AbstractBackgroundAdherence to adjuvant endocrine therapy is affected by medication side-effects and associated distress. Previous interventions focused on educating women to enhance adherence have proved minimally effective. We co-designed an Acceptance and Commitment Therapy (ACT) intervention to enhance medication decision-making and quality of life by targeting a broader range of factors, including side-effect management and psychological flexibility. This study aims to establish key trial parameters, assess the acceptability of the intervention and the extent to which it can be delivered with fidelity, and to demonstrate “proof of principle” regarding its efficacy on primary and process outcomes.MethodsThe ACTION intervention includes an individual 1:1 ACT session followed by three group sessions involving 8–10 women and two practitioner psychologists. Participants are also provided with access to a website containing evidence-based methods for self-managing side-effects. The ACT sessions were adapted during the COVID-19 pandemic to be remotely delivered via video conferencing software. To evaluate the feasibility and acceptability of this intervention, a multi-site, exploratory, two-arm, individually randomised external pilot trial with a nested qualitative study will be undertaken. Eighty women with early stage breast cancer prescribed adjuvant endocrine therapy will be randomised (1:1) to receive treatment as usual or treatment as usual plus the ACTION intervention. The planned future primary outcome is medication adherence assessed by the ASK-12 measure. Progression to a phase III RCT will be based on criteria related to recruitment and follow-up rates, acceptability to patients, competency and fidelity of delivery, and proof of principle for change in medication adherence.DiscussionThis external pilot trial will be used to ascertain the feasibility of undertaking a future phase III RCT to definitively evaluate an ACT-based intervention to support medication taking behaviour and quality of life in women with early stage breast cancer on adjuvant endocrine therapy.Trial registrationISRCTN: 12027752. Registered 24 December 2020,https://doi.org/10.1186/ISRCTN12027752

BACKGROUND:Preliminary studies using the FENIX™ (Torax Medical, Minneapolis, MN, USA) magnetic sphincter augmentation device suggest that it is safe to use for the treatment of adult faecal incontinence, but efficacy data are limited.OBJECTIVE:To compare FENIX with sacral nerve stimulation for the treatment of adult faecal incontinence in terms of safety, efficacy, quality of life and cost-effectiveness.DESIGN, SETTING AND PARTICIPANTS:Multicentre, parallel-group, unblinded, randomised trial comparing FENIX with sacral nerve stimulation in participants suffering moderate to severe faecal incontinence.INTERVENTIONS:Participants were randomised on an equal basis to either sacral nerve stimulation or FENIX. Follow-up occurred 2 weeks postoperatively and at 6, 12 and 18 months post randomisation.MAIN OUTCOME AND MEASURE:The primary outcome was success, defined as device in use and ≥ 50% improvement in Cleveland Clinic Incontinence Score at 18 months post randomisation. Secondary outcomes included complication rates, quality of life and cost-effectiveness. Between 30 October 2014 and 23 March 2017, 99 participants were randomised across 18 NHS sites (50 participants to FENIX vs. 49 participants to sacral nerve stimulation). The median time from randomisation to FENIX implantation was 57.0 days (range 4.0-416.0 days), and the median time from randomisation to permanent sacral nerve stimulation was 371.0 days (range 86.0-918.0 days). A total of 45 out of 50 participants underwent FENIX implantation and 29 out of 49 participants continued to permanent sacral nerve stimulation. The following results are reported, excluding participants for whom the corresponding outcome was not evaluable. Overall, there was success for 10 out of 80 (12.5%) participants, with no statistically significant difference between the two groups [FENIX 6/41 (14.6%) participants vs. sacral nerve stimulation 4/39 (10.3%) participants]. At least one postoperative complication was experienced by 33 out of 45 (73.3%) participants in the FENIX group and 9 out of 40 (22.5%) participants in the sacral nerve stimulation group. A total of 15 out of 50 (30%) participants in the FENIX group ultimately had to have their device explanted. Slightly higher costs and quality-adjusted life-years (incremental = £305.50 and 0.005, respectively) were observed in the FENIX group than in the sacral nerve stimulation group. This was reversed over the lifetime horizon (incremental = -£1306 and -0.23 for costs and quality-adjusted life-years, respectively), when sacral nerve stimulation was the optimal option (net monetary benefit = -£3283), with only a 45% chance of FENIX being cost-effective.LIMITATIONS:The SaFaRI study was terminated in 2017, having recruited 99 participants of the target sample size of 350 participants. The study is, therefore, substantially underpowered to detect differences between the treatment groups, with significant uncertainty in the cost-effectiveness analysis.CONCLUSIONS:The SaFaRI study revealed inefficiencies in the treatment pathways for faecal incontinence, particularly for sacral nerve stimulation. The success of both FENIX and sacral nerve stimulation was much lower than previously reported, with high postoperative morbidity in the FENIX group.FUTURE WORK:Further research is needed to clarify the treatment pathways for sacral nerve stimulation and to determine its true clinical and cost-effectiveness.TRIAL REGISTRATION:Current Controlled Trials ISRCTN16077538.FUNDING:This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 18. See the NIHR Journals Library website for further project information.

