To evaluate the use of single-fraction palliative radiation therapy (SFRT) for the management of bone metastases (BM) in Victoria, Australia.
This is a population-based cohort of patients with cancer ...who received radiation therapy for BM between 2012 and 2017 as captured in the Victorian Radiotherapy Minimum Data Set. The primary outcome was proportion of SFRT use. The Cochrane-Armitage test for trend was used to evaluate changes in practice over time. Multivariable logistic regression was used to assess factors associated with SFRT use.
Of the 18,158 courses of radiation therapy for BM delivered to a total of 10,956 patients, 17% were SFRT. There was no significant change in SFRT use over time, from 18% in 2012 to 19% in 2017 (P = .07). SFRT was less commonly given to the skull (4%) and spine (14%), compared with the shoulder (37%) and ribs (53%). Patients with lung cancer (21%) were most likely to receive SFRT, followed by those with prostate cancers (18%) and gastrointestinal cancers (16%). Patients from regional/remote areas were more likely to have SFRT compared with those in major cities (22% vs 16%, P < .001). Patients treated in public institutions were more likely to have SFRT compared with those treated in private institutions (22% vs 10%, P < .001). In multivariable analyses, increasing age, lung cancer, higher socioeconomic status, residence in regional/ remote areas, and being treated in public institutions were factors independently associated with increased likelihood of receiving SFRT.
SFRT appears underused for BM in Australia over time, with variation in practice by patient, tumor, sociodemographic, geographical, and institutional provider factors.
Infections caused by multi-resistant Gram-negative bacteria, particularly
Pseudomonas aeruginosa, are increasing worldwide. In patients with cystic fibrosis (CF), resistance in
P. aeruginosa to ...numerous anti-pseudomonal agents is becoming common. The absence since 1995, of new substances active against resistant Gram-negative bacteria, has caused increasing concern. Colistin, an old antibiotic also known as polymyxin E, has attracted more interest recently because of its significant activity against multi-resistant
P. aeruginosa,
Acinetobacter baumannii and
Klebsiella pneumoniae, and the low resistance rates to it. Because its use as an anti-pseudomonal agent was displaced by the potentially less toxic aminoglycosides in 1970s, our knowledge of this drug is limited. However, there has been a significant recent increase in the data gathered on colistin, focussing on its chemistry, antibacterial activity, mechanism of action and resistance, pharmacokinetics, pharmacodynamics and new clinical application. It is likely that colistin will be an important antimicrobial option against multi-resistant Gram-negative bacteria, for some years to come.
The association between body mass index (BMI) and risk of breast cancer depends on time of life, but it is unknown whether this association depends on a woman's familial risk.
We conducted a ...prospective study of a cohort enriched for familial risk consisting of 16,035 women from 6701 families in the Breast Cancer Family Registry and the Kathleen Cunningham Foundation Consortium for Research into Familial Breast Cancer followed for up to 20 years (mean 10.5 years). There were 896 incident breast cancers (mean age at diagnosis 55.7 years). We used Cox regression to model BMI risk associations as a function of menopausal status, age, and underlying familial risk based on pedigree data using the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA), all measured at baseline.
The strength and direction of the BMI risk association depended on baseline menopausal status (P < 0.001); after adjusting for menopausal status, the association did not depend on age at baseline (P = 0.6). In terms of absolute risk, the negative association with BMI for premenopausal women has a much smaller influence than the positive association with BMI for postmenopausal women. Women at higher familial risk have a much larger difference in absolute risk depending on their BMI than women at lower familial risk.
The greater a woman's familial risk, the greater the influence of BMI on her absolute postmenopausal breast cancer risk. Given that age-adjusted BMI is correlated across adulthood, maintaining a healthy weight throughout adult life is particularly important for women with a family history of breast cancer.
ObjectiveMost studies investigating the association between resting heart rate (RHR) and mortality have focused on cardiovascular disease (CVD) mortality, and measured RHR at only one time point. We ...aimed to assess associations of RHR and changes in RHR over approximately a decade with overall and cause-specific mortality.MethodsWe used data from participants in the Melbourne Collaborative Cohort Study with RHR measures at baseline (1990–1994; n=41 386; 9846 deaths) and at follow-up (2003–2007; n=21 692; 2818 deaths). RHR measures were taken by trained staff, using Dinamap monitors. Cox models were used to estimate HR and 95% CI for the associations between RHR and mortality. Vital status and cause of death were ascertained until August 2015 and December 2013, respectively.ResultsAfter adjustment for confounders, including blood pressure and known medical conditions but not arrhythmias or atrial fibrillation, RHR was associated with a higher risk of death of similar magnitude for CVD (HR per 10 beats per minute (bpm)=1.11, 95% CI 1.07 to 1.16), cancer (HR=1.10, 95% CI 1.06 to 1.13) and other causes (HR=1.20, 95% CI 1.16 to 1.25). Higher mortality was observed for most cancer sites, including breast (HR=1.16, 95% CI 1.03 to 1.31), colorectal (HR=1.18, 95% CI 1.08 to 1.29), kidney (HR=1.27, 95% CI 1.03 to 1.57) and lung cancer (HR=1.19, 95% CI 1.10 to 1.29). Temporal increases in RHR were associated with higher mortality, particularly for individuals whose RHR increased by more than 15 bpm.ConclusionsRHR and changes in RHR over a decade are associated with mortality risk, including from causes other than CVD such as breast, colorectal or lung cancer. Monitoring of RHR may have utility in identifying individuals at higher mortality risk.
