Women with atypical hyperplasia (AH) or lobular carcinoma in situ (LCIS) have a significantly increased risk of breast cancer, which can be substantially reduced with antiestrogen therapy for ...chemoprevention. However, antiestrogen therapy for breast cancer risk reduction remains underutilized. Improving knowledge about breast cancer risk and chemoprevention among high-risk patients and their healthcare providers may enhance informed decision-making about this critical breast cancer risk reduction strategy.
We are conducting a cluster randomized controlled trial to evaluate the effectiveness and implementation of patient and provider decision support tools to improve informed choice about chemoprevention among women with AH or LCIS. We have cluster randomized 26 sites across the U.S. through the SWOG Cancer Research Network. A total of 415 patients and 200 healthcare providers are being recruited. They are assigned to standard educational materials alone or combined with the web-based decision support tools. Patient-reported and clinical outcomes are assessed at baseline, after a follow-up visit at 6 months, and yearly for 5 years. The primary outcome is chemoprevention informed choice after the follow-up visit. Secondary endpoints include other patient-reported outcomes, such as chemoprevention knowledge, decision conflict and regret, and self-reported chemoprevention usage. Barriers and facilitators to implementing decision support into clinic workflow are assessed through patient and provider interviews at baseline and mid-implementation.
With this hybrid effectiveness/implementation study, we seek to evaluate if a multi-level intervention effectively promotes informed decision-making about chemoprevention and provide valuable insights on how the intervention is implemented in U.S. clinical settings.
NCT04496739
Background: Chronic exposure to traffic-related air pollution (TRAP) may contribute to premature mortality, but few studies to date have addressed this topic. Objectives: In this study we assessed ...the association between TRAP and mortality in Toronto, Ontario, Canada. Methods: We collected nitrogen dioxide samples over two seasons using duplicate two-sided Ogawa passive diffusion samplers at 143 locations across Toronto. We calibrated land use regressions to predict NO₂ exposure on a fine scale within Toronto. We used interpolations to predict levels of particulate matter with aerodynamic diameter ≤ 2.5 μm$({\rm PM}_{2.5})$and ozone levels. We assigned predicted pollution exposures to 2,360 subjects from a respiratory clinic, and abstracted health data on these subjects from medical billings, lung function tests, and diagnoses by pulmonologists. We tracked mortality between 1992 and 2002. We used standard and multilevel Cox proportional hazard models to test associations between air pollution and mortality. Results: After controlling for age, sex, lung function, obesity, smoking, and neighborhood deprivation, we observed a 17% increase in all-cause mortality and a 40% increase in circulatory mortality from an exposure contrast across the interquartile range of 4 ppb NO₂. We observed no significant associations with other pollutants. Conclusions: Exposure to TRAP was significantly associated with increased all-cause and circulatory mortality in this cohort. A high prevalence of cardiopulmonary disease in the cohort probably limits inference of the findings to populations with a substantial proportion of susceptible individuals.
This study aimed to identify a set of stable radiomic parameters in CT perfusion (CTP) maps with respect to CTP calculation factors and image discretization, as an input for future prognostic models ...for local tumor response to chemo-radiotherapy. Pre-treatment CTP images of eleven patients with oropharyngeal carcinoma and eleven patients with non-small cell lung cancer (NSCLC) were analyzed. 315 radiomic parameters were studied per perfusion map (blood volume, blood flow and mean transit time). Radiomics robustness was investigated regarding the potentially standardizable (image discretization method, Hounsfield unit (HU) threshold, voxel size and temporal resolution) and non-standardizable (artery contouring and noise threshold) perfusion calculation factors using the intraclass correlation (ICC). To gain added value for our model radiomic parameters correlated with tumor volume, a well-known predictive factor for local tumor response to chemo-radiotherapy, were excluded from the analysis. The remaining stable radiomic parameters were grouped according to inter-parameter Spearman correlations and for each group the parameter with the highest ICC was included in the final set. The acceptance level was 0.9 and 0.7 for the ICC and correlation, respectively. The image discretization method using fixed number of bins or fixed intervals gave a similar number of stable radiomic parameters (around 40%). The potentially standardizable factors introduced more variability into radiomic parameters than the non-standardizable ones with 56-98% and 43-58% instability rates, respectively. The highest variability was observed for voxel size (instability rate >97% for both patient cohorts). Without standardization of CTP calculation factors none of the studied radiomic parameters were stable. After standardization with respect to non-standardizable factors ten radiomic parameters were stable for both patient cohorts after correction for inter-parameter correlations. Voxel size, image discretization, HU threshold and temporal resolution have to be standardized to build a reliable predictive model based on CTP radiomics analysis.
