Development and validation of a predictive risk model for acute skin toxicity in patients undergoing breast radiotherapy

BackgroundClinically significant side-effects from radiotherapy affect around a quarter of breast cancer patients and may have a considerable impact on breast cosmesis and quality of life. If patients at high risk of radiation toxicity could be identified at breast cancer diagnosis, this could be taken into account when discussing treatment options. The aim of this study was to develop a predictive model for acute skin toxicity in patients undergoing breast radiotherapy.MethodsUsing multivariate logistic regression and backwards elimination, the risk model for acute skin toxicity (moderately brisk reaction and/or ≥1 acute desquamation) was first developed in patient cohorts treated by breast-conserving surgery and whole breast radiotherapy in three European centres (Leicester, Heidelberg/Mannheim, Cambridge; total n=2,012) with a biologically effective dose (BED) range from 47.1 to 67.2 Gy. It was externally validated in breast cancer patients enrolled in the multi-centre REQUITE cohort study (n=2,062; BED range 44.6 to 75.4 Gy).ResultsThe final model with the variables age, BED, cup size or BMI, and presence/absence of diabetes, smoking, and hypertension proved to give best prediction of acute skin toxicity with a c-statistic (AUC) of 0.79 in the development and 0.75 in the validation cohort and was well calibrated (Hosmer-Lemeshow p=0.53). ConclusionsA predictive model for radiotoxicity has the potential to give clinicians important information when planning treatment to reduce side-effects and optimise quality of life. The addition of prognostic genetic markers investigated as part of the REQUITE study is likely to improve model performance. Similar models can be developed for other toxicity endpoints, such as breast fibrosis, and should also be validated for patients undergoing chest wall radiotherapy and breast reconstruction. </p

Motivations to nurse: An exploration of what motivates students in Pacific Island countries to enter nursing

The aim of this study was to explore the motivations of student nurses enrolled in nursing courses across a variety of Pacific Island countries. The image of nursing, the desire to help others, family and friends in the profession, personal experience, security, travel opportunities and flexibility have all been identified as motivators for people to enter nursing. To date, what motivates students in Pacific Island countries to enrol in a nursing course has not been investigated. An exploratory qualitative approach using focus group interviews with 152 nursing students was undertaken. Data were analysed using thematic content analysis, revealing four themes: (i) helping others; (ii) 'making a difference for my people'; (iii) following in the footsteps of others; and (iv) financial and professional gain. In a time of health and nursing workforce shortages, developing a deeper understanding of what drives people can be used to improve recruitment strategies in the future. © 2013 Wiley Publishing Asia Pty Ltd

Strengthening and preparing: Enhancing nursing research for disaster management

© 2014 Elsevier Ltd.Nurses are often first line responders in a large scale emergency or disaster. This paper reports an evaluative study of a tailored research capacity building course for nurse delegates from the Asia Pacific Emergency and Disaster Nursing Network (APEDNN). Twenty-three participant delegates from 19 countries attended a three-week course that included learning and teaching about the critique and conduct of research. An outcome of the course was the collaborative design of a study now being implemented in a number of countries with the aim of investigating nurses' preparedness for disaster response. Formal mentoring relationships have also been established between more and less experienced peers and facilitators to provide support in implementing this collaborative study. Overall, participant delegates rated the planning, implementation and content of the course highly. Recommendations from this study include funding a mix of face-to-face and distance mentoring and writing for publication workshops to ensure the sustainability of outcomes from a research capacity building course such as the one described

Indigenous Health : ACTION on Prevention - 50th annual Australian Society for Medical Research National Scientific Conference

The 50th annual National Scientific Conference of the Australian Society for Medical Research was held in Cairns, Queensland, 13–16 November 2011. The theme, ‘Indigenous Health: ACTION on Prevention’ highlighted the direct action being undertaken by health and medical researchers, as well as allied health professionals, to improve long-term health outcomes for Indigenous Australians

Genetic Variants Predict Optimal Timing of Radiotherapy to Reduce Side-effects in Breast Cancer Patients

