Chronic obstructive pulmonary disease and the development of atrial fibrillation

Background: Chronic obstructive pulmonary disease (COPD) has been associated with atrial fibrillation (AF). More insight into the epidemiology and underlying mechanisms is required to optimize management. Methods: The Rotterdam Study is a large, population-based cohort study with long-term follow-up. Time dependent Cox proportional hazard models were constructed to study the effect of COPD on incident AF, adjusted for age, sex and pack years of cigarette smoking, and additionally stratified according to exacerbation frequency, left atrial size and baseline systemic inflammatory levels. Results: 1369 of 10,943 subjects had COPD, of whom 804 developed AF. The AF incidence rate was 14 per 1000 person years in COPD and 8 per 1000 person years in subjects without COPD. The adjusted hazard ratio (HR) for COPD subjects to develop AF as compared to subjects without COPD was 1.28 (95% CI [1.04, 1.57]). COPD subjects with frequent exacerbations had a twofold increased AF risk (HR 1.99 [1.42, 2.79]) and COPD subjectswith a left atrial size >= 40 mm also had an elevated AF risk (HR 1.77 [1.07, 2.94]). COPD subjects with baseline systemic inflammatory levels above the median had significantly increased AF risks (hsCRP=1.83 mg/L: HR 1.51 [1.13, 2.03] and IL6 >= 1.91 ng/L: HR 2.49 [1.18, 5.28]), whereas COPD subjects below the median had in both analyses no significantly increased AF risk. Conclusions: COPD subjects had a 28% increased AF risk, which further increased with frequent exacerbations and an enlarged left atrium. The risk was driven by COPD subjects having elevated systemic inflammatory levels

Acute toxicity and health-related quality of life after accelerated whole breast irradiation in 5 fractions with simultaneous integrated boost

Introduction: Acceleration of radiotherapy in 5 fractions for breast cancer can reduce the burden of treatment. We report on acute toxicity after whole-breast irradiation with a simultaneous integrated boost in 5 fractions over 10-12 days. Material and methods: Acute toxicity and health-related quality of life (HRQoL) of 200 patients, randomized between a 15or 5-fractions schedule, were collected, using the CTCAE toxicity scoring system, the Multidimensional Fatigue Inventory, EORTC QLQ-C30 and BR23 and the BREAST-Q questionnaire. The prescribed dose to the breast was either 15*2.67 Gy (40.05 Gy) or 5*5.7 Gy (28.5 Gy). 90% of patients received a SIB to a cumulative dose of 46.8 Gy (15*3.12 Gy) or 31 Gy (5*6.2 Gy). Results: Physician-assessed toxicity was lower for the 5-fractions group. A significant difference was observed for breast pain (p = 0.002), fatigue (p < 0.0001), breast edema (p = 0.001) and dermatitis (p = 0.003). Patients treated in 5 fractions reported better mean HRQoL scores for breast symptoms (p = 0.001) and physical well-being (p = 0.001). A clinically important deterioration in HRQoL of 10 points or more was also less frequently observed in the latter group for physical functioning (p = 0.0005), social functioning (p = 0.0007), fatigue (p = 0.003), breast symptoms (p = 0.0002) and physical wellbeing (p = 0.002). Conclusion: In this single institute study, acute toxicity of accelerated breast radiotherapy in 5 fractions over 10-12 days seems to compare favourably to hypofractionated breast radiotherapy in 15 fractions. Less breast edema, dermatitis, desquamation, breast pain and fatigue are seen. Social and physical functioning are also less disturbed and patients have a better future perspective

Feasibility study on pre or postoperative accelerated radiotherapy (POP-ART) in breast cancer patients

Background: In early-stage breast cancer, the cornerstone of treatment is surgery. After breast-conserving surgery, adjuvant radiotherapy has shown to improve locoregional control and overall survival rates. The use of breast radiotherapy in the preoperative (preop) setting is far less common. Nevertheless, it might improve disease-free survival as compared to postoperative radiotherapy. There is also a possibility of downsizing the tumour which might lead to a lower need for mastectomy. There are some obstacles that complicate its introduction into daily practice. It may complicate surgery or lead to an increase in wound complications or delayed wound healing. Another fear of preop radiotherapy is delaying surgery for too long. At Ghent University Hospital, we have experience with a 5-fraction radiotherapy schedule allowing radiotherapy delivery in a very short time span. Methods: Twenty female breast cancer patients with non-metastatic disease receiving preop chemotherapy will be randomized between preop or postoperative radiotherapy. The feasibility of preop radiotherapy will be evaluated based on overall treatment time. All patients will be treated in 5 fractions of 5.7 Gy to the whole breast with a simultaneous integrated boost to the tumour/tumour bed of 5 × 6.2 Gy. In case of lymph node irradiation, the lymph node regions will receive a dose of 27 Gy in 5 fractions of 5.4 Gy. The total duration of therapy will be 10 to 12 days. In the preop group, overall treatment time is defined as the time between diagnosis and the day of last surgery, in the postop group between diagnosis and last irradiation fraction. Toxicity related to surgery, radio-, and chemotherapy will be evaluated on dedicated case-report forms at predefined time points. Tumour response will be evaluated on the pathology report and on MRI at baseline and in the interval between chemotherapy and surgery. Discussion: The primary objective of the trial is to investigate the feasibility of preop radiotherapy. Secondary objectives are to search for biomarkers of response and toxicity and identify the involved cell death mechanisms and the effect of preop breast radiotherapy on the in-situ immune micro-environment

Effects of deep inspiration breath hold on prone photon or proton irradiation of breast and regional lymph nodes

