A Population-Based Family Case-Control Study of Sun Exposure and Follicular Lymphoma Risk.

BACKGROUND: Epidemiologic evidence suggests an inverse association between sun exposure and follicular lymphoma risk. METHODS: We conducted an Australian population-based family case-control study based on 666 cases and 459 controls (288 related, 171 unrelated). Participants completed a lifetime residence and work calendar and recalled outdoor hours on weekdays, weekends, and holidays in the warmer and cooler months at ages 10, 20, 30, and 40 years, and clothing types worn in the warmer months. We used a group-based trajectory modeling approach to identify outdoor hour trajectories over time and examined associations with follicular lymphoma risk using logistic regression. RESULTS: We observed an inverse association between follicular lymphoma risk and several measures of high lifetime sun exposure, particularly intermittent exposure (weekends, holidays). Associations included reduced risk with increasing time outdoors on holidays in the warmer months [highest category OR = 0.56; 95% confidence interval (CI), 0.42-0.76; Ptrend < 0.01], high outdoor hours on weekends in the warmer months (highest category OR = 0.71; 95% CI, 0.52-0.96), and increasing time outdoors in the warmer and cooler months combined (highest category OR = 0.66; 95% CI, 0.50-0.91; Ptrend 0.01). Risk was reduced for high outdoor hour maintainers in the warmer months across the decade years (OR = 0.71; 95% CI, 0.53-0.96). CONCLUSIONS: High total and intermittent sun exposure, particularly in the warmer months, may be protective against the development of follicular lymphoma. IMPACT: Although sun exposure is not recommended as a cancer control policy, confirming this association may provide insights regarding the future control of this intractable malignancy.

Occupational exposure to extremely low-frequency magnetic fields and follicular lymphoma risk: a family case-control study.

OBJECTIVES: We aimed to examine the relationship between occupational exposure to extremely low-frequency magnetic fields (ELF-MFs) and follicular lymphoma (FL) risk. METHODS: We conducted a family case-control study between 2011 and 2016 in Australia and included 681 cases. Controls were either a family member of cases (related (n=294), unrelated (n=179)) or were unrelated recruited for a similarly designed Australian multiple myeloma study (n=711). We obtained detailed job histories using lifetime work calendars. We assigned exposure to ELF-MFs using an enhanced job exposure matrix, with a lag period of 10 years. We examined associations with FL risk using logistic regression accounting for relatedness between cases and controls. We performed sensitivity analyses including by control type, by sex, complete case analyses, ELF-MF exposure percentiles in addition to quartiles, ELF-MF exposure in the maximum exposed job, a shorter lag period (1 year) and the cumulative exposure in the most recent time period (1-9 years). RESULTS: We observed no association with the average intensity, duration or lifetime cumulative exposure to occupational ELF-MF exposure in the primary or sensitivity analyses. CONCLUSIONS: Our findings do not support an association between occupational ELF-MF exposure and FL risk. Although the inclusion of family members as part of the larger control group may have biased our risk estimates towards the null, findings were similar in sensitivity analyses restricted to cases and unrelated controls. Further research incorporating enhanced exposure assessment to ELF-MF is warranted to inform occupational safety regulations and any potential role in lymphomagenesis.

Modifiable lifestyle risk factors and survival after diagnosis with multiple myeloma.

BACKGROUND: While remaining incurable, median overall survival for MM now exceeds 5 years. Yet few studies have investigated how modifiable lifestyle factors influence survival. We investigate whether adiposity, diet, alcohol, or smoking are associated with MM-related fatality. RESEARCH DESIGN AND METHODS: We recruited 760 incident cases of MM via cancer registries in two Australian states during 2010-2016. Participants returned questionnaires on health and lifestyle. Follow-up ended in 2020. Flexible parametric survival models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for lifestyle exposures and risk of all-cause and MM-specific fatality. RESULTS: Higher pre-diagnosis Alternative Healthy Eating Index (AHEI) scores were associated with reduced MM-specific fatality (per 10-unit score, HR = 0.84, 95%CI = 0.70-0.99). Pre-diagnosis alcohol consumption was inversely associated with MM-specific fatality, compared with nondrinkers (0.1-20 g per day, HR = 0.59, 95%CI = 0.39-0.90; >20 g per day, HR = 0.67, 95%CI = 0.40-1.13). Tobacco smoking was associated with increased all-cause fatality compared with never smoking (former smokers: HR = 1.44, 95%CI = 1.10-1.88; current smokers: HR = 1.30, 95%CI = 0.80-2.10). There was no association between pre-enrollment body mass index (BMI) and MM-specific or all-cause fatality. CONCLUSIONS: Our findings support established recommendations for healthy diets and against smoking. Higher quality diet, as measured by the AHEI, may improve survival post diagnosis with MM.

