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Summary Background Radical surgery via total mesorectal excision might not be the optimal first-line treatment for early-stage rectal cancer. An organ-preserving strategy with selective total mesorectal excision could reduce the adverse effects of treatment without substantially compromising oncological outcomes. We investigated the feasibility of recruiting patients to a randomised trial comparing an organ-preserving strategy with total mesorectal excision. Methods TREC was a randomised, open-label feasibility study done at 21 tertiary referral centres in the UK. Eligible participants were aged 18 years or older with rectal adenocarcinoma, staged T2 or lower, with a maximum diameter of 30 mm or less; patients with lymph node involvement or metastases were excluded. Patients were randomly allocated (1:1) by use of a computer-based randomisation service to undergo organ preservation with short-course radiotherapy followed by transanal endoscopic microsurgery after 8–10 weeks, or total mesorectal excision. Where the transanal endoscopic microsurgery specimen showed histopathological features associated with an increased risk of local recurrence, patients were considered for planned early conversion to total mesorectal excision. A non-randomised prospective registry captured patients for whom randomisation was considered inappropriate, because of a strong clinical indication for one treatment group. The primary endpoint was cumulative randomisation at 12, 18, and 24 months. Secondary outcomes evaluated safety, efficacy, and health-related quality of life assessed with the European Organisation for Research and Treatment of Cancer (EORTC) QLQ C30 and CR29 in the intention-to-treat population. This trial is registered with the ISRCTN Registry, ISRCTN14422743. Findings Between Feb 22, 2012, and Dec 19, 2014, 55 patients were randomly assigned at 15 sites; 27 to organ preservation and 28 to radical surgery. Cumulatively, 18 patients had been randomly assigned at 12 months, 31 at 18 months, and 39 at 24 months. No patients died within 30 days of initial treatment, but one patient randomly assigned to organ preservation died within 6 months following conversion to total mesorectal excision with anastomotic leakage. Eight (30%) of 27 patients randomly assigned to organ preservation were converted to total mesorectal excision. Serious adverse events were reported in four (15%) of 27 patients randomly assigned to organ preservation versus 11 (39%) of 28 randomly assigned to total mesorectal excision (p=0·04, χ2 test). Serious adverse events associated with organ preservation were most commonly due to rectal bleeding or pain following transanal endoscopic microsurgery (reported in three cases). Radical total mesorectal excision was associated with medical and surgical complications including anastomotic leakage (two patients), kidney injury (two patients), cardiac arrest (one patient), and pneumonia (two patients). Histopathological features that would be considered to be associated with increased risk of tumour recurrence if observed after transanal endoscopic microsurgery alone were present in 16 (59%) of 27 patients randomly assigned to organ preservation, versus 24 (86%) of 28 randomly assigned to total mesorectal excision (p=0·03, χ2 test). Eight (30%) of 27 patients assigned to organ preservation achieved a complete response to radiotherapy. Patients who were randomly assigned to organ preservation showed improvements in patient-reported bowel toxicities and quality of life and function scores in multiple items compared to those who were randomly assigned to total mesorectal excision, which were sustained over 36 months’ follow-up. The non-randomised registry comprised 61 patients who underwent organ preservation and seven who underwent radical surgery. Non-randomised patients who underwent organ preservation were older than randomised patients and more likely to have life-limiting comorbidities. Serious adverse events occurred in ten (16%) of 61 non-randomised patients who underwent organ preservation versus one (14%) of seven who underwent total mesorectal excision. 24 (39%) of 61 non-randomised patients who underwent organ preservation had high-risk histopathological features, while 25 (41%) of 61 achieved a complete response. Overall, organ preservation was achieved in 19 (70%) of 27 randomised patients and 56 (92%) of 61 non-randomised patients. Interpretation Short-course radiotherapy followed by transanal endoscopic microsurgery achieves high levels of organ preservation, with relatively low morbidity and indications of improved quality of life. These data support the use of organ preservation for patients considered unsuitable for primary total mesorectal excision due to the short-term risks associated with this surgery, and support further evaluation of short-course radiotherapy to achieve organ preservation in patients considered fit for total mesorectal excision. Larger randomised studies, such as the ongoing STAR-TREC study, are needed to more precisely determine oncological outcomes following different organ preservation treatment schedules. Funding Cancer Research UK.

