Background:We investigated the feasibility of dose-dense neoadjuvant chemotherapy (NACT) with paclitaxel and carboplatin before radical chemoradiation (CRT) and assessed the response rate to such a regimen.Methods:CxII is a single-arm phase II trial of 46 patients, with locally advanced cervical cancer (stage Ib2-IVa). Patients received dose-dense carboplatin (AUC2) and paclitaxel (80 mg m−2) weekly for six cycles followed by CRT (40 mg m−2 of weekly cisplatin, 50.4 Gy, 28 fractions plus brachytherapy). The primary end point was response rate 12 weeks post-CRT.Results:Baseline characteristics were: median age at diagnosis 43 years; 72% squamous, 22% adenocarcinoma and 7% adenosquamous histologies; FIGO stage IB2 (11%), II (50%), III (33%), IV (7%). Complete or partial response rate was 70% (95% CI: 54–82) post-NACT and 85% (95% CI: 71–94) post-CRT. The median follow-up was 39.1 months. Overall and progression-free survivals at 3 years were 67% (95% CI: 51–79) and 68% (95% CI: 51–79), respectively. Grade 3/4 toxicities were 20% during NACT (11% haematological, 9% non-haematological) and 52% during CRT (haematological: 41%, non-haematological: 22%).Conclusion:A good response rate is achieved by dose-dense weekly NACT with carboplatin and paclitaxel followed by radical CRT. This treatment regimen is feasible as evidenced by the acceptable toxicity of NACT and by the high compliance to radiotherapy (98%).

Objectives: Contrast-enhanced digital breast tomosynthesis (CE-DBT) is a novel imaging technique, combining contrast-enhanced spectral mammography (CESM) and tomosynthesis. This may offer an alternative imaging technique to breast MRI for monitoring of response to neoadjuvant chemotherapy. This paper addresses patient experience and preference regarding the two techniques. Methods: Conducted as part of a prospective pilot study; patients were asked to complete questionnaires pertaining to their experience of CE-DBT and MRI following pre-treatment and end-of-treatment imaging. Questionnaires consisted of eight questions answered on a categorical scale, two using a visual analogue scale (VAS), and a question to indicate preference of imaging technique. Statistical analysis was performed with SPSS v25 Wilcoxon signed rank test and McNemar test for related samples using SPSS v25. Results: Eighteen patients were enrolled in the pilot study. Matched CE-DBT and MRI questionnaires were completed after 22 patient episodes, patient preference was indicated after 31 patient episodes. Overall, on 77% of occasions patients preferred CE-DBT with no difference between pre-treatment and end-of-treatment imaging. Overall experience (p = 0.008), non-breast pain (p = 0.046), anxiety measured using VAS (p = 0.003), and feeling of being put at ease by staff (p = 0.023) was better for CE-DBT. However, more breast pain was experienced during CE-DBT when measured on both VAS (p = 0.011) and Likert scale (p = 0.021). Conclusion: Our paper suggests that patients prefer CE-DBT to MRI, adding further evidence in favour of contrast-enhanced mammographic techniques. Advances in knowledge: Contrast mammographic techniques offer an alternative, more accessible imaging technique to breast MRI. Whilst other studies have addressed patient experience of CESM, this is the first study to directly explore patient preference for contrast-enhanced DBT over MRI in the setting of neoadjuvant chemotherapy, finding that overall, patients preferred CE-DBT despite the need for longer breast compression.

