The effect of acute alcohol ingestion on systemic hemodynamics and sleep architecture in young, healthy men.

Objective Heightened nocturnal blood pressure (BP) may be attributed to the disruption of sleep, a condition worsened by alcohol ingestion. This study investigated the effects of acute alcohol ingestion on hemodynamics and sleep architecture in a young, healthy cohort of male. METHODS: Subjects (n = 17) underwent acute alcohol ingestion reaching a breath alcohol content of 0.08. Each subject endured a battery of hemodynamic tests and had their sleep architecture and nocturnal blood pressure monitored pre- and post-ingestion. Results: Systolic blood pressure (SBP) increased both 30 minutes and 12 hours after alcohol. Ambulatory nocturnal SBP significantly increased after alcohol compared to baseline measures. Minutes of total, rapid eye movement, and light sleep all increased after alcohol ingestion, while a decrease was observed for sleep latency. Conclusions: An acute bout of heavy alcohol consumption may attenuate nocturnal BP dipping that, in turn, may hasten the progression of hypertension-related cardiovascular disease.

Effects on carotid-femoral pulse wave velocity 24 h post exercise in young healthy adults.

Arterial stiffness, often measured by carotid-femoral pulse wave velocity (cfPWV), is a subclinical marker of cardiovascular disease that is known to be reduced by exercise training. Exercise is also known to have acute vascular effects, yet it is unclear whether exercise 24 h before cfPWV testing influences this outcome. Thirty healthy, young adults completed a supervised, 30-min bout of moderate-to-vigorous intensity treadmill running. cfPWV, systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) were measured both before (after 48 h of abstaining from exercise) and 24 h after (with no additional exercise) the exercise session. From pre-exercise to 24 h post exercise, cfPWV decreased from 6.05±0.82 to 5.84±0.87 m s(-1) (P=0.02), SBP from 119.7±13.8 to 116.8±11.4 mm Hg (P=0.03) and DBP from 65.1±5.7 to 63.2±5.4 mm Hg (P=0.02), with no significant changes in HR. cfPWV was positively correlated with SBP pre-exercise (r=0.54, P<0.01) and post exercise (r=0.53, P<0.01). Changes in blood pressure explained 4-5% of the variability in cfPWV change; adjustments slightly attenuated the 24-h effects of exercise on cfPWV. Some evidence of gender differences was observed with higher cfPWV in males across assessments (P<0.05) and statistically significant reductions in cfPWV in males (-0.36±0.54 m s(-1) (P=0.02)) but not in females (-0.07±0.31 m s(-1) (P=0.41)). In conclusion, cfPWV decreased 24 h after an exercise bout, suggesting that exercise completed in the past 24 h should be considered before cfPWV testing.

Patient reported outcome measures (PROMs) following forward planned field-in field IMRT: results from the Cambridge Breast IMRT trial.

BACKGROUND: The use of intensity-modulated radiotherapy (IMRT) in breast cancer reduces clinician-assessed breast tissue toxicity including fibrosis, telangectasia and sub-optimal cosmesis. Patient reported outcome measures (PROMs) are also important as they provide the patient's perspective. This longitudinal study reports on (a) the effect of forward planned field-in-field IMRT (∼simple IMRT) on PROMs compared to standard RT at 5 years after RT, (b) factors affecting PROMs at 5years after RT and (c) the trend of PROMs over 5 years of follow up. METHODS: PROMs were assessed at baseline (pre-RT), 6, 24 and 60 months after completion of RT using global health (EORTC QLQ C30) and 4 breast symptom questions (BR23). Also, 4 breast RT-specific questions were included at 6, 24 and 60 months: change in skin appearance, firmness to touch, reduction in breast size and overall change in breast appearance since RT. The benefits of simple IMRT over standard RT at 5 years after RT were assessed using standard t-test for global health and logistic regression analysis for breast symptom questions and breast RT-specific questions. Clinical factors affecting PROMs at 5 years were investigated using a multivariate analysis. A repeated mixed model was applied to explore the trend over time for each of PROMs. RESULTS: (89%) 727/815, 84%, 81% and 61% patients completed questionnaires at baseline, 6, 24 and 60 months respectively. Patients reported worse toxicity for all four BR23 breast symptoms at 6 months, which then improved over time (p<0.0001). They also reported improvement in skin appearance and breast hardness over time (p<0.0001), with no significant change for breast shrinkage (p=0.47) and overall breast appearance (p=0.13). At 5years, PROMs assessments did not demonstrate a benefit for simple IMRT over standard radiotherapy. Large breast volume, young age, baseline surgical cosmesis and post-operative infection were the most important variables to affect PROMs. CONCLUSIONS: This study was unable to demonstrate the benefits of IMRT on PROMs at 5years. PROMs are influenced by non-radiotherapy factors and surgical factors should be optimised to improve patients' outcome. Only a small proportion of patients report moderate-severe breast changes post radiotherapy, with most PROMs improving over time. The difference in clinician assessment and PROMs outcome requires further investigation.

Randomized controlled trial of intensity-modulated radiotherapy for early breast cancer: 5-year results confirm superior overall cosmesis.

