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Objective: Improving prognostication to direct personalised therapy remains an unmet need. This study prospectively investigated promising CT, genetic, and immunohistochemical markers to improve the prediction of colorectal cancer recurrence., Material and Methods: This multicentre trial (ISRCTN 95037515) recruited patients with primary colorectal cancer undergoing CT staging from 13 hospitals. Follow-up identified cancer recurrence and death. A baseline model for cancer recurrence at 3 years was developed from pre-specified clinicopathological variables (age, sex, tumour-node stage, tumour size, location, extramural venous invasion, and treatment). Then, CT perfusion (blood flow, blood volume, transit time and permeability), genetic (RAS, RAF, and DNA mismatch repair), and immunohistochemical markers of angiogenesis and hypoxia (CD105, vascular endothelial growth factor, glucose transporter protein, and hypoxia-inducible factor) were added to assess whether prediction improved over tumour-node staging alone as the main outcome measure., Results: Three hundred twenty-six of 448 participants formed the final cohort (226 male; mean 66 ± 10 years. 227 (70%) had ≥ T3 stage cancers; 151 (46%) were node-positive; 81 (25%) developed subsequent recurrence. The sensitivity and specificity of staging alone for recurrence were 0.56 [95% CI: 0.44, 0.67] and 0.58 [0.51, 0.64], respectively. The baseline clinicopathologic model improved specificity (0.74 [0.68, 0.79], with equivalent sensitivity of 0.57 [0.45, 0.68] for high vs medium/low-risk participants. The addition of prespecified CT perfusion, genetic, and immunohistochemical markers did not improve prediction over and above the clinicopathologic model (sensitivity, 0.58-0.68; specificity, 0.75-0.76)., Conclusion: A multivariable clinicopathological model outperformed staging in identifying patients at high risk of recurrence. Promising CT, genetic, and immunohistochemical markers investigated did not further improve prognostication in rigorous prospective evaluation., Clinical Relevance Statement: A prognostic model based on clinicopathological variables including age, sex, tumour-node stage, size, location, and extramural venous invasion better identifies colorectal cancer patients at high risk of recurrence for neoadjuvant/adjuvant therapy than stage alone., Key Points: Identification of colorectal cancer patients at high risk of recurrence is an unmet need for treatment personalisation. This model for recurrence, incorporating many patient variables, had higher specificity than staging alone. Continued optimisation of risk stratification schema will help individualise treatment plans and follow-up schedules., (© 2024. The Author(s).)

Background Most radiologists reporting CT colonography (CTC) do not undergo compulsory performance accreditation, potentially lowering diagnostic sensitivity. Purpose To determine whether 1-day individualized training in CTC reporting improves diagnostic sensitivity of experienced radiologists for 6-mm or larger lesions, the durability of any improvement, and any associated factors. Materials and Methods This prospective, multicenter cluster-randomized controlled trial was performed in National Health Service hospitals in England and Wales between April 2017 and January 2020. CTC services were cluster randomized into intervention (1-day training plus feedback) or control (no training or feedback) arms. Radiologists in the intervention arm attended a 1-day workshop focusing on CTC reporting pitfalls with individualized feedback. Radiologists in the control group received no training. Sensitivity for 6-mm or larger lesions was tested at baseline and 1, 6, and 12 months thereafter via interpretation of 10 CTC scans at each time point. The primary outcome was the mean difference in per-lesion sensitivity between arms at 1 month, analyzed using multilevel regression after adjustment for baseline sensitivity. Secondary outcomes included per-lesion sensitivity at 6- and 12-month follow-up, sensitivity for flat neoplasia, and effect of prior CTC experience. Results A total of 69 hospitals were randomly assigned to the intervention (31 clusters, 80 radiologists) or control (38 clusters, 59 radiologists) arm. Radiologists were experienced (median, 500-999 CTC scans interpreted) and reported CTC scans routinely (median, 151-200 scans per year). One-month sensitivity improved after intervention (66.4% [659 of 992]) compared with sensitivity in the control group (42.4% [278 of 655]; difference = 20.8%; 95% CI: 14.6, 27.0; P < .001). Improvements were maintained at 6 (66.4% [572 of 861] vs 50.5% [283 of 560]; difference = 13.0%; 95% CI: 7.4, 18.5; P < .001) and 12 (63.7% [310 of 487] vs 44.4% [187 of 421]; difference = 16.7%; 95% CI: 10.3, 23.1; P < .001) months. This beneficial effect applied to flat lesions (difference = 22.7%; 95% CI: 15.5, 29.9; P < .001) and was independent of career experience (≥1500 CTC scans: odds ratio = 1.09; 95% CI: 0.88, 1.36; P = .22). Conclusion For radiologists evaluating CT colonography studies, a 1-day training intervention yielded sustained improvement in detection of clinically relevant colorectal neoplasia, independent of previous career experience. Clinical trial registration no. NCT02892721 © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Pickhardt in this issue. An earlier incorrect version appeared online and in print. This article was corrected on February 28, 2022.

Purpose: This study assesses the potential for vascular-metabolic imaging with FluoroDeoxyGlucose (FDG)-Positron Emission Tomography/Computed Tomography (PET/CT) perfusion to provide markers of prognosis specific to the site and stage of colorectal cancer., Methods: This prospective observational study comprised of participants with suspected colorectal cancer categorized as either (a) non-metastatic colon cancer (M0colon), (b) non-metastatic rectal cancer (M0rectum), or (c) metastatic colorectal cancer (M+). Combined FDG-PET/CT perfusion imaging was successfully performed in 286 participants (184 males, 102 females, age: 69.60 ± 10 years) deriving vascular and metabolic imaging parameters. Vascular and metabolic imaging parameters alone and in combination were investigated with respect to overall survival., Results: A vascular-metabolic signature that was significantly associated with poorer survival was identified for each patient group: M0colon - high Total Lesion Glycolysis (TLG) with increased Permeability Surface Area Product/Blood Flow (PS/BF), Hazard Ratio (HR) 3.472 (95% CI: 1.441-8.333), p = 0.006; M0rectum - high Metabolic Tumour Volume (MTV) with increased PS/BF, HR 4.567 (95% CI: 1.901-10.970), p = 0.001; M+ participants, high MTV with longer Time To Peak (TTP) enhancement, HR 2.421 (95% CI: 1.162-5.045), p = 0.018. In participants with stage 2 colon cancer as well as those with stage 3 rectal cancer, the vascular-metabolic signature could stratify the prognosis of these participants., Conclusion: Vascular and metabolic imaging using FDG-PET/CT can be used to synergise prognostic markers. The hazard ratios suggest that the technique may have clinical utility., (© 2021. The Author(s).)

The incidence of gastrointestinal (GI) malignancy is increasing worldwide. In particular, there is a concerning rise in incidence of GI cancer in younger adults. Direct endoscopic visualisation of luminal tumour sites requires invasive procedures, which are associated with certain risks, but remain necessary because of limitations in current imaging techniques and the continuing need to obtain tissue for diagnosis and genetic analysis; however, management of GI cancer is increasingly reliant on non-invasive, radiological imaging to diagnose, stage, and treat these malignancies. Oesophageal, gastric, and colorectal malignancies require specialist investigation and treatment due to the complex nature of the anatomy, biology, and subsequent treatment strategies. As cancer imaging techniques develop, many opportunities to improve tumour detection, diagnostic accuracy and treatment monitoring present themselves. This review article aims to report current imaging practice, advances in various radiological modalities in relation to GI luminal tumour sites and describes opportunities for GI radiologists to improve patient outcomes., (Crown Copyright © 2021. Published by Elsevier Ltd. All rights reserved.)

People undergoing investigations for suspected cancer have to undergo a number of investigations before they know their full diagnosis and treatment plan. We examined predictors of distress among patients undergoing staging investigations for suspected colorectal or lung cancer. Patients were prospectively recruited to two multi-centre trials comparing WB-MRI with standard scans. Patients completed a questionnaire, administered at trial recruitment, measuring demographic and psychological variables (n = 129, 66 colorectal, 63 lung; median age 66.4, range: 31-89). Predictors of distress were analysed using logistic regression. Forty percent of patients reported high distress (a score of 4 or higher on the GHQ-12). Higher deprivation and greater intolerance of uncertainty (IU) predicted high distress in both unadjusted (low deprivation: OR 0.352, 95% CIs 0.144 to 0.860, p = 0.022; IU: OR 1.972, 95% CIs: 1.357 to 2.865, p < 0.001) and adjusted analyses (low deprivation: OR 0.243, 95% CIs 0.083 to 0.714, p = 0.010; IU: OR 2.231, 95% CIs 1.429 to 3.485, p < 0.001). Age, gender, presence of comorbid illness, cancer type, probable knowledge of cancer diagnosis, and a final diagnosis of cancer did not predict high distress. Future research should examine how to reduce distress in patients undergoing investigations for cancer, particularly among those who find uncertainty difficult to manage.

