Genetic testing to guide screening for pancreatic ductal adenocarcinoma: Results of a microsimulation model.

BACKGROUND: First-degree relatives (FDRs) of patients with pancreatic ductal adenocarcinoma (PDAC) have elevated PDAC risk, partially due to germline genetic variants. We evaluated the potential effectiveness of genetic testing to target MRI-based screening among FDRs. METHODS: We used a microsimulation model of PDAC, calibrated to Surveillance, Epidemiology, and End Results (SEER) data, to estimate the potential life expectancy (LE) gain of screening for each of the following groups of FDRs: individuals who test positive for each of eight variants associated with elevated PDAC risk (e.g., BRCA2, CDKN2A); individuals who test negative; and individuals who do not test. Screening was assumed to take place if LE gains were achievable. We simulated multiple screening approaches, defined by starting age and frequency. Sensitivity analysis evaluated changes in results given varying model assumptions. RESULTS: For women, 92% of mutation carriers had projected LE gains from screening for PDAC, if screening strategies (start age, frequency) were optimized. Among carriers, LE gains ranged from 0.1 days (ATM+ women screened once at age 70) to 510 days (STK11+ women screened annually from age 40). For men, LE gains were projected for all mutation carriers, ranging from 0.2 days (BRCA1+ men screened once at age 70) to 620 days (STK11+ men screened annually from age 40). For men and women who did not undergo genetic testing, or for whom testing showed no variant, screening yielded small LE benefit (0-2.1 days). CONCLUSIONS: Genetic testing of FDRs can inform targeted PDAC screening by identifying which FDRs may benefit.

Cost-Effectiveness of Treatment Thresholds for Subsolid Pulmonary Nodules in CT Lung Cancer Screening.

Background Guidelines such as the Lung CT Screening Reporting and Data System (Lung-RADS) are available for determining when subsolid nodules should be treated within lung cancer screening programs, but they are based on expert opinion. Purpose To evaluate the cost-effectiveness of varying treatment thresholds for subsolid nodules within a lung cancer screening setting by using a simulation model. Materials and Methods A previously developed model simulated 10 million current and former smokers undergoing CT lung cancer screening who were assumed to have a ground-glass nodule (GGN) at baseline. Nodules were allowed to grow and to develop solid components over time according to a monthly cycle and lifetime horizon. Management strategies generated by varying treatment thresholds, including the solid component size and use of the Brock risk calculator, were tested. For each strategy, average U.S. costs and quality-adjusted life years (QALYs) gained per patient were computed, and the incremental cost-effectiveness ratios (ICERs) of those on the efficient frontier were calculated. One-way and probabilistic sensitivity analyses of results were performed by varying several relevant parameters, such as treatment costs or malignancy growth rates. Results Variants of the Lung-RADS guidelines that did not treat pure GGNs were cost-effective. Strategies based on the Brock risk calculator did not reach the efficient frontier. The strategy with the highest QALYs under a willingness-to-pay threshold of $100 000 per QALY included no treatment of GGNs and a threshold of 4-mm solid component size for treatment of subsolid nodules. This strategy yielded an ICER of $52 993 per QALY (95% CI: 44 407, 64 372). Probabilistic sensitivity analysis showed this was the optimal strategy under a range of parameter variations. Conclusion Treatment of pure ground-glass nodules was not cost-effective. Strategies that use modifications of the Lung CT Screening Reporting and Data System guidelines were cost-effective for treating part-solid nodules; an optimal threshold of 4 mm for the solid component yielded the most quality-adjusted life years. © RSNA, 2021 Online supplemental material is available for this article.

Cost and Utilization of Lung Cancer End-of-Life Care Among Racial-Ethnic Minority Groups in the United States.