Previous literature has sought prognostic factors for the survival of anal cancer patients. The present study aimed to determine prognostic factors for local disease recurrence, distant metastasis and survival for patients treated with radical chemoradiotherapy (CRT) at the Rosemere Cancer Centre, Preston, UK.Patients treated with CRT for nonmetastatic squamous cell anal cancer between September 2000 and January 2013 were studied. Kaplan-Meier and Cox regression analysis assessed the prognostic value of age, sex, tumour size, the proportion of the anal canal circumference involved (ACCI), nodal disease, tumour location and pretreatment haemoglobin.One hundred and 48 patients with a mean age of 63 years were studied, of whom 15% suffered local disease recurrence and 10% developed distant metastasis. The 5-year overall and cancer-specific survival rates were 84% and 86%, respectively. Predictors of local recurrence were tumour size5 cm and over two-thirds ACCI (P 0.01). Predictors of distant metastasis and poor survival were tumour size5 cm (P 0.01), node positive disease on imaging (P 0.05), over two-thirds ACCI (P 0.01) and a pretreatment haemoglobin level below 130 g/l (P 0.05). Multivariate analysis found large tumour size to be the most significant factor for local recurrence (P = 0.002) and survival (P = 0.02) whilst over two-thirds ACCI was most predictive of distant metastasis (P 0.001). Age, gender, palpable lymph nodes and tumour location were not of prognostic value for local disease recurrence, distant metastasis or survival.Tumour size, nodal disease, over two-thirds ACCI and low pretreatment haemoglobin confer poorer prognostic and survival outcomes. Use of intensity-modulated radiation therapy may allow greater radiation doses to be given for locally advanced tumours, thus improving local control and survival and reducing morbidity.

Background: The influence of EGFR pathway mutations on cetuximab-containing rectal cancer preoperative chemoradiation (CRT) is uncertain. Methods: In a prospective phase II trial (EXCITE), patients with magnetic resonance imaging (MRI)-defined non-metastatic rectal adenocarinoma threatening/involving the surgical resection plane received pelvic radiotherapy with concurrent capecitabine, irinotecan and cetuximab. Resection was recommended 8 weeks later. The primary endpoint was histopathologically clear (R0) resection margin. Pre-planned retrospective DNA pyrosequencing (PS) and next generation sequencing (NGS) of KRAS, NRAS, PIK3CA and BRAF was performed on the pre-treatment biopsy and resected specimen. Results: Eighty-two patients were recruited and 76 underwent surgery, with R0 resection in 67 (82%, 90%CI: 73–88%) (four patients with clinical complete response declined surgery). Twenty–four patients (30%) had an excellent clinical or pathological response (ECPR). Using NGS 24 (46%) of 52 matched biopsies/resections were discrepant: ten patients (19%) gained 13 new resection mutations compared to biopsy (12 KRAS, one PIK3CA) and 18 (35%) lost 22 mutations (15 KRAS, 7 PIK3CA). Tumours only ever testing RAS wild-type had significantly greater ECPR than tumours with either biopsy or resection RAS mutations (14/29 [48%] vs 10/51 [20%], P=0.008), with a trend towards increased overall survival (HR 0.23, 95% CI 0.05–1.03, P=0.055). Conclusions: This regimen was feasible and the primary study endpoint was met. For the first time using pre-operative rectal CRT, emergence of clinically important new resection mutations is described, likely reflecting intratumoural heterogeneity manifesting either as treatment-driven selective clonal expansion or a geographical biopsy sampling miss.

The G17DT is a novel human immunogen that raises antibodies to the growth factor gastrin 17 (G17). The purpose of this study was to determine the safety and efficacy of G17DT in combination with irinotecan in patients refractory to irinotecan, and to correlate efficacy with anti-G17 immune response. Patients received G17DT immunogen as a single intramuscular injection of 500 μg at weeks 1, 5, 9, and 26. Irinotecan was administered as an intravenous infusion of 125 mg/m2 over 90 min starting at week 5. Each cycle of treatment consisted of irinotecan administered once weekly for 4 weeks, followed by a 2-week rest period. Of 161 patients who received G17DT, the best overall tumor response in the intent-to-treat population was complete response 0 (0 %), partial response 3 (3 %), stable disease 32 (32 %), and progressive disease 64 (65 %). Median survival was 217 days. About 94 (62 %) subjects evaluable for antibody titers were anti-G17 responders. Survival was significantly longer for anti-G17 responders compared with non-responders (9.0 vs. 5.6 months; P

Aim Following treatment for colorectal cancer it is common practice for patients to attend hospital clinics at regular intervals for routine monitoring, although debate persists on the benefits of this approach. Nurse-led telephone follow-up is effective in meeting information and psycho-social needs in other patient groups. We explored the potential benefits of nurse-led telephone follow-up for colorectal cancer patients. Method Sixty-five patients were randomized to either telephone or hospital follow-up in an exploratory randomized trial. Results The telephone intervention was deliverable in clinical practice and acceptable to patients and health professionals. Seventy-five per cent of eligible patients agreed to randomization. High levels of satisfaction were evident in both study groups. Appointments in the hospital group were shorter (median 14.0 min) 5