Prevalence of Australians exposed to potentially cardiotoxic cancer medicines: a population-based cohort study.

Background: Cardiovascular disease (CVD) and cancer are leading causes of death and people with cancer are at higher risk of developing CVD than the general population. Many cancer medicines have cardiotoxic effects but the size of the population exposed to these potentially cardiotoxic medicines is not known. We aimed to determine the prevalence of exposure to potentially cardiotoxic cancer medicines in Australia. Methods: We identified potentially cardiotoxic systemic cancer medicines through searching the literature and registered product information documents. We conducted a retrospective cohort study of Australians dispensed potentially cardiotoxic cancer medicines between 2005 and 2021, calculating age-standardised annual prevalence rates of people alive with exposure to a potentially cardiotoxic medicine during or prior to each year of the study period. Findings: We identified 108,175 people dispensed at least one potentially cardiotoxic cancer medicine; median age, 64 (IQR: 52-74); 57% female. Overall prevalence increased from 49 (95%CI: 48.7-49.3)/10,000 to 232 (95%CI: 231.4-232.6)/10,000 over the study period; 61 (95%CI: 60.5-61.5)/10,000 to 293 (95%CI: 292.1-293.9)/10,000 for females; and 39 (95%CI: 38.6-39.4)/10,000 to 169 (95%CI: 168.3-169.7)/10,000 for males. People alive five years following first exposure increased from 29 (95%CI: 28.8-29.2)/10,000 to 134 (95%CI: 133.6-134.4)/10,000; and from 22 (95%CI: 21.8-22.2)/10,000 to 76 (95%CI: 75.7-76.3)/10,000 for those alive at least 10 years following first exposure. Most people were exposed to only one potentially cardiotoxic medicine, rates of which increased from 39 (95%CI: 38.7-39.3)/10,000 in 2005 to 131 (95%CI: 130.6-131.4)/10,000 in 2021. Interpretation: The number of people exposed to efficacious yet potentially cardiotoxic cancer medicines in Australia is growing. Our findings can support the development of service planning and create awareness about the magnitude of cancer treatment-related cardiotoxicities. Funding: NHMRC Centre for Research Excellence in Medicines Intelligence, Cancer Institute NSW Early Career Fellowship.

Second Primary Cancers in People With HIV/AIDS: A National Data Linkage Study of Incidence and Risk Factors.

BACKGROUND: Evidence regarding the characteristics of second primary cancer (SPC) in people living with HIV (PLWHIV) is limited. SETTING: We performed a national population-based data linkage study to determine the incidence and risk factors of SPC in PLWHIV in Australia between 1982 and 2012. METHODS: We conducted a probabilistic data linkage study to compare the incidence of SPC over time, defined using HIV treatment eras, for SPCs related to oncogenic viral infection in comparison with non-infection-related SPCs. Risk factors considered included age at diagnosis of cancer, sex, HIV exposure modality, and CD4 + count. RESULTS: Of 29,383 individuals diagnosed with HIV, 3123 individuals who developed a first primary cancer were included in the analysis. Among them, 229 cases of SPC were identified across 27,398 person-years of follow-up. The most common SPCs were non-Hodgkin lymphomas (n = 71, 31%). The incidence of SPC overall did not change over time; however, there was an increase in individuals diagnosed with HIV in later eras ( P trend =0.001). The incidence of non-infection-related SPC increased over time and was associated with older age ( P trend = 0.005) and the acquisition of HIV in later eras ( P trend <0.001). Conversely, the incidence of infection-related SPC decreased ( P trend <0.001), but this was no longer significant after adjustment for age ( P trend = 0.14). CONCLUSIONS: The risk of SPC in PLWHIV in Australia remains high, with a temporal increase observed in non-infection-related cancer, likely due to aging of the population. Optimal screening and prevention strategies for SPC in PLWHIV are increasingly important.

