Hospital-diagnosed overweight and obesity related to cancer risk: a 40-year Danish cohort study.

BACKGROUND: Obesity is associated with metabolic abnormalities that predispose patients to increased cancer risk. Contemporary data on the long-term risk of specific cancers are sparse among patients with hospital-diagnosed overweight and obesity. OBJECTIVES: To examine the overall cancer incidence and specific site-related cancer incidences among patients with overweight and obesity, compared to the general Danish population. METHODS: For this 40-year (1977-2016), nationwide, Danish cohort study, we reviewed medical databases to identify individuals with hospital-based overweight and obesity diagnoses. We computed age- and gender-standardized incidence ratios (SIRs) for subsequent cancer compared to the general population. RESULTS: We observed 20 706 cancers among 313 321 patients diagnosed with overweight and obesity (median age 43 years; median follow-up 6.7 years, range 1-40 years) compared to the 18 480 cancers expected; thus, the SIR was 1.12 [95% confidence interval (95% CI): 1.11-1.14]. The SIR associated with overweight and obesity was increased with concomitant comorbidities, like type 2 diabetes (SIR: 1.18; 95% CI: 1.13-1.23) and alcoholism-related diseases (SIR: 1.62; 95% CI: 1.45-1.82). The SIR was 1.31 (95% CI: 1.28-1.34) for cancers previously identified as obesity-related, including pancreatic (SIR: 1.38; 95% CI; 1.27-1.49) and postmenopausal breast cancer (SIR: 1.14; 95% CI: 1.09-1.19). Obesity/overweight status also elevated the SIRs for haematological (SIR: 1.24; 95% CI: 1.18-1.29) and neurological cancers (SIR: 1.19; 95% CI: 1.11-1.27]. In contrast, SIRs were 1.01 (95% CI: 0.97-1.05) for immune-related cancers, 0.88 (95% CI: 0.82-0.95) for malignant melanoma, and 0.88 (95% CI: 0.85-0.92) for hormone-related cancers, other than postmenopausal breast cancer. CONCLUSION: In this large cohort study, overweight and obesity was associated with increased risk of several common cancers.

Global Cropland Connectivity: A Risk Factor for Invasion and Saturation by Emerging Pathogens and Pests.

The geographic pattern of cropland is an important risk factor for invasion and saturation by crop-specific pathogens and arthropods. Understanding cropland networks supports smart pest sampling and mitigation strategies. We evaluate global networks of cropland connectivity for key vegetatively propagated crops (banana and plantain, cassava, potato, sweet potato, and yam) important for food security in the tropics. For each crop, potential movement between geographic location pairs was evaluated using a gravity model, with associated uncertainty quantification. The highly linked hub and bridge locations in cropland connectivity risk maps are likely priorities for surveillance and management, and for tracing intraregion movement of pathogens and pests. Important locations are identified beyond those locations that simply have high crop density. Cropland connectivity risk maps provide a new risk component for integration with other factors-such as climatic suitability, genetic resistance, and global trade routes-to inform pest risk assessment and mitigation.

Breast cancer recurrence after reoperation for surgical bleeding.

BACKGROUND: Bleeding activates platelets that can bind tumour cells, potentially promoting metastatic growth in patients with cancer. This study investigated whether reoperation for postoperative bleeding is associated with breast cancer recurrence. METHODS: Using the Danish Breast Cancer Group database and the Danish National Patient Register (DNPR), a cohort of women with incident stage I-III breast cancer, who underwent breast-conserving surgery or mastectomy during 1996-2008 was identified. Information on reoperation for bleeding within 14 days of the primary surgery was retrieved from the DNPR. Follow-up began 14 days after primary surgery and continued until breast cancer recurrence, death, emigration, 10 years of follow-up, or 1 January 2013. Incidence rates of breast cancer recurrence were calculated and Cox regression models were used to quantify the association between reoperation and recurrence, adjusting for potential confounders. Crude and adjusted hazard ratios according to site of recurrence were calculated. RESULTS: Among 30 711 patients (205 926 person-years of follow-up), 767 patients had at least one reoperation within 14 days of primary surgery, and 4769 patients developed breast cancer recurrence. Median follow-up was 7·0 years. The incidence of recurrence was 24·0 (95 per cent c.i. 20·2 to 28·6) per 1000 person-years for reoperated patients and 23·1 (22·5 to 23·8) per 1000 person-years for non-reoperated patients. The overall adjusted hazard ratio was 1·06 (95 per cent c.i. 0·89 to 1·26). The estimates did not vary by site of breast cancer recurrence. CONCLUSION: In this large cohort study, there was no evidence of an association between reoperation for bleeding and breast cancer recurrence.

