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

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

New clinical and biological insights from the international TARGIT-A randomised trial of targeted intraoperative radiotherapy during lumpectomy for breast cancer

BACKGROUND: The TARGIT-A trial reported risk-adapted targeted intraoperative radiotherapy (TARGIT-IORT) during lumpectomy for breast cancer to be as effective as whole-breast external beam radiotherapy (EBRT). Here, we present further detailed analyses. METHODS: In total, 2298 women (≥45 years, invasive ductal carcinoma ≤3.5 cm, cN0-N1) were randomised. We investigated the impact of tumour size, grade, ER, PgR, HER2 and lymph node status on local recurrence-free survival, and of local recurrence on distant relapse and mortality. We analysed the predictive factors for recommending supplemental EBRT after TARGIT-IORT as part of the risk-adapted approach, using regression modelling. Non-breast cancer mortality was compared between TARGIT-IORT plus EBRT vs. EBRT. RESULTS: Local recurrence-free survival was no different between TARGIT-IORT and EBRT, in every tumour subgroup. Unlike in the EBRT arm, local recurrence in the TARGIT-IORT arm was not a predictor of a higher risk of distant relapse or death. Our new predictive tool for recommending supplemental EBRT after TARGIT-IORT is at https://targit.org.uk/addrt . Non-breast cancer mortality was significantly lower in the TARGIT-IORT arm, even when patients received supplemental EBRT, HR 0.38 (95% CI 0.17-0.88) P = 0.0091. CONCLUSION: TARGIT-IORT is as effective as EBRT in all subgroups. Local recurrence after TARGIT-IORT, unlike after EBRT, has a good prognosis. TARGIT-IORT might have a beneficial abscopal effect. TRIAL REGISTRATION: ISRCTN34086741 (21/7/2004), NCT00983684 (24/9/2009)

Intraoperative radiotherapy for early breast cancer: Do health professionals choose convenience or risk?

BACKGROUND: The randomized TARGIT trial comparing experimental intra-operative radiotherapy (IORT) to up to 7 weeks of daily conventional external beam radiotherapy (EBRT) recruited participants in Western Australia between 2003 and 2012. We aimed to understand preferences for this evolving radiotherapy treatment for early breast cancer (EBC) in health professionals, and how they changed over time and in response to emerging data. Preferences for single dose IORT or EBRT for EBC were elicited in 2004 and 2011, together with factors that may be associated with these preferences. METHODS: Western Australian health professionals working with breast cancer patients were invited to complete a validated, self-administered questionnaire. The questionnaire used hypothetical scenarios and trade-off methodology to determine the maximum increase in risk of local recurrence health professionals were willing to accept in order to have a single dose of IORT in the place of EBRT if they were faced with this decision themselves. RESULTS: Health professional characteristics were similar across the two time points although 2011 included a higher number of nurse (49% vs. 36%) and allied health (10% vs. 4%) participants and a lower number of radiation therapists (17% vs. 32% ) compared to 2004.Health professional preferences varied, with 7.5% and 3% judging IORT unacceptable at any risk, 18% and 21% judging IORT acceptable only if offering an equivalent risk, 56% and 59% judging IORT acceptable with a low maximum increase in risk (1-3%) and 19% and 17% judging a high maximum increase in risk acceptable (4-5%), in 2004 and 2011 respectively. A significantly greater number of nurses accepted IORT as a treatment option in 2011. CONCLUSIONS: Most Western Australian health professionals working with breast cancer patients are willing to accept an increase in risk of local recurrence in order to replace EBRT with IORT in a hypothetical setting. This finding was consistent over two time points spanning 7 years despite the duration of clinical experience with IORT and the publication of the early clinical results of IORT in 2010. These results need to be compared with preferences elicited from patient groups, and further investigation into the impact of personal preferences on health professionals\u27 advice to patients is warranted

Ultra-sound Shear Wave Elastography tissue stiffness and thickness assessment after adjuvant radiotherapy for breast cancer treatment: An exploratory study

Aim: This research investigated the feasibility of using B-mode ultrasound with Shear-Wave Elastography (SWE) to evaluate the structural and mechanical properties of multiple tissue layers in the pectoral region of women with chronic radiation fibrosis following breast cancer treatment. Method: Nine women between one and five years post unilateral conventional fractionated radiotherapy were evaluated. Both ultrasound and SWE were used to examine the thickness and stiffness of skin, subcutaneous adipose tissue, fascia and muscle in both their irradiated and non-irradiated sides. Linear mixed models were conducted to examine statistical differences in tissue thickness and stiffness between irradiated and non-irradiated sides with the arm resting by the side and also in abduction. Results:Significant differences were found between irradiated and non-irradiated tissues. Irradiated skin was significantly thicker (p=0.020) and stiffer (p Conclusion: Ultrasound with SWE shows potential to provide novel objective evaluation of radiation induced soft tissue fibrosis at multiple tissue layers in the pectoral region. Tissue thickness changes in irradiated tissue were evident in ultrasound images. Quantifying these tissue changes supports research development and introduction of clinical interventions to ameliorate the symptoms of morbidity that is currently considered irreversible