BACKGROUND:Eligibility criteria are a fundamental element of clinical trial design, defining who can and who should not participate in a trial. Problems with the design or application of criteria are known to occur and pose risks to participants' safety and trial integrity, sometimes also negatively impacting on trial recruitment and generalisability. We conducted a short, exploratory survey to gather evidence on UK recruiters' experiences interpreting and applying eligibility criteria and their views on how criteria are communicated and developed. METHODS:Our survey included topics informed by a wider programme of work at the Clinical Trials Research Unit, University of Leeds, on assuring eligibility criteria quality. Respondents were asked to answer based on all their trial experience, not only on experiences with our trials. The survey was disseminated to recruiters collaborating on trials run at our trials unit, and via other mailing lists and social media. The quantitative responses were descriptively analysed, with inductive analysis of free-text responses to identify themes. RESULTS:A total of 823 eligible respondents participated. In total, 79% of respondents reported finding problems with eligibility criteria in some trials, and 9% in most trials. The main themes in the types of problems experienced were criteria clarity (67% of comments), feasibility (34%), and suitability (14%). In total, 27% of those reporting some level of problem said these problems had led to patients being incorrectly included in trials; 40% said they had led to incorrect exclusions. Most respondents (56%) reported accessing eligibility criteria mainly in the trial protocol. Most respondents (74%) supported the idea of recruiter review of eligibility criteria earlier in the protocol development process. CONCLUSIONS:Our survey corroborates other evidence about the existence of suboptimal trial eligibility criteria. Problems with clarity were the most often reported, but the number of comments on feasibility and suitability suggest some recruiters feel eligibility criteria and associated assessments can hinder recruitment to trials. Our proposal for more recruiter involvement in protocol development has strong support and some potential benefits, but questions remain about how best to implement this. We invite other trialists to consider our other suggestions for how to assure quality in trial eligibility criteria.

