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Cancers
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Screening, Diagnosis and Staging of Lung Cancer
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Screening, Diagnosis and Staging of Lung Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Causes, Screening and Diagnosis".

Deadline for manuscript submissions: 10 June 2025 | Viewed by 9674

Special Issue Editors

Dr. Ioannis Gkiozos

E-Mail Website
Guest Editor
Oncology Unit GPP, Athens, Greece
Interests: lung cancer; mesothelioma; thoracic oncology
Dr. Andriani G. Charpidou

E-Mail Website
Guest Editor
Third Department of Internal Medicine, Sotiria Hospital, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece
Interests: cancer; lung cancer; treatment; immunotherapy; vaccine
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Lung cancer is the leading cause of cancer-related deaths and represents a significant health burden worldwide. Its well-established association with smoking has led to secondary prevention interventions (screening) of high-risk populations, defined by age and smoking history. Although such screening programs have been associated with a significant reduction in lung-cancer related mortality, their incorporation in national screening programs is not yet universal. It should be noted that despite the impressive advances of immunotherapy and targeted therapies in the therapeutics of lung cancer, the prognosis of advanced stages is still dismal, highlighting the need of early detection that would permit curative therapeutic approaches. 

Moreover, the optimal diagnostic and staging procedure of lung cancer is of utmost importance, since it shapes the overall oncological management. In particular, invasive procedures of mediastinal staging are recommended in non-metastatic stages due to their higher sensitivity and specificity compared to imaging. Importantly, the establishment of lung cancer reference centers with a multidisciplinary approach with all specialists who are involved in the management of lung cancer should be a priority.

The aim of this Special Issue is to encompass a broad spectrum of topics related to the screening, diagnosis and staging of lung cancer. We welcome original research, review articles, clinical trials, and perspectives. We are looking forward to your contributions!

Dr. Ioannis Gkiozos
Dr. Andriani G. Charpidou
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • screening lung cancer
  • diagnosis lung cancer
  • staging lung cancer
  • clinical trial
  • high-risk populations
  • lung-cancer related mortality
  • oncological management

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Published Papers (6 papers)