Purpose To assess long-term clinical outcomes of preoperative chemoradiotherapy of magnetic resonance imaging (MRI)–defined locally advanced rectal adenocarcinoma using concurrent irinotecan and capecitabine. Patients and Methods One hundred ten patients without distant metastases entered this phase II trial North West/North Wales Clinical Oncology Group (NWCOG) -2 after MRI demonstration of tumor threatening (≤ 2 mm) or involving mesorectal fascia. Pelvic radiotherapy was given to 45 Gy in 25 fractions over 5 weeks with concurrent oral capecitabine at 650 mg/m2 twice per day continuously days 1 through 35 and intravenous irinotecan at 60 mg/m2 once weekly weeks 1 to 4. One hundred seven patients subsequently underwent surgical resection. Results Comparing prechemoradiotherapy MRI scans with histology of the resected specimen, 72 patients (67%) had their initial MRI T stage downstaged and 64 patients (80%) had their N stage downstaged. Twenty-four patients (22%) demonstrated a pathologic complete response (ypCR) and 98 patients (92%) demonstrated a negative circumferential resection margin (> 1 mm). Three-year local recurrence-free survival was 96.9%, metastasis-free survival (MFS) was 71.1%, disease-free survival was (DFS) 63.5%, and overall survival (OS) was 88.2%. By univariate analysis, lower histologic stage was significantly associated with superior MFS, DFS, and OS, whether expressed as ypT0-2 versus ypT3-4, ypN0 versus ypN1-2, or ypCR/microfoci (near-ypCR) versus other patients. By multivariate analysis both ypN stage (P = .048) and ypCR/microfoci/others (P = .013) remained significant predictors of DFS but only ypCR/microfoci/others for OS (P = .005) with no difference in outcome between ypCR compared to microfoci. Conclusion This regimen demonstrates high response rates and promising long-term survival. Downstaging to ypCR/microfoci may be a useful short-term surrogate for long-term survival but needs validation in large phase III trials powered for survival outcomes.

Background. The optimal follow-up strategy for colorectal cancer is not known, and although patients are seen in traditional outpatient follow-up clinics, this system may not meet psycho-social and information needs. Design. An exploratory qualitative study. Method. In-depth interviews were conducted with 27 patients who had completed treatment for colorectal cancer. The data were analysed using thematic analysis. Results. One dominant theme emerged from the data with several sub-themes. The dominant theme was ‘knowing what to expect’ after bowel surgery. The subthemes related to ‘living with altered bowel function’, the ways patients gathered information about their condition through ‘trial and error’ and ‘information and support from specialist nurses’. Patients who did not have a stoma were particularly vulnerable and expressed a need for more information on knowing what to expect after surgery. The role of the colorectal nurse specialist was vital in providing information and support; in particular, nurse-led clinics provided continuity of care and information that was tailored to individual need. Conclusions. Traditional hospital follow-up does not always address patients’ psycho-social and information needs. Nurse-led services were commented on favourably in terms of providing information that was tailored to individual need as well as being responsive to urgent patient concerns; future innovative strategies for providing follow-up care for patients with colorectal cancer should draw on the specialist knowledge and skills of these nurses. Relevance to clinical practice. Nurse-led clinics and/or telephone follow-up by specialist nurses may be effective models of care for this particular patient group, providing appropriate access for meeting clinical, psycho-social and information needs.

Objectives To design and administer an attitude rating scale, exploring colorectal cancer patients’ views of involvement in decision making. To examine the impact of socio-demographic and/or treatment-related factors on decision making. To conduct principal components analysis to determine if the scale could be simplified into a number of factors for future clinical utility. Methods An attitude rating scale was constructed based on previous qualitative work and administered to colorectal cancer patients using a cross-sectional survey approach. Results 375 questionnaires were returned (81.7% response). For patients it was important to be informed and involved in the decision-making process. Information was not always used to make decisions as patients placed their trust in medical expertise. Women had more positive opinions on decision making and were more likely to want to make decisions. Written information was understood to a greater degree than verbal information. The scale could be simplified to a number of factors, indicating clinical utility. Conclusion Few studies have explored the attitudes of colorectal cancer patients towards involvement in decision making. This study presents new insights into how patients view the concept of participation; important when considering current policy imperatives in the UK of involving service users in all aspects of care and treatment.

In the UK, 10% of patients diagnosed with rectal cancer have inoperable disease at presentation. This study ascertained whether the resectability rate of inoperable locally advanced rectal cancer was improved by administration of intravenous irinotecan, 5-fluorouracil (5-FU) and pelvic radiotherapy. During phase I of the trial (n=12), the dose of irinotecan was escalated in three-patient cohorts from 50 mg m(-2) to 60 mg m(-2) to 70 mg m(-2) to identify the maximum tolerated dose (60 mg m(-2)). In phase II, 31 patients with non-resectable disease received 45 Gy radiotherapy and 5-FU infusions (200 mg m(-2) per day) for 5 weeks. Irinotecan (60 mg m(-2)) was given on days 1, 8, 15 and 22. After treatment, patients were operated on if possible. Thirty patients completed the protocol, 28 underwent surgery. Before surgery, MRI restaging of 24 patients showed that 19 (79%) had a reduction in tumour stage after treatment (seven complete clinical response and 12 partial). Of 27 patients followed up after surgery, 22 (81%) had clear circumferential resection margins. Disease-free and overall survival estimates at 3 years were 65 and 90%, respectively. The regimen was well tolerated. Irinotecan, 5-FU and radiotherapy results in tumour downgrading, allowing resection of previously inoperable tumour with acceptable toxicity.