Background: Protein biomarkers with associations with the activity and outcomes of diseases are being identified by modern proteomic technologies. They may be simple, accessible, cheap and safe tests that can inform diagnosis, prognosis, treatment selection, monitoring of disease activity and therapy and may substitute for complex, invasive and expensive tests. However, their potential is not yet being realised. Design and methods: The study consisted of three workstreams to create a framework for research: workstream 1, methodology – to define current practice and explore methodology innovations for biomarkers for monitoring disease; workstream 2, clinical translation – to create a framework of research practice, high-quality samples and related clinical data to evaluate the validity and clinical utility of protein biomarkers; and workstream 3, the ELF to Uncover Cirrhosis as an Indication for Diagnosis and Action for Treatable Event (ELUCIDATE) randomised controlled trial (RCT) – an exemplar RCT of an established test, the ADVIA Centaur® Enhanced Liver Fibrosis (ELF) test (Siemens Healthcare Diagnostics Ltd, Camberley, UK) [consisting of a panel of three markers – (1) serum hyaluronic acid, (2) amino-terminal propeptide of type III procollagen and (3) tissue inhibitor of metalloproteinase 1], for liver cirrhosis to determine its impact on diagnostic timing and the management of cirrhosis and the process of care and improving outcomes. Results: The methodology workstream evaluated the quality of recommendations for using prostate-specific antigen to monitor patients, systematically reviewed RCTs of monitoring strategies and reviewed the monitoring biomarker literature and how monitoring can have an impact on outcomes. Simulation studies were conducted to evaluate monitoring and improve the merits of health care. The monitoring biomarker literature is modest and robust conclusions are infrequent. We recommend improvements in research practice. Patients strongly endorsed the need for robust and conclusive research in this area. The clinical translation workstream focused on analytical and clinical validity. Cohorts were established for renal cell carcinoma (RCC) and renal transplantation (RT), with samples and patient data from multiple centres, as a rapid-access resource to evaluate the validity of biomarkers. Candidate biomarkers for RCC and RT were identified from the literature and their quality was evaluated and selected biomarkers were prioritised. The duration of follow-up was a limitation but biomarkers were identified that may be taken forward for clinical utility. In the third workstream, the ELUCIDATE trial registered 1303 patients and randomised 878 patients out of a target of 1000. The trial started late and recruited slowly initially but ultimately recruited with good statistical power to answer the key questions. ELF monitoring altered the patient process of care and may show benefits from the early introduction of interventions with further follow-up. The ELUCIDATE trial was an ‘exemplar’ trial that has demonstrated the challenges of evaluating biomarker strategies in ‘end-to-end’ RCTs and will inform future study designs. Conclusions: The limitations in the programme were principally that, during the collection and curation of the cohorts of patients with RCC and RT, the pace of discovery of new biomarkers in commercial and non-commercial research was slower than anticipated and so conclusive evaluations using the cohorts are few; however, access to the cohorts will be sustained for future new biomarkers. The ELUCIDATE trial was slow to start and recruit to, with a late surge of recruitment, and so final conclusions about the impact of the ELF test on long-term outcomes await further follow-up. The findings from the three workstreams were used to synthesise a strategy and framework for future biomarker evaluations incorporating innovations in study design, health economics and health informatics. Trial registration: Current Controlled Trials ISRCTN74815110, UKCRN ID 9954 and UKCRN ID 11930. Funding: This project was funded by the NIHR Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 6, No. 3. See the NIHR Journals Library website for further project information.

BACKGROUND:Although surgical resection has been considered the only curative option for colorectal liver metastases (CLM), thermal ablation has recently been suggested as an alternative curative treatment. A prospective randomised trial is required to define the efficacy of resection vs ablation for the treatment of colorectal liver metastases. METHODS:Design and setting: This is a multicentre, open, randomised controlled non-inferiority trial design with internal pilot and will be performed in tertiary liver centres in UK and The Netherlands. PARTICIPANTS:Eligible patients will be those with colorectal liver metastases at high surgical risk because of their age, co-morbidities or tumour burden and who would be suitable for liver resection or thermal ablation. INTERVENTION:Thermal ablation as per local policy. CONTROL:Surgical liver resection performed as per centre protocol. Co-interventions: Further chemotherapy will be offered to patients as per current practice. Outcomes Pilot study: Same as main study and in addition patients and clinicians' acceptability of the trial to assist in optimisation of recruitment. PRIMARY OUTCOME:Disease-free survival (DFS) at two years post randomisation. SECONDARY OUTCOMES:Overall survival, timing and site of recurrence, additional therapy after treatment failure, quality of life, complications, length of hospital stay, costs, trial acceptability, DFS measured from end of intervention. FOLLOW-UP:24 months from randomisation; five-year follow-up for overall survival. SAMPLE SIZE:330 patients to demonstrate non-inferiority of thermal ablation. DISCUSSION:This trial will determine the effectiveness and cost-effectiveness of thermal ablation vs surgical resection for high-risk people with colorectal liver metastases, and guide the optimal treatment for these patients. TRIAL REGISTRATION:ISRCTN Registry, ISRCTN52040363 . Registered on 9 March 2016.

