Background:Patients with advanced or recurrent endometrial cancer have poor survival outcomes because effective treatment options remain limited. We investigated the efficacy and safety of cediranib plus weekly paclitaxel or olaparib versus weekly paclitaxel alone after prior platinum-based chemotherapy. Methods:COPELIA was an open-label, randomised, phase 2 trial undertaken at 15 centres in the United Kingdom. Eligible participants were aged 16 years or older with histologically confirmed endometrial cancer, Eastern Cooperative Oncology Group performance status 0-1, a life expectancy greater than 16 weeks, and at least one previous line of platinum-based chemotherapy. Patients were randomly assigned to paclitaxel 80 mg/m2 on days 1, 8, and 15 of a 28-day cycle (arm 1, control); cediranib 20 mg daily plus the same paclitaxel schedule (arm 2, experimental); or cediranib 20 mg daily plus olaparib 300 mg twice daily (arm 3, experimental). Up to six cycles of paclitaxel were permitted. Patients in arm 2 with a Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 complete or partial response, or stable disease, after paclitaxel plus cediranib continued cediranib monotherapy. The primary endpoint was the proportion of patients free from RECIST-defined progression or death at 3 months (PFS at 3 months). Secondary endpoints included RECIST response, PFS at 6 months, median PFS, median overall survival (OS), safety, and quality of life. Translational analyses assessed vascular response, defined as a reduction of 5% or more in plasma Tie2 within 9 weeks of treatment initiation. The trial was registered with EudraCT (2016-004617-28), ISRCTN (16320634), and ClinicalTrials.gov (NCT03570437). Findings:Between May 1, 2018, and January 11, 2022, 124 patients were enrolled and randomised to arm 1 (n = 41), arm 2 (n = 41), or arm 3 (n = 42). Median follow-up in arms 1, 2, and 3 was 34.4 months (interquartile range [IQR] 11.6-37.6), 26.3 months (11.8-not evaluable), and 23.7 months (15.0-not evaluable), respectively. PFS at 3 months was significantly higher in arm 2 than in arm 1 (73.2% versus 48.8%; adjusted odds ratio [aOR] 3.2, lower limit of one-sided 80% confidence interval [CI] 2.1; p = 0.01). RECIST response was also higher in arm 2 versus arm 1 (56.4% versus 28.2%; aOR 5.7, 95% CI 1.8-17.6; p < 0.001). No differences were observed between arm 3 and arm 1 for PFS at 3 months (aOR 1.0, lower limit of one-sided 80% CI 0.71; p = 0.46) or RECIST response (aOR 0.8, 95% CI 0.3-2.6; p = 0.73). Median OS was 12.8 months (95% CI 7.3-16.8) in arm 1, 18.1 months (9.5-26.4; log-rank p = 0.42 versus arm 1) in arm 2, and 13.9 months (11.2-18.3; log-rank p = 0.86 versus arm 1) in arm 3. There was no difference in PFS at 6 months and median PFS between arm 1 and arm 2 or arm 3. Grade 3 adverse events occurring in ≥10% of patients in arm 2 included hypertension (15%), neutropenia (12%), and diarrhoea (10%). Quality-of-life differences favoured arm 1 over arm 2 for diarrhoea and gastrointestinal symptoms (p < 0.001). In multivariable analyses, cediranib-treated patients who achieved a Tie2-defined vascular response had significantly improved PFS (hazard ratio 0.54, 95% CI 0.33-0.88; p = 0.014). Interpretation:Paclitaxel plus cediranib improved 3-month PFS and RECIST response compared with paclitaxel alone in advanced or recurrent endometrial cancer. However, this effect diminished over time; with no difference in PFS observed at 6 months, nor median PFS or median OS. Plasma Tie2 identified cediranib-treated patients with improved PFS. Further evaluation of paclitaxel plus cediranib in patients previously treated with platinum-based chemotherapy and immunotherapy is warranted, ideally incorporating plasma Tie2 as a response biomarker to guide treatment continuation. Funding:AstraZeneca.

Introduction Despite repeated vaccinations against SARS-CoV-2 virus, patients who are immunocompromised remain at very high risk of catching SARS-CoV-2 virus and becoming unwell. AZD7442 (Evusheld) is a long-acting monoclonal antibody treatment that has been shown in clinical trials to prevent SARS-CoV-2 infection for up to a year after a single dose. Vaccines require a healthy immune system to generate protective immunity. AZD7442 may prevent SARS-CoV-2 infection in immunocompromised individuals that may not have responded to repeated vaccinations against SARS-CoV-2 virus. Unlike vaccinations, AZD7442 reaches effective levels within the body a few hours after a single dose. The RAPID-PROTECTION trial will determine the levels of immune protection that AZD7442 offers patients at the very highest risk of SARS-CoV-2 infection and whether this protection can be further enhanced by repeated vaccination against SARS-CoV-2 virus.Methods RAPID-PROTECTION is a multicentre, interventional and open-label adaptive platform trial that aims to recruit 350 immunocompromised participants across five UK centres. Participants will be administered AZD7442 on day 0 followed by a SARS-CoV-2 vaccination 28 days later. Participants will be randomised (1:1) to the Moderna vaccine or Pfizer/BioNTech vaccine. Participant samples will be taken at baseline and at multiple timepoints after the administration of AZD7442.Analysis The participant samples will be analysed to measure the function and magnitude of SARS-CoV-2 specific antibody and T-cell responses at baseline and at multiple timepoints after the administration of AZD7442. The immunological effect of the study interventions will be determined by comparison of the results of immunological assessments at baseline and subsequent timepoints.Ethics and dissemination The trial protocol was approved by the research ethics committee of the National Health Service (reference 22/HRA/0359), Health Research Authority and Health and Care Research Wales on 25 July 2022. Findings will be disseminated through peer-reviewed journals and presented at scientific conferences.Trial registration number ISRCTN53507177.