We report on a comparative dosimetrical study between deep inspiration breath hold (DIBH) and shallow breathing (SB) in prone crawl position for photon and proton radiotherapy of whole breast (WB) and locoregional lymph node regions, including the internal mammary chain (LN_MI). We investigate the dosimetrical effects of DIBH in prone crawl position on organs-at-risk for both photon and proton plans. For each modality, we further estimate the effects of lung and heart doses on the mortality risks of different risk profiles of patients. Thirty-one patients with invasive carcinoma of the left breast and pathologically confirmed positive lymph node status were included in this study. DIBH significantly decreased dose to heart for photon and proton radiotherapy. DIBH also decreased lung doses for photons, while increased lung doses were observed using protons because the retracting heart is displaced by low-density lung tissue. For other organs-at-risk, DIBH resulted in significant dose reductions using photons while minor differences in dose deposition between DIBH and SB were observed using protons. In patients with high risks for cardiac and lung cancer mortality, average thirty-year mortality rates from radiotherapy-related cardiac injury and lung cancer were estimated at 3.12% (photon DIBH), 4.03% (photon SB), 1.80% (proton DIBH) and 1.66% (proton SB). The radiationrelated mortality risk could not outweigh the similar to 8% disease-specific survival benefit of WB + LN_MI radiotherapy in any of the assessed treatments

Development and Optimization of a Machine-Learning Prediction Model for Acute Desquamation After Breast Radiation Therapy in the Multicenter REQUITE Cohort.

Some patients with breast cancer treated by surgery and radiation therapy experience clinically significant toxicity, which may adversely affect cosmesis and quality of life. There is a paucity of validated clinical prediction models for radiation toxicity. We used machine learning (ML) algorithms to develop and optimise a clinical prediction model for acute breast desquamation after whole breast external beam radiation therapy in the prospective multicenter REQUITE cohort study. Using demographic and treatment-related features (m = 122) from patients (n = 2058) at 26 centers, we trained 8 ML algorithms with 10-fold cross-validation in a 50:50 random-split data set with class stratification to predict acute breast desquamation. Based on performance in the validation data set, the logistic model tree, random forest, and naïve Bayes models were taken forward to cost-sensitive learning optimisation. One hundred and ninety-two patients experienced acute desquamation. Resampling and cost-sensitive learning optimisation facilitated an improvement in classification performance. Based on maximising sensitivity (true positives), the "hero" model was the cost-sensitive random forest algorithm with a false-negative: false-positive misclassification penalty of 90:1 containing m = 114 predictive features. Model sensitivity and specificity were 0.77 and 0.66, respectively, with an area under the curve of 0.77 in the validation cohort. ML algorithms with resampling and cost-sensitive learning generated clinically valid prediction models for acute desquamation using patient demographic and treatment features. Further external validation and inclusion of genomic markers in ML prediction models are worthwhile, to identify patients at increased risk of toxicity who may benefit from supportive intervention or even a change in treatment plan. [Abstract copyright: © 2022 The Authors.

Prone crawl breast couch : analysis of the translational development of a patient support device for breast cancer radiotherapy

Currently available prone support devices for breast cancer radiotherapy show different limitations, such as inconsistent patient positioning, patient discomfort and limited beam accessibility. Furthermore, medical devices tend to be developed with a top-down waterfall approach. For devices with complex use scenarios, this may impact efficacy. Therefore, we developed a patient support device with a Research through Design approach, supported by a co-design trajectory with different stakeholders. In this deductive case study, we analyze our development approach. We reflect on the NIH’s T-phases of translational research and the Stanford BioDesign Process. We conclude that the user-centred and iterative aspects of our approach were beneficial to the regulatory process and the quality of the product. Furthermore, cooperating with a university hospital enhanced the regulatory process by its access to clinical data. The outcomes of this interdisciplinary research may be beneficial to other types of cancer such as lung cancer

Four irradiation and three positioning techniques for whole breast radiotherapy : is sophisticated always better?

Purpose We report on a dosimetrical study of three patient positions (supine, prone dive, and prone crawl) and four irradiation techniques for whole-breast irradiation (WBI): wedged-tangential fields (W-TF), tangential-field intensity-modulated radiotherapy (TF-IMRT), multi-beam IMRT (MB-IMRT), and intensity-modulated arc therapy (IMAT). This is the first study to evaluate prone crawl positioning in WBI and the first study to quantify dosimetrical and anatomical differences with prone dive positioning. Methods We analyzed five datasets with left- and right-sided patients (n = 51). One dataset also included deep-inspiration breath hold (DIBH) data. A total of 252 new treatment plans were composed. Dose-volume parameters and indices of conformity were calculated for the planning target volume (PTV) and organs-at-risk (OARs). Furthermore, anatomical differences among patient positions were quantified to explain dosimetrical differences. Results Target coverage was inferior for W-TF and supine position. W-TF proved overall inferior, and IMAT proved foremost effective in supine position. TF-IMRT proved competitive to the more demanding MB-IMRT and IMAT in prone dive, but not in prone crawl position. The lung-sparing effect was overall confirmed for both prone dive and prone crawl positioning and was largest for prone crawl. For the heart, no differences were found between prone dive and supine positioning, whereas prone crawl showed cardiac advantages, although minor compared to the established heart-sparing effect of DIBH. Dose differences for contralateral breast were minor among the patient positions. In prone crawl position, the ipsilateral breast sags deeper and the PTV is further away from the OARs than in prone dive position. Conclusions The prone dive and prone crawl position are valid alternatives to the supine position in WBI, with largest advantages for lung structures. For the heart, differences are small, which establishes the role of DIBH in different patient positions. These results may be of particular interest to radiotherapy centers with limited technical resources