The Impact of Model Assumptions on Personalized Lung Cancer Screening Recommendations.

BACKGROUND: Recommendations regarding personalized lung cancer screening are being informed by natural-history modeling. Therefore, understanding how differences in model assumptions affect model-based personalized screening recommendations is essential. DESIGN: Five Cancer Intervention and Surveillance Modeling Network (CISNET) models were evaluated. Lung cancer incidence, mortality, and stage distributions were compared across 4 theoretical scenarios to assess model assumptions regarding 1) sojourn times, 2) stage-specific sensitivities, and 3) screening-induced lung cancer mortality reductions. Analyses were stratified by sex and smoking behavior. RESULTS: Most cancers had sojourn times <5 y (model range [MR]; lowest to highest value across models: 83.5%-98.7% of cancers). However, cancer aggressiveness still varied across models, as demonstrated by differences in proportions of cancers with sojourn times <2 y (MR: 42.5%-64.6%) and 2 to 4 y (MR: 28.8%-43.6%). Stage-specific sensitivity varied, particularly for stage I (MR: 31.3%-91.5%). Screening reduced stage IV incidence in most models for 1 y postscreening; increased sensitivity prolonged this period to 2 to 5 y. Screening-induced lung cancer mortality reductions among lung cancers detected at screening ranged widely (MR: 14.6%-48.9%), demonstrating variations in modeled treatment effectiveness of screen-detected cases. All models assumed longer sojourn times and greater screening-induced lung cancer mortality reductions for women. Models assuming differences in cancer epidemiology by smoking behaviors assumed shorter sojourn times and lower screening-induced lung cancer mortality reductions for heavy smokers. CONCLUSIONS: Model-based personalized screening recommendations are primarily driven by assumptions regarding sojourn times (favoring longer intervals for groups more likely to develop less aggressive cancers), sensitivity (higher sensitivities favoring longer intervals), and screening-induced mortality reductions (greater reductions favoring shorter intervals). IMPLICATIONS: Models suggest longer screening intervals may be feasible and benefits may be greater for women and light smokers. HIGHLIGHTS: Natural-history models are increasingly used to inform lung cancer screening, but causes for variations between models are difficult to assess.This is the first evaluation of these causes and their impact on personalized screening recommendations through easily interpretable metrics.Models vary regarding sojourn times, stage-specific sensitivities, and screening-induced lung cancer mortality reductions.Model outcomes were similar in predicting greater screening benefits for women and potentially light smokers. Longer screening intervals may be feasible for women and light smokers.

Pack-Year Smoking History: An Inadequate and Biased Measure to Determine Lung Cancer Screening Eligibility.

PURPOSE: Pack-year smoking history is an imperfect and biased measure of cumulative tobacco exposure. The use of pack-year smoking history to determine lung cancer screening eligibility in the current US Preventive Services Task Force (USPSTF) guideline may unintentionally exclude many high-risk individuals, especially those from racial and ethnic minority groups. It is unclear whether using a smoking duration cutoff instead of a smoking pack-year cutoff would improve the selection of individuals for screening. METHODS: We analyzed 49,703 individuals with a smoking history from the Southern Community Cohort Study (SCCS) and 22,126 individuals with a smoking history from the Black Women's Health Study (BWHS) to assess eligibility for screening under the USPSTF guideline versus a proposed guideline that replaces the ≥20-pack-year criterion with a ≥20-year smoking duration criterion. RESULTS: Under the USPSTF guideline, only 57.6% of Black patients with lung cancer in the SCCS would have qualified for screening, whereas a significantly higher percentage of White patients with lung cancer (74.0%) would have qualified (P < .001). Under the proposed guideline, the percentage of Black and White patients with lung cancer who would have qualified for screening increased to 85.3% and 82.0%, respectively, eradicating the disparity in screening eligibility between the groups. In the BWHS, using a 20-year smoking duration cutoff instead of a 20-pack-year cutoff increased the percentage of Black women with lung cancer who would have qualified for screening from 42.5% to 63.8%. CONCLUSION: Use of a 20-year smoking duration cutoff instead of a 20-pack-year cutoff greatly increases the proportion of patients with lung cancer who would qualify for screening and eliminates the racial disparity in screening eligibility between Black versus White individuals; smoking duration has the added benefit of being easier to calculate and being a more precise assessment of smoking exposure compared with pack-year smoking history.

