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Advancements in Lung Cancer Surgical Treatment and Prognosis

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A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: 15 August 2025 | Viewed by 9039

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Special Issue Editors

Prof. Dr. Sai Yendamuri

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Guest Editor

Roswell Park Cancer Institute, Elm & Carlton Streets, Buffalo, NY 14263, USA
Interests: thoracic

Dr. Kenneth Patrick Seastedt

E-Mail Website
Co-Guest Editor

Roswell Park Cancer Institute, Elm & Carlton Streets, Buffalo, NY 14263, USA
Interests: thoracic surgery

Special Issue Information

Dear Colleagues,

Lung cancer, a leading cause of cancer-related mortality worldwide, is on the cusp of a transformative era. With advancements in surgical techniques, targeted therapies, and the emergence of immunotherapies, our approach to combating this disease is evolving. Key factors include accurate staging, early biomarker detection, and insights from recent clinical trials, all shaping the future of cancer outcomes. This Special Issue will highlight the latest developments in lung cancer treatment. The aim is to explore the newest surgical techniques, prognosis, and the role of targeted and immunotherapies, and to engage in discussions that are changing the landscape of lung cancer care.

We are seeking insightful manuscripts that explore the forefront of lung cancer surgical techniques, the impact of targeted therapies, and the collaborative dialogues steering lung cancer care. Contributions that illuminate the nuances of precise staging, the critical importance of early molecular testing, and findings from contemporary clinical trials are particularly sought after. Comprehensive reviews that paint a clear picture of current lung cancer treatments, prognosis, and emerging trends are also highly encouraged.

Spotlight topics of interest include, but are not limited to, the following:

The Surgical Renaissance—Advancements in VATS and RATS and their impact on patient outcomes.
Resectability Redefined—The art of combining oncologic, physiologic, and anatomic insights for a standardized reporting structure.
Staging—The importance and challenges of accurate staging and early biomarker testing.
Segmentectomy vs. Wedge Resection in Early-Stage Lung Cancer—Surgical Outcomes, Oncologic Efficacy, and Future Directions.
Operable N2 Disease—Criteria, Controversies, and Clinical Outcomes.
Oligometastatic Disease—Defining the Spectrum, Therapeutic Approaches, and Future Directions.
Management of Complex Lung Cancers—Tackling tumors involving the chest wall, mediastinum, or other critical structures with techniques like cardiopulmonary bypass and ECMO.
Multimodality Therapy—Combining surgery, radiation, and systemic therapies for optimal lung cancer outcomes.
Immunotherapy and Oncogene-Targeted Therapies—Current status, challenges, and future directions in operable lung cancer.
Management of Treatment-Related Complications—Addressing complications from surgery, radiation, and systemic therapies.
Novel Biomarkers in Lung Cancer—Discovering and validating new biomarkers for early detection, operability, prognosis, and treatment response.
Artificial Intelligence in Thoracic Oncology—Using AI for enhanced imaging, treatment prediction, and patient outcomes.
Quality of Life and Survivorship—Addressing long-term effects of treatment, rehabilitation, and psychosocial challenges post-lung cancer surgery.
Diversity, Equity, and Inclusion (DEI) in Resectable Lung Cancer Care—Addressing Disparities, Challenges, and Pathways Forward.
Enhanced Recovery After Thoracic Surgery (ERATS)—Protocols to optimize post-operative outcomes and reduce hospitalization.

Prof. Dr. Sai Yendamuri
Dr. Kenneth Patrick Seastedt
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

lung cancer
surgical techniques
targeted therapies
immunotherapies
accurate staging
biomarker detection
clinical trials
multimodality therapy
artificial intelligence (AI) in thoracic oncology
enhanced recovery after thoracic surgery (ERATS)

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Published Papers (7 papers)

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Research

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12 pages, 1511 KiB

Open AccessArticle

Sex-Based Differences in Lung Cancer Incidence: A Retrospective Analysis of Two Large US-Based Cancer Databases

by Kalyan Ratnakaram, Sai Yendamuri, Adrienne Groman and Sukumar Kalvapudi

Cancers 2024, 16(19), 3244; https://doi.org/10.3390/cancers16193244 - 24 Sep 2024

