Dataset Information

Predicting colorectal cancer risk from adenoma detection via a two-type branching process model.

ABSTRACT: Despite advances in the modeling and understanding of colorectal cancer development, the dynamics of the progression from benign adenomatous polyp to colorectal carcinoma are still not fully resolved. To take advantage of adenoma size and prevalence data in the National Endoscopic Database of the Clinical Outcomes Research Initiative (CORI) as well as colorectal cancer incidence and size data from the Surveillance Epidemiology and End Results (SEER) database, we construct a two-type branching process model with compartments representing adenoma and carcinoma cells. To perform parameter inference we present a new large-size approximation to the size distribution of the cancer compartment and validate our approach on simulated data. By fitting the model to the CORI and SEER data, we learn biologically relevant parameters, including the transition rate from adenoma to cancer. The inferred parameters allow us to predict the individualized risk of the presence of cancer cells for each screened patient. We provide a web application which allows the user to calculate these individual probabilities at https://ccrc-eth.shinyapps.io/CCRC/. For example, we find a 1 in 100 chance of cancer given the presence of an adenoma between 10 and 20mm size in an average risk patient at age 50. We show that our two-type branching process model recapitulates the early growth dynamics of colon adenomas and cancers and can recover epidemiological trends such as adenoma prevalence and cancer incidence while remaining mathematically and computationally tractable.

SUBMITTER: Lang BM

PROVIDER: S-EPMC7001909 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Predicting colorectal cancer risk from adenoma detection via a two-type branching process model.

Lang Brian M BM Kuipers Jack J Misselwitz Benjamin B Beerenwinkel Niko N

PLoS computational biology 20200205 2

Despite advances in the modeling and understanding of colorectal cancer development, the dynamics of the progression from benign adenomatous polyp to colorectal carcinoma are still not fully resolved. To take advantage of adenoma size and prevalence data in the National Endoscopic Database of the Clinical Outcomes Research Initiative (CORI) as well as colorectal cancer incidence and size data from the Surveillance Epidemiology and End Results (SEER) database, we construct a two-type branching pr ...[more]

PMID: 32023238

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Project description:The proportion of screening colonoscopic examinations performed by a physician that detect one or more adenomas (the adenoma detection rate) is a recommended quality measure. However, little is known about the association between this rate and patients' risks of a subsequent colorectal cancer (interval cancer) and death.Using data from an integrated health care delivery organization, we evaluated the associations between the adenoma detection rate and the risks of colorectal cancer diagnosed 6 months to 10 years after colonoscopy and of cancer-related death. With the use of Cox regression, our estimates of attributable risk were adjusted for the demographic characteristics of the patients, indications for colonoscopy, and coexisting conditions.We evaluated 314,872 colonoscopies performed by 136 gastroenterologists; the adenoma detection rates ranged from 7.4 to 52.5%. During the follow-up period, we identified 712 interval colorectal adenocarcinomas, including 255 advanced-stage cancers, and 147 deaths from interval colorectal cancer. The unadjusted risks of interval cancer according to quintiles of adenoma detection rates, from lowest to highest, were 9.8, 8.6, 8.0, 7.0, and 4.8 cases per 10,000 person-years of follow-up, respectively. Among patients of physicians with adenoma detection rates in the highest quintile, as compared with patients of physicians with detection rates in the lowest quintile, the adjusted hazard ratio for any interval cancer was 0.52 (95% confidence interval [CI], 0.39 to 0.69), for advanced-stage interval cancer, 0.43 (95% CI, 0.29 to 0.64), and for fatal interval cancer, 0.38 (95% CI, 0.22 to 0.65). Each 1.0% increase in the adenoma detection rate was associated with a 3.0% decrease in the risk of cancer (hazard ratio, 0.97; 95% CI, 0.96 to 0.98).The adenoma detection rate was inversely associated with the risks of interval colorectal cancer, advanced-stage interval cancer, and fatal interval cancer. (Funded by the Kaiser Permanente Community Benefit program and the National Cancer Institute.).

