Prevention, Diagnosis and Treatments of Early-Stage NSCLC: New Advances and Future Prospective

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Pulmonology".

Deadline for manuscript submissions: 20 October 2024 | Viewed by 10566

Special Issue Editor


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Guest Editor
1. Department of Thoracic Surgery, IEO, European Institute of Oncology IRCCS, Milan, Italy
2. Department of Oncology and Hemato-oncology, University of Milan, Milan, Italy
Interests: minimally invasive surgery; robotic surgery; lung cancer; mediastinal tumors; pleural tumor
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Special Issue Information

Dear Colleagues,

Non–small-cell lung cancer (NSCLC) is a major cause of cancer death with a poor 5-year survival rate, mostly due to the fact that only 20% of NSCLC patients are diagnosed when the disease is still potentially resectable and curable. Thus, the diagnosis of NSCLC in the early stage becomes essential for its therapeutic and prognostic implications.

In the last two decades, with the further implementation of lung cancer screening programs, the detection rate of early-stage NSCLC has greatly increased, with significantly reduced mortality in high-risk individuals. Consequently, the field of thoracic surgery has seen a rapid development of minimally invasive techniques, such as video-assisted thoracoscopic surgery (VATS) and robotic-assisted thoracic surgery (RATS), which have nowadays become the gold-standard procedures for treating early-stage NSCLC cancer.

This Special Issue will include clinically oriented reviews and original papers on current and future diagnostic tools, as well as established and upcoming prevention, diagnosis, and treatments for NSCLC.

Dr. Monica Casiraghi
Guest Editor

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Keywords

  • non-small-cell lung cancer
  • NSCLC
  • minimally invasive surgery
  • screening
  • diagnosis

Published Papers (9 papers)

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Editorial

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4 pages, 205 KiB  
Editorial
Sublobar Resection for Early-Stage Lung Cancer: An Oncologically Valid Procedure?
by Ian Diebels, Marc Dubois and Paul E. Y. Van Schil
J. Clin. Med. 2023, 12(7), 2674; https://doi.org/10.3390/jcm12072674 - 3 Apr 2023
Cited by 2 | Viewed by 1260
Abstract
In the era of minimally invasive surgery, the role of sublobar resection comprising anatomical segmentectomy and wide wedge excision remains controversial [...] Full article