5586 Background: Chemoradiation (CRT) is the standard of care for locally advanced cervical cancer but survival is poor among women with large tumours, advanced stage, or positive nodes. Neoadjuvant chemotherapy (NACT) prior to CRT to down-stage tumours and lengthen the exposure to systemic treatment is designed to improve outcome. Methods: Patients (pts) with locally advanced cervical cancer received dose-dense carboplatin (AUC2) and paclitaxel (80 mg/m2) weekly, for 6 cycles, followed by CRT (external and brachytherapy) in week 7 with weekly cisplatin (40 mg/m2). The primary end-point was complete and partial response rate (RR) 12 weeks post CRT. Secondary objectives were RR for NACT at 6 weeks, toxicity and survival. The target RRs were 50% and 85% for NACT and post CRT (12-weeks) respectively. Results: Baseline characteristics were: median age at diagnosis 43 yrs (23–71); 74% squamous-, 20% adeno- and 6% adenosquamous carcinomas; FIGO stage IB2 (11%), II (50%), III (33%), IV (6%). The trial closed in Oct 08 with 46 pts. Of the first 36 pts enrolled 9 failed to complete protocol therapy (7 did not complete 6 NACT cycles, 2 did not complete the pre-specified minimum of 4 cycles of concomitant cisplatin). Using data currently available, the RR associated with NACT is 72% (95% CI 53–86%), and 81% at 12 weeks (95% CI 63–92%). Nonhaematological grade 3/4 toxicity was rare (<5%). There was grade 2 alopecia in 25% pts. Grade 3 and 4 haematological toxicity was seen in 10% and <3% of pts respectively. Updated results, including survival, will be presented for all pts. Conclusions: Dose-dense weekly NACT chemotherapy with carboplatin and paclitaxel followed by radical CRT is associated with a high response rate and is feasible. This approach merits further investigation in a phase III trial. [Table: see text]

The purpose is to develop and validate an automated method for detecting image unsharpness caused by patient motion blur in digital mammograms. The goal is that such a tool would facilitate immediate re-taking of blurred images, which has the potential to reduce the number of recalled examinations, and to ensure that sharp, high-quality mammograms are presented for reading. To meet this goal, an automated method was developed based on interpretation of the normalized image Wiener Spectrum. A preliminary algorithm was developed using 25 cases acquired using a single vendor system, read by two expert readers identifying the presence of blur, location, and severity. A predictive blur severity score was established using multivariate modeling, which had an adjusted coefficient of determination, R 2 =0.63±0.02, for linear regression against the average reader-scored blur severity. A heatmap of the relative blur magnitude showed good correspondence with reader sketches of blur location, with a Spearman rank correlation of 0.70 between the algorithmestimated area fraction with blur and the maximum of the blur area fraction categories of the two readers. Given these promising results, the algorithm-estimated blur severity score and heatmap are proposed to be used to aid observer interpretation. The use of this automated blur analysis approach, ideally with feedback during an exam, could lead to a reduction in repeat appointments for technical reasons, saving time, cost, potential anxiety, and improving image quality for accurate diagnosis.

Aims: to assess the feasibility and acceptability of large-gauge percutaneous removal of the axillary sentinel lymph node (SLN) using dual gamma probe and ultrasound guidance. Materials and Methods: Technetium nanocolloid was administered the day before surgery. On the day of surgery, potential SLNs were identified with gamma probe and ultrasound scanning. A 7G vacuum assisted biopsy (VAB) device was inserted percutaneously deep to the target node and the node(s) removed. The gamma probe was used to confirm removal of radiolabelled tissue. At surgery, any residual radiolabelled or blue nodes were removed. Morbidity was assessed via (i) a pain questionnaire immediately after the percutaneous procedure, (ii) relevant items from the FACT B+4 questionnaire 7-10 days after surgery, and (iii) case note review one month after surgery. Results: Twenty-two patients consented and 20 patients underwent the procedure. Radiolabelled nodal tissue was obtained in 18/20 (90%). The mean procedure time was 11 minutes. Four of 18 patients had metastatic disease identified in the VAB excision tissue with 100% sensitivity for axillary metastasis. At axillary surgery, additional intact SLN or fragments were found in 14 patients. No additional metastatic disease was found at surgery. One patient suffered a pneumothorax during instillation of local anaesthetic. The median pain score was 10/100 by visual analogue scale. Immediate post procedure haematoma was common (14 of 20) and prolonged manual compression frequent. Conclusion: VAB removal of sentinel nodes using dual scanning is feasible. Although preliminary sensitivity and specificity levels are encouraging, complications may discourage widespread implementation.