Associations between early-life growth pattern and body size and follicular lymphoma risk and survival: a family-based case-control study.

BACKGROUND: The influence of early-life growth pattern and body size on follicular lymphoma (FL) risk and survival is unclear. In this study, we aimed to investigate the association between gestational age, growth during childhood, body size, changes in body shape over time, and FL risk and survival. METHODS: We conducted a population-based family case-control study and included 706 cases and 490 controls. We ascertained gestational age, growth during childhood, body size and body shape using questionnaires and followed-up cases (median=83 months) using record linkage with national death records. We used a group-based trajectory modeling approach to identify body shape trajectories from ages 5-70. We examined associations with FL risk using unconditional logistic regression and used Cox regression to assess the association between body mass index (BMI) and all-cause and FL-specific mortality among cases. RESULTS: We found no association between gestational age, childhood height and FL risk. We observed a modest increase in FL risk with being obese 5 years prior to enrolment (OR=1.43, 95 %CI=0.99-2.06; BMI ≥30 kg/m2) and per 5-kg/m2 increase in BMI 5 years prior to enrolment (OR=1.14, 95 %CI=0.99-1.31). The excess risk for obesity 5 years prior to enrolment was higher for ever-smokers (OR=2.00, 95 %CI=1.08-3.69) than never-smokers (OR=1.14, 95 %CI=0.71-1.84). We found no association between FL risk and BMI at enrolment, BMI for heaviest lifetime weight, the highest categories of adult weight or height, trouser size, body shape at different ages or body shape trajectory. We also observed no association between all-cause or FL-specific mortality and excess adiposity at or prior to enrolment. CONCLUSION: We observed a weak association between elevated BMI and FL risk, and no association with all-cause or FL-specific mortality, consistent with previous studies. Future studies incorporating biomarkers are needed to elucidate possible mechanisms underlying the role of body composition in FL etiology.

Alcohol and tobacco use and risk of multiple myeloma: A case-control study.

Multiple myeloma (MM) is the second most common hematological cancer and causes significant mortality and morbidity. Knowledge regarding modifiable risk factors for MM remains limited. This analysis of an Australian population-based case-control family study investigates whether smoking or alcohol consumption is associated with risk of MM and related diseases. Incident cases (n = 789) of MM were recruited via cancer registries in Victoria and New South Wales. Controls (n = 1,113) were either family members of cases (n = 696) or controls recruited for a similarly designed study of renal cancers (n = 417). Adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional multivariable logistic regression. Heavy intake (>20 g ethanol/day) of alcohol had a lower risk of MM compared with nondrinkers (OR = 0.68, 95% CI: 0.50-0.93), and there was an inverse dose-response relationship for average daily alcohol intake (OR per 10 g ethanol per day = 0.92, 95% CI: 0.86-0.99); there was no evidence of an interaction with sex. There was no evidence of an association with MM risk for smoking-related exposures (p > 0.18). The associations between smoking and alcohol with MM are similar to those with non-Hodgkin lymphoma. Further research into potential underlying mechanisms is warranted.

Associations between Smoking and Alcohol and Follicular Lymphoma Incidence and Survival: A Family-Based Case-Control Study in Australia.

The association between smoking and alcohol consumption and follicular lymphoma (FL) incidence and clinical outcome is uncertain. We conducted a population-based family case-control study (709 cases: 490 controls) in Australia. We assessed lifetime history of smoking and recent alcohol consumption and followed-up cases (median = 83 months). We examined associations with FL risk using unconditional logistic regression and with all-cause and FL-specific mortality of cases using Cox regression. FL risk was associated with ever smoking (OR = 1.38, 95%CI = 1.08−1.74), former smoking (OR = 1.36, 95%CI = 1.05−1.77), smoking initiation before age 17 (OR = 1.47, 95%CI = 1.06−2.05), the highest categories of cigarettes smoked per day (OR = 1.44, 95%CI = 1.04−2.01), smoking duration (OR = 1.53, 95%CI = 1.07−2.18) and pack-years (OR = 1.56, 95%CI = 1.10−2.22). For never smokers, FL risk increased for those exposed indoors to >2 smokers during childhood (OR = 1.84, 95%CI = 1.11−3.04). For cases, current smoking and the highest categories of smoking duration and lifetime cigarette exposure were associated with elevated all-cause mortality. The hazard ratio for current smoking and FL-specific mortality was 2.97 (95%CI = 0.91−9.72). We found no association between recent alcohol consumption and FL risk, all-cause or FL-specific mortality. Our study showed consistent evidence of an association between smoking and increased FL risk and possibly also FL-specific mortality. Strengthening anti-smoking policies and interventions may reduce the population burden of FL.

