Faculty Bibliography

BACKGROUND:The frequency of cancer and accuracy of prediction models have not been studied in large, population-based samples of patients with incidental pulmonary nodules measuring > 8 mm in diameter. RESEARCH QUESTIONS:How does the frequency of cancer vary by size and smoking history among patients with incidental nodules? How accurate are two widely used models for identifying cancer in these patients? STUDY DESIGN AND METHODS:We assembled a retrospective cohort of individuals with incidental nodules measuring > 8 mm in diameter identified by chest CT imaging between 2006 and 2016. We used a validated natural language processing algorithm to identify nodules and their characteristics by scanning the text of dictated radiology reports. We reported patient and nodule characteristics stratified by the presence or absence of a lung cancer diagnosis within 27 months of nodule identification and estimated the area under the receiver operating characteristic curve (AUC) to compare the accuracy of the Mayo Clinic and Brock models for identifying cancer. RESULTS:The sample included 23,780 individuals with a nodule measuring > 8 mm, including 2,356 patients (9.9%) with a lung cancer diagnosis within 27 months of nodule identification. Cancer was diagnosed in 5.4% of never smokers, 12.2% of former smokers, and 17.7% of current smokers. Cancer was diagnosed in 5.7% of patients with nodules measuring 9 to 15 mm, 12.1% of patients with nodules > 15 to 20 mm, and 18.4% of patients with nodules > 20 to 30 mm. In the full sample, the Mayo Clinic model (AUC, 0.747; 95% CI, 0.737-0.757) was more accurate than the Brock model (AUC, 0.713; 95% CI, 0.702-0.724; P < .0001). When restricted to ever smokers, the Mayo Clinic model was still more accurate. Both models overestimated the probability of cancer. INTERPRETATION:Almost 10% of patients with an incidental pulmonary nodule measuring > 8 mm in diameter will receive a lung cancer diagnosis. Existing prediction models have only fair accuracy and overestimate the probability of cancer.

IMPORTANCE:The US Preventive Services Task Force (USPSTF) released updated lung cancer screening recommendations in 2021, lowering the screening age from 55 to 50 years and smoking history from 30 to 20 pack-years. These changes are expected to expand screening access to women and racial and ethnic minority groups. OBJECTIVE:To estimate the population-level changes associated with the 2021 USPSTF expansion of lung cancer screening eligibility by sex, race and ethnicity, sociodemographic factors, and comorbidities in 5 community-based health care systems. DESIGN, SETTING, AND PARTICIPANTS:This cohort study analyzed data of patients who received care from any of 5 community-based health care systems (which are members of the Population-based Research to Optimize the Screening Process Lung Consortium, a collaboration that conducts research to better understand how to improve the cancer screening processes in community health care settings) from January 1, 2010, through September 30, 2019. Individuals who had complete smoking history and were engaged with the health care system for 12 or more continuous months were included. Those who had never smoked or who had unknown smoking history were excluded. EXPOSURES:Electronic health record-derived age, sex, race and ethnicity, socioeconomic status (SES), comorbidities, and smoking history. MAIN OUTCOMES AND MEASURES:Differences in the proportion of the newly eligible population by age, sex, race and ethnicity, Charlson Comorbidity Index, chronic obstructive pulmonary disease diagnosis, and SES as well as lung cancer diagnoses under the 2013 recommendations vs the expected cases under the 2021 recommendations were evaluated using χ2 tests. RESULTS:As of September 2019, there were 341 163 individuals aged 50 to 80 years who currently or previously smoked. Among these, 34 528 had electronic health record data that captured pack-year and quit-date information and were eligible for lung cancer screening according to the 2013 USPSTF recommendations. The 2021 USPSTF recommendations expanded screening eligibility to 18 533 individuals, representing a 53.7% increase. Compared with the 2013 cohort, the newly eligible 2021 population included 5833 individuals (31.5%) aged 50 to 54 years, a larger proportion of women (52.0% [n = 9631]), and more racial or ethnic minority groups. The relative increases in the proportion of newly eligible individuals were 60.6% for Asian, Native Hawaiian, or Pacific Islander; 67.4% for Hispanic; 69.7% for non-Hispanic Black; and 49.0% for non-Hispanic White groups. The relative increase for women was 13.8% higher than for men (61.2% vs 47.4%), and those with a lower comorbidity burden and lower SES had higher relative increases (eg, 68.7% for a Charlson Comorbidity Index score of 0; 61.1% for lowest SES). The 2021 recommendations were associated with an estimated 30% increase in incident lung cancer diagnoses compared with the 2013 recommendations. CONCLUSIONS AND RELEVANCE:This cohort study suggests that, in diverse health care systems, adopting the 2021 USPSTF recommendations will increase the number of women, racial and ethnic minority groups, and individuals with lower SES who are eligible for lung cancer screening, thus helping to minimize the barriers to screening access for individuals with high risk for lung cancer.