Research

Jump to: Editorial

25 pages, 5319 KiB  
Article
Analysis of Selected Toll-like Receptors in the Pathogenesis and Advancement of Non-Small-Cell Lung Cancer
by Jolanta Smok-Kalwat, Paulina Mertowska, Sebastian Mertowski, Stanisław Góźdź, Izabela Korona-Głowniak, Wojciech Kwaśniewski and Ewelina Grywalska
J. Clin. Med. 2024, 13(10), 2793; https://doi.org/10.3390/jcm13102793 - 9 May 2024
Viewed by 382
Abstract
(1) Background: Non-small-cell lung cancer (NSCLC) represents a significant global health challenge, contributing to numerous cancer deaths. Despite advances in diagnostics and therapy, identifying reliable biomarkers for prognosis and therapeutic stratification remains difficult. Toll-like receptors (TLRs), crucial for innate immunity, now show potential [...] Read more.
(1) Background: Non-small-cell lung cancer (NSCLC) represents a significant global health challenge, contributing to numerous cancer deaths. Despite advances in diagnostics and therapy, identifying reliable biomarkers for prognosis and therapeutic stratification remains difficult. Toll-like receptors (TLRs), crucial for innate immunity, now show potential as contributors to cancer development and progression. This study aims to investigate the role of TLR expression as potential biomarkers in the development and progression of NSCLC. (2) Materials and Methods: The study was conducted on 89 patients diagnosed with NSCLC and 40 healthy volunteers, for whom the prevalence of TLR2, TLR3, TLR4, TLR7, TLR8, and TLR9 was assessed on selected subpopulations of T and B lymphocytes in the peripheral blood of recruited patients along with the assessment of their serum concentration. (3) Result: Our study showed several significant changes in NSCLC patients at the beginning of the study. This resulted in a 5-year follow-up of changes in selected TLRs in recruited patients. Due to the high mortality rate of NSCLC patients, only 16 patients survived the 5 years. (4) Conclusions: The results suggest that TLRs may constitute real biomarker molecules that may be used for future prognostic purposes in NSCLC. However, further validation through prospective clinical and functional studies is necessary to confirm their clinical utility. These conclusions may lead to better risk stratification and tailored interventions, benefiting NSCLC patients and bringing medicine closer to precision. Full article
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22 pages, 2210 KiB  
Article
Enhancing Immune Response in Non-Small-Cell Lung Cancer Patients: Impact of the 13-Valent Pneumococcal Conjugate Vaccine
by Jolanta Smok-Kalwat, Paulina Mertowska, Izabela Korona-Głowniak, Sebastian Mertowski, Paulina Niedźwiedzka-Rystwej, Dominika Bębnowska, Krzysztof Gosik, Andrzej Stepulak, Stanisław Góźdź, Jacek Roliński, Zofia Górecka, Jan Siwiec and Ewelina Grywalska
J. Clin. Med. 2024, 13(5), 1520; https://doi.org/10.3390/jcm13051520 - 6 Mar 2024
Viewed by 827
Abstract
Background: Non-small-cell lung cancer (NSCLC) is one of the most frequently diagnosed diseases among all types of lung cancer. Infectious diseases contribute to morbidity and mortality by delaying appropriate anti-cancer therapy in patients with NSCLC. Methods: The study aimed to evaluate the effectiveness [...] Read more.
Background: Non-small-cell lung cancer (NSCLC) is one of the most frequently diagnosed diseases among all types of lung cancer. Infectious diseases contribute to morbidity and mortality by delaying appropriate anti-cancer therapy in patients with NSCLC. Methods: The study aimed to evaluate the effectiveness of vaccination with the 13-valent pneumococcal conjugate vaccine (PCV13) in 288 newly diagnosed NSCLC patients. The analysis of the post-vaccination response was performed after vaccination by assessing the frequency of plasmablasts via flow cytometry and by assessing the concentration of specific anti-pneumococcal antibodies using enzyme-linked immunosorbent assays. Results: The results of the study showed that NSCLC patients responded to the vaccine with an increase in the frequencies of plasmablasts and antibodies but to a lesser extent than healthy controls. The immune system response to PCV13 vaccination was better in patients with lower-stage NSCLC. We found higher antibody levels after vaccination in NSCLC patients who survived 5 years of follow-up. Conclusions: We hope that our research will contribute to increasing patients′ and physicians′ awareness of the importance of including PCV13 vaccinations in the standard of oncological care, which will extend the survival time of patients and improve their quality of life. Full article
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13 pages, 8702 KiB  
Article
Long-Term Oncologic Outcomes in Robot-Assisted and Video-Assisted Lobectomies for Non-Small Cell Lung Cancer
by Giulia Fabbri, Federico Femia, Savvas Lampridis, Eleonora Farinelli, Alessandro Maraschi, Tom Routledge and Andrea Bille
