Seminars in respiratory and critical care medicine最新文献

Drug-induced pneumonitis is a significant and potentially life-threatening complication associated with multiple lung cancer therapies. As novel therapies are introduced and incorporated into updated treatment algorithms, it is crucial to anticipate, recognize, and manage these events readily and comprehensively. As experience with these agents accumulates in real-world settings, so too does our appreciation for patient risk factors, the need for personalized monitoring strategies, the heterogeneity of both clinical and radiographic presentations, and the persistent importance of a systematic approach to diagnosis and management. Novel therapies are responsible for significant improvements in lung cancer survival, but enthusiasm for this progress must be tempered by mitigation and management of inherent risks to avoid undue morbidity and mortality for our patients. Challenging clinical scenarios such as steroid-refractory pneumonitis highlight the importance of thorough evaluation, confident attribution, and aggressive early management. Future elucidation of the pathophysiology of these reactions will hopefully refine future diagnostic and therapeutic options. A collaborative, multidisciplinary approach is essential to optimize patient safety and outcomes in lung cancer care. In this study, we describe approaches to pretreatment assessment, evaluation of suspected pneumonitis, and management of pneumonitis on a drug-specific basis. We emphasize emerging data and drug classes, while also highlighting remaining areas of uncertainty.

In this review, we summarize recent evidence from approximately the last 5 years across the lung cancer screening (LCS) care continuum. First, we review the results from the NELSON trial, from the extended follow-up of other LCS randomized controlled trials (RCTs), and from a meta-analysis of RCTs. Together, these RCTs reported a 16% relative reduction in lung cancer mortality for low-dose CT (LDCT) LCS versus non-LDCT controls. Next, we summarize updates to clinical guidelines and recommendations around LCS in the United States, noting the current debate around the use of time since quit as an eligibility criterion. We also discuss the implementation of LCS focusing on the following areas: (1) global landscape, (2) selection criteria and approach, (3) LCS program structure, (4) shared decision making, (5) smoking cessation, (6) LCS uptake, (7) American College of Radiology Lung Reporting and Data System, (8) annual LCS adherence, (9) screen-detected findings and management, (10) incidental findings and management, and (11) disparities. Lastly, we highlight emerging data and considerations for personalized LCS and new technologies, with an emphasis on risk prediction models, biomarkers, and artificial intelligence. This review highlights the latest changes to LCS and the ongoing need to monitor and evaluate LCS as it diffuses into clinical practice across various real-world settings.

Lung cancer is the leading cause of cancer deaths worldwide, claiming more lives than other age-related and screen-detectable cancers. Cigarette smoking remains the most important risk factor. However, despite common perceptions, risk is not related solely to cigarette smoking. Several vulnerable and special populations experience a disproportionate burden of lung cancer, often complicated by overlapping medical issues, diagnostic challenges, and treatment limitations. This review highlights four populations (people with HIV, persons who are immunocompromised, lung cancer in nonsmoking women, and individuals with interstitial lung disease [ILD]) who experience unique risks that impact early detection, diagnosis, and management of lung cancer. Three of these populations are frequently underrepresented in clinical trials, yet they may be at elevated risk due to chronic inflammation, immune dysregulation, or previous medical therapies. Individuals with HIV have a significantly increased incidence of lung cancer, often presenting at younger ages and with more advanced disease. Similarly, patients who are immunocompromised following organ or stem cell transplantation are at heightened risk due to prolonged immune dysfunction and prior exposures to toxic therapies. Individuals with ILD, especially idiopathic pulmonary fibrosis (IPF), have an increased risk of developing lung cancer, which is challenging to detect with imaging given architectural distortion and even more challenging to treat given limited pulmonary reserve. We also highlight women, as there has been a striking trend of rising incidence of lung cancer among women worldwide, particularly among those who have never smoked. The intersection of these risks with traditional lung cancer risk factors like tobacco smoking highlights a critical need for increased awareness, improved risk stratification, and adapted screening strategies that take these complexities into account. In this review, we explore the epidemiology, clinical presentation, and early detection and management challenges unique to each population, underscoring the necessity of precision approaches to support individualized care.

Small-cell lung cancer (SCLC) is a high-grade, aggressive neuroendocrine tumor with a particularly poor prognosis, characterized by early metastases and rapid development of therapy resistance. There have historically been few treatment options for advanced or extensive stage SCLC, which comprises 70% of patients at the time of diagnosis, and 5-year survival rates for these patients have been under 5% for decades. Treatment of SCLC is now undergoing rapid changes due to advances in the field and many promising clinical trials, with several new therapy approvals within the last year. Advanced SCLC treatment is now a combination of chemotherapy and immunotherapy in the first line, with multiple second and later-line options. Early-stage SCLC is treated with chemoradiation followed by consolidative immunotherapy, a change in practice based on a recent clinical trial demonstrating an improvement of almost 2 years in median overall survival. In the era of immunotherapy and novel agents, prognosis has improved for advanced-stage disease, with 3-year survival rates of 16 and 17% in clinical trials for chemoimmunotherapy combinations. Despite these advances, most patients will progress within 6 months of starting first-line chemoimmunotherapy; thus, this disease continues to represent an area of unmet need. This update will highlight current standard of care practices and updates of recent promising trials that have improved outcomes, including survival, for SCLC patients.

