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Cancers
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Treatment Modalities for Non-small Cell Lung Cancer—A Clinical Survey
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Treatment Modalities for Non-small Cell Lung Cancer—A Clinical Survey

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

Deadline for manuscript submissions: closed (14 September 2023) | Viewed by 21758

Special Issue Editor

Dr. Joerg Lindenmann

E-Mail Website
Guest Editor
Division of Thoracic and Hyperbaric Surgery, Department of Surgery, Medical University of Graz, 8036 Graz, Austria
Interests: oncological thoracic surgery; photodynamic therapy (PDT); oncological immunology; tumor microenvironment; biomarkers and prognostic parameters; palliative tumor therapy

Special Issue Information

Dear Colleagues,

Lung cancer is one of the most aggressive types of cancer, with non-small-cell lung cancer being the most common histologic subtype of primary lung cancer. Despite continuous progress in surgery, chemotherapy, radiation therapy, and immune and targeted therapies, the prognosis of non-small-cell lung cancer patients still remains modest, especially those with advanced tumor disease. For this reason, this Special Issue of Cancers will highlight the different surgical and non-surgical treatment modalities available for non-small-cell lung cancer, focusing on the clinical aspect and related research activity. In this context, special attention will be paid to the current multimodal treatment options, to the impact of oncological immunology, and to the role of the tumor microenvironment in order to provide a comprehensive overview of this challenging topic.

Dr. Joerg Lindenmann
Guest Editor

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

  • minimally-invasive thoracic surgery
  • extended resections
  • photodynamic therapy
  • immune therapy
  • targeted therapy
  • radiation therapy
  • multimodality treatment
  • tumor microenvironment
  • prognostic markers

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Published Papers (7 papers)

