Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
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In 2021, the U.S. Preventive Services Task Force (USPSTF) revised its lung cancer screening recommendations expanding its eligibility. As more smokers become eligible, cessation interventions at the point of screening could enhance the benefits. Here, we evaluate the effects of joint screening and cessation interventions under the new recommendations. ⋯ Joint screening and cessation interventions would result in considerable lung cancer deaths averted and life-years gained. Adding a one-time cessation intervention of modest effectiveness (15%) results in comparable life-years gained as increasing screening uptake from 30% to 100% because while cessation decreases mortality from many causes, screening only reduces lung cancer mortality. This simulation indicates that incorporating cessation programs into screening practice should be a priority as it can maximize overall benefits.
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KRAS mutations have been recognized as undruggable for many years. Recently, novel KRAS G12C inhibitors, such as sotorasib and adagrasib, are being developed in clinical trials and have revealed promising results in metastatic NSCLC. Nevertheless, it is strongly anticipated that acquired resistance will limit their clinical use. In this study, we developed in vitro models of the KRAS G12C cancer, derived from resistant clones against sotorasib and adagrasib, and searched for secondary KRAS mutations as on-target resistance mechanisms to develop possible strategies to overcome such resistance. ⋯ We identified many secondary KRAS mutations causing resistance to sotorasib, adagrasib, or both, in vitro. The differential activities of these two inhibitors depending on the secondary mutations suggest sequential use in some cases. In addition, switching to BI-3406 plus trametinib might be a useful strategy to overcome acquired resistance owing to the secondary Y96D and Y96S mutations.
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The workup and longitudinal monitoring for subjects presenting with pulmonary nodules is a pressing clinical problem. A blood-based biomarker panel potentially has utility for identifying subjects at higher risk for harboring a malignant nodule for whom additional workup would be indicated or subjects at reduced risk for whom imaging-based follow-up would be indicated. ⋯ A four-marker biomarker panel, previously validated to improve lung cancer risk prediction, was found to also have utility in distinguishing benign from malignant indeterminate pulmonary nodules. Its performance in improving sensitivity at a high specificity indicates potential utility of the marker panel in assessing likelihood of malignancy in otherwise indeterminate nodules.
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Disparities exist in lung cancer outcomes between African American and white people. The current United States Preventive Services Task Force (USPSTF) lung cancer screening eligibility criteria, which is based solely on age and smoking history, may exacerbate racial disparities. We evaluated whether the PLCOm2012 risk prediction model more effectively selects African American ever-smokers for screening. ⋯ The PLCOm2012 model was found to be preferable over the USPSTF criteria at identifying African American ever-smokers for lung cancer screening. The broader use of this model in racially diverse populations may help overcome disparities in lung cancer screening and outcomes.
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Editorial Comment
Osimertinib for Leptomeningeal Disease in EGFR-Mutated NSCLC.