Small for gestational age (SGA: birth weight below 10th percentile), low birth weight at term (LBWT: birth weight below 2500 g at 37 or more weeks gestation), and preterm birth (PTB: born before 37 ...completed weeks gestation) are increasing in Canada, contribute to infant mortality and morbidity, and linked to the maternal exposome, including exposure to environmental hazards. We assessed province-level associations of birth events (n = 2,525,645; years 2006–2012) classified as SGA, LBWT, and PTB with prenatal exposures to industrial air pollutants (n = 228) and land activities (n = 8). We used GIS to spatially and temporally assign variables to the maternal residences at birth. We used logistic regression to identify which industrial chemical emissions or land activities had associations for thirteen provinces/territories. There were twenty-four chemicals, including ammonia, benzene, carbon monoxide, methyl ethyl ketone, and particulate matter – fifteen of which are known or suspected developmental toxicants that may affect SGA/LBWT/PTB. There were geographical differences in exposures and associations. The provinces that had statistically significant adverse birth outcome associations with: (i) only chemicals were in Ontario, Nunavut, and Yukon; (ii) predominantly chemicals were in Alberta, Newfoundland, and Québec; (iii) only land activities were in Manitoba, New Brunswick, Nova Scotia, Prince Edward Island, and Saskatchewan; and (iv) predominantly land activities were in British Columbia. Pollutants released to the air or potential hazards from land-based activities may be more important depending on where one lives.
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•Understanding atmospheric and anthropogenic risk factors for adverse birth outcomes•Seven years of birth data associated with shared sources of maternal exposures•Spatiotemporal population-level exposures differed for each Canadian province/territory.•Air pollutants or land-based hazards may be more important depending on location.
•17.3% of patients developed brain image changes, all were asymptomatic.•Most image changes occurred in patients with nasopharyngeal or sinonasal cancer.•Lesions were found in the temporal lobe, ...frontal lobe and cerebellum.•Lesions were stable/still in progression in eight patients and improved/resolved in ten.•To reduce risk, focal high doses to the brain should be minimized.
To characterize patterns and outcomes of brain MR image changes after proton therapy (PT) for skull base head and neck cancer (HNC).
Post-treatment MRIs ≥6 months were reviewed for radiation-associated image changes (RAIC) in 127 patients. All patients had received at least a point dose of 40 Gy(RBE) to the brain. The MRIs were rigidly registered to planning CTs and RAIC lesions were contoured both on T1 weighted (post-contrast) and T2 weighted sequences, and dose–volume parameters extracted. Probability of RAIC was calculated using multistate survival analysis. Univariate/multivariate analyses were performed using Cox Regression. Recursive partitioning analysis was used to investigate dose–volume correlates of RAIC development.
17.3% developed RAIC. All RAIC events were asymptomatic and occurred in the temporal lobe (14), frontal lobe (6) and cerebellum (2). The median volume of the contrast enhanced RAIC lesion was 0.5 cc at their maximum size. The RAIC resolved or improved in 45.5% of the patients and were stable or progressed in 36.4%. The 3-year actuarial rate of developing RAIC was 14.3%. RAIC was observed in 63% of patients when V67 Gy(RBE) of the brain ≥0.17 cc.
Small RAIC lesions after PT occurred in 17.3% of the patients; the majority in nasopharyngeal or sinonasal cancer. The estimated dose–volume correlations confirm the importance of minimizing focal high doses to brain when achievable.
•The use of oral stents during RT was associated with reduced late morbidity.•OPC patients with bilateral RT and tongue-depressing stents had less dysphagia.•Patients with unilateral RT and ...tongue-deviating stent had better taste/appetite.
To evaluate whether the use of oral stents during intensity modulated radiation therapy (IMRT) for oropharyngeal cancer (OPC) is associated with long-term patient reported symptoms.
Data was obtained from a prospective observational study of disease-free head and neck cancer survivors. Radiation-associated patient reported symptoms were assessed using the MD Anderson Symptom Inventory Head and Neck module (MDASI-HN). Scores of ≥5 (11-point Likert scale, 0-10) were considered moderate/severe. Stratification was performed regarding IMRT volume (uni- versus bilateral neck) and stent utilization, with non-parametric analyses between groups.
462 OPC survivors formed the cohort (54% tonsil, 46% base of tongue primaries). A tongue-deviating stent was used in 17%, tongue-depressing stent in 46%, and no stent in 37%. Median prescribed dose to the high dose clinical target volume was 66.0 Gy. Median follow-up from RT to MDASI-HN assessment was 68 months. Twenty percent had received unilateral neck RT (all had tonsil primaries), in whom a significant improvement in the proportion of patients with moderate/severe taste impairment (2% vs. 15%, p = 0.047) and lack of appetite (0% vs. 9%, p = 0.019) was associated with the use of tongue-deviating stents compared to no oral stent. In those who had received bilateral neck RT, a significant improvement in the proportion of patients with moderate/severe difficulty swallowing/chewing was associated with use of a tongue-depressing stent (21% vs. 31% without oral stent, p = 0.013).
Disease-site specific select use of oral stents during IMRT was associated with reduced long-term patient reported symptoms in OPC survivors.
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