grade 1 or 2, >60Gy for grade 3 and >65Gy for grade 4. Considering low tumor grade (thus low dose) existing in periphery region, IMRT can deliver the required non-uniform distributions while keeping or improving normal-tissue sparing compared to the conventional uniform dose delivery. The dose can be escalated even higher than the required value in a high-grade region. The non-uniform dose plans yield higher tumor EUD and lower or the same normal-tissue EUD as compared to the conventional plan, indicating that the non-uniform doses are more effective. Conclusion: It is dosimetrically feasible to plan non-uniform dose distributions to account for inhomogeneous radiosensitivity. This prepares a framework for biological imaging guided radiotherapy of malignant gliomas, a leading cause of cancer mortality in people with young ages.