Incidence and risk factors of hypertension therapy in Australian cancer patients treated with vascular signalling pathway inhibitors.

BACKGROUND: Clinical trials report systemic hypertension is an adverse effect of vascular signalling pathway inhibitor (VSPi) use. There are limited data from routine clinical practice. We aimed to estimate the real-world incidence and risk factors of new-onset and aggravated hypertension for cancer patients dispensed VSPi in whole-of-population Australian setting. METHODS: We used dispensing records for a 10% random sample of Australians to identify treatment with subsidised VSPi from 2013 to 2018. We further identified dispensings of oral antihypertensive medicines 6 months before and 12 months after VSPi therapy. We defined (i) new-onset hypertension in people first dispensed antihypertensives after VSPi and (ii) aggravated hypertension in people with prior antihypertensive use dispensed an additional, or higher strength, antihypertensive after VSPi. We applied the Fine-Gray cumulative incidence function and Cox proportional hazard regression. RESULTS: 1802 patients were dispensed at least one VSPi. The mean age of the cohort was 65 years and 57% were male. The incidence of new-onset treated hypertension was 24.3% (95%CI: 21.2-27.8); age ≥ 60 years (HR 1.74; 95%CI: 1.32-2.31) and treatment with oral tyrosine kinase inhibitors compared to bevacizumab (HR 1.96; 95%CI: 1.16-3.31) were risk factors. The incidence of aggravated hypertension was 25.2% (95%CI: 22.0-28.7) and risk was elevated for patients with renal cancer (HR 2.84; 95%CI: 1.49-5.41) and cancers other than colorectal (HR 1.85; 95%CI: 1.12-3.03). CONCLUSIONS: Our real-world estimates of incident hypertension appear comparable to those observed in clinical trials (21.6-23.6%). Our population-based study provides some insight into the burden of hypertension in patients commencing VSPi in routine practice.

Time trends in cancer incidence in Australian people living with HIV between 1982 and 2012.

OBJECTIVES: The aim of the study was to describe time trends in cancer incidence in people living with HIV (PLHIV) in Australia between 1982 and 2012. METHODS: A population-based prospective study was conducted using data linkage between the national HIV and cancer registries. Invasive cancers identified in PLHIV were grouped into AIDS-defining cancers (ADCs), infection-related non-ADCs (NADCs), and non-infection-related NADCs. Crude and age-standardized incidence rates of cancers were calculated and compared over five time periods: 1982-1995, 1996-1999, 2000-2004, 2005-2008 and 2009-2012, roughly reflecting advances in HIV antiretroviral therapy. Standardized incidence ratios (SIRs) compared with the Australian general population were calculated for each time period. Generalized linear models were developed to assess time trends in crude and age-standardized incidences. RESULTS: For ADCs, the crude and age-standardized incidences of Kaposi sarcoma and non-Hodgkin lymphoma substantially declined over time (P-trend < 0.001 for all) but SIRs remained significantly elevated. For infection-related NADCs, there were significant increases in the crude incidences of anal, liver and head and neck cancers. Age-standardized incidences increased for anal cancer (P-trend = 0.002) and liver cancer (P-trend < 0.001). SIRs were significantly elevated for anal cancer, liver cancer and Hodgkin lymphoma. For non-infection-related NADCs, the crude incidence of colorectal, lung and prostate cancers increased over time, but age-standardized incidences remained stable. CONCLUSIONS: Continuous improvements and high coverage of antiretroviral therapy have reduced the incidence of ADCs in PLHIV in Australia. Clinical monitoring of anal and liver cancers in people living with HIV should be performed, given the increasing incidence of these cancers.

Dietary intake of animal-based products and likelihood of follicular lymphoma and survival: A population-based family case-control study.

