Seminars In Oncology[JOURNAL]
Sun
200 papers
Impact of CT screening in lung cancer: Scientific evidence and literature review.
Kennedy K, Hulbert A, Pasquinelli M … +1 more , Feldman LE
Semin Oncol · 2022 Jun · PMID 36114033 · Publisher ↗
The treatment of lung cancer has improved significantly in recent years however, lung cancer remains as a leading cause of cancer-related mortality worldwide. Lung cancer screening has been explored, over the past severa...
The treatment of lung cancer has improved significantly in recent years however, lung cancer remains as a leading cause of cancer-related mortality worldwide. Lung cancer screening has been explored, over the past several decades, as a means of reducing lung cancer mortality, to identify asymptomatic disease when it is potentially curable. The National Lung Screening Trial (NLST) established that low-dose computed tomography (LDCT) scans of the chest can be instrumental in reducing lung cancer mortality but the criteria for screening implemented in this trial may not be equitably sensitive across racial and sex subpopulations. Furthermore, the high false detection rate reported in this trial has raised concerns regarding overdiagnosis with LDCT alone. The aim of this review is to summarize the history of lung cancer screening trials, limitations of lung cancer screening, the impact of alternative risk prediction models in reducing disparities, and the use of biomarkers in conjunction with imaging to improve diagnostic authenticity.
The psychosocial and emotional experiences of cancer patients during the COVID-19 pandemic: A systematic review.
Muls A, Georgopoulou S, Hainsworth E … +4 more , Hartley B, O'Gara G, Stapleton S, Cruickshank S
Semin Oncol · 2022 Oct · PMID 36089413 · Full text
BACKGROUND: COVID-19 was declared a pandemic by the World Health Organization on March 11th, 2020. Global social lockdowns were instigated to reduce spread and prevent health-services from becoming overwhelmed. People ha...
BACKGROUND: COVID-19 was declared a pandemic by the World Health Organization on March 11th, 2020. Global social lockdowns were instigated to reduce spread and prevent health-services from becoming overwhelmed. People having treatment for cancer are known to have heightened psychological/emotional burden. The combined impact of managing pandemic regulations alongside this may present additional burden. The purpose of this systematic review is to examine current evidence of the psychological and emotional impact of COVID-19 on people with cancer, early in the pandemic. METHODS: Five electronic databases were searched (Embase, Global Health, HMIC, PsychINFO, CINAHL) from September 2019 to October 2021. Qualitative, quantitative and mixed-method primary research studies exploring emotional and psychological impacts of COVID-19 on cancer patients, limited to English language, were included. Quality appraisal was conducted using the MMAT. RESULTS: Fifty-one papers, with 27,356 people from 21 countries treated for cancer, were included. 43 studies were quantitative with a survey method approach, six studies qualitative and four used a mixed methods design. MMAT score was mostly two or three. Four themes were identified: Emotional aspects and Quality of Life; Psychosocial aspects; Impact of COVID-19 on self; Impact of COVID-19 on cancer, with themes overlapping. CONCLUSION: Whilst emotional/psychological impacts such as anxiety, isolation, employment fears, and uncertainty about the future were potentially universal concerns early in the pandemic, they may have been particularly acute for people living with cancer and represent complex, overlapping factors. As COVID-19 continues to impact health-services and society, it is important to focus on any ongoing impact to the experience of cancer patients. Most of the studies reviewed used tools that do not provide deeper understanding of how and why emotional states of people with cancer were affected. Further qualitative work may reveal patterns of what was unique to cancer patients during the pandemic, compared to general populations.
Surgery for early-stage lung cancer with video-assisted thoracoscopic surgery versus open thoracotomy: A narrative review.
Alban J, Kennedy K, Hulbert A … +6 more , Lighter M, Pasquinelli M, Rubinstein I, Ghelani S, Clayburn A, Feldman LE
Semin Oncol · 2022 Jun · PMID 36088130 · Publisher ↗
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 deter...
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 v 5 days, P = 0.027 and P = 0.008), while 2 found no difference. Increased in-hospital complications were seen in 2 studies (P = 0.008 and P = 0.039). VATS was associated with decreased pain scores, better self-reported QOL at 52 weeks (P = 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.
Influence of Cancer on COVID-19 Incidence, Outcomes, and Vaccine Effectiveness: A Prospective Cohort Study of U.S. Veterans.