Unspoken Truths: Mental Health Among Academic Surgeons.

OBJECTIVE: To characterize the current state of mental health within the surgical workforce in the United States. BACKGROUND: Mental illness and suicide is a growing concern in the medical community; however, the current state is largely unknown. METHODS: Cross-sectional survey of the academic surgery community assessing mental health, medical error, and suicidal ideation. The odds of suicidal ideation adjusting for sex, prior mental health diagnosis, and validated scales screening for depression, anxiety, post-traumatic stress disorder (PTSD), and alcohol use disorder were assessed. RESULTS: Of 622 participating medical students, trainees, and surgeons (estimated response rate=11.4%-14.0%), 26.1% (141/539) reported a previous mental health diagnosis. In all, 15.9% (83/523) of respondents screened positive for current depression, 18.4% (98/533) for anxiety, 11.0% (56/510) for alcohol use disorder, and 17.3% (36/208) for PTSD. Medical error was associated with depression (30.7% vs. 13.3%, P <0.001), anxiety (31.6% vs. 16.2%, P =0.001), PTSD (12.8% vs. 5.6%, P =0.018), and hazardous alcohol consumption (18.7% vs. 9.7%, P =0.022). Overall, 13.2% (73/551) of respondents reported suicidal ideation in the past year and 9.6% (51/533) in the past 2 weeks. On adjusted analysis, a previous history of a mental health disorder (aOR: 1.97, 95% CI: 1.04-3.65, P =0.033) and screening positive for depression (aOR: 4.30, 95% CI: 2.21-8.29, P <0.001) or PTSD (aOR: 3.93, 95% CI: 1.61-9.44, P =0.002) were associated with increased odds of suicidal ideation over the past 12 months. CONCLUSIONS: Nearly 1 in 7 respondents reported suicidal ideation in the past year. Mental illness and suicidal ideation are significant problems among the surgical workforce in the United States.

Risk Model-Based Lung Cancer Screening : A Cost-Effectiveness Analysis.

BACKGROUND: In their 2021 lung cancer screening recommendation update, the U.S. Preventive Services Task Force (USPSTF) evaluated strategies that select people based on their personal lung cancer risk (risk model-based strategies), highlighting the need for further research on the benefits and harms of risk model-based screening. OBJECTIVE: To evaluate and compare the cost-effectiveness of risk model-based lung cancer screening strategies versus the USPSTF recommendation and to explore optimal risk thresholds. DESIGN: Comparative modeling analysis. DATA SOURCES: National Lung Screening Trial; Surveillance, Epidemiology, and End Results program; U.S. Smoking History Generator. TARGET POPULATION: 1960 U.S. birth cohort. TIME HORIZON: 45 years. PERSPECTIVE: U.S. health care sector. INTERVENTION: Annual low-dose computed tomography in risk model-based strategies that start screening at age 50 or 55 years, stop screening at age 80 years, with 6-year risk thresholds between 0.5% and 2.2% using the PLCOm2012 model. OUTCOME MEASURES: Incremental cost-effectiveness ratio (ICER) and cost-effectiveness efficiency frontier connecting strategies with the highest health benefit at a given cost. RESULTS OF BASE-CASE ANALYSIS: Risk model-based screening strategies were more cost-effective than the USPSTF recommendation and exclusively comprised the cost-effectiveness efficiency frontier. Among the strategies on the efficiency frontier, those with a 6-year risk threshold of 1.2% or greater were cost-effective with an ICER less than $100 000 per quality-adjusted life-year (QALY). Specifically, the strategy with a 1.2% risk threshold had an ICER of $94 659 (model range, $72 639 to $156 774), yielding more QALYs for less cost than the USPSTF recommendation, while having a similar level of screening coverage (person ever-screened 21.7% vs. USPSTF's 22.6%). RESULTS OF SENSITIVITY ANALYSES: Risk model-based strategies were robustly more cost-effective than the 2021 USPSTF recommendation under varying modeling assumptions. LIMITATION: Risk models were restricted to age, sex, and smoking-related risk predictors. CONCLUSION: Risk model-based screening is more cost-effective than the USPSTF recommendation, thus warranting further consideration. PRIMARY FUNDING SOURCE: National Cancer Institute (NCI).

