RESUMEN
BACKGROUND: Post-treatment detection of circulating tumour DNA (ctDNA) in early-stage triple negative breast cancer (TNBC) patients predicts high risk of relapse. c-TRAK-TN assessed the utility of prospective ctDNA surveillance in TNBC and the activity of pembrolizumab in patients with ctDNA detected (ctDNA+). PATIENTS AND METHODS: c-TRAK-TN, a multi-centre phase II trial, with integrated prospective ctDNA surveillance by digital PCR, enrolled patients with early-stage TNBC and residual disease following neoadjuvant chemotherapy, or, stage II/III with adjuvant chemotherapy. ctDNA surveillance comprised three monthly blood sampling to 12 months (18 months if samples were missed due to COVID), and ctDNA+ patients were randomised 2:1; intervention:observation. ctDNA results were blinded unless patients were allocated to intervention, when staging scans were done and those free of recurrence were offered pembrolizumab. A protocol amendment (16/09/2020) closed the observation group; all subsequent ctDNA+ patients were allocated to intervention. Co-primary endpoints were i) ctDNA detection rate ii) sustained ctDNA clearance rate on pembrolizumab (NCT03145961). RESULTS: 208 patients registered between 30/01/18 - 06/12/19, 185 had tumour sequenced, 171 (92·4%) had trackable mutations, and 161 entered ctDNA surveillance. Rate of ctDNA detection by 12 months was 27·3% (44/161,95%CI:20·6-34·9). Seven patients relapsed without prior ctDNA detection. 45 patients entered the therapeutic component (intervention n=31; observation n=14; 1 observation patient was re-allocated to intervention following protocol amendment). Of patients allocated intervention, 72% (23/32) had metastases on staging at time of ctDNA+, and 4 patients declined pembrolizumab. Of the five patients who commenced pembrolizumab, none achieved sustained ctDNA clearance. CONCLUSION: c-TRAK-TN is the first prospective study to assess whether ctDNA assays have clinical utility in guiding therapy in TNBC. Patients had a high rate of metastatic disease on ctDNA detection. Findings have implications for future trial design, emphasising the importance of commencing ctDNA testing early, with more sensitive and/or frequent ctDNA testing regimes.
RESUMEN
Aims/Objectives/BackgroundThe Children’s Emergency Department (CED) in the Bristol Royal Hospital for Children (BRHC) runs ‘Review Clinics’ by a Paediatric Emergency Consultant. These were suspended in March 2020 due to the Covid-19 pandemic and new patient pathways were put in place. Our aim was to assess the effectiveness of these pathways and to evaluate if they should continue once the pressures of Covid-19 have eased.Methods/DesignWe reviewed all the attendances to the ED Review Clinic over a six-week period in 2019 and identified common conditions that are seen in this clinic – abscesses, cellulitis, scaphoid fracture, toddler fracture, limp, headache, peri-orbital cellulitis, torticollis, and neck lumps (accounting for 66% of all attendances).We then identified all of the ED attendances with these conditions over the same six-week period during the Covid-19 pandemic and performed a service review using medical notes.Results/ConclusionsAll children presenting with a limp during the Covid-19 pandemic were discharged with a leaflet and advised to return in one week if the limp persisted. None of them re-attended.Scaphoid and toddler fractures that presented during the Covid-19 pandemic were followed-up by Orthopaedics with a combination of telephone and face-to-face reviews. The toddler fractures were put into soft casts to be removed at home - 93% of parents were happy to do this. Orthopaedic review was quicker than the previous ED Review Clinic (an average of 63 hours compared to 216 for scaphoid fractures and 67 hours compared to 235 for toddler fractures).The results suggest that ED Review Clinics can and should change. Children with a limp can be sent home safely with clear advice. There is a greater role for telephone reviews, in particular, for injuries such as toddler fractures. This would be quicker, less time-consuming for patients, parents and physicians and more cost effective for the department.