Leuva H, Zhou M, Brau N … +7 more , Brown ST, Mundi P, Rosenberg TM, Luhrs C, Bates SE, Park YA, Fojo T
Semin Oncol · 2022 Oct · PMID 36055952 · Full text
PURPOSE: Coronavirus disease 2019 (COVID-19) has been a constant health threat since its emergence. Amongst risk factors proposed, a diagnosis of cancer has been worrisome. We report the impact of cancer and other risk f...
PURPOSE: Coronavirus disease 2019 (COVID-19) has been a constant health threat since its emergence. Amongst risk factors proposed, a diagnosis of cancer has been worrisome. We report the impact of cancer and other risk factors in US Veterans receiving care at Veterans Administration (VA) Hospitals, their adjusted odds ratio (aOR) for infection and death, and report on the impact of vaccines on the incidence and severity of COVID-19 infections in Veterans without/with cancer. METHODS: We conducted a cohort study of US Veterans without/with cancer by mining VA COVID-19 Shared Data Resource (CSDR) data using the VA Informatics and Computing Infrastructure (VINCI). Our observation period includes index dates from 14DEC2020 to 25JAN2022, encompassing both the delta and omicron waves in the US. RESULTS: We identified 915,928 Veterans, 24% of whom were African Americans who had undergone COVID testing-688,541 were and 227,387 were not vaccinated. 157,072 had a cancer diagnosis in the preceding two years. Age emerged as the major risk factor, with gender, BMI, and (Elixhauser) comorbidity contributing less. Among veterans with solid tumors other than lung cancer, risks of infection and death within 60 days were comparable to Veterans without cancer. However, those with hematologic malignancies fared worse. Vaccination was highly effective across all cancer cohorts; the respective rates of infection and death after infection were 8% and 5% among the vaccinated compared to 47% and 10% in the unvaccinated. Amongst vaccinated, increased risk of infection was noted in both, Veterans with hematologic malignancy treated with chemotherapy (HR, 2.993, P < 0.0001) or targeted therapies (HR, 1.781, P < 0.0001), and in solid tumors treated with either chemotherapy (HR 2.328, 95%CI 2.075-2.611, P < 0.0001) or targeted therapies (HR 1.328, P < 0.0001) when compared to those not on treatment. CONCLUSIONS: Risk for COVID-19 infection and death from infection vary based on cancer type and therapies administered. Importantly and encouragingly, the duration of protection from infection following vaccination in Veterans with a diagnosis of cancer was remarkably like those without a cancer diagnosis. Veterans with hematologic malignancies are especially vulnerable, with lower vaccine effectiveness (VE).
Comorbidity and life expectancy in shared decision making for lung cancer screening.
Bade B, Gwin M, Triplette M … +2 more , Wiener RS, Crothers K
Semin Oncol · 2022 Jun · PMID 35940959 · Publisher ↗
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, tobac...
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.
Exploring the effects of racial and socioeconomic factors on timeliness of lung cancer diagnosis and treatment in Baltimore Veterans.
Alghanim F, Li KZ, An M … +4 more , Verceles AC, Grier WR, Abbas H, Deepak J
Semin Oncol · 2022 Jun · PMID 35927100 · Publisher ↗
OBJECTIVES: 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. METHOD...
OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Barriers and facilitators to lung cancer screening and follow-up.
Bernstein E, Bade BC, Akgün KM … +2 more , Rose MG, Cain HC
Semin Oncol · 2022 Jun · PMID 35927099 · Publisher ↗
Two randomized trials have shown that lung cancer screening (LCS) with low dose computed tomography (LDCT) reduces lung cancer mortality in patients at high-risk for lung malignancy by identifying early-stage cancers, wh...