OBJECTIVE:Cytotoxic chemotherapy for ovarian cancer can be augmented by co-administration of vascular endothelial growth factor inhibitors but these are contraindicated in patients with bowel obstruction due to the risk of gastrointestinal perforation. We evaluated the safety and feasibility of paclitaxel plus cediranib to treat patients with platinum-resistant ovarian cancer at risk of malignant bowel obstruction. METHODS:A phase II trial included eligible patients between March 2018 and February 2021, identified by clinical symptoms and radiographic risk factors for malignant bowel obstruction. Cediranib (20 mg/day) was added to paclitaxel (70 mg/m2/week) within 9 weeks of starting paclitaxel if pretreatment bowel symptoms had improved. The primary endpoint was the number of patients treated for ≥5 days with cediranib that were free of grade 3-5 gastrointestinal perforation or fistula. Secondary endpoints were hospitalization for bowel obstruction, grade ≥3 adverse events, treatment compliance assessed by relative dose intensity, objective response, progression-free survival, and overall survival. RESULTS:Thirty patients were recruited. Of these, 12 received paclitaxel alone and 17 received paclitaxel and cediranib in combination. One patient died before starting treatment. No patient developed a grade 3-5 gastrointestinal perforation or fistula (one sided 95% confidence interval (CI) upper limit 0.16). One patient required hospitalization for bowel obstruction but recovered with conservative management. The most common cediranib-related grade ≥3 adverse events were fatigue (3/17), diarrhorea (2/17), and hypomagnesemia (2/17). Relative dose intensity for paclitaxel was 90% (interquartile range (IQR) 85-100%; n=29) and for cediranib 88% (IQR 76-93%; n=17). The objective response in patients who received paclitaxel and cediranib was 65.0% (one complete and 10 partial responses). Median progression-free survival was 6.9 months (95% CI 4.4-11.5 months; n=17) and overall survival was 19.4 months (95% CI 10.1-20.4 months; n=17). Median follow-up was 12.4 months (8.9-not reached; n=17). CONCLUSIONS:The unexpectedly high withdrawal rate during paclitaxel alone, before introducing cediranib, meant we were unable to definitely conclude that paclitaxel plus cediranib did not cause gastrointestinal perforation or fistula. The regimen was however tolerated. TRIAL REGISTRATION NUMBER:EudraCT 2016-004618-93.

Objective: To describe the prevalence of potentially clinically relevant gut pathogens and associations with the carriage of resistant organisms in UK care home residents. Methods: Stool samples were collected pre-randomisation from care home residents participating in a randomised placebo-controlled trial. Cultivable clinically relevant bacteria were analysed. Antimicrobial susceptibility testing was performed by agar dilution (amoxicillin, co-amoxiclav, gentamicin, trimethoprim, nitrofurantoin, and ciprofloxacin). We also aimed to detect resistance to third-generation cephalosporins, carbapenems, and vancomycin. Results: Stool samples were available for 159/310 residents participating in the trial (51%) from 23 care homes between 2016 and 2018. In total, 402 bacterial isolates were cultured from 158 stool samples and 29 different species were cultured. The five most common species were Escherichia coli (155/158, 98%), Pseudomonas aeruginosa (40/158, 25%), Enterococcus faecalis (35/158, 22%), Enterococcus faecium (30/158, 19%), and Proteus mirabilis (25/158, 16%). Enterobacterales isolates were cultured from 157 samples (99%), and resistance to at least one of the tested antimicrobials was found in 119 of these (76%). There were high levels of variation in outcomes by care home. Discussion: We demonstrated that care home residents harbour significant levels of antimicrobialresistant organisms in their stool. This work emphasises the importance of both enhanced infection control practices and antimicrobial stewardship programmes to support the appropriate use of antimicrobials in this setting. David Gillespie, Clin Microbiol Infect 2023;29:1437 (c) 2023 The Author(s). Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/4.0/).

