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Surgical Treatment of Lung Cancer

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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: closed (31 March 2021) | Viewed by 47912

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Dr. Tetsuya Mitsudomi

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Department of Surgery, Division of Thoracic Surgery, Kindai University Faculty of Medicine, Osaka-Sayama, 377-2, Ohnohigashi, Osaka-sayama, Osaka, Japan
Interests: surgical treatment; targeted therapy; immunotherapy; liquid biopsy; translational research; biomarker

Special Issue Information

Dear Colleagues,

Since the first success of pulmonary resection by Graham in 1933, surgery for non-small lung cancer (NSCLC) has made remarkable progress in its efficacy and safety. In recent years, less-invasive procedures such as video-assisted thoracic surgery and robot-assisted lung resections have made great strides in conjunction with the advances in medical engineering in reducing the length of hospital stay and enabling patients to return to work sooner than in the past.

On the other hand, the progress of drug therapies for metastatic NSCLC has been remarkable since the turn of the century. Currently, patients with stage IV NSCLC are initially tested for driver gene mutations. If positive, patients will receive respective kinase inhibitors, and, if negative, patients will receive PD-1 antibody monotherapy or PD-1or PD-L1 inhibitor plus platinum doublet-chemotherapy depending on PD-L1 expression. The application of these drugs to the earlier, resectable diseases have recently been extensively evaluated.

This Special Issue will highlight the current status and future perspectives of lung cancer surgery and also features topics concerning the surgical treatment of NSCLC.

Dr. Tetsuya Mitsudomi
Guest Editor

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Keywords

lung cancer
surgical treatment
staging system
ground-glass nodule
VATS
RATS
limited resection
adjuvant therapy
neoadjuvant therapy
minimal residual disease
lymph node dissection
COVID-19

Published Papers (12 papers)

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Research

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16 pages, 3322 KiB

Open AccessArticle

Lung Cancer Surgery after Treatment with Anti-PD1/PD-L1 Immunotherapy for Non-Small-Cell Lung Cancer: A Case—Cohort Study

by Kinan El Husseini, Nicolas Piton, Marielle De Marchi, Antoine Grégoire, Roman Vion, Pierre Blavier, Luc Thiberville, Jean-Marc Baste and Florian Guisier

Cancers 2021, 13(19), 4915; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13194915 - 30 Sep 2021

Cited by 7 | Viewed by 2469

Abstract

Background: Immune checkpoint inhibitors (ICIs) are the standard of care for non-resectable non-small-cell lung cancer and are under investigation for resectable disease. Some authors have reported difficulties during lung surgery following ICI treatment. This retrospective study investigated the perioperative outcomes of lung resection in patients with preoperative ICI. Methods: Patients with major lung resection after receiving ICIs were included as cases and were compared to patients who received preoperative chemotherapy without ICI. Surgical, clinical, and imaging data were collected. Results: A total of 25 patients were included in the ICI group, and 34 were included in the control group. The ICI patients received five (2–18) infusions of ICI (80% with pembrolizumab). Indications for surgery varied widely across groups (p < 0.01). Major pathological response was achieved in 44% of ICI patients and 23.5% of the control group (p = 0.049). Surgery reports showed a higher rate of tissue fibrosis/inflammation in the ICI group (p < 0.01), mostly in centrally located tumours (7/13, 53.8% vs. 3/11, 27.3% of distal tumours, p = 0.24), with no difference in operating time (p = 0.81) nor more conversions (p = 0.46) or perioperative complications (p = 0.94). There was no 90-day mortality. Disease-free survival was higher in the ICI group (HR = 0.30 (0.13–0.71), p = 0.02). Conclusions: This study further supports the safety and feasibility of lung resection in patients following preoperative treatment with ICI. Full article

(This article belongs to the Special Issue Surgical Treatment of Lung Cancer)

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18 pages, 793 KiB

Open AccessArticle

Effect of COVID-19 on Thoracic Oncology Surgery in Spain: A Spanish Thoracic Surgery Society (SECT) Survey

by Néstor J. Martínez-Hernández, Usue Caballero Silva, Alberto Cabañero Sánchez, José Luis Campo-Cañaveral de la Cruz, Andrés Obeso Carillo, José Ramón Jarabo Sarceda, Sebastián Sevilla López, Ángel Cilleruelo Ramos, José Luis Recuero Díaz, Sergi Call, Felipe Couñago, Florentino Hernando Trancho and on behalf of the Scientific Committee of the Spanish Thoracic Surgery Society