J. Clin. Med. 2023, 12(20), 6609; https://doi.org/10.3390/jcm12206609 - 19 Oct 2023
Cited by 1 | Viewed by 909
Abstract
This study compares long-term outcomes in patients undergoing video-assisted thoracic surgery (VATS) and robotic-assisted thoracic surgery (RATS) lobectomy for non-small cell lung cancer (NSCLC); all consecutive patients who underwent RATS or VATS lobectomy for NSCLC between July 2015 and December 2021 in our [...] Read more.
This study compares long-term outcomes in patients undergoing video-assisted thoracic surgery (VATS) and robotic-assisted thoracic surgery (RATS) lobectomy for non-small cell lung cancer (NSCLC); all consecutive patients who underwent RATS or VATS lobectomy for NSCLC between July 2015 and December 2021 in our center were enrolled in a single-center prospective study. The primary outcomes were overall survival (OS), disease-free survival (DFS), and recurrence rate. The secondary outcomes were complication rate, length of hospitalization (LOS), duration of chest tubes (LOD), and number of lymph node stations harvested. A total of 619 patients treated with RATS (n = 403) or VATS (n = 216) were included in the study. There was no significant difference in OS between the RATS and VATS groups (3-year OS: 75.9% vs. 82.3%; 5-year OS: 70.5% vs. 68.5%; p = 0.637). There was a statistically significant difference in DFS between the RATS and VATS groups (3-year DFS: 92.4% vs. 81.2%; 5-year DFS: 90.3% vs. 77.6%; p < 0.001). Subgroup analysis according to the pathological stage also demonstrated a significant difference between RATS and VATS groups in DFS in stage I (3-year DFS: 94.4% vs. 88.9%; 5-year DFS: 91.8% vs. 85.2%; p = 0.037) and stage III disease (3-year DFS: 82.4% vs. 51.1%; 5-year DFS: 82.4% vs. 37.7%; p = 0.024). Moreover, in multivariable Cox regression analysis, the surgical approach was significantly associated with DFS, with an HR of 0.46 (95% CI 0.27–0.78, p = 0.004) for RATS compared to VATS. VATS lobectomy was associated with a significantly higher recurrence rate compared to RATS (21.8% vs. 6.2%; p < 0.001). LOS and LOD, as well as complication rate and in-hospital and 30-day mortality, were similar among the groups. RATS lobectomy was associated with a higher number of lymph node stations harvested compared to VATS (7 [IQR:2] vs. 5 [IQR:2]; p < 0.001). In conclusion, in our series, RATS lobectomy for lung cancer led to a significantly higher DFS and significantly lower recurrence rate compared to the VATS approach. RATS may allow more extensive nodal dissection, and this could translate into reduced recurrence. Full article
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15 pages, 4516 KiB  
Article
Comparison of Quality of Life after Robotic, Video-Assisted, and Open Surgery for Lung Cancer
by Nicole Asemota, Alessandro Maraschi, Savvas Lampridis, John Pilling, Juliet King, Corinne Le Reun and Andrea Bille
J. Clin. Med. 2023, 12(19), 6230; https://doi.org/10.3390/jcm12196230 - 27 Sep 2023
Cited by 1 | Viewed by 851
Abstract
Post-operative quality of life (QOL) has become crucial in choosing operative approaches in thoracic surgery. However, compared to VATS and thoracotomy, QOL results post-RATS are limited. We compared QOL before and after RATS and between RATS, VATS, and thoracotomy. We conducted a retrospective [...] Read more.
Post-operative quality of life (QOL) has become crucial in choosing operative approaches in thoracic surgery. However, compared to VATS and thoracotomy, QOL results post-RATS are limited. We compared QOL before and after RATS and between RATS, VATS, and thoracotomy. We conducted a retrospective review of lung cancer surgical patients from 2015 to 2020. Patients completed validated EORTC QOL questionnaires (QLQ-C30 and QLQ-LC13). Results were analysed using the EORTC Scoring Guide, with statistical analysis. A total of 47 (94%) pre- and post-RATS questionnaires were returned. Forty-two patients underwent anatomical lung resections. In addition, 80% of patients experienced uncomplicated recovery. All global and functional QOL domains improved post-operatively, as did most symptoms (13/19). Only four symptoms worsened, including dyspnoea (p = 0.017), with two symptoms unchanged. Of the 148 returned questionnaires for all approaches (open-22/VATS-79/RATS-47), over 70% showed a high pre-operative performance status. Most patients underwent anatomical lung resection, with only VATS patients requiring conversion (n = 6). Complications were slightly higher in RATS, with one patient requiring re-intubation. RATS patients demonstrated the highest global and functional QOL. Physical QOL was lowest after thoracotomy (p = 0.002). RATS patients reported the fewest symptoms, including dyspnoea (p = 0.046), fatigue (p < 0.001), and pain (p = 0.264). Overall, RATS results in a significantly better post-operative QOL and should be considered the preferred surgical approach for lung cancer patients. Full article
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10 pages, 873 KiB  