Skin cancer is the most common malignancy in the UK, and up to a third of lesions are ulcerated at the time of excision. Ulceration has been shown to increase the risk of developing surgical site infection following excision, with some studies finding infection rates of 33%. However, no specific guidelines for the use of antibiotic prophylaxis in such cases exist. We surveyed 129 clinicians (covering Dermatology, Plastic Surgery, Ear, Nose and Throat Surgery, and Oral and Maxillofacial Surgery) who all excise skin lesions on a regular basis. There was significant variability in their practice with regard to antibiotic prophylaxis, with 9% always prescribing them and 19% never prescribing them. Variation exists both among and between specialities. This variation increases the risk of antimicrobial resistance and shows a paucity of good clinical evidence, indicating that a well-designed clinical trial is needed to guide future practice.

Introduction/Background Systemic treatment of platinum-resistant advanced ovarian cancers (PROC) utilises cytotoxic chemotherapy and vascular endothelial growth factor receptor (VEGFR) inhibitors. However, patients at risk for malignant bowel obstruction (MBO) are excluded from this efficacious combination due to risk of bowel perforation. Methodology We conducted a Simon’s two-stage trial combining oral VEGFR inhibitor cediranib (20 mg/day) with weekly paclitaxel (70 mg/m2), in participants with recurrent PROC and clinical and/or radiological features indicating an increased risk of developing MBO. Primary endpoint was number of patients free of grade 3–5 gastrointestinal perforation (GIP) or fistula, from those who received ≥5 days and ≤18 weeks cediranib, causally related to cediranib. With 90% power and 5% significance, 24 evaluable patients were required, with 22 free of GIP or fistula to demonstrate safety. Cediranib could start with chemotherapy, or at cycle 2 or 3, once bowel symptoms were CTCAE grade ≤2. Previous bevacizumab exposure and prior MBO were permitted. Patients were continued on cediranib maintenance after paclitaxel completion, and optionally proceeded to cediranib plus olaparib (300 mg bd) at disease progression. Results 30 participants were enrolled from March 2018 to February 2021. 90% ECOG 0–1, 97% had symptoms showing risk of bowel obstruction. 1 patient died before any treatment. 12 received paclitaxel only (bowel symptoms didn’t improve or deterioration) and subsequently progressed. 17 patients were evaluable for primary endpoint; none developed GIP or fistula. Three cediranib+paclitaxel participants developed bowel obstruction (any grade; including one receiving cediranib+olaparib). Three participants had grade 3+ SAEs causally related to cediranib+/-olaparib (one diarrhoea; one diarrhoea and TIA; one vomiting). Median progression-free survival was 5.4 months (95%CI: 4.18–8.25), and overall survival 15.2 months (95%CI: 8.52–20.5). Conclusion There is no evidence that combining cediranib and taxane chemotherapy is associated with serious toxicity or of developing GIP/fistula, although this is underpowered due to participant withdrawal.

Aim: This is the first randomised study to evaluate toxicity and survival outcomes of two neoadjuvant chemoradiotherapy (CRT) regimens for patients with localised oesophageal adenocarcinoma (OAC) or gastro-oesophageal junction (GOJ) adenocarcinoma. The initial results showed comparable toxicity between regimens and pathological complete response (pCR) rate favouring CarPacRT. Herein, we report survival, progression patterns, and long-term toxicity after a median follow-up of 40.7 months. Methods: NeoSCOPE was an open-label, UK multicentre, randomised, phase II trial. Eightyfive patients with resectable OAC or GOJ adenocarcinoma, >= cT3 and/or >= cN1 (TNM v7), suitable for neoadjuvant CRT, were recruited between October 2013 and February 2015. Patients were randomised to OxCapRT (oxaliplatin 85 mg/m(2) on Days 1, 15, and 29; capecitabine 625 mg/m(2) orally twice daily on days of radiotherapy [RT]) or CarPacRT (carboplatin AUC2; paclitaxel 50 mg/m(2) on Days 1, 8, 15, 22, and 29). RT dose was 45 Gy/25 fractions/5 weeks. Both arms received induction chemotherapy (two cycles oxaliplatin 130 mg/m(2) on Day 1, capecitabine 625 mg/m(2) orally twice daily on Days 1-21) before CRT. Surgery was performed 6-8 weeks after CRT. The primary end-point was pCR. Secondary end-points were toxicity, progression-free survival (PFS), overall survival (OS), and patterns of progression. Results: Eighty-five patients were recruited from 17 UK centres. The median OS was 41.7 months (95% confidence interval [CI] 19.6 to not reached) in the OxCapRT arm and was not reached in the CarPacRT arm (multivariable hazard ratio [HR] = 0.48, 95% CIs: 0.24-0.95, P = 0.035). The median PFS was 32.6 months (95% CIs: 17.1 to not reached) in the OxCapRT arm and was not reached in the CarPacRT arm (multivariable HR = 0.54, 95% CIs: 0.29-1.01, P = 0.053). In both arms, the distant progression was twice as common as locoregional progression. Conclusions: OS and PFS favoured neoadjuvant CarPacRT over OxCapRT. Distant was more common than locoregional progression; therefore, priority should be given to optimising the systemic treatment component. (C) 2021 The Author(s). Published by Elsevier Ltd.