Cancers 2021, 13(12), 2897; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13122897 - 09 Jun 2021

Cited by 14 | Viewed by 2749

Abstract

After the first wave of COVID-19, the Spanish Society of Thoracic Surgeons (SECT) surveyed its members to assess the impact of the pandemic on thoracic oncology surgery in Spain. In May 2020, all SECT members were invited to complete an online, 40-item, multiple choice questionnaire. The questionnaire was developed by the SECT Scientific Committee and sent via email. The overall response rate was 19.2%. The respondents answered at least 91.5% of the items, with only one exception (a question about residents). Most respondents (89.3%) worked in public hospitals. The reported impact of the pandemic on routine clinical activity was considered extreme or severe by 75.5% of respondents (25.5% and 50%, respectively). Multidisciplinary tumour boards were held either with fewer members attending or through electronic platforms (44.6% and 35.9%, respectively). Surgical activity decreased by 95.7%, with 41.5% of centers performing surgery only on oncological patients and 11.7% only in emergencies. Nearly 60% of respondents reported modifying standard protocols for early-stage cancer and in the preoperative workup. Most centers (≈80%) reported using full personal protective equipment when operating on COVID-19 positive patients. The COVID-19 pandemic severely affected thoracic oncology surgery in Spain. The lack of common protocols led to a variable care delivery to lung cancer patients. Full article

(This article belongs to the Special Issue Surgical Treatment of Lung Cancer)

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22 pages, 5791 KiB

Open AccessArticle

Total Psoas Area and Total Muscular Parietal Area Affect Long-Term Survival of Patients Undergoing Pneumonectomy for Non-Small Cell Lung Cancer

by Elisa Daffrè, Mathilde Prieto, Katharina Martini, Trieu-Nghi Hoang-Thi, Nara Halm, Hervè Dermine, Antonio Bobbio, Guillaume Chassagnon, Marie Pierre Revel and Marco Alifano

Cancers 2021, 13(8), 1888; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13081888 - 14 Apr 2021

Cited by 7 | Viewed by 1781

Abstract

There is no standardization in methods to assess sarcopenia; in particular the prognostic significance of muscular fatty infiltration in lung cancer patients undergoing surgery has not been evaluated so far. We thus performed several computed tomography (CT)-based morphometric measurements of sarcopenia in 238 consecutive non-small cell lung-cancer patients undergoing pneumonectomy from 1 January 2007 to 31 December 2015. Sarcopenia was assessed by the following CT-based parameters: cross-sectional total psoas area (TPA), cross-sectional total muscle area (TMA), and total parietal muscle area (TPMA), defined as TMA without TPA. Measures were performed at the level of the third lumbar vertebra and were obtained for the entire muscle surface, as well as by excluding fatty infiltration based on CT attenuation. Findings were stratified for gender, and a threshold of the 33rd percentile was set to define sarcopenia. Furthermore, we assessed the possibility of being sarcopenic at both the TPA and TPMA level, or not, by taking into account of not fatty infiltration. Five-year survival was 39.1% for the whole population. Lower TPA, TMA, and TPA were associated with lower survival at univariate analysis; taking into account muscular fatty infiltration did not result in more powerful discrimination. Being sarcopenic at both psoas and parietal muscle level had the optimum discriminating power. At the multivariable analysis, being sarcopenic at both psoas and parietal muscles (considering the whole muscle areas, including muscular fat), male sex, increasing age, and tumor stage, as well as Charlson Comorbidity Index (CCI), were independently associated with worse long-term outcomes. We conclude that sarcopenia is a powerful negative prognostic factor in patients with lung cancer treated by pneumonectomy. Full article

(This article belongs to the Special Issue Surgical Treatment of Lung Cancer)

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11 pages, 1410 KiB

Open AccessArticle

Survival Analysis in Single N2 Station Lung Adenocarcinoma: The Prognostic Role of Involved Lymph Nodes and Adjuvant Therapy

by Marco Chiappetta, Filippo Lococo, Giovanni Leuzzi, Isabella Sperduti, Emilio Bria, Leonardo Petracca Ciavarella, Felice Mucilli, Pier Luigi Filosso, Giovannibattista Ratto, Lorenzo Spaggiari, Francesco Facciolo and Stefano Margaritora

Cancers 2021, 13(6), 1326; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13061326 - 16 Mar 2021