BACKGROUND: The end-of-life period is a crucial time in lung cancer care. To have a better understanding of the racial-ethnic disparities in health care expenditures, access, and quality, we evaluated these disparities specifically in the end-of-life period for patients with lung cancer in the U.S. MATERIALS AND METHODS: We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare database to analyze characteristics of lung cancer care among those diagnosed between the years 2000 and 2011. Linear and logistic regression models were constructed to measure racial-ethnic disparities in end-of-life care cost and utilization among non-Hispanic (NH) Asian, NH black, Hispanic, and NH white patients while controlling for other risk factors such as age, sex, and SEER geographic region. RESULTS: Total costs and hospital utilization were, on average, greater among racial-ethnic minorities compared with NH white patients in the last month of life. Among patients with NSCLC, the relative total costs were 1.27 (95% confidence interval [CI], 1.21-1.33) for NH black patients, 1.36 (95% CI, 1.25-1.49) for NH Asian patients, and 1.21 (95% CI, 1.07-1.38) for Hispanic patients. Additionally, the odds of being admitted to a hospital for NH black, NH Asian, and Hispanic patients were 1.22 (95% CI, 1.15-1.30), 1.47 (95% CI, 1.32-1.63), and 1.18 (95% CI, 1.01-1.38) times that of NH white patients, respectively. Similar results were found for patients with SCLC. CONCLUSION: Minority patients with lung cancer have significantly higher end-of-life medical expenditures than NH white patients, which may be explained by a greater intensity of care in the end-of-life period. IMPLICATIONS FOR PRACTICE: This study investigated racial-ethnic disparities in the cost and utilization of medical care among lung cancer patients during the end-of-life period. Compared with non-Hispanic white patients, racial-ethnic minority patients were more likely to receive intensive care in their final month of life and had statistically significantly higher end-of-life care costs. The findings of this study may lead to a better understanding of the racial-ethnic disparities in end-of-life care, which can better inform future end-of-life interventions and help health care providers develop less intensive and more equitable care, such as culturally competent advanced care planning programs, for all patients.

A Decision Analysis of Follow-up and Treatment Algorithms for Nonsolid Pulmonary Nodules.

Purpose To evaluate management strategies and treatment options for patients with ground-glass nodules (GGNs) by using decision-analysis models. Materials and Methods A simulation was developed for 1 000 000 hypothetical patients with GGNs undergoing follow-up per the Lung Imaging Reporting and Data System (Lung-RADS) recommendations. The initial age range was 55-75 years (mean, 64 years). Nodules could grow and develop solid components over time. Clinically significant malignancy rates were calibrated to data from the National Lung Screening Trial. Annual versus 3-year-interval follow-up of Lung-RADS category 2 nodules was compared, and different treatment strategies were tested (stereotactic body radiation therapy, surgery, and no therapy). Results Overall, 2.3% (22 584 of 1 000 000) of nodules were clinically significant malignancies; 6.3% (62 559 of 1 000 000) of nodules were treated. Only 30% (18 668 of 62 559) of Lung-RADS category 4B or 4X nodules were clinically significant malignancies. The risk of clinically significant malignancy for persistent nonsolid nodules after baseline was higher than Lung-RADS estimates for categories 2 and 3 (3% vs <1% and 1%-2%, respectively). Overall survival (OS) at 10 years was 72% (527 827 of 737 306; 95% confidence interval [CI]: 71%, 72%) with annual follow-up and 71% (526 507 of 737 306; 95% CI: 71%, 72%) with 3-year-interval follow-up (P < .01). At 10 years, OS among patients whose nodules progressed to Lung-RADS category 4B or 4X was 80% after radiation therapy (49 945 of 62 559; 95% CI: 80%, 80%), 79% after surgery (49 139 of 62 559; 95% CI: 78%, 79%), and 74% after no therapy (46 512 of 62 559; 95% CI: 74%, 75%) (P < .01). Conclusion Simulation modeling suggests that the follow-up interval for evaluating ground-glass nodules can be increased from 1 year to 3 years with minimal change in outcomes. Stereotactic body radiation therapy demonstrated the best outcomes compared with lobectomy and with no therapy for nonsolid nodules. © RSNA, 2018 Online supplemental material is available for this article.

Progression to pancreatic ductal adenocarcinoma from pancreatic intraepithelial neoplasia: Results of a simulation model.

OBJECTIVES: To gain insight into the natural history and carcinogenesis pathway of Pancreatic Intraepithelial Neoplasia (PanIN) lesions by building a calibrated simulation model of PanIN progression to pancreatic ductal adenocarcinoma (PDAC) METHODS: We revised a previously validated simulation model of solid PDAC, calibrating the model to fit data from the National Cancer Institute's Surveillance, Epidemiology, and End Results program and published literature on PanIN prevalence by age. We estimated the likelihood of progression from PanIN states (1, 2, and 3) to PDAC and the time between PanIN onset and PDAC (dwell time). We evaluated a hypothetical intervention to test for and treat PanIN 3 lesions to estimate the potential benefits from PanIN detection. RESULTS: We estimated the lifetime probability of progressing from PanIN 1 to PDAC to be 1.5% (men), 1.3% (women). Progression from PanIN 1 to PDAC took 33.6 years and 35.3 years, respectively, and from PanIN 3 to PDAC took 11.3 years and 12.3 years. A hypothetical test for PanIN 3 detection and treatment could provide a maximum, average life expectancy gain of 40 days. CONCLUSIONS: Our modeling analysis estimates PanINs have a relatively indolent course to PDAC, supporting the feasibility of potential future early detection strategies.

