Seminars in oncology最新文献

Shared decision making (SDM) is an important part of lung cancer screening (LCS) that includes discussing the risks and benefits of screening, potential outcomes, patient eligibility and willingness to participate, tobacco cessation, and tailoring a strategy to an individual patient. More than other cancer screening tests, eligibility for LCS is nuanced, incorporating the patient's age as well as tobacco use history and overall health status. Since comorbidities and multimorbidity (ie, 2 or more comorbidities) impact the risks and benefits of LCS, these topics are a fundamental part of decision-making. However, there is currently little evidence available to guide clinicians in addressing comorbidities and an individual's “appropriateness” for LCS during SDM visits. Therefore, this literature review investigates the impact of comorbidities and multimorbidity among patients undergoing LCS. Based on available evidence and guideline recommendations, we identify comorbidities that should be considered during SDM conversations and review best practices for navigating SDM conversations in the context of LCS. Three conditions are highlighted since they concomitantly portend higher risk of developing lung cancer, potentially increase risk of screening-related evaluation and treatment complications and can be associated with limited life expectancy: chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, and human immunodeficiency virus infection.

Lung cancer screening begins at age 50, with yearly low dose computed tomography (LDCT) scans until age 80, for patients determined to be high risk due to tobacco smoking. Veterans serving from World War II to the Gulf War are now at the age where LDCT is recommended. This recommendation from the United States Preventative Service Task Force includes patients who have a 20-pack year tobacco history and currently smoke or quit within the last 15 years. This recommendation does not consider additional risk factors such as exposures to lung carcinogens. We discuss unique operational and occupational exposures encountered while serving in the armed forces, which may potentially increase the risk of lung cancers in the Veteran population. The additional risk of lung cancer due to military exposure history is unclear and more work is needed to identify and quantify risk at an individual level. Increasing awareness at the provider level regarding the carcinogenic exposures encountered may allow a larger population of Veterans, not meeting traditional LDCT criteria, to benefit from lung cancer screening.

Establishing a lung cancer screening (LCS) program is an important endeavor that delivers life-saving healthcare to an at-risk population. However, developing a comprehensive LCS program requires critical elements including obtaining institutional level buy-in, hiring necessary personnel, developing appropriate infrastructure and actively engaging primary care providers, subspecialty services, and radiology. The process required to connect such services to deliver an organized LCS program that reaches all eligible candidates must be individualized to each institution's needs and infrastructure. Here we provide detailed experiences from two successful LCS programs, one using a primary care provider-based service and the other using a consult-based service. In each case, we provide the pros and cons of each system. We propose that the decision to setup an ideal LCS program could include a hybrid design that combines aspects of each system.

Emerging evidence suggests that STK11 alterations, frequently found in non–small-cell lung cancers, may be prognostic and/or predictive of response to therapy, particularly immunotherapy. STK11 affects multiple important cellular pathways, and mutations lead to tumor growth by creating an immunosuppressive and altered metabolic environment through changes in AMPK, STING, and vascular endothelial growth factor pathways. We illustrate the questions surrounding STK11 genomic alteration in NSCLC with a case series comprising six United States Veterans from a single institution. We discuss the history of STK11, review studies on its clinical impact, and describe putative mechanisms of how loss of STK11 might engender resistance to immunotherapy or other therapies. While the exact impact of STK11 alteration in non–small-cell lung cancer remain to be fully elucidated, future research and ongoing clinical trials will help us better understand its role in cancer development and devise more effective treatment strategies.

Lung cancer is one of the most common and deadly cancers in the world. However, over the last several years, research into lung cancer screening and novel therapeutic approaches have provided promise that earlier detection combined with new treatment strategies may result in significantly improved outcomes. Biomarkers will most certainly play a major role in identifying those who may benefit from, and how to apply, these new treatment strategies. Here we discuss potential biomarkers, including the microbiome, in both detection and treatment strategies for early stage lung cancer.

Liquid biopsy refers to the identification of tumor-derived materials in body fluids including in blood circulation. In the age of immunotherapy and targeted therapies used for the treatment of advanced malignancies, molecular analysis of the tumor is considered a crucial step to guide management. In lung cancer, the concept of liquid biopsies is particularly relevant given the invasiveness of tumor biopsies in certain locations, and the potential risks of biopsy in a patient population with significant co-morbidities. Liquid biopsies have many advantages including non-invasiveness, lower cost, potential for genomic testing, ability to monitor tumor evolution through treatment, and the ability to overcome spatial and temporal intertumoral heterogeneity. The potential clinical applications of liquid biopsy are vast and include screening, detection of minimal residual disease and/or early relapse after curative intent treatment, monitoring response to immunotherapy, and identifying mutations that might be targetable or can confer resistance. Herein, we review the potential role of circulating tumor DNA and circulating tumor cells as forms of liquid biopsies and blood biomarkers in non-small cell lung cancer. We discuss the methodologies/platforms available for each, clinical applications, and limitations/challenges in incorporation into clinical practice. We additionally review emerging forms of liquid biopsies including tumor educated platelets, circular RNA, and exosomes.

Advanced lung cancer is a deadly malignancy that is a common cause of death among Veterans. Significant advancements in lung cancer therapeutics have been made over the past decade and survival outcomes have improved. The Veteran population is older, has more medical comorbidities and frailty compared to the general population. These factors must be accounted for when evaluating patients for treatment and selecting treatment options. This article explores the impact of these important issues in the management of advanced lung cancer. Recent clinical trials leading to the approval of modern therapies will be outlined and treatment outcomes specific to older patients discussed. The impact of key comorbidities that are common in Veterans and their impact on lung cancer treatment will be reviewed. There is no gold standard frailty index for assessment of frailty in patients with advanced lung cancer and the ability to predict tolerability and benefit from systemic therapies. Currently available systemic therapies are associated with higher risk of adverse events and lower potential for clinically meaningful improvement in outcomes. Future research needs to focus on designing better frailty indices and developing novel therapies that are safer and more effective therapies for frail patients, who constitute a considerable proportion of individuals diagnosed with lung cancer.

Current radiographic methods of measuring treatment response for patients with nonsmall cell lung cancer have significant limitations. Recently, new modalities using standard of care images or minimally invasive blood-based DNA tests have gained interest as methods of evaluating treatment response. This article highlights three emerging modalities: radiomic analysis, kinetic analysis and serum-based measurement of circulating tumor DNA, with a focus on the clinical evidence supporting these methods. Additionally, we discuss the possibility of combining these modalities to develop a robust biomarker with strong correlation to clinically meaningful outcomes that could impact clinical trial design and patient care. At Last, we focus on how these methods specifically apply to a Veteran population.

Two large randomized controlled trials have shown mortality benefit from lung cancer screening (LCS) in high-risk groups. Updated guidelines by the United State Preventative Service Task Force in 2020 will allow for inclusion of more patients who are at high risk of developing lung cancer and benefit from screening. As medical clinics and lung cancer screening programs around the country continue to work on perfecting the LCS workflow, it is important to understand some controversial issues surrounding LCS that should be addressed. In this article, we identify some of these issues, including false positive rates of low-dose CT, over-diagnosis, cost expenditure, LCS disparities in minorities, and utility of biomarkers. We hope to provide clarity, potential solutions, and future directions on how to address these controversies.