Viewed by 899

Abstract

Background/Objectives: Non-small cell lung cancer (NSCLC) has seen a relative rise in incidence among females versus males in recent years, although males still have a higher overall incidence. However, it is unclear whether this trend is consistent across all populations. Therefore, we retrospectively examined this relationship in two large high-risk clinical cohorts. Methods: First, we analyzed lung cancer incidence among individuals with a smoking history of over 40 pack-years in the National Lung Screening Trial (NLST). Then, we investigated the incidence of second primary NSCLC in patients who underwent lobectomy for previous stage I lung cancer using the Surveillance, Epidemiology, and End Results (SEER) database. We performed both univariate and multivariable time-to-event analyses to investigate the relationship between sex and lung cancer incidence. Results: In the NLST cohort (n = 37,627), females had a higher risk of developing primary NSCLC than males (HR = 1.11 [1.007–1.222], p = 0.035) after adjusting for age and pack-year history. In the SEER cohort (n = 19,327), females again exhibited an increased risk of developing a second primary lung cancer (HR = 1.138 [1.02–1.269], p = 0.021), after adjusting for age, race, grade, and histology. Conclusions: Our analysis reveals that females have a modestly higher lung cancer incidence than males in high-risk populations. These findings underscore the importance of further researching the underlying cellular processes that may cause sex-specific differences in lung cancer incidence. Full article

(This article belongs to the Special Issue Advancements in Lung Cancer Surgical Treatment and Prognosis)

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9 pages, 502 KiB

Open AccessArticle

Musculoskeletal Disorders Related to Upper Limb Disability after One-Year Lung Cancer Resection

by Javier Martín Núñez, Julia Raya Benítez, Florencio Quero Valenzuela, Andrés Calvache Mateo, Alba Navas Otero, Alejandro Heredia Ciuró and Marie Carmen Valenza

Cancers 2024, 16(12), 2279; https://doi.org/10.3390/cancers16122279 - 19 Jun 2024

Viewed by 859

Abstract

Lung resection represents the main curative treatment in lung cancer; however, this surgical process leads to several disorders in tissues and organs. Previous studies have reported cardiovascular, pulmonary, and muscular disturbances that affect the functional capacity of these patients in the short, mid, and long term. However, upper limb impairment has been scarcely explored in the long term, despite the relevance in the independence of the patients. The aim of this study was to characterize the upper limb impairment in survivors of lung cancer one year after pulmonary resection. In this observational trial, patients who underwent lung cancer surgery were compared to control, healthy subjects matched by age and gender. Upper limb musculoskeletal disorders (shoulder range of motion, pain pressure threshold, nerve-related symptoms) and functional capacity (upper limb exercise capacity) were evaluated one-year post-surgery. A total of 76 survivors of lung cancer and 74 healthy subjects were included in the study. Significant differences between groups were found for active shoulder mobility (p < 0.05), widespread hypersensitivity to mechanical pain (p < 0.001), mechanosensitivity of the neural tissue (p < 0.001), and upper limb exercise capacity (p < 0.001). Patients who undergo lung cancer surgery show upper limb musculoskeletal disorders and upper limb functional impairment after a one-year lung resection. This clinical condition could limit the functionality and quality of life of patients with lung cancer. Full article

(This article belongs to the Special Issue Advancements in Lung Cancer Surgical Treatment and Prognosis)

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22 pages, 8863 KiB

Open AccessArticle

LKB1 Loss Correlates with STING Loss and, in Cooperation with β-Catenin Membranous Loss, Indicates Poor Prognosis in Patients with Operable Non-Small Cell Lung Cancer

by Eleni D. Lagoudaki, Anastasios V. Koutsopoulos, Maria Sfakianaki, Chara Papadaki, Georgios C. Manikis, Alexandra Voutsina, Maria Trypaki, Eleftheria Tsakalaki, Georgia Fiolitaki, Dora Hatzidaki, Emmanuel Yiachnakis, Dimitra Koumaki, Dimitrios Mavroudis, Maria Tzardi, Efstathios N. Stathopoulos, Kostas Marias, Vassilis Georgoulias and John Souglakos

