Patient preferences for adjuvant radiotherapy in early breast cancer are strongly influenced by treatment received through random assignment

Objective: TARGIT‐A randomised women with early breast cancer to receive external beam radiotherapy (EBRT) or intraoperative radiotherapy (TARGIT‐IORT). This study aimed to identify what extra risk of recurrence patients would accept for per‐ ceived benefits and risks of different radiotherapy treatments. Methods: Patient preferences were determined by self‐rated trade‐off question‐ naires in two studies: Stage (1) 209 TARGIT‐A participants (TARGIT‐IORT n = 108, EBRT n = 101); Stage (2) 123 non‐trial patients yet to receive radiotherapy (pre‐treat‐ ment group), with 85 also surveyed post‐radiotherapy. Patients traded‐off risks of local recurrence in preference selection between TARGIT‐IORT and EBRT. Results: TARGIT‐IORT patients were more accepting of IORT than EBRT patients with 60% accepting the highest increased risk presented (4%–6%) compared to 12% of EBRT patients, and 2% not accepting IORT at all compared to 43% of EBRT pa‐ tients. Pre‐treatment patients were more accepting of IORT than post‐treatment pa‐ tients with 23% accepting the highest increased risk presented compared to 15% of post‐treatment patients, and 15% not accepting IORT at all compared to 41% of pre‐ treatment patients. Conclusions: Breast cancer patients yet to receive radiotherapy accept a higher recurrence risk than the actual risk found in TARGIT‐A. Measured patient preferences are highly influenced by experience of treatment received. This finding challenges the validity of post‐treatment preference studies

Optical palpation for the visualization of tumor in human breast tissue

Australian Research Council; Cancer Council Western Australia; Department of Health, Government of Western Australia; OncoResMedical; William and Marlene Schrader Trust of The University of Western AustraliaAccurate and effective removal of tumor in one operation is an important goal of breast-conserving surgery. However, it is not always achieved. Surgeons often utilize manual palpation to assess the surgical margin and/or the breast cavity. Manual palpation, however, is subjective and has relatively low resolution. Here, we investigate a tactile imaging technique, optical palpation, for the visualization of tumor. Optical palpation generates maps of the stress at the surface of tissue under static preload compression. Stress is evaluated by measuring the deformation of a contacting thin compliant layer with known mechanical properties using optical coherence tomography. In this study, optical palpation is performed on 34 freshly excised human breast specimens. Wide field-of-view (up to ~46 × 46 mm) stress images, optical palpograms, are presented from four representative specimens, demonstrating the capability of optical palpation to visualize tumor. Median stress reported for adipose tissue, 4 kPa, and benign dense tissue, 8 kPa, is significantly lower than for invasive tumor, 60 kPa. In addition, we demonstrate that optical palpation provides contrast consistent with a related optical technique, quantitative micro-elastography. This study demonstrates that optical palpation holds promise for visualization of tumor in breast-conserving surgery.PostprintPeer reviewe

Investigation of optical coherence micro-elastography as a method to visualize micro-architecture in human axillary lymph nodes

This project is supported with funding from the Australian Research Council; and Cancer Council WA, which allowed us to develop the technology; Department of Health of Western Australia, National Breast Cancer Foundation (Australia); and the National Health and Medical Research Council, Australia, which allowed us to design and implement the clinical protocol, and to perform the clinical measurements.Background : Evaluation of lymph node involvement is an important factor in detecting metastasis and deciding whether to perform axillary lymph node dissection (ALND) in breast cancer surgery. As ALND is associated with potentially severe long term morbidity, the accuracy of lymph node assessment is imperative in avoiding unnecessary ALND. The mechanical properties of malignant lymph nodes are often distinct from those of normal nodes. A method to image the micro-scale mechanical properties of lymph nodes could, thus, provide diagnostic information to aid in the assessment of lymph node involvement in metastatic cancer. In this study, we scan axillary lymph nodes, freshly excised from breast cancer patients, with optical coherence micro-elastography (OCME), a method of imaging micro-scale mechanical strain, to assess its potential for the intraoperative assessment of lymph node involvement. Methods : Twenty-six fresh, unstained lymph nodes were imaged from 15 patients undergoing mastectomy or breast-conserving surgery with axillary clearance. Lymph node specimens were bisected to allow imaging of the internal face of each node. Co-located OCME and optical coherence tomography (OCT) scans were taken of each sample, and the results compared to standard post-operative hematoxylin-and-eosin-stained histology. Results : The optical backscattering signal provided by OCT alone may not provide reliable differentiation by inspection between benign and malignant lymphoid tissue. Alternatively, OCME highlights local changes in tissue strain that correspond to malignancy and are distinct from strain patterns in benign lymphoid tissue. The mechanical contrast provided by OCME complements the optical contrast provided by OCT and aids in the differentiation of malignant tumor from uninvolved lymphoid tissue. Conclusion : The combination of OCME and OCT images represents a promising method for the identification of malignant lymphoid tissue. This method shows potential to provide intraoperative assessment of lymph node involvement, thus, preventing unnecessary removal of uninvolved tissues and improving patient outcomes.Publisher PDFPeer reviewe

