Person:

Hur, Chin

Background: Thyroid cancer affects over ½ million people in the U.S. and the incidence of thyroid cancer has increased worldwide at a rate higher than any other cancer, while survival has remained largely unchanged. The aim of this research was to develop, calibrate and verify a mathematical disease model to simulate the natural history of papillary thyroid cancer, which will serve as a platform to assess the effectiveness of clinical and cancer control interventions. Methods: Herein, we modeled the natural pre-clinical course of both benign and malignant thyroid nodules with biologically relevant health states from normal to detected nodule. Using established calibration techniques, optimal parameter sets for tumor growth characteristics, development rate, and detection rate were used to fit Surveillance Epidemiology and End Results (SEER) incidence data and other calibration targets. Results: Model outputs compared to calibration targets demonstrating sufficient calibration fit and model validation are presented including primary targets of SEER incidence data and size distribution at detection of malignancy. Additionally, we show the predicted underlying benign and malignant prevalence of nodules in the population, the probability of detection based on size of nodule, and estimates of growth over time in both benign and malignant nodules. Conclusions: This comprehensive model provides a dynamic platform employable for future comparative effectiveness research. Future model analyses will test and assess various clinical management strategies to improve patient outcomes related to thyroid cancer and optimize resource utilization for patients with thyroid nodules.

Barrett’s esophagus (BE) develops as a consequence of chronic esophageal acid exposure, and is the major risk factor for esophageal adenocarcinoma (EAC). The practices of endoscopic screening for—and surveillance of—BE, while widespread, have failed to reduce the incidence of EAC. The majority of EACs are diagnosed in patients without a known history of BE, and current diagnostic tools are lacking in their ability to stratify patients with BE into those at low risk and those at high risk for progression to malignancy. Nonetheless, advances in endoscopic imaging and mucosal therapeutics have provided unprecedented opportunities for intervention for BE, and have vastly altered the approach to management of BE-associated mucosal neoplasia.

Background: BRCA2 mutation carriers are at increased risk for multiple cancers including pancreatic adenocarcinoma (PAC). Our goal was to compare the effectiveness of different PAC screening strategies in BRCA2 mutation carriers, from the standpoint of life expectancy. Methods: A previously published Markov model of PAC was updated and extended to incorporate key aspects of BRCA2 mutation carrier status, including competing risks of breast- and ovarian-cancer specific mortality. BRCA2 mutation carriers were modeled and analyzed as the primary cohort for the analysis. Additional higher risk BRCA2 cohorts that were stratified according to the number of first-degree relatives (FDRs) with PAC were also analyzed. For each cohort, one-time screening and annual screening were evaluated, with screening starting at age 50 in both strategies. The primary outcome was net gain in life expectancy (LE) compared to no screening. Sensitivity analysis was performed on key model parameters, including surgical mortality and MRI test performance. Findings: One-time screening at age 50 resulted in a LE gain of 3.9 days for the primary BRCA2 cohort, and a gain of 5.8 days for those with BRCA2 and one FDR. Annual screening resulted in LE loss of 12.9 days for the primary cohort and 1.3 days for BRCA2 carriers with 1 FDR, but resulted in 20.6 days gained for carriers with 2 FDRs and 260 days gained for those with 3 FDRs. For patients with ≥ 3 FDRs, annual screening starting at an earlier age (i.e. 35–40) was optimal. Interpretation Among BRCA2 mutation carriers, aggressive screening regimens may be ineffective unless additional indicators of elevated risk (e.g., 2 or more FDRs) are present. More clinical studies are needed to confirm these findings. Funding American Cancer Society – New England Division – Ellison Foundation Research Scholar Grant (RSG-15-129-01-CPHPS).