Assessing Bias and Limitations of Clinical Validation Studies of Molecular Diagnostic Tests for Indeterminate Thyroid Nodules: Systematic Review and Meta-Analysis.

Background: Molecular tests for thyroid nodules with indeterminate fine needle aspiration results are increasingly used in clinical practice; however, true diagnostic summaries of these tests are unknown. A systematic review and meta-analysis were completed to (1) evaluate the accuracy of commercially available molecular tests for malignancy in indeterminate thyroid nodules and (2) quantify biases and limitations in studies that validate those tests. Summary: PubMed, EMBASE, and Web of Science were systematically searched through July 2021. English language articles that reported original clinical validation attempts of molecular tests for indeterminate thyroid nodules were included if they reported counts of true-negative, true-positive, false-negative, and false-positive results. We performed screening and full-text review, followed by assessment of eight common biases and limitations, extraction of diagnostic and histopathological information, and meta-analysis of clinical validity using a bivariate linear mixed-effects model. Forty-nine studies were included. Meta-analysis of Afirma Gene expression classifiers (GEC; n = 38 studies) revealed a sensitivity of 0.92 (confidence interval: 0.90-0.94), specificity of 0.26 (0.20-0.32), negative likelihood ratio (LR-) of 0.32 (0.23-0.44), positive LR+ of 1.24 (1.15-1.35), and area under the curve (AUC) of 0.83 (0.74-0.89). Afirma Genomic Sequencing Classifier (GSC; n = 10) had a sensitivity of 0.94 (0.89-0.96), specificity of 0.38 (0.27-0.50), LR- of 0.18 (0.10-0.30), LR+ of 1.52 (1.28-1.87), and AUC of 0.91 (0.62-0.92). ThyroSeq v1 and v2 (n = 10) had a sensitivity of 0.86 (0.82-0.90), specificity of 0.74 (0.59-0.85), LR- of 0.19 (0.13-0.26), LR+ of 3.52 (2.08-5.92), and AUC of 0.86 (0.81-0.90). ThyroSeq v3 (n = 6) had a sensitivity of 0.92 (0.86-0.95), specificity of 0.41 (0.18-0.69), LR- of 0.24 (0.09-0.62), LR+ of 1.67 (1.09-2.98), and AUC of 0.90 (0.63-0.92). Fourteen percent of studies conducted a blinded histopathologic review of excised thyroid nodules, and 8% made the decision to go to surgery blind to molecular test results. Conclusions: Meta-analyses reveal a high diagnostic accuracy of molecular tests for thyroid nodule assessment of malignancy risk; however, these studies are subject to several limitations. Limitations and their potential clinical impacts must be addressed and, when feasible, adjusted for using valid statistical methodologies.

Cost-effectiveness Evaluation of the 2021 US Preventive Services Task Force Recommendation for Lung Cancer Screening.

