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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).)

Objectives: The simple ultrasound activity score for Crohn's disease (SUS-CD) and bowel ultrasound score (BUSS) are promising intestinal ultrasound (IUS) indices of CD, but studied mainly in small settings with few sonographers. We compared SUS-CD and BUSS against histological and magnetic resonance enterography (MRE) reference standards in a post hoc analysis of a prospective multicentre, multireader trial., Methods: Participants recruited to the METRIC trial (ISRCTN03982913) were studied, including those with available terminal ileal (TI) biopsies. Sensitivity and specificity of SUS-CD and BUSS for TI CD activity were calculated with 95% confidence intervals (CI), from the prospective observations of the original METRIC trial sonographers against the histological activity index (HAI) and the simplified magnetic resonance index of activity (sMARIA)., Results: We included 284 patients (median 31.5 years, IQR 23-46) from 8 centres, who underwent IUS and MRE. Of these, 111 patients had available terminal ileal biopsies with HAI scoring. Against histology, sensitivity and specificity for active disease were 79% (95% CI 69-86%) and 50% (31-69%) for SUS-CD, and 66% (56-75%) and 68% (47-84%) for BUSS, respectively. Compared to sMARIA, the sensitivity and specificity for active CD were 81% (74-86%) and 75% (66-83%) for SUS-CD, and 68% (61-74%) and 85% (76-91%) for BUSS, respectively. The sensitivity of SUS-CD was significantly greater than that of BUSS against HAI and sMARIA (p < 0.001), but its specificity was significantly lower than of BUSS against the MRE reference standard (p = 0.003)., Conclusions: Particularly when compared to MRE activity scoring, SUS-CD and BUSS are promising tools in a real-world clinical setting., Clinical Relevance Statement: When tested using data from a multicentre, multireader diagnostic accuracy trial, the simple ultrasound activity score for Crohn's disease (SUS-CD) and bowel ultrasound score (BUSS) were clinically viable intestinal ultrasound indices that were reasonably sensitive and specific for terminal ileal Crohn's disease, especially when compared to a magnetic resonance reference standard., Key Points: The simple ultrasound activity score for Crohn's disease and bowel ultrasound score are promising intestinal ultrasound indices of Crohn's disease but to date studied mainly in small settings with few sonographers. Compared to histology and the magnetic resonance reference standard in a multicentre, multireader setting, the sensitivity of simple ultrasound activity score for Crohn's disease is significantly greater than that of bowel ultrasound score. The specificity of simple ultrasound activity score for Crohn's disease was significantly lower than that of bowel ultrasound score compared to the magnetic resonance enterography reference standard. The specificity of both indices was numerically higher when the magnetic resonance enterography reference standard was adopted., (© 2023. The Author(s).)