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IntroductionLiver resection is the only curative treatment for colorectal liver metastases (CLM). Resectability decision-making is therefore a key determinant of outcomes. Wide variation has been demonstrated in resectability decision-making, despite the existence of criteria. This paper summarises a study protocol to evaluate the potential added value of two novel assessment tools in assessing CLM technical resectability: the Hepatica preoperative MR scan (MR-based volumetry, Couinaud segmentation, liver tissue characteristics and operative planning tool) and the LiMAx test (hepatic functional capacity).Methods and analysisThis study uses a systematic multistep approach, whereby three preparatory workstreams aid the design of the final international case-based scenario survey:Workstream 1: systematic literature review of published resectability criteria.Workstream 2: international hepatopancreatobiliary (HPB) interviews.Workstream 3: international HPB questionnaire.Workstream 4: international HPB case-based scenario survey.The primary outcome measures are change in resectability decision-making and change in planned operative strategy, resulting from the novel test results. Secondary outcome measures are variability in CLM resectability decision-making and opinions on the role for novel tools.Ethics and disseminationThe study protocol has been approved by a National Health Service Research Ethics Committee and registered with the Health Research Authority. Dissemination will be via international and national conferences. Manuscripts will be published.Registration detailsThe CoNoR Study is registered with ClinicalTrials.gov (registration numberNCT04270851). The systematic review is registered on the PROSPERO database (registration number CRD42019136748).

Introduction Chemo-radiotherapy (CRT) is the first line treatment in patients with anal squamous cell carcinoma (ASCC). Clinical lymph node positivity (LN+) is considered an adverse prognosticator. Accurate lymph node staging impacts on treatment, such that in LN+ patients, lymphatic fields are treated with prophylactic phase I wide volume radiotherapy. Modern imaging modalities, namely magnetic resonance imaging (MRI) and PET-CT scanning increase sensitivity to detect LN+, but It is unclear whether enhanced pre-treatment staging impacts upon oncological outcome. Method From 1990 to 2014 we characterised the pattern of changes in the detection rates of LN+ in patients with ASCC through a dedicated anal cancer MDT serving a population of 3 million. We divided time periods as: (i) pre-MRI era; (ii) MRI era; and (iii) MRI + PET-CT era. In patients receiving curative CRT, we determined actuarial rates for loco-regional and inguinal relapses, and cancer-specific survival (CSS), using Kaplan-Meier curves. Imaging modalities were compared using log-rank tests, and Cox multivariate models that also conditioned for period and cohort effects. Results From 971 patients with new ASSC, 550 were treated with CRT [M, F: 207:343, median age (range): 61 (29–89)]. In the pre-MRI era (pre-2004), LN+ was identified in 18% (36/200); with the use of MRI the detection rate increased to 34% (62/185); and further increased to 48% (58/120) with the use of MRI and PET-CT in combination (post-2011) (p Conclusion MRI and PET scans improve pre-treatment staging in anal cancer although precise characterisation of the specific lymphatic fields involved needs further evaluation. Demonstration of the Will Roger’s effect challenges the prognostic value of pre-treatment nodal status in anal cancer and current treatment algorithms. This study was generously supported by the BDRF. Disclosure of interest None Declared.

Introduction The combination of peritoneal metastases (PMCR) and liver metastases in colorectal cancer (CRLM) has been considered a relative contra-indication to surgical treatment of either lesion. In the UK joint resection has not been widely undertaken and there is no published UK data. We present a cohort of eight synchronous liver resections with cytoreduction and heated intraperitoneal chemotherapy (CRS+HIPEC) at a single UK centre. Method All patients undergoing CRS+HIPEC with a hepatobiliary surgeon were identified from the prospectively kept PTS database. Patients who had only liver mobilisation were excluded. Outcome data was gathered from the electronic patient record and the PTS database. Post-hepatectomy liver failure was defined using International Study Group of Liver Surgery criteria. Results Seven patients underwent eight CRS+HIPEC procedures with synchronous liver resection for metastasis of colorectal origin over 5 years. Median PCI was 9 (range 3–17), with CC-0/1 resection in all patients. The median volume of resected liver was 90.6 cm 3 (2760 cm 3 – 15 cm 3 ). Median CCU stay was 2 (1–3) days and hospital stay 11 (8–20) days. Two patients experienced grade 3–4 complications: one grade-A post-hepatectomy liver failure and one sepsis. There was no 30 day mortality. Median CCU stay, inpatient stay, and grade 3–4 complication rate for patients undergoing CRS+HIPEC without liver resection for PMCR (n = 85) in our unit is 2 (0–16) days 12 (4–141) days and 21% respectively. Three patients are alive at a median follow-up of 59.2(39–61) months. All surviving patients had CC0 resections and PCI Conclusion In selected patients with metastatic colorectal cancer, synchronous liver resection with CRS+HIPEC is safe, with inpatient stay, CCU stay and complication rates comparable to CRS+HIPEC without liver resection in our unit. Our outcomes and survival figures are consistent with published data which suggests improved overall survival compared to modern systemic chemotherapy. Disclosure of interest None Declared.