Article
Swiss Pilot Low-Dose CT Lung Cancer Screening Study: First Baseline Screening Results
by Lisa Jungblut, Harry Etienne, Caroline Zellweger, Alessandra Matter, Miriam Patella, Thomas Frauenfelder and Isabelle Opitz
J. Clin. Med. 2023, 12(18), 5771; https://doi.org/10.3390/jcm12185771 - 5 Sep 2023
Cited by 2 | Viewed by 882
Abstract
This pilot study conducted in Switzerland aims to assess the implementation, execution, and performance of low-dose CT lung cancer screening (LDCT-LCS). With lung cancer being the leading cause of cancer-related deaths in Switzerland, the study seeks to explore the potential impact of screening [...] Read more.
This pilot study conducted in Switzerland aims to assess the implementation, execution, and performance of low-dose CT lung cancer screening (LDCT-LCS). With lung cancer being the leading cause of cancer-related deaths in Switzerland, the study seeks to explore the potential impact of screening on reducing mortality rates. However, initiating a lung cancer screening program poses challenges and depends on country-specific factors. This prospective study, initiated in October 2018, enrolled participants meeting the National Lung Cancer Study criteria or a lung cancer risk above 1.5% according to the PLCOm2012 lung cancer risk-model. LDCT scans were assessed using Lung-RADS. Enrollment and follow-up are ongoing. To date, we included 112 participants, with a median age of 62 years (IQR 57–67); 42% were female. The median number of packs smoked each year was 45 (IQR 38–57), and 24% had stopped smoking before enrollment. The mean PLCOm2012 was 3.7% (±2.5%). We diagnosed lung cancer in 3.6% of participants (95%, CI:1.0–12.1%), with various stages, all treated with curative intent. The recall rate for intermediate results (Lung-RADS 3,4a) was 15%. LDCT-LCS in Switzerland, using modified inclusion criteria, is feasible. Further analysis will inform the potential implementation of a comprehensive lung cancer screening program in Switzerland. Full article
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11 pages, 8709 KiB  
Article
Do More with Less? Lobectomy vs. Segmentectomy for Patients with Congenital Pulmonary Malformations
by Beatrice Trabalza Marinucci, Cecilia Menna, Paolo Scanagatta, Silvia Fiorelli, Matteo Tiracorrendo, Giuseppe Naldi, Alessandro Inserra, Francesco Macchini, Erino Angelo Rendina and Mohsen Ibrahim
J. Clin. Med. 2023, 12(16), 5237; https://doi.org/10.3390/jcm12165237 - 11 Aug 2023
Cited by 1 | Viewed by 1076
Abstract
Background: Congenital Pulmonary Malformations (CPMs) are rare benign lesions potentially causing infective complications and/or malignant transformation, requiring surgery even when asymptomatic. CPMs are rare in adulthood but potentially detected at any age. There is not a consensus on the correct extent of resection [...] Read more.
Background: Congenital Pulmonary Malformations (CPMs) are rare benign lesions potentially causing infective complications and/or malignant transformation, requiring surgery even when asymptomatic. CPMs are rare in adulthood but potentially detected at any age. There is not a consensus on the correct extent of resection in both adults and paediatrics. This retrospective multicentric study aims to identify the appropriate surgical resection to prevent the recurrence of the related respiratory symptoms. Methods: Between 2010 and 2020, a total of 96 patients (adults and pediatrics) underwent surgery for CPMs in 4 centers. A 2:1 propensity score matching (considering sex and lesion side) was performed, identifying 2 groups: 50 patients underwent lobectomy (group A) and 25 sub-lobar resections (group B). Clinical and histopathological characteristics, early and late complications, and symptom recurrence were retrospectively analyzed and compared between the two groups by univariate and multivariate analysis. Results: Patients who underwent lobectomy had a statistically significant lower rate of recurrence (4% vs. 24% of group B, p = 0.014) and a lower rate of intraoperative complications (p = 0.014). Logistic regression identified sub-lobar resection (p = 0.040), intra- and post-operative complications (p = 0.105 and 0.022),and associated developed neoplasm (p = 0.062) as possible risk factors for symptom recurrence after surgery. Conclusions: Pulmonary lobectomy seems to be the most effective surgical treatment for CPMs, guaranteeing the stable remission of symptoms and a lower rate of intra- and postoperative complications. To our knowledge, this is one of the largest studies comparing lobectomy and sub-lobar resections in patients affected by CPMs, considering the low incidence worldwide. Full article
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11 pages, 1263 KiB  
Article
Rate and Predictors of Unforeseen PN1/PN2-Disease in Surgically Treated cN0 NSCLC-Patients with Primary Tumor > 3 cm: Nationwide Results from Italian VATS-Group Database
