Aim The study aimed to investigate whether textural features of rectal cancer on MRI can predict long-term survival in patients treated with long-course chemoradiotherapy.Method Textural analysis (TA) using a filtration similar to histogram technique of T2-weighted pre-and 6-week post-chemoradiotherapy MRI was undertaken using TexRAD, a proprietary software algorithm. Regions of interest enclosing the largest cross-sectional area of the tumour were manually delineated on the axial images and the filtration step extracted features at different anatomical scales (fine, medium and coarse) followed by quantification of statistical features [mean intensity, standard deviation, entropy, skewness, kurtosis and mean of positive pixels (MPP)] using histogram analysis. Cox multiple regression analysis determined which univariate features including textural, radiological and histological independently predicted overall survival (OS), disease-free survival (DFS) and recurrence- free survival (RFS).Results MPP [fine texture, hazard ratio (HR) 6.9, 95% CI: 2.43-19.55, P < 0.001], mean (medium texture, HR 5.6, 95% CI: 1.4-21.7, P = 0.007) and extramural venous invasion (EMVI) on MRI ( HR 2.96, 95% CI: 1.04-8.37, P = 0.041) independently predicted OS while mean (medium texture, HR 4.53, 95% CI: 1.5812.94, P = 0.003), MPP (fine texture, HR 3.36, 95% CI: 1.36-8.31, P = 0.008) and threatened circumferential resection margin (CRM) on MRI (HR 3.1, 95% CI: 1.01-9.46, P = 0.046) predicted DFS. For OS, EMVI on MRI (HR 4.23, 95% CI: 1.41-12.69, P = 0.01) and for DFS kurtosis (medium texture, HR 3.97, 95% CI: 1.44-10.94, P = 0.007) and CRM involvement on MRI (HR 3.36, 95% CI: 1.21-9.32, P = 0.02) were the independent post-treatment factors. Only TA independently predicted RFS on pre-orpost-treatment analyses.Conclusion MR based TA of rectal cancers can predict outcome before undergoing surgery and could potentially select patients for individualized therapy.

Introduction: The rising cost of healthcare requires rethinking in terms of resource utilisation care delivery. Nurse-led PSA phone follow-up clinics may provide a suitable option. Materials and methods: 815 patients were recruited for the nurse-led stable prostate cancer telephone follow-up service. A convenience sample was selected for postal questionnaire assessment of their satisfaction. Results: 815 patients had 3683 phone-call follow ups over 10 years. Patients’ own understanding of condition varied from average (76.3%) and good (9.2%) in the majority. 87.2% found the service convenient and 75.6% informative. 95.3% found the telephone assessment preferable to attending the outpatient department. 87.2% were keen on savings on transport/travel. 53.5% found it more reassuring. 91.9% of patients felt that everything they wanted to talk about was covered. Discussion: This service can be delivered in a high volume nurse-led service, with high levels of patient satisfaction, as an innovative service development.

The optimum interval between CRT and surgery for locally advanced rectal cancer remains controversial. If greater downstaging occurs with a longer interval to surgery, this may impact on rates of sphincter preservation and survival. A prospective, randomised, multicentre trial was undertaken to determine whether greater rectal cancer downstaging and regression occurs when surgery is delayed to 12 compared to 6-weeks. The primary endpoint was difference in proportion of patients in each arm downstaged according to MRI T-stage - defined as any reduction in T-stage/sub-stage. A sample size of 218 patients was required. Secondary endpoints included pCR and mrTRG 1-2 rates. A total of 237 patients were randomised: 122 (51%) into the 6-week and 115 (49%) to the 12-week arm. A significantly greater proportion downstaged in the 12-week (58%) compared with 43% in the 6-week arm (p = 0.019). The pCR rate was 9% in the 6-week versus 20% for the 12-week arm (p < 0.05). The mrTRG 1-2 rate in the 6-week arm was 34% versus 52% in the 12-week arm (p < 0.05). Waiting 12-weeks after CRT results in significantly more mrT downstaging, pCR and improved mrTRG. Since mrTRG is a validated predictor of disease free survival, undertaking surgery before maximal regression may be disadvantageous.