Cost-Effectiveness Analysis of Screening for Pancreatic Cancer Among High-Risk Populations.

PURPOSE: We evaluated the potential cost-effectiveness of combined magnetic resonance imaging (MRI) and endoscopic ultrasound (EUS) screening for pancreatic ductal adenocarcinoma (PDAC) among populations at high risk for the disease. METHODS: We used a microsimulation model of the natural history of PDAC to estimate the lifetime health benefits, costs, and cost-effectiveness of PDAC screening among populations with specific genetic risk factors for PDAC, including BRCA1 and BRCA2, PALB2, ATM, Lynch syndrome, TP53, CDKN2A, and STK11. For each high-risk population, we simulated 29 screening strategies, defined by starting age and frequency. Screening included MRI with follow-up EUS in a subset of patients. Costs of tests were based on Medicare reimbursement for MRI, EUS, fine-needle aspiration biopsy, and pancreatectomy. Cancer-related cost by stage of disease and phase of treatment was based on the literature. For each high-risk population, we performed an incremental cost-effectiveness analysis, assuming a willingness-to-pay (WTP) threshold of $100,000 US dollars (USD) per quality-adjusted life year (QALY) gained. RESULTS: For men with relative risk (RR) 12.33 (CDKN2A) and RR 28 (STK11), annual screening was cost-effective, starting at age 55 and 40 years, respectively. For women, screening was only cost-effective for those with RR 28 (STK11), with annual screening starting at age 45 years. CONCLUSION: Combined MRI/EUS screening may be a cost-effective approach for the highest-risk populations (among mutations considered, those with RR >12). However, for those with moderate risk (RR, 5-12), screening would only be cost-effective at higher WTP thresholds (eg, $200K USD/QALY) or with once-only screening.

Ultrasound Surveillance of Small, Incidentally Detected Gallbladder Polyps: Projected Benefits by Sex, Age, and Comorbidity Level.

OBJECTIVE: Incidentally detected gallbladder polyps are commonly encountered when performing upper abdominal ultrasound. Our purpose was to estimate the life expectancy (LE) benefit of ultrasound-based gallbladder surveillance in patients with small (6-7 to <10 mm), incidentally detected gallbladder polyps, accounting for patient sex, age, and comorbidity level. METHODS: We developed a decision-analytic Markov model to evaluate hypothetical cohorts of women and men with small gallbladder polyps, with varying age (66-80 years) and comorbidity level (none, mild, moderate, severe). Drawing from current evidence, in the base case, we assumed no increased risk of gallbladder cancer in patients with small gallbladder polyps. To estimate maximal possible LE gains from surveillance, we assumed perfect cancer control consequent to 5 years of surveillance. We varied key assumptions including cancer risk and test performance characteristics in sensitivity analysis. RESULTS: Projected LE gains from surveillance were <3 days across most cohorts and scenarios evaluated. For 66- and 80-year-olds with no comorbidities, LE gains were 1.46 and 1.45 days, respectively, for women, and 0.67 and 0.75 days for men. With 10 years of surveillance, LE gains increased to 2.94 days for 66-year-old women with no comorbidities (men: 1.35 days). If we assumed a 10% increase in gallbladder cancer risk among individuals with polyps, LE gains increased slightly to 1.60 days for 66-year-old women with no comorbidities (men: 0.74 days). Results were sensitive to test performance and surgical mortality. DISCUSSION: Even under unrealistic, optimistic assumptions of cancer control, ultrasound surveillance of incidentally detected small gallbladder polyps provided limited benefit.

Racial/ethnic disparities in colorectal cancer treatment utilization and phase-specific costs, 2000-2014.

