BackgroundBoth oxaliplatin/capecitabine-based chemoradiation (OXCAP-RT) and carboplatin-paclitaxel based radiation (CarPac-RT) are active regimens in oesophageal adenocarcinoma, but no randomised study has compared their efficacy and toxicity. This randomised phase II “pick a winner” trial will identify the optimum regimen to take forward to a future phase III trial against neo-adjuvant chemotherapy, the current standard in the UK.Methods/DesignPatients with resectable adenocarcinoma of the oesophagus or Siewert Type 1–2 gastro-oesophageal junction (GOJ), ≥T3 and/or ≥ N1 are eligible for the study. Following two cycles of induction OXCAP chemotherapy (oxaliplatin 130 mg/m2 D1, Cape 625 mg/m2 D1-21, q 3 wk), patients are randomised 1:1 to OXCAP-RT (oxaliplatin 85 mg/m2 Day 1,15,29; capecitabine 625 mg/m2 twice daily on days of RT; RT-45 Gy/25 fractions/5 weeks) or CarPac-RT (Carboplatin AUC2 and paclitaxel 50 mg/m2 Day 1,8,15,22,29; RT-45 Gy/25 fractions/5 weeks). Restaging CT/PET-CT is performed 4–6 weeks after CRT, and a two-phase oesophagectomy with two-field lymphadenectomy is performed six to eight weeks after CRT. The primary end-point is pathological complete response rate (pCR) at resection and will include central review. Secondary endpoints include: recruitment rate, toxicity, 30-day surgical morbidity/mortality, resection margin positivity rate and overall survival (median, 3- and 5-yr OS. 76 patients (38/arm) gives 90% power and one-sided type 1 error of 10% if patients on one novel treatment have a response rate of 35% while the second treatment has a response rate of 15%. A detailed RT Quality Assurance (RTQA) programme includes a detailed RT protocol and guidance document, pre-accrual RT workshop, outlining exercise, and central evaluation of contouring and planning. This trial has been funded by Cancer Research UK (C44694/A14614), sponsored by Velindre NHS Trust and conducted through the Wales Cancer Trials Unit at Cardiff University on behalf of the NCRI Upper GI CSG.DiscussionFollowing encouraging results from previous trials, there is an interest in neo-adjuvant chemotherapy and CRT containing regimens for treatment of oesophageal adenocarcinoma. NEOSCOPE will first establish the efficacy, safety and feasibility of two different neo-adjuvant CRT regimens prior to a potential phase III trial.Trial registrationEudract No: 2012-000640-10. ClinicalTrials.gov: NCT01843829.

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Background and purpose: Current automated radiotherapy planning solutions do not allow for the intuitive exploration of different treatment options during protocol calibration. This work introduces an automated planning solution, which aims to address this problem through incorporating Pareto navigation techniques into the calibration process. Materials and methods: For each tumour site a set of planning goals is defined. Utilising Pareto navigation techniques an operator calibrates the solution through intuitively exploring different treatment options: selecting the optimum balancing of competing planning goals for the given site. Once calibrated, fully automated plan generation is possible, with specific algorithms implemented to ensure trade-off balancing of new patients is consistent with that during calibration. Using the proposed methodology the system was calibrated for prostate and seminal vesicle treatments. The resultant solution was validated through quantitatively comparing the dose distribution of automatically generated plans (VMAT Auto) against the previous clinical plan, for ten randomly selected patients. Results: VMAT Auto yielded statistically significant improvements in: PTV conformity indices, high dose bladder metrics, mean bowel dose, and the majority of rectum dose metrics. Of particular note was the reduction in mean rectum dose (median 25.1 Gy vs. 27.5 Gy), rectum V 24.3Gy (median 41.1% vs. 46.4%), and improvement in the conformity index for the primary PTV (median 0.86 vs. 0.79). Dosimetric improvements were not at the cost of other dose metrics. Conclusions: An automated planning methodology with a Pareto navigation based calibration has been developed, which enables the complex balancing of competing trade-offs to be intuitively incorporated into automated protocols.

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BackgroundSCOPE 1 was the first UK based multi-centre trial involving radiotherapy of the oesophagus. A comprehensive radiotherapy trials quality assurance programme was launched with two main aims:To assist centres, where needed, to adapt their radiotherapy techniques in order to achieve protocol compliance and thereby enable their participation in the trial.To support the trial’s clinical outcomes by ensuring the consistent planning and delivery of radiotherapy across all participating centres. MethodsA detailed information package was provided and centres were required to complete a benchmark case in which the delineated target volumes and organs at risk, dose distribution and completion of a plan assessment form were assessed prior to recruiting patients into the trial. Upon recruiting, the quality assurance (QA) programme continued to monitor the outlining and planning of radiotherapy treatments. Completion of a questionnaire was requested in order to gather information about each centre’s equipment and techniques relating to their trial participation and to assess the impact of the trial nationally on standard practice for radiotherapy of the oesophagus. During the trial, advice was available for individual planning issues, and was circulated amongst the SCOPE 1 community in response to common areas of concern using bulletins.Results36 centres were supported through QA processes to enable their participation in SCOPE1. We discuss the issues which have arisen throughout this process and present details of the benchmark case solutions, centre questionnaires and on-trial protocol compliance. The range of submitted benchmark case GTV volumes was 29.8–67.8cm3; and PTV volumes 221.9–513.3 cm3. For the dose distributions associated with these volumes, the percentage volume of the lungs receiving 20Gy (V20Gy) ranged from 20.4 to 33.5%. Similarly, heart V40Gy ranged from 16.1 to 33.0%. Incidence of incorrect outlining of OAR volumes increased from 50% of centres at benchmark case, to 64% on trial. Sixty-five percent of centres, who returned the trial questionnaire, stated that their standard practice had changed as a result of their participation in the SCOPE1 trial.ConclusionsThe SCOPE 1 QA programme outcomes lend support to the trial’s clinical conclusions. The range of patient planning outcomes for the benchmark case indicated, at the outset of the trial, the significant degree of variation present in UK oesophageal radiotherapy planning outcomes, despite the presence of a protocol. This supports the case for increasingly detailed definition of practice by means of consensus protocols, training and peer review. The incidence of minor inconsistencies of technique highlights the potential for improved QA systems and the need for sufficient resource for this to be addressed within future trials. As indicated in questionnaire responses, the QA exercise as a whole has contributed to greater consistency of oesophageal radiotherapy in the UK via the adoption into standard practice of elements of the protocol.Trial regis...