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Research

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13 pages, 707 KiB  
Article
Uniportal Video-Assisted Thoracoscopic Surgery Completion Lobectomy Long after Wedge Resection or Segmentectomy in the Same Lobe: A Bicenter Study
by Elisa Meacci, Majed Refai, Dania Nachira, Michele Salati, Khrystyna Kuzmych, Diomira Tabacco, Edoardo Zanfrini, Giuseppe Calabrese, Antonio Giulio Napolitano, Maria Teresa Congedo, Marco Chiappetta, Leonardo Petracca-Ciavarella, Carolina Sassorossi, Marco Andolfi, Francesco Xiumè, Michela Tiberi, Gian Marco Guiducci, Maria Letizia Vita, Alberto Roncon, Anna Chiara Nanto and Stefano Margaritoraadd Show full author list remove Hide full author list
Cancers 2024, 16(7), 1286; https://doi.org/10.3390/cancers16071286 - 26 Mar 2024
Viewed by 1001
Abstract
Background: Completion lobectomy (CL) following a prior resection in the same lobe may be complicated by severe pleural or hilar adhesions. The role of uniportal video-assisted thoracoscopic surgery (U-VATS) has never been evaluated in this setting. Methods: Data were collected from two Italian [...] Read more.
Background: Completion lobectomy (CL) following a prior resection in the same lobe may be complicated by severe pleural or hilar adhesions. The role of uniportal video-assisted thoracoscopic surgery (U-VATS) has never been evaluated in this setting. Methods: Data were collected from two Italian centers. Between 2015 and 2022, 122 patients (60 men and 62 women, median age 67.7 ± 8.913) underwent U-VATS CL at least 4 weeks after previous lung surgery. Results: Twenty-eight (22.9%) patients were affected by chronic obstructive pulmonary disease (COPD) and twenty-five (20.4%) were active smokers. Among the cohort, the initial surgery was performed using U-VATS in 103 (84.4%) patients, triportal-VATS in 8 (6.6%), and thoracotomy in 11 (9.0%). Anatomical segmentectomy was the initial surgery in 46 (37.7%) patients, while hilar lymphadenectomy was performed in 16 (13.1%) cases. CL was performed on 110 (90.2%) patients, segmentectomy on 10 (8.2%), and completion pneumonectomy on 2 (1.6%). Upon reoperation, moderate pleural adhesions were observed in 38 (31.1%) patients, with 2 (1.6%) exhibiting strong adhesions. Moderate hilar adhesions were found in 18 (14.8%) patients and strong adhesions in 11 (9.0%). The median operative time was 203.93 ± 74.4 min. In four (3.3%) patients, PA taping was performed. One patient experienced intraoperative bleeding that did not require conversion to thoracotomy. Conversion to thoracotomy was necessary in three (2.5%) patients. The median postoperative drainage stay and postoperative hospital stay were 5.67 ± 4.44 and 5.52 ± 2.66 days, respectively. Postoperative complications occurred in 34 (27.9%) patients. Thirty-day mortality was null. Histology was the only factor found to negatively influence intraoperative outcomes (p = 0.000). Factors identified as negatively impacting postoperative outcomes at univariate analyses were male sex (p = 0.003), age > 60 years (p = 0.003), COPD (p = 0.014), previous thoracotomy (p = 0.000), previous S2 segmentectomy (p = 0.001), previous S8 segmentectomy (p = 0.008), and interval between operations > 5 weeks (p= 0.005). In multivariate analysis, only COPD confirmed its role as an independent risk factor for postoperative complications (HR: 5.12, 95% CI (1.07–24.50), p = 0.04). Conclusions: U-VATS CL seems feasible and safe after wedge resection and anatomical segmentectomy. Full article
(This article belongs to the Special Issue Treatment Modalities for Non-small Cell Lung Cancer—A Clinical Survey)
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12 pages, 2952 KiB  
Article
Identification of Metastatic Lymph Nodes Using Indocyanine Green Fluorescence Imaging
by Kyungsu Kim, Kook Nam Han, Byeong Hyeon Choi, Jiyun Rho, Jun Hee Lee, Jae Seon Eo, Chungyeul Kim, Beop-Min Kim, Ok Hwa Jeon and Hyun Koo Kim
Cancers 2023, 15(7), 1964; https://doi.org/10.3390/cancers15071964 - 25 Mar 2023
Cited by 3 | Viewed by 2202
Abstract
Indocyanine green (ICG) has been used to detect several types of tumors; however, its ability to detect metastatic lymph nodes (LNs) remains unclear. Our goal was to determine the feasibility of ICG in detecting metastatic LNs. We established a mouse model and evaluated [...] Read more.
Indocyanine green (ICG) has been used to detect several types of tumors; however, its ability to detect metastatic lymph nodes (LNs) remains unclear. Our goal was to determine the feasibility of ICG in detecting metastatic LNs. We established a mouse model and evaluated the potential of ICG. The feasibility of detecting metastatic LNs was also evaluated in patients with lung or esophageal cancer, detected with computed tomography (CT) or positron-emission tomography (PET)/CT, and scheduled to undergo surgical resection. Tumors and metastatic LNs were successfully detected in the mice. In the clinical study, the efficacy of ICG was evaluated in 15 tumors and fifty-four LNs with suspected metastasis or anatomically key regional LNs. All 15 tumors were successfully detected. Among the fifty-four LNs, eleven were pathologically confirmed to have metastasis; all eleven were detected in ICG fluorescence imaging, with five in CT and seven in PET/CT. Furthermore, thirty-four LNs with no signals were pathologically confirmed as nonmetastatic. Intravenous injection of ICG may be a useful tool to detect metastatic LNs and tumors. However, ICG is not a targeting agent, and its relatively low fluorescence makes it difficult to use to detect tumors in vivo. Therefore, further studies are needed to develop contrast agents and devices that produce increased fluorescence signals. Full article