Two randomized trials have shown that lung cancer screening (LCS) with low dose computed tomography (LDCT) reduces lung cancer mortality in patients at high-risk for lung malignancy by identifying early-stage cancers, when local cure and control is achievable. The implementation of LCS in the United States has revealed multiple barriers to preventive cancer care. Rates of LCS are disappointingly low with estimates between 5%-18% of eligible patients screened. Equally concerning, follow-up after baseline screening is far lower than that of clinical trials (44-66% v >90%). To optimize the benefits of LCS, programs must identify and address factors related to LCS participation and follow-up while concurrently recognizing and mitigating barriers. As a relatively new screening test, the most effective processes for LCS are uncertain. Therefore, LCS programs have adopted a wide range of approaches without clearly established best practices to guide them, particularly in rural and resource-limited settings. In this narrative review, we identify barriers and facilitators to LCS, focusing on those studies in non-clinical trial settings - reflecting "real world" challenges. Our goal is to identify effective and scalable LCS practices that will increase LCS participation, improve adherence to follow-up, inform strategies for quality improvement, and support new research approaches.
Assessing Outcomes in NSCLC: Radiomic analysis, kinetic analysis and circulating tumor DNA.
Maniar A, Wei AZ, Dercle L … +4 more , Bien HH, Fojo T, Bates SE, Schwartz LH
Semin Oncol · 2022 Jun · PMID 35914982 · Publisher ↗
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-ba...
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.
Biomarkers and the microbiome in the detection and treatment of early-stage non-small cell lung cancer.
Klein M, Pragman AA, Wendt C
Semin Oncol · 2022 Jun · PMID 35914981 · Publisher ↗
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 detecti...
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.
Controversies and challenges in lung cancer screening.
Rampariag R, Chernyavskiy I, Al-Ajam M … +1 more , Tsay JJ
Semin Oncol · 2022 Jun · PMID 35907666 · Publisher ↗
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 incl...
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.
Analysis of actionable genetic alterations in lung carcinoma from the VA National Precision Oncology Program.
Jalal SI, Guo A, Ahmed S … +1 more , Kelley MJ
Semin Oncol · 2022 Jun · PMID 35902275 · Publisher ↗
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 freq...
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: ALK rearrangement 0.8%, BRAF V600E 2.1%, EGFR exon 20 insertion mutation 0.48%, EGFR sensitizing mutations 6.6%, ERBB2 small variants 1.2%, KRAS G12C 14.0%, MET exon 14 skipping mutation 1.5%, NTRK rearrangement 0.1%, RET rearrangement 0.4%, and ROS1 rearrangement 0.3%. The frequency of EGFR mutations, RET rearrangement, MET exon 14 and ERBB2 small variants frequencies were significantly lower in NPOP compared to other published reports while MET 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.
Military exposures and lung cancer in United States Veterans.
Grier W, Abbas H, Gebeyehu RR … +5 more , Singh AK, Ruiz J, Hines S, Alghanim F, Deepak J
Semin Oncol · 2022 Jun · PMID 35882571 · Publisher ↗
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 W...
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.
Non-small cell lung cancer in the era of immunotherapy.
Huang Q, Kemnade J, Cornwell L … +3 more , Kheradmand F, Sabichi AL, Das D
Semin Oncol · 2022 Jun · PMID 35879123 · Publisher ↗
Immunotherapy for non-small cell lung cancer (NSCLC) has revolutionized treatment for those with advanced disease, and recent data have emerged providing evidence for its benefits in earlier stages of the disease. Severa...
Immunotherapy for non-small cell lung cancer (NSCLC) has revolutionized treatment for those with advanced disease, and recent data have emerged providing evidence for its benefits in earlier stages of the disease. Several pivotal clinical trials provide compelling data that adaptive immune cells may be highly effective and possibly even curative for NSCLC. Immune checkpoint inhibitors (ICIs) can unleash highly reactive memory immune responses to tumor antigens with durable effects against advanced or recurrent disease. Despite these encouraging results, many critical questions remain in the field including, for example, how to identify the subsets of NSCLC patients who most benefit from ICI treatment, and how ICI efficacy might be enhanced by utilizing combinations or sequencing of agents. A deeper understanding of biological mechanisms involved in lung cancer offers a unique opportunity to further explore the interaction between the adaptive immune landscape and NSCLC. Given the high incidence of lung cancer in Veterans and many Veterans being treated with immunotherapy for this disease, it is timely to have their adequate representation in future clinical trials. New clinical trials focused on Veterans can assist in exploring ways to mitigate resistant mechanisms as well as to investigate predictive and prognostic biomarkers for response to ICIs and other treatments. This paper will review current data and indications for immunotherapy in NSCLC, introduce new areas of research within immunotherapy, and discuss its applicability to the Veteran population.