Aim. The aim of this study was to explore views on patient participation in decision making, as described by health professionals caring for people with colorectal cancer. Background. Patient participation in health-care decision making is on the policy agenda at an international level. However, many aspects of cancer care and treatment are complex and it is unclear how health professionals view their role as promoters of patient participation. Design. A qualitative exploratory study. Methods. In depth interviews with 35 health professionals in clinical practice. Data were analysed using thematic content analysis, assisted by a computer software package for analysis of qualitative data (N-VIVO). Results. Choices in relation to surgical treatment were viewed as limited. Although it was perceived that patients could be more involved in decisions related to adjuvant treatment, providing information on various chemotherapy regimes was challenging. It was acknowledged that patients could be involved in treatment choices but there was far less clarity concerning aspects of physical and psychological care. Age was a factor when determining which patients should be offered treatment choices. Conclusion. The availability and presentation of choices to patients is context specific and tailored to the preferences of individuals. If health professionals focus only on aspects of decision making related to treatment, the potential for shared partnerships with patients in relation to choices about physical and psychological care may be lost. This may be particularly pertinent for nurses and allied professions who engage with patients throughout the illness trajectory. Relevance to clinical practice. Policy makers should arguably appreciate that health professionals have an awareness of current thinking on patient participation, but may find policy recommendations challenging to implement in clinical practice when faced with the individual needs and preferences of patients and the complexities and uncertainties of disease management.

Induction of a clinical complete response with chemoradiotherapy, followed by observation via a watch-and-wait approach, has emerged as a management option for patients with rectal cancer. We aimed to address the shortage of evidence regarding the safety of the watch-and-wait approach by comparing oncological outcomes between patients managed by watch and wait who achieved a clinical complete response and those who had surgical resection (standard care).Oncological Outcomes after Clinical Complete Response in Patients with Rectal Cancer (OnCoRe) was a propensity-score matched cohort analysis study, that included patients of all ages diagnosed with rectal adenocarcinoma without distant metastases who had received preoperative chemoradiotherapy (45 Gy in 25 daily fractions with concurrent fluoropyrimidine-based chemotherapy) at a tertiary cancer centre in Manchester, UK, between Jan 14, 2011, and April 15, 2013. Patients who had a clinical complete response were offered management with the watch-and-wait approach, and patients who did not have a complete clinical response were offered surgical resection if eligible. We also included patients with a clinical complete response managed by watch and wait between March 10, 2005, and Jan 21, 2015, across three neighbouring UK regional cancer centres, whose details were obtained through a registry. For comparative analyses, we derived one-to-one paired cohorts of watch and wait versus surgical resection using propensity-score matching (including T stage, age, and performance status). The primary endpoint was non-regrowth disease-free survival from the date that chemoradiotherapy was started, and secondary endpoints were overall survival, and colostomy-free survival. We used a conservative p value of less than 0·01 to indicate statistical significance in the comparative analyses.259 patients were included in our Manchester tertiary cancer centre cohort, 228 of whom underwent surgical resection at referring hospitals and 31 of whom had a clinical complete response, managed by watch and wait. A further 98 patients were added to the watch-and-wait group via the registry. Of the 129 patients managed by watch and wait (median follow-up 33 months [IQR 19-43]), 44 (34%) had local regrowths (3-year actuarial rate 38% [95% CI 30-48]); 36 (88%) of 41 patients with non-metastatic local regrowths were salvaged. In the matched analyses (109 patients in each treatment group), no differences in 3-year non-regrowth disease-free survival were noted between watch and wait and surgical resection (88% [95% CI 75-94] with watch and wait vs 78% [63-87] with surgical resection; time-varying p=0·043). Similarly, no difference in 3-year overall survival was noted (96% [88-98] vs 87% [77-93]; time-varying p=0·024). By contrast, patients managed by watch and wait had significantly better 3-year colostomy-free survival than did those who had surgical resection (74% [95% CI 64-82] vs 47% [37-57]; hazard ratio 0·445 [95% CI 0·31-0·63; p0·0001), with a 26% (95% CI 13-39) absolute difference in patients who avoided permanent colostomy at 3 years between treatment groups.A substantial proportion of patients with rectal cancer managed by watch and wait avoided major surgery and averted permanent colostomy without loss of oncological safety at 3 years. These findings should inform decision making at the outset of chemoradiotherapy.Bowel Disease Research Foundation.