Body mass index, risk of allogeneic red blood cell transfusion, and mortality in elderly patients undergoing hip fracture surgery.

UNLABELLED: Despite improvements in preoperative and postoperative treatment, hip fracture surgery may lead to blood transfusion. Little is known about the impact of body mass index on transfusion risk and subsequent mortality. Opposite overweight and obese patients, underweight patients had increased risk of transfusion and death within 1 year of surgery. INTRODUCTION: Despite improvements in preoperative and postoperative treatment of hip fracture patients, hip fracture surgery may lead to blood loss. We examined the risk of red blood cell transfusion (as an indirect measure of blood loss) and subsequent mortality by body mass index level in patients aged 65 and over undergoing hip fracture surgery. METHODS: This is a population-based cohort study using medical databases. We included all patients who underwent surgery for hip fracture during 2005-2013. We calculated the cumulative risk of red blood cell transfusion within 7 days of surgery treating death as a competing risk and, among transfused patients, short- (8-30 days postsurgery) and long-term mortality (31-365 days postsurgery). RESULTS: Among 56,420 patients, 47.7 % received at least one red blood cell transfusion within 7 days of surgery. In patients with normal weight, the risk was 48.8 % compared with 57.0 % in underweight patients (adjusted RR = 1.11; CI 1.08-1.15), 42.1 % in overweight patients (adjusted RR = 0.89; CI 0.86-0.91), and 42.2 % in obese patients (adjusted RR = 0.87; CI 0.84-0.91). Among transfused patients, adjusted HRs for short-term mortality were 1.52 (CI 1.34-1.71), 0.70 (CI 0.61-0.80), and 0.58 (CI 0.43-0.77) for underweight, overweight, and obese patients, respectively, compared with normal-weight patients. The corresponding adjusted HRs for long-term mortality were 1.45 (CI 1.33-1.57), 0.80 (CI 0.74-0.86), and 0.58 (CI 0.50-0.69). Similar association between BMI and mortality was observed also among non-transfused patients. CONCLUSIONS: Underweight patients had a higher risk of red blood cell transfusion and death in the first year of surgery than normal-weight patients, even when controlling for age and comorbidity. Opposite findings were seen for overweight and obese patients.

Glucocorticoid prescriptions and breast cancer recurrence: a Danish nationwide prospective cohort study.

BACKGROUND: Treatment with synthetic glucocorticoids (GCs) depresses the immune response and may therefore modify cancer outcomes. We investigated the association between GC use and breast cancer recurrence. MATERIALS AND METHODS: We conducted a population-based cohort study to examine the risk of breast cancer recurrence associated with GC use among incident stage I-III female breast cancer patients aged >18 years diagnosed 1996-2003 in Denmark. Data on patients, clinical and treatment factors, recurrence, and comorbidities as well as data on GC prescriptions and potential confounders were obtained from Danish population-based medical registries. GCs were categorized according to administrative route: systemic, inhaled, or intestinal. Women were followed for up to 10 years or until 31 December 2008. We used Cox proportional hazards regression models to compute hazard ratios (HRs) and associated 95% confidence intervals (95% CIs) to evaluate the association between GC use and recurrence. Time-varying drug exposures were lagged by 1 year. RESULTS: We included 18 251 breast cancer patients. Median recurrence follow-up was 6.9 years; 3408 women developed recurrence during follow-up. Four thousand six hundred two women filled at least one GC prescription after diagnosis. In unadjusted models, no association was observed among users of systemic, inhaled, and intestinal GCs (HRsystemic = 1.1, 95% CI 0.9-1.3; HRinhaled = 0.9, 95% CI 0.7-1.0; and HRintestinal = 1.0, 95% CI 0.9-1.2) versus nonusers. In adjusted models, the results were also near null (HRsystemic = 1.1, 95% CI 0.9-1.2; HRinhaled = 0.8, 95% CI 0.7-1.0; and HRintestinal = 1.0, 95% CI 0.8-1.2). CONCLUSION: We found no evidence of an effect of GC use on breast cancer recurrence.

Circulating C-reactive protein levels as a prognostic biomarker in breast cancer across body mass index groups.