Introduction: Whole body magnetic resonance imaging (WB-MRI) may be more efficient in staging cancers, but can be harder for patients to tolerate. We examined predictors of patient preference for WB-MRI vs. CT/ PET-CT for staging colorectal or lung cancer., Methods: Patients recruited prospectively to two multicentre trials comparing diagnostic accuracy of WB-MRI with standard staging scans were sent two questionnaires: the first, administered at trial registration, captured demographics, educational level and comorbidities; the second, administered after staging completion, measured emotional distress (GHQ-12), positive mood (PANAS), perceived scan burden, patients' beliefs about WB-MRI, and preference for either WB-MRI or CT (colorectal trial), WB-MRI or PET-CT (lung trial). Preference for WB-MRI or CT/ PET-CT was analysed using logistic regression., Results: Baseline and post-staging questionnaires were completed by 97 and 107 patients, respectively. Overall, 56/107 (52%) preferred WB-MRI over standard scans and were more likely to have no additional comorbidities, higher positive mood, greater awareness of potential benefits of WB-MRI and lower levels of perceived WB-MRI scan burden. In adjusted analyses, only awareness of potential WB-MRI benefits remained a significant predictor (OR: 1.516, 95% CIs 1.006-2.284, P = 0.047). Knowledge that WB-MRI does not use radiation predicted preference (adjusted OR: 3.018, 95% CIs 1.099-8.288, P = 0.032), although only 45/107 (42%) patients were aware of this attribute., Conclusions: A small majority of patients undergoing staging of colorectal or lung cancer prefer WB-MRI to CT/ PET-CT. Raising awareness of the potential benefits of WB-MRI, notably lack of ionizing radiation, could influence preference., (© 2020 The Authors. Journal of Medical Imaging and Radiation Oncology published by John Wiley & Sons Australia, Ltd on behalf of Royal Australian and New Zealand College of Radiologists.)

Aim: To evaluate the association between the image quality of cancer staging whole-body magnetic resonance imaging (WB-MRI) and patient demographics, distress, and perceived scan burden., Materials and Methods: A sample of patients recruited prospectively to multicentre trials comparing WB-MRI with standard scans for staging lung and colorectal cancer were invited to complete two questionnaires. The baseline questionnaire, administered at recruitment, collated data on demographics, distress and co-morbidity. The follow-up questionnaire, completed after staging investigations, measured perceived WB-MRI scan burden (scored 1 low to 7 high). WB-MRI anatomical coverage, and technical quality was graded by a radiographic technician and grading combined to categorise the scan as "optimal", "sub-optimal" or "degraded". A radiologist categorised 30 scans to test interobserver agreement. Data were analysed using the chi-square, Fisher's exact, t-tests, and multinomial regression., Results: One hundred and fourteen patients were included in the study (53 lung, 61 colorectal; average age 65.3 years, SD=11.8; 66 men [57.9%]). Overall, 45.6% (n=52), scans were classified as "optimal" quality, 39.5% (n=45) "sub-optimal", and 14.9% (n=17) as "degraded". In adjusted analyses, greater deprivation level and higher patient-reported scan burden were both associated with a higher likelihood of having a sub-optimal versus an optimal scan (odds ratio [OR]: 4.465, 95% confidence interval [CI]: 1.454 to 13.709, p=0.009; OR: 1.987, CI: 1.153 to 3.425, p=0.013, respectively). None of the variables predicted the likelihood of having a degraded scan., Conclusions: Deprivation and patients' perceived experience of the WB-MRI are related to image quality. Tailored protocols and individualised patient management before and during WB-MRI may improve image quality., (Copyright © 2019 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Background: Whole-body magnetic resonance imaging is advocated as an alternative to standard pathways for staging cancer., Objectives: The objectives were to compare diagnostic accuracy, efficiency, patient acceptability, observer variability and cost-effectiveness of whole-body magnetic resonance imaging and standard pathways in staging newly diagnosed non-small-cell lung cancer (Streamline L) and colorectal cancer (Streamline C)., Design: The design was a prospective multicentre cohort study., Setting: The setting was 16 NHS hospitals., Participants: Consecutive patients aged ≥ 18 years with histologically proven or suspected colorectal (Streamline C) or non-small-cell lung cancer (Streamline L)., Interventions: Whole-body magnetic resonance imaging. Standard staging investigations (e.g. computed tomography and positron emission tomography-computed tomography)., Reference Standard: Consensus panel decision using 12-month follow-up data., Main Outcome Measures: The primary outcome was per-patient sensitivity difference between whole-body magnetic resonance imaging and standard staging pathways for metastasis. Secondary outcomes included differences in specificity, the nature of the first major treatment decision, time and number of tests to complete staging, patient experience and cost-effectiveness., Results: Streamline C - 299 participants were included. Per-patient sensitivity for metastatic disease was 67% (95% confidence interval 56% to 78%) and 63% (95% confidence interval 51% to 74%) for whole-body magnetic resonance imaging and standard pathways, respectively, a difference in sensitivity of 4% (95% confidence interval -5% to 13%; p  = 0.51). Specificity was 95% (95% confidence interval 92% to 97%) and 93% (95% confidence interval 90% to 96%) respectively, a difference of 2% (95% confidence interval -2% to 6%). Pathway treatment decisions agreed with the multidisciplinary team treatment decision in 96% and 95% of cases, respectively, a difference of 1% (95% confidence interval -2% to 4%). Time for staging was 8 days (95% confidence interval 6 to 9 days) and 13 days (95% confidence interval 11 to 15 days) for whole-body magnetic resonance imaging and standard pathways, respectively, a difference of 5 days (95% confidence interval 3 to 7 days). The whole-body magnetic resonance imaging pathway was cheaper than the standard staging pathway: £216 (95% confidence interval £211 to £221) versus £285 (95% confidence interval £260 to £310). Streamline L - 187 participants were included. Per-patient sensitivity for metastatic disease was 50% (95% confidence interval 37% to 63%) and 54% (95% confidence interval 41% to 67%) for whole-body magnetic resonance imaging and standard pathways, respectively, a difference in sensitivity of 4% (95% confidence interval -7% to 15%; p  = 0.73). Specificity was 93% (95% confidence interval 88% to 96%) and 95% (95% confidence interval 91% to 98%), respectively, a difference of 2% (95% confidence interval -2% to 7%). Pathway treatment decisions agreed with the multidisciplinary team treatment decision in 98% and 99% of cases, respectively, a difference of 1% (95% confidence interval -2% to 4%). Time for staging was 13 days (95% confidence interval 12 to 14 days) and 19 days (95% confidence interval 17 to 21 days) for whole-body magnetic resonance imaging and standard pathways, respectively, a difference of 6 days (95% confidence interval 4 to 8 days). The whole-body magnetic resonance imaging pathway was cheaper than the standard staging pathway: £317 (95% confidence interval £273 to £361) versus £620 (95% confidence interval £574 to £666). Participants generally found whole-body magnetic resonance imaging more burdensome than standard imaging but most participants preferred the whole-body magnetic resonance imaging staging pathway if it reduced time to staging and/or number of tests., Limitations: Whole-body magnetic resonance imaging was interpreted by practitioners blinded to other clinical data, which may not fully reflect how it is used in clinical practice., Conclusions: In colorectal and non-small-cell lung cancer, the whole-body magnetic resonance imaging staging pathway has similar accuracy to standard staging pathways, is generally preferred by patients, improves staging efficiency and has lower staging costs. Future work should address the utility of whole-body magnetic resonance imaging for treatment response assessment., Trial Registration: Current Controlled Trials ISRCTN43958015 and ISRCTN50436483., Funding: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 23, No. 66. See the NIHR Journals Library website for further project information., Competing Interests: Stuart A Taylor reports personal fees from Robarts Clinical Trials Inc. (London, ON, Canada) outside the submitted work. Andrea Rockall reports personal fees from Guerbet (Paris, France) outside the submitted work. Vicky Goh and Anwar Padhani report grants from Siemens AG (Erlangen, Germany) outside the submitted work. Steve Halligan reports non-financial support from iCad Inc. (Nashua, NH, USA) outside the submitted work and was a member of the Health Technology Assessment (HTA) commissioning board (2008–14). Stephen Morris declares past membership of the National Institute for Health Research (NIHR) HTA Clinical Evaluation and Trials Board (2007–9), HTA Commissioning Board (2009–13), Public Health Research Board (2011–17), Health Services and Delivery Research (HSDR) Commissioning Board (2014–16) and HSDR Board (2014–18), and current membership of the NIHR Programme Grants for Applied Research expert subpanel (2015–present) and HSDR Evidence Synthesis Sub Board (2016–present).

