In the Young Boost trial (YBT), breast cancer patients ≤50 years of age, treated with breast conserving therapy (BCT) were randomized between a 26 Gy boost dose and a 16 Gy boost dose, with local ...recurrence as primary and cosmetic outcome (CO) as secondary endpoint. Data of the YBT was used to investigate which factors are related with worse cosmetic outcome after BCT.
From 2004 to 2011, 2421 cT1-2N0-2a breast cancer patients were randomized. CO was scored subjectively by the patient and physician, and objectively using BCCT.core: at baseline, one and four years after treatment. Associations between potential risk factors for worse cosmetic outcome, based on the objective BCCT.core, were investigated using a proportional odds model.
At four years, CO was significantly better in the standard boost group for all three scoring methods (satisfied CO ±65% vs 55%). A photon boost, high boost dose, poor cosmesis before radiation therapy, large boost volume and adjuvant chemotherapy significantly deteriorated CO.
Important risk factors for worse CO were the use of a photon boost instead of an electron boost, a high boost dose, cosmesis at baseline, adjuvant chemotherapy and boost volume. These results can be used to define strategies aimed at improving CO.
Abstract Purpose To investigate which factors are related to patient reported cosmetic outcome (PRCO) after breast conserving therapy. Methods From 2004 to 2011, 2421 cT1-2N0-2a breast cancer ...patients were randomised in the Young Boost Trial between a 16 and a 26 Gy boost to the tumour bed. Cosmesis was scored subjectively by the patient and physician, and objectively using BCCT.core, at baseline, one and four years after treatment. Presence of fibrosis, QoL and rib pain at four years were also scored. Data were complete for 864 patients. The relation between the separate components was investigated using a proportional odds model. Results Of the 7 BCCT.core parameters, the distance from nipple to inframammary fold and the length of the breast contour were significantly related to the overall PRCO at four years. Patients with more fibrosis and poorer QoL scored their cosmesis worse, while rib pain was not related. The agreement between the different scores was low (kappa 0.26–0.42). Conclusion The distance from nipple to inframammary fold, the length of the breast contour and the severity of fibrosis were the main factors related to patient-reported cosmetic outcome. Patients with better QoL scored their cosmesis better.
To compare set-up and 2-dimensional (2D) electronic portal imaging device (EPID) dosimetry data of breast cancer patients treated during voluntary moderately deep inspiration breath hold (vmDIBH) and ...free breathing (FB).
Set-up data were analyzed for 29 and 51 consecutively treated patients, irradiated during FB and vmDIBH, respectively. Of the 51 vmDIBH patients, the first 25 had undergone an extra trained computed tomography (CT) scan and used an additional "breathing stick" (vmDIBH_trained). The last 26 patients did not use the breathing stick and did not undergo a trained CT (vmDIBH_untrained). The delivered 2D transit dose was measured with EPID in 15 FB and 28 vmDIBH patients and compared with a 2D predicted dose by calculating global gamma values γ using 5% and 5 mm as dose difference and distance-to-agreement criteria, respectively. Measurements with a percentage of pixels with an absolute gamma value > 1 (|γ| > 1) greater than 10% were classified as deviating.
Only small, sub-millimeter differences were seen in the set-up data between the different patient groups. The mean of means, systematic error, and random error ranged from - 0.6 mm to 3.3 mm. The percentage of pixels with |γ| > 1 for all patients was 9.8% (2-25.8). No statistically significant differences were observed between the patient groups. In total, 38% of the gamma images were classified as deviating: 43.6% in vmDIBH_untrained patients compared with 38.0% in vmDIBH_trained patients and 33.3% in FB patients (P > .05).
Both set-up and 2D EPID dosimetry data indicate that reproducibility of radiation therapy for patients treated during FB and vmDIBH is similar. Small but not significant differences in 2D EPID dosimetry were observed. Further investigation with 3-dimensional EPID dosimetry is recommended to investigate the clinical relevance of deviant gamma images.
A paradigm shift from current population based medicine to personalized and participative medicine is underway. This transition is being supported by the development of clinical decision support ...systems based on prediction models of treatment outcome. In radiation oncology, these models ‘learn’ using advanced and innovative information technologies (ideally in a distributed fashion — please watch the animation: http://youtu.be/ZDJFOxpwqEA) from all available/appropriate medical data (clinical, treatment, imaging, biological/genetic, etc.) to achieve the highest possible accuracy with respect to prediction of tumor response and normal tissue toxicity. In this position paper, we deliver an overview of the factors that are associated with outcome in radiation oncology and discuss the methodology behind the development of accurate prediction models, which is a multi-faceted process. Subsequent to initial development/validation and clinical introduction, decision support systems should be constantly re-evaluated (through quality assurance procedures) in different patient datasets in order to refine and re-optimize the models, ensuring the continuous utility of the models. In the reasonably near future, decision support systems will be fully integrated within the clinic, with data and knowledge being shared in a standardized, dynamic, and potentially global manner enabling truly personalized and participative medicine.
