Letter. Intensity-modulated radiotherapy for the treatment of breast cancer

In the systematic review of intensity-modulated radiotherapy (IMRT) in the treatment of breast cancer reported in Clinical Oncology by Dayes and colleagues [1], the only prospective randomised clinical trial (n = 306) testing forward-planned IMRT to have reported a 5 year outcome for adverse effects [2] was excluded on the spurious grounds that no outcomes of interest were reported (Appendix 3). In this trial, the control arm patients were 1.7 times more likely to have a change in breast appearance than the IMRT arm patients after adjustment for the year of photographic assessment (95% confidence interval 1.2–2.5, P = 0.008)

Radiotherapy trial set-up in the UK: identifying inefficiencies and potential solutions

Aims: Radiotherapy clinical trials are integral to the development of new treatments to improve the outcomes of patients with cancer. A collaborative study by the National Cancer Research Institute Clinical and Translational Radiotherapy Research Working Group and the National Institute for Health Research was carried out to understand better if and why inefficiencies occur in the set-up of radiotherapy trials in the UK. Materials and methods: Two online surveys collected information on the time taken for UK radiotherapy trials to reach key milestones during set-up and the research support currently being provided to radiotherapy centres to enable efficient clinical trial set-up. Semi-structured interviews with project managers and chief investigators identified better ways of working to improve trial set-up in the future. Results: The timelines for the set-up of 39 UK radiotherapy trials were captured in an online survey showing that the median time from grant approval to trial opening was 600 days (range 169–1172). There were 38 responses from radiotherapy centres to a survey asking about the current support provided for radiotherapy research. Most of these centres have more than one type of staff member dedicated to supporting radiotherapy research. The most frequent barrier to radiotherapy trial set-up identified was lack of physicists' time and lack of time for clinical oncologists to carry out research activities. Four main themes around trial set-up were identified from semi-structured interviews: the importance of communication and building relationships, the previous experience of the chief investigator and clinical trials units, a lack of resources and having the time and personnel required to produce trial documentation and to process trial approval requests. Conclusions: This unique, collaborative project has provided up to date information about the current landscape of trial set-up and research support in the UK and identified several avenues on which to focus future efforts in order to support the excellent radiotherapy trial work carried out across the UK

Normal tissue complication probability (NTCP) parameters for breast fibrosis: pooled results from two randomised trials

Introduction: the dose–volume effect of radiation therapy on breast tissue is poorly understood. We estimate NTCP parameters for breast fibrosis after external beam radiotherapy.Materials and methods: we pooled individual patient data of 5856 patients from 2 trials including whole breast irradiation followed with or without a boost. A two-compartment dose volume histogram model was used with boost volume as the first compartment and the remaining breast volume as second compartment. Results from START-pilot trial (n?=?1410) were used to test the predicted models.Results: 26.8% patients in the Cambridge trial (5?years) and 20.7% patients in the EORTC trial (10?years) developed moderate-severe breast fibrosis. The best fit NTCP parameters were BEUD3(50)?=?136.4?Gy, ?50?=?0.9 and n?=?0.011 for the Niemierko model and BEUD3(50)?=?132?Gy, m?=?0.35 and n?=?0.012 for the Lyman Kutcher Burman model. The observed rates of fibrosis in the START-pilot trial agreed well with the predicted rates.Conclusions: this large multi-centre pooled study suggests that the effect of volume parameter is small and the maximum RT dose is the most important parameter to influence breast fibrosis. A small value of volume parameter ‘n’ does not fit with the hypothesis that breast tissue is a parallel organ. However, this may reflect limitations in our current scoring system of fibrosi

A two-dimensional organic-exciton polariton lattice fabricated using laser patterning

Exciton-polaritons in 2D lattice geometries now attract considerable attention as systems in which to explore new physics. However, such structures are relatively difficult to fabricate as this can involve sophisticated milling or etching of cavity layers to create arrays of defects. Here, a straightforward technique is reported that allows rapid fabrication of 2D polariton lattices that operate at room temperature. Specifically, laser patterning has been used to write a 2D square lattice of defects into a sacrificial polymer layer. An organic microcavity structure is then built on top of the patterned polymer, with the morphology of the patterned polymer propagating through the subsequent layers and spatially modifying the optical path-length of the active cavity region. Using real- and momentum-space spectroscopy, the formation of gapped polaritonic band structures has been demonstrated at room temperature. The optical writing approach discussed here opens up the way for fabrication of more complex 2D-lattice geometries for studying topological physics at room temperature

Targeting the Ataxia Telangiectasia Mutated-null Phenotype in Chronic Lymphocytic Leukemia with Pro-oxidants

Inactivation of the Ataxia Telangiectasia Mutated gene in chronic lymphocytic leukemia results in resistance to p53-dependent apoptosis and inferior responses to treatment with DNA damaging agents. Hence, p53-independent strategies are required to target Ataxia Telangiectasia Mutated-deficient chronic lymphocytic leukemia. As Ataxia Telangiectasia Mutated has been implicated in redox homeostasis, we investigated the effect of the Ataxia Telangiectasia Mutated-null chronic lymphocytic leukemia genotype on cellular responses to oxidative stress with a view to therapeutic targeting. We found that in comparison to Ataxia Telangiectasia Mutated-wild type chronic lymphocytic leukemia, pro-oxidant treatment of Ataxia Telangiectasia Mutated-null cells led to reduced binding of NF-E2 p45-related factor-2 to antioxidant response elements and thus decreased expression of target genes. Furthermore, Ataxia Telangiectasia Mutated-null chronic lymphocytic leukemia cells contained lower levels of antioxidants and elevated mitochondrial reactive oxygen species. Consequently, Ataxia Telangiectasia Mutated-null chronic lymphocytic leukemia, but not tumours with 11q deletion or TP53 mutations, exhibited differentially increased sensitivity to pro-oxidants both in vitro and in vivo. We found that cell death was mediated by a p53- and caspase-independent mechanism associated with apoptosis inducing factor activity. Together, these data suggest that defective redox-homeostasis represents an attractive therapeutic target for Ataxia Telangiectasia Mutated-null chronic lymphocytic leukemia