AIM:This is the first randomised study to evaluate toxicity and survival outcomes of two neoadjuvant chemoradiotherapy (CRT) regimens for patients with localised oesophageal adenocarcinoma (OAC) or gastro-oesophageal junction (GOJ) adenocarcinoma. The initial results showed comparable toxicity between regimens and pathological complete response (pCR) rate favouring CarPacRT. Herein, we report survival, progression patterns, and long-term toxicity after a median follow-up of 40.7 months. METHODS:NeoSCOPE was an open-label, UK multicentre, randomised, phase II trial. Eighty-five patients with resectable OAC or GOJ adenocarcinoma, ≥cT3 and/or ≥cN1 (TNM v7), suitable for neoadjuvant CRT, were recruited between October 2013 and February 2015. Patients were randomised to OxCapRT (oxaliplatin 85 mg/m2 on Days 1, 15, and 29; capecitabine 625 mg/m2 orally twice daily on days of radiotherapy [RT]) or CarPacRT (carboplatin AUC2; paclitaxel 50 mg/m2 on Days 1, 8, 15, 22, and 29). RT dose was 45 Gy/25 fractions/5 weeks. Both arms received induction chemotherapy (two cycles oxaliplatin 130 mg/m2 on Day 1, capecitabine 625 mg/m2 orally twice daily on Days 1-21) before CRT. Surgery was performed 6-8 weeks after CRT. The primary end-point was pCR. Secondary end-points were toxicity, progression-free survival (PFS), overall survival (OS), and patterns of progression. RESULTS:Eighty-five patients were recruited from 17 UK centres. The median OS was 41.7 months (95% confidence interval [CI] 19.6 to not reached) in the OxCapRT arm and was not reached in the CarPacRT arm (multivariable hazard ratio [HR] = 0.48, 95% CIs: 0.24-0.95, P = 0.035). The median PFS was 32.6 months (95% CIs: 17.1 to not reached) in the OxCapRT arm and was not reached in the CarPacRT arm (multivariable HR = 0.54, 95% CIs: 0.29-1.01, P = 0.053). In both arms, the distant progression was twice as common as locoregional progression. CONCLUSIONS:OS and PFS favoured neoadjuvant CarPacRT over OxCapRT. Distant was more common than locoregional progression; therefore, priority should be given to optimising the systemic treatment component. CLINICAL TRIAL INFORMATION:EudraCT Number: 2012-000640-10; ClinicalTrials.gov: NCT01843829.

373 Background: Initial results of the NEOSCOPE trial comparing pre-operative CarPac vs OxCap based chemoradiotherapy (CRT) in patients with adenocarcinoma of the oesophagus or oesophagogastric junction showed comparable toxicity and improvement in pathological complete response (pCR) in favour of the CarPacRT. Here we report survival after a median follow-up of 40.7 months (95% CI: 45.1-53.6). Methods: NEOSCOPE was an open, randomised, ‘pick a winner’ phase II trial. Patients with resectable oesophageal adenocarcinoma ≥ cT3 and/or ≥ cN1 were randomised to OxCapRT (oxaliplatin 85 mg/m2 day 1, 15, 29; capecitabine 625 mg/m2 bd on days of RT) or CarPacRT (carboplatin AUC2; paclitaxel 50 mg/m2 day 1, 8, 15, 22, 29). RT dose was 45 Gy/25 fractions/5 weeks. Induction OxCap (2 cycles) was given prior to CRT. Surgery was performed 6–8 weeks after CRT.The primary endpoint was pCR, secondary endpoints were toxicity, PFS and OS. Results: Between Oct 2013 and Feb 2015, 85 patients were recruited from 17 UK centres. Median OS was not reached in the CarPacRT group and was 41.72 months (95% CI 19.58-.)in the OxCap group (HR 0.56[95% CI 0.29-1.07]; p=0.079). 3-year and 5-year OS rates were 74% (95% CI 58%-85%) and 54% (95% CI 34%-71%) (CarPacRT), and 52% (95% CI 35%-67%) and 39% (95% CI 21%-56%) (OxCapRT). Median PFS (not reached vs 35.3 months, HR=0.61 [95% CI 0.33-1.12]; p=0.111) and metastatic PFS (not reached vs 39.0 months, HR=0.61 [95% CI 0.32-1.14], p=0.118) both favoured the CarPacRT arm. Local recurrence rate was low (OxCapRT= 10%; CarPacRT= 7%). The OS benefit for CarPacRT was consistent across subgroups but not statistically significant. Conclusions: In this longer term analysis there was some evidence that induction OxCap followed by switch to CarPacRT was superior to continuing OxCapRT, with efficacy similar to that seen in other published studies such as ‘CROSS’ and ‘FLOT’. Taken together with the previously published pCR results CarPacRT rather than OxCapRT warrants inclusion in future trials. Funding: Cancer Research UK (C44694/A14614). Clinical trial information: NCT01843829.