In The BMJ on Saturday 18 October, Ham wrote that “politicians are understandably reluctant to promise more than they can realistically deliver.”1 Contrastingly, on Sunday, Ed Miliband promised the public cancer diagnoses within seven days. On Monday, the Royal College of Radiologists’ press release said (I paraphrase) “blimey, you will need a lot more radiologists.” A weekend, let alone a week, is clearly …

BackgroundRadiotherapy is an alternative to cystectomy in patients with muscle-invasive bladder cancer. In other disease sites, synchronous chemoradiotherapy has been associated with increased local control and improved survival, as compared with radiotherapy alone.MethodsIn this multicenter, phase 3 trial, we randomly assigned 360 patients with muscle-invasive bladder cancer to undergo radiotherapy with or without synchronous chemotherapy. The regimen consisted of fluorouracil (500 mg per square meter of body-surface area per day) during fractions 1 to 5 and 16 to 20 of radiotherapy and mitomycin C (12 mg per square meter) on day 1. Patients were also randomly assigned to undergo either whole-bladder radiotherapy or modified-volume radiotherapy (in which the volume of bladder receiving full-dose radiotherapy was reduced) in a partial 2-by-2 factorial design (results not reported here). The primary end point was survival free of locoregional disease. Secondary end points included overall survival and toxic effects.ResultsAt 2 years, rates of locoregional disease-free survival were 67% (95% confidence interval [CI], 59 to 74) in the chemoradiotherapy group and 54% (95% CI, 46 to 62) in the radiotherapy group. With a median follow-up of 69.9 months, the hazard ratio in the chemoradiotherapy group was 0.68 (95% CI, 0.48 to 0.96; P = 0.03). Five-year rates of overall survival were 48% (95% CI, 40 to 55) in the chemoradiotherapy group and 35% (95% CI, 28 to 43) in the radiotherapy group (hazard ratio, 0.82; 95% CI, 0.63 to 1.09; P = 0.16). Grade 3 or 4 adverse events were slightly more common in the chemoradiotherapy group than in the radiotherapy group during treatment (36.0% vs. 27.5%, P = 0.07) but not during follow-up (8.3% vs. 15.7%, P = 0.07).ConclusionsSynchronous chemotherapy with fluorouracil and mitomycin C combined with radiotherapy significantly improved locoregional control of bladder cancer, as compared with radiotherapy alone, with no significant increase in adverse events. (Funded by Cancer Research U.K.; BC2001 Current Controlled Trials number, ISRCTN68324339.)

536^ Background: COIN-B is a trial of intermittent chemotherapy (ICT) plus intermittent cetuximab (C) vs ICT plus continuous C in the first-line treatment of aCRC. It complements the COIN trial by investigating how C might safely and effectively be added to an ICT strategy. Methods: Patients (pts) had measurable aCRC; no prior CT for metastases; WHO PS 0-2 and good organ function. Randomisation was: Arm D - continuous OxFU + weekly C for 12 wks then a planned break from all therapy; Arm E - OxFU + weekly C for 12 wks then weekly C. Upon RECIST progression on either arm, OxFU (or FU) plus C was restarted and continued until progression on maximal tolerated therapy. Prospective KRAS testing was introduced in May 2008. Primary outcome measure is Failure-Free Survival (FFS) at 10 months (mo) in KRAS-wt pts who had not progressed, died or failed the treatment strategy within 3 mo of randomisation. The trial was powered to differentiate between a desired 10-mo FFS rate of 50% and a minimum of 35%, in 136 pts (168 allowing for drop-outs). Secondary outcome measures included safety, overall survival (OS) and toxicity. Results: 169 KRAS-wt pts were randomised 07/07 to 06/10, 77 arm D / 92 arm E. Median age 64 years (IQR 55-70); 92% PS 0-1. In Arms D and E respectively, 65 (84%) and 67 (73%) pts were eligible for the primary analysis; 10-mo FFS rates were 48% vs 54% (one-sided 95% confidence limit 37% and 43% respectively). Median FFS was 12.0 vs 13.7 mo respectively (IQR 6.1-20.3 and 8.6-23.2). Median OS was 20.1 vs 18.4 mo. First CFI length was 3.7 mo vs 5.1 mo (IQR 2.5-6.2 and 2.5-8.9). In pre-planned exploratory analysis, median time to progression/death after chemo break was 3.1 mo (IQR 2.1-8.1) in Arm D and 6.0 mo (IQR 2.9-10.9) in Arm E. Toxicity was similar and only 1 arm D pt had G 3 hypersensitivity following C reintroduction. Analyses by BRAF & NRAS (tested retrospectively) will be presented. Conclusions: C was safely incorporated in 2 ICT strategies. Continuous C as maintenance was associated with a longer CFI and longer time to progression/death. This encouraging strategy of incorporating biological maintenance therapy needs validation in phase III trials.

Laparoscopic total mesorectal excision (TME) of locally advanced rectal cancer after long-course chemoradiotherapy (LCRT) is surgically and oncologically challenging. We have assessed the feasibility, timing, and short-term oncological outcome of laparoscopic TME after LCRT.

