Over the past four decades, the proportion of women among both first and senior physician-authors of original research in the United States has significantly increased. Nevertheless, women still compose a minority of the authors of original research and guest editorials in the journals studied.
Purpose Radiotherapy reduces the absolute risk of breast cancer mortality by a few percentage points in suitable women but can cause a second cancer or heart disease decades later. We estimated the absolute long-term risks of modern breast cancer radiotherapy. Methods First, a systematic literature review was performed of lung and heart doses in breast cancer regimens published during 2010 to 2015. Second, individual patient data meta-analyses of 40,781 women randomly assigned to breast cancer radiotherapy versus no radiotherapy in 75 trials yielded rate ratios (RRs) for second primary cancers and cause-specific mortality and excess RRs (ERRs) per Gy for incident lung cancer and cardiac mortality. Smoking status was unavailable. Third, the lung or heart ERRs per Gy in the trials and the 2010 to 2015 doses were combined and applied to current smoker and nonsmoker lung cancer and cardiac mortality rates in population-based data. Results Average doses from 647 regimens published during 2010 to 2015 were 5.7 Gy for whole lung and 4.4 Gy for whole heart. The median year of irradiation was 2010 (interquartile range [IQR], 2008 to 2011). Meta-analyses yielded lung cancer incidence ≥ 10 years after radiotherapy RR of 2.10 (95% CI, 1.48 to 2.98; P < .001) on the basis of 134 cancers, indicating 0.11 (95% CI, 0.05 to 0.20) ERR per Gy whole-lung dose. For cardiac mortality, RR was 1.30 (95% CI, 1.15 to 1.46; P < .001) on the basis of 1,253 cardiac deaths. Detailed analyses indicated 0.04 (95% CI, 0.02 to 0.06) ERR per Gy whole-heart dose. Estimated absolute risks from modern radiotherapy were as follows: lung cancer, approximately 4% for long-term continuing smokers and 0.3% for nonsmokers; and cardiac mortality, approximately 1% for smokers and 0.3% for nonsmokers. Conclusion For long-term smokers, the absolute risks of modern radiotherapy may outweigh the benefits, yet for most nonsmokers (and ex-smokers), the benefits of radiotherapy far outweigh the risks. Hence, smoking can determine the net effect of radiotherapy on mortality, but smoking cessation substantially reduces radiotherapy risk.
Background Female physician-researchers do not achieve career success at the same rate as men. Differences in nonprofessional responsibilities may partially explain this gap. Objective To investigate the division of domestic labor by gender in a motivated group of early-career physician-researchers. Design Nationwide postal survey between 2010 and 2011. Setting United States. Participants Physician recipients of National Institutes of Health K08 or K23 awards between 2006 and 2009 with active academic affiliation at the time of the survey. Measurements Time spent on parenting and domestic tasks was determined through self-report. Among married or partnered respondents with children, a linear regression model of time spent on domestic activities was constructed considering age, gender, race, specialty, MD or MD/PhD status, age of youngest child, number of children, work hours, K award type, and spousal employment. Results A 74% response rate was achieved, and 1049 respondents were academic physicians. Women were more likely than men to have spouses or domestic partners who were employed full-time (85.6% [95% CI, 82.7% to 89.2%] vs. 44.9% [CI, 40.8% to 49.8%]). Among married or partnered respondents with children, after adjustment for work hours, spousal employment, and other factors, women spent 8.5 more hours per week on domestic activities. In the subgroup with spouses or domestic partners who were employed full-time, women were more likely to take time off during disruptions of usual child care arrangements than men (42.6% [CI, 36.6% to 49.0%] vs. 12.4% [CI, 5.4% to 19.5%]). Limitations Analyses relied on self-reported data. The study design did not enable investigation of the relationship between domestic activities and professional success. Conclusion In this sample of career-oriented professionals, gender differences in domestic activities existed among those with children. Most men's spouses or domestic partners were not employed full-time, which contrasted sharply with the experiences of women.