Project description:ImportanceAlthough colonoscopy is frequently performed in the United States, there is limited evidence to support threshold values for physician adenoma detection rate as a quality metric.ObjectiveTo evaluate the association between physician adenoma detection rate values and risks of postcolonoscopy colorectal cancer and related deaths.Design, setting, and participantsRetrospective cohort study in 3 large integrated health care systems (Kaiser Permanente Northern California, Kaiser Permanente Southern California, and Kaiser Permanente Washington) with 43 endoscopy centers, 383 eligible physicians, and 735 396 patients aged 50 to 75 years who received a colonoscopy that did not detect cancer (negative colonoscopy) between January 2011 and June 2017, with patient follow-up through December 2017.ExposuresThe adenoma detection rate of each patient's physician based on screening examinations in the calendar year prior to the patient's negative colonoscopy. Adenoma detection rate was defined as a continuous variable in statistical analyses and was also dichotomized as at or above vs below the median for descriptive analyses.Main outcomes and measuresThe primary outcome (postcolonoscopy colorectal cancer) was tumor registry-verified colorectal adenocarcinoma diagnosed at least 6 months after any negative colonoscopy (all indications). The secondary outcomes included death from postcolonoscopy colorectal cancer.ResultsAmong 735 396 patients who had 852 624 negative colonoscopies, 440 352 (51.6%) were performed on female patients, median patient age was 61.4 years (IQR, 55.5-67.2 years), median follow-up per patient was 3.25 years (IQR, 1.56-5.01 years), and there were 619 postcolonoscopy colorectal cancers and 36 related deaths during more than 2.4 million person-years of follow-up. The patients of physicians with higher adenoma detection rates had significantly lower risks for postcolonoscopy colorectal cancer (hazard ratio [HR], 0.97 per 1% absolute adenoma detection rate increase [95% CI, 0.96-0.98]) and death from postcolonoscopy colorectal cancer (HR, 0.95 per 1% absolute adenoma detection rate increase [95% CI, 0.92-0.99]) across a broad range of adenoma detection rate values, with no interaction by sex (P value for interaction = .18). Compared with adenoma detection rates below the median of 28.3%, detection rates at or above the median were significantly associated with a lower risk of postcolonoscopy colorectal cancer (1.79 vs 3.10 cases per 10 000 person-years; absolute difference in 7-year risk, -12.2 per 10 000 negative colonoscopies [95% CI, -10.3 to -13.4]; HR, 0.61 [95% CI, 0.52-0.73]) and related deaths (0.05 vs 0.22 cases per 10 000 person-years; absolute difference in 7-year risk, -1.2 per 10 000 negative colonoscopies [95%, CI, -0.80 to -1.69]; HR, 0.26 [95% CI, 0.11-0.65]).Conclusions and relevanceWithin 3 large community-based settings, colonoscopies by physicians with higher adenoma detection rates were significantly associated with lower risks of postcolonoscopy colorectal cancer across a broad range of adenoma detection rate values. These findings may help inform recommended targets for colonoscopy quality measures.

Project description:Colonoscopy is the most commonly used colorectal cancer screening test in the United States. Its quality, as measured by adenoma detection rates (ADRs), varies widely among physicians, with unknown consequences for the cost and benefits of screening programs.To estimate the lifetime benefits, complications, and costs of an initial colonoscopy screening program at different levels of adenoma detection.Microsimulation modeling with data from a community-based health care system on ADR variation and cancer risk among 57,588 patients examined by 136 physicians from 1998 through 2010.Using modeling, no screening was compared with screening initiation with colonoscopy according to ADR quintiles (averages 15.3%, quintile 1; 21.3%, quintile 2; 25.6%, quintile 3; 30.9%, quintile 4; and 38.7%, quintile 5) at ages 50, 60, and 70 years with appropriate surveillance of patients with adenoma.Estimated lifetime colorectal cancer incidence and mortality, number of colonoscopies, complications, and costs per 1000 patients, all discounted at 3% per year and including 95% confidence intervals from multiway probabilistic sensitivity analysis.In simulation modeling, among unscreened patients the lifetime risk of colorectal cancer incidence was 34.2 per 1000 (95% CI, 25.9-43.6) and risk of mortality was 13.4 per 1000 (95% CI, 10.0-17.6). Among screened patients, simulated lifetime incidence decreased with lower to higher ADRs (26.6; 95% CI, 20.0-34.3 for quintile 1 vs 12.5; 95% CI, 9.3-16.5 for quintile 5) as did mortality (5.7; 95% CI, 4.2-7.7 for quintile 1 vs 2.3; 95% CI, 1.7-3.1 for quintile 5). Compared with quintile 1, simulated lifetime incidence was on average 11.4% (95% CI, 10.3%-11.9%) lower for every 5 percentage-point increase of ADRs and for mortality, 12.8% (95% CI, 11.1%-13.7%) lower. Complications increased from 6.0 (95% CI, 4.0-8.5) of 2777 colonoscopies (95% CI, 2626-2943) in quintile 1 to 8.9 (95% CI, 6.1-12.0) complications of 3376 (95% CI, 3081-3681) colonoscopies in quintile 5. Estimated net screening costs were lower from quintile 1 (US $2.1 million, 95% CI, $1.8-$2.4 million) to quintile 5 (US $1.8 million, 95% CI, $1.3-$2.3 million) due to averted cancer treatment costs. Results were stable across sensitivity analyses.In this microsimulation modeling study, higher adenoma detection rates in screening colonoscopy were associated with lower lifetime risks of colorectal cancer and colorectal cancer mortality without being associated with higher overall costs. Future research is needed to assess whether increasing adenoma detection would be associated with improved patient outcomes.

