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Pancreatic cancer (PC) is highly fatal, and its incidence is increasing in the United States. Population-based registry studies suggest associations between a few autoimmune conditions and PC risk, albeit based on a relatively small number of cases. We conducted a population-based, nested case-control study to examine the associations between autoimmune conditions and PC risk within the Surveillance, Epidemiology, and End Results Program (SEER)-Medicare population. Incident primary malignant PC cases (n = 80 074) were adults ≥66 years and diagnosed between 1992 and 2015. Controls (n = 320 296) were alive at the time cases were diagnosed and frequency-matched to cases (4:1 ratio) by age, sex, and year of diagnosis. We used multivariable-adjusted, unconditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for 45 autoimmune conditions identified from Medicare claims. Eight autoimmune conditions including ankylosing spondylitis (OR = 1.45; 95% CI: 1.14-1.84), Graves' disease (OR = 1.18; 95% CI: 1.03-1.34), localized scleroderma (OR = 1.27; 95% CI: 1.06-1.52), pernicious anemia (OR = 1.08; 95% CI: 1.02-1.14), primary sclerosing cholangitis (OR = 1.37; 95% CI: 1.18-1.59), pure red cell aplasia (OR = 1.31; 95% CI: 1.16-1.47), type 1 diabetes (OR = 1.11; 95% CI: 1.07-1.15), and ulcerative colitis (OR = 1.18; 95% CI: 1.07-1.31) were associated with increased PC risk (false discovery rate-adjusted P values.10). In subtype analyses, these conditions were associated with pancreatic ductal adenocarcinoma, whereas only ulcerative colitis was associated with pancreatic neuroendocrine tumors. Our results support the hypothesis that autoimmune conditions may play a role in PC development.

Background Body mass index (BMI) during adulthood has been associated with pancreatic ductal adenocarcinoma (PDAC), however, patterns of body size across the adult life course have not been studied extensively. We comprehensively evaluated the association between adiposity across adulthood and PDAC. Methods We conducted a prospective analysis of 269 480 (162 735 males, 106 745 females) National Institutes of Health–AARP Diet and Health Study participants, aged 50-71 years (1995-1996) who self-reported height and weight history. Participants were followed through December 31, 2011. We examined associations between BMI (kg/m2) at ages 18, 35, 50, and 50-71 (baseline) years, their trajectories determined from latent-class trajectory modeling, and incident PDAC. Cox proportional hazard models were used to calculate multivariable adjusted hazards ratios (HRs) and 95% confidence intervals (CIs). Results During up to 15.2 years of follow-up, 3092 (2020 males, 1072 females) patients with incident PDAC were identified. BMI at all 4 ages were statistically significantly associated with increased PDAC (per 5-unit increase, HR = 1.09-1.13) with higher magnitude associations in males than females at ages 35 years and older (Pinteraction Conclusions High BMI and BMI trajectories that result in overweight or obesity during adulthood were positively associated with PDAC, with stronger associations among those with early onset adiposity and those with male sex. Avoidance of excess body weight throughout the adult life course may prevent PDAC.

Pancreatic cancer (PC) is highly fatal, and its incidence is increasing in the United States. Population-based registry studies suggest associations between a few autoimmune conditions and PC risk, albeit based on a relatively small number of cases. We hypothesize that autoimmune conditions are associated with risk of PC. We conducted a population-based, nested case-control study to examine the association between autoimmune conditions and PC risk within the Surveillance, Epidemiology, and End Results Program (SEER)-Medicare population. Incident primary malignant PC cases (n=80,074) were adults > 66 years and diagnosed between 1992 and 2015. Controls (n=320,296) were alive at the time cases were diagnosed and frequency-matched to cases (4:1 ratio) by age, sex, and year of diagnosis. We used multivariable-adjusted, unconditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for 45 autoimmune conditions identified from Medicare claims. Eight autoimmune conditions including ankylosing spondylitis (OR = 1.45; 95% CI: 1.14-1.84), Graves’ disease (OR = 1.18; 95% CI: 1.03-1.34), localized scleroderma (OR = 1.27; 95% CI: 1.06-1.52), pernicious anemia (OR = 1.08; 95% CI: 1.02-1.14), primary sclerosing cholangitis (OR = 1.37; 95% CI: 1.18-1.59), pure red cell aplasia (OR = 1.31; 95% CI: 1.16-1.47), type 1 diabetes (OR = 1.11; 95% CI: 1.07-1.15), and ulcerative colitis (OR = 1.18; 95% CI: 1.07-1.31) were associated with increased PC risk (false discovery rate-adjusted P values < 0.10). In subtype analyses, these conditions were associated with pancreatic ductal adenocarcinoma, whereas only ulcerative colitis was associated with pancreatic neuroendocrine tumors. Our results support the hypothesis that autoimmune conditions may play a role in PC development. Citation Format: Fancheng Yuan, Ruth M. Pfeiffer, Sachelly Julian-Serrano, Simran Arjani, Michael J. Barrett, Jill Koshiol, Rachael Z. Stolzenberg-Solomon. Autoimmune conditions and pancreatic cancer risk in older American adults [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr B082.