The costs of medical research are a concern. Clinical Trials Units (CTUs) need to better understand variations in the costs of their activities.

Faecal incontinence is a physically, psychologically and socially disabling condition. NICE guidance (2007) recommends surgical intervention, including sacral nerve stimulation (SNS), after failed conservative therapies. The FENIX™ magnetic sphincter augmentation (MSA) device is a novel continence device consisting of a flexible band of interlinked titanium beads with magnetic cores that is placed around the anal canal to augment anal sphincter tone through passive attraction of the beads. Preliminary studies suggest the FENIX™ MSA is safe, but efficacy data is limited. Rigorous evaluation is required prior to widespread adoption.

Background: The main toxicity of irinotecan in advanced colorectal cancer (CRC) is delayed diarrhoea. Intestinal SN-38, released by deconjugation of the parent glucuronide excreted into the bile or produced in situ by intestinal carboxylesterase, is toxic to the intestinal epithelium. The canalicular transport of irinotecan and SN-38G is mediated by ABCC2 (MRP2) and ABCB1 (MDR1) which are both inhibited by ciclosporin. We tested whether irinotecan and ciclosporin was non-inferior for anti-cancer efficacy and superior for toxicity compared with single-agent irinotecan.Methods: Six hundred and seventy-two patients with advanced, measurable CRC following prior fluoropyrimidine-containing chemotherapy were randomised to either irinotecan 3-weekly 350 mg/m(2) (or 300 mg/m(2) if age >70 or performance status (PS) = 2) or 3-weekly irinotecan at 140 mg/m(2) (120 mg/m(2) if age >70 or PS = 2) with ciclosporin 3 mg/kg t.d.s. for three days by mouth starting on the morning before irinotecan. The primary end-point was the proportion of patients alive and progression-free at 12 weeks. The key secondary end-point was the incidence of grade >= 3 diarrhoea within 12 weeks of randomisation.Results: The proportion of patients progression-free at 12 weeks with irinotecan was 53.4% compared to 47.2% with irinotecan plus ciclosporin (difference = -6.3%, 95% confidence interval (CI) [-13.8%, 1.3%]). Since the lower limit of the 95% CI crossed the pre-specified non-inferiority margin of -10.6%, non-inferiority of irinotecan plus ciclosporin compared to irinotecan alone was not statistically demonstrated. 15.0% patients developed severe diarrhoea on irinotecan compared to 13.8% on irinotecan plus ciclosporin, a non-significant difference.Interpretation: The pharmacokinetic biomodulation of irinotecan using oral ciclosporin does not improve the therapeutic index of irinotecan in advanced CRC.Funding: The trial was funded by Cancer Research UK and supported by Amgen Pharma. (C) 2013 Elsevier Ltd. All rights reserved.