IMPORTANCE: The US Preventive Services Task Force (USPSTF) issued its 2021 recommendation on lung cancer screening, which lowered the starting age for screening from 55 to 50 years and the minimum cumulative smoking exposure from 30 to 20 pack-years relative to its 2013 recommendation. Although costs are expected to increase because of the expanded screening eligibility criteria, it is unknown whether the new guidelines for lung cancer screening are cost-effective. OBJECTIVE: To evaluate the cost-effectiveness of the 2021 USPSTF recommendation for lung cancer screening compared with the 2013 recommendation and to explore the cost-effectiveness of 6 alternative screening strategies that maintained a minimum cumulative smoking exposure of 20 pack-years and an ending age for screening of 80 years but varied the starting ages for screening (50 or 55 years) and the number of years since smoking cessation (≤15, ≤20, or ≤25). DESIGN, SETTING, AND PARTICIPANTS: A comparative cost-effectiveness analysis using 4 independently developed microsimulation models that shared common inputs to assess the population-level health benefits and costs of the 2021 recommended screening strategy and 6 alternative screening strategies compared with the 2013 recommended screening strategy. The models simulated a 1960 US birth cohort. Simulated individuals entered the study at age 45 years and were followed up until death or age 90 years, corresponding to a study period from January 1, 2005, to December 31, 2050. EXPOSURES: Low-dose computed tomography in lung cancer screening programs with a minimum cumulative smoking exposure of 20 pack-years. MAIN OUTCOMES AND MEASURES: Incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY) of the 2021 vs 2013 USPSTF lung cancer screening recommendations as well as 6 alternative screening strategies vs the 2013 USPSTF screening strategy. Strategies with a mean ICER lower than $100 000 per QALY were deemed cost-effective. RESULTS: The 2021 USPSTF recommendation was estimated to be cost-effective compared with the 2013 recommendation, with a mean ICER of $72 564 (range across 4 models, $59 493-$85 837) per QALY gained. The 2021 recommendation was not cost-effective compared with 6 alternative strategies that used the 20 pack-year criterion. Strategies associated with the most cost-effectiveness included those that expanded screening eligibility to include a greater number of former smokers who had not smoked for a longer duration (ie, ≤20 years and ≤25 years since smoking cessation vs ≤15 years since smoking cessation). In particular, the strategy that screened former smokers who quit within the past 25 years and began screening at age 55 years was associated with screening coverage closest to that of the 2021 USPSTF recommendation yet yielded greater cost-effectiveness, with a mean ICER of $66 533 (range across 4 models, $55 693-$80 539). CONCLUSIONS AND RELEVANCE: This economic evaluation found that the 2021 USPSTF recommendation for lung cancer screening was cost-effective; however, alternative screening strategies that maintained a minimum cumulative smoking exposure of 20 pack-years but included individuals who quit smoking within the past 25 years may be more cost-effective and warrant further evaluation.

Trends in Thyroid Surgery and Guideline-Concordant Care in the United States, 2007-2018.

Background: The American Thyroid Association (ATA) published the 2015 Management Guidelines for patients with thyroid nodules and differentiated thyroid cancer, recommending a shift to less aggressive diagnostic, surgical, and postoperative treatment strategies. At the same time and perhaps related to the new guidelines, there has been a shift to outpatient thyroid surgery. The aim of the current study was to assess physician adherence to these recommendations by identifying and quantifying temporal trends in the rates and indications for thyroid procedures in the inpatient and outpatient settings. Methods: Using the IBM® MarketScan® Commercial database, we identified employer-insured patients in the United States who underwent outpatient and inpatient thyroid surgery from 2007 to 2018. Thyroid surgery was classified as total thyroidectomy (TT), thyroid lobectomy (TL), or a completion thyroidectomy. The surgical indication diagnosis was also determined and classified as either benign or malignant thyroid disease. We compared outpatient and inpatient trends in surgery between benign and malignant thyroid disease both before and after the release of the 2015 ATA guidelines. Results: A total of 220,088 patients who underwent thyroid surgery were included in the analysis. Approximately 80% of TLs were performed in the outpatient setting versus 70% of TTs. Longitudinal analysis showed a statistically significant changepoint for TT proportion occurring in November 2015. The proportion of TT as compared with TL decreased from 80% in September 2015 to 39% by December 2018. For thyroid cancer, there is an increasing trend in performing TL over TT, increasing from 17% in 2015 to 28% by the end of 2018. Conclusions: There was a significant changepoint occurring in November 2015 in the operative and management trends for benign and malignant thyroid disease.

Music during image-guided breast biopsy reduces patient anxiety levels.

PURPOSE: Interventions to decrease anxiety associated with image-guided breast biopsy are needed. Music intervention has been shown to be helpful in other outpatient procedural settings but data are limited regarding its effectiveness in the setting of breast biopsy. The purpose of this study was to determine whether listening to self-selected music during image-guided breast biopsy lowers anxiety. MATERIALS AND METHODS: This randomized controlled trial was approved by the institutional review board and was HIPAA-compliant. 157 women between 18 and 75 (mean, 49.7 years) years of age, undergoing stereotactic or ultrasound-guided core biopsy, were enrolled in the study and were prospectively randomized to music or usual care. Patients in the music group listened to music of their choice during the biopsy. All patients completed the State Trait Anxiety Inventory (STAI) before and after the biopsy. Differences in pre-biopsy and post-biopsy anxiety levels were compared between the two groups using the Mann-Whitney U test. RESULTS: Baseline trait anxiety scores in the two groups were similar (34.0 music, 31.5 control, p = .11). Patients in both groups showed lower state anxiety levels after the biopsy (45.6 to 34.3 music, 41.0 to 33.8 control, p < .001 for both). Patients who listened to music showed a greater reduction in anxiety (mean decrease 11.2 music, 7.3 control, p = .03). Post-biopsy anxiety levels were similar to normative values for working women in the same age group. CONCLUSION: Listening to self-selected music reduces anxiety in patients undergoing breast biopsy.