BACKGROUND: Our study analyzed disparities in utilization and phase-specific costs of care among older colorectal cancer patients in the United States. We also estimated the phase-specific costs by cancer type, stage at diagnosis, and treatment modality. METHODS: We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare database to identify patients aged 66 or older diagnosed with colon or rectal cancer between 2000-2013, with follow-up to death or December 31, 2014. We divided the patient's experience into separate phases of care: staging or surgery, initial, continuing, and terminal. We calculated total, cancer-attributable, and patient-liability costs. We fit logistic regression models to determine predictors of treatment receipt and fit linear regression models to determine relative costs. All costs are reported in 2019 US dollars. RESULTS: Our cohort included 90,023 colon cancer patients and 25,581 rectal cancer patients. After controlling for patient and clinical characteristics, Non-Hispanic Blacks were less likely to receive treatment but were more likely to have higher cancer-attributable costs within different phases of care. Overall, in both the colon and rectal cancer cohorts, mean monthly cost estimates were highest in the terminal phase, next highest in the staging phase, decreased in the initial phase, and were lowest in the continuing phase. CONCLUSIONS: Racial/ethnic disparities in treatment utilization and costs persist among colorectal cancer patients. Additionally, colorectal cancer costs are substantial and vary widely among stages and treatment modalities. This study provides information regarding cost and treatment disparities that can be used to guide clinical interventions and future resource allocation to reduce colorectal cancer burden.

Cost-Effectiveness of Follow-Up for Subsolid Pulmonary Nodules in High-Risk Patients.

OBJECTIVE: To evaluate the cost-effectiveness of a number of follow-up guidelines and variants for subsolid pulmonary nodules. METHODS: We used a simulation model informed by data from the literature and the National Lung Screening Trial to simulate patients with ground-glass nodules (GGNs) detected at baseline computed tomography undergoing follow-up. The nodules were allowed to grow and develop solid components over time. We tested the guidelines generated by varying follow-up recommendations for low-risk nodules, that is, pure GGNs or those stable over time. For each guideline, we computed average US costs and quality-adjusted life-years (QALYs) gained per patient and identified the incremental cost-effectiveness ratios of those on the efficient frontier. In addition, we compared the costs and effects of the most recently released version of the Lung Computed Tomography Screening Reporting and Data System (Lung-RADS), version 1.1, with those of the previous version, 1.0. Finally, we performed sensitivity analyses of our results by varying several relevant parameters. RESULTS: Relative to the no follow-up scenario, the follow-up guideline system that was cost-effective at a willingness-to-pay of $100,000/QALY and had the greatest QALY assigned low-risk nodules a 2-year follow-up interval and stopped follow-up after 2 years for GGNs and after 5 years for part-solid nodules; this strategy yielded an incremental cost-effectiveness ratio of $99,970. Lung-RADS version 1.1 was found to be less costly but no less effective than Lung-RADS version 1.0. These findings were essentially stable under a range of sensitivity analyses. CONCLUSIONS: Ceasing follow-up for low-risk subsolid nodules after 2 to 5 years of stability is more cost-effective than perpetual follow-up. Lung-RADS version 1.1 was cheaper but similarly effective to version 1.0.

Esophageal cancer treatment costs by phase of care and treatment modality, 2000-2013.

BACKGROUND: Detailed cost estimates are not widely available for esophageal cancer. Our study estimates phase-specific costs for esophageal cancer by age, year, histology, stage, and treatment for older patients in the United States and compares these costs within stage and treatment modalities. METHODS: We identified 8061 esophageal cancer patients in the Surveillance, Epidemiology, and End Results-Medicare database for years 1998-2013. Total, cancer-attributable, and patient-liability costs were calculated based on separate phases of care-staging (or surgery), initial, continuing, and terminal. We estimated costs by treatment modality within stage and phase for esophageal adenocarcinoma and squamous cell carcinoma separately. We fit linear regression models using log transformation to determine cost by age and calendar year. All costs are reported in 2018 US dollars. RESULTS: Overall, mean (95% CI) monthly total cost estimates were high during the staging ($8953 [$8385-$9485]) and initial phases ($7731 [$7492-$7970]), decreased over the continuing phase ($2984 [$2814-$3154]), and increased substantially during the 6-month terminal phase ($18 150 [$17 211-$19 089]). This pattern of high staging and initial phase costs, decreasing continuing phase costs, and increasing terminal phase costs was seen in all stages. The highest staging costs were in stages III ($9249, $8025-$10 474) and II ($9171, $7642-$10 699). The highest initial phase cost was in stage IV, $9263 ($8758-49 768), the lowest continuing phase cost was in stage I, $2338 ($2160-$2517), and the highest terminal phase costs were in stages II ($20 533, $17 772-$23 293) and III ($20 599, $18 268-$22 929). The linear regression models showed that cancer-attributable costs remained stable over the study period and were unaffected by age for most histology, stage, and treatment modality subgroups. CONCLUSIONS: Our estimates demonstrate that esophageal cancer costs can vary widely by histology, stage, and treatment. These cost estimates can be used to guide future resource allocation for esophageal cancer care and research.