Project description:The adenoma detection rate (ADR) varies widely between physicians, possibly due to patient population differences, hampering direct ADR comparison. We developed and validated a prediction model for adenoma detection in an effort to determine if physicians' ADRs should be adjusted for patient-related factors.Screening and surveillance colonoscopy data from the cross-sectional multicenter cluster-randomized Endoscopic Quality Improvement Program-3 (EQUIP-3) study (NCT02325635) was used. The dataset was split into two cohorts based on center. A prediction model for detection of ?1 adenoma was developed using multivariable logistic regression and subsequently internally (bootstrap resampling) and geographically validated. We compared predicted to observed ADRs.The derivation (5 centers, 35 physicians, overall-ADR: 36%) and validation (4 centers, 31 physicians, overall-ADR: 40%) cohort included respectively 9934 and 10034 patients (both cohorts: 48% male, median age 60 years). Independent predictors for detection of ?1 adenoma were: age (optimism-corrected odds ratio (OR): 1.02; 95%-confidence interval (CI): 1.02-1.03), male sex (OR: 1.73; 95%-CI: 1.60-1.88), body mass index (OR: 1.02; 95%-CI: 1.01-1.03), American Society of Anesthesiology physical status class (OR class II vs. I: 1.29; 95%-CI: 1.17-1.43, OR class ?III vs. I: 1.57; 95%-CI: 1.32-1.86), surveillance versus screening (OR: 1.39; 95%-CI: 1.27-1.53), and Hispanic or Latino ethnicity (OR: 1.13; 95%-CI: 1.00-1.27). The model's discriminative ability was modest (C-statistic in the derivation: 0.63 and validation cohort: 0.60). The observed ADR was considerably lower than predicted for 12/66 (18.2%) physicians and 2/9 (22.2%) centers, and considerably higher than predicted for 18/66 (27.3%) physicians and 4/9 (44.4%) centers.The substantial variation in ADRs could only partially be explained by patient-related factors. These data suggest that ADR variation could likely also be due to other factors, e.g. physician or technical issues.

Project description:OBJECTIVES: The decision tree underlying current practice guidelines for post polypectomy surveillance relies on risk stratification based on predictive attributes gleaned from adenomas removed on screening colonoscopy examination. Our primary aim was to estimate the magnitude of association between baseline adenoma attributes and the risk of adenoma recurrence and invasive colorectal adenocarcinoma (CRC). Our secondary aims were to estimate the adenoma detection rate (ADR) of surveillance compared with screening colonoscopies and describe time trends in preventive colonoscopy utilization. METHODS: We used prospective analyses of retrospectively collected clinical data from electronic health records. A cohort of primary care patients eligible for colorectal cancer screening was assembled encompassing 110,452 subjects, of which 3,300 had adenomas removed on screening examination. Of those patients who had a follow-up surveillance colonoscopy (defined as a patient with a documented adenoma on prior colonoscopy) recorded during the study period, 537 had a recurrent adenoma. RESULTS: Of those recurrent adenomas, 354 had a high-risk attributes. High-risk attributes were described at >3 adenomas, at least one adenoma >10 mm in size, high-grade dysplasia, or villous features. The risk of developing invasive CRC among post polypectomy patients was significantly higher if the baseline adenomas displayed any of the following attributes: more numerous than 3 (4.3-fold higher risk, 95% confidence interval (CI) low, high 1.4, 12.9), larger than 10 mm in size (5.2-fold higher risk, 95% CI low, high 1.8, 15.1), high-grade dysplasia (13.2-fold risk, 95% CI low, high 2.8, 62.1), or villous features (7.4-fold higher risk, 95% CI low, high 2.5, 21.5). These attributes combined added a net value of 22.8% to the probability of correctly predicting CRC. There was a threefold increase in surveillance utilization relative to screening from 2005 to 2011. The ADR of surveillance (34.1%) was 1.5-fold higher than that of screening (23.1%). CONCLUSIONS: These results emphasize the need to mitigate excessive risk by performing timely surveillance colonoscopies in patients with baseline adenomas displaying high-risk attributes as recommended in practice guidelines.

Dataset Information

Predicting colorectal cancer risk from adenoma detection via a two-type branching process model.

Publications

Predicting colorectal cancer risk from adenoma detection via a two-type branching process model.

Similar Datasets

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