Independent validation is essential to justify use of models of breast cancer risk prediction and inform decisions about prevention options and screening. Few independent validations had been done ...using cohorts for common breast cancer risk prediction models, and those that have been done had small sample sizes and short follow-up periods, and used earlier versions of the prediction tools. We aimed to validate the relative performance of four commonly used models of breast cancer risk and assess the effect of limited data input on each one's performance.
In this validation study, we used the Breast Cancer Prospective Family Study Cohort (ProF-SC), which includes 18 856 women from Australia, Canada, and the USA who did not have breast cancer at recruitment, between March 17, 1992, and June 29, 2011. We selected women from the cohort who were 20–70 years old and had no previous history of bilateral prophylactic mastectomy or ovarian cancer, at least 2 months of follow-up data, and information available about family history of breast cancer. We used this selected cohort to calculate 10-year risk scores and compare four models of breast cancer risk prediction: the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm model (BOADICEA), BRCAPRO, the Breast Cancer Risk Assessment Tool (BCRAT), and the International Breast Cancer Intervention Study model (IBIS). We compared model calibration based on the ratio of the expected number of breast cancer cases to the observed number of breast cancer cases in the cohort, and on the basis of their discriminatory ability to separate those who will and will not have breast cancer diagnosed within 10 years as measured with the concordance statistic (C-statistic). We did subgroup analyses to compare the performance of the models at 10 years in BRCA1 or BRCA2 mutation carriers (ie, BRCA-positive women), tested non-carriers and untested participants (ie, BRCA-negative women), and participants younger than 50 years at recruitment. We also assessed the effect that limited data input (eg, restriction of the amount of family history and non-genetic information included) had on the models' performance.
After median follow-up of 11·1 years (IQR 6·0–14·4), 619 (4%) of 15 732 women selected from the ProF-SC cohort study were prospectively diagnosed with breast cancer after recruitment, of whom 519 (84%) had histologically confirmed disease. BOADICEA and IBIS were well calibrated in the overall validation cohort, whereas BRCAPRO and BCRAT underpredicted risk (ratio of expected cases to observed cases 1·05 95% CI 0·97–1·14 for BOADICEA, 1·03 0·96–1·12 for IBIS, 0·59 0·55–0·64 for BRCAPRO, and 0·79 0·73–0·85 for BRCAT). The estimated C-statistics for the complete validation cohort were 0·70 (95% CI 0·68–0·72) for BOADICEA, 0·71 (0·69–0·73) for IBIS, 0·68 (0·65–0·70) for BRCAPRO, and 0·60 (0·58–0·62) for BCRAT. In subgroup analyses by BRCA mutation status, the ratio of expected to observed cases for BRCA-negative women was 1·02 (95% CI 0·93–1·12) for BOADICEA, 1·00 (0·92–1·10) for IBIS, 0·53 (0·49–0·58) for BRCAPRO, and 0·97 (0·89–1·06) for BCRAT. For BRCA-positive participants, BOADICEA and IBIS were well calibrated, but BRCAPRO underpredicted risk (ratio of expected to observed cases 1·17 95% CI 0·99–1·38 for BOADICEA, 1·14 0·96–1·35 for IBIS, and 0·80 0·68–0·95 for BRCAPRO). We noted similar patterns of calibration for women younger than 50 years at recruitment. Finally, BOADICEA and IBIS predictive scores were not appreciably affected by limiting input data to family history for first-degree and second-degree relatives.
Our results suggest that models that include multigenerational family history, such as BOADICEA and IBIS, have better ability to predict breast cancer risk, even for women at average or below-average risk of breast cancer. Although BOADICEA and IBIS performed similarly, further improvements in the accuracy of predictions could be possible with hybrid models that incorporate the polygenic risk component of BOADICEA and the non-family-history risk factors included in IBIS.