AIMS: Radiotherapy is an important treatment for many types of cancer, but a minority of patients suffer long-term side-effects of treatment. Multiple lines of evidence suggest a role for circadian rhythm in the development of radiotherapy late side-effects. MATERIALS AND METHODS: We carried out a study to examine the effect of radiotherapy timing in two breast cancer patient cohorts. The retrospective LeND cohort comprised 535 patients scored for late effects using the Late Effects of Normal Tissue-Subjective Objective Management Analytical (LENT-SOMA) scale. Acute effects were assessed prospectively in 343 patients from the REQUITE study using the CTCAE v4 scales. Genotyping was carried out for candidate circadian rhythm variants. RESULTS: In the LeND cohort, patients who had radiotherapy in the morning had a significantly increased incidence of late toxicity in univariate (P = 0.03) and multivariate analysis (P = 0.01). Acute effects in the REQUITE group were also significantly increased in univariate analysis after morning treatment (P = 0.03) but not on multivariate analysis. Increased late effects in the LeND group receiving morning radiotherapy were associated with carriage of the PER3 variable number tandem repeat 4/4 genotype (P = 6 × 10-3) and the NOCT rs131116075 AA genotype (P = 5 × 10-3). CONCLUSION: Our results suggest that it may be possible to reduce toxicity associated with breast cancer radiotherapy by identifying gene variants that affect circadian rhythm and scheduling for appropriate morning or afternoon radiotherapy

Acute toxicity and quality of life in breast cancer patients treated by radiotherapy - results from the REQUITE multi-centre cohort study

BackgroundAlthough patient-reported outcomes (PROs) to assess health-related quality-of-life (QoL) are increasingly incorporated in radiotherapy trials, QoL in the acute period following treatment remains under-reported. This study assessed the relationship between QoL in the acute treatment phase, toxicity, patient and treatment variables in breast cancer patients.MethodsBreast cancer patients (n = 2,072) were recruited following breast-conserving surgery across eight centres in Europe and North America into a multicentre prospective cohort study (www.requite.eu). Treatment data, toxicity scored according to CTCAE v4.0, and PROs from EORTC-QLQ-C30 and –B23 were available for 1,750 patients at baseline and on completion of radiotherapy. Association of acute toxicity endpoints (dichotomised) and worsening QoL (≥ 10 point change from baseline) was investigated using multivariate logistic regression, adjusted for age, BMI, total radiotherapy dose, seroma, chemotherapy, tamoxifen, analgesic use, smoking and alcohol intake.ResultsBy the end of radiotherapy, 24.2 % of patient experienced ≥ grade 2 erythema, 31.6 % ≥ grade 1 oedema, and 9.5 % were affected by acute desquamation (skin loss). Global health status, fatigue, pain, and breast symptoms worsened significantly compared to baseline. Acute erythema and acute desquamation were significantly associated with worsening breast symptoms (OR 1.71, 95 % CI 1.41-2.06; and OR 1.77, 1.18-2.67), while acute erythema was also associated with worsening pain (1.24, 1.03-1.50). There was no significant association of any acute toxicity endpoint with worsening global health status.ConclusionsManagement of early toxicities that affect breast-specific symptoms and pain may improve QoL during radiotherapy. Overall QoL (global health status) during breast radiotherapy is likely to be influenced by a range of non-treatment factors.</p

The REQUITE-AB study: Validating predictive models and biomarkers of radiotherapy toxicity to reduce side-effects and improve quality of life in breast cancer patients

Clinically significant side-effects from radiotherapy affect around a quarter of breast cancer patients and may impact considerably on outcomes from treatment. An increasing number of replicated genetic associations for radiotherapy toxicity are being reported[1],[2]. The EU-funded REQUITE consortium aims to validate genetic markers and clinical factors implicated in radiotoxicity. The purpose of the REQUITE-AB project is to develop an integrated set of predictors for acute radiotherapy side-effects in breast cancer patients to be used as a clinical decision-making tool.As part of the REQUITE prospective cohort study, 2,000 patients eligible for adjuvant breast radiotherapy will be recruited in nine centres across Europe and North America between April 2014 and August 2016, with centralised data management, biobanking and two years’ follow-up using a standardised data collection protocol. Patient characteristics and treatment details being captured also include dose-volume histograms and DICOM files. Genotyping will take place in fall 2016. Primary endpoints are acute skin toxicity (CTC-AE v4.0) and quality-of-life (QoL) on completion of radiotherapy and at 3 months from start of radiotherapy. Secondary endpoints are late side-effects including change in breast appearance.1,766 breast cancer patients have been recruited to date with standardized documentation of toxicity and QoL. Among patients who completed radiotherapy so far, 21.6% of patients developed grade 2 skin toxicity (brisk erythema) and 1.3% grade 3 (moist desquamation). The ability of patient, treatment and genetic variables to predict clinical outcomes and QoL will be examined. The REQUITE study includes the largest radiogenomics cohort of breast cancer patients to date recruited under a single standardised protocol. Findings of the REQUITE-AB project are likely to inform the development of interventional biomarker trials and personalise breast cancer care in the future. [1] Talbot et al, Br J Cancer, 2012; 107: 748-53.[2] Seibold et al, Int J Radiat Oncol Biol Phys, 2015; 92: 1084-92</div