BACKGROUND: Neoadjuvant chemotherapy (NAC) allows earlier treatment of rectal cancer micro-metastases but is not standard of care. There are currently no biomarkers predicting long-term progression-free survival (PFS) benefit from NAC. PATIENTS AND METHODS: In this single arm phase II trial, patients with non-metastatic magnetic resonance imaging (MRI)defined operable rectal adenocarcinoma at high risk of post-operative metastatic recurrence, received 8 weeks of oxaliplatin/ fluorouracil NAC then short-course preoperative radiotherapy (SCPRT) before immediate surgery. Sixteen weeks of post-operative adjuvant chemotherapy (AC) was planned. A pelvic MRI was performed at week 9 immediately post-NAC, before SCPRT. The primary end point was feasibility assessed by completion of protocol treatment up to and including surgery. Secondary endpoints included compliance, toxicity, downstaging efficacy, and PFS. RESULTS: In total 60 patients were recruited May 2012-June 2014. In total 57 patients completed protocol treatment, meeting the primary endpoint. Compliance with NAC was much better than AC: Comparing NAC vs. AC, the median percentage dose intensity for fluoropyrimidine was 100% vs. 63% and for oxaliplatin 100% vs. 45%. Treatment-related toxicity was acceptable with no treatment-related deaths. Post-NAC MRI showed 44 tumours (73%) were T-downstaged and 22 (37%) had excellent MRI tumour regression grade (mrTRG 1-2). Median follow-up was 27 months with 2-year PFS of 86.2% (10 events). On exploratory analysis, post-NAC mrTRG predicted PFS with no event among those with excellent regression. CONCLUSION: The regimen was well tolerated with effective downstaging and encouraging PFS. mrTRG response to NAC may be a new prognostic factor for long-term PFS, but needs validation in larger studies.

SCALOP, a randomised, phase II trial, tested the activity and safety of gemcitabine (GEM)-based and capecitabine (CAP)-based chemoradiation (CRT) for locally advanced pancreatic cancer (LAPC). Here we present the long-term outcomes. Eligibility: histologically proven LAPC ⩽7 cm. Following 12 weeks of induction GEMCAP chemotherapy (three cycles: GEM 1000 mg m−2 days 1, 8, 15; CAP 830 mg m−2 days 1–21 q28 days) patients with stable/responding disease, tumour ⩽6 cm, and WHO Performance Status 0–1 were randomised to receive one cycle GEMCAP followed by CAP (830 mg m−2 b.d. on weekdays only) or GEM (300 mg m−2 weekly) with radiation (50.4 Gy per 28 fractions). One-hundred fourteen patients (28 UK centres) were registered between 24 December 2009 and 25 October 2011, and 74 were randomised (CAP-RT=36; GEM-RT=38). At the time of this analysis, 105 of the 114 patients had died and the surviving 9 patients had been followed up for a median of 10.9 months (IQR: 2.9–18.7). Updated median OS was 17.6 months (95% CI: 14.6–22.7) in the CAP-CRT arm and 14.6 months (95% CI: 11.1–16.0) in the GEM-CRT arm (intention-to-treat adjusted hazard ratio (HR): 0.68 (95% CI: 0.38–1.21, P=0.185)); median progression-free survival (PFS) was 12.0 months (95% CI: 10.0–15.2) in the CAP-CRT arm and 10.4 months (95% CI: 8.8–12.7) in the GEM-CRT arm (intention-to-treat adjusted HR: 0.60 (95% CI: 0.32–1.14, P=0.120)). In baseline multivariable model, age ⩾65 years, better performance status, CA19.9<613 IU l−1, and shorter tumour diameter predicted improved OS. CAP-CRT, age ⩾65 years, better performance status, CA19.9 <46 IU ml−1 predicted improved OS and PFS in the pre-radiotherapy model. Nine-month PFS was highly predictive of OS. CAP-CRT remains the superior regimen. SCALOP showed that patients with CA19.9 <46 IU ml−1 after induction chemotherapy are more likely to benefit from CRT.

The SCOPE-1 study tested the role of adding cetuximab to conventional definitive chemoradiotherapy (dCRT), and demonstrated greater toxicity and worse survival outcomes. We present the long-term outcomes and patterns of recurrence. SCOPE-1 was a phase II/III trial in which patients were randomised to cisplatin 60 mg m−2 (day 1) and capecitabine 625 mg m−2 bd (days 1–21) for four cycles +/− cetuximab 400 mg m−2 day 1 then by 250 mg m−2 weekly. Radiotherapy consisted of 50 Gy/25# given concurrently with cycles 3 and 4. Recruitment was between February 2008 and February 2012, when the IDMC recommended closure on the basis of futility. About 258 patients (dCRT=129; dCRT+cetuximab (dCRT+C)=129) were recruited from 36 centres. About 72.9% (n=188) had squamous cell histology. The median follow-up (IQR) was 46.2 (35.9–48.3) months for surviving patients. The median overall survival (OS; months; 95% CI) was 34.5 (24.7–42.3) in dCRT and 24.7 (18.6–31.3) in dCRT+C (hazard ratio (HR)=1.25, 95% CIs: 0.93–1.69, P=0.137). Median progression-free survival (PFS; months; 95% CI) was 24.1 (15.3–29.9) and 15.9 (10.7–20.8) months, respectively (HR=1.28, 95% CIs: 0.94–1.75; P=0.114). On multivariable analysis only earlier stage, full-dose RT, and higher cisplatin dose intensity were associated with improved OS. The mature analysis demonstrates that the dCRT regimen used in the study provided useful survival outcomes despite its use in patients who were largely unfit for surgery or who had inoperable disease. Given the competing risk of systemic and local failure, future studies should continue to focus on enhancing local control as well as optimising systemic therapy.