Cancers 2024, 16(10), 1818; https://doi.org/10.3390/cancers16101818 - 10 May 2024

Viewed by 1351

Abstract

To investigate the incidence and prognostically significant correlations and cooperations of LKB1 loss of expression in non-small cell lung cancer (NSCLC), surgical specimens from 188 metastatic and 60 non-metastatic operable stage I-IIIA NSCLC patients were analyzed to evaluate their expression of LKB1 and pAMPK proteins in relation to various processes. The investigated factors included antitumor immunity response regulators STING and PD-L1; pro-angiogenic, EMT and cell cycle targets, as well as metastasis-related (VEGFC, PDGFRα, PDGFRβ, p53, p16, Cyclin D1, ZEB1, CD24) targets; and cell adhesion (β-catenin) molecules. The protein expression levels were evaluated via immunohistochemistry; the RNA levels of LKB1 and NEDD9 were evaluated via PCR, while KRAS exon 2 and BRAF^V600E mutations were evaluated by Sanger sequencing. Overall, loss of LKB1 protein expression was observed in 21% (51/248) patients and correlated significantly with histotype (p < 0.001), KRAS mutations (p < 0.001), KC status (concomitant KRAS mutation and p16 downregulation) (p < 0.001), STING loss (p < 0.001), and high CD24 expression (p < 0.001). STING loss also correlated significantly with loss of LKB1 expression in the metastatic setting both overall (p = 0.014) and in lung adenocarcinomas (LUACs) (p = 0.005). Additionally, LKB1 loss correlated significantly with a lack of or low β-catenin membranous expression exclusively in LUACs, both independently of the metastatic status (p = 0.019) and in the metastatic setting (p = 0.007). Patients with tumors yielding LKB1 loss and concomitant nonexistent or low β-catenin membrane expression experienced significantly inferior median overall survival of 20.50 vs. 52.99 months; p < 0.001 as well as significantly greater risk of death (HR: 3.32, 95% c.i.: 1.71–6.43; p <0.001). Our findings underscore the impact of the synergy of LKB1 with STING and β-catenin in NSCLC, in prognosis. Full article

(This article belongs to the Special Issue Advancements in Lung Cancer Surgical Treatment and Prognosis)

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11 pages, 3631 KiB

Open AccessArticle

Pulmonary Metastasectomy for Adrenocortical Carcinoma—Not If, but When

by Shamus R. Carr, Frank Villa Hernandez, Diana Grace Varghese, Hyoyoung Choo-Wosoba, Seth M. Steinberg, Martha E. Teke, Jaydira Del Rivero, David S. Schrump and Chuong D. Hoang

Cancers 2024, 16(4), 702; https://doi.org/10.3390/cancers16040702 - 7 Feb 2024

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Abstract

Background: Adrenocortical carcinoma (ACC) commonly metastasizes to the lungs, and pulmonary metastasectomy (PM) is utilized due to limited systemic options. Methods: All ACC patients with initially only lung metastases (LM) from a single institution constituted this observational case series. Kaplan-Meier and Cox proportional hazard analyses evaluated the association with potential prognostic factors and outcomes. Overall survival (OS) was calculated from the date of the PM or, in those patients who did not undergo surgery, from the development of LM. Results: A total of 75 ACC patients over a 45-year period met the criteria; 52 underwent PM, and 23 did not. The patients undergoing PM had a median OS of 3.1 years (95% CI: 2.4, 4.7 years) with the 5- and 10-year OS being 35.5% and 32.8%, respectively. The total resected LM did not impact the OS nor the DFS. The patients who developed LM after 11 months from the initial ACC resection had an improved OS (4.2 years; 95% CI: 3.2, NR; p = 0.0096) compared to those developing metastases earlier (2.4 years; 95% CI: 1.6, 2.8). Patients who underwent PM within 11 months of adrenalectomy demonstrated a reduced OS (2.2 years; 95% CI: 1.0, 2.7) compared to those after 11 months (3.6 years, 95% CI: 2.6, NR; p = 0.0045). PM may provide benefit to those patients with LM at presentation (HR: 0.5; p = 0.2827), with the time to first PM as a time-varying covariate. Conclusions: PM appears to have a role in ACC patients. The number of nodules should not be an exclusion factor. Patients developing LM within a year of primary tumor resection may benefit from waiting before further surgeries, which may provide additional insight into who may benefit from PM. Full article