Background: The association between dietary intake of foods of animal origin and follicular lymphoma (FL) risk and survival is uncertain. In this study, we examined the relationship between dietary intake of dairy foods and fats, meat, fish and seafoods, and the likelihood of FL and survival. Methods: We conducted a population-based family case-control study in Australia between 2011 and 2016 and included 710 cases, 303 siblings and 186 spouse/partner controls. We assessed dietary intake of animal products prior to diagnosis (the year before last) using a structured food frequency questionnaire and followed-up cases over a median of 6.9 years using record linkage to national death data. We examined associations with the likelihood of FL using logistic regression and used Cox regression to assess association with all-cause and FL-specific mortality among cases. Results: We observed an increased likelihood of FL with increasing daily quantity of oily fish consumption in the year before last (highest category OR = 1.96, CI = 1.02-3.77; p-trend 0.06) among cases and sibling controls, but no associations with spouse/partner controls. We found no association between the likelihood of FL and the consumption of other types of fish or seafood, meats or dairy foods and fats. In FL cases, we found no association between meat or oily fish intake and all-cause or FL-specific mortality. Conclusion: Our study showed suggestive evidence of a positive association between oily fish intake and the likelihood of FL, but findings varied by control type. Further investigation of the potential role of environmental contaminants in oily fish on FL etiology is warranted.

A systematic review and meta-analysis of occupational exposures and risk of follicular lymphoma.

BACKGROUND: The etiology of follicular lymphoma (FL), a common non-Hodgkin lymphoma subtype, is largely unknown. OBJECTIVE: We performed a systematic review and meta-analysis of observational studies examining the relationship between occupational exposures and FL risk. METHODS: We searched Ovid MEDLINE, Ovid EMBASE, and Web of Science for eligible observational studies examining job titles or occupational exposures prior to January 1, 2020. We performed a narrative synthesis and used random-effects models to generate meta-estimates of relative risk (RR) with 95% confidence intervals (95%CI) for exposures reported by three or more studies. RESULTS: Fifty-eight studies were eligible. Ten cohort and 37 case-control studies quantified FL risk in relation to any exposure to one or more occupational groups or agents. Eight cohort and 19 case-control studies examined dose-response relationships. We found evidence of a positive association with increasing plasma concentration of dichlorodiphenyldichloroethylene (DDE; meta-RR = 1.51, 95%CI = 0.99, 2.31; I2 = 0.0%) and polychlorinated biphenyls (PCBs; meta-RR = 1.47, 95%CI = 0.97, 2.24; I2 = 8.6%). We observed a positive association with exposure to any solvent (meta-RR = 1.16, 95%CI = 1.00, 1.34; I2 = 0.0%) and chlorinated solvents (meta-RR = 1.35, 95%CI = 1.09, 1.68; I2 = 0.0%). Single studies reported a significant positive dose-response association for exposure to any pesticide, hexachlorobenzene, any organophosphate, diazinon, metolachlor, carbaryl, lindane, trichloroethylene, oils/greases, and extremely low-frequency magnetic fields. Job title-only analyses suggested increased risk for medical doctors and spray painters, and decreased risk for bakers and teachers. Overall, studies demonstrated low risk of bias, but most studies examined small numbers of exposed cases. CONCLUSIONS: Current evidence indicates a positive association between FL and occupational exposure to DDE, PCBs, any solvent and chlorinated solvents. Our findings may help guide policies and practices on the safe use of solvents and inform models of lymphomagenesis. Future studies with larger sample sizes and comprehensive quantitative exposure measures may elucidate other avoidable carcinogenic exposures.

Lifestyle and risk of follicular lymphoma: a systematic review and meta-analysis of observational studies.

PURPOSE: To investigate the relationship between follicular lymphoma (FL) risk and common modifiable lifestyle factors, specifically smoking, alcohol, body mass index (BMI), and hair dye use. METHODS: We performed a systematic review and meta-analysis of observational studies published prior to 01 January 2020. We searched Ovid MEDLINE, Ovid EMBASE, and Web of Science and the reference lists of original studies and review articles. We used random-effects models to generate meta-estimates of relative risk (RR) with 95% confidence intervals (95% CI). RESULTS: Twenty-four cohort and ten case-control studies were eligible. Ten articles examined smoking, 11 alcohol, 13 BMI, and four hair dye use and risk of FL. The meta-estimate for current smoking was 1.11 (95% CI 0.92-1.35; I2 = 51%) and there was no significant dose-response per 5-year increase in duration (p-trend = 0.087). Current alcohol intake was inversely associated with FL risk (meta-RR 0.87, 95% CI 0.81-0.94; I2 = 0%) and there was a significant dose-response per 5 drinks/week increase in intake (p-trend = 0.008). There was no association with 5 kg/m2 increase in early adulthood BMI (meta-RR 1.05, 95% CI 0.91-1.20; I2 = 7%) or being overweight (meta-RR 0.99, 95% CI 0.92-1.07; I2 = 0%) or obese (meta-RR 1.08, 95% CI 0.99-1.17; I2 = 0%) as an adult. Hair dye use before 1980 was positively associated with FL risk (meta-RR 1.66, 95% CI 1.22-2.25; I2 = 55%) and no evidence of effect after 1980. CONCLUSION: We found consistent evidence of an inverse association between current alcohol intake and FL risk, and a significant increased risk with hair dye use before 1980. The evidence for smoking is heterogeneous, but most studies did not support an association. Further research is required to understand the mechanisms underlying these associations and the potential for prevention strategies.

