Seminars in oncology最新文献

{"title":"Loss of function STK11 alterations and poor outcomes in non–small-cell lung cancer: Literature and case series of US Veterans","authors":"Hafsa Farooq ,&nbsp;Harold Bien ,&nbsp;Victor Chang ,&nbsp;Daniel Becker ,&nbsp;Yeun-Hee Park ,&nbsp;Susan E. Bates","doi":"10.1053/j.seminoncol.2022.06.008","DOIUrl":"10.1053/j.seminoncol.2022.06.008","url":null,"abstract":"<div><p>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.</p></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"49 3","pages":"Pages 319-325"},"PeriodicalIF":4.0,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0093775422000483/pdfft?md5=d0bdad1db8edbd63244a1de4545aa12c&pid=1-s2.0-S0093775422000483-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40519069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomarkers and the microbiome in the detection and treatment of early-stage non-small cell lung cancer","authors":"Mark Klein ,&nbsp;Alexa A. Pragman ,&nbsp;Christine Wendt","doi":"10.1053/j.seminoncol.2022.06.011","DOIUrl":"10.1053/j.seminoncol.2022.06.011","url":null,"abstract":"<div><p>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.</p></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"49 3","pages":"Pages 285-297"},"PeriodicalIF":4.0,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0093775422000513/pdfft?md5=138993754f3c3e2485b6a1ee7cb96982&pid=1-s2.0-S0093775422000513-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9948407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular biomarkers and liquid biopsies in lung cancer","authors":"Kamya Sankar ,&nbsp;Mina Zeinali ,&nbsp;Sunitha Nagrath ,&nbsp;Nithya Ramnath","doi":"10.1053/j.seminoncol.2022.06.007","DOIUrl":"10.1053/j.seminoncol.2022.06.007","url":null,"abstract":"<div><p>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.</p></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"49 3","pages":"Pages 275-284"},"PeriodicalIF":4.0,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0093775422000471/pdfft?md5=578251d67cb50f8af9ec14a06a205fb2&pid=1-s2.0-S0093775422000471-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40515813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treating advanced lung cancer in older Veterans with comorbid conditions and frailty","authors":"Theodore Thomas ,&nbsp;Bindiya Patel ,&nbsp;Joshua Mitchell ,&nbsp;Alison Whitmer ,&nbsp;Eric Knoche ,&nbsp;Pankaj Gupta","doi":"10.1053/j.seminoncol.2022.06.004","DOIUrl":"10.1053/j.seminoncol.2022.06.004","url":null,"abstract":"<div><p>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.</p></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"49 3","pages":"Pages 353-361"},"PeriodicalIF":4.0,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0093775422000446/pdfft?md5=0487170be9d8ac006471529b86d5b8c6&pid=1-s2.0-S0093775422000446-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40536462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing Outcomes in NSCLC: Radiomic analysis, kinetic analysis and circulating tumor DNA","authors":"Ashray Maniar ,&nbsp;Alexander Z. Wei ,&nbsp;Laurent Dercle ,&nbsp;Harold H. Bien ,&nbsp;Tito Fojo ,&nbsp;Susan E. Bates ,&nbsp;Lawrence H. Schwartz","doi":"10.1053/j.seminoncol.2022.06.002","DOIUrl":"10.1053/j.seminoncol.2022.06.002","url":null,"abstract":"<div><p>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.</p></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"49 3","pages":"Pages 298-305"},"PeriodicalIF":4.0,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0093775422000422/pdfft?md5=8ef37df94d68daa4d4d5aea225d2cd3e&pid=1-s2.0-S0093775422000422-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40574026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Controversies and challenges in lung cancer screening","authors":"Ravindra Rampariag ,&nbsp;Igor Chernyavskiy ,&nbsp;Mohammad Al-Ajam ,&nbsp;Jun-Chieh J. Tsay","doi":"10.1053/j.seminoncol.2022.07.002","DOIUrl":"10.1053/j.seminoncol.2022.07.002","url":null,"abstract":"<div><p>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.</p></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"49 3","pages":"Pages 191-197"},"PeriodicalIF":4.0,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0093775422000562/pdfft?md5=7490a688638850a3721d3503cf457ed0&pid=1-s2.0-S0093775422000562-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40650994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the effects of racial and socioeconomic factors on timeliness of lung cancer diagnosis and treatment in Baltimore Veterans","authors":"Fahid Alghanim ,&nbsp;Kevin Z. Li ,&nbsp;Max An ,&nbsp;Avelino C. Verceles ,&nbsp;William R. Grier ,&nbsp;Hatoon Abbas ,&nbsp;Janaki Deepak","doi":"10.1053/j.seminoncol.2022.07.001","DOIUrl":"10.1053/j.seminoncol.2022.07.001","url":null,"abstract":"<div><h3>Objectives</h3><p>To characterize the effect of racial and socioeconomic factors on the timeliness of lung cancer diagnosis and treatment in a single-center Veterans Affair Medical Center (VAMC) pulmonary nodule clinic.