(This article belongs to the Special Issue Advancements in Lung Cancer Surgical Treatment and Prognosis)

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16 pages, 543 KiB

Open AccessArticle

Influencing Factors on the Quality of Lymph Node Dissection for Stage IA Non-Small Cell Lung Cancer: A Retrospective Nationwide Cohort Study

by Piotr Gabryel, Piotr Skrzypczak, Magdalena Roszak, Alessio Campisi, Dominika Zielińska, Maciej Bryl, Katarzyna Stencel and Cezary Piwkowski

Cancers 2024, 16(2), 346; https://doi.org/10.3390/cancers16020346 - 13 Jan 2024

Cited by 3 | Viewed by 1279

Abstract

Lymphadenectomy is an essential part of complete surgical operation for non-small cell lung cancer (NSCLC). This retrospective, multicenter cohort study aimed to identify factors that influence the lymphadenectomy quality. Data were obtained from the Polish Lung Cancer Study Group Database. The primary endpoint was lobe-specific mediastinal lymph node dissection (L-SMLND). The study included 4271 patients who underwent VATS lobectomy for stage IA NSCLC, operated between 2007 and 2022. L-SMLND was performed in 1190 patients (27.9%). The remaining 3081 patients (72.1%) did not meet the L-SMLND criteria. Multivariate logistic regression analysis showed that patients with PET-CT (OR 3.238, 95% CI: 2.315 to 4.529; p < 0.001), with larger tumors (pT1a vs. pT1b vs. pT1c) (OR 1.292; 95% CI: 1.009 to 1.653; p = 0.042), and those operated on by experienced surgeons (OR 1.959, 95% CI: 1.432 to 2.679; p < 0.001) had a higher probability of undergoing L-SMLND. The quality of lymphadenectomy decreased over time (OR 0.647, 95% CI: 0.474 to 0.884; p = 0.006). An analysis of propensity-matched groups showed that more extensive lymph node dissection was not related to in-hospital mortality, complication rates, and hospitalization duration. Actions are needed to improve the quality of lymphadenectomy for NSCLC. Full article

(This article belongs to the Special Issue Advancements in Lung Cancer Surgical Treatment and Prognosis)

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12 pages, 883 KiB

Open AccessArticle

Association between the Preoperative Standard Uptake Value (SUV) and Survival Outcomes after Robotic-Assisted Segmentectomy for Resectable Non-Small Cell Lung Cancer (NSCLC)

by Aihab Aboukheir Aboukheir, Emilio Q. Villanueva III, Joseph R. Garrett, Carla C. Moodie, Jenna R. Tew, Eric M. Toloza, Jacques P. Fontaine and Jobelle J. A. R. Baldonado

Cancers 2023, 15(22), 5379; https://doi.org/10.3390/cancers15225379 - 12 Nov 2023

