International comparison of cosmetic outcomes of breast conserving surgery and radiation therapy for women with ductal carcinoma in situ of the breast

Purpose: To assess the cosmetic impact of breast conserving surgery (BCS), whole breast irradiation (WBI) fractionation and tumour bed boost (TBB) use in a phase III trial for women with ductal carcinoma in situ (DCIS) of the breast. Materials and methods: Baseline and 3-year cosmesis were assessed using the European Organization for Research and Treatment of Cancer (EORTC) Cosmetic Rating System and digital images in a randomised trial of non-low risk DCIS treated with postoperative WBI +/- TBB. Baseline cosmesis was assessed for four geographic clusters of treating centres. Cosmetic failure was a global score of fair or poor. Cosmetic deterioration was a score change from excellent or good at baseline to fair or poor at three years. Odds ratios for cosmetic deterioration by WBI dose-fractionation and TBB use were calculated for both scoring systems. Results: 1608 women were enrolled from 11 countries between 2007 and 2014. 85-90% had excellent or good baseline cosmesis independent of geography or assessment method. TBB (16 Gy in 8 fractions) was associated with a >2-fold risk of cosmetic deterioration (p

First clinical experience with real-time portal imaging-based breath-hold monitoring in tangential breast radiotherapy

Background and purpose: Real-time treatment monitoring with the electronic portal imaging device (EPID) can conceptually provide a more accurate assessment of the quality of deep inspiration breath-hold (DIBH) and patient movement during tangential breast radiotherapy (RT). A system was developed to measure two geometrical parameters, the lung depth (LD) and the irradiated width (named here skin distance, SD), along three user-selected lines in MV EPID images of breast tangents. The purpose of this study was to test the system during tangential breast RT with DIBH. Materials and methods: Measurements of LDs and SDs were carried out in real time. DIBH was guided with a commercial system using a marker block. Results from 17 patients were assessed. Mean midline LDs, , per tangent were compared to the planned mLDs; differences between the largest and smallest observed () per tangent were calculated. Results: For 56% (162/288) of the tangents tested, were outside the tolerance window. All but one patient had at least one fraction showing this behaviour. The largest difference found between an and its planned mLD was −16.9 mm. The accuracy of patient positioning and the quality of marker-block-based DIBH guidance contributed to the differences. Fractions with patient position verification using a single EPID image taken before treatment showed a lower rate (34%), suggesting reassessment of setup procedures. Conclusions: Real-time treatment monitoring of the internal anatomy during DIBH delivery of tangential breast RT is feasible and useful. The new system requires no additional radiation for the patient

Adaptive study design to assess effect of TRPV4 inhibition in patients with chronic cough

Objective Airway sensory nerves involved in the cough reflex are activated by adenosine triphosphate (ATP) agonism of P2X purinoceptor 3 (P2X3) receptors. Transient receptor potential vanilloid 4 (TRPV4) channel activation causes ATP release from airway cells, and it is hypothesised that a TRPV4-ATP-P2X3 axis contributes to chronic cough. An adaptive study was run to determine if TRPV4 inhibition, using the selective TRPV4 channel blocker GSK2798745, was effective in reducing cough. Methods A two-period randomised, double blinded, placebo-controlled crossover study was designed with interim analyses for futility and sample size adjustment. Refractory chronic cough patients received either GSK2798745 or placebo once daily for 7 days with a washout between treatments. Pharmacokinetic samples were collected for analysis of GSK2798745 at end of study. The primary end-point was total cough counts assessed objectively during day-time hours (10 h) following 7 days of dosing. Results Interim analysis was performed after 12 participants completed both treatment periods. This showed a 32% increase in cough counts on Day 7 for GSK2798745 compared to placebo; the pre-defined negative criteria for the study were met and the study was stopped. At this point 17 participants had been enrolled (mean 61 years; 88% female), and 15 had completed the study. Final study results for posterior median cough counts showed a 34% (90% credible interval: −3%, +85%) numerical increase for GSK2798745 compared to placebo. Conclusion There was no evidence of an anti-tussive effect of GSK2798745. The study design allowed the decision on lack of efficacy to be made with minimal participant exposure to the investigational drug