Challenges in initiating a lung cancer screening program: Experiences from two VA medical centers.
Bujarski S, Flowers R, Alkhunaizi M … +5 more , Cuvi D, Sathya S, Melcher J, Kheradmand F, Holt G
Semin Oncol · 2022 Jun · PMID 35853765 · Publisher ↗
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 includ...
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.
Treating advanced lung cancer in older Veterans with comorbid conditions and frailty.
Thomas T, Patel B, Mitchell J … +3 more , Whitmer A, Knoche E, Gupta P
Semin Oncol · 2022 Jun · PMID 35853764 · Publisher ↗
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. Th...
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.
Targeting EZH2 to overcome the resistance to immunotherapy in lung cancer.
Shin DS, Park K, Garon E … +1 more , Dubinett S
Semin Oncol · 2022 Jun · PMID 35851153 · Publisher ↗
Unleashing the immune system to fight cancer has been a major breakthrough in cancer therapeutics since 2014 when anti-PD-1 antibodies (pembrolizumab and nivolumab) were approved for patients with metastatic melanoma. Th...
Unleashing the immune system to fight cancer has been a major breakthrough in cancer therapeutics since 2014 when anti-PD-1 antibodies (pembrolizumab and nivolumab) were approved for patients with metastatic melanoma. Therapeutic indications have rapidly expanded for many types of advanced cancer, including lung cancer. A variety of antibodies targeting the PD-1/PD-L1 checkpoint are contributing to this paradigm shift. The field now confronts two salient challenges: first, to improve the therapeutic outcome given the low response rate across the histologies; second, to identify biomarkers for improved patient selection. Pre-clinical and clinical studies are underway to evaluate combinatorial treatments to improve the therapeutic outcome paired with correlative studies to identify the factors associated with response and resistance. One of the emerging strategies is to combine epigenetic modifiers with immune checkpoint blockade (ICB) based on the evidence that targeting epigenetic elements can enhance anti-tumor immunity by reshaping the tumor microenvironment (TME). We will briefly review pleotropic biological functions of enhancer of zeste homolog 2 (EZH2), the enzymatic subunit of polycomb repressive complex 2 (PRC2), clinical developments of oral EZH2 inhibitors, and potentially promising approaches to combine EZH2 inhibitors and PD-1 blockade for patients with advanced solid tumors, focusing on lung cancer.
Improving the efficacy of immunotherapy in small cell lung cancer: Leveraging recent scientific discoveries and tumor-specific antigens.
Hiatt JB, Romine PE, Wu DY
Semin Oncol · 2022 Jun · PMID 35843737 · Publisher ↗
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...
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.
Lung cancer screening at the VA: Past, present and future.
Maurice NM, Tanner NT
Semin Oncol · 2022 Jun · PMID 35831214 · Publisher ↗
Lung cancer is responsible for more deaths annually in the United States than breast, prostate and colon cancers combined. Lung cancer screening with annual low-dose computed tomography reduces lung cancer mortality in h...
Lung cancer is responsible for more deaths annually in the United States than breast, prostate and colon cancers combined. Lung cancer screening with annual low-dose computed tomography reduces lung cancer mortality in high-risk patients through early detection. The incidence of lung cancer is higher in the veteran population compared to the general population due, in part, to the prevalence of tobacco use. Early detection of lung cancer is therefore an important goal of the Veterans Health Administration (VHA), the largest integrated health care system in the United States. The following will review previous and current initiatives undertaken by the VHA to implement and expand access to lung cancer screening and will highlight target areas of interest to improve uptake and quality of lung cancer screening. Through these initiatives and programs, the VHA aims to provide high quality and equitable access to lung cancer screening for all Veterans that incorporates research that will improve outcomes and potentially inform and optimize the practice of Lung cancer screening across the United States.
Loss of function STK11 alterations and poor outcomes in non-small-cell lung cancer: Literature and case series of US Veterans.
Farooq H, Bien H, Chang V … +3 more , Becker D, Park YH, Bates SE
Semin Oncol · 2022 Jun · PMID 35831213 · Publisher ↗
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...
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.
Molecular biomarkers and liquid biopsies in lung cancer.
Sankar K, Zeinali M, Nagrath S … +1 more , Ramnath N
Semin Oncol · 2022 Jun · PMID 35820969 · Publisher ↗
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, mol...
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.
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