119 Background: Failure to adhere to trial protocols for target volume delineation (TVD) within radiotherapy (RT) trials may have an adverse effect on, and potentially invalidate trial outcomes. NeoSCOPE, a UK phase II study RCT of two neo-adjuvant CRT regimens in oesophageal cancer, undertook prospective individual case-reviews (ICR) to identify and correct such variations. Methods: All participating centres had passed a pre-accrual outlining benchmark case with detailed feedback provided. Prospective ICR was undertaken for all patients. Real time review (feedback to centres within 3 working days) was performed on the first 20 patients recruited and the first case submitted from each participating centre. Subsequent cases were subject to ‘timely retrospective review’, with review within 2 weeks of the start of RT. Target volumes (including organ at risk), along with diagnostic information, were submitted in DICOM format to the RTQA centre. Each case was reviewed by an upper gastrointestinal radiation oncologist, against pre-determined acceptable and unacceptable variations, using a standardised proforma. Unacceptable variation required re-submission. The outlining reviews were complimented by prospective review of planning. Results: 83 cases were reviewed in total, 39 (47%) of which were real-time and 44 (53%) timely- retrospective. 9(11%) cases required re-submission, of which 6 were real-time reviews and 3 timely-retrospective. Delineation of the tumour (GTV) and elective nodal areas (CTVB) were the most common unacceptable variations. 29 (74%) of real time reviews were returned within 3 working days and 100% of retrospective returned by 3 rd fraction. The review process did not result in any delay in starting treatment. Conclusions: Prospective review of outlining in the NeoSCOPE trial has enabled identification and correction of unacceptable variations from the protocol without introducing treatment delays. The reduction in the re-submission rate for timely-retrospective review cases suggests an educational benefit from the pre-trial RTQA and the real-time review process. Clinical trial information: NCT01843829.

Introduction: The SCALOP trial tested the safety and efficacy of gemcitabine (Gem) versus capecitabine (Cap) based CRT following induction chemotherapy and showed that GemRT was associated with greater toxicity and worse survival. Here we present the long-term outcomes. Methods: Open-label, 2-arm, randomised Phase II trial. All patients received 3 cycles of induction chemotherapy (GEMCAP: Gemcitabine 1000mg/m2 on days 1,8,15 and capecitabine 830mg/m2 twice daily on days 1-21 of 28-day cycle). Patients with responding/stable disease, PS 0-1 with maximum tumour diameter 6cm or less were randomised. 1:1 randomisation (stratified on centre, WHO performance status [0 vs 1], and disease location [head vs body or tail]): 1 cycle of GEMCAP followed by either Gemcitabine (300mg/m2 weekly) or Capecitabine (830mg/m2 twice daily on days of RT) based CRT. RT: 50.4Gy in 28 fractions. Recruitment: Dec 2009 - Oct 2011. The study was sponsored by Cardiff University and funded by Cancer Research UK (Grant No. 07/040). ISRCTN: 96169987. Results: 114 patients were recruited from 28 centres in the UK, and 74 patients (CapRT = 36; GemRT = 38) were randomised. At the time of this analysis, 34/36 patients in CapRT arm and 35/38 in GemRT have died. The surviving 5 patients have been followed up for a median of 12.2 months (IQR: 7.5-41.9). Median OS months (95% CI) was 17.6 months (95% CI: 14.6-22.7) in CapRT arm and 14.6 months (95% CI: 11.1-16.0) in GemRT arm. HR: Unadjusted: 0.73 (95% CI: 0.46-1.18, p = 0.203). Adjusted: 0.67 (95% CI: 0.38-1.21, p = 0.185). Median PFS was 12.0 months (95% CI: 10.0-15.2) in the CapRT and 10.4 months (95% CI: 8.8-12.7) in the GemRT arm. HR: Unadjusted: 0.73 (95% CI: 0.44-1.23, p = 0.244). Adjusted: 0.60 (95% CI: 0.32-1.14, p = 0.120). On multivariable analysis by baseline characteristics in all 114 recruited patients, age ≥65 (p = 0.013), WHO PS 0 (vs 1-2) (p < 0.001), baseline CA19-9 <613 (p < 0.001) and smaller tumour diameter (p = 0.005) were associated with improved OS. Conclusion: The mature analysis shows that the excellent survival following CapRT in LAPC is maintained and outcomes are comparable to surgical series of borderline resectable tumours treated with downstaging CRT and surgery. Survival inferiority of GemRT is no longer statistically significant. Further analyses on PFS, treatment effect and patterns of recurrence are ongoing and will be presented.