Background Therapeutic antibodies targeting EGFR have activity in advanced colorectal cancer, but results from clinical trials are inconsistent and the population in which most benefit is derived is uncertain. Our aim was to assess the addition of panitumumab to irinotecan in pretreated advanced colorectal cancer.Methods In this open-label, randomised trial, we enrolled patients who had advanced colorectal cancer progressing after fluoropyrimidine treatment with or without oxaliplatin from 60 centres in the UK. From December, 2006 until June, 2008, molecularly unselected patients were recruited to a three-arm design including irinotecan (control), irinotecan plus ciclosporin, and irinotecan plus panitumumab (IrPan) groups. From June 10, 2008, in response to new data, the trial was amended to a prospectively stratified design, restricting panitumumab randomisation to patients with KRAS wild-type tumours; the results of the comparison between the irinotcan and IrPan groups are reported here. We used a computer-generated randomisation sequence (stratified by previous EGFR targeted therapy and then minimised by centre, WHO performance status, previous oxaliplatin, previous bevacizumab, previous dose modifications, and best previous response) to randomly allocate patients to either irinotecan or IrPan. Patients in both groups received 350 mg/m(2) intravenous irinotecan every 3 weeks (300 mg/m(2) if aged >= 70 years or a performance status of 2); patients in the IrPan group also received intravenous panitumumab 9 mg/kg every 3 weeks. The primary endpoint was overall survival in KRAS wild-type patients who had not received previous EGFR targeted therapy, analysed by intention to treat. Tumour DNA was pyrosequenced for KRAS(c.146), BRAF, NRAS, and PIK3CA mutations, and predefined molecular subgroups were analysed for interaction with the effect of panitumumab. This study is registered, number ISRCTN93248876.Results Between Dec 4, 2006, and Aug 31, 2010, 1198 patients were enrolled, of whom 460 were included in the primary population of patients with KRAS(c.12-13,61) wild-type tumours and no previous EGFR targeted therapy. 230 patients were randomly allocated to irinotecan and 230 to IrPan. There was no difference in overall survival between groups (HR 1.01, 95% CI 0.83-1.23; p=0.91), but individuals in the IrPan group had longer progression-free survival (0.78, 0.64-0.95; p=0.015) and a greater number of responses (79 [34%] patients vs 27 [12%]; p<0.0001) than did individuals in the irinotecan group. Grade 3 or worse diarrhoea (64 [29%] of 219 patients vs 39 [18%] of 218 patients), skin toxicity (41 [19%] vs none), lethargy (45 [21]% vs 24 [11%]), infection (42 [19%] vs 22 [10%]) and haematological toxicity (48 [22%] vs 27 [12%]) were reported more commonly in the IrPan group than in the irinotecan group. We recorded five treatment-related deaths, two in the IrPan group and three in the irinotecan group.Interpretation Adding panitumumab to irinotecan did not improve the overall survival of patients with wild-type KRAS tumours. Further refinement of molecular selection is needed for substantial benefits to be derived from EGFR targeting agents.

3523 Background: Phase III trials show inconsistent effects when anti-EGFR drugs are added to cytotoxic therapy in aCRC. Benefits, when present, are confined to patients (pts) determined retrospectively to have KRAS wild-type (wt) tumours. PICCOLO is a multicentre randomized controlled trial, amended in June 2008 to include prospective KRAS testing, to evaluate the addition of panitumumab (Pan) to single-agent irinotecan (Ir) as second- or subsequent-line therapy for KRAS-wt aCRC. METHODS Eligible pts had: measurable aCRC progressing during/after ≥1 prior regimen with fluoropyrimidines ± other drugs; no prior Ir; WHO PS 0-2. Until June '08, pts were allocated 1:1:1 to Ir, IrPan or Ir/ciclosporin, with retrospective KRAS analysis. Thereafter, KRAS was tested prospectively (by pyrosequencing of c.12-13 and 61) and pts with KRAS-wt were allocated 1:1 to Ir (Ir 350 mg/m2 [300 mg/m2 if ≥70 yrs or PS2], q3w) or IrPan (same Ir plus Pan 9 mg/kg, q3w). Primary analysis is ITT overall survival (OS) in KRAS-wt pts not pretreated with anti-EGFR therapy (80% power, HR 0.70, α=0.05, 2-sided). Secondary endpoints include % progression-free at 12 wks, PFS, RR, toxicity and QL. Planned molecular subgroups include BRAF, NRAS, KRAS c.146 and PIK3CA. RESULTS 460 KRAS-wt pts were recruited to the primary analysis (324 after June '08, KRAS-tested prospectively); median age 63 yrs; 94% PS0-1; 95% had received prior oxaliplatin. With 312 events and median follow-up of survivors 10.2 mo, OS was not improved: median IrPan = 10.4 mo, Ir = 10.5 mo, HR 0.91 (95%CI [0.73, 1.14], p=0.44), but trended towards improved survival after 12 mo. Planned subgroup analysis shows worse survival, and disbenefit with Pan in BRAF-mut pts (n=63, HR=1.87, [95%CI 1.07, 3.27]); conversely, KRAS/BRAF-wt pts show a stronger but still non-significant trend towards benefit (n=348, HR=0.86 [0.66, 1.11]). CONCLUSIONS PICCOLO did not meet its primary endpoint of improved OS with panitumumab in KRAS-wt aCRC, but a trend was seen towards survival benefit after 12 months, especially in KRAS/BRAF-wt pts. Conversely, pts with BRAF-mut tumours had significant disbenefit with Pan. Full results, including PFS and planned molecular subgroups, will be presented.