Diagnostic and health service pathways to diagnosis of cancer-registry notified cancer of unknown primary site (CUP).

BACKGROUND: Cancer of unknown primary (CUP) is a late-stage malignancy with poor prognosis, but we know little about what diagnostic tests and procedures people with CUP receive prior to diagnosis. The purpose of this study was to determine how health service utilisation prior to diagnosis for people with cancer-registry notified CUP differs from those notified with metastatic cancer of known primary. METHODS: We identified people with a cancer registry notification of CUP (n = 327) from the 45 and Up Study, a prospective cohort of 266,724 people ≥45 years in New South Wales, Australia, matched with up to three controls with a diagnosis of metastatic cancer of known primary (n = 977). Baseline questionnaire data were linked to population health data to identify all health service use, diagnostic tests, and procedures in the month of diagnosis and 3 months prior. We used conditional logistic regression to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: After adjusting for age and educational attainment, people with a cancer-registry notified CUP diagnosis were more likely to be an aged care resident (OR = 2.78, 95%CI 1.37-5.63), have an emergency department visit (OR = 1.65, 95%CI 1.23-2.21), serum tumor marker tests (OR = 1.51, 95%CI 1.12-2.04), or a cytology test without immunohistochemistry (OR = 2.01, 95%CI 1.47-2.76), and less likely to have a histopathology test without immunohistochemistry (OR = 0.43, 95%CI 0.31-0.59). Neither general practitioner, specialist, allied health practitioner or nurse consultations, hospitalisations, nor imaging procedures were associated with a CUP diagnosis. CONCLUSIONS: The health service and diagnostic pathway to diagnosis differs markedly for people notified with CUP compared to those with metastatic cancer of known primary. While these differences may indicate missed opportunities for earlier detection and appropriate management, for some patients they may be clinically appropriate.

Cardiovascular Toxicity of Targeted Therapies for Cancer: An Overview of Systematic Reviews.

BACKGROUND: Several targeted therapies for cancer have been associated with cardiovascular toxicity. The evidence for this association has not been synthesized systematically nor has the quality of evidence been considered. We synthesized systematic review evidence of cardiovascular toxicity of individual targeted agents. METHODS: We searched MEDLINE, Embase, and the Cochrane Database of Systematic Reviews for systematic reviews with meta-analyses of cardiovascular outcomes for individual agents published to May 2020. We selected reviews according to prespecified eligibility criteria (International Prospective Register of Systematic Reviews CRD42017080014). We classified evidence of cardiovascular toxicity as sufficient, probable, possible, or indeterminate for specific cardiovascular outcomes based on statistical significance, study quality, and size. RESULTS: From 113 systematic reviews, we found at least probable systematic review evidence of cardiovascular toxicity for 18 agents, including high- and all-grade hypertension for bevacizumab, ramucirumab, axitinib, cediranib, pazopanib, sorafenib, sunitinib, vandetanib, aflibercept, abiraterone, and enzalutamide, and all-grade hypertension for nintedanib; high- and all-grade arterial thromboembolism (includes cardiac and/or cerebral events) for bevacizumab and abiraterone, high-grade arterial thromboembolism for trastuzumab, and all-grade arterial thromboembolism for sorafenib and tamoxifen; high- and all-grade venous thromboembolism (VTE) for lenalidomide and thalidomide, high-grade VTE for cetuximab and panitumumab, and all-grade VTE for bevacizumab; high- and all-grade left ventricular ejection fraction decline or congestive heart failure for bevacizumab and trastuzumab, and all-grade left ventricular ejection fraction decline/congestive heart failure for pazopanib and sunitinib; and all-grade corrected QT interval prolongation for vandetanib. CONCLUSIONS: Our review provides an accessible summary of the cardiovascular toxicity of targeted therapy to assist clinicians and patients when managing cardiovascular health.

