Dose-escalated simultaneous integrated boost radiotherapy in early breast cancer (IMPORT HIGH): a multicentre, phase 3, non-inferiority, open-label, randomised controlled trial.

BACKGROUND: A tumour-bed boost delivered after whole-breast radiotherapy increases local cancer-control rates but requires more patient visits and can increase breast hardness. IMPORT HIGH tested simultaneous integrated boost against sequential boost with the aim of reducing treatment duration while maintaining excellent local control and similar or reduced toxicity. METHODS: IMPORT HIGH is a phase 3, non-inferiority, open-label, randomised controlled trial that recruited women after breast-conserving surgery for pT1-3pN0-3aM0 invasive carcinoma from radiotherapy and referral centres in the UK. Patients were randomly allocated to receive one of three treatments in a 1:1:1 ratio, with computer-generated random permuted blocks used to stratify patients by centre. The control group received 40 Gy in 15 fractions to the whole breast and 16 Gy in 8 fractions sequential photon tumour-bed boost. Test group 1 received 36 Gy in 15 fractions to the whole breast, 40 Gy in 15 fractions to the partial breast, and 48 Gy in 15 fractions concomitant photon boost to the tumour-bed volume. Test group 2 received 36 Gy in 15 fractions to the whole breast, 40 Gy in 15 fractions to the partial breast, and 53 Gy in 15 fractions concomitant photon boost to the tumour-bed volume. The boost clinical target volume was the clip-defined tumour bed. Patients and clinicians were not masked to treatment allocation. The primary endpoint was ipsilateral breast tumour relapse (IBTR) analysed by intention to treat; assuming 5% 5-year incidence with the control group, non-inferiority was predefined as 3% or less absolute excess in the test groups (upper limit of two-sided 95% CI). Adverse events were assessed by clinicians, patients, and photographs. This trial is registered with the ISRCTN registry, ISRCTN47437448, and is closed to new participants. FINDINGS: Between March 4, 2009, and Sept 16, 2015, 2617 patients were recruited. 871 individuals were assigned to the control group, 874 to test group 1, and 872 to test group 2. Median boost clinical target volume was 13 cm3 (IQR 7 to 22). At a median follow-up of 74 months there were 76 IBTR events (20 for the control group, 21 for test group 1, and 35 for test group 2). 5-year IBTR incidence was 1·9% (95% CI 1·2 to 3·1) for the control group, 2·0% (1·2 to 3·2) for test group 1, and 3·2% (2·2 to 4·7) for test group 2. The estimated absolute differences versus the control group were 0·1% (-0·8 to 1·7) for test group 1 and 1·4% (0·03 to 3·8) for test group 2. The upper confidence limit for test group 1 versus the control group indicated non-inferiority for 48 Gy. Cumulative 5-year incidence of clinician-reported moderate or marked breast induration was 11·5% for the control group, 10·6% for test group 1 (p=0·40 vs control group), and 15·5% for test group 2 (p=0·015 vs control group). INTERPRETATION: In all groups 5-year IBTR incidence was lower than the 5% originally expected regardless of boost sequencing. Dose-escalation is not advantageous. 5-year moderate or marked adverse event rates were low using small boost volumes. Simultaneous integrated boost in IMPORT HIGH was safe and reduced patient visits. FUNDING: Cancer Research UK.

Psychosocial aspects of risk communication and mutation testing in familial breast-ovarian cancer.

PURPOSE OF REVIEW: As cancer genetics services develop, psychosocial research evaluating risk communication and mutation testing for familial breast-ovarian cancer has expanded rapidly. It is timely to review findings in key areas. These will inform risk counselling practice and help prepare women making risk management decisions. RECENT FINDINGS: The psychological effect of risk communication and genetic counselling has been elucidated and women's risk perceptions explored. Knowledge of optimal risk communication strategies is lacking, but recent research shows both consistency in information giving and deficiencies in specific communication skills; the need for personally tailored risk information, which addresses counsellees' concerns, is highlighted. Outcome assessments of risk communication, such as risk perception and psychological distress, are useful but insufficient to evaluate the complex communication process, and decision making in this context is underresearched. Subsequent diffusion of risk information and interfamily communication pose difficulties for high-risk individuals. The short-term psychological consequences of predictive mutation testing are an important focus of research and are largely reassuring, but long-term outcomes are sparse. SUMMARY: Our understanding of the psychological benefits and limitations of risk counselling and mutation testing can now inform clinical practice, but insufficient knowledge exists of long-term outcomes. Most women are unlikely to be distressed following risk communication, but some may need psychosocial support in the short term following predictive testing for BRCA1/2. Different approaches to risk communication need to be developed and evaluated in parallel with communications skills training to ensure an adequate focus on the women's agenda.

Costs and benefits of a one stop clinic compared with a dedicated breast clinic: randomised controlled trial.

OBJECTIVE: To determine the cost to the NHS and the impact on anxiety of a one stop clinic for assessing women with suspected breast cancer. STUDY DESIGN: Randomised controlled trial. PARTICIPANTS: Women aged 35 or over referred with a breast lump. STUDY SETTING: Teaching hospital, north west England. INTERVENTIONS: Women were randomly allocated to attend a one stop clinic or a dedicated breast clinic. OUTCOME MEASURES: Reduction in mean anxiety from baseline at 24 hours after the first visit and at 3 weeks and 3 months after diagnosis; mean cost per patient. RESULTS: 670 women were randomised. Compared with women who attended the dedicated clinic, patients attending the one stop clinic were less anxious 24 hours after the visit (adjusted mean change in state anxiety _5.7 (95% confidence interval _8.4 to _3.0)) but not at 3 weeks or 3 months after diagnosis. The additional cost to the NHS of a one stop attendance was pound 32 per woman; this was largely explained by greater cytopathological and radiological staff costs. CONCLUSION: One stop clinics may not be justified in terms of a reduction in short term anxiety.