3566 Background: Phase I/II data showed that ciclosporin (Cs) profoundly reduces the hepatobiliary clearance of irinotecan (Ir), and suggested that 40% standard dose Ir with concurrent Cs (IrCs) may give equal efficacy to standard Ir, with less diarrhoea. PICCOLO is a multicentre randomized controlled trial in which patients (pts) with aCRC, progressing after prior therapy, were randomised to Ir or IrCs. It was designed to detect non-inferior efficacy with reduced toxicity. Methods: Eligible pts had: measurable aCRC, progressive during/after ≥1 prior regimen with fluoropyrimidines ± other drugs; no prior Ir; WHO PS 0-2. Before summer 2008, pts were allocated 1:1:1 (without prospective KRAS analysis) to Ir, IrCs or Ir/panitumumab. Thereafter, KRAS was analysed prospectively and pts with mutated or undetermined KRAS were allocated 1:1 to Ir (irinotecan 350 mg/m2 [300 mg/m2 if ≥70 yrs or PS2], q3w), or IrCs (irinotecan 140 mg/m2 [120 mg/m2 if ≥70 yrs or PS2] d1, Cs 3 mg/kg tds d0-2, q3w). The primary efficacy endpoint was % pts alive and progression-free at 12 wks, with a lower non-inferiority boundary of -10.6% (80% power, 2.5% significance). Grade ≥3 diarrhoea within 12 wks was a key secondary endpoint. PFS, OS, RR, QoL and loperamide use were also assessed. Analysis was performed on both the ITT and per-protocol populations. Results: 672 pts were randomised between Ir and IrCs. Median age was 64 yrs; 92% were PS0/1; 95% had received prior oxaliplatin; KRAS was mut in 60%, wt in 25%, unknown in 15%. ITT analysis showed 179/335 (53.4%) patients to be progression-free at 12 wks in the Ir arm, 159/337 (47.2%) in the IrCs arm. The difference was therefore -6.3% and the 95% CI crossed the prespecified non-inferiority margin (13.8%, +1.3%). Gr ≥3 diarrhoea was uncommon in both arms (Ir 12.2%; IrCs 10.1% pts), but fewer IrCs patients took loperamide within 12 wks (Ir 67.8%; IrCs 52.2%, p<0.001). Conclusions: As anticipated, IrCs was associated with less diarrhoea as assessed by loperamide use, but severe diarrhoea was uncommon in both arms. However, we failed to prove non-inferiority of IrCs compared with Ir, so cannot recommend it as a standard treatment option based on these data.

Background MRI might improve diagnosis of breast cancer, reducing rates of reoperation efficacy of contrast-enhanced MRI in women with primary breast cancer.Methods We undertook an open, parallel group trial in 45 UK centres, with 1623 women aged 18 years or older with biopsy-proven primary breast cancer who were scheduled for wide local excision after triple assessment. Patients were randomly assigned to receive either MRI (n=816) or no further imaging (807), with use of a minimisation algorithm incorporating a random element. The primary endpoint was the proportion of patients undergoing a repeat operation or further mastectomy within 6 months of random assignment, or a pathologically avoidable mastectomy at initial operation. Analysis was by intention to treat. This study is registered, ISRCTN number 57474502.Findings 816 patients were randomly assigned to MRI and 807 to no MRI. Addition of MRI to conventional triple assessment was not significantly associated with reduced a reoperation rate, with 153 (19%) needing reoperation in the MRI group versus 156 (19%) in the no MRI group, (odds ratio 0.96, 95% CI 0.75-1.24; p=0.77).