Cited by 4 | Viewed by 1769

Abstract

Background: Prognostic factors in patients with single mediastinal station (sN2) involvement continues to be a debated issue. Methods: Data on 213 adenocarcinoma patients with sN2 involvement and who had undergone complete anatomical lung resection and lymphadenectomy, were retrospectively reviewed. Clinical and pathological characteristics together with adjuvant therapy (AD) and node (N) status classifications (number of resected nodes (#RN), number of metastatic nodes (#MN), and node ratio (#MN/#RN = NR) were analyzed. Results: Univariable analysis confirmed that age (0.009), #MN (0.009), NR (0.003), #N1 involved stations (p = 0.003), and skip metastases (p = 0.005) were related to overall survival (OS). Multivariable analysis confirmed, as independent prognostic factors, age <66 years and NR with a three-year OS (3YOS) of 78.7% in NR < 10% vs. 46.6% in NR > 10%. In skip metastases, NR (HR 2.734, 95% CI 1.417–5.277, p = 0.003) and pT stage (HR2.136, 95% CI 1.001–4.557, p = 0.050) were confirmed as independent prognostic factors. AD did not influence the OS of patients with singular positive lymph nodes (p = 0.41), while in patients with multiple lymph nodes and AD, a significantly better 3YOS was demonstrated, i.e., 49.1% vs. 30% (p = 0.004). In patients with N2 + N1 involvement, age (p = 0.002) and AD (p = 0.022) were favorable prognostic factors. Conclusions: Adenocarcinoma patients with single N2 station involvement had a favorable outcome in the case of skip metastases and low NR. Adjuvant therapy improves survival with multiple nodal involvement, while its role in single node involvement should be clarified. Full article

(This article belongs to the Special Issue Surgical Treatment of Lung Cancer)

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Review

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16 pages, 1053 KiB

Open AccessReview

Safety and Feasibility of Lung Cancer Surgery under the COVID-19 Circumstance

by Lawek Berzenji, Leonie Vercauteren, Suresh K. Yogeswaran, Patrick Lauwers, Jeroen M. H. Hendriks and Paul E. Van Schil

Cancers 2022, 14(5), 1334; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14051334 - 04 Mar 2022

Cited by 2 | Viewed by 2037

Abstract

The current coronavirus disease 2019 (COVID-19) pandemic has forced healthcare providers worldwide to adapt their practices. Our understanding of the effects of COVID-19 has increased exponentially since the beginning of the pandemic. Data from large-scale, international registries has provided more insight regarding risk factors for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and has allowed us to delineate specific subgroups of patients that have higher risks for severe complications. One particular subset of patients that have significantly higher risks of SARS-CoV-2 infection with higher morbidity and mortality rates are those that require surgical treatment for lung cancer. Earlier studies have shown that COVID-19 infections in patients that underwent lung cancer surgery is associated with higher rates of respiratory failure and mortality. However, deferral of cancer treatments is associated with increased mortality as well. This creates difficult situations in which healthcare providers are forced to weigh the benefits of surgical treatment against the possibility of SARS-CoV-2 infections. A number of oncological and surgical organizations have proposed treatment guidelines and recommendations for patients planned for lung cancer surgery. In this review, we summarize the latest data and recommendations for patients undergoing lung cancer surgery in the COVID-19 circumstance. Full article

(This article belongs to the Special Issue Surgical Treatment of Lung Cancer)

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9 pages, 958 KiB

Open AccessReview

Management of Ground-Glass Nodules: When and How to Operate?

by Young Tae Kim

Cancers 2022, 14(3), 715; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14030715 - 29 Jan 2022

Cited by 10 | Viewed by 12763

Abstract

With the increased popularity of low-dose computed tomography (LDCT), many patients present with pulmonary ground-glass nodules (GGNs), and the appropriate diagnostic and management strategy of those lesions make physicians be on the horn of the clinical dilemma. As there is not enough data available to set universally acceptable guidelines, the management of GGNs may be different. If GGN is an incidental finding through LDCT, the lesion should be followed according to the current guidelines. We recommend a multidisciplinary team discussion to be initiated if a new solid component develops or the solid portion size grows on follow-up CT as the risk of malignancy is high. Attempts to preoperatively biopsy solid components in part-solid GGNs are often not feasible and not helpful in clinical settings. Currently, if malignancy is suspected, a surgical biopsy with the guidance of various localization methods is recommended. If malignancy is confirmed, sub-lobar resection may provide an excellent oncologic outcome. Full article

(This article belongs to the Special Issue Surgical Treatment of Lung Cancer)