</p></div><div><h3>Methods</h3><p>We conducted a single-center retrospective review of all patients seen at the Baltimore VAMC pulmonary nodule clinic between 2013 and 2019 to identify key demographic factors, measures of neighborhood socioeconomic disadvantage, cancer staging and histopathologic information, and time elapsed between diagnosis and treatment. We excluded patients with pulmonary nodules undergoing active surveillance, prior history of lung cancer, metastases of a different primary origin, insufficient followup, or who had received care outside the VHA system.</p></div><div><h3>Results</h3><p>Median times to diagnosis and treatment of lung cancer were 28 and 73 days. There were no statistically significant differences in overall timeliness of diagnosis and treatment when stratified by race or measures of neighborhood socioeconomic disadvantage.</p></div><div><h3>Conclusions</h3><p>The authors found no differences in timeliness of lung cancer care by race and socioeconomic status within the system. Despite general adherence to national standards in timeliness of care, there continues to be a need for improvements in the operational workflows to reduce time to diagnosis and treatment for all Veterans.</p></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"49 3","pages":"Pages 247-253"},"PeriodicalIF":4.0,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0093775422000550/pdfft?md5=bfb9041c676541e5c2399d40393430e8&pid=1-s2.0-S0093775422000550-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40584630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improving the efficacy of immunotherapy in small cell lung cancer: Leveraging recent scientific discoveries and tumor-specific antigens","authors":"Joseph B. Hiatt ,&nbsp;Perrin E. Romine ,&nbsp;Daniel Y. Wu","doi":"10.1053/j.seminoncol.2022.06.003","DOIUrl":"10.1053/j.seminoncol.2022.06.003","url":null,"abstract":"<div><p>Small cell lung cancer (SCLC) is an aggressive neuroendocrine neoplasm with poor survival outcomes and little change to treatment standards over decades. SCLC is associated with heavy tobacco exposure and a high rate of somatic mutations in tumor cells, leading to hope that immune checkpoint inhibitors would dramatically reshape the treatment landscape of SCLC. Instead, immune checkpoint inhibitors have led to real but modest gains in outcomes, with only a small minority of patients deriving more durable benefit. Furthermore, biomarkers of ICI efficacy that have succeeded in other tumor types have not been validated in SCLC. However, recent research advances have suggested that epigenetic heterogeneity and plasticity play especially key roles in SCLC biology. Leveraging this emerging perspective, a new slate of candidate biomarkers of immune checkpoint inhibitor benefit have been described, and the novel treatment strategies combining rational epigenetic perturbation with immune checkpoint inhibitors are being developed. Finally, other immunotherapy strategies targeting SCLC-specific mechanisms are being tested. Together, these developments may lead to a second generation of much more efficacious immunotherapies in SCLC.</p></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"49 3","pages":"Pages 344-352"},"PeriodicalIF":4.0,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0093775422000434/pdfft?md5=63c4dbba000514f2a6d37c78a0e05a6a&pid=1-s2.0-S0093775422000434-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40609581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of actionable genetic alterations in lung carcinoma from the VA National Precision Oncology Program","authors":"Shadia I. Jalal ,&nbsp;Aixia Guo ,&nbsp;Sara Ahmed ,&nbsp;Michael J. Kelley","doi":"10.1053/j.seminoncol.2022.06.014","DOIUrl":"10.1053/j.seminoncol.2022.06.014","url":null,"abstract":"<div><p>Lung cancer is the leading cause of cancer mortality in men and women. Genomic sequencing of non-small cell lung cancer (NSCLC) is critical for the optimal treatment of NSCLC. In this study we sought to describe the frequencies of highly actionable