OBJECTIVESTo determine whether the addition of magnetic resonance imaging (MRI) to current patient evaluation by triple assessment would aid tumour localisation within the breast and thus reduce the reoperation rate in women with primary breast tumours who are scheduled for wide local excision (WLE), and to assess whether the addition of MRI would be cost-effective for the UK NHS.DESIGNA multicentre, randomised controlled, open, parallel group trial with equal randomisation. The main design was supplemented with a qualitative study to assess patients' experiences of the treatment process and care pathway, and involved the development of a non-scheduled standardised interview (NSSI).SETTINGThe study took place at 45 hospitals throughout the UK.PARTICIPANTSWomen aged 18 years or over with biopsy-proven primary breast cancer who had undergone triple assessment, were scheduled for WLE, and were capable of providing written informed consent.INTERVENTIONSPatients were randomised to receive MRI or no MR1. Randomisation was performed using minimisation, incorporating a random element. All MRI was performed at 1.5 T or 1.0 T with a dedicated bilateral breast coil.MAIN OUTCOME MEASURESThe primary end point of the trial was the reoperation rate. Secondary outcome measures included discrepancies between imaging and histopathology, and the effectiveness of using both procedures; change in clinical management after using MRI; the clinical significance of MRI-only-detected lesions; the rate of interventions; the ipsilateral tumour recurrence rate; patient quality of life (QoL); and cost-effectiveness.RESULTSFrom a total of 1623 patients, 816 were randomised to MRI and 807 to no MRI. No differences in reoperation rates were found between the two groups of patients [MRI patients 18.75%, no MRI 19.33%, difference 0.58%, 95% confidence interval (CI) -3.24 to 4.40]. Therefore, the addition of MRI to conventional triple assessment was not found to be statistically significantly associated with a reduced reoperation rate (odds ratio = 0.96, 95% CI 0.75-1.24, p = 0.7691). The best agreement between all imaging modalities and histopathology with regard to tumour size and extent of disease was found in patients over 50 years old with ductal tumours NST and who were node negative. In the imaging arm, mastectomy was found to be pathologically avoidable for 16 (27.6%) out of 58 patients who underwent the procedure. There were no significant differences between the groups regarding the proportion of patients receiving chemotherapy, radiotherapy or additional adjuvant therapies, as well as for local recurrence-free interval rates and QoL. An acceptable NSSI was developed for use in this population of patients. Economic analysis found no difference in outcomes between the two trial arms.CONCLUSIONSThe addition of MRI to triple assessment did not result in a reduction in operation rates, and the use of MRI would thus consume extra resource with few or no benefits in terms of cost-effectiveness or HRQoL. However, MRI showed potential to improve tumour localisation, and preoperative biopsy of MRI-only-detected lesions is likely to minimise the incidence of inappropriate mastectomy.TRIAL REGISTRATIONCurrent Controlled Trials ISRCTN57474502.

Abstract Abstract #51 The role of the addition of MR imaging (MRI) to routine techniques for loco-regional staging of primary breast cancer is unclear. The UK NIHR HTA multicentre COMICE trial considered whether adding an MRI scan to conventional triple assessment (mammogram, ultrasound and biopsy) assisted loco-regional staging and thereby reduced re-operation rates, for patients with primary breast cancer scheduled for wide local excision. The primary endpoint of the COMICE trial considered the proportion of patients undergoing a repeat operation or mastectomy at further surgery within six months of randomisation, or an avoidable mastectomy at initial surgery (re-operation rate). This was compared using logistic regression adjusting for age, breast density, and surgeon. Between December 2001 and January 2007 1625 patients were randomised to receive MRI (817) or not (808). Re-operation rate within six months (primary outcome) was 18.8% (MRI) and 19.3% (no MRI). No significant difference between the arms was detected (odds ratio=0.96, 95% CI=[0.75, 1.24], p=0.7691). Secondary endpoints included quality of life, imaging effectiveness and local recurrence. The results of the COMICE trial indicate no significant benefit in terms of reduction in re-operation rates, by the addition of MRI to conventional triple assessment for this patient group. These results have importance from both health economic and patient burden perspectives. This project was funded by the NIHR Health Technology Assessment (HTA) Programme (project number 99/27/05) and will be published in full in an HTA report.The view and opinions expressed therein are those of the authors and do not necessarily reflect those of the UK Department of Health. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 51.