Objectives: To determine the importance placed by patients on attributes associated with whole-body MRI (WB-MRI) and standard cancer staging pathways and ascertain drivers of preference., Methods: Patients recruited to two multi-centre diagnostic accuracy trials comparing WB-MRI with standard staging pathways in lung and colorectal cancer were invited to complete a discrete choice experiment (DCE), choosing between a series of alternate pathways in which 6 attributes (accuracy, time to diagnosis, scan duration, whole-body enclosure, radiation exposure, total scan number) were varied systematically. Data were analysed using a conditional logit regression model and marginal rates of substitution computed. The relative importance of each attribute and probabilities of choosing WB-MRI-based pathways were estimated., Results: A total of 138 patients (mean age 65, 61% male, lung n = 72, colorectal n = 66) participated (May 2015 to September 2016). Lung cancer patients valued time to diagnosis most highly, followed by accuracy, radiation exposure, number of scans, and time in the scanner. Colorectal cancer patients valued accuracy most highly, followed by time to diagnosis, radiation exposure, and number of scans. Patients were willing to wait 0.29 (lung) and 0.45 (colorectal) weeks for a 1% increase in pathway accuracy. Patients preferred WB-MRI-based pathways (probability 0.64 [lung], 0.66 [colorectal]) if they were equivalent in accuracy, total scan number, and time to diagnosis compared with a standard staging pathway., Conclusions: Staging pathways based on first-line WB-MRI are preferred by the majority of patients if they at least match standard pathways for diagnostic accuracy, time to diagnosis, and total scan number., Key Points: • WB-MRI staging pathways are preferred to standard pathways by the majority of patients provided they at least match standard staging pathways for accuracy, total scan number, and time to diagnosis. • For patients with lung cancer, time to diagnosis was the attribute valued most highly, followed by accuracy, radiation dose, number of additional scans, and time in a scanner. Preference for patients with colorectal cancer was similar. • Most (63%) patients were willing to trade attributes, such as faster diagnosis, for improvements in pathway accuracy and reduced radiation exposure.

Background: Whole-body MRI (WB-MRI) could be an alternative to multimodality staging of colorectal cancer, but its diagnostic accuracy, effect on staging times, number of tests needed, cost, and effect on treatment decisions are unknown. We aimed to prospectively compare the diagnostic accuracy and efficiency of WB-MRI-based staging pathways with standard pathways in colorectal cancer., Methods: The Streamline C trial was a prospective, multicentre trial done in 16 hospitals in England. Eligible patients were 18 years or older, with newly diagnosed colorectal cancer. Exclusion criteria were severe systemic disease, pregnancy, contraindications to MRI, or polyp cancer. Patients underwent WB-MRI, the result of which was withheld until standard staging investigations were complete and the first treatment decision made. The multidisciplinary team recorded its treatment decision based on standard investigations, then on the WB-MRI staging pathway (WB-MRI plus additional tests generated), and finally on all tests. The primary outcome was difference in per-patient sensitivity for metastases between standard and WB-MRI staging pathways against a consensus reference standard at 12 months, in the per-protocol population. Secondary outcomes were difference in per-patient specificity for metastatic disease detection between standard and WB-MRI staging pathways, differences in treatment decisions, staging efficiency (time taken, test number, and costs), and per-organ sensitivity and specificity for metastases and per-patient agreement for local T and N stage. This trial is registered with the International Standard Randomised Controlled Trial registry, number ISRCTN43958015, and is complete., Findings: Between March 26, 2013, and Aug 19, 2016, 1020 patients were screened for eligibility. 370 patients were recruited, 299 of whom completed the trial; 68 (23%) had metastasis at baseline. Pathway sensitivity was 67% (95% CI 56 to 78) for WB-MRI and 63% (51 to 74) for standard pathways, a difference in sensitivity of 4% (-5 to 13, p=0·51). No adverse events related to imaging were reported. Specificity did not differ between WB-MRI (95% [95% CI 92-97]) and standard pathways (93% [90-96], p=0·48). Agreement with the multidisciplinary team's final treatment decision was 96% for WB-MRI and 95% for the standard pathway. Time to complete staging was shorter for WB-MRI (median, 8 days [IQR 6-9]) than for the standard pathway (13 days [11-15]); a 5-day (3-7) difference. WB-MRI required fewer tests (median, one [95% CI 1 to 1]) than did standard pathways (two [2 to 2]), a difference of one (1 to 1). Mean per-patient staging costs were £216 (95% CI 211-221) for WB-MRI and £285 (260-310) for standard pathways., Interpretation: WB-MRI staging pathways have similar accuracy to standard pathways and reduce the number of tests needed, staging time, and cost., Funding: UK National Institute for Health Research., (Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objective: To evaluate perceived patient burden and acceptability of whole body MRI (WB-MRI) compared to standard staging investigations, and identify predictors of reduced tolerance., Methods: Patients recruited to multicentre trials comparing WB-MRI with standard staging scans for lung and colorectal cancer were invited to complete two questionnaires: a baseline questionnaire at recruitment, measuring demographics, comorbidities, and distress; and a follow-up questionnaire after staging, measuring recovery time, comparative acceptability/satisfaction between WB-MRI and CT (colorectal cancer) and PET-CT (lung cancer), and perceived scan burden (scored 1, low; 7, high).  Results: 115 patients (median age 66.3 years; 67 males) completed follow up and 103 baseline questionnaires. 69 (63.9%) reported "immediate" recovery from WB-MRI and 73 (65.2%) judged it "very acceptable". Perceived WB-MRI burden was greater than for CT (p < 0.001) and PET-CT (p < 0.001). High distress and comorbidities were associated with greater WB-MRI burden in adjusted analyses, with deprivation only approaching significance (adjusted regression β = 0.223, p = 0.025; β = 0.191, p = 0.048; β = -0.186, p = 0.059 respectively). Age (p = 0.535), gender (p = 0.389), ethnicity (p = 0.081) and cancer type (p = 0.201) were not predictive of WB-MRI burden., Conclusion:  WB-MRI is marginally less acceptable and more burdensome than standard scans, particularly for patients with pre-existing distress and comorbidities.  Advances in knowledge: This research shows that WB-MRI scan burden, although low, is higher than for current staging modalities among patients with suspected colorectal or lung cancer. Psychological and physical comorbidities adversely impact on patient experience of WB-MRI. Patients with high distress or comorbid illness may need additional support to undergo a WB-MRI.

