Putting data to work for precision medicine.

We discuss the One Stop Shop for Clinical Research (OSCAR) project that links clinical data, patient-reported outcomes, genomic data, and health registry data, employing a rigorous data privacy protection technology, to provide insights into treatment efficacy and safety and serve as a comparator for single-arm trials. This could inspire further initiatives to advance precision medicine.

Long-term risk of colorectal cancer after screen-detected adenoma: Experiences from a Danish gFOBT-positive screening cohort.

Fecal occult blood test (FOBT) screening for colorectal cancer (CRC) is implemented in several countries. Approximately half of all FOBT-positive persons have screen-detected adenomas. Despite removal of these, patients with large/multiple adenomas have increased risk of later developing new advanced adenomas and CRC. International guidelines exist for colonoscopic surveillance following adenoma removal. These divide patients into low-, intermediate- and high-risk groups. We followed 711 FOBT-positive patients with screening adenoma identified during population-based CRC screening in two Danish counties in 2005-2006. As reference population, we included 1,240,348 persons in the same age group from the rest of Denmark not included in the screening. We estimated the long-term CRC risk stratified by adenoma findings during screening and compared to the reference group. After 12 years follow-up, the CRC incidence among all adenoma patients was 322 cases per 100,000 person-years (95% confidence interval [CI]: 212-489) ranging from 251 (95% CI: 94-671) to 542 (95% CI: 300-978) cases per 100,000 person-years in the low- and high-risk groups, respectively. In the reference population, the CRC incidence was 244 (95% CI: 242-247) per 100,000. Patients with screen-detected high-risk adenomas after a positive FOBT had an almost doubled risk of CRC compared to the reference population (adjusted hazard ratio [aHR] 1.95, 95% CI: 1.08-3.51), and the incidence in those with no follow-up visits was over 3.6 (aHR 3.64, 95% CI: 1.82-7.29) times the incidence in the reference population. The increased CRC risk could be controlled if high-risk patients underwent follow-up colonoscopy (aHR 0.87, 95% CI: 0.28-2.69).

Long-term risk of colorectal cancer after negative colonoscopy in a Danish gFOBT screening cohort.

Faecal occult blood test (FOBT) screening for colorectal cancer (CRC) is implemented in several countries. Approximately half of all screen positive persons have negative colonoscopy, but consensus is lacking on how these persons should be followed up. Health authorities in Denmark and The Netherlands recommend suspending screening for 8-10 years, while patients in UK are invited to screening after 2 years. In this cohort-study, we followed 166,277 individuals invited to FOBT-screening in 2005-2006 and a reference group comprising the remaining 1,240,348 Danes of the same age. We linked Danish population and health service registers to obtain information about colonoscopy outcome and incident CRC. We estimated CRC risk by colonoscopy outcome (adenoma, other colorectal pathology or negative colonoscopy) for the reference group, the screening group, and subgroups. Persons with positive screening FOBT followed by negative colonoscopy had the same long-term CRC risk as persons with adenoma detected due to a positive screening FOBT (aHR 1.33, 95% CI: 0.65-2.71). We found no difference in the long-term CRC risk between persons with negative colonoscopy after a positive FOBT screening test and the unscreened reference population (aHR 1.05, 95% CI: 0.62-1.78). Since FOBT screen positive persons in our study remained at average risk of CRC despite of a negative index colonoscopy, we question the safety of suspending FOBT screening for this group. It needs to be monitored whether recent efforts to improve colonoscopy quality have been successful in ensuring low CRC risk after negative colonoscopy also in FOBT positive persons.

Colorectal cancer mortality 10†years after a single round of guaiac faecal occult blood test (gFOBT) screening: experiences from a Danish screening cohort.

BACKGROUND: In Denmark, colorectal cancer (CRC) is the third most frequent cancer. Randomised trials have shown that guaiac faecal occult blood test (gFOBT) screening can reduce CRC mortality, but a recent large randomised study from Finland did not find any effect. A feasibility study was carried out in Denmark in 2005-2006 where residents aged 50-74 years in 2 Danish counties were invited once to participate in gFOBT screening. We used the unique Danish registers to assess the impact of gFOBT screening in this group on CRC incidence and mortality. METHODS: In this cohort study, we followed a group comprising 166 277 individuals invited to screening and a reference group comprising the remaining 1 240 348 Danes of the same age. We linked the Danish population and health service registers to obtain information about colonoscopies, polypectomies, incident CRC and cause of death. RESULTS: After a median follow-up time of 8.9 years, the CRC mortality was significantly lower in the screening group than in the reference group with an adjusted HR (aHR) of 0.92 (95% CI 0.86 to 0.99), while the aHR for all-cause mortality was 0.95 (95% CI 0.94 to 0.96). For screening participants, the aHR for CRC mortality and all-cause mortality was 0.72 (0.64 to 0.80) and 0.59 (0.57 to 0.60), respectively. CONCLUSIONS: About 10 years after a single round of gFOBT screening, we found a significant 8% deficit in CRC mortality in the screening group compared with other Danes. We found almost the same deficit in all-cause mortality, and on this basis, it is not possible to conclude that one screening round had an effect on CRC mortality. Our study indicated that close monitoring of the outcome of CRC screening is warranted.

Risk stratification and detection of new colorectal neoplasms after colorectal cancer screening with faecal occult blood test: experiences from a Danish screening cohort.

BACKGROUND: Limited data exist on adenoma surveillance as recommended in the European guidelines for quality assurance in colorectal cancer (CRC) screening and diagnosis after faecal occult blood test (FOBT) screening. OBJECTIVE: To assess the European guidelines for adenoma surveillance after CRC screening with FOBT. MATERIALS AND METHODS: This was a population-based cohort-study of 176 782 Danish individuals aged 50-74 years invited for CRC screening in 2005-2006. Adenoma patients were stratified into risk groups (low A, medium B, high C) in accordance with the European guidelines and followed up for recurrence of new neoplasms until the end of 2011. Risk ratios (RR) between the risk groups were calculated to assess differences in the recurrence rates of neoplasms. RESULTS: Among 84 803 screening participants, 2059 had positive FOBT, of whom 1861 underwent colonoscopy, and 709 patients had screen-detected adenomas. During a median follow-up period of 72.7 months, detection of new advanced adenomas (B+C) was significantly higher in risk group C than group A (RR 2.25, 95% confidence interval: 1.13-4.48). Nine patients were diagnosed with CRC: one in risk group A, two in B and six in C. The detection rate of CRC was higher in risk group C than A (RR 5.20, 95% confidence interval: 0.63-42.58), but not statistically significant. In risk group C, half of new advanced adenomas were detected within the first year and four of nine CRC were detected within 3 years. CONCLUSION: Risk stratification of adenoma patients, as recommended by the European guidelines, is appropriate for postpolypectomy surveillance after FOBT screening.