Colorectal DiseaseVolume 12, Issue 3 p. 269-270 MRI for the assessment of locally advanced rectal cancer – a window of opportunity T. Arulampalam, T. Arulampalam ICENI Centre, Colchester Hospital University NHS Foundation Trust, Colchester, Essex, UK.E-mail: [email protected]Search for more papers by this authorB. Sizer, B. Sizer ICENI Centre, Colchester Hospital University NHS Foundation Trust, Colchester, Essex, UK.E-mail: [email protected]Search for more papers by this authorN. Lacey, N. Lacey ICENI Centre, Colchester Hospital University NHS Foundation Trust, Colchester, Essex, UK.E-mail: [email protected]Search for more papers by this authorR. Motson, R. Motson ICENI Centre, Colchester Hospital University NHS Foundation Trust, Colchester, Essex, UK.E-mail: [email protected]Search for more papers by this author T. Arulampalam, T. Arulampalam ICENI Centre, Colchester Hospital University NHS Foundation Trust, Colchester, Essex, UK.E-mail: [email protected]Search for more papers by this authorB. Sizer, B. Sizer ICENI Centre, Colchester Hospital University NHS Foundation Trust, Colchester, Essex, UK.E-mail: [email protected]Search for more papers by this authorN. Lacey, N. Lacey ICENI Centre, Colchester Hospital University NHS Foundation Trust, Colchester, Essex, UK.E-mail: [email protected]Search for more papers by this authorR. Motson, R. Motson ICENI Centre, Colchester Hospital University NHS Foundation Trust, Colchester, Essex, UK.E-mail: [email protected]Search for more papers by this author First published: 17 February 2010 https://doi.org/10.1111/j.1463-1318.2009.02021.xRead the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. References 1 The MERCURY Study Group. Diagnostic accuracy of preoperative magnetic resonance imaging in predicting curative resection of rectal cancer: prospective observational study. BMJ 2006; 333: 779. 2 Suppiah A, Hunter IA, Cowley J, Garimella V, Cast J, Hartley JE, Monson JR. Magnetic resonance imaging accuracy in assessing tumour down-staging following chemoradiation in rectal cancer. Colorectal Dis 2009; 11: 249–53. 3 Sizer B, Arulampalam T, Austin R, Basu D, Lacey N, Menzies D, Motson R. Individualizing the interval between neoadjuvant chemoradiation with uracil-tegafur (UFT) and total mesorectal excision in magnetic resonance imaging (MRI) defined poor risk rectal cancer. J Clin Oncol 2007; 25: 14557. 4 Johnston DF, Lawrence KM, Sizer BF, Arulampalam TH, Motson RW, Dove E, Lacey N. Locally advanced rectal cancer: histopathological correlation and predictive accuracy of serial MRI after neoadjuvant chemoradiotherapy. Br J Radiol 2009; 82: 332–6. 5 Allen SD, Padhani AR, Dzik-Jurasz AS, Glynne-Jones R. Rectal Carcinoma: MRI with histological correlation before and after chemoradiation therapy. Am J Roentgenol 2007; 188: 442–51. 6 Kulkarni T, Gollins S, Maw A, Hobson P, Byrne R, Widdowson D. Magnetic resonance imaging in rectal cancer downstaged using neoadjuvant chemoradiation: accuracy of prediction of tumour stage and circumferential resection margin status. Colorectal Dis 2008; 188: 442–51. 7 Habr-Gama A, Perez RO, Proscurshin I, Campos FG, Nadalin W, Kiss D, Gama-Rodrigues J. Patterns of failure and survival for nonoperative treatment of stage c0 distal rectal cancer following neoadjuvant chemoradiation therapy. J Gastrointest Surg 2006; 10: 1319–28. 8 Sizer BF, Arulampalam T, Austin R, Lacey N, Menzies D, Motson R. MRI in predicting curative resection of rectal cancer. Defining a “window of opportunity” for laparoscopic surgery. BMJ 2006; 333: 808–9. Volume12, Issue3March 2010Pages 269-270 ReferencesRelatedInformation

Sir — We were interested to read the paper by Dhadda et al.[ 1 Dhadda A.S. Zaitoun A.M. Bessell E.M. Regression of rectal cancer with radiotherapy with or without concurrent capecitabine — optimising the timing of surgical resection. Clin Oncol. 2009; 21: 23-31 Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar ] on optimising the timing of surgical resection of rectal cancer after long-course radiotherapy (LCRT) by calculating ‘volume-halving times’. In their series of 106 patients, they noted that the median tumour volume was 54 cm3 and the median tumour-halving time was 14 days (i.e. 10 volume-halving times, 140 days), such that an interval of 20 weeks after the start of radiotherapy would be required to achieve tumour regression to <0.1 cm3.