Obesity and systemic inflammation are associated with breast cancer (BC) outcomes. Systemic inflammation is increased in obesity. We examined the association between C-reactive protein (CRP) and disease-free survival (DFS) and overall survival (OS) overall, and according to body mass index (BMI). We assembled a cohort of women with BC (stage I-III) seen at Aarhus University Hospital between 2010 and 2020 who donated blood at BC diagnosis (N = 2673). CRP levels were measured and divided into quartiles. We followed patients from surgery to recurrence, contralateral BC, other malignancy, death, emigration, or end-of-follow-up. We used Cox regression to estimate hazard ratios (HRs) with 95% confidence intervals (95% CIs) to compare outcomes across CRP quartiles, overall and stratified by BMI (normal-weight (18.5 ≤ BMI < 25 kg/m2), overweight (25 ≤ BMI < 30 kg/m2), and obesity (BMI ≥ 30 kg/m2)). During follow-up, 368 events (212 recurrences, 38 contralateral BCs, and 118 deaths) occurred (median follow-up 5.55 years). For DFS, high CRP (CRP ≥ 3.19 mg/L) was associated with an increased risk of events (HRadj:1.62 [95% CI = 1.14-2.28]). In BMI-stratified analyses, high CRP was associated with elevated risk of events in normal-weight and overweight (HRadj:1.70 [95% CI = 1.09-2.66]; HRadj:1.75 [95% CI = 1.08-2.86]), but in obesity, the estimate was less precise (HRadj:1.73 [95% CI = 0.78-3.83]). For OS, high CRP was associated with increased risk of death (HRadj:2.47 [95% CI = 1.62-3.76]). The association was strong in normal-weight and overweight (HRadj:3.66 [95% CI = 1.95-6.87]; HRadj:1.92 [95% CI = 1.06-3.46]), but less clear in obesity (HRadj:1.40 [95% CI = 0.64-3.09]). To sum up, high CRP levels at BC diagnosis were associated with inferior prognosis in early BC irrespective of BMI, although less clear in patients with obesity.

The effectiveness of radon preventive and remedial measures in Irish homes.

It is estimated that approximately 100 000 Irish homes have radon concentrations above the reference level of 200 Bq m(-3). To minimise the number of new homes with this problem, building regulations require that all new homes built since July 1998 in high radon areas are installed with radon barriers during construction. Measurements on local authority homes in a number of high radon areas have allowed the impact of these new regulations to be assessed. In County Cork a reduction of up to 70% in the mean radon concentration was observed in homes built since 1998 relative to those built before this date. A reduction in both the number of homes exceeding the reference level and the maximum concentration measured in homes was also measured. Homes exceeding the reference level were remediated with the use of an active sump. The results of this remedial work are also presented and show that the mean reduction in radon concentration achieved was 92%.

Antidepressant use and colorectal cancer risk: a Danish population-based case-control study.

BACKGROUND: Earlier research suggests that use of selective serotonin reuptake inhibitors (SSRIs), but not tricyclic antidepressants (TCAs), reduces the risk of colorectal cancer (CRC). METHODS: We conducted a population-based case-control study to investigate the association between antidepressant use and CRC risk. Cases were diagnosed with a first primary CRC from 1991 through 2008. We selected 10 population controls matched to cases on sex, birth year, and residence from the Danish Civil Registration System using risk-set sampling. We estimated the odds ratios (ORs) and 95% confidence intervals (CIs) associating antidepressant use with colorectal cancer occurrence, controlling for potential confounders. RESULTS: The study included 9,979 cases and 99,790 controls. We found no notable reduction in CRC risk in ever users (≥2 prescriptions) of TCAs (OR=0.94; 95% CI: 0.84, 1.05), SSRIs (OR=0.97; 95% CI: 0.90, 1.05), or other antidepressants (OR=0.95; 95% CI: 0.83, 1.07). Associations for recent and former use of antidepressants were also near null. Intensity of antidepressant use (number of pills divided by total duration of use), regardless of duration, was not associated with CRC risk. CONCLUSIONS: We found no evidence that antidepressant use substantially reduces the risk of colorectal cancer.

Utilization of oncology services and receipt of treatment: a comparison between patients with breast, colon, rectal, or lung cancer.