Cosmetic outcome as rated by patients, doctors, nurses and BCCT.core software assessed over 5 years in a subset of patients in the TARGIT-A trial

Background: The purpose of this research was to assess agreement between four rating systems of cosmetic outcome measured in a subset of patients with early breast cancer participating in the randomised TARGIT-A trial. TARGIT-A compared risk-adapted single-dose intra-operative radiotherapy (TARGIT-IORT) to whole breast external beam radiotherapy (EBRT). Methods: Patients, their Radiation Oncologist and Research Nurse completed a subjective cosmetic assessment questionnaire before radiotherapy and annually thereafter for five years. Objective data previously calculated by the validated BCCT.core software which utilizes digital photographs to score symmetry, colour and scar was also used. Agreement was assessed by the Kappa statistic and longitudinal changes were assessed by generalized estimating equations. Results: Overall, an Excellent-Good (EG) cosmetic result was scored more often than a Fair-Poor (FP) result for both treatment groups across all time points, with patients who received TARGIT-IORT scoring EG more often than those who received EBRT however this was statistically significant at Year 5 only. There was modest agreement between the four rating systems with the highest Kappa score being moderate agreement which was between nurse and doctor scores at Year 1 with Kappa = 0.46 (p \u3c 0.001), 95% CI (0.24, 0.68). Conclusion: Despite similar overall findings between treatment groups and rating systems, the inter-rater agreement was only modest. This suggests that the four rating systems utilized may not necessarily be used interchangeably and it is arguable that for an outcome such as cosmetic appearance, the patient’s point of view is the most important. Trial Registration: TARGIT-A ISRCTN34086741, Registered 21 July 2004, retrospectively registered

Diagnosis of breast cancer using elastic-scattering spectroscopy: preliminary clinical results

We report on the first stages of a clinical study designed to test elastic-scattering spectroscopy, mediated by fiberoptic probes, for three specific clinical applications in breast-tissue diagnosis: (1) a transdermal-needle (interstitial) measurement for instant diagnosis with minimal invasiveness similar to fine-needle aspiration but with sensitivity to a larger tissue volume, (2) a hand-held diagnostic probe for use in assessing tumor/resection margins during open surgery, and (3) use of the same probe for real-time assessment of the `sentinel' node during surgery to determine the presence or absence of tumor (metastatic). Preliminary results from in vivo measurements on 31 women are encouraging. Optical spectra were measured on 72 histology sites in breast tissue, and 54 histology sites in sentinel nodes. Two different artificial intelligence methods of spectral classification were studied. Artificial neural networks yielded sensitivities of 69% and 58%, and specificities of 85% and 93%, for breast tissue and sentinel nodes, respectively. Hierarchical cluster analysis yielded sensitivities of 67% and 91%, and specificities of 79% and 77%, for breast tissue and sentinel nodes, respectively. These values are expected to improve as the data sets continue to grow and more sophisticated data preprocessing is employed. The study will enroll up to 400 patients over the next two years

Label-free optical imaging technologies for rapid translation and use during intraoperative surgical and tumor margin assessment

The biannual International Conference on Biophotonics was recently held on April 30 to May 1, 2017, in Fremantle, Western Australia. This continuing conference series brought together key opinion leaders in biophotonics to present their latest results and, importantly, to participate in discussions on the future of the field and what opportunities exist when we collectively work together for using biophotonics for biological discovery and medical applications. One session in this conference, entitled "Tumor Margin Identification: Critiquing Technologies," challenged invited speakers and attendees to review and critique representative label-free optical imaging technologies and their application for intraoperative assessment and guidance in surgical oncology. We are pleased to share a summary in this outlook paper, with the intent to motivate more research inquiry and investigations, to challenge these and other optical imaging modalities to evaluate and improve performance, to spur translation and adoption, and ultimately, to improve the care and outcomes of patient

Association between long-term use of calcium channel blockers (CCB) and the risk of breast cancer:a retrospective longitudinal observational study protocol