COVID-19 has proved enormously disruptive to the provision of cancer screening, which does not just represent an initial test but an entire process, including risk detection, diagnostic follow-up, and treatment. Successful delivery of services at all points in the process has been negatively affected by the pandemic. There is a void in empirical high-quality evidence to support a specific strategy for administering cancer screening during a pandemic and its resolution phase, but several pragmatic considerations can help guide prioritization efforts. Targeting guideline-eligible people who have never been screened, or those who are significantly out of date with screening, has the potential to maximize benefits now and into the future. Disruptions to care due to the pandemic could represent an unparalleled opportunity to reassess early detection programs towards an explicit, thoughtful, and just prioritization of populations historically experiencing cancer disparities. By focusing screening services on populations that have the most to gain, and by careful and deliberate planning for the period following the pandemic, we can positively affect cancer outcomes for all.

Cancer interception refers to actively blocking the cancer development process by preventing progression of premalignancy to invasive disease. The rate-limiting steps for effective lung cancer interception are the incomplete understanding of the earliest molecular events associated with lung carcinogenesis, the lack of preclinical models of pulmonary premalignancy, and the challenge of developing highly sensitive and specific methods for early detection. Recent advances in cancer interception are facilitated by developments in next-generation sequencing, computational methodologies, as well as the renewed emphasis in precision medicine and immuno-oncology. This review summarizes the current state of knowledge in the areas of molecular abnormalities in lung cancer continuum, preclinical human models of lung cancer pathogenesis, and the advances in early lung cancer diagnostics.

OBJECTIVES:Second-line immune checkpoint inhibition (ICI) was recently shown to have a survival advantage over placebo in malignant pleural mesothelioma (MPM), but the survival comparison to chemotherapy in patients with MPM receiving routine clinical care is unknown. Our objective was to examine the effectiveness of second-line ICI versus chemotherapy on overall survival (OS) outcomes in real-world patients with advanced MPM. MATERIALS AND METHODS:We performed a multicenter retrospective cohort study of real-world adult patients with advanced MPM who received first-line platinum-based chemotherapy and at least two total lines of systemic therapy. Patients received either second-line chemotherapy (gemcitabine and/or vinorelbine) or ICI therapy (pembrolizumab or nivolumab ± ipilimumab). The primary outcome was OS, defined as the time from second-line therapy initiation to death or end of the observation period. We used Kaplan-Meier methods and Cox proportional hazards modeling with adjustment for relevant patient demographic and clinical variables to compare OS between the two second-line treatment groups. RESULTS:Of the 176 patients with MPM, the median age was 75 years (IQR: 69-79.5 years), and most were white (77%), male (74%), and had epithelioid histology (67%). Thirty-five percent (61) received second-line chemotherapy and 65% (115) ICI therapy (80 pembrolizumab, 31 nivolumab, and 4 nivolumab + ipilimumab). Treatment with ICI was associated with significantly longer median OS compared to chemotherapy (8.7 vs 5.0 months, p=0.001; adjusted hazard ratio: 0.52, 95% CI: 0.34-0.81). The estimated 12-month OS probability was 36.7% (95% CI: 27.6%-45.8%) and 15.6% (95% CI: 7.7%-26.1%) in the ICI and chemotherapy groups, respectively. CONCLUSION:In this "real-world" population of patients with MPM, treatment with ICI was associated with improved OS outcomes compared to chemotherapy in the second-line setting, in contrast with a recent clinical trial. Our findings suggest that ICI may benefit patients with advanced MPM and progression after initial platinum-based chemotherapy.