BACKGROUND: Higher awareness could translate into better care for patients with breast cancer than for those with other cancers. This study examines utilization of two key oncology services across cancer sites: consultation with an oncologist and receipt of treatment. PATIENTS AND METHODS: All residents of Alberta, Canada, who were diagnosed in 2005 with breast, colon, rectal, or lung cancer and had a disease stage that should be treated with chemotherapy, radiation therapy, or hormonal therapy were included. Data were obtained from the Alberta Cancer Registry and electronic cancer medical records. Percentages of patients who had a consultation and who received treatment were compared. Multivariable log-binomial regression models were used to identify patient characteristics associated with not having the outcomes. RESULTS: A much higher percentage of patients with breast cancer had consultations and received treatment (92% and 83%, respectively) than those with colon (83% and 59%), rectal (86% and 73%), or lung (77% and 66%) cancer. Age, disease stage, region of residence, and surgery status are related to having a consultation and/or receiving treatment but the relationship varies by cancer site. CONCLUSION: Efforts are needed to eliminate disparities in utilization of key cancer services across cancer sites.

Radon potential mapping of the Tralee-Castleisland and Cavan areas (Ireland) based on airborne gamma-ray spectrometry and geology.

The probability of homes in Ireland having high indoor radon concentrations is estimated on the basis of known in-house radon measurements averaged over 10 km × 10 km grid squares. The scope for using airborne gamma-ray spectrometer data for the Tralee-Castleisland area of county Kerry and county Cavan to predict the radon potential (RP) in two distinct areas of Ireland is evaluated in this study. Airborne data are compared statistically with in-house radon measurements in conjunction with geological and ground permeability data to establish linear regression models and produce radon potential maps. The best agreement between the percentage of dwellings exceeding the reference level (RL) for radon concentrations in Ireland (% > RL), estimated from indoor radon data, and modelled RP in the Tralee-Castleisland area is produced using models based on airborne gamma-ray spectrometry equivalent uranium (eU) and ground permeability data. Good agreement was obtained between the % > RL from indoor radon data and RP estimated from eU data in the Cavan area using terrain specific models. In both areas, RP maps derived from eU data are spatially more detailed than the published 10 km grid map. The results show the potential for using airborne radiometric data for producing RP maps.

Estimating population lung cancer risk from radon using a resource efficient stratified population weighted sample survey protocol - Lessons and results from Ireland.

A 2018 estimate indicates that there were 226,057 radon-attributable lung cancer deaths in 66 countries that had representative radon surveys. This is a shocking figure, and as it comes from only 66 countries it underestimates the worldwide death toll. Any research that enables countries to conduct representative radon surveys and to understand better the risk to citizens from radon is surely welcome. We hope this paper provides a useful methodology for estimating population risk. The estimation of population weighted average indoor radon levels requires statistically valid sampling methodologies that use a representative sample of occupied homes throughout the country. A literature review indicates that in many population weighted surveys, the sampling methodology may not have been designed to do this. This paper describes a simple, resource efficient methodology which produces statistically valid and reliable estimates based on a small scale sample that is representative of the population distribution. The resource efficient design of this study enables it to be repeated at frequent intervals providing for a longitudinal analysis of the population risk from indoor radon. This survey was conducted in Ireland using 653 measurements and a representative sampling strategy to provide a baseline population weighted radon exposure for future comparisons. This study estimates the average population weighted indoor radon concentration in Ireland to be 97.83 Bq m-3 (95% Confidence Interval 90.69 Bq m-3 to 105.53 Bq m-3), and that there are an estimated 350 lung cancer cases and 255 deaths per year due to radon exposure. The mortality rate of 5.3 per 100,000 due to indoor radon, demonstrates that radon remains one of the highest preventable causes of death in Ireland.

Hospitalisation for venous thromboembolism in cancer patients and the general population: a population-based cohort study in Denmark, 1997-2006.