Introduction Calcium channel blockers (CCB), a commonly prescribed antihypertensive (AHT) medicine, may be associated with increased risk of breast cancer. The proposed study aims to examine whether long-term CCB use is associated with the development of breast cancer and to characterise the dose-response nature of any identified association, to inform future hypertension management. Methods and analysis The study will use data from 2 of Australia's largest cohort studies; the Australian Longitudinal Study on Women's Health, and the 45 and Up Study, combined with the Rotterdam Study. Eligible women will be those with diagnosed hypertension, no history of breast cancer and no prior CCB use at start of follow-up (2004-2009). Cumulative dose-duration exposure to CCB and other AHT medicines will be captured at the earliest date of: the outcome (a diagnosis of invasive breast cancer); a competing risk event (eg, bilateral mastectomy without a diagnosis of breast cancer, death prior to any diagnosis of breast cancer) or end of follow-up (censoring event). Fine and Gray competing risks regression will be used to assess the association between CCB use and development of breast cancer using a generalised propensity score to adjust for baseline covariates. Time-varying covariates related to interaction with health services will also be included in the model. Data will be harmonised across cohorts to achieve identical protocols and a two-step random effects individual patient-level meta-analysis will be used. Ethics and dissemination Ethical approval was obtained from the following Human research Ethics Committees: Curtin University (ref No. HRE2022-0335), NSW Population and Health Services Research Ethics Committee (2022/ETH01392/2022.31), ACT Research Ethics and Governance Office approval under National Mutual Acceptance for multijurisdictional data linkage research (2022.STE.00208). Results of the proposed study will be published in high-impact journals and presented at key scientific meetings.</p

Handheld probe for quantitative micro-elastography

Funding: Australian Research Council (ARC); Department of Health, Western Australia; Cancer Council, Western Australia; OncoRes Medical.Optical coherence elastography (OCE) has been proposed for a range of clinical applications. However, the majority of these studies have been performed using bulks, lab based imaging systems. A compact. handheld imaging probe would accelerate clinical translation, however, to date. tins had been inhibited by the slow scan rates of compact devices and the motion artifact induced by the user's hand. In this paper, we present a proof-of-concept. handheld quantitative micro-elastography (QME) probe capable of scanning a 6 x 6 x 1 mm volume of tissue in 3.4 seconds. This handheld probe is enabled by a novel QME acquisition protocol that incorporates a custom bidirectional scan pattern driving a microelectromechanical system (MEMS) scanner, synchronized with the sample deformation induced by an annular PZT actuator. The custom scan pattern reduces the total acquisition time and the time difference between B-scans used to generate displacement maps. minimizing the impact of motion artifact. We test the feasibility of the handheld QME probe on a tissue-mimicking silicone phantom, demonstrating comparable image quality to a bench-mounted setup. In addition, we present the first handheld QME scans performed on human breast tissue specimens. For each specimen, quantitative micro-elastograms are co-registered with, and validated by, histology, demonstrating the ability-to distinguish stiff cancerous tissue from surrounding soft benign tissue.Publisher PDFPeer reviewe

Exercise for health: a randomized, controlled trial evaluating the impact of a pragmatic, translational exercise intervention on the quality of life, function and treatment-related side effects following breast cancer

Exercise for Health was a randomized, controlled trial designed to evaluate two modes of delivering (face-to-face [FtF] and over-the-telephone [Tel]) an 8-month translational exercise intervention, commencing 6-weeks post-breast cancer surgery (PS). Outcomes included quality of life (QoL), function (fitness and upper body) and treatment-related side effects (fatigue, lymphoedema, body mass index, menopausal symptoms, anxiety, depression and pain). Generalised estimating equation modelling determined time (baseline [5 weeks PS], mid-intervention [6 months PS], post-intervention [12 months PS]), group (FtF, Tel, Usual Care [UC]) and time-by-group effects. 194 women representative of the breast cancer population were randomised to the FtF (n = 67), Tel (n = 67) and UC (n = 60) groups. There were significant (p < 0.05) interaction effects on QoL, fitness and fatigue with differences being observed between the treatment groups and the UC group. Trends observed for the treatment groups were similar. The treatment groups reported improved QoL, fitness and fatigue over time and changes observed between baseline and post-intervention were clinically relevant. In contrast, the UC group experienced no change, or worsening QoL, fitness and fatigue, mid-intervention. Although improvements in the UC group occurred by 12-months post-surgery, the change did not meet the clinically relevant threshold. There were no differences in other treatment-related side effects between groups. This translational intervention trial, delivered either FtF or Tel, supports exercise as a form of adjuvant breast cancer therapy that can prevent declines in fitness and function during treatment and optimise recovery post-treatment