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6 pages, 186 KiB

Open AccessEditorial

Current Challenges and Future Advances in Lung Cancer: Genetics, Instrumental Diagnosis and Treatment

by Giovanni Vicidomini

Cancers 2023, 15(14), 3710; https://doi.org/10.3390/cancers15143710 - 21 Jul 2023

Cited by 3 | Viewed by 1619

Abstract

Lung cancer is a malignancy with a poor prognosis, with only 20% of patients having an overall survival longer than five years from diagnosis, and this prognosis has still not significantly improved despite developments in understanding the genetic evolution of lung cancer; improvements [...] Read more.

Lung cancer is a malignancy with a poor prognosis, with only 20% of patients having an overall survival longer than five years from diagnosis, and this prognosis has still not significantly improved despite developments in understanding the genetic evolution of lung cancer; improvements in the accuracy of diagnostic procedures; and refinements in the treatments with multimodal regimens, including surgery, radiotherapy and systemic therapy (chemotherapy, immunotherapy and targeted therapy) [...] Full article

(This article belongs to the Special Issue Current Challenge and Future Advances for Lung Cancer: Genetics, Instrumental Diagnosis and Treatment)

Research

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14 pages, 1217 KiB

Open AccessArticle

Systemic Inflammation and Lung Cancer: Is It a Real Paradigm? Prognostic Value of Inflammatory Indexes in Patients with Resected Non-Small-Cell Lung Cancer

by Antonio Mazzella, Elena Maiolino, Patrick Maisonneuve, Mauro Loi and Marco Alifano

Cancers 2023, 15(6), 1854; https://doi.org/10.3390/cancers15061854 - 20 Mar 2023

Cited by 6 | Viewed by 2161

Abstract

Background (1): Our goal was to investigate if and how pre-operative inflammatory status can influence the long-term prognosis of patients undergoing lung surgery for cancer. Materials and Methods (2): This prospective observational study includes the agreement of all operable patients to the study, [...] Read more.

Background (1): Our goal was to investigate if and how pre-operative inflammatory status can influence the long-term prognosis of patients undergoing lung surgery for cancer. Materials and Methods (2): This prospective observational study includes the agreement of all operable patients to the study, who were referred to our department between 1 January 2017 and 30 December 2018. The inflammatory pre-operative status of the patients was investigated by calculating albumin, CPR (c-protein reactive), complete blood count (neutrophils, lymphocytes, platelets, hemoglobin), and some other indexes referring to inflammatory status, namely the HALP amalgamated index, platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocytes ratio (NLR), systemic immune-inflammation index (SII), and advanced lung cancer inflammation Index (ALI). The follow-up ended in November 2021. Patient overall survival was assessed using the Kaplan–Meier method. The log-rank test was used to compare survival rates. Variables significantly associated with survival at univariate analysis were entered int Cox multivariate analysis (stepwise mode) to assess their independent character. Hazard ratios and their 95% confidence intervals were calculated. Variables associated with p < 0.05 were considered significative. Results (3): We enrolled 257 patients in our study. The overall survival of the cohort was as follows: 1 year, 96.1%; 3 year, 81.3%; and 4 year, 74.2%. Univariate analysis showed risk factors for overall survival as follows: Thoracoscore ≥ 2 (p = 0.002); histology (p = 0.002); HALP < 32.2 (p = 0.0002); SII ≥ 808.9 (p = 0.0004); ALI < 34.86 (p = 0.0005); NLr ≥ 2.29 (p = 0.01); hemoglobin < 13 g/dl (p = 0.01); PLR ≥ 196.1 (p = 0.005); pN+ (p < 0.0001); pleural invasion (p = 0.0002); and presence of vascular or lymphatic tumor emboli (p = 0.0002). Multivariate Cox analysis (stepwise model) identified Thoracoscore ≥ 2 (p = 0.02); histology, HALP < 32.2 (p = 0.004), and pN (p < 0.0001) as independent predictors of death. Conclusion (4): Pre-operative inflammatory status strongly influences long-term prognosis in patients affected by NSCLC and undergoing surgery. Full article

(This article belongs to the Special Issue Current Challenge and Future Advances for Lung Cancer: Genetics, Instrumental Diagnosis and Treatment)