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BackgroundData collection is a substantial part of trial workload for participants and staff alike. How these hours of work are spent is important because stakeholders are more interested in some outcomes than others. The ORINOCO study compared the time spent collecting primary outcome data to the time spent collecting secondary outcome data in a cohort of trials.MethodsWe searched PubMed for phase III trials indexed between 2015 and 2019. From these, we randomly selected 120 trials evaluating a therapeutic intervention plus an additional random selection of 20 trials evaluating a public health intervention. We also added eligible trials from a cohort of 189 trials in rheumatology that had used the same core outcome set.We then obtained the time taken to collect primary and secondary outcomes in each trial. We used a hierarchy of methods that included data in trial reports, contacting the trial team, and approaching individuals with experience of using the identified outcome measures. We calculated the primary:secondary data collection time ratio and notional data collection cost for each included trial.ResultsWe included 161 trials (120 Phase III; 21 Core outcome set; 20 Public health), which together collected 230 primary and 688 secondary outcomes. Full primary and secondary timing data were obtained for 134 trials. The median time spent on primaries was 56 hours (range 0.0 – 10,747) and the median time spent on secondaries was 191 hours (range 0.0 – 1,356,833). The median primary:secondary data collection time ratio was 1:3.0 (i.e. for every minute spent on primary outcomes, 3.0 were spent on secondaries. The ratio varied by trial type: Phase III trials were 1: 3.1, Core outcome set 1:3.4 and Public health trials 1:2.2. The median notional overall data collection cost was £8,016 (range £53 – £31,899,141).ConclusionsDepending on trial type, between two and three times as much time is spent collecting secondary outcome data than collecting primary outcome data. Trial teams should explicitly consider how long it will take to collect the data for an outcome and decide whether that time is worth it given importance of the outcome to the trial.

BackgroundNeoadjuvant chemotherapy (NACT) is used to downstage breast cancer prior to surgery. Image monitoring is essential to guide treatment and to assess in vivo chemosensitivity. Breast MRI is considered the gold-standard imaging technique; however, it is contraindicated or poorly tolerated in some patients and may be hard to access. Evidence suggests contrast enhanced spectral mammography (CESM) may approach the accuracy of MRI. This novel pilot study investigates whether the addition of digital breast tomosynthesis (DBT) to CESM increases the accuracy of response prediction.ResultsSixteen cancers in fourteen patients were imaged with CESM+DBT and MRI following completion of NACT. Ten cancers demonstrated pathological complete response (pCR) defined as absence of residual invasive disease. Greatest accuracy for predicting pCR was with CESM contrast-enhancement only (accuracy 81.3%, sensitivity 100%, specificity 57.1%), followed by MRI (accuracy 62.5%, sensitivity 44.4%, specificity 85.7%). Concordance with invasive tumour size was greater for CESM than MRI, concordance-coefficients 0.70 vs 0.66 respectively. MRI demonstrated greatest concordance with whole tumour size followed by CESM contrast-enhancement plus microcalcification, concordance-coefficients 0.86 vs 0.69. The addition of DBT did not improve accuracy for prediction of pCR or residual disease size. Whereas CESM+DBT tended to underestimate size of residual disease, MRI tended to overestimate but no significant differences were seen (p>0.05).ConclusionsCESM contrast-enhancement plus microcalcification is similar to MRI for predicting residual disease post-NACT. Size of enhancement alone demonstrates best concordance with invasive disease. Inclusion of residual microcalcification improves concordance with DCIS. The addition of DBT to CESM does not improve accuracy.HighlightsNo benefit of adding DBT to CESM for NACT response predictionCESM appears similar to MRI for predicting response to NACTCESM has greatest accuracy for residual invasive tumour size.CESM+calcification has greater accuracy for predicting residual in situ disease.