Background: CT colonography is highly sensitive for colorectal cancer, but interval or post-imaging colorectal cancer rates (diagnosis of cancer after initial negative CT colonography) are unknown, as are their underlying causes. We did a systematic review and meta-analysis of post-CT colonography and post-imaging colorectal cancer rates and causes to address this gap in understanding., Methods: We systematically searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials. We included randomised, cohort, cross-sectional, or case-control studies published between Jan 1, 1994, and Feb 28, 2017, using CT colonography done according to international consensus standards with the aim of detecting cancer or polyps, and reporting post-imaging colorectal cancer rates or sufficient data to allow their calculation. We excluded studies in which all CT colonographies were done because of incomplete colonoscopy or if CT colonography was done with knowledge of colonoscopy findings. We contacted authors of component studies for additional data where necessary for retrospective CT colonography image review and causes for each post-imaging colorectal cancer. Two independent reviewers extracted data from the study reports. Our primary outcome was prevalence of post-imaging colorectal cancer 36 months after CT colonography. We used random-effects meta-analysis to estimate pooled post-imaging colorectal cancer rates, expressed using the total number of cancers and total number of CT colonographies as denominators, and per 1000 person-years. This study is registered with PROSPERO, number CRD42016042437., Findings: 2977 articles were screened and 12 studies were eligible for analysis. These studies reported data for 19 867 patients (aged 18-96 years; of 11 590 with sex data available, 6532 [56%] were female) between March, 2002, and May, 2015. At a mean of 34 months' follow-up (range 3-128·4 months), CT colonography detected 643 colorectal cancers. 29 post-imaging colorectal cancers were subsequently diagnosed. The pooled post-imaging colorectal cancer rate was 4·42 (95% CI 3·03-6·42) per 100 cancers detected, corresponding to 1·61 (1·11-2·33) post-imaging colorectal cancers per 1000 CT colonographies or 0·64 (0·44-0·92) post-imaging colorectal cancers per 1000 person-years. Heterogeneity was low (I 2 =0%). 17 (61%) of 28 post-imaging colorectal cancers were attributable to perceptual error and were visible in retrospect., Interpretation: CT colonography does not lead to an excess of post-test cancers relative to colonoscopy within 3-5 years, and the low 5-year post-imaging colorectal cancer rate confirms that the recommended screening interval of 5 years is safe. Since most post-imaging colorectal cancers arise from perceptual errors, radiologist training and quality assurance could help to reduce post-imaging colorectal cancer rates., Funding: St Mark's Hospital Foundation and the UK National Institute for Health Research via the UCL/UCLH Biomedical Research Centre., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background and Aims: Rapid and accurate cancer staging following diagnosis underpins patient management, in particular the identification of distant metastatic disease. Current staging guidelines recommend sequential deployment of various imaging platforms such as computerised tomography (CT) and positron emission tomography (PET) which can be time and resource intensive and onerous for patients. Recent studies demonstrate that whole body magnetic resonance Imaging (WB-MRI) may stage cancer efficiently in a single visit, with potentially greater accuracy than current staging investigations. The Streamline trials aim to evaluate whether WB-MRI increases per patient detection of metastases in non-small cell lung and colorectal cancer compared to standard staging pathways., Methods: The Streamline trials are multicentre, non-randomised, single-arm, prospective diagnostic accuracy studies with a novel design to capture patient management decisions during staging pathways. The two trials recruit adult patients with proven or highly suspected new diagnosis of primary colorectal (Streamline C) or non-small cell lung cancer (Streamline L) referred for staging. Patients undergo WB-MRI in addition to standard staging investigations. Strict blinding protocols are enforced for those interpreting the imaging. A first major treatment decision is made by the multi-disciplinary team prior to WB-MRI revelation based on standard staging investigations only, then based on the WB-MRI and any additional tests precipitated by WB-MRI, and finally based on all available test results. The reference standard is derived by a multidisciplinary consensus panel who assess 12 months of follow-up data to adjudicate on the TNM stage at diagnosis. Health psychology assessment of patients' experiences of the cancer staging pathway will be undertaken via interviews and questionnaires. A cost (effectiveness) analysis of WB-MRI compared to standard staging pathways will be performed., Discussion: We describe a novel approach to radiologist and clinician blinding to ascertain the 'true' diagnostic accuracy of differing imaging pathways and discuss our approach to assessing the impact of WB-MRI on clinical decision making in real-time. The Streamline trials will compare WB-MRI and standard imaging pathways in the same patients, thereby informing the most accurate and efficient approach to staging., Trial Registration: Streamline C ISRCTN43958015 (registered 25/7/2012). Streamline L ISRCTN50436483 (registered 31/7/2012).

Background Screening participants with abnormal faecal occult blood test results who do not attend further testing are at high risk of colorectal cancer, yet little is known about their reasons for non-attendance. Methods We conducted a medical record review of 170 patients from two English Bowel Cancer Screening Programme centres who had abnormal guaiac faecal occult blood test screening tests between November 2011 and April 2013 but did not undergo colonoscopy. Using information from patient records, we coded and categorized reasons for non-attendance. Results Of the 170 patients, 82 were eligible for review, of whom 66 had at least one recorded reason for lack of colonoscopy follow-up. Reasons fell into seven main categories: (i) other commitments, (ii) unwillingness to have the test, (iii) a feeling that the faecal occult blood test result was a false positive, (iv) another health issue taking priority, (v) failing to complete bowel preparation, (vi) practical barriers (e.g. lack of transport), and (vii) having had or planning colonoscopy elsewhere. The most common single reasons were unwillingness to have a colonoscopy and being away. Conclusions We identify a range of apparent reasons for colonoscopy non-attendance after a positive faecal occult blood test screening. Education regarding the interpretation of guaiac faecal occult blood test findings, offer of alternative confirmatory test options, and flexibility in the timing or location of subsequent testing might decrease non-attendance of diagnostic testing following positive faecal occult blood test.

Objective: To investigate patient experience of CT colonography (CTC) and colonoscopy in a national screening programme., Methods: Retrospective analysis of patient experience postal questionnaires. We included screenees from a fecal occult blood test (FOBt) based screening programme, where CTC was performed when colonoscopy was incomplete or deemed unsuitable. We analyzed questionnaire responses concerning communication of test risks, test-related discomfort and post-test pain, as well as complications. CTC and colonoscopy responses were compared using multilevel logistic regression., Results: Of 67,114 subjects identified, 52,805 (79 %) responded. Understanding of test risks was lower for CTC (1712/1970 = 86.9 %) than colonoscopy (48783/50975 = 95.7 %, p < 0.0001). Overall, a slightly greater proportion of screenees found CTC unexpectedly uncomfortable (506/1970 = 25.7 %) than colonoscopy (10,705/50,975 = 21.0 %, p < 0.0001). CTC was tolerated well as a completion procedure for failed colonoscopy (unexpected discomfort; CTC = 26.3 %: colonoscopy = 57.0 %, p < 0.001). Post-procedural pain was equally common (CTC: 288/1970,14.6 %, colonoscopy: 7544/50,975,14.8 %; p = 0.55). Adverse event rates were similar in both groups (CTC: 20/2947 = 1.2 %; colonoscopy: 683/64,312 = 1.1 %), but generally less serious with CTC., Conclusions: Even though CTC was reserved for individuals either unsuitable for or unable to complete colonoscopy, we found only small differences in test-related discomfort. CTC was well tolerated as a completion procedure and was extremely safe. CTC can be delivered across a national screening programme with high patient satisfaction., Key Points: • High patient satisfaction at CTC is deliverable across a national screening programme. • Patients who cannot tolerate screening colonoscopy are likely to find CTC acceptable. • CTC is extremely safe; complications are rare and almost never serious. • Patients may require more detailed information regarding the expected discomfort of CTC.

Background and Study Aims: Terminal digit preference bias for "pleasing" numbers has been described in many areas of medicine. The aim of this study was to determine whether endoscopists, radiologists, and pathologists exhibit such bias when measuring colorectal polyp diameters., Methods: Colorectal polyp diameters measured at endoscopy, computed tomographic colonography (CTC), and histopathology were collated from a colorectal cancer screening program and two parallel multicenter randomized trials. Smoothing models were fitted to the data to estimate the expected number of polyps at 1-mm increments, assuming no systematic measurement bias. The difference between the expected and observed numbers of polyps was calculated for each terminal digit using statistical modeling. The impact of measurement bias on per-patient detection rates of polyps ≥ 10 mm was estimated for each modality., Results: A total of 92 124 individual polyps were measured by endoscopy (91 670 screening and 454 from trials), 2385 polyps were measured by CTC (1664 screening, 721 trials), and 79 272 were measured by histopathology (78 783 screening, 489 trials). Clustering of polyp diameter measurements at 5-mm intervals was demonstrated for all modalities, both in the screening program and the trials. The statistical models estimated that per-patient detection rates of polyps ≥ 10 mm were over-inflated by 2.4 % for endoscopy, 3.1 % for CTC, and 3.3 % for histopathology in the screening program, with similar trends in the randomized trials., Conclusion: Endoscopists, radiologists, and pathologists all exhibit terminal digit preference when measuring colorectal polyps. This will bias trial data, referral rates for further testing, adenoma surveillance regimens, and comparisons between tests., (© Georg Thieme Verlag KG Stuttgart · New York.)

