TPS416 Background: Despite recent improvements in oncological and surgical treatment for patients with oesophageal and gastric cancer, 60% of patients with locally advanced disease who are treated with a curative intent will develop tumour recurrence and die within three years of completing treatment. In the absence of robust scientific evidence national or international guidelines have failed to reach consensus on the optimal surveillance strategy after primary treatment of oesophageal or gastric cancer. Methods: The primary research question of the proposed randomised controlled trial (RCT) is does the routine use of a structured follow-up program with regular radiological and endoscopic investigations improve survival in patients who have had surgical treatment for oesophageal or gastric cancer with curative intent? We aim to assess whether structured follow-up, including radiological and endoscopic investigations after completing curatively intended treatment, improves survival in patients with oesophageal or gastric cancer. The secondary aims of this RCT are to determine the impact of a structured post-treatment surveillance upon the detection and treatment of cancer recurrence and health-related quality of life, including anxiety and to assess the cost-effectiveness. We will undertake a national prospective, multi-centre, randomised controlled trial of structured follow-up including radiological and endoscopic investigations versus standard clinical follow-up. The setting will be at least 24 large oesophago-gastric cancer UK cancer centres. We will aim to recruit 952 oesophageal and gastric cancer patients receiving surgical resection for curatively intended treatment of oesophageal or gastric cancer +/- neoadjuvant/adjuvant chemo(radio or immuno)therapy. At 4-12 weeks after surgery for oesophageal or gastric cancer, patients will be assessed for eligibility for inclusion in the trial. Patients will be randomised 1:1 to receive either intensive follow-up for up to 3-years, with clinical and computerised tomography (CT) investigation every 6 months, and an endoscopy at 12 months or to current standard NHS follow-up, i.e. clinical review at 6 and 12 months followed by targeted investigation as required based upon the onset of new symptoms. The primary outcome is 3-year all-cause mortality and secondary outcomes include health-related quality of life (including anxiety), 3-year disease-specific mortality, pattern and treatment of tumour recurrence, and cost-effectiveness of follow-up in both study arms. The findings of this RCT will inform national and international guidelines for patients with oesophageal and gastric cancer, as this will be the first RCT to provide robust evidence concerning the value of surveillance in this population. Clinical trial information: 14417629.

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.

ESPAC-4 : A Multicenter, International, Randomized Controlled Phase III Trial of Adjuvant Combination Chemotherapy of Gemcitabine (GEM) and Capecitabine (CAP), Versus Monotherapy Gemcitabine in Patients With Resected Pancreatic Ductal Adenocarcinoma

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.

103 Background: Malnutrition is common in oesophageal cancer and may be related to the disease or treatment. We aimed to identify nutritional prognostic factors and the outcome of nutritional intervention in patients recruited to the SCOPE1 trial. Methods: 258 patients were randomly allocated to dCRT with or without the addition of cetuximab. Data was collected prior to induction chemotherapy (iCT) and before commencing concurrent CRT. Nutritional Risk Index (NRI) was calculated and categorised; ≥ 100 (no risk of malnutrition), 97.5-100 (mild risk), and < 97.5 (moderate to severe risk). The maximal nutritional intervention (MNI) received was classified as: none, dietary advice, oral supplementation or major intervention (enteral feeding/tube placement). Univariate and multivariate analyses using Cox proportional hazard modelling were conducted to identify predictive factors and important interactions involving MNI. Results: An NRI score < 100 at baseline strongly predicted reduced median overall survival (OS) in multivariate analysis (HR = 12.45, 95% CI 5.24 – 29.57; p = < 0.001). Furthermore, OS was improved in this group if they received dietary advice (HR = 0.12, p = 0.004), oral supplementation (HR = 0.13, p = < 0.001) or major intervention (HR = 0.13, p = 0.003) prior to commencement of iCT, but there was no benefit if intervention occurred after commencement of iCT. Patients on cetuximab arm undergoing major intervention had worse outcomes compared to control (13 months vs 28 months, p = 0.003). Conclusions: Assessment and correction of poor nutritional state at baseline may improve survival outcomes in oesophageal cancer patients treated with dCRT. The benefit of intervention is no longer observed once treatment has commenced, highlighting the need for early nutritional assessment and intervention. Reason for poor OS in patients on cetuximab requiring major intervention is unclear. Clinical trial information: 47718479.

91 Background: The REAL3 trial evaluated the addition of panitumumab (P) to epirubicin, oxaliplatin and capecitabine (EOC) in advanced OGA. We previously reported that addition of panitumumab was not associated with improvement in survival endpoints. In this analysis we aimed to explore factors associated with OS in the REAL3 population. Methods: Analysis performed in ITT population (n=553). OS was evaluated in relation to the baseline characteristics displayed in the table below. Cox regression was used to obtain HRs and 95% CIs. Factors with p<0.2 were included in a forward stepwise model and factors with p<0.1 were regarded as significant in the final model. OS was also assessed using the RMH Prognostic Index score which comprises 4 adverse variables: PS 2; liver mets; peritoneal mets; ALP >100 U/L. Results: Results of the univariate analysis are shown in the table below. In multi-variate analysis, the factors which remained statistically significant for OS were: PS (p=0.080): 1 vs 0 HR 1.24 (95% CI 0.99-1.57); 2 vs 0 HR 1.57 (95%CI 0.97-2.54) Disease extent (p=0.054): Met disease vs LA HR 1.42 (95% CI 0.99-2.02) Baseline global health score (p=0.005): Low vs high HR 1.52 (95% CI 1.16-2.00); middle vs high HR 1.45 (95% CI 1.11-1.89) Patients with an RMH Prognostic Index score of 0 (good prognosis) had median OS of 13.1 mo. This compared to 9.5 mo in patients with 1-2 adverse features (intermediate prognosis) (HR 1.37, 95% CI 1.12-1.68; p=0.002) and 4.7 mo in patients with 3-4 adverse features (poor prognosis) (HR 4.02, 95% CI 1.96-8.22; p<0.001). Conclusions: Baseline global quality of life may represent a useful adjunct to clinical parameters to guide prognostication in advanced OGA. These findings also validate the RMH Prognostic Index score in the REAL3 population. Clinical trial information: 2007-005976-15.[Table: see text]