(This article belongs to the Special Issue Treatment Modalities for Non-small Cell Lung Cancer—A Clinical Survey)
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13 pages, 651 KiB  
Article
Factors Associated with the Decision to Decline Chemotherapy in Metastatic Non-Small Cell Lung Cancer
by Iktej Singh Jabbal, Saad Sabbagh, Mira Itani, Barbara Dominguez, Mohamed Mohanna, Valencia Henry, Hong Liang, Diana Saravia, Tiffany George, Zeina Nahleh, Evan Alley and Rafael Arteta-Bulos
Cancers 2023, 15(6), 1686; https://doi.org/10.3390/cancers15061686 - 9 Mar 2023
Viewed by 2124
Abstract
(1) Background: Disparities in cancer treatment and outcomes have long been well-documented in the medical literature. With the eruption of advances in new treatment modalities, the long-existing disparities are now being further uncovered and brought to the attention of the medical community. While [...] Read more.
(1) Background: Disparities in cancer treatment and outcomes have long been well-documented in the medical literature. With the eruption of advances in new treatment modalities, the long-existing disparities are now being further uncovered and brought to the attention of the medical community. While social health determinants have previously been linked to treatment disparities in lung cancer, we analyzed data from the National Cancer Database to explore sociodemographic and geographic factors related to accepting or declining physician-recommended chemotherapy. Patients diagnosed with metastatic lung cancer between 2004 and 2016 who declined chemotherapy recommended by their physicians were included in this study. Multivariate logistic regression analysis was performed. Cox Regression and Kaplan-Meier analyses were performed to look for survival characteristics. (2) Results: 316,826 patients with Stage IV lung cancer were identified. Factors related to a higher rate of refusal by patients included older age > 70, female sex, low income, lack of insurance coverage, residency in the New England region, and higher comorbidity. Patients living in areas with lower education were less likely to decline chemotherapy. (3) Conclusion: Further understanding of the factors impacting treatment decisions would be essential to improve the efficacy of care delivery in patients with cancer and reduce reversible causes of disparity. Full article
(This article belongs to the Special Issue Treatment Modalities for Non-small Cell Lung Cancer—A Clinical Survey)
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14 pages, 1557 KiB  
Article
Circulating Low Density Neutrophils Are Associated with Resistance to First Line Anti-PD1/PDL1 Immunotherapy in Non-Small Cell Lung Cancer
by Hugo Arasanz, Ana Isabel Bocanegra, Idoia Morilla, Joaquín Fernández-Irigoyen, Maite Martínez-Aguillo, Lucía Teijeira, Maider Garnica, Ester Blanco, Luisa Chocarro, Karina Ausin, Miren Zuazo, Gonzalo Fernández-Hinojal, Miriam Echaide, Leticia Fernández-Rubio, Sergio Piñeiro-Hermida, Pablo Ramos, Laura Mezquita, David Escors, Ruth Vera and Grazyna Kochan
Cancers 2022, 14(16), 3846; https://doi.org/10.3390/cancers14163846 - 9 Aug 2022
Cited by 26 | Viewed by 3817
Abstract
Single-agent immunotherapy has been widely accepted as frontline treatment for advanced non-small cell lung cancer (NSCLC) with high tumor PD-L1 expression, but most patients do not respond and the mechanisms of resistance are not well known. Several works have highlighted the immunosuppressive activities [...] Read more.
Single-agent immunotherapy has been widely accepted as frontline treatment for advanced non-small cell lung cancer (NSCLC) with high tumor PD-L1 expression, but most patients do not respond and the mechanisms of resistance are not well known. Several works have highlighted the immunosuppressive activities of myeloid subpopulations, including low-density neutrophils (LDNs), although the context in which these cells play their role is not well defined. We prospectively monitored LDNs in peripheral blood from patients with NSCLC treated with anti-PD-1 immune checkpoint inhibitors (ICIs) as frontline therapy, in a cohort of patients treated with anti-PD1 immunotherapy combined with chemotherapy (CT+IT), and correlated values with outcomes. We explored the underlying mechanisms through ex vivo experiments. Elevated baseline LDNs predict primary resistance to ICI monotherapy in patients with NSCLC, and are not associated with response to CT+IT. Circulating LDNs mediate resistance in NSCLC receiving ICI as frontline therapy through humoral immunosuppression. A depletion of this population with CT+IT might overcome resistance, suggesting that patients with high PD-L1 tumor expression and high baseline LDNs might benefit from this combination. The activation of the HGF/c-MET pathway in patients with elevated LDNs revealed by quantitative proteomics supports potential drug combinations targeting this pathway. Full article
(This article belongs to the Special Issue Treatment Modalities for Non-small Cell Lung Cancer—A Clinical Survey)
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Review

