Molecular profiling of longitudinally observed small colorectal polyps: A cohort study

Background: Knowledge of the natural history of colorectal adenomas is limited because these lesions are removed upon detection. The few studies in which small adenomas have been left in situ for a limited period of time, have shown that most lesions remain stable or even completely regress. Specific DNA copy number changes (‘cancer associated events’ or CAEs) are associated with progression of adenomas to cancer. In this study we evaluated whether molecular features of progression correlated with growth of small polyps. Methods: Small (6–9 mm) colorectal precursor lesions detected on CT-colonography (CTC) were left in situ and re-evaluated with CTC after three years. Based o

Burden of waiting for surveillance CT colonography in patients with screen-detected 6–9 mm polyps

Purpose: We assessed the burden of waiting for surveillance CT colonography (CTC) performed in patients having 6–9 mm colorectal polyps on primary screening CTC. Additionally, we compared the burden of primary and surveillance CTC. Materials and methods: In an invitational population-based CTC screening trial, 101 persons were diagnosed with <3 polyps 6–9 mm, for which surveillance CTC after 3 years was advised. Validated questionnaires regarding expected and perceived burden (5-point Likert scales) were completed before and after index and surveillance CTC, also including items on burden of waiting for surveillance CTC. McNemar’s test was used for comparison after dichotomization. Results: Seventy-eight (77 %) of 101 invitees underwent surveillance CTC, of which 66 (85 %) completed the expected and 62 (79 %) the perceived burden questionnaire. The majority of participants (73 %) reported the experience of waiting for surveillance CTC as ‘never’ or ‘only sometimes’ burdensome. There was almost no difference in expected and perceived burden between surveillance and index CTC. Waiting for the results after the procedure was significantly more burdensome for surveillance CTC than for index CTC (23 vs. 8 %; p = 0.012). Conclusion: Waiting for surveillance CTC after primary CTC screening caused little or no burden for surveillance participants. In general, the burden of surveillance and index CTC were comparable. Key points: • Waiting for surveillance CTC withi

Computer tomography colonography participation and yield in patients under surveillance for 6-9 mm polyps in a population-based screening trial

Purpose: Surveillance CT colonography (CTC) is a viable option for 6-9 mm polyps at CTC screening for colorectal cancer. We established participation and diagnostic yield of surveillance and determined overall yield of CTC screening. Material and methods: In an invitational CTC screening trial 82 of 982 participants harboured 6-9 mm polyps as the largest lesion(s) for which surveillance CTC was advised. Only participants with one or more lesion(s) ≥6 mm at surveillance CTC were offered colonoscopy (OC); 13 had undergone preliminary OC. The surveillance CTC yield was defined as the number of participants with advanced neoplasia in the 82 surveillance participants, and was added to the primary screening yield. Results: Sixty-five of 82 participants were eligible for surveillance CTC of which 56 (86.2 %) participated. Advanced neoplasia was diagnosed in 15/56 participants (26.8 %) and 9/13 (69.2 %) with preliminary OC. Total surveillance yield was 24/82 (29.3 %). No carcinomas were detected. Adding surveillance results to initial screening CTC yield significantly increased the advanced neoplasia yield per 100 CTC participants (6.1 to 8.6; p < 0.001) and per 100 invitees (2.1 to 2.9; p < 0.001). Conclusion: Surveillance CTC for 6-9 mm polyps has a substantial yield of advanced adenomas and significantly increased the CTC yield in population screening. Key Points: • The participation rate in surveillance CT colonography (CTC) is 86 %. • Advanced adenoma prevalence in a 6-9 mm CTC surveillance population is high. • Surveillance CTC significantly increases the yield of population screening by CTC. • Surveillance CTC for 6-9 mm polyps is a safe strategy. • Sur

Molecular profiling of longitudinally observed small colorectal polyps: A cohort studyResearch in context

Background: Knowledge of the natural history of colorectal adenomas is limited because these lesions are removed upon detection. The few studies in which small adenomas have been left in situ for a limited period of time, have shown that most lesions remain stable or even completely regress. Specific DNA copy number changes (‘cancer associated events’ or CAEs) are associated with progression of adenomas to cancer. In this study we evaluated whether molecular features of progression correlated with growth of small polyps. Methods: Small (6–9 mm) colorectal precursor lesions detected on CT-colonography (CTC) were left in situ and re-evaluated with CTC after three years. Based on volumetric change, polyps were classified as either grown, stable or regressed. Surveillance CTC was followed by colonoscopy, during which all lesions were resected. Using DNA isolated from FFPE polyp tissues, low-coverage whole genome sequencing was performed to determine DNA copy number profiles, as well as target enrichment mutation analysis and CpG island methylation phenotype (CIMP) analysis. Expression of DNA mismatch repair (MMR) proteins was determined by immunohistochemistry. Samples were marked as MMR proficient if all MMR proteins were expressed. Findings: Out of 68 polyps resected at colonoscopy, for 65 (96%) material was available. Of these, 31 (48%) had grown, 27 (41%) remained stable and 7 (11%) regressed. Polyps with at least one CAE had higher growth rates compared to polyps without CAEs (difference 91% growth (95% CI 13–169), p = .023). CAEs were absent in lesions that had partially regressed. Mutations occurred in 94% of the polyps, with higher growth rates being associated with polyps having ≥2 mutations compared to lesions with only 0–1 mutations (difference 99% growth (95% CI 9–189), p = .032). All samples were MMR proficient. No relation between growth and CIMP was observed. Interpretation: Molecular alterations associated with colorectal cancer, correlated with growth of small polyps and were absent in polyps that regressed. Therefore, this longitudinal study provides in vivo support in the human setting for the functional role of these molecular alterations, that have mostly been identified by cross sectional observations in tissue samples of colorectal adenomas and cancers. Fund: Alpe d'Huzes- Dutch Cancer Society (project number NKI2013-6338). Keywords: Colorectal polyps, Natural behaviour, Growth, Molecular profilin