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16 pages, 2326 KiB

Open AccessArticle

Different Tyrosine Kinase Inhibitors Used in Treating EGFR-Mutant Pulmonary Adenocarcinoma with Brain Metastasis and Intracranial Intervention Have No Impact on Clinical Outcomes

by Chia-Yu Kuo, Ming-Ju Tsai, Jen-Yu Hung, Kuan-Li Wu, Ying-Ming Tsai, Yu-Chen Tsai, Cheng-Hao Chuang, Tai-Huang Lee, Huang-Chi Chen, Chih-Jen Yang and Inn-Wen Chong

Cancers 2023, 15(1), 187; https://doi.org/10.3390/cancers15010187 - 28 Dec 2022

Cited by 2 | Viewed by 1629

Abstract

Brain metastasis in patients with non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations is a factor of poor prognosis. We conducted a retrospective study to determine the optimal treatment strategy for EGFR-mutant NSCLC patients with brain metastasis receiving or not [...] Read more.

Brain metastasis in patients with non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations is a factor of poor prognosis. We conducted a retrospective study to determine the optimal treatment strategy for EGFR-mutant NSCLC patients with brain metastasis receiving or not receiving intracranial intervention. A total of 186 patients treated with an EGFR TKI were enrolled in the study, and 79 (42%) received intracranial intervention. Patients who received intracranial intervention and those who did not had a similar treatment response rate (RR), progression-free survival (PFS) (median PFS: 11.0 vs. 10.0 months, p = 0.4842), and overall survival (OS) (median OS: 23.0 vs. 23.2 months, p = 0.2484). Patients treated with gefitinib, erlotinib, afatinib, or osimertinib had a similar RR (63%, 76%, 81%, or 100%, respectively, p = 0.1390), but they had significantly different PFS (median PFS: 7.5, 10.0, 14.8 months, or not reached, respectively, p = 0.0081). In addition, OS tended to be different between different EGFR TKI treatments (median OS of 19.2, 23.7, or 33.0 months for gefitinib, erlotinib, or afatinib treatments, respectively, p = 0.0834). Afatinib and osimertinib both demonstrated significantly longer PFS than gefitinib in a Cox regression model. Graded prognostic assessment (GPA) versions 2017 and 2022 stratified patients with different OS; patients with higher GPA index scores had significantly longer OS (p = 0.0368 and 0.0407 for version 2017 and 2022, respectively). Full article

(This article belongs to the Special Issue Current Challenge and Future Advances for Lung Cancer: Genetics, Instrumental Diagnosis and Treatment)

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17 pages, 4210 KiB

Open AccessArticle

Attempting to Identify Bacterial Allies in Immunotherapy of NSCLC Patients

by Anna Grenda, Ewelina Iwan, Paweł Krawczyk, Małgorzata Frąk, Izabela Chmielewska, Arkadiusz Bomba, Aleksandra Giza, Anna Rolska-Kopińska, Michał Szczyrek, Robert Kieszko, Tomasz Kucharczyk, Bożena Jarosz, Dariusz Wasyl and Janusz Milanowski

Cancers 2022, 14(24), 6250; https://doi.org/10.3390/cancers14246250 - 19 Dec 2022

Cited by 10 | Viewed by 2069

Abstract

Introduction: Factors other than PD-L1 (Programmed Death Ligand 1) are being sought as predictors for cancer immuno- or chemoimmunotherapy in ongoing studies and long-term observations. Despite high PD-L1 expression on tumor cells, some patients do not benefit from immunotherapy, while others, without the [...] Read more.

Introduction: Factors other than PD-L1 (Programmed Death Ligand 1) are being sought as predictors for cancer immuno- or chemoimmunotherapy in ongoing studies and long-term observations. Despite high PD-L1 expression on tumor cells, some patients do not benefit from immunotherapy, while others, without the expression of this molecule, respond to immunotherapy. Attention has been paid to the composition of the gut microbiome as a potential predictive factor for immunotherapy effectiveness. Materials and Methods: Our study enrolled 47 Caucasian patients with stage IIIB or IV non-small cell lung cancer (NSCLC). They were eligible for treatment with first- or second-line immunotherapy or chemoimmunotherapy. We collected stool samples before the administration of immunotherapy. We performed next-generation sequencing (NGS) on DNA isolated from the stool sample and analyzed bacterial V3 and V4 of the 16S rRNA gene. Results: We found that bacteria from the families Barnesiellaceae, Ruminococcaceae, Tannerellaceae, and Clostridiaceae could modulate immunotherapy effectiveness. A high abundance of Bacteroidaaceae, Barnesiellaceae, and Tannerellaceae could extend progression-free survival (PFS). Moreover, the risk of death was significantly higher in patients with a high content of Ruminococcaceae family (HR = 6.3, 95% CI: 2.6 to 15.3, p < 0.0001) and in patients with a low abundance of Clostridia UCG-014 (HR = 3.8, 95% CI: 1.5 to 9.8, p = 0.005) regardless of the immunotherapy line. Conclusions: The Clostridia class in gut microbiota could affect the effectiveness of immunotherapy, as well as the length of survival of NSCLC patients who received this method of treatment. Full article