Patterns of immediate breast reconstruction in New South Wales, Australia: a population-based study.

BACKGROUND: The rate of immediate breast reconstruction (IBR) following mastectomy for breast cancer in Australia is low and varies between regions. To date, no previous Australian studies have examined IBR rates between all hospitals within a particular jurisdiction, despite hospitals being an important known contributor to variation in IBR rates in other countries. METHODS: We used cross-classified random-effects logistic regression models to examine the inter-hospital variation in IBR rates by using data on 7961 women who underwent therapeutic mastectomy procedures in New South Wales (NSW) between January 2012 and June 2015. We derived IBR rates by patient-, residential neighbourhood- and hospital-related factors and investigated the underlying drivers for the variation in IBR. RESULTS: We estimated the mean IBR rate across all hospitals performing mastectomy to be 17.1% (95% Bayesian credible interval (CrI) 12.1-23.1%) and observed wide inter-hospital variation in IBR (variance 4.337, CrI 2.634-6.889). Older women, those born in Asian countries (odds ratio (OR) 0.5, CrI 0.4-0.6), residing in neighbourhoods with lower socioeconomic status (OR 0.7, CrI 0.5-0.8 for the most disadvantaged), and who underwent surgery in public hospitals (OR 0.4, CrI 0.1-1.0) were significantly less likely to have IBR. Women residing in non-metropolitan areas and attending non-metropolitan hospitals were significantly less likely to undergo IBR than their metropolitan counterparts attending metropolitan hospitals. CONCLUSION: Wide inter-hospital variation raises concerns about potential inequities in access to IBR services and unmet demand in certain areas of NSW. Explaining the underlying drivers for IBR variation is the first step in identifying policy solutions to redress the issue.

Cardiovascular toxicity of targeted therapies for cancer: a protocol for an overview of systematic reviews.

INTRODUCTION: The introduction of targeted therapies for cancer has contributed to dramatic improvements in patient survival. Nevertheless, several targeted therapies have been associated with 'off-target' adverse effects, based on varying levels of evidence. To date, this evidence has not been systematically synthesised. We will synthesise published systematic review evidence of cardiovascular toxicity associated with targeted cancer therapies. METHODS AND ANALYSIS: We will include systematic reviews of randomised controlled trials and observational studies that report on cardiovascular outcomes for individual agents. We will identify systematic reviews by applying predeveloped, standardised search strategies within Embase, Medline and Cochrane Central. Two independent reviewers will identify reviews published up to 31 December 2016 using predefined eligibility criteria. They will resolve ambiguous cases through consensus, arbitrated by a third reviewer if required. The reviewers will extract and report data according to methodological guidelines for overviews provided by the Cochrane Collaboration, Joanna Briggs Institute and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols. They will assess the quality of included reviews by applying the Assessment of Multiple Systematic Reviews tool. They will judge the quality of evidence in included reviews based on their assessment of bias and incorporation into the interpretation of findings. In synthesising the evidence, we will classify agents based on systematic review evidence of toxicity (sufficient, probable, possible or indeterminate) for specific cardiovascular outcomes (congestive heart failure, myocardial infarction, ischaemic heart disease, left ventricular ejection fraction decline, cerebrovascular disease, pulmonary embolism, thrombosis and hypertension). This will provide clinicians and patients with an accessible synthesis based on robust methodology. ETHICS AND DISSEMINATION: Ethics approval is not required for overviews. We will conduct the study in collaboration with consumer representatives. We will submit results for peer-review publication, and disseminate them through established clinical and consumer networks. PROSPERO REGISTRATION NUMBER: CRD42017080014.

Reoperation after breast-conserving surgery for cancer in Australia: statewide cohort study of linked hospital data.