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14 pages, 2703 KiB

Open AccessReview

Perioperative Therapy for Non-Small Cell Lung Cancer with Immune Checkpoint Inhibitors

by Junichi Soh, Akira Hamada, Toshio Fujino and Tetsuya Mitsudomi

Cancers 2021, 13(16), 4035; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13164035 - 10 Aug 2021

Cited by 19 | Viewed by 5793

Abstract

The emergence of immune checkpoint inhibitors (ICIs) has dramatically changed the treatment landscape for patients with metastatic non-small cell lung cancer (NSCLC). These achievements inspired investigators and pharmaceutical companies to conduct clinical trials in patients with early-stage NSCLC because both adjuvant and neoadjuvant platinum-based doublet chemotherapies (PT-DCs) showed only a 5% improvement in 5-year overall survival. IMpower010, a phase 3 trial (P3), showed that adjuvant PT-DC followed by maintenance atezolitumab significantly prolonged disease-free survival over adjuvant PT-DC alone (hazard ratio, 0.79; stage II to IIIA). Since conventional therapies, including chemotherapy and radiotherapy, can promote immunogenic cell death, releasing tumour antigens from dead tumour cells, ICI combination therapies with conventional therapies are widely proposed. The Checkmate 816 trial (P3) indicated a significantly higher pathological complete response rate of neoadjuvant nivolumab/PT-DC combination therapy than of neoadjuvant PT-DC alone (odds ratio, 13.9, for stage IB to IIIA). Detection of circulating tumour DNA is highly anticipated for the evaluation of minimal residual disease. Multimodal approaches and new ICI agents are being attempted to improve the efficacy of ICI treatment in phase 2 trials. This review presents the development of perioperative treatment using ICIs in patients with NSCLC while discussing problems and perspectives. Full article

(This article belongs to the Special Issue Surgical Treatment of Lung Cancer)

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15 pages, 451 KiB

Open AccessReview

Lung Cancer Surgery after Neoadjuvant Immunotherapy

by Dirk Stefani, Till Plönes, Jan Viehof, Kaid Darwiche, Martin Stuschke, Martin Schuler and Clemens Aigner

Cancers 2021, 13(16), 4033; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13164033 - 10 Aug 2021

Cited by 10 | Viewed by 3075

Abstract

In early-stage lung cancer, recurrences are observed even after curative resection. Neoadjuvant immunotherapy might be a promising approach to eliminate micrometastasis and to potentially reduce recurrence rates and improve survival. Early trials have shown encouraging rates of pathologic response to neoadjuvant therapy and have demonstrated that surgery can be safely performed after neoadjuvant immunotherapy with various agents and in combination with chemo-(radio)therapy. However, whether these response rates translate into improved disease-free survival rates and overall survival rates remains to be determined by ongoing phase III studies. Full article

(This article belongs to the Special Issue Surgical Treatment of Lung Cancer)

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17 pages, 1842 KiB

Open AccessReview

Atrial Fibrillation after Lung Cancer Surgery: Prediction, Prevention and Anticoagulation Management

by Gennaro Carmine Semeraro, Carlo Ambrogio Meroni, Carlo Maria Cipolla and Daniela Maria Cardinale

Cancers 2021, 13(16), 4012; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13164012 - 09 Aug 2021

Cited by 8 | Viewed by 3595

Abstract

Atrial fibrillation (AF) is a common complication of the early postoperative period of various types of surgery, including that for lung cancer. Although induced by the homeostatic alterations related to surgery, there is evidence that it is not a mere stand-alone transitory event, but it represents a relevant complication of surgery, bearing considerable prognostic consequences. Different methods have therefore been explored to predict the occurrence of postoperative atrial fibrillation (POAF) and prevent it. In particular, the age among clinical factors, and N-terminal prohormone of brain natriuretic peptide (NT-proBNP), as a marker, have proven to be good predictors, and the use of beta-blockers or amiodarone in primary prevention seems to reduce its incidence significantly. There is growing evidence that POAF significantly increases the risk of stroke and global mortality in the long term; therefore, it should be managed in the same way as spontaneous atrial fibrillation. In this review, we will present the strongest evidence found so far and the most recent findings regarding the management of POAF, with a special focus on patients undergoing thoracic surgery for lung cancer. Full article

(This article belongs to the Special Issue Surgical Treatment of Lung Cancer)