Objectives: Barrett’s esophagus (BE) is the only known precursor to esophageal adenocarcinoma. Data examining the association of aspirin with the onset of BE, particularly for women, are scant and conflicting. Methods: We leveraged data from 121,700 women enrolled in the Nurses’ Health Study, a large prospective cohort study, who biennially provided detailed information regarding endoscopy and use of aspirin. We used unconditional logistic regression to obtain multivariable (MV)-adjusted odds ratios (ORs) and 95% confidence intervals (CI) to estimate the risk of BE in regular aspirin users (≥2 times/week) compared to non-regular users. Results: Among 27,881 women who had undergone upper GI endoscopy, we documented 667 BE cases over 18 years of follow-up. Compared to non-regular users, women who regularly used aspirin had a MV-adjusted OR for BE of 0.85 (95%CI: 0.72, 0.99). The corresponding OR was 0.73 (95%CI: 0.56, 0.96) for BE at least 1 cm long. Compared with women who did not use any aspirin, the MV-adjusted OR for any BE was 0.91 (95% CI, 0.69, 1.20) for women taking 0.5-1.5 tablets/week; 0.92 (95%CI 0.76, 1.11) for 2–5 tablets/week; and 0.71 (95%CI 0.55, 0.92) for ≥6 tablets/week (p-trend=0.01). Compared with non-regular users, the MV-adjusted OR for BE risk was 0.90 (95%CI 0.67, 1.20) for women who regularly used aspirin for 1–5 years, 0.84 (95%CI 0.65, 1.09) for 6–10 years, and 0.81 (95%CI 0.67, 0.97) for >10 years (p-trend=0.03). Conclusion: Regular aspirin use was associated with a reduction in the risk of Barrett’s esophagus in women. The reduction in risk appeared related to higher dose and longer duration of use.

Background and study aims The objective of this study was to assess patient involvement in decision-making, decision confidence, and decision regret among patients who had undergone endoscopic eradication therapy (EET) or esophagectomy for Barrett’s esophagus (BE) associated neoplasia. Patients and methods Patients with BE high grade dysplasia or intramucosal (T1a) adenocarcinoma who had undergone EET or esophagectomy were invited to complete a survey. Results: The cohort included 50 subjects, 70 % (35/50) of whom had undergone EET and 30 % (15/50) of whom had undergone esophagectomy. Subjects who underwent esophagectomy were more likely to report post-treatment dysphagia (47 % vs 14 %, P = 0.03), post-treatment dietary modification (73 % vs 6 %, P < 0.0001), and were less likely to view their post-treatment health favorably. However, when asked whether they had selected the right treatment, a high degree of confidence was reported by both groups (mean 9.8 for EET vs 9.3 for esophagectomy on a 0 – 10 scale, P = 0.12). In fact, 97 % (34/35) of EET patients and 80 % (12/15) of esophagectomy patients indicated they would select the same treatment option ( P = 0.08). Conclusions: Patients who have undergone EET or surgery for BE neoplasia report a high degree of involvement in the decision-making process. Although EET patients report fewer symptom-specific outcomes, measures of decision confidence and decision regret do not differ between the two treatment groups.

Abstract Age, sex, and racial/ethnic disparities exist, but are understudied in pancreatic adenocarcinoma (PDAC). We used the Surveillance, Epidemiology, and End Results (SEER)–Medicare linked database to determine whether survival and treatment disparities persist after adjusting for demographic and clinical characteristics. Our study included PDAC patients diagnosed between 1992 and 2011. We used Cox regression to compare survival across age, sex, and race/ethnicity within early‐stage and late‐stage cancer subgroups, adjusting for marital status, urban location, socioeconomics, SEER region, comorbidities, stage, lymph node status, tumor location, tumor grade, diagnosis year, and treatment received. We used logistic regression to compare differences in treatment received across age, sex, and race/ethnicity. Among 20,896 patients, 84% were White, 9% Black, 5% Asian, and 2% Hispanic. Median age was 75; 56% were female and 53% had late‐stage cancer. Among early‐stage patients in the adjusted Cox model, older patient subgroups had worse survival compared with ages 66–69 (HR > 1.1, P < 0.01 for groups >69); no survival differences existed between sexes. Black (HR = 1.1, P = 0.01) and Hispanic (HR = 1.2, P < 0.01) patients had worse survival compared with White. Among late‐stage cancer patients, patients over age 84 had worse survival than those aged 66–69 (HR = 1.1, P < 0.01), and males (HR = 1.08, P < 0.01) had worse survival than females; there were no racial/ethnic differences. Older age and minority race/ethnicity were associated with lower likelihood of receiving chemotherapy, radiation, and/or surgery. Age and racial/ethnic disparities in survival outcomes and treatment received exist for PDAC patients; these disparities persist after adjusting for differences in demographic and clinical characteristics.