Aim: To determine the detection rates and positive predictive value (PPV) of computed tomography (CT) colonography (CTC) according to the magnitude of faecal occult blood test (FOBt) positivity., Materials and Methods: Anonymised data from individuals undergoing CTC after a positive FOBt in the English Bowel Cancer Screening Programme were analysed. The detection of colorectal cancer (CRC), advanced neoplasia, and ≥ 6 mm polyps were stratified by the number of positive FOBt windows. The PPV was calculated by reference to subsequent endoscopy results. The influence of the FOBt result on detection rates was estimated with multilevel logistic regression. PPV, CRC stage, and location were compared across groups according to FOBt positivity., Results: Four thousand, six hundred and one individuals were included (mean = 66.7 years, 54.2% men). Detection rates of CRC and advanced neoplasia increased with greater numbers of positive FOBt windows (odds ratio [OR] for CRC = 1.41; 95% confidence interval [CI]: 1.31-1.52; OR for advanced neoplasia = 1.17; 95%CI: 1.12-1.23; both p < 0.0001). The PPV was significantly greater at higher FOBt levels (p = 0.020). The number of positive FOBt windows had no significant effect on stage (p = 0.30) or location (p = 0.20) of confirmed CRC., Conclusions: The magnitude of FOBt positivity influences the PPV and detection rates when screening for colorectal neoplasia. CTC may be particularly useful for FOBt patients with few positive test windows., (Copyright © 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Purpose: To determine the maximum rate of false-positive diagnoses that patients and health care professionals were willing to accept in exchange for detection of extracolonic malignancy by using computed tomographic (CT) colonography for colorectal cancer screening., Materials and Methods: After obtaining ethical approval and informed consent, 52 patients and 50 health care professionals undertook two discrete choice experiments where they chose between unrestricted CT colonography that examined intra- and extracolonic organs or CT colonography restricted to the colon, across different scenarios. The first experiment detected one extracolonic malignancy per 600 cases with a false-positive rate varying across scenarios from 0% to 99.8%. One experiment examined radiologic follow-up generated by false-positive diagnoses while the other examined invasive follow-up. Intracolonic performance was identical for both tests. The median tipping point (maximum acceptable false-positive rate for extracolonic findings) was calculated overall and for both groups by bootstrap analysis., Results: The median tipping point for radiologic follow-up occurred at a false-positive rate greater than 99.8% (interquartile ratio [IQR], 10 to >99.8%). Participants would tolerate at least a 99.8% rate of unnecessary radiologic tests to detect an additional extracolonic malignancy. The median tipping-point for invasive follow-up occurred at a false-positive rate of 10% (IQR, 2 to >99.8%). Tipping points were significantly higher for patients than for health care professionals for both experiments (>99.8 vs 40% for radiologic follow-up and >99.8 vs 5% for invasive follow-up, both P < .001)., Conclusion: Patients and health care professionals are willing to tolerate high rates of false-positive diagnoses with CT colonography in exchange for diagnosis of extracolonic malignancy. The actual specificity of screening CT colonography for extracolonic findings in clinical practice is likely to be highly acceptable to both patients and health care professionals. Online supplemental material is available for this article., (© RSNA, 2014.)

This is an official guideline of the European Society of Gastrointestinal Endoscopy (ESGE) and the European Society of Gastrointestinal and Abdominal Radiology (ESGAR). It addresses the clinical indications for the use of computed tomographic colonography (CTC). A targeted literature search was performed to evaluate the evidence supporting the use of CTC. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was adopted to define the strength of recommendations and the quality of evidence. Main recommendations 1 ESGE/ESGAR recommend computed tomographic colonography (CTC) as the radiological examination of choice for the diagnosis of colorectal neoplasia. ESGE/ESGAR do not recommend barium enema in this setting (strong recommendation, high quality evidence). 2 ESGE/ESGAR recommend CTC, preferably the same or next day, if colonoscopy is incomplete. Delay of CTC should be considered following endoscopic resection. In the case of obstructing colorectal cancer, preoperative contrast-enhanced CTC may also allow location or staging of malignant lesions (strong recommendation, moderate quality evidence). 3 When endoscopy is contraindicated or not possible, ESGE/ESGAR recommend CTC as an acceptable and equally sensitive alternative for patients with symptoms suggestive of colorectal cancer (strong recommendation, high quality evidence). 4 ESGE/ESGAR recommend referral for endoscopic polypectomy in patients with at least one polyp  ≥  6  mm in diameter detected at CTC. CTC surveillance may be clinically considered if patients do not undergo polypectomy (strong recommendation, moderate quality evidence). 5 ESGE/ESGAR do not recommend CTC as a primary test for population screening or in individuals with a positive first-degree family history of colorectal cancer (CRC). However, it may be proposed as a CRC screening test on an individual basis providing the screenee is adequately informed about test characteristics, benefits, and risks (weak recommendation, moderate quality evidence)., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: The methylation of DNA is recognized as a key epigenetic mechanism and evidence for its role in the development of several malignancies is accumulating. We evaluated the relationship between global methylation in DNA derived from normal appearing colon mucosal tissue and blood leukocytes, and colorectal adenoma risk., Methods: Patients, aged 40 to 65, scheduled for a screening colonoscopy were recruited. During the colonoscopy, two pinch biopsies of healthy, normal appearing mucosa were obtained from the descending colon. A fasting blood sample was also collected. The methylation status of LINE-1 (long interspersed nuclear element-1) repetitive sequences, as a surrogate measure of global methylation, was quantified in DNA extracted from normal colon mucosa and blood leukocytes. Statistical analysis of the relationship between global DNA methylation and adenoma risk was conducted on 317 participants, 108 subjects with at least one pathologically confirmed adenoma and 209 subjects with a normal colonoscopy., Results: A statistically significant inverse relationship was observed between LINE-1 methylation in colon tissue DNA and adenoma risk for males and for both sexes combined for the lowest methylation quartile compared to the highest (adjusted ORs = 2.94 and 2.26 respectively). For blood, although the overall pattern of odds ratio estimates was towards an increase in risk for lower methylation quartiles compared to the highest methylation quartile, there were no statistically significant relationships observed. A moderate correlation was found between LINE-1 methylation levels measured in tissue and blood (Pearson correlation 0.36)., Conclusions: We observed that lower levels of LINE-1 DNA methylation in normal appearing background colon mucosa were associated with increased adenoma risk for males, and for both sexes combined. Though these findings provide some support for a relationship between LINE-1 DNA methylation in colon mucosal tissue and adenoma risk, large prospective cohort studies are needed to confirm results. Until such investigations are done, the clinical usefulness of LINE-1 methylation as a biomarker of increased adenoma risk is uncertain. Regardless, this study contributes to a better understanding of the role of global DNA methylation as an early event in CR carcinogenesis with implications for future etiologic research.

Aim: To describe our experience using a 5 year audit of computed tomography colonography (CTC) practice and identify factors that influence diagnostic performance to guide implementation in other centres., Material and Methods: Consecutive patients referred for CTC at a single institution over a 5 year period were identified, and reporting rates and positive predictive value (PPV) calculated for small polyps, large polyps, and colorectal cancer. Diagnostic performance was compared using the Chi-squared test, and trends over time were examined with logistic regression. The effect of faecal tagging and an intravenous spasmolytic were investigated using Fisher's exact test., Results: In total, 4355 CTC examinations were performed. Overall reporting rates and PPV were 17% and 92%, respectively. Negative predictive value (NPV) for cancer was 99.9%. A significant decrease in reporting rate (p < 0.001) was accompanied by an increase in PPV for small polyps (p = 0.02) following the introduction of faecal tagging. Adequacy rates for CTC improved over time (96% to 99%), with improved adequacy rates when using a spasmolytic, 98% versus 96% without. A significant difference in reporting rates, but not PPV, was found between radiologists., Conclusion: Accurate colonic investigation using CTC can be delivered safely to a high-risk patient population at a single centre. Faecal tagging and an intravenous spasmolytic improve diagnostic performance., (Copyright © 2014. Published by Elsevier Ltd.)