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20 pages, 7002 KiB

Open AccessFeature PaperReview

The Emerging Importance of Tumor Genomics in Operable Non-Small Cell Lung Cancer

by Harry B. Lengel, James G. Connolly, Gregory D. Jones, Raul Caso, Jian Zhou, Francisco Sanchez-Vega, Brooke Mastrogiacomo, James M. Isbell, Bob T. Li, Yuan Liu, Natasha Rekhtman and David R. Jones

Cancers 2021, 13(15), 3656; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13153656 - 21 Jul 2021

Cited by 8 | Viewed by 3338

Abstract

During the last two decades, next-generation sequencing (NGS) has played a key role in enhancing non-small cell lung cancer treatment paradigms through the application of “targeted therapy” in advanced and metastatic disease. The use of specific tyrosine kinase inhibitors in patients with oncogenic driver alterations, such as EGFR, ALK, ROS1, BRAF V600E, MET, and NTRK mutations, among others, has changed treatment approaches and improved outcomes in patients with late-stage disease. Although NGS technology has mostly been used in the setting of systemic therapy to identify targets, response to therapy, and mechanisms of resistance, it has multiple potential applications for patients with earlier-stage disease, as well. In this review, we discuss the emerging role of NGS technologies to better understand tumor biology in patients with non-small cell lung cancer who are undergoing surgery with curative intent. In this patient cohort, we examine tumor heterogeneity, the underlying tumor genomics associated with lung adenocarcinoma subtypes, the prediction of recurrence after complete surgical resection, the use of plasma circulating tumor DNA for detection of early cancers and monitoring for minimal residual disease, the differentiation of separate primaries from intrapulmonary metastases, and the use of NGS to guide induction and adjuvant therapies. Full article

(This article belongs to the Special Issue Surgical Treatment of Lung Cancer)

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16 pages, 2798 KiB

Open AccessReview

Technical Advances in Segmentectomy for Lung Cancer: A Minimally Invasive Strategy for Deep, Small, and Impalpable Tumors

by Takashi Eguchi, Toshihiko Sato and Kimihiro Shimizu

Cancers 2021, 13(13), 3137; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13133137 - 23 Jun 2021

Cited by 21 | Viewed by 3804

Abstract

With the increased detection of early-stage lung cancer and the technical advancement of minimally invasive surgery (MIS) in the field of thoracic surgery, lung segmentectomy using MIS, including video- and robot-assisted thoracic surgery, has been widely adopted. However, lung segmentectomy can be technically challenging for thoracic surgeons due to (1) complex segmental and subsegmental anatomy with frequent anomalies, and (2) difficulty in localizing deep, small, and impalpable tumors, leading to difficulty in obtaining adequate margins. In this review, we summarize the published evidence and discuss key issues related to MIS segmentectomy, focusing on preoperative planning/simulation and intraoperative tumor localization. We also demonstrate two of our techniques: (1) three-dimensional computed tomography (3DCT)-based resection planning using a novel 3DCT processing software, and (2) tumor localization using a novel radiofrequency identification technology. Full article

(This article belongs to the Special Issue Surgical Treatment of Lung Cancer)

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13 pages, 287 KiB

Open AccessPerspective

Future Perspectives on the TNM Staging for Lung Cancer

by Ramón Rami-Porta

Cancers 2021, 13(8), 1940; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13081940 - 17 Apr 2021

Cited by 17 | Viewed by 3006

Abstract

Since its conception by Pierre Denoix in the mid-20th century, the tumor, node, and metastasis (TNM) classification has undergone seven revisions. The North American database managed by Clifton Mountain was used to inform the 2nd to the 6th editions, and an international database collected by the International Association for the Study of Lung Cancer, promoted by Peter Goldstraw, was used to inform the 7th and the 8th editions. In these two latest editions, it was evident that the impact of tumor size was much greater than it was suggested in previous editions; that the amount of nodal disease had prognostic relevance; and that the number and location of the distant metastases had prognostic implications. However, the TNM classification is not the only prognostic factor. Data are being collected now to inform the 9th edition of the TNM classification, scheduled for publication in 2024. Patient-, environment-, and tumor-related factors, including biomarkers (genetic biomarkers, copy number alterations, and protein alterations) are being collected to combine them in prognostic groups to enhance the prognosis provided by the mere anatomic extent of the tumor, and to offer a more personalized prognosis to an individual patient. International collaboration is essential to build a large and detailed database to achieve these objectives. Full article

(This article belongs to the Special Issue Surgical Treatment of Lung Cancer)

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