Viewed by 1717

Abstract

Background: Lung-sparing procedures, specifically segmentectomies and wedge resections, have increased over the years to treat early-stage non-small cell lung cancer (NSCLC). We investigate here the perioperative and long-term outcomes of patients who underwent robotic-assisted segmentectomy (RAS) at an NCI-designated cancer center and aim to show associations between the preoperative standard update value (SUV) to tumor stage, recurrence patterns, and overall survival. Methods: A retrospective analysis was performed on 166 consecutive patients who underwent RAS at a single institution from 2010 to 2021. Of this number, 121 robotic-assisted segmentectomies were performed for primary NSCLC, and a total of 101 patients were evaluated with a PET-CT scan. The SUV from the primary tumor was determined from the PET-CT. The clinical, surgical, and pathologic profiles and perioperative outcomes were summarized via descriptive statistics. Numerical variables were described as the median and interquartile range because all numerical variables were not normally distributed as assessed by the Shapiro–Wilk test of normality. Categorical variables were described as the count and proportion. Chi-square or Fisher’s exact test was used for association. The main outcomes were overall survival (OS) and recurrence-free survival (RFS). Kaplan–Meier (KM) curves were constructed to visualize the OS and RFS, which were also stratified according to tumor histology, the pathologic stage, and standard uptake value. A log-rank test for the equality of survival curves was performed to determine significant differences between groups. Results: The most common postoperative complications were atrial fibrillation (8.8%, 9/102), persistent air leak (7.84%, 8/102), and pneumonia (4.9%, 5/102). The median operative duration was 168.5 min (IQR 59), while the median estimated blood loss was 50 mL (IQR 125). The conversion rate to thoracotomy in this cohort was 3.9% (4/102). Intraoperative complications occurred in 2.9% (3/102). The median hospital length of stay was 3 days (IQR 3). The median chest tube duration was 3 days (IQR 2), but 4.9% (5/102) of patients were sent home with a chest tube. The recurrence for this cohort was 28.4% (29/102). The time to recurrence was 353 days (IQR 504), while the time to mortality was 505 days (IQR 761). The NSCLC patients were divided into the following two groups: low SUV (<5, n = 55) and high SUV (≥5, n = 47). Statistically significant associations were noted between SUV and the tumor histology (p = 0.019), tumor grade (p = 0.002), lymph-vascular invasion (p = 0.029), viscera-pleural invasion (p = 0.008), recurrence (p < 0.001) and the site of recurrence (p = 0.047). KM survival analysis showed significant differences in the curves for OS (log-rank p-value 0.0204) and RFS (log-rank p-value 0.0034) between the SUV groups. Conclusion: Robotic-assisted segmentectomy for NSCLC has reasonable perioperative and oncologic outcomes. Furthermore, we demonstrate here the prognostic implication of preoperative SUV to pathologic outcomes, recurrence-free survival, and overall survival. Full article

(This article belongs to the Special Issue Advancements in Lung Cancer Surgical Treatment and Prognosis)

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Review

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15 pages, 638 KiB

Open AccessReview

The Surgical Renaissance: Advancements in Video-Assisted Thoracoscopic Surgery and Robotic-Assisted Thoracic Surgery and Their Impact on Patient Outcomes

by Jennifer M. Pan, Ammara A. Watkins, Cameron T. Stock, Susan D. Moffatt-Bruce and Elliot L. Servais

Cancers 2024, 16(17), 3086; https://doi.org/10.3390/cancers16173086 - 5 Sep 2024

Viewed by 829

Abstract

Minimally invasive thoracic surgery has advanced the treatment of lung cancer since its introduction in the 1990s. Video-assisted thoracoscopic surgery (VATS) and robotic-assisted thoracic surgery (RATS) offer the advantage of smaller incisions without compromising patient outcomes. These techniques have been shown to be safe and effective in standard pulmonary resections (lobectomy and sub-lobar resection) and in complex pulmonary resections (sleeve resection and pneumonectomy). Furthermore, several studies show these techniques enhance patient outcomes from early recovery to improved quality of life (QoL) and excellent oncologic results. The rise of RATS has yielded further operative benefits compared to thoracoscopic surgery. The wristed instruments, neutralization of tremor, dexterity, and magnification allow for more precise and delicate dissection of tissues and vessels. This review summarizes of the advancements in minimally invasive thoracic surgery and the positive impact on patient outcomes. Full article

(This article belongs to the Special Issue Advancements in Lung Cancer Surgical Treatment and Prognosis)

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