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22 pages, 689 KiB  
Review
Multimodality Treatment including Surgery Related to the Type of N2 Involvement in Locally Advanced Non-Small Cell Lung Cancer
by Toon Allaeys, Lawek Berzenji, Patrick Lauwers, Suresh Krishan Yogeswaran, Jeroen M. H. Hendriks, Charlotte Billiet, Charlotte De Bondt and Paul E. Van Schil
Cancers 2022, 14(7), 1656; https://doi.org/10.3390/cancers14071656 - 25 Mar 2022
Cited by 8 | Viewed by 3012
Abstract
For patients with locally advanced non-small cell lung cancer (NSCLC) or positive N1 nodes, multimodality treatment is indicated. However, the optimal management of patients presenting with ipsilateral positive mediastinal nodes (N2 disease) has not been determined yet. Different treatment regimens consisting of chemotherapy, [...] Read more.
For patients with locally advanced non-small cell lung cancer (NSCLC) or positive N1 nodes, multimodality treatment is indicated. However, the optimal management of patients presenting with ipsilateral positive mediastinal nodes (N2 disease) has not been determined yet. Different treatment regimens consisting of chemotherapy, radiation therapy, and surgery have been proposed and implemented previously. In more recent years, immunotherapy and targeted therapies have been added as therapeutic options. The role of surgery is currently redefined. Recent studies have shown that surgical resection after induction immunotherapy or targeted therapy is feasible and yields good short-term results. In this review, we summarize the latest data on multimodality treatment options for stage IIIA-N2 locally advanced NSCLC, depending on the extent of nodal involvement. Full article
(This article belongs to the Special Issue Treatment Modalities for Non-small Cell Lung Cancer—A Clinical Survey)
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11 pages, 762 KiB  
Review
Primary Lung Cancer Organoids for Personalized Medicine—Are They Ready for Clinical Use?
by Raphael S. Werner, Michaela B. Kirschner and Isabelle Opitz
Cancers 2021, 13(19), 4832; https://doi.org/10.3390/cancers13194832 - 28 Sep 2021
Cited by 5 | Viewed by 3972
Abstract
Despite many developments in recent years, non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related death worldwide. Therefore, additional research, aiming to further elucidate the underlying molecular mechanisms of malignant transformation and development of therapy resistance, as well as the identification [...] Read more.
Despite many developments in recent years, non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related death worldwide. Therefore, additional research, aiming to further elucidate the underlying molecular mechanisms of malignant transformation and development of therapy resistance, as well as the identification of additional novel therapeutic avenues, is crucial. For this purpose, reliable in vitro models are indispensable, as they allow for quick identification of suspected oncogenic drivers or evaluation of novel therapeutic strategies in a timely and cost-effective fashion. However, standard two-dimensional cell culture systems, the most frequently used in vitro model, are usually not truly representative of the situation in a patient as these models lack the tumor heterogeneity, the surrounding tumor microenvironment and the three-dimensional complexity of a tumor in vitro. For this reason, 3D cell culture systems, in particular organoids generated from normal non-malignant cells or tumor cell-based organoids (tumoroids), have in recent years gained much attention as alternative in vitro model systems that more closely resemble the actual primary tumor. In this review, we provide an overview of the available literature in the field of NSCLC organoids, which might still be in its infancy, but is gaining momentum. Full article
(This article belongs to the Special Issue Treatment Modalities for Non-small Cell Lung Cancer—A Clinical Survey)
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18 pages, 821 KiB  
Review
Current Knowledge about Mechanisms of Drug Resistance against ALK Inhibitors in Non-Small Cell Lung Cancer
by Elisabeth Smolle, Valentin Taucher, Joerg Lindenmann, Philipp J. Jost and Martin Pichler
Cancers 2021, 13(4), 699; https://doi.org/10.3390/cancers13040699 - 9 Feb 2021
Cited by 15 | Viewed by 3752
Abstract
Non-small cell lung cancer (NSCLC) accounts for the majority of lung cancer subtypes. Two to seven percent of NSCLC patients harbor gene rearrangements of the anaplastic lymphoma kinase (ALK) gene or, alternatively, harbor chromosomal fusions of ALK with echinoderm microtubule-associated protein-like 4 (EML4). [...] Read more.
Non-small cell lung cancer (NSCLC) accounts for the majority of lung cancer subtypes. Two to seven percent of NSCLC patients harbor gene rearrangements of the anaplastic lymphoma kinase (ALK) gene or, alternatively, harbor chromosomal fusions of ALK with echinoderm microtubule-associated protein-like 4 (EML4). The availability of tyrosine kinase inhibitors targeting ALK (ALK-TKIs) has significantly improved the progression-free and overall survival of NSCLC patients carrying the respective genetic aberrations. Yet, increasing evidence shows that primary or secondary resistance to ALK-inhibitors during the course of treatment represents a relevant clinical problem. This necessitates a switch to second- or third-generation ALK-TKIs and a close observation of NSCLC patients on ALK-TKIs during the course of treatment by repetitive molecular testing. With this review of the literature, we aim at providing an overview of current knowledge about resistance mechanisms to ALK-TKIs in NSCLC. Full article
(This article belongs to the Special Issue Treatment Modalities for Non-small Cell Lung Cancer—A Clinical Survey)
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