Breast cancer risk, worry, and anxiety: Effect on patient perceptions of false-positive screening results.

OBJECTIVE: The impact of mammography screening recall on quality-of-life (QOL) has been studied in women at average risk for breast cancer, but it is unknown whether these effects differ by breast cancer risk level. We used a vignette-based survey to evaluate how women across the spectrum of breast cancer risk perceive the experience of screening recall. METHODS: Women participating in mammography or breast MRI screening were recruited to complete a vignette-based survey. Using a numerical rating scale (0-100), women rated QOL for hypothetical scenarios of screening recall, both before and after benign results were known. Lifetime breast cancer risk was calculated using Gail and BRCAPRO risk models. Risk perception, trait anxiety, and breast cancer worry were assessed using validated instruments. RESULTS: The final study cohort included 162 women at low (n = 43, 26%), intermediate (n = 66, 41%), and high-risk (n = 53, 33%). Actual breast cancer risk was not a predictor of QOL for any of the presented scenarios. Across all risk levels, QOL ratings were significantly lower for the period during diagnostic uncertainty compared to after benign results were known (p < 0.05). In multivariable regression analyses, breast cancer worry was a significant predictor of decreased QoL for all screening scenarios while awaiting results, including scenarios with non-invasive imaging alone or with biopsy. High trait anxiety and family history predicted lower QOL scores after receipt of benign test results (p < 0.05). CONCLUSIONS: Women with high trait anxiety and family history may particularly benefit from discussions about the risk of recall when choosing a screening regimen.

Is Less More? A Microsimulation Model Comparing Cost-effectiveness of the Revised American Thyroid Association's 2015 to 2009 Guidelines for the Management of Patients With Thyroid Nodules and Differentiated Thyroid Cancer.

OBJECTIVE: To assess relative clinical and economic performance of the revised American Thyroid Association (ATA) thyroid cancer guidelines compared to current standard of care. BACKGROUND: Diagnosis of thyroid cancer in the United States has tripled whereas mortality has only marginally increased. Most patients present with small papillary carcinomas and have historically received at least a total thyroidectomy as a treatment. In 2015, the ATA released the revised guidelines recommending an option for active surveillance (AS) of small papillary thyroid carcinoma and thyroid lobectomy for larger unifocal tumors. METHODS: We created a Markov microsimulation model to evaluate the performance of the ATA's 2015 guidelines compared to the ATA's 2009 guidelines. We modeled a cohort of simulated patients with demographic and thyroid nodule characteristics representative of those presenting clinically in the United States. Outcome measures include life expectancy, quality-adjusted life years, costs, and frequency of surgical adverse events. RESULTS: In our base case analysis, the ATA 2015 strategy dominates the ATA 2009 strategy. The ATA 2015 strategy delivers greater discounted average quality-adjusted life years (13.09 vs 12.43) at a lower discounted average cost ($14,752 vs $20,126). Deaths due to thyroid cancer under the 2015 strategy are higher than the 2009 strategy but this is offset by a reduction in surgical deaths, leading to greater average life expectancy under the ATA 2015 strategy. The optimal strategy is sensitive to patients who experience a greater decrement in quality of life while undergoing AS. CONCLUSIONS: The ATA 2015 Guidelines represent a cost-effective strategy regarding AS and extent of surgery.

A decision analysis comparing 3 active surveillance protocols for the treatment of patients with low-risk prostate cancer.