Objective: To examine use of CT colonography (CTC) in the English Bowel Cancer Screening Programme (BCSP) and investigate detection rates., Design: Retrospective analysis of routinely coded BCSP data. Guaiac faecal occult blood test (gFOBt)-positive screenees undergoing CTC from June 2006 to July 2012 as their first-line colonic investigation were included. Abnormalities found at CTC, subsequent polyp, adenoma and cancer detection and positive predictive value (PPV) were calculated. Detection rates were compared with those observed in gFOBt-positive screenees investigated by colonoscopy. Multilevel logistic regression was used to examine factors associated with variable detection., Results: 2731 screenees underwent CTC. Colorectal cancer (CRC) or polyps were suspected in 1027 individuals (37.6%; 95% CI 33.8% to 41.4%); 911 of these underwent confirmatory testing. 124 screenees had CRC (4.5%) and 533 had polyps (19.5%), 468 adenomatous (17.1%). Overall detection was 24.1% (95% CI 21.5% to 26.6%) for CRC or polyps and 21.7% (95% CI 19.2% to 24.1%) for CRC or adenoma. Advanced neoplasia was detected in 504 screenees (18.5%; 95% CI 16.1% to 20.8%). PPV for CRC or polyp was 72.1% (95% CI 66.6% to 77.6%). By comparison, 9.0% of 72 817 screenees undergoing colonoscopy had cancer and 50.6% had polyps; advanced neoplasia was detected in 32.7%. CTC detection rates and PPV were higher at centres with experienced radiologists (>1000 examinations) and at high-volume centres (>175 cases/radiologist/annum). Centres using three-dimensional interpretation detected more neoplasia., Conclusions: In the BCSP, detection rates after positive gFOBt are lower for CTC than colonoscopy, although populations undergoing the two tests are different. Centres with more experienced radiologists have higher detection and accuracy. Rigorous quality assurance of BCSP radiology is needed.

Objective: CT colonography (CTC) is recommended after positive faecal occult blood testing (FOBt) when colonoscopy is incomplete or infeasible. We aimed to estimate the sensitivity and specificity of CTC for colorectal cancer and adenomatous polyps following positive FOBt via systematic review., Methods: The MEDLINE, EMBASE, AMED and Cochrane Library databases were searched for CTC studies reporting sensitivity and specificity for colorectal cancer and adenomatous polyps. Included subjects had tested FOBt-positive by guaiac or immunochemical methods. Per-patient detection rates were summarized via forest plots. Meta-analysis of sensitivity and specificity was conducted using a bivariate random effects model and the average operating point calculated., Results: Of 538 articles considered, 5 met inclusion criteria, describing results from 622 patients. Research study quality was good. CTC had a high per-patient average sensitivity of 88.8 % (95 % CI 83.6 to 92.5 %) for ≥6 mm adenomas or colorectal cancer, with low between-study heterogeneity. Specificity was both more heterogeneous and lower, at an average of 75.4 % (95 % CI 58.6 to 86.8 %)., Conclusion: Few studies have investigated CTC in FOBt-positive individuals. CTC is sensitive at a ≥6 mm threshold but specificity is lower and variable. Despite the limited data, these results suggest that CTC may adequately substitute for colonoscopy when the latter is undesirable., Key Points: • FOBt is the most common mass screening test for colorectal cancer. • Few studies evaluate CT colonography after positive FOBt. • CTC is approximately 89 % sensitive for ≥6 mm adenomas/cancer in this setting. • Specificity is lower, at approximately 75 %, and more variable. • CT colonography is a good alternative when colonoscopy is undesirable.

Unlabelled: This study explores the potential for multifunctional imaging to provide a signature for V-KI-RAS2 Kirsten rat sarcoma viral oncogene homolog (KRAS) gene mutations in colorectal cancer., Methods: This prospective study approved by the institutional review board comprised 33 patients undergoing PET/CT before surgery for proven primary colorectal cancer. Tumor tissue was examined histologically for presence of the KRAS mutations and for expression of hypoxia-inducible factor-1 (HIF-1) and minichromosome maintenance protein 2 (mcm2). The following imaging parameters were derived for each tumor: (18)F-FDG uptake ((18)F-FDG maximum standardized uptake value [SUVmax]), CT texture (expressed as mean of positive pixels [MPP]), and blood flow measured by dynamic contrast-enhanced CT. A recursive decision tree was developed in which the imaging investigations were applied sequentially to identify tumors with KRAS mutations. Monte Carlo analysis provided mean values and 95% confidence intervals for sensitivity, specificity, and accuracy., Results: The final decision tree comprised 4 decision nodes and 5 terminal nodes, 2 of which identified KRAS mutants. The true-positive rate, false-positive rate, and accuracy (95% confidence intervals) of the decision tree were 82.4% (63.9%-93.9%), 0% (0%-10.4%), and 90.1% (79.2%-96.0%), respectively. KRAS mutants with high (18)F-FDG SUVmax and low MPP showed greater frequency of HIF-1 expression (P = 0.032). KRAS mutants with low (18)F-FDG SUV(max), high MPP, and high blood flow expressed mcm2 (P = 0.036)., Conclusion: Multifunctional imaging with PET/CT and recursive decision-tree analysis to combine measurements of tumor (18)F-FDG uptake, CT texture, and perfusion has the potential to identify imaging signatures for colorectal cancers with KRAS mutations exhibiting hypoxic or proliferative phenotypes.

Purpose: To establish the relative weighting given by patients and healthcare professionals to gains in diagnostic sensitivity versus loss of specificity when using CT colonography (CTC) for colorectal cancer screening., Materials and Methods: Following ethical approval and informed consent, 75 patients and 50 healthcare professionals undertook a discrete choice experiment in which they chose between "standard" CTC and "enhanced" CTC that raised diagnostic sensitivity 10% for either cancer or polyps in exchange for varying levels of specificity. We established the relative increase in false-positive diagnoses participants traded for an increase in true-positive diagnoses., Results: Data from 122 participants were analysed. There were 30 (25%) non-traders for the cancer scenario and 20 (16%) for the polyp scenario. For cancer, the 10% gain in sensitivity was traded up to a median 45% (IQR 25 to >85) drop in specificity, equating to 2250 (IQR 1250 to >4250) additional false-positives per additional true-positive cancer, at 0.2% prevalence. For polyps, the figure was 15% (IQR 7.5 to 55), equating to 6 (IQR 3 to 22) additional false-positives per additional true-positive polyp, at 25% prevalence. Tipping points were significantly higher for patients than professionals for both cancer (85 vs 25, p<0.001) and polyps (55 vs 15, p<0.001). Patients were willing to pay significantly more for increased sensitivity for cancer (p = 0.021)., Conclusion: When screening for colorectal cancer, patients and professionals believe gains in true-positive diagnoses are worth much more than the negative consequences of a corresponding rise in false-positives. Evaluation of screening tests should account for this.

Aims: To explore the relative value patients place on comfort and convenience versus test sensitivity and specificity in the context of computed tomographic colonography (CTC) screening., Materials and Methods: Twenty semi-structured interviews were carried out with patients attending hospital for radiological tests unrelated to CTC. Preferences for CTC with different types of bowel preparation for CTC screening were examined and interviews were analysed thematically. The discussion guide included separate sections on CTC, bowel preparation methods (non-, reduced- and full-laxative), and sensitivity and specificity. Patients were given information on each topic in turn and asked about their views and preferences during each section., Results: Following information about the test, patients' attitudes towards CTC were positive. Following information on bowel preparation, full-laxative purgation was anticipated to cause more adverse physical and lifestyle effects than using reduced- or non-laxative preparation. However, stated preferences were approximately equally divided, largely due to patients anticipating that non-laxative preparations would reduce test accuracy (because the bowel was not thoroughly cleansed). Following information on sensitivity and specificity (which supported patients' expectations), the predominant stated preference was for full-laxative preparation., Conclusions: Patients are likely to value test sensitivity and specificity over a more comfortable and convenient preparation. Future research should test this hypothesis on a larger sample., (Copyright © 2013 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Aim: To obtain information regarding the provision of computed tomography colonography (CTC) services to the National Health Service (NHS) Bowel Cancer Screening Programme (BCSP)., Materials and Methods: Specialist screening practitioners at the 58 BCSP screening centres and lead BCSP radiologists at 110 hospitals performing CTC for the Programme were contacted and completed a semi-structured questionnaire administered by telephone. Responses were collated and descriptive statistics derived., Results: One hundred and seven (98%) SSPs and 103 (94%) radiologists were surveyed. All screening centres had access to CTC at 110 hospital sites. All sites used CTC for failed or contraindicated colonoscopy, 24% used it for patients taking anticoagulants, and 17% for those with fear of colonoscopy. Patient preference was not an indication at any site. Multidetector CT (100%), carbon dioxide insufflators (94%), and CTC software (95%) were almost universal. Ninety-one percent of radiographers and 98% of radiologists were trained in CTC image acquisition and interpretation, respectively. Seventy-five percent of the radiologists were gastrointestinal subspecialists and two-thirds had interpreted more than 300 examinations in clinical practice, although 5% had interpreted fewer than 100. Eighty-one percent of radiologists favoured some form of accreditation for CTC interpretation., Conclusions: CTC is widely available to the BCSP. Appropriate hardware and software is almost ubiquitous. Most radiographers and radiologists offering CTC to the BCSP have received specific training. Formal service evaluation is patchy. The majority of radiologists would welcome national accreditation for CTC., (Copyright © 2012 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Objective: The purpose of this article is to assess the effect of observers on combined metabolic-vascular parameters in colorectal cancer., Subjects and Methods: Twenty-five prospective patients (12 men and 13 women; mean age, 66.9 years) with proven primary colorectal adenocarcinoma underwent integrated (18)F-FDG PET/perfusion CT to assess tumor metabolism (mean and maximum standardized uptake value [SUV(mean) and SUV(max), respectively]) and vascularization (blood flow [BF], blood volume [BV], permeability surface-area product, and standardized perfusion value). Intra- and interobserver agreement for PET, perfusion CT, and combined metabolic-flow parameters were determined by Bland-Altman statistics and intraclass correlation coefficients (ICCs)., Results: The mean tumor size was 3.8 ± 1.6 cm; there were five stage IA/B, six stage IIA/B, eight stage IIIA/B, and six stage IV tumors. Intra- and interobserver agreement for individual parameters was fair to good, with mean differences between observers of -0.74 for SUV(max), -0.16 for SUV(mean), 9.72 for BF, 0.15 for BV, -0.76 for permeability surface-area product, and 0.09 for standardized perfusion value. ICCs were 0.44-0.99 and 0.38-0.89 for intra- and interobserver agreement, respectively. Interobserver agreement was variable for combined metabolic-flow parameters but better for metabolic-flow difference than for metabolic-flow ratio: ICCs were 0.69-0.88 for the metabolic-flow difference and 0.44-0.94 for the metabolic-flow ratio., Conclusion: Combined parameters to assess the metabolic-flow relationship are influenced by observer variation. Intra- and interobserver agreement are better for the metabolic-flow differences than for the ratios, suggesting that metabolic-flow differences may be a more robust parameter for clinical practice.