4067 Background: REAL3 evaluated EOC + P in advanced oesophago-gastric adenocarcinoma. We previously reported that addition of P was associated with increased diarrhoea, skin rash and mucositis without improvement in survival endpoints. This analysis reports QoL outcomes for participants in both arms of the trial. Methods: QoL was assessed via EORTC QLQ-C30 questionnaires requested at baseline (BA), post-cycles 4 (C4) and 8 (C8), and at 3 months follow-up (3M). Functional and symptomatic scores were calculated using recommended EORTC methods. Comparison of differences between study arms was performed using one sample t-test with 2-sided p-values and repeated measures analysis investigated scores over time. A threshold of 0.05 indicated statistical significance. Data in both arms was censored at time of early trial closure (Oct 2011) when all patients crossed to EOC. Results: 553 patients were recruited between June 2008 and October 2011. Excluding duplicates and those censored, the questionnaire response rate at each timepoint was: BA 470/553 (85%); C4 163/418 (39%); C8 72/196 (37%); 3M 35/64 (55%) with similar response rate in both arms. Irrespective of treatment allocation there was a non-significant decrease in global health score during chemotherapy which recovered by 3M. A similar trend was observed for physical, role and social function scales with no difference between arms. Cognitive function scores showed more marked deterioration in patients receiving EOC+P with mean decrease of 15 points between BA and 3M, compared to no change in patients receiving EOC (p=0.026). Chemotherapy was associated with a trend towards improved nausea and vomiting, appetite, and pain scores in both arms. Conversely it worsened scores related to fatigue, dyspnoea and diarrhoea. Diarrhoea was increased by addition of P (p=0.007) with no other significant differences in symptom scores between arms. Conclusions: Chemotherapy did not have a detrimental effect on global QoL and seemed to improve some disease-related symptoms. Increased scores related to diarrhoea with addition of P are in keeping with the known toxicity profile. Clinical trial information: 2007-005976-15.

LBA4000 Background: EGFR overexpression occurs in 27-50% of esophagogastric adenocarcinomas (OGA), and correlates with poor prognosis. The REAL3 trial evaluated the addition of the anti-EGFR antibody panitumumab (P) to epirubicin, oxaliplatin and capecitabine (EOC) in advanced OGA. Methods: Patients with untreated, metastatic or locally advanced OGA were randomised to EOC (E 50mg/m2, O 130mg/m2, C 1250mg/m2/day) or mEOC+P (E 50mg/m2, O 100mg/m2, C 1000mg/m2/day, P 9mg/kg). Primary endpoint was overall survival (OS); secondary endpoints were progression-free survival (PFS), response rate (RR), toxicity, and biomarker evaluation. Response was evaluated by RECIST after 4 and 8 cycles. Following IDMC review in October 2011 trial recruitment was halted and panitumumab withdrawn. Data for patients on treatment were censored at this timepoint. Results: 553 patients were recruited (EOC 275, mEOC+P 278), with median follow-up 5.0 and 5.2 months respectively. Median OS was 11.3 months with EOC compared to 8.8 months with mEOC+P (HR 1.37: 95% CI 1.07-1.76, p=0.013). Median PFS was 7.4 and 6.0 months respectively (HR 1.22: 95% CI 0.98-1.52, p=0.068), with RR being 42% compared to 46% (odds ratio 1.16: 95% CI 0.81-1.57, p=0.467). mEOC+P was associated with ↑ G3/4 diarrhoea (17% vs 11%), skin rash (14% vs 1%) and thrombotic events (12% vs 7%), but ↓ haem toxicity (>G3 neutropenia 14% vs 31%). In the mEOC+P arm, OS was significantly improved in patients with G1-3 rash (77%, n=209) on treatment compared to those without (23%, n=63); median OS 10.2 vs 4.3 months (p<0.001), with similar significant improvements seen in RR and PFS. Biomarker analysis in the first 200 patients has not identified other predictive markers associated with P therapy. Multivariate analysis for OS in these patients demonstrated a negatively prognostic role for KRAS mutation (HR 2.1: 95% CI 1.10-4.05, p=0.025) and PIK3CA mutation (HR 3.2: 95% CI 1.01-10.40, p=0.048). Conclusions: Addition of P to EOC chemotherapy was associated with worsening of OS in an unselected advanced OGA population. This may be in part due to lowered doses of O and C in the mEOC+P regimen. Outcomes in patients treated with P varied by grade of skin toxicity.