SummaryBackgroundNeoadjuvant chemotherapy (NACT) for early breast cancer can make breast-conserving surgery more feasible and might be more likely to eradicate micrometastatic disease than might the same chemotherapy given after surgery. We investigated the long-term benefits and risks of NACT and the influence of tumour characteristics on outcome with a collaborative meta-analysis of individual patient data from relevant randomised trials.MethodsWe obtained information about prerandomisation tumour characteristics, clinical tumour response, surgery, recurrence, and mortality for 4756 women in ten randomised trials in early breast cancer that began before 2005 and compared NACT with the same chemotherapy given postoperatively. Primary outcomes were tumour response, extent of local therapy, local and distant recurrence, breast cancer death, and overall mortality. Analyses by intention-to-treat used standard regression (for response and frequency of breast-conserving therapy) and log-rank methods (for recurrence and mortality).FindingsPatients entered the trials from 1983 to 2002 and median follow-up was 9 years (IQR 5–14), with the last follow-up in 2013. Most chemotherapy was anthracycline based (3838 [81%] of 4756 women). More than two thirds (1349 [69%] of 1947) of women allocated NACT had a complete or partial clinical response. Patients allocated NACT had an increased frequency of breast-conserving therapy (1504 [65%] of 2320 treated with NACT vs 1135 [49%] of 2318 treated with adjuvant chemotherapy). NACT was associated with more frequent local recurrence than was adjuvant chemotherapy: the 15 year local recurrence was 21·4% for NACT versus 15·9% for adjuvant chemotherapy (5·5% increase [95% CI 2·4–8·6]; rate ratio 1·37 [95% CI 1·17–1·61]; p=0·0001). No significant difference between NACT and adjuvant chemotherapy was noted for distant recurrence (15 year risk 38·2% for NACT vs 38·0% for adjuvant chemotherapy; rate ratio 1·02 [95% CI 0·92–1·14]; p=0·66), breast cancer mortality (34·4% vs 33·7%; 1·06 [0·95–1·18]; p=0·31), or death from any cause (40·9% vs 41·2%; 1·04 [0·94–1·15]; p=0·45).InterpretationTumours downsized by NACT might have higher local recurrence after breast-conserving therapy than might tumours of the same dimensions in women who have not received NACT. Strategies to mitigate the increased local recurrence after breast-conserving therapy in tumours downsized by NACT should be considered—eg, careful tumour localisation, detailed pathological assessment, and appropriate radiotherapy.FundingCancer Research UK, British Heart Foundation, UK Medical Research Council, and UK Department of Health.
Purpose Cardiac toxicity is an important sequela of breast radiotherapy. However, the relationship between dose to cardiac structures and subsequent toxicity has not been well defined, partially due to variation in substructure delineation, which can lead to inconsistent dose reporting and the failure to detect potential correlations. Here we have developed a heart atlas and evaluated its effect on contour accuracy and concordance. Methods and Materials A detailed cardiac CT atlas was developed jointly by cardiology, cardiac radiology, and radiation oncology. Seven radiation oncologists were recruited to delineate the whole heart (WH), left main (LM), left anterior descending interventricular branch (LAD), and right coronary arteries (RCA) on four cases before and after studying the atlas. Contour accuracy was assessed by percent overlap with gold standard (GS) atlas volumes. The concordance index (CI) was also calculated. Standard radiation fields were applied. Doses to observer-contoured cardiac (OC) structures were calculated, and compared with GS contour doses. Pre- and post- atlas values were analyzed using a paired t-test. Results The cardiac atlas significantly improved contour accuracy and concordance. Percent overlap and CI of OC and GS volumes improved for all structures, by up to 2.3-fold (p<0.002). After application of the atlas, reported WH, LM, LAD, and RCA mean doses were within 0.1, 0.9, 2.6, and 0.6 Gy of GS doses. Conclusions This validated University of Michigan cardiac atlas may serve as a useful tool in future studies assessing cardiac toxicity and in clinical trials which include dose volume constraints to the heart.
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