BACKGROUND: Active surveillance (AS) is a viable management option for approximately 50% of men who are newly diagnosed with prostate cancer. To the authors' knowledge, no direct comparisons between the different variants of AS protocols have been conducted to date. The authors developed a microsimulation decision model to evaluate which of 3 alternative AS protocols is optimal for men with low-risk prostate cancer, and compared each of these with immediate treatment. METHODS: Men who were diagnosed with low-risk prostate cancer at age 65 years were modeled as having been treated with either immediate therapy or via each of 3 AS protocols. Modeled AS protocols represent those in the literature; a modified AS protocol was included in a sensitivity analysis. Immediate therapy included radical prostatectomy, external-beam radiotherapy, or brachytherapy. Outcome measures were quality-adjusted life-years (QALYs) and costs. Cost-effectiveness analysis and deterministic and probabilistic sensitivity analyses were performed. RESULTS: Immediate therapy produced fewer QALYs than all variants of AS. Of the AS protocols evaluated, biennial biopsy was found to be the only efficient option, with an incremental cost-effectiveness ratio of $3490 per QALY compared with immediate therapy. It delayed the need for curative therapy by a mean of 56 months, and was found to be preferred in >86.9% of cases in probabilistic sensitivity analysis. A modified version of low-intensity AS dominated all other options. CONCLUSIONS: For a 65-year-old man with low-risk prostate cancer, AS with biennial biopsy appears to be highly cost-effective compared with common alternatives. An AS protocol using triennial biopsy was found to dominate all other strategies and should be considered for men who are comfortable with a longer period between biopsies. The optimal strategy depends on a patient's tolerance for periodic biopsies and comfort with delaying radical treatment. Physicians should incorporate these patient preferences into decision making.

Predictors of surveillance mammography outcomes in women with a personal history of breast cancer.

PURPOSE: To identify predictors of poor mammography surveillance outcomes based on clinico-pathologic features. METHODS: This study was HIPAA compliant and IRB approved. We performed an electronic medical record review for a cohort of women with American Joint Committee on Cancer (AJCC) Stage I or II invasive breast cancer treated with breast conservation therapy who developed subsequent in-breast treatment recurrence (IBTR) or contralateral breast cancer (CBC). Poor surveillance outcome was defined as second breast cancer not detected by surveillance mammography, including interval cancers (diagnosed within 365 days of surveillance mammogram with negative results) and clinically detected cancers (diagnosed without a surveillance mammogram in the preceding 365 days). Univariate and multivariate logistic regression were performed to identify predictors of poor mammography surveillance outcome, including patient and primary tumor characteristics, breast density, mode of primary tumor detection, and time to second cancer diagnosis. RESULTS: 164 women met inclusion criteria (65 with IBTR, 99 with CBC); 124 had screen-detected second cancers. On univariate analysis, poor surveillance outcome (n = 40) was associated with age at primary cancer diagnosis < 50 years (p < 0.0001), AJCC stage II primary cancers (p = 0.007), and heterogeneously or extremely dense breasts (p = 0.04). On multivariate analysis, age < 50 years at primary breast cancer diagnosis remained a significant predictor of poor surveillance outcome (p = 0.001). CONCLUSION: Women younger than age 50 at primary breast cancer diagnosis are at risk of poor surveillance mammography outcomes, and may be appropriate candidates for more intensive clinical and imaging surveillance.

The thyroid cancer policy model: A mathematical simulation model of papillary thyroid carcinoma in The U.S. population.

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.

Evaluating lung cancer screening in China: Implications for eligibility criteria design from a microsimulation modeling approach.

More than half of males in China are current smokers and evidence from western countries tells us that an unprecedented number of smoking-attributable deaths will occur as the Chinese population ages. We used the China Lung Cancer Policy Model (LCPM) to simulate effects of computed tomography (CT)-based lung cancer screening in China, comparing the impact of a screening guideline published in 2015 by a Chinese expert group to a version developed for the United States by the U.S. Centers for Medicare & Medicaid Services (CMS). The China LCPM, built using an existing lung cancer microsimulation model, can project population outcomes associated with interventions for smoking-related diseases. After calibrating the model to published Chinese smoking prevalence and lung cancer mortality rates, we simulated screening from 2016 to 2050 based on eligibility criteria from the CMS and Chinese guidelines, which differ by age to begin and end screening, pack-years smoked, and years since quitting. Outcomes included number of screens, mortality reduction, and life-years saved for each strategy. We projected that in the absence of screening, 14.98 million lung cancer deaths would occur between 2016 and 2050. Screening with the CMS guideline would prevent 0.72 million deaths and 5.8 million life-years lost, resulting in 6.58% and 1.97% mortality reduction in males and females, respectively. Screening with the Chinese guideline would prevent 0.74 million deaths and 6.6 million life-years lost, resulting in 6.30% and 2.79% mortality reduction in males and females, respectively. Through 2050, 1.43 billion screens would be required using the Chinese screening strategy, compared to 988 million screens using the CMS guideline. In conclusion, CT-based lung cancer screening implemented in 2016 and based on the Chinese screening guideline would prevent about 20,000 (2.9%) more lung cancer deaths through 2050, but would require about 445 million (44.7%) more screens than the CMS guideline.