OBJECTIVES: To investigate between-hospital variation in the probability of reoperation within 90 days of initial breast-conserving surgery (BCS), and the contribution of health system-level and other factors. DESIGN: Population-based, retrospective cohort study. SETTING: New South Wales (NSW), Australia. PARTICIPANTS: Linked administrative hospitalisation data were used to define a cohort of adult women undergoing initial BCS for breast cancer in NSW between 1 July 2002 and 31 December 2013. PRIMARY OUTCOME MEASURES: Multilevel, cross-classified models with patients clustered within hospitals and residential areas were used to examine factors associated with any reoperation, and either re-excision or mastectomy, within 90 days. RESULTS: Of 34 458 women undergoing BCS, 29.1% underwent reoperation within 90 days, half of which were mastectomies. Overall, the probability of reoperation decreased slightly over time. However, there were divergent patterns by reoperation type; the probability of re-excision increased alongside a concomitant decrease in the probability of mastectomy. Significant between-hospital variation was observed. Non-metropolitan location and surgery at low-volume hospitals were associated with a higher overall probability of reoperation, and of mastectomy specifically, after accounting for patient-level factors, calendar year and area-level socioeconomic status. The magnitude of association with geographical location and surgical volume decreased over time. CONCLUSIONS: Reoperation rates within 90 days of BCS varied significantly between hospitals. For women undergoing mastectomy after BCS, this represents a dramatic change in clinical course. Multilevel modelling suggests unwarranted clinical variation may be an issue, likely due to disparities in access to multidisciplinary breast cancer care and preoperative diagnostic procedures. However, the observed reduction in disparities over time is encouraging and indicates that guidelines and policy initiatives have the potential to improve regional breast cancer care.

Patterns and trends in the incidence of paediatric and adult germ cell tumours in Australia, 1982-2011.

PURPOSE: Germ cell tumour (GCT) aetiology is uncertain and comprehensive epidemiological studies of GCT incidence are few. METHODS: Nationwide data on all malignant GCTs notified to Australian population-based cancer registries during 1982-2011 were obtained. Age- and sex-specific, and World age-standardised incidence rates were calculated for paediatric (0-14) and adult (15+) cases using the latest WHO subtype classification scheme. Temporal trends were examined using Joinpoint regression. RESULTS: There were 17,279 GCTs (552 paediatric, 16,727 adult). Age-specific incidence in males (all histologies combined) was bimodal, with peaks during infancy for most sites, and second, larger, peaks during young adulthood. Incidence of ovarian tumours peaked at age 15-19. Around half of paediatric tumours were extragonadal, whereas adult tumours were mostly gonadal. Yolk sac tumours and teratomas predominated in infants, whereas germinomas became more frequent towards adulthood. Increasing incidence trends for some adult gonadal tumours have stabilised; the trend for male extragonadal tumours is also declining. CONCLUSION: Broad similarities in the shape of age-specific incidence curves, particularly for gonadal, central nervous system, and mediastinal tumours provide epidemiological support for commonalities in aetiology among clinically disparate GCT subtypes. Differences in peak ages reflect underlying subtype-specific biological differences. Declining incidence trends for some adult gonadal tumours accords with the global transition in GCT incidence, and supports the possibility of a reduction in prevalence of shared aetiological exposures.

Examining the quality of name code record linkage: what is the impact on death and cancer risk estimates? A validation study.

OBJECTIVE: To examine the validity and impact of record linkage using name code compared to full name records. METHODS: A registry of 45,419 opioid substitution clients (1985-2007) was linked with national population-based death and cancer registries using registrant's name, date of birth, sex, state, postcode and date of death. Records were linked using full name and then using the first two letters of the given and surname (2×2 name code). Sensitivity and specificity were computed and regression analysis used to identify factors related to linkage accuracy. Standardised mortality ratios (SMR) and standardised cancer incidence ratios (SIR) were estimated. RESULTS: The sensitivity and specificity of name code compared to full name linkage were 65.31% and 99.91% for death records and 76.81% and 99.89% for cancer records. Registrants' age and sex and accuracy of the registries were associated with risk of false linkages. Death and cancer risks (SMR 6.98, 95%CI 6.77-7.19; SIR 1.16, 95%CI 1.08-1.24) were significantly under-estimated using name code linkage (SMR 4.39, 95%CI 4.23-4.56; SIR 0.92, 95%CI 0.85-0.99). CONCLUSION: Record linkage using 2×2 name code has low sensitivity but high specificity, resulting in conservative estimates of death and cancer risk. This may translate to meaningful differences in outcomes.