This paper reviews the development of the current edition (Ninth) of the Tumor, Node, and Metastasis (TNM) classification of lung cancer. This classification was proposed from the analyses of a global database of 124,581 patients diagnosed between 2011 and 2019 established by The International Association of the Study of Lung Cancer. Overall survival was calculated using the Kaplan-Meier method, and prognosis assessed using multivariable-adjusted Cox proportional hazards regression to guide proposed changes to the Eighth Edition TNM classification. The innovations in the Ninth Edition TNM are: the T categories remain the same as in the Eighth Edition but descriptors previously considered separately were transferred to the official list of descriptors; the N2 category was subdivided into N2a (involvement of a single N2 station) and N2b (involvement of multiple N2 stations); the M1c category was subdivided into M1c1 (multiple extrathoracic metastases in a single organ system) and M1c2 (multiple extrathoracic metastases in multiple organ systems); and tumor cells spread through air spaces was introduced as an additional pathological descriptor. The Ninth Edition TNM classification of lung cancer aids in the understanding of the prognostic relevance of the anatomical extent of lung cancer but requires thorough clinical and pathological evaluations to benefit from the changes in clinical practice and in research.

Lung cancer remains the leading cause of cancer-related deaths worldwide, with its burden shaped by evolving risk factors, demographic changes, and healthcare disparities. Over the past decades, while age-standardized incidence and mortality rates have declined, the absolute number of cases has risen due to population growth and aging. Tobacco smoking remains the most common risk factor, accounting for approximately 60% of cases globally, though its contribution has declined in high-income regions due to effective tobacco control. Conversely, countries with lower socioeconomic development, particularly in East and South Asia, face rising incidence and mortality driven by increasing smoking prevalence, air pollution, and limited access to healthcare. Emerging risk factors, such as ambient air pollution and genetic predisposition, are increasingly significant, particularly in regions with lower Human Development Index scores. Sex disparities are evident, with lung cancer rates declining among men in many high-income countries but rising among women globally. Early-onset lung cancer is also an emerging concern, especially in middle socio-demographic index regions, driven by smoking, environmental exposures, and genetic factors. By 2035, it is predicted that lung cancer deaths could reach 3 million annually. To address the impact of the growing lung cancer burden, a multifaceted approach is needed, including strengthened tobacco control, improved air quality, promotion of clean cooking fuels, and expanded low-dose computed tomography screening, particularly in resource-constrained regions.

Lung cancer is a leading cause of cancer-related mortality, but advances in screening and early detection have improved opportunities for curative treatment. Therapeutic intent surgical resection remains a cornerstone for managing clinical stage IA disease. However, the optimal extent of surgical resection in this population has been a subject of ongoing debate. This review, guided by an introductory case-based vignette, provides a primer on the technical aspects of resection, pretreatment patient-level factors underlying decision-making, and other determinants of outcomes that may influence decisions to pursue lobar versus sublobar resection. We then offer a critique of the evidence base, focusing on the results of four randomized controlled trials: the Lung Cancer Study Group, DRKS00004897, JCOG0802/WJOG4607L, and CALGB140503. Following an interpretation of the available evidence, the review highlights contemporary practice patterns and the challenges of preference-based decisions. Finally, evidence gaps are highlighted as opportunities for future study to improve patient outcomes and experiences.

Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related deaths worldwide. The past two decades have brought advances in molecular profiling and the advent of therapies that specifically target genetic and/or molecular alterations in NSCLC. There are now many FDA-approved targeted therapies for patients with metastatic lung cancer who harbor oncogenic driver alterations, including those in epidermal growth factor receptor, ALK receptor tyrosine kinase, KRAS proto-oncogene, GTPase, and others. These advances epitomize personalized medicine and improve patient outcomes compared with conventional cytotoxic chemotherapy. This review highlights the current and evolving landscape of targeted therapies in NSCLC, emphasizing key targets, resistance mechanisms, and new approaches poised to improve patient outcomes in the era of precision oncology. The next decade will likely be marked by further improvements in the specificity, duration of action, and toxicity profiles of targeted therapies, allowing patients to live longer and better lives.

Lung cancer represents the most common cause of cancer-related mortality globally, with non-small cell lung cancer (NSCLC) comprising the vast majority of cases. Outcomes for stage II-III NSCLC remain suboptimal due to late presentation, biological heterogeneity, and limited efficacy of traditional therapies. Recent advances have reshaped the therapeutic landscape, with immunotherapy and targeted treatments now integrated into the management of resectable NSCLC. Landmark trials such as CheckMate 816 demonstrated improved event-free and overall survival with neoadjuvant chemoimmunotherapy approaches. Similarly, adjuvant targeted therapies such as osimertinib and alectinib have shown benefit in patients with EGFR and ALK alterations, respectively. This review provides an overview of evolving diagnostic strategies, highlights pivotal clinical trials, and explores multidisciplinary treatment approaches across stages I to III NSCLC. We also address key challenges including optimal treatment sequencing, patient selection, and duration of therapy. As clinical trial data continue to mature, personalized multimodal strategies guided by molecular and clinical features remain central to improving long-term outcomes in resectable NSCLC.