Early Pancreatic Ductal Adenocarcinoma Survival Is Dependent on Size: Positive Implications for Future Targeted Screening.

OBJECTIVES: Pancreatic ductal adenocarcinoma (PDAC) has not experienced a meaningful mortality improvement for the past few decades. Successful screening is difficult to accomplish because most PDACs present late in their natural history, and current interventions have not provided significant benefit. Our goal was to identify determinants of survival for early PDAC to help inform future screening strategies. METHODS: Early PDACs from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program database (2000-2010) were analyzed. We stratified by size and included carcinomas in situ (Tis). Overall cancer-specific survival was calculated. A Cox proportional hazards model was developed and the significance of key covariates for survival prediction was evaluated. RESULTS: A Kaplan-Meier plot demonstrated significant differences in survival by size at diagnosis; these survival benefits persisted after adjustment for key covariates in the Cox proportional hazards analysis. In addition, relatively weaker predictors of worse survival included older age, male sex, black race, nodal involvement, tumor location within the head of the pancreas, and no surgery or radiotherapy. CONCLUSIONS: For early PDAC, we found tumor size to be the strongest predictor of survival, even after adjustment for other patient characteristics. Our findings suggest that early PDAC detection can have clinical benefit, which has positive implications for future screening strategies.

Combined Biomarker and Computed Tomography Screening Strategies for Lung Cancer: Projections of Health and Economic Tradeoffs in the US Population.

BACKGROUND: Lung cancer screening with computed tomography (CT) of individuals who meet certain age and smoking history criteria is the current standard-of-care. METHODS: Using a published simulation model, we compared outcomes associated with seven biomarker+CT screening strategies to CT screening alone using CMS eligibility criteria. We assumed that the biomarker: had conditionally independent performance; was used for first-line screening in some, or all, individuals screened; and could be extended to CMS-ineligible smokers. Strategies differed by inclusion criteria (e.g. pack-years) and proportion of individuals for whom CT remained the first-line test. Each model run simulated a combined cohort of one million men and one million women born in 1950. Primary outcomes were cancer-specific mortality reduction and screening costs; biomarker costs were measured relative to CT. Efficiency frontiers identified optimal health and economic trade-offs. Sensitivity analysis evaluated the stability of results. RESULTS: Standard-of-care screening yielded an 8.3% cancer-specific mortality reduction in the simulated U.S. population (screened+unscreened individuals). For a biomarker test with 75% sensitivity and 95% specificity, mortality reductions across biomarker+CT strategies ranged from 7.0% to 23.9%. If the biomarker's cost was >0.86× that of CT, standard-of-care screening remained on the efficiency frontier, indicating that health and economic trade-offs were equally (or more) efficient relative to all biomarker+CT strategies. Biomarker+CT strategy costs were principally driven by biomarker specificity; mortality reduction was driven by sensitivity. CONCLUSION: Combined biomarker+CT strategies have the potential to improve future lung cancer screening effectiveness in the U.S. and achieve economic efficiency that is greater than the current standard-of-care.

Cost-Effectiveness of Screening for Primary Aldosteronism and Subtype Diagnosis in the Resistant Hypertensive Patients.