Introduction Human Papilloma Viruses (HPV) infection may occur in 40% of rectal adenocarcinomas (RCa). HPV positivity (mainly HPV16) at other tumour sites is a predictor for treatment response to chemo-radiotherapy (CRT). Here, we performed a ‘proof of concept’ study in patients with RCa testing the hypothesis that HPV16 tumour positivity is a treatment predictive biomarker for complete response (CR) to CRT. Method The study was a case-control design in 118 patients undergoing CRT for RCa (CR, 30: non-CR, 88) from two UK cancer centres (2008 to 2013). DNA was extracted from pre-treatment paraffin-embedded blocks with histologically verified carcinoma. High-sensitivity multiplex PCR for HPVs was performed using two sets of primers for each HPV to identify genotypes: HPV6, 16, 18, 33. The probability of a CR was expressed as odd ratios (ORs) using logistic regression models. Results Any HPV positivity was noted in 25% of tumours. Individual genotype frequencies were: HPV16, 16%; HPV18, 6%; HPV33, 3%; HPV6, 3%. In multivariate models that included age, gender, pre-treatment T-size and N status, there was no association between either any HPV positivity (OR = 1.095, 95% CIs: 0.394, 3.044) or HPV16 positivity (OR = 1.072, 95% CIs: 0.332, 3.465), and complete response to CRT. Conclusion In this stage 2 biomarker discovery study using high-sensitivity HPV multi-valent assays, we found tumour HPV positivity rates lower than those reported elsewhere in the literature. We found no clear ‘signal’ to take forward HPV genotyping for validation as a predictive biomarker for chemo-radiotherapy response in patients with rectal cancer. This study was generously supported by the BDRF. Disclosure of interest None Declared. References Baricevic-Jones, et al . High-sensitivity HPV genotyping reveals near universal positivity in anal squamous cell carcinoma: different implications for vaccine prevention and prognosis. Eur J Cancer [in press]

Introduction The mainstay of treatment for anal squamous cell carcinoma (ASCC) is chemo-radiotherapy (CRT). Less than 5% of initial presentations are confined to the anal margin and amenable to local excision (LE) with or without post-operative (C)RT. However, treatment is poorly defined and outcome is understudied. Method PLATO is the next UK anal cancer trial; a three-part umbrella trial where the first stream (ACT 3) is a phase II study to assess the use of LE, for T1N0 anal margin tumours, combined with low-dose post-operative CRT (41.4Gy in 23 fractions) for close margins (≤ 1 mm), evaluated against a minimally tolerated loco-regional actuarial relapse rate of 10%. To inform this trial, we report the characteristics, treatment and outcomes of patients treated through a large anal cancer MDT (2004 to 2013), supplemented by a literature review. Results From 446 patients with new ASSC, there were 20 (4%) anal margin tumours treated by LE. Thirteen (65%) were T1; 7 (35%) were T2. All were N0 and M0. The lateral and deep margins were close (≤ 1 mm) in seven patients (35%). Five patients had additional therapy: 2 RT; 3 CRT. With a median follow-up of 38.6 months, there were no primary site recurrences; 3 patients developed nodal relapses (3-year loco-regional relapse = 11%). Three patients died attributed to their disease – the 3-year disease-free survival rate was 89%. The literature search identified six studies – there was a near total paucity of data on tumour characteristics, excision margin status, and the impact of these on subsequent treatment or outcome. Conclusion There is a need for a contemporaneous prospective study of this sub-population of patients with anal cancer, through centralisation of patients to anal cancer MDTs with pro-active identification and recruitment of these patients for the ACT3 trial. Disclosure of interest None Declared.