(This article belongs to the Special Issue Current Challenge and Future Advances for Lung Cancer: Genetics, Instrumental Diagnosis and Treatment)

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18 pages, 2781 KiB

Open AccessArticle

Pten and p53 Loss in the Mouse Lung Causes Adenocarcinoma and Sarcomatoid Carcinoma

by Sara Lázaro, Corina Lorz, Ana Belén Enguita, Iván Seller, Jesús M. Paramio and Mirentxu Santos

Cancers 2022, 14(15), 3671; https://doi.org/10.3390/cancers14153671 - 28 Jul 2022

Cited by 4 | Viewed by 1949

Abstract

Lung cancer remains the leading cause of cancer deaths worldwide. Among the Non-Small Cell Carcinoma (NSCLC) category, Adenocarcinoma (ADC) represents the most common type, with different reported driver mutations, a bunch of models described and therapeutic options. Meanwhile, Pulmonary Sarcomatoid Carcinoma (PSC) is [...] Read more.

Lung cancer remains the leading cause of cancer deaths worldwide. Among the Non-Small Cell Carcinoma (NSCLC) category, Adenocarcinoma (ADC) represents the most common type, with different reported driver mutations, a bunch of models described and therapeutic options. Meanwhile, Pulmonary Sarcomatoid Carcinoma (PSC) is one of the rarest, with very poor outcomes, scarce availability of patient material, no effective therapies and no models available for preclinical research. Here, we describe that the combined deletion of Pten and Trp53 in the lungs of adult conditional mice leads to the development of both ADC and PSC irrespective of the lung targeted cell type after naphthalene induced airway epithelial regeneration. Although this model shows long latency periods and incomplete penetrance for tumor development, it is the first PSC mouse model reported so far, and sheds light on the relationships between ADC and PSC and their cells of origin. Moreover, human ADC show strong transcriptomic similarities to the mouse PSC, providing a link between both tumor types and the human ADC. Full article

(This article belongs to the Special Issue Current Challenge and Future Advances for Lung Cancer: Genetics, Instrumental Diagnosis and Treatment)

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10 pages, 253 KiB

Open AccessArticle

Effectiveness of Outpatient Pulmonary Rehabilitation in Patients with Surgically Resected Lung Cancer: A Retrospective Real-World Analysis

by Oliver Illini, Arschang Valipour, Dietlinde Gattinger, Milos Petrovic, Hannah Fabikan, Maximilian Johannes Hochmair and Ralf Harun Zwick

Cancers 2022, 14(14), 3479; https://doi.org/10.3390/cancers14143479 - 18 Jul 2022

Cited by 5 | Viewed by 1881

Abstract

Patients with lung cancer frequently suffer from physical deconditioning, low exercise capacity, and reduced quality of life. There is little evidence on the effects of a structured outpatient pulmonary rehabilitation program (OPR) on exercise capacity and symptom load in these patients. We performed [...] Read more.

Patients with lung cancer frequently suffer from physical deconditioning, low exercise capacity, and reduced quality of life. There is little evidence on the effects of a structured outpatient pulmonary rehabilitation program (OPR) on exercise capacity and symptom load in these patients. We performed a retrospective, single-center analysis of surgically resected lung cancer patients, who underwent a multiprofessional 6-week OPR. The primary endpoint was a change in the six-minute walk test distance (6 MWT). Secondary endpoints included changes in maximal workload and constant work-rate test results during cycle-ergometry, upper and lower extremity strength, and inspiratory muscle strength. The COPD Assessment Test (CAT) was used to assess symptom burden. Fifty-seven patients were included. Of those, fifty-two (91.2%) completed the full 6 weeks of OPR. The mean age was 56.4 (SD 9.2) years, and 58% were female. At completion of OPR, there was a statistically significant mean of a 50 m (95% CI, 29.6–70.7; p < 0.001) increase in 6 MWT. Significant improvements were also seen in all other exercise and strength tests (p < 0.001), accompanied by a significant reduction in the CAT score (mean difference −3.1, p = 0.001). No adverse effects were reported. OPR for surgically resected lung cancer patients was safe and effective and showed high adherence in the current study. Full article