driver mutations in lung adenocarcinoma (LUAD), squamous cell (LUSQ) and other NSCLC histologies (LUOT) in Veterans tested through the VA's National Precision Oncology Program (NPOP) and compare these frequencies to other published datasets from highly specialized academic cancer centers. The NPOP cohort included 3,376 unique Veterans with a diagnosis of lung carcinoma tested between February 2019 and January 2021 including 1892 with LUAD, 940 with LUSQ, and 549 with LUOT. Among patients with LUAD, 27.5% had highly actionable genetic variants. The frequency of targetable mutations was as follows: <em>ALK</em> rearrangement 0.8%, <em>BRAF</em> V600E 2.1%, <em>EGFR</em> exon 20 insertion mutation 0.48%, <em>EGFR</em> sensitizing mutations 6.6%, <em>ERBB2</em> small variants 1.2%, <em>KRAS</em> G12C 14.0%, <em>MET</em> exon 14 skipping mutation 1.5%, <em>NTRK</em> rearrangement 0.1%, RET rearrangement 0.4%, and <em>ROS1</em> rearrangement 0.3%. The frequency of <em>EGFR</em> mutations, <em>RET</em> rearrangement, <em>MET</em> exon 14 and ERBB2 small variants frequencies were significantly lower in NPOP compared to other published reports while <em>MET</em> amplification was more common in NPOP. Combined rates of highly actionable genetic variants were 2.7% and 13.4% in LUSQ and LUOT, respectively. In this study, 27.5% of Veterans with lung adenocarcinoma have actionable genetic alterations eligible for FDA approved targeted therapies, a frequency only slightly lower than other published datasets despite higher smoking rates in Veterans. Genomic sequencing should be performed in all Veterans with advanced LUAD and LUOT.</p></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"49 3","pages":"Pages 265-274"},"PeriodicalIF":4.0,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0093775422000549/pdfft?md5=ef9e86fd49cb026f651bf2bf4c0cef59&pid=1-s2.0-S0093775422000549-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40643108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Surgery for early-stage lung cancer with video-assisted thoracoscopic surgery versus open thoracotomy: A narrative review","authors":"Juan Alban ,&nbsp;Kathleen Kennedy ,&nbsp;Alicia Hulbert ,&nbsp;Melani Lighter ,&nbsp;Mary Pasquinelli ,&nbsp;Israel Rubinstein ,&nbsp;Seema Ghelani ,&nbsp;Andrew Clayburn ,&nbsp;Lawrence E. Feldman","doi":"10.1053/j.seminoncol.2022.06.012","DOIUrl":"10.1053/j.seminoncol.2022.06.012","url":null,"abstract":"<div><p>Recommending video-assisted thoracic surgery (VATS) over open thoracotomy to patients with early-stage non-small-cell lung cancer (NSCLC) is controversial. Accordingly, we reviewed randomized comparative studies to determine the risks and benefits of VATS lobectomy. Electronic searches on PubMed with standard search terms revealed 97 comparative studies published between 1990 and 2022. Of those, only 5 were randomized controlled clinical trials (RCT) and 1 is still ongoing although initial data has been published as an abstract form. A total of 918 patients were evaluated in 5 RCT's. All studies included patients with known or suspected primary lung cancer randomized in a 1:1 ratio to VATS or thoracotomy. Between 2 studies, reports of 1-year, 3-year and 5-year overall survival were found to be similar across surgical modalities. Additionally, no differences were found in the rates of locoregional and distant recurrence. Three studies reported no statistical differences in the number of hilar and mediastinal lymph nodes sampled. Two studies found decreased length of stay following VATS (4 days <em>v</em> 5 days, <em>P</em> = 0.027 and <em>P</em> = 0.008), while 2 found no difference. Increased in-hospital complications were seen in 2 studies (<em>P</em> = 0.008 and <em>P</em> = 0.039). VATS was associated with decreased pain scores, better self-reported QOL at 52 weeks (<em>P</em> = 0.014). Few randomized clinical trials comparing VATS lobectomy to open thoracotomy and lobectomy in early stage NSCLC have been reported. These studies suggest that VATS lobectomy offers similar outcomes with decreased in-hospital complications, pain, length of stay, and improved physical functioning when compared to thoracotomy.</p></div>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"49 3","pages":"Pages 261-264"},"PeriodicalIF":4.0,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0093775422000525/pdfft?md5=dd5023c572f73eef603c68cd39333d05&pid=1-s2.0-S0093775422000525-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33458634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}