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In the field of work, there is a shift towards more value-based approaches to study the sustainable employability of the present-day worker. The capability approach offers a value based and ...innovative conceptualisation and framework of sustainable employability characterized by contextuality, normativity and diversity. The capabilities of Dutch employees have been established and validated, yet it is not known which conversion factors on a personal, work and organizational level enable employees to achieve value in work in different Dutch occupational sectors. Our qualitative approach included seven focus groups in different occupational sectors including elderly care, higher education, insurance work, facility management and the oil-, car- and chemical industry. Each focus group included 5-11 participants and took approximately one and a half hour. A qualitative content analysis was used to analyse the data, by combining deductive and inductive coding respectively. Deductive coding involved assigning themes to the conversion of resources into capabilities at the organizational, work and personal level. On the organizational conversion level, important themes were cultural aspects, power relations, shortage of personnel and policies for self-management. On the work conversion level, social contacts, communication and workload, tasks and schedules were identified. Social contacts were described as a work value in itself, but also conditional for achieving other work values. On the personal conversion level, experienced work stress, motivation and the ability to achieve values informally within the company. From our findings it follows that focus groups are sensitive to identify conversion factors on all three levels of conversion. In addition, companies and their employees might effectively increase work capabilities by being sensitive to all three conversion levels simultaneously. Further research is necessary to study the effect of a capability-based intervention at the work floor.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Being gifted with a very high IQ (> 98 percentile) can provide an advantage in the occupational context but can also come with its` own specific challenges. Where some studies found higher than ...average levels of wellbeing at work and successful careers amongst the gifted, other studies report boredom and less job satisfaction. This poses the question what gifted people value in work, and which factors are associated with the achievement of valued work related outcomes, wellbeing and sustainable employability. In this study these questions were explored using the value driven capability approach as a theoretical framework.
A qualitative approach was chosen and 16 in-depth semi-structured interviews with gifted workers (IQ > 130) were conducted. The transcripts were analysed using a reflexive thematic analysis aimed at identifying the work related outcomes participants aspired to achieve and the contextual and personal factors that affected the actualisation of these outcomes.
Participants placed great value on the opportunity to learn, to use their knowledge and skills, and tended to have high ethical standards. If realized, these values contributed to wellbeing whereas if not fulfilled, this often resulted in frustration and sadness. The most important personal factors associated with wellbeing at work and sustainable employability were the level of organizational awareness, self-knowledge, a willingness to compromise, and fear of stigmatisation. Contextually a facilitating leadership style of managers was important, allowing the worker autonomy and decision latitude. Socially, participants enjoyed others as sparring partners but often had an aversion to small talk which could lead to social avoidance and loneliness.
If gifted workers managed (to get) what they valued in work, this was associated with wellbeing and sustainable employment Coaching aimed at improving organizational awareness, specific social skills (e.g. small talk, adaptability) and understanding their own cognitive processes could be valuable. The application of an autonomy supporting facilitative leadership style by supervisors would be beneficial. Further research should try to confirm the findings using quantitative methods and needs to examine more closely the impact of stigmatisation and leadership styles.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In patients with aneurysmal subarachnoid haemorrhage, short-term antifibrinolytic therapy with tranexamic acid has been shown to reduce the risk of rebleeding. However, whether this treatment ...improves clinical outcome is unclear. We investigated whether ultra-early, short-term treatment with tranexamic acid improves clinical outcome at 6 months.
In this multicentre prospective, randomised, controlled, open-label trial with masked outcome assessment, adult patients with spontaneous CT-proven subarachnoid haemorrhage in eight treatment centres and 16 referring hospitals in the Netherlands were randomly assigned to treatment with tranexamic acid in addition to care as usual (tranexamic acid group) or care as usual only (control group). Tranexamic acid was started immediately after diagnosis in the presenting hospital (1 g bolus, followed by continuous infusion of 1 g every 8 h, terminated immediately before aneurysm treatment, or 24 h after start of the medication, whichever came first). The primary endpoint was clinical outcome at 6 months, assessed by the modified Rankin Scale, dichotomised into a good (0–3) or poor (4–6) clinical outcome. Both primary and safety analyses were according to intention to treat. This trial is registered at ClinicalTrials.gov, NCT02684812.
Between July 24, 2013, and July 29, 2019, we enrolled 955 patients; 480 patients were randomly assigned to tranexamic acid and 475 patients to the control group. In the intention-to-treat analysis, good clinical outcome was observed in 287 (60%) of 475 patients in the tranexamic acid group, and 300 (64%) of 470 patients in the control group (treatment centre adjusted odds ratio 0·86, 95% CI 0·66–1·12). Rebleeding after randomisation and before aneurysm treatment occurred in 49 (10%) patients in the tranexamic acid and in 66 (14%) patients in the control group (odds ratio 0·71, 95% CI 0·48–1·04). Other serious adverse events were comparable between groups.