Objectives: To investigate how the histological scoring of microvessel density affects correlations between integrated (18)F-FDG-PET/perfusion CT parameters and CD105 microvessel density., Methods: A total of 53 patients were enrolled from 2007 to 2010. Integrated (18)F-FDG-PET/perfusion CT was successful in 45 patients, 35 of whom underwent surgery without intervening treatment. Tumour SUV(max), SUV(mean) and regional blood flow (BF) were derived. Immunohistochemical staining for CD105 expression and analysis were performed for two hot spots, four hot spots and the Chalkley method. Correlations between metabolic flow parameters and CD105 expression were assessed using Spearman's rank correlation., Results: Mean (SD) for tumour size was 38.5 (20.5) mm, for SUV(max), SUV(mean) and BF it was 19.1 (4.5), 11.6 (2.5) and 85.4 (40.3) mL/min/100 g tissue, and for CD105 microvessel density it was 71.4 (23.6), 66.8 (22.9) and 6.18 (2.07) for two hot spots, four hot spots and the Chalkley method, respectively. Positive correlation between BF and CD105 expression was modest but higher for Chalkley than for four hot spots analysis (r = 0.38, P = 0.03; r = 0.33, P = 0.05, respectively). There were no significant correlations between metabolic parameters (SUV(max) or SUV(mean)) and CD105 expression (r = 0.08-0.22, P = 0.21-0.63)., Conclusions: The histological analysis method affects correlations between tumour CD105 expression and BF but not SUV(max) or SUV(mean)., Key Points: • FDG-PET/perfusion CT offers new surrogate biomarkers of angiogenesis. • Microvessel density scoring influences histopathological correlations with CT blood flow. • Highest correlations were found with the Chalkley analysis method. • Correlations between SUV and CD105 are not affected by the scoring method.

Computed tomographic (CT) colonography is being implemented increasingly in the USA and Europe, and in many centers it has become the radiological technique of choice for imaging the whole colorectum. Although high diagnostic accuracy has been demonstrated in both screening and symptomatic populations, controversy persists regarding implementation, who should interpret the examination, and its cost effectiveness, particularly in the context of primary colorectal cancer screening. Published research in recent years has demonstrated efficacy in a wide range of patient groups, striking technical improvements, and high levels of patient acceptability. New developments continue in the fields of computer aided detection, digital cleansing, and integration into positron emission tomography. The purpose of this review is to bring the reader up-to-date with the latest developments in CT colonography, in particular, those of the last year.

Aim: To obtain information regarding the demographics of attendees of computed tomography colonography (CTC) training workshops organized by the European Society of Gastrointestinal and Abdominal Radiology (ESGAR), in particular their prior expertise and current practice., Materials and Methods: Attendees at five CTC training workshops conducted in Edinburgh (UK), Malmo (Sweden), Amsterdam (Netherlands), Pisa and Stresa (Italy) between February 2007 and April 2010 completed an online questionnaire. Responses were collated and descriptive statistics produced., Results: Three hundred and forty-eight delegates responded; a response rate of 73%. There was wide geographical variability encompassing 20 European member-states and seven countries outside Europe. The overwhelming majority were radiologists (336; 97%). Of the respondents, 299 (86%) were already interpreting CTC in clinical practice but of these, 158 (54%) had no prior formal training in CTC whereas 21 (8%) had attended a previous workshop. Furthermore, of those reporting CTC, 227 (76%) had interpreted fewer than 50 cases., Conclusions: Despite political imperatives for other groups to interpret CTC, the vast majority of those attending training are radiologists. Worryingly, a significant proportion of these are apparently reporting CTC in clinical practice without adequate training., (Copyright © 2011 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Objectives: Computer-aided detection (CAD) for CT colonography (CTC) has been developed to detect benign polyps in asymptomatic patients. We aimed to determine whether such a CAD system can also detect cancer in symptomatic patients., Methods: CTC data from 137 symptomatic patients subsequently proven to have colorectal cancer were analysed by a CAD system at 4 different sphericity settings: 0, 50, 75 and 100. CAD prompts were classified by an observer as either true-positive if overlapping a cancer or false-positive if elsewhere. Colonoscopic data were used to aid matching., Results: Of 137 cancers, CAD identified 124 (90.5%), 122 (89.1%), 119 (86.9%) and 102 (74.5%) at a sphericity of 0, 50, 75 and 100, respectively. A substantial proportion of cancers were detected on either the prone or supine acquisition alone. Of 125 patients with prone and supine acquisitions, 39.3%, 38.3%, 43.2% and 50.5% of cancers were detected on a single acquisition at a sphericity of 0, 50, 75 and 100, respectively. CAD detected three cancers missed by radiologists at the original clinical interpretation. False-positive prompts decreased with increasing sphericity value (median 65, 57, 45, 24 per patient at values of 0, 50, 75, 100, respectively) but many patients were poorly prepared., Conclusion: CAD can detect symptomatic colorectal cancer but must be applied to both prone and supine acquisitions for best performance.

Objective: To determine how commercial software platform upgrades impact on derived parameters for colorectal cancer., Materials and Methods: Following ethical approval, 30 patients with suspected colorectal cancer underwent Perfusion CT using integrated 64 detector PET/CT before surgery. Analysis was performed using software based on modified distributed parameter analysis (Perfusion software version 4; Perfusion 4.0), then repeated using the previous version (Perfusion software version 3; Perfusion 3.0). Tumour blood flow (BF), blood volume (BV), mean transit time (MTT) and permeability surface area product (PS) were determined for identical regions-of-interest. Slice-by-slice and 'whole tumour' variance was assessed by Bland-Altman analysis., Results: Mean BF, BV and PS was 20.4%, 59.5%, and 106% higher, and MTT 14.3% shorter for Perfusion 4.0 than Perfusion 3.0. The mean difference (95% limits of agreement) were +13.5 (-44.9 to 72.0), +2.61 (-0.06 to 5.28), -1.23 (-6.83 to 4.36), and +14.2 (-4.43 to 32.8) for BF, BV, MTT and PS respectively. Within subject coefficient of variation was 36.6%, 38.0%, 27.4% and 60.6% for BF, BV, MTT and PS respectively indicating moderate to poor agreement., Conclusion: Software version upgrades of the same software platform may result in significantly different parameter values, requiring adjustments for cross-version comparison.