Circulating Tumour Cells (CTC), Head and Neck Cancer and Radiotherapy; Future Perspectives

Head and neck cancer is the seventh most common cancer in Australia and globally. Despite the current improved treatment modalities, there is still up to 50–60% local regional recurrence and or distant metastasis. High-resolution medical imaging technologies such as PET/CT and MRI do not currently detect the early spread of tumour cells, thus limiting the potential for effective minimal residual detection and early diagnosis. Circulating tumour cells (CTCs) are a rare subset of cells that escape from the primary tumour and enter into the bloodstream to form metastatic deposits or even re-establish themselves in the primary site of the cancer. These cells are more aggressive and accumulate gene alterations by somatic mutations that are the same or even greater than the primary tumour because of additional features acquired in the circulation. The potential application of CTC in clinical use is to acquire a liquid biopsy, by taking a reliable minimally invasive venous blood sample, for cell genotyping during radiotherapy treatment to monitor the decline in CTC detectability, and mutational changes in response to radiation resistance and radiation sensitivity. Currently, very little has been published on radiation therapy, CTC, and circulating cancer stem cells (CCSCs). The prognostic value of CTC in cancer management and personalised medicine for head and neck cancer radiotherapy patients requires a deeper understanding at the cellular level, along with other advanced technologies. With this goal, this review summarises the current research of head and neck cancer CTC, CCSC and the molecular targets for personalised radiotherapy response

Cosmesis and Breast-Related Quality of Life Outcomes After Intraoperative Radiation Therapy for Early Breast Cancer: A Substudy of the TARGIT-A Trial

PurposeTo report the first comprehensive investigation of patient-reported cosmesis and breast-related quality of life (QOL) outcomes comparing patients randomized to risk-adapted single-dose intraoperative radiation therapy (TARGIT-IORT) versus external beam radiation therapy (EBRT) on the TARGIT-A trial.Methods and MaterialsLongitudinal cosmesis and QOL data were collected from a subset of TARGIT-A participants who received TARGIT-IORT as a separate procedure (postpathology). Patients completed a cosmetic assessment before radiation therapy and annually thereafter for at least 5 years. Patients also completed the combined European Organization for Research and Treatment of Cancer (EORTC) core questionnaire and Breast-Specific Module in addition to the Body Image after Breast Cancer Questionnaire at baseline and annually thereafter. The combined EORTC questionnaires were also collected 3, 6, and 9 months after wide local excision.ResultsAn Excellent–Good cosmetic result was scored more often than a Fair–Poor result for both treatment groups across all time points. The TARGIT-IORT patients reported better breast-related QOL than EBRT patients. Statistically and clinically significant differences were seen at month 6 and year 1, with EBRT patients having moderately worse breast symptoms (a statistically significant difference of more than 10 in a 100-point scale) than TARGIT-IORT patients at these time points.ConclusionPatients treated with TARGIT-IORT on the TARGIT-A trial have similar self-reported cosmetic outcome but better breast-related QOL outcomes than patients treated with EBRT. This important evidence can facilitate the treatment decision-making process for patients who have early breast cancer suitable for breast-conserving surgery and inform their clinicians

Objective assessment of cosmetic outcome after targeted intraoperative radiotherapy in breast cancer: Results from a randomised controlled trial

The international randomised targeted intraop-erative radiotherapy (TARGIT) trial has demonstratedevidence of non-inferiority between the novel technique of TARGIT (intra-operative radiotherapy with Intrabeam)and conventional external beam radiotherapy (EBRT) inwomen with early breast cancer in terms of the primaryoutcome measure of risk of local relapse within the treated breast. Cosmesis is an increasingly important outcome of breast conserving treatment with both surgery and radio-therapy contributing to this. It was unknown if the single high dose of TARGIT may lead to damaging fibrosis and thus impair cosmesis further, so we objectively evaluated the aesthetic outcome of patients within the TARGIT randomised controlled trial. We have used an objective assessment tool for evaluation of cosmetic outcome. Frontal digital photographs were taken at baseline (before TARGIT or EBRT) and yearly thereafter for up to 5 years. The photographs were analysed by BCCT.core, a validated software which produces a composite score based on symmetry, colour and scar. 342 patients were assessed, median age at baseline 64 years (IQR 59–68). The scores were dichotomised into Excellent and Good (EG), and Fair and Poor (FP). There were statistically significant increases in the odds of having an outcome of EG for patients in the TARGIT group relative to the EBRT group at year 1 (OR 2.07, 95 % CI 1.12–3.85, p = 0.021) and year 2 (OR 2.11, 95 % CI 1.0–4.45, p = 0.05). Following a totally objective assessment in a randomised setting, the aesthetic outcome of patients demonstrates that those treated with TARGIT have a superior cosmetic result to those patients who received conventional external beam radiotherapy