Objectives: To explore patient views on participation in treatment, physical care and psychological care decisions and factors that facilitate and hinder patients from making decisions. Design: Qualitative study using semi-structured interviews with patients. Setting and participants: Three NHS Trusts in the north-west of England. Theoretical sampling including 41 patients who had been treated for colorectal cancer. Results: For patients, participation in the decision-making process was about being informed and feeling involved in the consultation process, whether patients actually made decisions or not. The perceived availability of treatment choices (surgery, radiotherapy, chemotherapy) was related to type of treatment. Factors that impacted on whether patients wanted to make decisions included a lack of information, a lack of medical knowledge and trust in medical expertise. Patients perceived that they could have a more participatory role in decisions related to physical and psychological care. Conclusion: This study has implications for health professionals aiming to implement policy guidelines that promote patient participation and shared partnerships. Patients in this study wanted to be well informed and involved in the consultation process but did not necessarily want to use the information they received to make decisions. The presentation of choices and preferences for participation may be context specific and it cannot be assumed that patients who do not want to make decisions about one aspect of their care and treatment do not want to make decisions about other aspects of their care and treatment.

To explore patient perceptions of their experiences of follow-up care after treatment for colorectal cancer.The optimal follow-up strategy for colorectal cancer is not known, and although patients are seen in traditional outpatient follow-up clinics, this system may not meet psycho-social and information needs.An exploratory qualitative study.In-depth interviews were conducted with 27 patients who had completed treatment for colorectal cancer. The data were analysed using thematic analysis.One dominant theme emerged from the data with several sub-themes. The dominant theme was 'knowing what to expect' after bowel surgery. The subthemes related to 'living with altered bowel function', the ways patients gathered information about their condition through 'trial and error' and 'information and support from specialist nurses'. Patients who did not have a stoma were particularly vulnerable and expressed a need for more information on knowing what to expect after surgery. The role of the colorectal nurse specialist was vital in providing information and support; in particular, nurse-led clinics provided continuity of care and information that was tailored to individual need.Traditional hospital follow-up does not always address patients' psycho-social and information needs. Nurse-led services were commented on favourably in terms of providing information that was tailored to individual need as well as being responsive to urgent patient concerns; future innovative strategies for providing follow-up care for patients with colorectal cancer should draw on the specialist knowledge and skills of these nurses.Nurse-led clinics and/or telephone follow-up by specialist nurses may be effective models of care for this particular patient group, providing appropriate access for meeting clinical, psycho-social and information needs.

Purpose To explore patient satisfaction on different aspects of follow-up service provision following treatment for colorectal cancer and amenability to an alternative strategy for follow-up care. Methods and sample A postal survey was administered to 297 eligible patients who had been treated for colorectal cancer at a large hospital in the North West of England. Patients were asked to indicate responses to questions comprising likert scales, including views on organisation of care, information and advice, personal experience of care, satisfaction with information and care, views on specialist nursing services and amenability to telephone follow-up. Key results One hundred and eighty-seven completed surveys were returned (62.97% response rate). Analysis of scale data indicated high levels of satisfaction on all outcome measures but sub-optimal rates of satisfaction on some items. Respondents indicated high levels of satisfaction with information related to disease and treatment but lower levels of satisfaction for items related to genetic risk, sexual attractiveness and self care. Colorectal nurse specialists were highly rated, especially in terms of information provision and personal experience of care. Patients were generally amenable to telephone follow-up, although male patients indicated higher levels of willingness to accept this approach than females. Conclusions Satisfaction with traditional medical based follow-up is generally high in this patient cohort but there is room for improvement in terms of service delivery. High levels of satisfaction with the care delivered by colorectal nurse specialists and patient acceptance of telephone follow-up suggests nurse-led telephone follow-up is a viable alternative to traditional hospital based follow-up.

BackgroundThis was an economic evaluation of hospital versus telephone follow-up by specialist nurses after treatment for breast cancer.MethodsA cost minimization analysis was carried out from a National Health Service (NHS) perspective using data from a trial in which 374 women were randomized to telephone or hospital follow-up. Primary analysis compared NHS resource use for routine follow-up over a mean of 24 months. Secondary analyses included patient and carer travel and productivity costs, and NHS and personal social services costs of care in patients with recurrent breast cancer.ResultsPatients who had telephone follow-up had approximately 20 per cent more consultations (634 versus 524). The longer duration of telephone consultations and the frequent use of junior medical staff in hospital clinics resulted in higher routine costs for telephone follow-up (mean difference £55 (bias-corrected 95 per cent confidence interval (b.c.i.) £29 to £77)). There were no significant differences in the costs of treating recurrence, but patients who had hospital-based follow-up had significantly higher travel and productivity costs (mean difference £47 (95 per cent b.c.i. £40 to £55)).ConclusionTelephone follow-up for breast cancer may reduce the burden on busy hospital clinics but will not necessarily lead to cost or salary savings.