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Research

Jump to: Review

15 pages, 22161 KiB  
Article
Historic p87 Is Diagnostic for Lung Cancer Preceding Clinical Presentation by at Least 4 Years
by Martin Tobi, Daniel Ezekwudo, Yosef Y. Tobi, Xiaoqing Zhao, Fadi Antaki, MaryAnn Rambus, Edi Levi, Harvinder Talwar and Benita McVicker
Cancers 2025, 17(6), 952; https://doi.org/10.3390/cancers17060952 - 12 Mar 2025
Viewed by 192
Abstract
Lung cancer remains the most common cancer worldwide, with a limited prognosis despite personalized treatment regimens. Low-dose computed tomography (CT) scanning as a means of early diagnosis has been disappointing due to the high false positive rate. Other non-invasive means of testing need [...] Read more.
Lung cancer remains the most common cancer worldwide, with a limited prognosis despite personalized treatment regimens. Low-dose computed tomography (CT) scanning as a means of early diagnosis has been disappointing due to the high false positive rate. Other non-invasive means of testing need to be developed that offer both timely diagnosis and predict prognosis. Methods: In the course of stool testing in large-scale testing of 2922 patients at increased risk of CRC, we were able to ascertain 112 patients documented to have prospectively been diagnosed with lung cancer. Stool and colonic effluents were tested for p87 with anti-adenoma antibody (Adnab-9) reactivity by ELISA and Western blot. Survival data were obtained where available. Results: Of 112 cancers, approximately 27.6% were squamous (SSC), 17.9% were adenocarcinoma, 8% were small, 6.25% were large cell, 3.57% were designated non-small cell cancer (NSCLC), 0.89% were indeterminate, 0.89% were lepidic spread, 3.57% had metastasis, and in 31.25%, data were unavailable. In total, 49.1% of the lung cancer patients had fecal Adnab-9 testing. Overall, 60% had positive testing compared to 38%, which was significant (OR2.19 [1.06–4.53]; p = 0.045). Cancers with higher lethality were less likely to test positive (approximately 8.5% each for both small and large cell lung cancers) and higher, with 56% for SCC and 25% for adenocarcinoma (0% NSCLC). In the larger groups, overall survival was worse in those testing positive: 474 testing positives versus 844 days in SCC and 54 testing positive versus 749 days in adenocarcinoma patients. Most importantly, the time from a positive test to the clinical diagnosis ranged from 2.72 years for small cell, 3.13 for adenocarcinoma, 5.07 for NSCLC, 6.07 for SSC, and 6.24 for large cell cancer. In excluded cases where cancer in the lung was believed to be metastatic, 83.3% of cancers were positive. Conclusions: At a projected real-world sensitivity of 0.60 and specificity of 0.60, and the ability to predate diagnosis by up to 4.7 years overall, this test could help direct lung cancer screening. In addition, the Adnab-9 testing selectively detects worse tumor types (87.5%) and those with worse prognoses amongst the more common, favorable phenotypes, thus making early diagnosis possible in those patients who stand to benefit most from this strategy. Metastatic lung cancer, also detected by the test, should be identified by the follow-up imaging studies and, therefore, would not be considered to be a major pitfall. Full article
(This article belongs to the Special Issue Screening, Diagnosis and Staging of Lung Cancer)
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19 pages, 3790 KiB  
Article
Predicting Postoperative Lung Cancer Recurrence and Survival Using Cox Proportional Hazards Regression and Machine Learning
by Lucy Pu, Rajeev Dhupar and Xin Meng
Cancers 2025, 17(1), 33; https://doi.org/10.3390/cancers17010033 - 26 Dec 2024
Cited by 2 | Viewed by 957
Abstract
Background: Surgical resection remains the standard treatment for early-stage lung cancer. However, the recurrence rate after surgery is unacceptably high, ranging from 30% to 50%. Despite extensive efforts, accurately predicting the likelihood and timing of recurrence remains a significant challenge. This study aims [...] Read more.
Background: Surgical resection remains the standard treatment for early-stage lung cancer. However, the recurrence rate after surgery is unacceptably high, ranging from 30% to 50%. Despite extensive efforts, accurately predicting the likelihood and timing of recurrence remains a significant challenge. This study aims to predict postoperative recurrence by identifying novel image biomarkers from preoperative chest CT scans. Methods: A cohort of 309 patients was selected from 512 non-small-cell lung cancer patients who underwent lung resection. Cox proportional hazards regression analysis was employed to identify risk factors associated with recurrence and was compared with machine learning (ML) methods for predictive performance. The goal is to improve the ability to predict the risk and time of recurrence in seemingly “cured” patients, enabling personalized surveillance strategies to minimize lung cancer recurrence. Results: The Cox hazards analyses identified surgical procedure, TNM staging, lymph node involvement, body composition, and tumor characteristics as significant determinants of recurrence risk, both for local/regional and distant recurrence, as well as recurrence-free survival (RFS) and overall survival (OS) (p < 0.05). ML models and Cox models exhibited comparable predictive performance, with an area under the receiver operative characteristic (ROC) curve (AUC) ranging from 0.75 to 0.77. Conclusions: These promising findings demonstrate the feasibility of predicting postoperative lung cancer recurrence and survival time using preoperative chest CT scans. However, further validation using larger, multisite cohort is necessary to ensure robustness and facilitate integration into clinical practice for improved cancer management. Full article