(This article belongs to the Special Issue Current Challenge and Future Advances for Lung Cancer: Genetics, Instrumental Diagnosis and Treatment)

17 pages, 3199 KiB

Open AccessArticle

by Zeinab Kosibaty, Odd Terje Brustugun, Inger Johanne Zwicky Eide, Georgios Tsakonas, Oscar Grundberg, Luigi De Petris, Marc McGowan, Per Hydbring and Simon Ekman

Cancers 2022, 14(14), 3430; https://doi.org/10.3390/cancers14143430 - 14 Jul 2022

Cited by 4 | Viewed by 2562

Abstract

Treatment with the tyrosine kinase inhibitor (TKI) osimertinib is the standard of care for non-small cell lung cancer (NSCLC) patients with activating mutations in the epidermal growth factor receptor (EGFR). Osimertinib is also used in T790M-positive NSCLC that may occur de novo or [...] Read more.

Treatment with the tyrosine kinase inhibitor (TKI) osimertinib is the standard of care for non-small cell lung cancer (NSCLC) patients with activating mutations in the epidermal growth factor receptor (EGFR). Osimertinib is also used in T790M-positive NSCLC that may occur de novo or be acquired following first-line treatment with other EGFR TKIs (i.e., gefitinib, erlotinib, afatinib, or dacomitinib). However, patients treated with osimertinib have a high risk of developing resistance to the treatment. A substantial fraction of the mechanisms for resistance is unknown and may involve RNA and/or protein alterations. In this study, we investigated the full transcriptome of parental and osimertinib-resistant cell lines, revealing 131 differentially expressed genes. Knockdown screening of the genes upregulated in resistant cell lines uncovered eight genes to partly confer resistance to osimertinib. Among them, we detected the expression of Ras-related protein Rab-32 (RAB32) and thrombospondin 1 (THBS1) in plasmas sampled at baseline and at disease progression from EGFR-positive NSCLC patients treated with osimertinib. Both genes were upregulated in progression samples. Moreover, we found that knockdown of RAB32 and THBS1 reduced the expression of phosphorylated focal adhesion kinase (FAK). Combination of osimertinib with a FAK inhibitor resulted in synergistic toxicity in osimertinib-resistant cells, suggesting a potential therapeutic drug combination for overcoming resistance to osimertinib in NSCLC patients. Full article

(This article belongs to the Special Issue Current Challenge and Future Advances for Lung Cancer: Genetics, Instrumental Diagnosis and Treatment)

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11 pages, 1613 KiB

Open AccessArticle

Peripheral Blood Mononuclear Cells Predict Therapeutic Efficacy of Immunotherapy in NSCLC

by Jacobo Rogado, Fernando Pozo, Kevin Troule, José Miguel Sánchez-Torres, Nuria Romero-Laorden, Rebeca Mondejar, Olga Donnay, Anabel Ballesteros, Vilma Pacheco-Barcia, Javier Aspa, Fátima Al-Shahrour, Arantzazu Alfranca and Ramon Colomer

Cancers 2022, 14(12), 2898; https://doi.org/10.3390/cancers14122898 - 12 Jun 2022

Cited by 5 | Viewed by 2587

Abstract

In lung cancer immunotherapy, biomarkers to guide clinical decisions are limited. We now explore whether the detailed immunophenotyping of circulating peripheral blood mononuclear cells (PBMCs) can predict the efficacy of anti-PD-1 immunotherapy in patients with advanced non-small-cell lung cancer (NSCLC). We determined 107 [...] Read more.

In lung cancer immunotherapy, biomarkers to guide clinical decisions are limited. We now explore whether the detailed immunophenotyping of circulating peripheral blood mononuclear cells (PBMCs) can predict the efficacy of anti-PD-1 immunotherapy in patients with advanced non-small-cell lung cancer (NSCLC). We determined 107 PBMCs subpopulations in a prospective cohort of NSCLC patients before starting single-agent anti-PD-1 immunotherapy (study group), analyzed by flow cytometry. As a control group, we studied patients with advanced malignancies before initiating non-immunotherapy treatment. The frequency of PBMCs was correlated with treatment outcome. Patients were categorized as having either high or low expression for each biomarker, defined as those above the 55th or below the 45th percentile of the overall marker expression within the cohort. In the study group, three subpopulations were associated with significant differences in outcome: high pretreatment levels of circulating CD4+CCR9+, CD4+CCR10+, or CD8+CXCR4+ T cells correlated with poorer overall survival (15.7 vs. 35.9 months, HR 0.16, p = 0.003; 22.0 vs. NR months, HR 0.10, p = 0.003, and 22.0 vs. NR months, HR 0.29, p = 0.02). These differences were specific to immunotherapy-treated patients. High baseline levels of circulating T cell subpopulations related to tissue lymphocyte recruitment are associated with poorer outcomes of immunotherapy-treated advanced NSCLC patients. Full article