The mainstay of curative treatment for rectal cancer is surgery and the surgical technique of total mesorectal excision (TME), wherein meticulous sharp dissection is carried out in the plane of the mesorectal fascia, has been shown to reduce the chance of local recurrence (MacFarlane et al, 1993; Kapiteijn et al, 2001). Perioperative RT can reduce the chance of local recurrence following rectal cancer surgery (Colorectal Collaborative Group, 2001). The FFCD 9203 and EORTC 22921 trials have shown that for operable rectal cancer combined fluoropyrimidine chemotherapy and long-course RT confers an advantage in terms of reducing local pelvic recurrence compared with RT alone (Bosset et al, 2006; Gerard et al, 2006). A large randomised trial has definitively shown that preoperative chemoradiation (CRT) reduces local recurrence in operable rectal cancer compared with postoperative CRT (13 vs 6%), with reduced acute and late toxicity (Sauer et al, 2004). Involvement of the circumferential resection margin (CRM) has been shown to be an important, independent prognostic factor, resulting in high rates of local recurrence (Quirke et al, 1986; Wibe et al, 2002), distant metastases (Hall et al, 1998; Mawdsley et al, 2005) and worse survival (Birbeck et al, 2002; Nagtegaal and Quirke, 2008), even after TME surgery (Marijnen et al, 2003). Several potential mechanisms have been described in which the histological CRM may be positive including direct or discontinuous tumour spread, lymph node spread, lymphovascular spread and perineural spread (Nagtegaal and Quirke, 2008). CRM positivity is also strongly related to the quality of surgery (Nagtegaal et al, 2002; Quirke et al, 2009). In the United Kingdom and increasingly elsewhere, preoperative MRI scanning of the pelvis is viewed as the gold standard for judging threatening or involvement of the mesorectal fascial potential surgical TME resection plane. In 311 patients with operable rectal cancer who were shortly due to undergo surgery, the MERCURY trial showed that preoperative MRI has high accuracy, negative predictive value and specificity in the identification of a potentially involved CRM (MERCURY Study Group, 2006). Approximately 20–30% of rectal cancer patients present with disease which threatens or involves the potential mesorectal surgical excision margin. These patients might be considered to have ‘locally advanced inoperable' disease with a high risk of local recurrence unless some form of downstaging is carried out before surgery. As an indication of what might be achieved in the modern era using downstaging CRT with a single agent fluoropyrimidine as a radiation sensitiser in patients with locally advanced carcinomas, a single UK cancer network audit has been reported in 150 patients with locally advanced rectal cancer (Mawdsley et al, 2005). Sixty-one percent were T4 and approximately one-third had been staged by MRI. Concurrent bolus 5-FU was administered in weeks 1 and 5 of radiotherapy as per the EORTC 22921 and FFCD 9203 trials. On an intention to treat (ITT) analysis, an R0 resection was achieved in only 65% of patients and the poor prognostic significance of involved CRM post-downstaging CRT was confirmed with 3-year local recurrence at 10 vs 62% and 3-year disease-free survival at 52 vs 9% for R0 vs R1/2 resections, respectively. There is a need to improve on the potency of currently available downstaging CRT regimes and one potential way of achieving this is by adding in a second chemotherapy agent to form a doublet in addition to a fluoropyrimidine. The topoisomerase-I inhibitor irinotecan is one possible agent to use in this context in view of radiosensitising properties demonstrated in vitro (Chen et al, 1997). Several early phase studies have been reported (Mehta et al, 2003; Klautke et al, 2005; Mohiuddin et al, 2006; Navarro et al, 2006; Glynne-Jones et al, 2007) including by our own group (Iles et al, 2008) concerning rectal cancer CRT regimes using the doublet of 5FU plus irinotecan as radiation sensitisers. Rates of grade 3 or 4 toxicity have varied from between 12–37% (mostly diarrhoea) with promising pathological complete response (pCR) rates of between 14–37% for resected specimens. There are potential advantages in using the oral 5FU prodrug capecitabine rather than 5FU itself including the avoidance of a central venous catheter to administer continuous infusional 5FU. In addition, the final enzymatic conversion of capecitabine is mediated via thymidine phosphorylase which often occurs in a higher concentration in cancer tissue compared with adjacent normal tissue with the potential advantage of improving the therapeutic ratio compared with 5FU (Glynne-Jones et al, 2006). Thymidine phosphorylase is upregulated by RT (Sawada et al, 1999). This study represents a progression of previous research reported by our group (the North West/North Wales Clinical Oncology Group) which used irinotecan and infusional 5FU as a doublet of concurrent radiation sensitisers in the preoperative downstaging of locally advanced rectal cancer (Iles et al, 2008). This study is a phase I trial in patients with MRI-defined locally advanced rectal cancer which is threatening or involving the mesorectal fascia and replaces the infusional 5FU with continuous oral capecitabine. The doses of irinotecan and capecitabine were gradually increased, keeping the radiation dose constant, with toxicity being the primary end point.