by Filippo Lococo, Dania Nachira, Marco Chiappetta, Isabella Sperduti, Maria Teresa Congedo, Elisa Meacci, Fausto Leoncini, Rocco Trisolini, Roberto Crisci, Carlo Curcio, Monica Casiraghi, Stefano Margaritora and on the behalf of the Italian VATS Group
J. Clin. Med. 2023, 12(6), 2345; https://doi.org/10.3390/jcm12062345 - 17 Mar 2023
Viewed by 1406
Abstract
Background. Since no robust data are available on the real rate of unforeseen N1-N2 disease (uN) and the relative predictive factors in clinical-N0 NSCLC with peripheral tumours > 3 cm, the usefulness of performing a (mini)invasive mediastinal staging in this setting is debated. [...] Read more.
Background. Since no robust data are available on the real rate of unforeseen N1-N2 disease (uN) and the relative predictive factors in clinical-N0 NSCLC with peripheral tumours > 3 cm, the usefulness of performing a (mini)invasive mediastinal staging in this setting is debated. Herein, we investigated these issues in a nationwide database. Methods. From 01/2014 to 06/2020, 15,784 thoracoscopic major lung resections were prospectively recorded in the “Italian VATS-Group” database. Among them, 1982 clinical-N0 peripheral solid-type NSCLC > 3 cm were identified, and information was retrospectively reviewed. A mean comparison of more than two groups was made by ANOVA (Bonferroni correction for multiple comparisons), while associations between the categorical variables were estimated with a Chi-square test. The multivariate logistic regression model and Kaplan–Meyer method were used to identify the independent predictors of nodal upstaging and survival results, respectively. Results. At pathological staging, 229 patients had N1-involvement (11.6%), and 169 had uN2 disease (8.5%). Independent predictors of uN1 were SUVmax (OR: 1.98; CI 95: 1.44–2.73, p = 0.0001) and tumour-size (OR: 1.52; CI: 1.11–2.10, p = 0.01), while independent predictors of uN2 were age (OR: 0.98; CI 95: 0.96–0.99, p = 0.039), histology (OR: 0.48; CI 95: 0.30–0.78, p = 0.003), SUVmax (OR: 2.07; CI 95: 1.15–3.72, p = 0.015), and the number of resected lymph nodes (OR: 1.03; CI 95: 1.01–1.05, p = 0.002). Conclusions. The unforeseen N1-N2 disease in cN0/NSCLCs > 3 cm undergoing VATS resection is observable in between 12 and 8% of all cases. We have identified predictors that could guide physicians in selecting the best candidate for (mini)invasive mediastinal staging. Full article
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10 pages, 607 KiB  
Article
Surgically Treated pT2aN0M0 (Stage IB) Non-Small Cell Lung Cancer: A 20-Year Single-Center Retrospective Study
by Monica Casiraghi, Francesco Petrella, Claudia Bardoni, Shehab Mohamed, Giulia Sedda, Juliana Guarize, Antonio Passaro, Filippo De Marinis, Patrick Maisonneuve and Lorenzo Spaggiari
J. Clin. Med. 2023, 12(5), 2081; https://doi.org/10.3390/jcm12052081 - 6 Mar 2023
Viewed by 2193
Abstract
Introduction The suitability of adjuvant therapy (AT) in patients with stage IB non-small cell lung cancer (NSCLC) is still under debate considering the cost–benefit ratio between improvement in survival and side effects. We retrospectively evaluated survival and incidence of recurrence in radically resected [...] Read more.
Introduction The suitability of adjuvant therapy (AT) in patients with stage IB non-small cell lung cancer (NSCLC) is still under debate considering the cost–benefit ratio between improvement in survival and side effects. We retrospectively evaluated survival and incidence of recurrence in radically resected stage IB NSCLC, to determine whether AT could significantly improve prognosis. Methods Between 1998 and 2020, 4692 consecutive patients underwent lobectomy and systematic lymphadenectomy for NSCLC. Two hundred nineteen patients were pathological T2aN0M0 (>3 and ≤4 cm) NSCLC 8th TNM. None received preoperative or AT. Overall survival (OS), cancer specific survival (CSS) and the cumulative incidence of relapse were plotted and log-rank or Gray’s tests were used to assess the difference in outcome between groups. Results The most frequent histology was adenocarcinoma (66.7%). Median OS was 146 months. The 5-, 10-, and 15-year OS rates were 79%, 60%, and 47%, whereas the 5-, 10-, and 15-year CSS were 88%, 85%, and 83%, respectively. OS was significantly related to age (p < 0.001) and cardiovascular comorbidities (p = 0.04), whereas number of LNs removed was an independent prognostic factor of CSS (p = 0.02). Cumulative incidence of relapse at 5-, 10-, and 15-year were 23%, 31%, and 32%, respectively, and significantly related to the number of LNs removed (p = 0.01). Patients with more than 20 LNs removed and clinical stage I had a significantly lower relapse (p = 0.02). Conclusions Excellent CSS, up to 83% at 15-year, and relatively low risk of recurrence for stage IB NSCLC (8th TNM) patients suggested that AT for those patients could be reserved only for very selected high-risk cases. Full article
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