With the recent publication of international computed tomography (CT) colonography standards, which aim to improve quality of examinations, this review informs radiologists about the significance of flat polyps (adenomas and hyperplastic polyps) in colorectal cancer pathways. We describe flat polyp classification systems and propose how flat polyps should be reported to ensure patient management strategies are based on polyp morphology as well as size. Indeed, consistency when describing flat polyps is of increasing importance given the strengthening links between CT colonography and endoscopy., (Copyright © 2010 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

CT colonography (CTC) is increasingly advocated as an effective initial screening tool for colorectal cancer. Nowadays, policy-makers are increasingly interested in cost-effectiveness issues. A number of studies assessing the cost-effectiveness of CTC have been published to date. The majority of findings indicate that CTC is probably not cost-effective when colonoscopy is available, but this conclusion is sensitive to a number of key parameters. This review discusses the findings of these studies, and considers those factors which most influence final conclusions, notably intervention costs, compliance rates, effectiveness of colonoscopy, and the assumed prevalence and natural history of diminutive advanced polyps.

Meta-analysis of data from studies of CT colonography suggests that it has excellent per-patient average sensitivity and average specificity for detection of adenomatous polyps and cancer. However, while its potential as a screening test is undoubted, there are several current limitations that will need to be overcome before it can be considered seriously by health policy makers. These revolve around issues of generalisability, which is inhibited most by a lack of trained observers and access to CT scanners, and a paucity of data relating to cost-effectiveness. Whether offering CT colonography as an alternative to competing strategies will genuinely enhance compliance also needs further and more detailed attention.

The aim of this study was to compare the confidence of experienced radiologists in excluding colonic neoplasia with CT colonography (CTC) compared with barium enema. 78 patients (median age 70 years, range 61-87 years, 44 women) underwent same day CTC and barium enema. Two radiologists experienced in reporting barium enema assessed whether the examination had excluded a polyp 6 mm or greater as "yes", "probably" or "no" for each of 6 colonic segments. Two different radiologists experienced in CTC independently performed the same assessment on the CT datasets. Responses were compared using a paired exact test. Formal barium enema and CT reports were compared with any endoscopic examination performed within 1 year. Studies reporting polyps 6 mm+ in patients not subsequently undergoing endoscopy were reviewed by two independent observers. Radiologists stated they had confidently excluded a significant lesion in 314 (71%) and 382 (86%) of 444 segments with barium enema and CTC, respectively (p<0.001). Confidence was significantly higher with CTC in the in the descending and ascending colon (p = 0.02 and p<0.001, respectively), and caecum (p<0.001). 22 patients underwent some form of endoscopy. Of five patients with proven colorectal neoplasia (including two with cancer), CTC and barium enema correctly identified five and three, respectively. In 56 patients not undergoing endoscopy, CTC reported 17 polyps 6 mm+, of which 16 were retrospectively classified as definite or probable. 11 could not be identified on the barium enema, even in retrospect. Confidence in excluding polyps 6 mm or larger is significantly greater with CT colonography particularly in the proximal colon.

Purpose: To assess the methodologic quality of available data in published reports of computed tomographic (CT) colonography by performing systematic review and meta-analysis., Materials and Methods: The MEDLINE database was searched for colonography reports published between 1994 and 2003, without language restriction. The terms colonography, colography, CT colonoscopy, CT pneumocolon, virtual colonoscopy, and virtual endoscopy were used. Studies were selected if the focus was detection of colorectal polyps verified with within-subject reference colonoscopy by using key methodologic criteria based on information presented at the Fourth International Symposium on Virtual Colonoscopy (Boston, Mass). Two reviewers independently abstracted methodologic characteristics. Per-patient and per-polyp detection rates were extracted, and authors were contacted, when necessary. Per-patient sensitivity and specificity were calculated for different lesion size categories, and Forest plots were produced. Meta-analysis of paired sensitivity and specificity was conducted by using a hierarchical model that enabled estimation of summary receiver operating characteristic curves allowing for variation in diagnostic threshold, and the average operating point was calculated. Per-polyp sensitivity was also calculated., Results: Of 1398 studies considered for inclusion, 24 met our criteria. There were 4181 patients with a study prevalence of abnormality of 15%-72%. Meta-analysis of 2610 patients, 206 of whom had large polyps, showed high per-patient average sensitivity (93%; 95% confidence interval [CI]: 73%, 98%) and specificity (97%; 95% CI: 95%, 99%) for colonography; sensitivity and specificity decreased to 86% (95% CI: 75%, 93%) and 86% (95% CI: 76%, 93%), respectively, when the threshold was lowered to include medium polyps. When polyps of all sizes were included, studies were too heterogeneous in sensitivity (range, 45%-97%) and specificity (range, 26%-97%) to allow meaningful meta-analysis. Of 150 cancers, 144 were detected (sensitivity, 95.9%; 95% CI: 91.4%, 98.5%). Data reporting was frequently incomplete, with no generally accepted format., Conclusion: CT colonography seems sufficiently sensitive and specific in the detection of large and medium polyps; it is especially sensitive in the detection of symptomatic cancer. Studies are poorly reported, however, and the authors propose a minimum data set for study reporting., (RSNA, 2005)

Aim: Patients referred under the Department of Health 2-week wait initiative with symptoms of colorectal cancer frequently undergo whole-colon examination. We investigated the use of computed tomography (CT) colonography as an alternative to colonoscopy in this scenario., Materials and Methods: Fifty-four consecutive patients, referred via the 2-week wait initiative and scheduled for colonoscopy, consented to undergo multidetector CT colonography immediately before endoscopy. The site and morphology of any polyp or cancer detected by CT was noted and comparison made with subsequent colonoscopy., Results: Colonoscopy detected polyps or cancer in 29 patients (53.7%). CT colonography prospectively detected 18 of 41 (44%) polyps of 1-5 mm, three of four (75%) polyps of 6-9 mm, four of four (100%) polyps 10 mm or larger, and five of six (83%) cancers. The missed cancer occurred early in the series and was a perceptive error. The overall sensitivity, specificity, positive predictive value and negative predictive value of CT colonography for cancer and polyps 10 mm or greater on a per patient basis were 90, 100, 100 and 98%, respectively. CT detected one renal cancer and one colonic cancer, initially missed due to incomplete colonoscopy., Conclusion: CT colonography is a robust technique for investigation of symptomatic patients. The learning curve must be overcome for optimal performance.

Computed tomography colonography (CTC) is a relatively new technique that is currently challenging more established methods of large bowel imaging. Several workers have suggested CTC surpasses the barium enema and approaches conventional endoscopy for detection of colorectal neoplasia. Accurate diagnosis relies on technically good studies, the main aim of which is adequate bowel cleansing and distension. Furthermore, the learning curve is steep and normal colonic anatomy has to be re-learned in a CT context. This review aims to describe the technique, revise the imaging features of both normal and pathological colon, and to highlight potential diagnostic pitfalls and their avoidance., (Copyright 2003 The Royal College of Radiologists)

Fifty evaluable patients with advanced colorectal cancer, but without prior chemotherapy or immunotherapy, were randomized to one of two schedules of recombinant gamma-interferon (rGIFN). Twenty-four evaluable patients received rGIFN as a 2-h intravenous infusion daily x 5 every other week at a starting dose of 4.0 x 10(6) IU/m2/day (arm I). Twenty-six evaluable patients received rGIFN as a 24-h continuous intravenous infusion daily x 5 every month at a starting dose of 2.6 x 10(6) IU/m2/day (arm II). Toxicities on both schedules included flu-like symptoms, fevers/rigors, nausea/vomiting, hypotension, leukopenia, hepatotoxicity, nephrotoxicity, diarrhea, anemia, confusion, and ileus. Toxicity appeared to be more severe on arm I. No antitumor responses were observed, with 95% confidence intervals of 0 to 14% for arm I and 0 to 13% for arm II.

Based on the high response rates seen among patients with colon cancer receiving high dose Melphalan with autologous marrow infusion, the Southwest Oncology Group conducted a Phase II trial of the compound at a conventional dose. The initial starting dose of 40 mg/m2 was reduced to 30 mg/m2 after severe myelotoxicity was encountered in the first five patients. Toxicity was primarily myeloid and was moderate to severe in most patients with one treatment related death. There were two complete and one partial response among 43 patients. Melphalan at 30 mg/m2 has little activity among patients with metastatic colorectal carcinoma.