Objective: We sought to develop a process that would allow us to perform a prospective review of outlining in trials using expert reviewers based in multiple centres.Methods: We implemented a specific information technology infrastructure and workflow that could serve all organizations involved in the radiotherapy quality assurance (RTQA) process.Results: Data were processed and packaged in the computational environment for radiotherapy research (CERR) binary format and securely transmitted to the expert reviewer at the designated remote organization. It was opened and reviewed using the distributed CERR-compiled application, and a standardized report was sent to the respective centre. Centres were expected to correct any unacceptable deviations and resubmit outlining for approval prior to commencing treatment. 75% of reviews were completed and fed back to centres within 3 working days. There were no delays in treatment start date.Conclusion: Our distributed RTQA review approach provides a method of prospective outlining review at multiple centres, without compromising the quality, delaying the start of treatment or the need for significant additional infrastructure resources. Future progress in the area of prospective individual case review will need to be supported by additional resources for clinician time to undertake the reviews.Advances in knowledge: Trial groups around the world have formulated different approaches to address the need for the prospective review of radiotherapy (RT) data with clinical trials, in line with available resources. We report a UK solution that has allowed the workload for outlining review to be distributed across a wider group of volunteer reviewers without the need for any additional infrastructure costs and has already been adopted within the UK RT trials community.

3609 Background: Feasibility was assessed of giving NAC prior to SCPRT then immediate surgery in ORC at high risk of metastatic relapse. Methods: Patients (pts) had non-metastatic rectal adenocarcinoma. Pre-treatment pelvic MRI showed resection margin was not at risk (disease > 1mm from mesorectal fascia) but adverse risk factors were present (disease > T3b or node positive or extramural vascular invasion). Pts received 4x2-weekly cycles of oxaliplatin 85mg/m² + levofolinic acid 175 mg, fluorouracil (FU) 400 mg/m² (bolus), then FU 2400 mg/m² (continuous IV in 46 hr). Within 14 days pts had pelvic SCPRT to 25 Gy in 5 daily fractions. Definitive surgery then occurred within a week. Post surgery pts received 16 weeks of OxMdG or oxaliplatin/capecitabine. The primary endpoint was the proportion of pts completing protocol treatment including surgery. Results: 60 UK pts were recruited May 2012-June 2014. At baseline: male 44 (73%), median age 63 (IQR: 56.5-70), WHO PS 0/1 55/5. On pre-treatment MRI tumour was T2/3x/3a/3b/3c/3d/4 in 2/2/16/24/12/1/3 and N0/1/2 in 7/40/13 pts. All pts commenced OxMdG with 57(95%) receiving all 4 cycles. 20 pts (33%) needed a dose reduction and 22 (37%) a dose delay. 58 pts commenced SCPRT (all received full dose) and 57 underwent surgery: anterior resection in 43 (75%), abdominoperineal resection in 11 (19%), Hartmanns in 3 (5%). Three pts withdrew prior to surgery: one lost to follow up after SCPRT, one pt choice and one due to cardiospasm during NAC. Median gap between OxMdG and starting SCPRT was 10 days (IQR: 5-15) and between completing SCPRT and surgery 10 days (IQR: 5-13). Postoperative histology was T0/1/2/3a/3b/3c/4a in 7/3/19/8/9/10/1 pts, N0/1/2 in 39/13/5 pts and ypT0ypN0 in 7/57 pts (12%). All 57 resected pts had a clear (R0) resection margin with no 30 day postoperative mortality. Conclusions: This is the first trial to report on giving NAC prior to SCPRT then surgery within a short time interval in ORC, which proved feasible with good compliance and promising efficacy. The UK NCRI intend to include a similar regimen in a future phase III trial. Clinical trial information: NCT01263171.

Background: Limited data describe patient-reported outcomes (PROs) of localised oesophageal cancer treated with definitive chemoradiotherapy(CRT). The phase 2/3 SCOPE-1 trial assessed the effectiveness of CRT±cetuximab. The trial for the first time provided an opportunity to describe PROs from a multi-centre group of patients treated with CRT that are presented here. Methods: Patients undergoing CRT±cetuximab within the SCOPE-1 trial (258 patients from 36 UK centres) completed generic-, disease- and treatment-specific health-related quality of life (HRQL) questionnaires (EORTC QLQ-C30, QLQ-OES18, Dermatology Life-Quality Index (DLQI)) at baseline and at 7, 13, 24, 52 and 104 weeks. Mean EORTC functional scale scores (>15 point change significant), DLQI scores (>4 point change significant) and proportions of patients (>15% significant) with ‘minimal’ or ‘severe’ symptoms are presented. Results: Questionnaire response rates were good. At baseline, EORTC functional scores were high (>75%) and few symptoms were reported except for severe problems with fatigue, insomnia and eating-related symptoms (e.g., appetite loss, dysphagia, dry mouth) in both groups(>15%). Functional aspects of health deteriorated and symptoms increased with treatment and by week 13 global quality of life, physical, role and social function significantly deteriorated and more problems with fatigue, dyspnoea, appetite loss and trouble with taste were reported. Recovery occurred by 6 months (except severe fatigue and insomnia in >15% of patients) and maintained at follow-up with no differences between groups. Conclusions: CRT for localised oesophageal cancer has a significant detrimental impact on many aspects of HRQL; however, recovery is achieved by 6 months and maintained with the exception of persisting problems with severe fatigue and insomnia. The data suggest that the HRQL recovery after definitive CRT is quicker, and there is little lasting deficit compared with treatment including surgery. These data need to be compared with HRQL data from studies evaluating treatments including surgery for oesophageal cancer.