(This article belongs to the Special Issue Screening, Diagnosis and Staging of Lung Cancer)
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12 pages, 511 KiB  
Article
Disruptions in Lung Cancer Detection During COVID-19
by Trisha Lal, Uriel Kim, Christina S. Boutros, Natalie N. Chakraborty, Susan J. Doh, Christopher W. Towe and Richard S. Hoehn
Cancers 2024, 16(23), 4001; https://doi.org/10.3390/cancers16234001 - 29 Nov 2024
Viewed by 707
Abstract
Objective: To quantify the extent of the disruption and recovery of lung cancer detection during the first two years of the pandemic, focusing on disparities across demographic and community factors. Methods: This retrospective cohort study used the SEER database to identify lung cancer [...] Read more.
Objective: To quantify the extent of the disruption and recovery of lung cancer detection during the first two years of the pandemic, focusing on disparities across demographic and community factors. Methods: This retrospective cohort study used the SEER database to identify lung cancer cases from 2001 to 2021. Expected incidence rates for 2020 and 2021 were projected based on pre-pandemic trends (2000–2019) using the NCI’s Joinpoint Regression program. Percent differences between expected and observed incidence rates were calculated. Multivariate and propensity score analyses were conducted to quantify changes in the odds of being diagnosed with metastatic disease during the pandemic. Results: Lung cancer incidence fell by 10% in 2020 compared to pre-pandemic projections, with rural populations, non-Hispanic Black and Asian patients, and females disproportionately affected. By 2021, detection rates partially recovered but remained 5% below expected levels. Localized disease detection improved significantly, while rural communities not adjacent to metropolitan areas faced further declines. Adjusted analyses showed that patients with small-cell lung cancer (SCLC) and those of Hispanic, non-Hispanic Black, or Asian/Pacific Islander ethnicity had persistently higher rates of distant disease presentation through 2021. Conclusions: The pandemic significantly reduced lung cancer detection, with only partial recovery by 2021. Persistent gaps, particularly in rural and minoritized populations, highlight the need for targeted interventions to reengage these communities. Full article
(This article belongs to the Special Issue Screening, Diagnosis and Staging of Lung Cancer)
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19 pages, 1401 KiB  
Article
Shall We Screen Lung Cancer with Volume Computed Tomography in Austria? A Cost-Effectiveness Modelling Study
by Hilde ten Berge, Dianne Ramaker, Greta Piazza, Xuanqi Pan, Bernd Lamprecht, Arschang Valipour and Helmut Prosch
Cancers 2024, 16(15), 2623; https://doi.org/10.3390/cancers16152623 - 23 Jul 2024
Cited by 1 | Viewed by 4495
Abstract
This study assessed the cost-effectiveness of a lung cancer screening (LCS) program using low-dose computed tomography (LDCT) in Austria. An existing decision tree with an integrated Markov model was used to analyze the cost-effectiveness of LCS versus no screening from a healthcare payer [...] Read more.
This study assessed the cost-effectiveness of a lung cancer screening (LCS) program using low-dose computed tomography (LDCT) in Austria. An existing decision tree with an integrated Markov model was used to analyze the cost-effectiveness of LCS versus no screening from a healthcare payer perspective over a lifetime horizon. A simulation was conducted to model annual LCS for an asymptomatic high-risk population cohort aged 50–74 with a smoking history using the Dutch–Belgian Lung Cancer Screening Study (NEderlands-Leuvens Longkanker ScreeningsONderzoek, NELSON) screening outcomes. The principal measure utilized to assess cost-effectiveness was the incremental cost-effectiveness ratio (ICER). Sensitivity and scenario analyses were employed to determine uncertainties surrounding the key model inputs. At an uptake rate of 50%, 300,277 eligible individuals would participate in the LCS program, yielding 56,122 incremental quality-adjusted life years (QALYs) and 84,049 life years gained compared to no screening, with an ICER of EUR 24,627 per QALY gained or EUR 16,444 per life-year saved. Additionally, LCS led to the detection of 25,893 additional early-stage lung cancers and averted 11,906 premature lung cancer deaths. It was estimated that LCS would incur EUR 945 million additional screening costs and EUR 386 million additional treatment costs. These estimates were robust in sensitivity analyses. Implementation of annual LCS with LDCT for a high-risk population, using the NELSON screening outcomes, is cost-effective in Austria, at a threshold of EUR 50,000 per QALY. Full article
(This article belongs to the Special Issue Screening, Diagnosis and Staging of Lung Cancer)
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Review