(This article belongs to the Special Issue Current Challenge and Future Advances for Lung Cancer: Genetics, Instrumental Diagnosis and Treatment)

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14 pages, 4799 KiB

Open AccessArticle

The Diagnostic Utility of Cell-Free DNA from Ex Vivo Bronchoalveolar Lavage Fluid in Lung Cancer

by Sotaro Otake, Taichiro Goto, Rumi Higuchi, Takahiro Nakagomi, Yosuke Hirotsu, Kenji Amemiya, Toshio Oyama, Hitoshi Mochizuki and Masao Omata

Cancers 2022, 14(7), 1764; https://doi.org/10.3390/cancers14071764 - 30 Mar 2022

Cited by 4 | Viewed by 1892

Abstract

Although bronchoscopy is generally performed to diagnose lung cancer, its diagnostic yield remains unsatisfactory. Assuming that lung cancer cells release cell-free DNA into the epithelial lining fluid, we hypothesized that lung cancer could be diagnosed by analyzing gene mutations in cell-free DNA in [...] Read more.

Although bronchoscopy is generally performed to diagnose lung cancer, its diagnostic yield remains unsatisfactory. Assuming that lung cancer cells release cell-free DNA into the epithelial lining fluid, we hypothesized that lung cancer could be diagnosed by analyzing gene mutations in cell-free DNA in this fluid. This study included 32 patients with lung cancer who underwent surgery at our hospital. Bronchoalveolar lavage (BAL) was performed on the resected lung samples (ex vivo BAL model) after lobectomy. Each DNA sample (i.e., BAL fluid, primary lesion, and plasma) underwent deep targeted sequencing. Gene mutation analyses in the BAL fluid samples identified mutations identical to those in the primary lesions in 30 (93.8%) of 32 patients. In contrast, the microscopic cytology of the same BAL fluid samples yielded a diagnosis of lung cancer in only one of 32 patients, and the analysis of plasma samples revealed gene mutations identical to those in the primary lesions in only one of 32 patients. In conclusion, cell-free DNA released from lung cancer cells exists more abundantly in the airway than in the blood. The collection and analysis of the BAL fluid containing cell-free DNA derived from lung cancer can thus allow lung cancer diagnosis and the screening of driver mutations. Full article

(This article belongs to the Special Issue Current Challenge and Future Advances for Lung Cancer: Genetics, Instrumental Diagnosis and Treatment)

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Review

Jump to: Editorial, Research

13 pages, 1727 KiB

Open AccessReview

T4 Lung Carcinoma with Infiltration of the Thoracic Aorta: Indication and Surgical Procedure

by Marc Irqsusi, Tamer Ghazy, Sebastian Vogt, Nikolas Mirow and Andreas Kirschbaum

Cancers 2023, 15(19), 4847; https://doi.org/10.3390/cancers15194847 - 4 Oct 2023

Viewed by 1614

Abstract

Lung carcinomas infiltrate the aorta mostly on the left side and are altogether rare. As an initial step, complete staging is performed and the results are evaluated in an interdisciplinary tumor board. If the patient’s general condition including cardiopulmonary reserves is sufficient, and [...] Read more.