Background: Adiposity is associated with pancreatic ductal adenocarcinoma (PDAC), but the effects of weight excess over an adult life course have not been studied extensively. We examined the association between trajectories of body mass index (BMI) from ages 18 up to 71 years and risk of subsequent PDAC. Methods: Our analysis included 270,722 (163,873 men, 106,849 women) NIH-AARP Diet and Health Study participants, 50-71y, who successfully completed questionnaires with self-reported height and weight at ages 18, 35, 50 and at baseline (50-71y, 1995-1996) and from which BMI (kg/m2) was calculated. We used latent class growth mixture modeling to identify BMI trajectories using adult BMI reported at each of the four timepoints. We identified BMI trajectories for all sample combined and separately for men and women. We then examined the association between BMI trajectories and incident PDAC using Cox proportional hazards models to calculate age, smoking, and sex adjusted hazard ratios (HR) and 95% confidence intervals (CI) overall and by sex. Participants that maintained normal weight status over their adulthood were set as the referent group. Results: Over an average follow-up time of 13.1 years (max: 15.17 years), 3105 incident PDAC cases (2033 men, 1072 women) were identified in the overall cohort. We identified four overall and sex specific BMI trajectory groups, each with one maintainer and three increasers. Participants either maintained normal weight (N-N, 37.1% of the cohort), or increased from normal-overweight (N-OW, 36.4%), normal-obese (N-O, 20.7%), or normal-severely obese (N-SO, 5.8%). The male cohort was divided into N-N (35.5%), N-OW (23.3%), normal-higher overweight (N-HOW, 34.8%), and N-SO (6.6%) while the female cohort was divided into N-N (51.6%), N-OW (34.5%), N-SO (11.3%), and OW-SO (2.7%). Compared to N-N, the N-OW (HR=1.12, 95% CI 1.03-1.21), N-O (1.22, 1.11-1.35) and N-SO (1.22, 1.04-1.45) groups were at significantly increased risk for PDAC. Compared to the sex-specific maintainer groups, men in the N-OW (1.14, 1.02-1.28), N-HOW (1.16, 1.04-1.29), and N-SO (1.39, 1.15-1.67) groups were significantly associated with PDAC, while only women in the N-OW (1.12, 1.00-1.29) group showed a borderline significant association. Adding diabetes to the models slightly attenuated the associations by less than 10% with the greatest attenuation observed in the SO groups. The overall associations were not significantly modified by sex (P-interaction = 0.10) or smoking status (never, former, current, P-interaction = 0.17). Conclusions: In this large prospective cohort study, increasing BMI throughout adulthood was associated with a greater risk for PDAC. Citation Format: Simran Arjani, Pedro F. Saint-Maurice, Sachelly Julian-Serrano, Rachael Stolzenberg-Solomon. Body mass index trajectories across the adult life course and pancreatic cancer risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 853.

e16079 Background: The most commonly used treatment options for gastric cancer include complete resection with adequate margins with either perioperative chemotherapy (PCT) or adjuvant chemoradiotherapy (CRT). While both treatment strategies have shown superiority over surgical resection alone, it is not clear which treatment strategy is more optimal. Methods: Our decision tree model was built to analyze the survival and costs associated with the two major management methods: perioperative chemotherapy and adjuvant chemoradiation therapy. Costs were obtained from Medicare reimbursement rates using a third-party payer perspective. Our model’s effectiveness was represented using quality-adjusted life years (QALYs). Our analysis tested the robustness of our conclusions by utilizing one-way, two-way, and probabilistic sensitivity analyses. Results: PCT was the preferred treatment strategy for diagnosed gastric cancer over CRT, with a cost of $54,326.10 and 4.08 QALYs. CRT was the costliest economic strategy with a cost of $77,987.52 and 4.28 QALYs and an ICER of 115,907.48. We set a threshold of $100,000 per QALYs gained which CRT surpassed making PCT the preferred treatment modality. Over 100,000 simulations, 51.4% of simulations favored PCT. CRT became favored when CRT non-curative procedure rates rose 3% higher than PCT non-curative procedure rates and when PCT complication rates rose 15% higher than CRT complication rates. Conclusions: In our simulated patients with diagnosed gastric cancer, the most cost-effective treatment strategy was PCT. We see cost-effectiveness alternating to favor CRT with changes in non-curative procedure rates and adjuvant therapy complication rates.[Table: see text]