BACKGROUND: Venous thromboembolism (VTE) frequently complicates cancer. Data on tumour-specific VTE predictors are limited, but may inform strategies to prevent thrombosis. METHODS: We computed incidence rates (IRs) with 95% confidence intervals (CIs) for VTE hospitalisation in a cohort of cancer patients (n=57,591) and in a comparison general-population cohort (n=287,476) in Denmark. The subjects entered the study in 1997-2005, and the follow-up continued through 2006. Using Cox proportional-hazards regression, we estimated relative risks (RRs) for VTE predictors, while adjusting for comorbidity. RESULTS: Throughout the follow-up, VTE IR was higher among the cancer patients (IR=8.0, 95% CI=7.6-8.5) than the general population (IR=4.7, 95% CI=4.3-5.1), particularly in the first year after cancer diagnosis (IR=15.0, 95% CI=13.8-16.2, vs IR=8.6, 95% CI=7.6-9.9). Incidence rates of VTE were highest in patients with pancreas (IR=40.9, 95% CI=29.5-56.7), brain (IR=17.7, 95% CI=11.3-27.8) or liver (IR=20.4, 95% CI=9.2-45.3) tumours, multiple myeloma (IR=22.6, 95% CI=15.4-33.2) and among patients with advanced-stage cancers (IR=27.7, 95% CI=24.0-32.0) or those who received chemotherapy or no/symptomatic treatment. The adjusted RR (aRR) for VTE was highest among patients with pancreas (aRR=16.3, 95% CI=8.1-32.6) or brain cancer (aRR=19.8 95% CI=7.1-55.2), multiple myeloma (aRR=46.1, 95% CI=13.1-162.0) and among patients receiving chemotherapy, either alone (aRR=18.5, 95% CI=11.9-28.7) or in combination treatments (aRR=16.2, 95% CI=12.0-21.7). CONCLUSIONS: Risk of VTE is higher among cancer patients than in the general population. Predictors of VTE include recency of cancer diagnosis, cancer site, stage and the type of cancer-directed treatment.

Treatment-emergent hypertension and outcomes in patients with advanced non-small-cell lung cancer receiving chemotherapy with or without the vascular endothelial growth factor receptor inhibitor cediranib: NCIC Clinical Trials Group Study BR24.

BACKGROUND: Hypertension (HTN), a recognized adverse effect of angiogenesis inhibitors, may be a potential biomarker of activity of these agents. We conducted a retrospective analysis to examine the incidence and predictors of the development of on-treatment HTN with the vascular endothelial growth factor receptor tyrosine kinase inhibitor cediranib, and the relationship of this adverse event with treatment outcomes. PATIENTS AND METHODS: BR24 was a double-blind placebo-controlled phase II trial of carboplatin/paclitaxel chemotherapy with either daily oral cediranib or placebo in patients (n = 296) with advanced non-small-cell lung cancer (NSCLC). Exploratory analyses characterized relationships between HTN, baseline variables, and efficacy outcomes. RESULTS: New onset or worsening of preexisting HTN (treatment-emergent HTN) was more frequent in patients receiving cediranib (68 versus 45%, P < 0.0001). Factors associated with HTN in all randomized patients were good performance status and treatment with cediranib. In both arms, treatment-emergent HTN was associated with improved efficacy outcomes, but there was no evidence of a differential treatment effect, with nonsignificant interaction P values. CONCLUSIONS: In advanced NSCLC, HTN is frequent in patients receiving chemotherapy, with or without cediranib. The development of HTN was favorably prognostic in these patients, but not predictive of a differential outcome with cediranib.

Treatment of non-small-cell lung cancer after progression on nivolumab or pembrolizumab.

Background: Although PD-1 antibodies (PD1 Ab) are the standard of care for advanced non-small-cell lung cancer (ansclc), most patients will progress. We compared survival outcomes for patients with ansclc who received systemic therapy (st) after progression and for those who did not. Additionally, clinical characteristics that predicted receipt of st after PD1 Ab failure were evaluated. Methods: All patients with ansclc in British Columbia initiated on nivolumab or pembrolizumab between June 2015 and November 2017, with subsequent progression, were identified. Eligibility criteria for additional st included an Eastern Cooperative Oncology Group (ecog) performance status (ps) of 3 or less and survival for more than 30 days from the last PD1 Ab treatment. Post-progression survival (pps) was assessed by landmark analysis. Baseline characteristics associated with pps were identified by multivariable analysis. Results: Of 94 patients meeting the eligibility criteria, 33 received st after progression. In 75.6%, a PD1 Ab was received as first- or second-line treatment. The most common sts were erlotinib (36.4%) and docetaxel (27.3%). No statistically significant difference in median pps was observed between patients who did and did not receive st within 30 days of their last PD1 Ab treatment (6.9 months vs. 3.6 months, log-rank p = 0.15.) In multivariable analysis, factors associated with increased pps included an ecog ps of 0 or 1 compared with 2 or 3 [hazard ratio (hr): 0.42; 95% confidence interval (ci): 0.24 to 0.73; p = 0.002] and any response compared with no response to PD1 Ab (hr: 0.54; 95% ci: 0.33 to 0.90; p = 0.02). Conclusions: In this cohort, only 35.1% of patients eligible for post-PD1 Ab therapy received st. Post-progression survival was not significantly affected by receipt of post-progression therapy. Prospective trials are needed to clarify the benefit of post-PD1 Ab treatments.