Health economics of targeted intraoperative radiotherapy (TARGIT-IORT) for early breast cancer: a cost-effectiveness analysis in the United Kingdom

Objective: The clinical effectiveness of targeted intraoperative radiotherapy (TARGIT-IORT) has been confirmed in the randomised TARGIT-A (targeted intraoperative radiotherapy-alone) trial to be similar to a several weeks’ course of whole-breast external-beam radiation therapy (EBRT) in patients with early breast cancer. This study aims to determine the cost effectiveness of TARGIT-IORT to inform policy decisions about its wider implementation. Setting TARGIT-A randomised clinical trial (ISRCTN34086741) which compared TARGIT with traditional EBRT and found similar breast cancer control, particularly when TARGIT was given simultaneously with lumpectomy. Methods: Cost-utility analysis using decision analytic modelling by a Markov model. A cost-effectiveness Markov model was developed using TreeAge Pro V.2015. The decision analytic model compared two strategies of radiotherapy for breast cancer in a hypothetical cohort of patients with early breast cancer based on the published health state transition probability data from the TARGIT-A trial. Analysis was performed for UK setting and National Health Service (NHS) healthcare payer’s perspective using NHS cost data and treatment outcomes were simulated for both strategies for a time horizon of 10 years. Model health state utilities were drawn from the published literature. Future costs and effects were discounted at the rate of 3.5%. To address uncertainty, one-way and probabilistic sensitivity analyses were performed. Main outcome measures: Quality-adjusted life-years (QALYs). Results: In the base case analysis, TARGIT-IORT was a highly cost-effective strategy yielding health gain at a lower cost than its comparator EBRT. Discounted TARGITIORT and EBRT costs for the time horizon of 10 years were £12 455 and £13 280, respectively. TARGIT-IORT gained 0.18 incremental QALY as the discounted QALYs gained by TARGIT-IORT were 8.15 and by EBRT were 7.97 showing TARGIT-IORT as a dominant strategy over EBRT. Model outputs were robust to one-way and probabilistic sensitivity analyses. Conclusions: TARGIT-IORT is a dominant strategy over EBRT, being less costly and producing higher QALY gain

Fraction of normal remaining life span: a new method for expressing survival in cancer

This article does not have an abstract

Organic Nanodelivery Systems as a New Platform in the Management of Breast Cancer: A Comprehensive Review from Preclinical to Clinical Studies

Breast cancer accounts for approximately 25% of cancer cases and 16.5% of cancer deaths in women, and the World Health Organization predicts that the number of new cases will increase by almost 70% over the next two decades, mainly due to an ageing population. Effective diagnostic and treatment strategies are, therefore, urgently required for improving cure rates among patients since current therapeutic modalities have many limitations and side effects. Nanomedicine is evolving as a promising approach for cancer management, including breast cancer, and various types of organic and inorganic nanomaterials have been investigated for their role in breast cancer diagnosis and treatment. Following an overview on breast cancer characteristics and pathogenesis and challenges of the current treatment strategies, the therapeutic potential of biocompatible organic-based nanoparticles such as liposomes and polymeric micelles that have been tested in breast cancer models are reviewed. The efficacies of different drug delivery and targeting strategies are documented, ranging from synthetic to cell-derived nanoformulations together with a summary of the interaction of nanoparticles with externally applied energy such as radiotherapy. The clinical translation of nanoformulations for breast cancer treatment is summarized including those undergoing clinical trials

Effects of awareness of breast cancer overdiagnosis among women with screen-detected or incidentally found breast cancer: a qualitative interview study

Objectives To explore experiences of women who identified themselves as having a possible breast cancer overdiagnosis. Design Qualitative interview study using key components of a grounded theory analysis. Setting International interviews with women diagnosed with breast cancer and aware of the concept of overdiagnosis. Participants Twelve women aged 48–77 years from the UK (6), USA (4), Canada (1) and Australia (1) who had breast cancer (ductal carcinoma in situ n=9, (invasive) breast cancer n=3) diagnosed between 2004 and 2019, and who were aware of the possibility of overdiagnosis. Participants were recruited via online blogs and professional clinical networks. Results Most women (10/12) became aware of overdiagnosis after their own diagnosis. All were concerned about the possibility of overdiagnosis or overtreatment or both. Finding out about overdiagnosis/overtreatment had negative psychosocial impacts on women’s sense of self, quality of interactions with medical professionals, and for some, had triggered deep remorse about past decisions and actions. Many were uncomfortable with being treated as a cancer patient when they did not feel ‘diseased’. For most, the recommended treatments seemed excessive compared with the diagnosis given. Most found that their initial clinical teams were not forthcoming about the possibility of overdiagnosis and overtreatment, and many found it difficult to deal with their set management protocols. Conclusion The experiences of this small and unusual group of women provide rare insight into the profound negative impact of finding out about overdiagnosis after breast cancer diagnosis. Previous studies have found that women valued information about overdiagnosis before screening and this knowledge did not reduce subsequent screening uptake. Policymakers and clinicians should recognise the diversity of women’s perspectives and ensure that women are adequately informed of the possibility of overdiagnosis before screening