Objective To compare traditional hospital follow-up with telephone follow-up by specialist nurses after treatment for breast cancer.\ud \ud \ud Design A two centre randomised equivalence trial in which women remained in the study for a mean of 24 months.\ud \ud \ud Setting Outpatient clinics in two NHS hospital trusts in the north west of England\ud \ud \ud Participants 374 women treated for breast cancer who were at low to moderate risk of recurrence.\ud \ud Interventions Participants were randomised to traditional hospital follow-up (consultation, clinical examination, and mammography as per hospital policy) or telephone follow-up by specialist nurses (consultation with structured intervention and mammography according to hospital policy).\ud \ud Main outcome measures Psychological morbidity (state-trait anxiety inventory, general health questionnaire (GHQ-12)), participants’ needs for information, participants’ satisfaction, clinical investigations ordered, and time to detection of recurrent disease.\ud \ud Results The 95% confidence interval for difference in mean state-trait scores adjusted for treatment received (−3.33 to 2.07) was within the predefined equivalence region (−3.5 to 3.5). The women in the telephone group were no more anxious as a result of foregoing clinic examinations and face-to-face consultations and reported higher levels of satisfaction than those attending hospital clinics (intention to treat P\ud Conclusions Telephone follow-up was well received by participants, with no physical or psychological disadvantage. It is suitable for women at low to moderate risk of recurrence and those with long travelling distances or mobility problems and decreases the burden on busy hospital clinics.\ud \ud Trial registration National Cancer Research Institute 1477.

Objective Our aim was to determine the range of neo-adjuvant therapy the multidisciplinary team (MDT) currently offers patients with curable (M0) rectal cancer. Method A senior oncologist from each of the four oncology centres in north Wales and the north-west of England (approximate target population 8 million – Glan Clwyd, Clatterbridge, Christie and Preston) reviewed his/her understanding of the current evidence of neo-adjuvant therapy in rectal cancer. Then a representative from each centre was asked to identify which of three neo-adjuvant options (no neo-adjuvant therapy, short-course radiotherapy 25 Gy over five fractions and long-course chemoradiotherapy) he/she would use for a rectal cancer in the upper, middle or lower third of the rectum staged by magnetic resonance imaging as being T2–T4 and/or N0–N2. Results In all cases of locally advanced rectal cancer (T3a N1–T4), oncologists from the four oncology centres recommended long-course chemoradiotherapy before rectal resection. This consensus was maintained for cases of lower third T3a N0 cancers. Thereafter, the majority of patients with rectal cancer are offered adjuvant short-course radiotherapy. Conclusion Neo-adjuvant therapy is less likely to be offered if the tumour is early (T2, N0) and/or situated in the upper third of the rectum.

Epithelioid haemangioendothelioma (EHE) is a rare, welldifferentiated vascular tumour of bone, accounting for only 0.5–1% of malignant primary bone tumours [1]. Weiss and Enzinger first described it in 1982 in soft tissues [2]. EHE is the most common epithelioid vascular neoplasm of bone. EHE can present in locations other than bone, such as skin, soft tissue, liver, lungs, heart, intestine, nervous system, retroperitoneum and other body sites. However, it is most common in liver, soft tissues and bone [3]. EHE in bone typically affects adults in the second or third decade, though all age groups can be affected. Sixty percent of EHE cases occur in the long bones with tibia (23%), femur (18%) and humerus (13%) being the commonest sites [4]. Metaphysis and diaphysis are usually involved. EHE presents as synchronous or metachronous disease in 20–50% of patients [4]. Multicentric presentation has been described in 50–62%, with a predilection for bones of the lower extremities in one anatomic region [5]. Nearby or distant soft tissues and skin (Fig. 4) can be involved, and metastases to the lung have also been reported. Conventional radiography of EHE shows an expansile, lytic and often poorly demarcated lesion. A coarse trabecular or honeycombing pattern is commonly seen, with a distinctive ‘soap bubble’ matrix. A well-defined sclerotic rim is seen in most lesions [6]. Calcification is rare, and periosteal reaction is not seen unless complicated by pathologic fracture [7]. Lesions with ill-defined borders are considered more aggressive (Fig. 1). On MR imaging, the lesions are of intermediate signal intensity on T1-weighted images and high signal intensity on T2-weighted images. Homogenous enhancement is seen after administration of gadolinium. Flow voids due to vascular channels are not typically seen on MRI of EHE, and if present, should suggest an alternative diagnosis [4]. This could be due to the small size of the vascular channels [7] (Fig. 3). Bone scintigraphy is often undertaken to identify the multicentric involvement of EHE. Increased uptake is seen at sites of involvement (Fig. 2). Doughnut-shaped lesions have been described at the site of involvement [8]. This appearance on bone scan can also be seen in benign or malignant lesions, but multiple lesions should raise the suspicion of a vascular lesion, such as haemangioendothelioma. The case presentation can be found at doi:10.1007/s00256-011-1127-1.

e15000 Background: Tumour size, nodal involvement and sex are recognized prognostic factors in squamous cell anal cancer. Our study aims to evaluate survival and potential prognostic factors amongs...