BACKGROUND: Primary aldosteronism (PA) is a common and underdiagnosed disease with significant morbidity potentially cured by surgery. We aim to assess if the long-term cardiovascular benefits of identifying and treating surgically correctable PA outweigh the upfront increased costs in patients at the time patients are diagnosed with resistant hypertension (RH). METHODS AND RESULTS: A decision-analytic model compares aggregate costs and systolic blood pressure changes of 6 recommended or implemented diagnostic strategies for PA in a simulated population of at-risk RH patients. We also evaluate a 7th "treat all" strategy wherein all patients with RH are treated with a mineralocorticoid-receptor antagonist without further testing at RH diagnosis. Changes in systolic blood pressure are subsequently converted into gains in quality-adjusted life years (QALYs) by applying National Health and Nutrition Examination Survey data on concomitant risk factors to an existing cardiovascular disease simulation model. QALYs and lifetime costs were then used to calculate incremental cost-effectiveness ratios for the competing strategies. The incremental cost-effectiveness ratio for the strategy of computerized tomography (CT) followed by adrenal venous sampling (AVS) was $82,000/QALY compared with treat all. Incremental cost-effectiveness ratios for CT alone and AVS alone were $200,000/QALY and $492,000/QALY; the other strategies were more costly and less effective. Integrating differential patient-reported health-related quality of life adjustments for patients with PA, and incremental cost-effectiveness ratios for screening patients with CT followed by AVS, CT alone, and AVS alone were $52,000/QALY, $114,000/QALY, and $269,000/QALY gained. CONCLUSIONS: CT scanning followed by AVS was a cost-effective strategy to screen for PA among patients with RH.

Five-year risk of interval-invasive second breast cancer.

BACKGROUND: Earlier detection of second breast cancers after primary breast cancer (PBC) treatment improves survival, yet mammography is less accurate in women with prior breast cancer. The purpose of this study was to examine women presenting clinically with second breast cancers after negative surveillance mammography (interval cancers), and to estimate the five-year risk of interval-invasive second cancers for women with varying risk profiles. METHODS: We evaluated a prospective cohort of 15 114 women with 47 717 surveillance mammograms diagnosed with stage 0-II unilateral PBC from 1996 through 2008 at facilities in the Breast Cancer Surveillance Consortium. We used discrete time survival models to estimate the association between odds of an interval-invasive second breast cancer and candidate predictors, including demographic, PBC, and imaging characteristics. All statistical tests were two-sided. RESULTS: The cumulative incidence of second breast cancers after five years was 54.4 per 1000 women, with 325 surveillance-detected and 138 interval-invasive second breast cancers. The five-year risk of interval-invasive second cancer for women with referent category characteristics was 0.60%. For women with the most and least favorable profiles, the five-year risk ranged from 0.07% to 6.11%. Multivariable modeling identified grade II PBC (odds ratio [OR] = 1.95, 95% confidence interval [CI] = 1.15 to 3.31), treatment with lumpectomy without radiation (OR = 3.27, 95% CI = 1.91 to 5.62), interval PBC presentation (OR = 2.01, 95% CI 1.28 to 3.16), and heterogeneously dense breasts on mammography (OR = 1.54, 95% CI = 1.01 to 2.36) as independent predictors of interval-invasive second breast cancers. CONCLUSIONS: PBC diagnosis and treatment characteristics contribute to variation in subsequent-interval second breast cancer risk. Consideration of these factors may be useful in developing tailored post-treatment imaging surveillance plans.

Personalizing annual lung cancer screening for patients with chronic obstructive pulmonary disease: A decision analysis.

BACKGROUND: Lung cancer screening with annual chest computed tomography (CT) is recommended for current and former smokers with a ≥30-pack-year smoking history. Patients with chronic obstructive pulmonary disease (COPD) are at increased risk of developing lung cancer and may benefit from screening at lower pack-year thresholds. METHODS: We used a previously validated simulation model to compare the health benefits of lung cancer screening in current and former smokers ages 55-80 with ≥30 pack-years with hypothetical programs using lower pack-year thresholds for individuals with COPD (≥20, ≥10, and ≥1 pack-years). Calibration targets for COPD prevalence and associated lung cancer risk were derived using the Framingham Offspring Study limited data set. We performed sensitivity analyses to evaluate the stability of results across different rates of adherence to screening, increased competing mortality risk from COPD, and increased surgical ineligibility in individuals with COPD. The primary outcome was projected life expectancy. RESULTS: Programs using lower pack-year thresholds for individuals with COPD yielded the highest life expectancy gains for a given number of screens. Highest life expectancy was achieved when lowering the pack-year threshold to ≥1 pack-year for individuals with COPD, which dominated all other screening strategies. These results were stable across different adherence rates to screening and increases in competing mortality risk for COPD and surgical ineligibility. CONCLUSIONS: Current and former smokers with COPD may disproportionately benefit from lung cancer screening. A lower pack-year threshold for screening eligibility may benefit this high-risk patient population.