In patients with CT-proven subarachnoid haemorrhage, presumably caused by a ruptured aneurysm, ultra-early, short-term tranexamic acid treatment did not improve clinical outcome at 6 months, as measured by the modified Rankin Scale.
Fonds NutsOhra.
The mechanisms linking immune responses and inflammation with tumor development are not well understood. Here, we show that the soluble form of the extracellular matrix proteoglycan decorin controls ...inflammation and tumor growth through PDCD4 (programmed cell death 4) and miR-21 (microRNA-21) by two mechanisms. First, decorin acted as an endogenous ligand of Toll-like receptors 2 and 4 and stimulated production of proinflammatory molecules, including PDCD4, in macrophages. Second, decorin prevented translational repression of PDCD4 by decreasing the activity of transforming growth factor-β1 and the abundance of oncogenic miR-21, a translational inhibitor of PDCD4. Moreover, increased PDCD4 abundance led to decreased release of the anti-inflammatory cytokine interleukin-10, thereby making the cytokine profile more proinflammatory. This pathway operates in both pathogen-mediated and sterile inflammation, as shown here for sepsis and growth retardation of established tumor xenografts, respectively. Decorin was an early response gene evoked by septic inflammation, and protein concentrations of decorin were increased in the plasma of septic patients and mice. In cancer, decorin reduced the abundance of anti-inflammatory molecules and increased that of proinflammatory molecules, thereby shifting the immune response to a proinflammatory state associated with reduced tumor growth. Thus, by stimulating proinflammatory PDCD4 and decreasing the abundance of miR-21, decorin signaling boosts inflammatory activity in sepsis and suppresses tumor growth.
The ULTRA trial showed that ultra-early and short-term tranexamic acid treatment after subarachnoid hemorrhage did not improve clinical outcome at 6 months. An expected proportion of the included ...patients experienced nonaneurysmal subarachnoid hemorrhage. In this post hoc study, we will investigate whether ultra-early and short-term tranexamic acid treatment in patients with aneurysmal subarachnoid hemorrhage improves clinical outcome at 6 months.
The ULTRA trial is a multicenter, prospective, randomized, controlled, open-label trial with blinded outcome assessment, conducted between July 24, 2013, and January 20, 2020. After confirmation of subarachnoid hemorrhage on noncontrast CT, patients were allocated to either ultra-early and short-term tranexamic acid treatment with usual care or usual care only. In this post hoc analysis, we included all ULTRA participants with a confirmed aneurysm on CT angiography and/or digital subtraction angiography. The primary endpoint was clinical outcome at 6 months, assessed by the modified Rankin scale (mRS), dichotomized into good (0-3) and poor (4-6) outcomes.
Of the 813 ULTRA trial patients who experienced an aneurysmal subarachnoid hemorrhage, 409 (50%) were assigned to the tranexamic acid group and 404 (50%) to the control group. In the intention-to-treat analysis, 233 of 405 (58%) patients in the tranexamic acid group and 238 of 399 (60%) patients in the control group had a good clinical outcome (adjusted odds ratio aOR 0.92; 95% CI 0.69-1.24). None of the secondary outcomes showed significant differences between the treatment groups: excellent clinical outcome (mRS 0-2) (aOR 0.76; 95% CI 0.57-1.03), all-cause mortality at 30 days (aOR 0.91; 95% CI 0.65-1.28), and all-cause mortality at 6 months (aOR 1.10; 95% CI 0.80-1.52).
Ultra-early and short-term tranexamic acid treatment did not improve clinical outcomes at 6 months in patients with aneurysmal subarachnoid hemorrhage and therefore cannot be recommended.
ClinicalTrials.gov (NCT02684812; submission date February 18, 2016, first patient enrollment on July 24, 2013).
This study provides Class II evidence that tranexamic acid does not improve outcomes in patients presenting with aneurysmal subarachnoid hemorrhage.
Non-invasive imaging of angiogenesis could ease the optimization of antiangiogenesis treatments for cancer. In this study, we evaluated the role of VEGF-PET as a biomarker of dynamic angiogenic ...changes in tumors following treatment with the kinase inhibitor sunitinib. The effects of sunitinib treatment and withdrawal on the tumor was investigated using the new VEGF-PET tracer (89)Zr-ranibizumab as well as (18)F-FDG PET, and (15)O-water PET in mouse xenograft models of human cancer. The obtained imaging results were compared with tumor growth, VEGF plasma levels and immunohistologic analyzes. In contrast to (18)F-FDG and (15)O-water PET, VEGF-PET demonstrated dynamic changes during sunitinib treatment within the tumor with a strong decline in signal in the tumor center and only minimal reduction in tumor rim, with a pronounced rebound after sunitinib discontinuation. VEGF-PET results corresponded with tumor growth and immunohistochemical vascular- and tumor- markers. Our findings highlight the strengths of VEGF-PET imaging to allow serial analysis of angiogenic changes in different areas within a tumor.
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