14557 Background: The importance of achieving negative circumferential resection margins (CRM) for patients (pts) with MRI - defined poor - risk rectal cancer (PRRC) has led to an increase in the use of pre-operative chemoradiotherapy (CRT) employing long fractionation schedules, usually with an interval of 4 to 6 weeks before surgery. We report our experience of using serial MRI post CRT to optimise the timing of total mesorectal excision (TME) surgery at maximal radiological response for each pt. Methods: Data was collected prospectively from 4/03 to 10/06 on toxicity and response for 50 consecutive patients ( 36 male; median age 64 years, range 39 - 76 years), 47 with biopsy - proven PRRC by MRI criteria (threatened / definite CRM involvement, T3 > 5mm into perirectal fat, T4 tumours, and / or multiple nodes) and 3 pts with localised recurrence after previous anterior resection. Pts received 2 phase, conformal external beam radiotherapy ( 45 - 50.4 Gy / 25 - 28 fractions / 5 weeks), concurrently with their choice of either oral UFT (n = 44, 88%), 240mg/m2/d d 1 - 28 with Leucovorin (LV) 90mg/d or iv bolus 5 FU (n= 6) 300mg/m2 d 1,8,15,22,29 with LV 20 mg/m2). Clinical re-assessment q 2 wkly from 4 weeks post CRT, with serial MRIs 4-weekly, from 6 wks. Results: 48 pts (96%) completed CRT, worst toxicity, diarrhoea Grade 3, 6%. Mean number of MRI scans per pt post CRT 1.48, with response seen in 46 pts (92%), of whom 43 (86%) underwent resection, 27 (63%) of which were performed laparoscopically. Median time to surgery was 11 weeks (range 8 to 15 wks). 37pts (86% of those undergoing surgery) achieved R0 resection, mean CRM 6.1mm, mean no. of identifiable lymph nodes 6.4, most frequent pathology ypT3 pN0 26%, pCR 16%, Tmic, 21%. Surgical morbidities included small bowel adhesions requiring laparotomy 8%, infection/abscess 14%. Post-operative mortality 5%. 1 PRRC pt developed liver metastases prior to surgery. Conclusions: CRT with UFT/LV is well tolerated and effective in achieving substantial tumour regression pre-operatively for PRRC. The optimal timing of surgery post CRT at maximal response can be documented with serial MRI, resulting in a high rate of R0 resections. Laparoscopic TME is feasible in this group of pts. [Table: see text]

EDITOR—The MERCURY Study Group provides clear evidence that preoperative magnetic resonance imaging can accurately predict surgical resection margins,1 and its work in particular, has already led to a paradigm shift in the preoperative investigation and treatment of rectal cancer, at least in the United Kingdom. This is at least implicitly acknowledged in that both previous letters focus on magnetic resonance imaging in …

3631 Background: Tegafur-uracil (UFT) is an effective oral fluoropyrimidine for patients with mCRC. Aims of this prospective phase II study were to evaluate quality of life (QoL), patient preference and healthcare resource use in patients receiving oral UFT/LV or i.v. 5-FU/LV as first-line therapy for mCRC. Safety and efficacy were also assessed. Methods: 243 patients in 3 countries (Austria, Italy and UK) were randomized in a 2:1 ratio to receive either UFT 300mg/m2/d + LV 90mg/d for 28d q5w, or i.v. 5-FU 425mg/m2/d + LV 20mg/m2/d for 5d q4w. Patients were assessed at baseline and every cycle for symptoms, adverse events (AEs), and overall response rate (ORR). QoL was evaluated using EORTC QLQ-C30, and patients completed a preference questionnaire at baseline, end of cycle 1, and end of study. Data on hospital attendances (in- and out-patient), physician visits, concomitant medication use and other healthcare resources were collected for every cycle and during study follow up. Results: 162 patients received UFT/LV (median 3 cycles) and 81 i.v. bolus 5-FU/LV (median 4 cycles). Patient demographics were similar in both groups: median age was 70y (range 39–83) for UFT/LV and 69y (41–80) for 5-FU/LV; 92% of patients were ECOG PS ≤1. QoL was maintained in the UFT/LV group with little variation across time whereas QoL deteriorated with 5-FU/LV. Most patients in the UFT/LV (85–95%) and 5-FU/LV (49–66%) groups stated a preference for oral treatment with the most common reason being ‘taken at home’ (83%). Fewer UFT/LV patients had one or more hospitalizations for AEs (21% vs. 36%). Clinical benefit (ORR+SD) was 32% with UFT/LV (41% evaluable for response) and 32% with 5-FU/LV (45% evaluable). Median time to disease progression was 173d (95% CI 140–199) for UFT/LV and 168d (95% CI 133–205) for 5-FU/LV. Median overall survival was 385d (95% CI 296–472) for UFT/LV and 330d (95% CI 252–484) for 5-FU/LV. Conclusions: UFT with LV has comparable efficacy to i.v. 5-FU/LV in first-line mCRC, with the advantages of favorable QoL, patient preference for oral treatment, and fewer hospitalizations for managing AEs. [Table: see text]