The REQUITE project: integrating biomarkers and clinical predictors of radiotherapy side effects

The European Union funded REQUITE consortium aims to validate predictors of radiotherapy-related adverse reactions to develop clinically useful tools. Potential predictors include clinical and dose parameters, genetic markers, gene expression and the radiation-induced lymphocyte apoptosis (RILA)

Use of angiotensin converting enzyme inhibitors is associated with reduced risk of late bladder toxicity following radiotherapy for prostate cancer

Background and purposeGenome-wide association studies (GWAS) of late hematuria following prostate cancer radiotherapy identified single nucleotide polymorphisms (SNPs) near AGT, encoding angiotensinogen. We tested the hypothesis that patients taking angiotensin converting enzyme inhibitors (ACEi) have a reduced risk of late hematuria. We additionally tested genetically-defined hypertension.Materials and methodsProstate cancer patients undergoing potentially-curative radiotherapy were enrolled onto two multi-center observational studies, URWCI (N = 256) and REQUITE (N = 1,437). Patients were assessed pre-radiotherapy and followed prospectively for development of toxicity for up to four years. The cumulative probability of hematuria was estimated by the Kaplan-Meier method. Multivariable grouped relative risk models assessed the effect of ACEi on time to hematuria adjusting for clinical factors and stratified by enrollment site. A polygenic risk score (PRS) for blood pressure was tested for association with hematuria in REQUITE and our Radiogenomics Consortium GWAS.ResultsPatients taking ACEi during radiotherapy had a reduced risk of hematuria (HR 0.51, 95%CI 0.28 to 0.94, p = 0.030) after adjusting for prior transurethral prostate and/or bladder resection, heart disease, pelvic node radiotherapy, and bladder volume receiving 70 Gy, which are associated with hematuria. A blood pressure PRS was associated with hypertension (odds ratio per standard deviation 1.38, 95%CI 1.31 to 1.46, n = 5,288, p ConclusionsOur study is the first to show a radioprotective effect of ACEi on bladder in an international, multi-site study of patients receiving pelvic radiotherapy. Mechanistic studies are needed to understand how targeting the angiotensin pathway protects the bladder.</div

A unified call to action from Australian nursing and midwifery leaders: Ensuring that Black lives matter

Nurses and midwives of Australia now is the time for change! As powerfully placed, Indigenous and non-Indigenous nursing and midwifery professionals, together we can ensure an effective and robust Indigenous curriculum in our nursing and midwifery schools of education. Today, Australia finds itself in a shifting tide of social change, where the voices for better and safer health care ring out loud. Voices for justice, equity and equality reverberate across our cities, our streets, homes, and institutions of learning. It is a call for new songlines of reform. The need to embed meaningful Indigenous health curricula is stronger now than it ever was for Australian nursing and midwifery. It is essential that nursing and midwifery leadership continue to build an authentic collaborative environment for Indigenous curriculum development. Bipartisan alliance is imperative for all academic staff to be confident in their teaching and learning experiences with Indigenous health syllabus. This paper is a call out. Now is the time for Indigenous and non-Indigenous nurses and midwives to make a stand together, for justice and equity in our teaching, learning, and practice. Together we will dismantle systems, policy, and practices in health that oppress. The Black Lives Matter movement provides us with a ‘now window’ of accepted dialogue to build a better, culturally safe Australian nursing and midwifery workforce, ensuring that Black Lives Matter in all aspects of health care