PURPOSE: There are few randomized controlled trial data to confirm that improved homogeneity with simple intensity-modulated radiotherapy (IMRT) decreases late breast tissue toxicity. The Cambridge Breast IMRT trial investigated this hypothesis, and the 5-year results are reported. PATIENTS AND METHODS: Standard tangential plans of 1,145 trial patients were analyzed; 815 patients had inhomogeneous plans (≥ 2 cm(3) receiving 107% of prescribed dose: 40 Gy in 15 fractions over 3 weeks) and were randomly assigned to standard radiotherapy (RT) or replanned with simple IMRT; 330 patients with satisfactory dose homogeneity were treated with standard RT and underwent the same follow-up as the randomly assigned patients. Breast tissue toxicities were assessed at 5 years using validated methods: photographic assessment (overall cosmesis and breast shrinkage compared with baseline pre-RT photographs) and clinical assessment (telangiectasia, induration, edema, and pigmentation). Comparisons between different groups were analyzed using polychotomous logistic regression. RESULTS: On univariate analysis, compared with standard RT, fewer patients in the simple IMRT group developed suboptimal overall cosmesis (odds ratio [OR], 0.68; 95% CI, 0.48 to 0.96; P = .027) and skin telangiectasia (OR, 0.58; 95% CI, 0.36 to 0.92; P = .021). No evidence of difference was seen for breast shrinkage, breast edema, tumor bed induration, or pigmentation. The benefit of IMRT was maintained on multivariate analysis for both overall cosmesis (P = .038) and skin telangiectasia (P = .031). CONCLUSION: Improved dose homogeneity with simple IMRT translates into superior overall cosmesis and reduces the risk of skin telangiectasia. These results are practice changing and should encourage centers still using two-dimensional RT to implement simple breast IMRT.

Randomized controlled trial of forward-planned intensity modulated radiotherapy for early breast cancer: interim results at 2 years.

PURPOSE: This single-center randomized trial was designed to investigate whether intensity-modulated radiotherapy (IMRT) reduces late toxicity in patients with early-stage breast cancer. METHODS AND MATERIALS: The standard tangential plans of 1,145 nonselected patients were analyzed. The patients with inhomogeneous plans were randomized to a simple method of forward-planned IMRT or standard radiotherapy (RT). The primary endpoint was serial photographic assessment of breast shrinkage. RESULTS: At 2 years, no significant difference was found in the development of any photographically assessed breast shrinkage between the patients randomized to the interventional or control group (odds ratio, 1.51; 95% confidence interval, 0.83-1.58; p = .41). The patients in the control group were more likely to develop telangiectasia than those in the IMRT group (odds ratio, 1.68; 95% confidence interval 1.13-2.40; p = .009). Poor baseline surgical cosmesis resulted in poor overall cosmesis at 2 years after RT. In patients who had good surgical cosmesis, those randomized to IMRT were less likely to deteriorate to a moderate or poor overall cosmesis than those in the control group (odds ratio, 0.63; 95% confidence interval, 0.39-1.03, p = .061). CONCLUSIONS: IMRT can lead to a significant reduction in telangiectasia at comparatively early follow-up of only 2 years after RT completion. An important component of breast induration and shrinkage will actually result from the surgery and not from the RT. Surgical cosmesis is an important determinant of overall cosmesis and could partially mask the longer term benefits of IMRT at this early stage.

A randomised controlled trial of forward-planned radiotherapy (IMRT) for early breast cancer: baseline characteristics and dosimetry results.

BACKGROUND AND PURPOSE: This large trial was designed to investigate whether correction of dose inhomogeneities using intensity-modulated radiotherapy (IMRT) reduces late toxicity and improves quality of life in patients with early breast cancer. This paper reports baseline characteristics of trial participants and dosimetry results. MATERIALS AND METHODS: Standard tangential plans of 1145 trials were analysed. Patients with inhomogeneous plans, defined by ICRU recommendations, were randomised to forward-planned IMRT or standard radiotherapy. RESULTS: Twenty-nine percentage of patients had adequate dosimetry with standard 2D radiotherapy. In the randomised patients, the decreases in mean volumes receiving greater than 107% (Vol>107) and less than 95% (Vol<95) of the prescribed dose in the IMRT compared with the control group were 34.0 cm(3) (95% CI 26.4-41.6; P<0.0001) and 48.1 cm(3) (95% CI 34.4-61.9; P<0.0001), respectively. In this study, 90% of patients who had a breast separation greater > or = 21 cm had Vol>107>2 cm(3) on standard radiotherapy plans. CONCLUSION: This large trial, in which patients with all breast sizes were eligible, confirmed that breast dosimetry can be significantly improved with a simple method of forward-planned IMRT and has little impact on radiotherapy resources. It is shown that patients with larger breasts are more likely to have dose inhomogeneities and breast separation gives some indication of this likelihood. Photographic assessment of patients at 2 years after radiotherapy, as the next part of this randomised controlled trial, will show whether these results for IMRT translate into improved cosmetic outcome in patients with early breast cancer. This would provide impetus for the widespread adoption of 3D planning and IMRT.