Introduction In patients with rectal cancer, management by ‘watch and wait’ (W&W), with potential avoidance of surgical resection (SR), has emerged as a management option following a clinical complete response (cCR) after pre-operative chemoradiotherapy (CRT). However, precise quantification of oncological outcomes after this treatment pathway is unclear. Method Between 2010 and 2013, we followed a consecutive series of 259 patients with non-metastatic rectal cancer who completed pre-operative CRT (majority: 45 Gy in 25 daily fractions with concurrent fluoropyrimidine-based chemotherapy). Post-CRT, 31 patients (12%) were considered at a multi-disciplinary meeting to have cCR and offered W&W on a protocolised pathway. We supplemented these cases with a registry of 89 patients managed across four cancer treatment centres in the North West of England and North Wales (total cCRs: 120). Primary endpoint was actuarial rate of intraluminal re-growth. Secondary endpoints were non-intraluminal disease-free survival (niDFS) and colostomy-free survival (CFS). Comparisons with standard care (SR) were performed using propensity score matched-treatment analysis and using time-dependent survival analyses to account for differences in times to W&W decision and salvage SR. Results With a mean follow-up from WW and 3 underwent Papillon local radiotherapy. After propensity score matching, there were no deleterious effect on niDFS for patients treated by WW 0.269 to 1.174). However, there was a significant improvement in 3-year CFS rates for patients treated by W&W versus SR: 83% and 54% (log rank, p Conclusion Approximately two-thirds of patients with rectal cancer managed by W&W after cCR avoided surgical resection with improvement in colostomy-free survival, without loss of oncological safety. The outcomes from this multi-centred clinical cohort will assist the rectal cancer patient and oncologist with decision making at the outset of long-course CRT. This study was generously supported by the BDRF. Disclosure of interest None Declared.

Objective: To review the evidence from clinical trials of follow up of patients after curative resection for colorectal cancer. Design: Systematic review and meta-analysis of randomised controlled trials of intensive compared with control follow up. Main outcome measures: All cause mortality at five years (primary outcome). Rates of recurrence of intraluminal, local, and metastatic disease and metachronous (second colorectal primary) cancers (secondary outcomes). Results: Five trials, which included 1342 patients, met the inclusion criteria. Intensive follow up was associated with a reduction in all cause mortality (combined risk ratio 0.81, 95% confidence interval 0.70 to 0.94, P=0.007). The effect was most pronounced in the four extramural detection trials that used computed tomography and frequent measurements of serum carcinoembryonic antigen (risk ratio 0.73, 0.60 to 0.89, P=0.002). Intensive follow up was associated with significantly earlier detection of all recurrences (difference in means 8.5 months, 7.6 to 9.4 months, P Conclusions: Intensive follow up after curative resection for colorectal cancer improves survival. Large trials are required to identify which components of intensive follow up are most beneficial. What is already known on this topic There is a lack of direct evidence that intensive follow up after initial curative treatment for colorectal cancer leads to increased survival Guidelines are inconclusive and clinical practice varies widely What this study adds The cumulative analysis of available data supports the view that intensive follow up after curative resection for colorectal cancer improves survival If computed tomography and frequent measurements of serum carcinoembryonic antigen are used during follow up mortality related to cancer is reduced by 9-13% This survival benefit is partly attributable to the earlier detection of all recurrences, particularly the increased detection of isolated recurrent disease

Evidence indicates a modest increase in risk of bowel cancer among people with type 2 diabetes For two decades, investigators have recognised the overlapping risk factors for type 2 diabetes mellitus and colorectal cancer—obesity, Western diet, and sedentary lifestyle—and speculated about a link between these two common diseases. Accumulating evidence shows that type 2 diabetes mellitus is associated with a 40-60% increased risk of cancer of the large bowel,1 2 and specifically, proximal colonic malignancy.3 These associations are independent of body mass index and are more consistently reported than those with breast and endometrial cancers. Recent data from the European Prospective Investigation into Cancer (EPIC-Norfolk) study show that this increased risk is largely explained by changes in glycated haemoglobin (HbA1c) concentrations.4 This implies that glycaemic control is likely to be important in determining which patients develop colorectal cancer. In contrast to type 2 diabetes mellitus, no associations have been found between colorectal cancer risk and type 1 diabetes mellitus, nor gestational diabetes.5 Recently published data from the large US Cancer …

We welcome the joint work of the British Society of Gastroenterology and the Association of Coloproctology of Great Britain and Ireland in commissioning guidelines for colorectal cancer screening in high risk groups ( Gut 2002; 51 (suppl 5):V13–14). In the absence of direct evidence from randomised trials for most of the groups, the various authors have balanced a wealth of recent genetic and epidemiological evidence estimating an individual’s levels of elevated risk against the risks associated with screening. The end result is the recognition that within the label “high risk” there is a spectrum of risks such that colonoscopic screening and surveillance must be tailored accordingly. This avoids the ineffective, costly, and potentially harmful “blanket-type” approach, which formerly prevailed. However, within the guideline series, there is one exception—screening and surveillance in patients with acromegaly. We and other researchers1–3 have repeatedly stated that the studies undertaken by the authors of these guidelines have overestimated the risk of colorectal cancer in this patient group. They report a 13–14-fold increase in risk based on colorectal cancer detection rates among acromegalics undergoing colonoscopy at Barts compared with …