Single-dose intraoperative radiotherapy during lumpectomy for breast cancer:an innovative patient-centred treatment

In the randomised TARGIT-A trial, risk-adapted targeted intraoperative radiotherapy (TARGIT-IORT) during lumpectomy was non-inferior to whole-breast external beam radiotherapy, for local recurrence. In the long-term, no difference was found in any breast cancer outcome, whereas there were fewer deaths from non-breast-cancer causes. TARGIT-IORT should be included in pre-operative consultations with eligible patients

A 3D Automated Classification Scheme for the TAUVEX data pipeline

In order to develop a pipeline for automated classification of stars to be observed by the TAUVEX ultraviolet space Telescope, we employ an artificial neural network (ANN) technique for classifying stars by using synthetic spectra in the UV region from 1250\AA to 3220\AA as the training set and International Ultraviolet Explorer (IUE) low resolution spectra as the test set. Both the data sets have been pre-processed to mimic the observations of the TAUVEX ultraviolet imager. We have successfully classified 229 stars from the IUE low resolution catalog to within 3-4 spectral sub-class using two different simulated training spectra, the TAUVEX spectra of 286 spectral types and UVBLUE spectra of 277 spectral types. Further, we have also been able to obtain the colour excess (i.e. E(B-V) in magnitude units) or the interstellar reddening for those IUE spectra which have known reddening to an accuracy of better than 0.1 magnitudes. It has been shown that even with the limitation of data from just photometric bands, ANNs have not only classified the stars, but also provided satisfactory estimates for interstellar extinction. The ANN based classification scheme has been successfully tested on the simulated TAUVEX data pipeline. It is expected that the same technique can be employed for data validation in the ultraviolet from the virtual observatories. Finally, the interstellar extinction estimated by applying the ANNs on the TAUVEX data base would provide an extensive extinction map for our galaxy and which could in turn be modeled for the dust distribution in the galaxy.Comment: 8 pages, 12 figures, Accepted for publication in MNRAS; High resolution figures available from the authors on reques

Breast cancer and the black swan

Publication costs for this article were supported by ecancer (UK Charity number 1176307).Peer reviewedPublisher PD

Breast Conserving Surgery in Combination With Targeted Intraoperative Radiotherapy Compared to Mastectomy for In-breast-tumor-recurrence

BACKGROUND/AIM: Mastectomy is the standard treatment of in-breast-recurrence of breast cancer after breast conserving surgery (BCS) and external beam radiation therapy (EBRT). In selected cases, it is possible to preserve the breast if targeted intraoperative radiotherapy (TARGIT-IORT) can be given during the second lumpectomy. This is a comparative analysis of overall survival and quality of life (QoL). PATIENTS AND METHODS: Patients in our database with in-breast-recurrence and either mastectomy or BCS and TARGIT-IORT were included. Identified patients were offered participation in a prospective QoL-analysis using the BREAST-Q questionnaire. The cohorts were compared for confounding parameters, overall survival, and QoL. RESULTS: Thirty-six patients treated for in-breast-recurrence were included, 21 had received a mastectomy and 16 patients had received BCS with TARGIT-IORT. Mean follow-up was 12.8 years since primary diagnosis and 4.2 years since recurrence. Both groups were balanced regarding prognostic parameters. Overall survival was numerically longer for BCS and TARGIT-IORT, but the numbers were too small for formal statistical analysis. No patient had further in-breast-recurrence. Psychosocial and sexual wellbeing did not differ between both groups. Physical wellbeing was significantly superior for those whose breast could be preserved (p-value=0.021). Patient-reported incidence and severity of lymphedema of the arm was significantly worse in the mastectomy group (p=0.007). CONCLUSION: Preserving the breast by use of TARGIT-IORT was safe with no re-recurrence and no detriment to overall survival in our analysis and led to a statistically significant improvement in physical wellbeing and incidence of lymphedema. These data should increase the confidence in offering breast preservation after in-breast-recurrence of breast cancer