Lung carcinomas infiltrate the aorta mostly on the left side and are altogether rare. As an initial step, complete staging is performed and the results are evaluated in an interdisciplinary tumor board. If the patient’s general condition including cardiopulmonary reserves is sufficient, and if there is neither distant metastasis nor an N2 situation, surgical resection may be indicated. The option for neoadjuvant chemotherapy should always be taken into consideration. Depending on the anatomic tumor location, partial lung resection and resection of the affected aortic wall are performed employing a cardiopulmonary bypass. The resected aortic wall is replaced by a vascular prosthesis. In recent years, this proven procedure has partly been replaced by an alternative one, avoiding extracorporeal circulation. An endoaortic stent is implanted in the affected area followed by partial lung resection and resection of the diseased aortic wall. This new procedure has significantly reduced perioperative mortality and morbidity. With proper patient selection, long-term survival can be improved even in this complex malignoma. Full article

(This article belongs to the Special Issue Current Challenge and Future Advances for Lung Cancer: Genetics, Instrumental Diagnosis and Treatment)

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20 pages, 2693 KiB

Open AccessReview

Advances in the Management of Central Nervous System Metastases in Non-Small Cell Lung Cancer

by Angelica D’Aiello, Emily Miao and Haiying Cheng

Cancers 2023, 15(3), 844; https://doi.org/10.3390/cancers15030844 - 30 Jan 2023

Cited by 2 | Viewed by 2923

Abstract

Central nervous system (CNS) metastases are common among patients with non-small cell lung cancer (NSCLC). While the presence of brain metastases has historically portended poor prognosis, recent advances in local and systemic therapies have greatly improved outcomes for NSCLC patients with CNS involvement. [...] Read more.

Central nervous system (CNS) metastases are common among patients with non-small cell lung cancer (NSCLC). While the presence of brain metastases has historically portended poor prognosis, recent advances in local and systemic therapies have greatly improved outcomes for NSCLC patients with CNS involvement. Stereotactic radiology surgery (SRS) has emerged as an effective radiotherapy technique with fewer toxicities compared to whole brain radiotherapy (WBRT). Furthermore, multi-generation tyrosine kinase inhibitors (TKIs) with CNS overall response rates (ORR) of up to 70–80% are now an accepted first-line approach for a subset of advanced NSCLC patients with targetable molecular alterations. In addition, while the CNS was once considered an immunologic sanctuary site, growing evidence shows that immune checkpoint inhibitors (ICIs) can induce durable responses in brain metastases as well. Ongoing efforts to optimize CNS metastases management are necessary to refine multimodal treatment approaches and develop new therapeutics with better CNS penetrance. Full article

(This article belongs to the Special Issue Current Challenge and Future Advances for Lung Cancer: Genetics, Instrumental Diagnosis and Treatment)

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17 pages, 325 KiB

Open AccessReview

Moving Immune Checkpoint Inhibitors to Early Non-Small Cell Lung Cancer: A Narrative Review

by Giuseppe Viscardi, Fabiana Vitiello, Alberto Servetto, Valerio Gristina, Elio Gregory Pizzutilo, Maria Anna Canciello, Paola Maria Medusa, Fabio Salomone, Gaetano Di Guida, Mariano Mollica, Luigi Aronne, Roberto Scaramuzzi, Filomena Napolitano, Ciro Battiloro, Francesca Caputo, Marina Gilli, Giuseppe Totaro, Carlo Curcio, Danilo Rocco and Vincenzo Montesarchio

Cancers 2022, 14(23), 5810; https://doi.org/10.3390/cancers14235810 - 25 Nov 2022

Cited by 3 | Viewed by 1979

Abstract

Lung cancer is the leading cause of cancer-related death worldwide. Since prognosis of early-stage non-small cell lung cancer (NSCLC) remains dismal for common relapses after curative surgery, considerable efforts are currently focused on bringing immunotherapy into neoadjuvant and adjuvant settings. Previously, perioperative chemotherapy [...] Read more.

Lung cancer is the leading cause of cancer-related death worldwide. Since prognosis of early-stage non-small cell lung cancer (NSCLC) remains dismal for common relapses after curative surgery, considerable efforts are currently focused on bringing immunotherapy into neoadjuvant and adjuvant settings. Previously, perioperative chemotherapy showed only a modest but significative improvement in overall survival. The presence of broad tumor neoantigens load at primary tumor prior to surgery as well as the known immunosuppressive status following resection represent the main rationale for immunotherapy in early disease. Several trials have been conducted in recent years, leading to atezolizumab and nivolumab approval in the adjuvant and neoadjuvant setting, respectively, and perioperative immunotherapy in NSCLC remains a field of active clinical and preclinical investigation. Unanswered questions in perioperative therapy in NSCLC include the optimal sequence and timing of chemotherapy and immunotherapy, the potential of combination strategies, the role of predictive biomarkers for patient selection and the choice of useful endpoints in clinical investigation. Full article

(This article belongs to the Special Issue Current Challenge and Future Advances for Lung Cancer: Genetics, Instrumental Diagnosis and Treatment)

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