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18 pages, 311 KiB  
Review
Endobronchial Ultrasound Access to Pulmonary Vasculature in Thoracic Malignancy
by Evangelia Koukaki, Nektarios Anagnostopoulos, Aikaterini Bakiri, Stavroula Zaneli and Grigorios Stratakos
Cancers 2025, 17(4), 616; https://doi.org/10.3390/cancers17040616 - 11 Feb 2025
Viewed by 1213
Abstract
Endobronchial ultrasound (EBUS) has evolved beyond conventional applications in mediastinal staging and central pulmonary tumor diagnosis. It encompasses the assessment of pulmonary vasculature in patients with thoracic malignancies. EBUS can visualize major vessels and allow assessment of pulmonary embolism, differential diagnosis of endovascular [...] Read more.
Endobronchial ultrasound (EBUS) has evolved beyond conventional applications in mediastinal staging and central pulmonary tumor diagnosis. It encompasses the assessment of pulmonary vasculature in patients with thoracic malignancies. EBUS can visualize major vessels and allow assessment of pulmonary embolism, differential diagnosis of endovascular lesions, and T staging. Additionally, EBUS-guided transvascular needle aspiration (TVNA) has proven valuable for sampling lesions behind vessels and diagnosing conditions such as pulmonary artery sarcoma and tumor embolism, with low complication rates reported. The PubMed and SCOPUS databases were searched up to November 2024 for articles in the English language reporting the use of EBUS for pulmonary vasculature assessment. References were also searched for relevant articles. The integration of EBUS with other modalities enhances staging and diagnostic capabilities in thoracic malignancies. Despite promising findings, limitations include suboptimal image quality and challenges in extensively assessing all the vasculature. Safety concerns, particularly with transvascular biopsy, remain minimal with expert handling, although further studies are needed to assess specific risks like hematogenous tumor seeding. EBUS continues to evolve, suggesting its potential to become the cornerstone in advanced thoracic diagnostics and treatment planning. This review systematically explores the feasibility, safety, and diagnostic utility of EBUS in pulmonary vasculature assessment, highlighting its potential as an indispensable tool in thoracic diagnostics and treatment planning. Full article
(This article belongs to the Special Issue Screening, Diagnosis and Staging of Lung Cancer)
22 pages, 1082 KiB  
Review
The Adenosinergic Pathway in Non-Small Cell Lung Cancer
by Olivier Van Kerkhove, Saartje Verfaillie, Brigitte Maes and Kristof Cuppens
Cancers 2024, 16(18), 3142; https://doi.org/10.3390/cancers16183142 - 13 Sep 2024
Viewed by 1456
Abstract
Immune checkpoint inhibitors (ICIs) targeting PD-(L)1 and CTLA-4 have revolutionized the systemic treatment of non-small cell lung cancer (NSCLC), achieving impressive results. However, long-term clinical benefits are only seen in a minority of patients. Extensive research is being conducted on novel potential immune [...] Read more.
Immune checkpoint inhibitors (ICIs) targeting PD-(L)1 and CTLA-4 have revolutionized the systemic treatment of non-small cell lung cancer (NSCLC), achieving impressive results. However, long-term clinical benefits are only seen in a minority of patients. Extensive research is being conducted on novel potential immune checkpoints and the mechanisms underlying ICI resistance. The tumor microenvironment (TME) plays a critical role in modulating the immune response and influencing the efficacy of ICIs. The adenosinergic pathway and extracellular adenosine (eADO) are potential targets to improve the response to ICIs in NSCLC patients. First, this review delves into the adenosinergic pathway and the impact of adenosine within the TME. Second, we provide an overview of relevant preclinical and clinical data on molecules targeting this pathway, particularly focusing on NSCLC. Full article
(This article belongs to the Special Issue Screening, Diagnosis and Staging of Lung Cancer)
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