US National Institutes of Health, National Cancer Institute, Breast Cancer Research Foundation, Australian National Health and Medical Research Council, Victorian Health Promotion Foundation, Victorian Breast Cancer Research Consortium, Cancer Australia, National Breast Cancer Foundation, Queensland Cancer Fund, Cancer Councils of New South Wales, Victoria, Tasmania, and South Australia, and Cancer Foundation of Western Australia.
To determine the clinical characteristics, outcomes and longitudinal trends of sepsis occurring in cancer patients.
Retrospective study using statewide Victorian Cancer Registry data linked to ...various administrative datasets.
Among 215,763 incident cancer patients, incidence of sepsis within one year of cancer diagnosis was estimated at 6.4%. The incidence of sepsis was higher in men, younger patients, patients diagnosed with haematological malignancies and those with de novo metastatic disease. Of the 13,316 patients with a first admission with sepsis, 55% had one or more organ failures, 29% required care within an intensive care unit and 13% required mechanical ventilation. Treatments associated with the highest sepsis incidence were stem cell/bone marrow transplant (33%), major surgery (4.4%), chemotherapy (1.1%) and radical radiotherapy (0.6%). The incidence of sepsis with organ failure increased between 2008 and 2015, while 90‐day mortality decreased.
Sepsis in patients with cancer has high mortality and occurs most frequently in the first year after cancer diagnosis.
The number of cancer patients diagnosed with sepsis is expected to increase, causing a substantial burden on patients and the healthcare system.
To compare breast cancer prognosis in BRCA1 and BRCA2 mutation carriers with that in patients with sporadic disease.
An international population-based cohort study was conducted in Canada, the United ...States, and Australia of 3,220 women with incident breast cancer diagnosed between 1995 and 2000 and observed prospectively. Ninety-three had BRCA1 mutations; 71, BRCA2 mutations; one, both mutations; 1,550, sporadic breast cancer; and 1,505, familial breast cancer (without known BRCA1 or BRCA2 mutation). Distant recurrence and death were analyzed.
Mean age at diagnosis was 45.3 years; mean follow-up was 7.9 years. Risks of distant recurrence and death did not differ significantly between BRCA1 mutation carriers and those with sporadic disease in univariable and multivariable analyses. Risk of distant recurrence was higher for BRCA2 mutation carriers compared with those with sporadic disease in univariable analysis (hazard ratio HR, 1.63; 95% CI, 1.02 to 2.60; P = .04). Risk of death was also higher in BRCA2 carriers in univariable analysis (HR, 1.81; 95% CI, 1.15 to 2.86; P = .01). After adjustment for age, tumor stage and grade, nodal status, hormone receptors, and year of diagnosis, no differences were observed for distant recurrence (HR, 1.00; 95% CI, 0.62 to 1.61; P = 1.00) or death (HR, 1.12; 95% CI, 0.70 to 1.79; P = .64).
Outcomes of BRCA1 mutation carriers were similar to those of patients with sporadic breast cancer. Worse outcomes in BRCA2 mutation carriers in univariable analysis seem to reflect the presence of more adverse tumor characteristics in these carriers. Similar outcomes were identified in BRCA2 carriers and those with sporadic disease in multivariable analyses.
Various subtypes of breast cancer defined by estrogen receptor (ER), progesterone receptor (PR), and HER2 exhibit etiologic differences in reproductive factors, but associations with other risk ...factors are inconsistent. To clarify etiologic heterogeneity, we pooled data from nine cohort studies. Multivariable, joint Cox proportional hazards regression models were used to estimate HRs and 95% confidence intervals (CI) for molecular subtypes. Of 606,025 women, 11,741 invasive breast cancers with complete tissue markers developed during follow-up: 8,700 luminal A-like (ER
or PR
/HER2
), 1,368 luminal B-like (ER
or PR
/HER2
), 521 HER2-enriched (ER
/PR
/HER2
), and 1,152 triple-negative (ER
/PR
/HER2
) disease. Ever parous compared with never was associated with lower risk of luminal A-like (HR, 0.78; 95% CI, 0.73-0.83) and luminal B-like (HR, 0.74; 95% CI, 0.64-0.87) as well as a higher risk of triple-negative disease (HR, 1.23; 95% CI, 1.02-1.50;
value for overall tumor heterogeneity < 0.001). Direct associations with luminal-like, but not HER2-enriched or triple-negative, tumors were found for age at first birth, years between menarche and first birth, and age at menopause (
value for overall tumor heterogeneity < 0.001). Age-specific associations with baseline body mass index differed for risk of luminal A-like and triple-negative breast cancer (
value for tumor heterogeneity = 0.02). These results provide the strongest evidence for etiologic heterogeneity of breast cancer to date from prospective studies.
These findings comprise the largest study of prospective data to date and contribute to the accumulating evidence that etiological heterogeneity exists in breast carcinogenesis.
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