A simulation study of the effect of lung cancer screening in China, Japan, Singapore, and South Korea.

More than 50% of the world's lung cancer cases occur in Asia and more than 20% of cancer deaths in Asia are attributable to lung cancer. The U.S. National Lung Screening Trial has shown that lung cancer screening with computed tomography (CT) can reduce lung cancer deaths. Using the Lung Cancer Policy Model-Asia (LCPM-Asia), we estimated the potential mortality reduction achievable through the implementation of CT-based lung cancer screening in China, Japan, Singapore, and South Korea. The LCPM-Asia was calibrated to the smoking prevalence of each of the aforementioned countries based on published national surveys and to lung cancer mortality rates from the World Health Organization. The calibrated LCPM-Asia was then used to simulate lung cancer deaths under screening and no-screening scenarios for the four countries. Using screening eligibility criteria recommended by the U.S. Centers for Medicare & Medicaid Services (CMS), which are based on age and smoking history, we estimated the lung cancer mortality reduction from screening through year 2040. By 2040, lung cancer screening would result in 91,362 life-years gained and 4.74% mortality reduction in South Korea; 290,325 life-years gained and 4.33% mortality reduction in Japan; 3,014,215 life-years gained and 4.22% mortality reduction in China; and 8,118 life-years gained and 3.76% mortality reduction in Singapore. As for mortality reduction by smoker type, current smokers would have the greatest mortality reduction in each country, ranging from 5.56% in Japan to 6.86% in Singapore. Among the four countries, lung cancer screening under CMS eligibility criteria was most effective in South Korea and least effective in Singapore. Singapore's low smoking prevalence and South Korea's aging population and higher smoking prevalence may partially explain the discrepancy in effectiveness. CT screening was shown to be promising as a means of reducing lung cancer mortality in the four countries.

Lung cancer costs by treatment strategy and phase of care among patients enrolled in Medicare.

BACKGROUND: We studied trends in lung cancer treatment cost over time by phase of care, treatment strategy, age, stage at diagnosis, and histology. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database for years 1998-2013, we allocated total and patient-liability costs into the following phases of care for 145 988 lung cancer patients: prediagnosis, staging, surgery, initial, continuing, and terminal. Patients served as self-controls to determine cancer-attributable costs based on individual precancer diagnosis healthcare costs. We fit linear regression models to determine cost by age and calendar year for each stage at diagnosis, histology, and treatment strategy and presented all costs in 2017 US dollars. RESULTS: Monthly healthcare costs prior to lung cancer diagnosis were $861 for a 70 years old in 2017 and rose by an average of $17 per year (P < 0.001). Surgery in 2017 cost $30 096, decreasing by $257 per year (P = 0.007). Chemotherapy and radiation costs remained stable or increased for most stage and histology groups, ranging from $4242 to $8287 per month during the initial six months of care. Costs during the final six months of life decreased for those who died of lung cancer or other causes. CONCLUSIONS: Cost-effectiveness analyses of lung cancer control interventions in the United States have been using outdated and incomplete treatment cost estimates. Our cost estimates enable updated cost-effectiveness analyses to determine the benefit of lung cancer control from a health economics point of view.

Pancreatic cancer treatment costs, including patient liability, by phase of care and treatment modality, 2000-2013.

OBJECTIVES: Our study provides phase-specific cost estimates for pancreatic cancer based on stage and treatment. We compare treatment costs between the different phases and within the stage and treatment modality subgroups. METHODS: Our cohort included 20,917 pancreatic cancer patients from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database diagnosed between 2000 and 2011. We allocated costs into four phases of care-staging (or surgery), initial, continuing, and terminal- and calculated the total, cancer-attributable, and patient-liability costs in 2018 US dollars. We fit linear regression models using log transformation to determine whether costs were predicted by age and calendar year. RESULTS: Monthly cost estimates were high during the staging and surgery phases, decreased over the initial and continuing phases, and increased during the three-month terminal phase. Overall, the linear regression models showed that cancer-attributable costs either remained stable or increased by year, and either were unaffected by age or decreased with older age; continuing phase costs for stage II patients increased with age. CONCLUSIONS: Our estimates demonstrate that pancreatic cancer costs can vary widely by stage and treatment received. These cost estimates can serve as an important baseline foundation to guide resource allocation for cancer care and research in the future.