458 Background: Little data exists comparing pre- and post-CRT EGFR pathway mutations in LARC. Methods: Patients had MRI-defined LARC threatening or involving the surgical resection margin. CRT used pelvic radiotherapy (RT) 45Gy in 25 daily fractions with concurrent capecitabine (650mg/m2 bid PO 5 days/week), IV cetuximab (400mg/m2 one week prior then weekly at 250mg/m2 weeks 1-5) and IV irinotecan (weekly at 60mg/m2weeks 1-4). Surgery was 8 weeks after CRT. EGFR pathway mutations were not assessed prospectively. After study completion DNA was extracted from pre-treatment biopsies and post-resection specimens by macrodissecting areas of greatest tumour cell density. KRAS codons 12, 13, 61, 146, NRAS codons 12, 13, 61, PIK3CA codons 542, 545, 546, 1047 and the BRAF V600E hotspot were then pyrosequenced. Results: From 04/09-10/11, 80 patients commenced RT. 76 patients had surgery, with pathological complete response (CR) in 14 (18%) and near-complete (microfoci) in 6 (8%). Four patients had no surgery due to clinical CR. Pre-treatment mutation status was available in 78 patients with a KRAS codon mutation in 34 patients, BRAF in 3, NRAS in 3, PIK3CA in 10 and pathway (any mutation) in 45 (58%). Post-resection data in 54 patients showed 35 mutated codons in 32 patients (59%). 18 patients (33%) showed a discrepancy compared to pre-treatment biopsy. In 17 this was at a single codon, from wild-type (wt) to mutant (mut) in 9 (7x KRAS 12, 1x KRAS 13, 1x PIK3CA 542), from mut to mut in 1 (KRAS 12 c.35G>A to c.34G>T) and mut to wt in 7 (1x KRAS 12, 2x KRAS 13, 2x KRAS 146, 1x PIK3CA 542, 1x PIK3CA 545). One patient changed in 3 codons (mut to wt at KRAS 146 and PIK3CA 545 and wt to mut at KRAS 12). In 12 patients (22%) this changed overall EGFR pathway status (6x wt to mut and 6x mut to wt). Conclusions: Intratumour heterogeneity may explain the EGFR pathway codon changes causing sequencing from single areas of macrodissection to underestimate the tumour genomic landscape and presenting a challenge to personalised medicine. Cetuximab may also drive growth of undetectable mutant clones to detectable levels on pyrosequencing. Clinical trial information: 2007-006701-25.

3636 Background: There is a need to increase the efficacy of preoperative downstaging CRT in locally advanced rectal cancer. Methods: Patients (median age 62 ), with rectal adenocarcinoma without d...

13519 Background: Preoperative downstaging chemoradiation has become standard treatment for locally advanced unresectable rectal cancer. Oral CAP is potentially more convenient as a radiation sensitiser than infusional fluoropyrimidine regimes. This study evaluated the dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and recommended dose (RD) of daily CAP plus weekly i.v. CPT-11 when used in combination with RT in locally advanced rectal cancer. Methods: Patients had an adenocarcinoma of the rectum (lower limit within 12 cm of the anal verge) which on MRI was T3 within 2 mm of the mesorectal outer edge, T4, or any T3 within 5 cm of the anal verge. There were no distant metastases on staging investigations. Patients received planned pelvic RT to 45 Gy in 25 daily fractions over five weeks, concurrent with oral CAP daily throughout RT (including weekends) and a 60 minute infusion of i.v. CPT-11 weeks 1, 2, 3 and 4. Doses of CAP and CPT-11 were gradually escalated in cohorts of three patients. Results: The most common DLT was diarrhoea. Initially dose level (D/L) 3 was chosen as the recommended dose for phase II. However, unacceptable toxicity was encountered in the first 12 patients treated at D/L 3 (see Table). Thus D/L 2 is now being expanded to 60 patients for phase II. 40 patients have thus far potentially been eligible for resection: 5 (13%) could not be resected (2 deteriorated, 2 developed metastases, 1 died during treatment), 32 (80%) had R0 and 3 (7%) R1 resection. 9 (25%) had a pathological complete response (pCR) and 7 (20%) ‘near’ pCR. 5 (9%) of 57 patients had a defunctioning stoma pre-RT. Conclusions: The RD for this regime is 60 mg/m2 i.v. CPT-11 weeks 1, 2, 3, 4 and 650 mg/m2 bd of oral CAP daily. This demonstrates promising signs of efficacy. The RD is currently being studied in an expanded phase II cohort of 60 patients. D=diarrhea; F=febrile neutropenia; A=anorexia; L=lethargy; N=nausea/vomiting. [Table: see text] No significant financial relationships to disclose.

3565 Background: Preoperative downstaging chemoradiation has become standard treatment for locally advanced unresectable rectal cancer. Oral CAP is potentially more convenient as a radiation sensit...