INTRODUCTION/BACKGROUND:Since the July 2017 National Comprehensive Cancer Network (NCCN) malignant pleural mesothelioma (MPM) guideline revision recommended second-line immune checkpoint inhibitors (ICIs), studies have suggested a greater response to ICI among patients with nonepithelioid MPM. Nevertheless, little is known regarding adoption of ICI in routine practice and if uptake differs by histologic subtype. Our objectives were to evaluate the real-world uptake of second-line ICI among patients with MPM and to reveal its association with histologic subtype. METHODS:This was a multicenter, retrospective cohort study of real-world patients with MPM receiving at least two lines of systemic therapy between 2011 and 2019. We found the uptake of second-line ICI over time and evaluated the association between histologic subtype and ICI use, adjusting for relevant patient demographic and clinical factors. RESULTS:Among the 426 patients with MPM in our cohort, 310 had epithelioid and 116 nonepithelioid histologic subtype. The median age was 73 years (interquartile range: 67-78). Overall, 144 patients (33.8%) received second-line ICI and 282 (66.2%) traditional chemotherapy. ICI uptake began in early 2015 before the NCCN guideline revision and increased rapidly to 2019. After the 2017 NCCN guideline revision, patients with nonepithelioid MPM histologic subtypes had more than 3 times the odds of receiving second-line ICI (OR = 3.26; 95% confidence interval: 1.41-7.54). CONCLUSIONS:Among real-world patients with MPM, second-line ICI uptake began over two years before the 2017 NCCN guideline recommendations and was associated with nonepithelioid histologic subtype after contemporary studies suggested increased clinical benefit in this population, reflecting prompt integration of scientific discovery into clinical practice.

BACKGROUND:A shared decision-making (SDM) process for lung cancer screening (LCS) includes a discussion between clinicians and patients about benefits and potential harms. Expert-driven taxonomies consider mortality reduction a benefit and consider false-positives, incidental findings, overdiagnosis, overtreatment, radiation exposure, and direct and indirect costs of LCS as potential harms. OBJECTIVE:To explore whether patients conceptualize the attributes of LCS differently from expert-driven taxonomies. DESIGN:Cross-sectional study with semistructured interviews and a card-sort activity. PARTICIPANTS:Twenty-three Veterans receiving primary care at a Veterans Affairs Medical Center, 55 to 73 y of age with 30 or more pack-years of smoking. Sixty-one percent were non-Hispanic African American or Black, 35% were non-Hispanic White, 4% were Hispanic, and 9% were female. APPROACH:Semistructured interviews with thematic coding. MAIN MEASURES:The proportion of participants categorizing each attribute as a benefit or harm and emergent themes that informed this categorization. KEY RESULTS:In addition to categorizing reduced lung cancer deaths as a benefit (22/23), most also categorized the following as benefits: routine annual screening (8/9), significant incidental findings (20/23), follow-up in a nodule clinic (20/23), and invasive procedures (16/23). Four attributes were classified by most participants as a harm: false-positive (13/22), overdiagnosis (13/23), overtreatment (6/9), and radiation exposure (20/22). Themes regarding the evaluation of LCS outcomes were 1) the value of knowledge about body and health, 2) anticipated positive and negative emotions, 3) lack of clarity in terminology, 4) underlying beliefs about cancer, and 5) risk assessment and tolerance for uncertainty. CONCLUSIONS:Anticipating discordance between patient- and expert-driven taxonomies of the benefits and harms of LCS can inform the development and interpretation of value elicitation and SDM discussions.

PURPOSE/OBJECTIVE:The aim of this study was to examine radiologists' beliefs about existing guidelines for pulmonary nodule evaluation. METHODS:A self-administered survey was developed to ascertain awareness of, agreement with, and adherence to published guidelines, including those from the Fleischner Society and the Lung CT Screening Reporting and Data System (Lung-RADS™). Surveys were distributed to 514 radiologists at 13 health care systems that are participating in a large, pragmatic trial of pulmonary nodule evaluation. Prespecified comparisons were made among groups defined by type of health system, years of experience, reader volume, and study arm. RESULTS:The response rate was 26.3%. Respondents were most familiar with guidelines from Fleischner (94%) and Lung-RADS (71%). For both incidental and screening-detected nodules, self-reported adherence to preferred guidelines was very high (97% and 94%, respectively), and most respondents believed that the benefits of adherence outweigh the harms (81% and 74%, respectively). Underlying evidence was thought to be high in quality by 68% of respondents for screening-detected nodules and 41% for incidental nodules. Approximately 70% of respondents believed that the frequency of recommended follow-up was "just right" for both guidelines. Radiologists who practice in nonintegrated health care systems were more likely to believe that the evidence was high in quality (79.5% versus 57.1%) and that the benefits of adherence outweigh the harms (85.1% versus 67.5%). Low-volume readers had lower awareness and self-reported adherence than higher volume readers. CONCLUSIONS:Radiologists reported high levels of familiarity and agreement with and adherence to guidelines for pulmonary nodule evaluation, but many overestimated the quality of evidence in support of the recommendations.