Deviations from trial protocols are associated with adverse outcome and can be minimized by a robust Radiation therapy Quality Assurance (RTQA) Program. Our center is one of the four designated RTQA units in the UK making up the NCRI RTTQA Group. It has undertaken the RTQA on several Cancer Research UK funded GI trials including SCOPE 1 (grant number C20177/A7256), ARISTOTLE (C19942/A10016) and NeoSCOPE (C44694/A14614). Review of patient-specific outlining in SCOPE 1 was retrospective (R), not allowing deviations to be identified and corrected prior to trial entry. The move to prospective (P) review in ARISTOTLE and NeoSCOPE posed significant challenges as national waiting-time targets require patients to start curative treatment within 4 weeks of diagnosis. Here we report on how this was achieved in our RTQA center. All trials had a pre-trial benchmark outlining exercise before centers were approved for trial participation. Methods for patient-specific outline review in our RTQA center have developed over the 3 trials. The short timescales involved and the limit of expertise in a single center requires clinicians from other non-RTQA centers to participate in the process, requiring safe and reliable methods of data transfer. Outlines for all trials were submitted in DICOM-RT format to the RTQA center, along with diagnostic information, then made available for clinician review. Method of review varied according to the trial (see table). Outlining review within ARISTOTLE relied on a single investigator. For NeoSCOPE, using a compiled version of CERR (Computational Environment for Radiation therapy Research), we were able to involve more reviewers, using the same tools across multiple remote centers and different computing platforms, with the same quality as in the RTQA center. Our distributed RTQA review approach provides a method of prospective outlining review at multiple centers, without compromising quality, delaying start of treatment or need for significant additional resources.Scientific Abstract 3330; TableResultsTrialReviewTiming of P reviewCasesNo of reviewersNo of reviewer sitesMethod of reviewSCOPE 1 (esophagus)RNA10% of all (random)11 (RTQA center)VODCAARISTOTLE (rectum)PPrior to RT planning1st from center, 10% of all (random)11 (RTQA center)CERR and VODCANeoSCOPE (esophagus)PPrior to RT planning1st from each center1st 2010% of all (random)51 RTQA center, 3 remoteCompiled version of CERR Open table in a new tab

Background: Both oxaliplatin/capecitabine-based chemoradiation (OXCAP-RT) and carboplatin-paclitaxel based radiation (CarPac-RT) are active regimens in oesophageal cancer, but no randomized study has compared their efficacy/toxicity. This study compares the two regimens to identify the optimum regimen to take forward to a phase III trial against neo-adjuvant chemotherapy, the current standard in the UK. Methods: Eligibility: Resectable adenocarcinoma of oesophagus and Type 1-2 Gastro-Osophageal Junction; ≥T3 and/or ≥N1 staged with EUS and PET-CT; PS 0-1. Intervention: Both arms receive 2 cycles induction OXCAP (oxaliplatin 130mg/m2 D1, Cape 625mg/m2 D1-21, q 3wk) followed by randomization to OXCAP-RT (oxali 85mg/m2 Day 1,15,29; cape 625mg/m2 on days of RT; RT-45Gy/25 fractions/5weeks) or CarPac-RT (Carbo AUC2 and paclitaxel 50mg/m2 Day 1,8,15,22,29; RT-45Gy/25 fractions/5weeks). Restaging CT/PET-CT 4-6 weeks after CRT, and 2-phase oesophagectomy with 2-field lymphadenectomy 6-8 weeks after CRT. Primary End-Point: Pathological complete response. Secondary: 1) Feasibility of recruitment; Toxicity; 30-day surgical morbidity/mortality; resection margin positivity rate; median, 3- and 5-yr OS. Statistics: Randomised phase II with 1:1 randomisation; planned accrual 76 patients (38/arm) over 18 months. In each arm, this sample size gives 90% power and one-sided type 1 error of 10% to detect that pCR is not 35%. Interim safety analysis: Toxicity analysis after 10 patients have completed treatment. RT Quality Assurance: Pre-trial: Detailed RT protocol and guidance document, RT workshop, central evaluation of test-case contours and adequacy of RT plan. On-trial: Real-time central review of contours and plans of first 20 patients on trial, 1st case from each centre, and 10% of cases selected at random.