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Non-small cell lung cancer (NSCLC) accounts for 75-80% of all lung cancer cases. Stage III NSCLC represents a highly heterogenous stage characterized by different disease presentations and a wide range of treatment options. For patients with good performance status and unresectable-stage III NSCLC with programmed death-ligands 1 (PD-L1) tumor proportion score (TPS) ≥1%, durvalumab consolidation immunotherapy after a platinum-based chemo-radiotherapy is strongly recommended. However, age, poor performance status, underlying comorbidities may represent contraindications for chemotherapy to be used in a subgroup of patients. Herein, we report a case of an 80-year-old male affected by a stage IIIB lung adenocarcinoma with overexpression of PD-L1 (TPS 90%) treated with pembrolizumab, an immune checkpoint inhibitor targeting PD-1/PD-L1 pathways, which shows a complete resolution of lung lesion after four cycles of treatment. Although randomized controlled trials are required, this case report may suggest the potential role of pembrolizumab for chemotherapy unsuitable patients with overexpressing PD-L1 unresectable-stage III NSCLC.

Introduction: Many data already suggested that cancer and IPF are underlined by a number of common pathogenic biologic pathways. However, fewer data regards the interconnections, in terms of synergy or increased toxicities, of drugs used in cancer and IPF. Particularly, how the specific therapy influences the concurrent condition and prognostic factors of response in patients with both lung cancer and IPF are far to be clarified. Similarly, identification of features of IPF patients with higher risk of developing pulmonary adverse events when treated with chemotherapy, immune checkpoint inhibitors, TKIs, or radiotherapy is of primary importance in clinical practice., Areas Covered: We will discuss the scientific rationale, based on the extensive analysis of literature data, by consulting several databases for combining anticancer and antifibrotic treatments and for the design of novel therapeutic strategies. The role of immunotherapy in cancer aroused in IPF context will be discussed with specific interested, based on the continuously increasing role of immune checkpoint inhibition against lung tumors., Expert Opinion: This work will help to improve knowledge, based on a multidisciplinary perspective, on IPF and cancer patients, which identify an unmet clinical need. A better management during each phase of disease progression will require the design innovative trials and the development of new drugs and molecules both in the oncologic and respiratory medicine pipeline.

Alectinib is a highly selective tyrosine kinase inhibitor of anaplastic lymphoma kinase (ALK) that is approved as first-line treatment in adult patients with ALK-positive non-small cell lung cancer (NSCLC) and as second-line in patients previously treated with crizotinib, and has been shown in the literature to significantly prolong progression-free survival compared to chemotherapy in patients with advanced non-small cell lung cancer. The authors describe a clinical case of a 24-year-old woman with malignant massive pleural effusion caused by ALK rearranged pulmonary adenocarcinoma with pleural and pericardial metastasis, in which, despite a dramatic clinical debut, the correct and timely management of the diagnostic and therapeutic path allowed for extraordinary therapeutic success.

Background: Previous studies regarding the prevalence of frailty in patients with lung cancer and mortality in frail patients with lung cancer are inconsistent and require clarification., Research Question: What is the prevalence and impact of frailty in patients with lung cancer?, Study Design and Methods: This systematic review and meta-analysis used a combination of free-text terms and medical subject headings terms, according to the database requirements in MEDLINE/PubMed, Scopus, and Cochrane Library from inception until November 15, 2020., Results: A total of 2,571 articles were identified, and 16 articles involving 4,183 patients were included for study. The prevalence of frailty in lung cancer was 45% (95% CI, 28-61; I 2  = 99.5%; P < .0001). In patients with lung cancer, frailty was associated with an increased hazard ratio for mortality (hazard ratio, 3.01; 95% CI, 1.77-5.10; P < .001)., Interpretation: The prevalence of frailty in lung cancer is 45%, which has a significant negative impact on survival of patients with lung cancer. These results highlight the importance of measuring frailty, which provides important prognostic information, and may provide opportunities for interventions to improve outcomes in patients with lung cancer., (Copyright © 2022 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Lung cancer (LC) and chronic obstructive pulmonary disease (COPD) represent leading causes of morbidity and mortality worldwide. Common risk factors lead to an increased inflammatory response, enhances oxidative stress, and changes in lung microenvironment contributing to fine-tuned interaction between these respiratory disorders. Despite evidence that COPD represents a main risk factor for LC, assessment of LC risk features among COPD patients is not routinely considered in the clinical practice. In LC patients concurrent COPD may impact on clinical scenario influencing the response to treatment. Better understanding LC and COPD coexistence may impact on clinical scenario influencing therapeutic approach. In this review, we describe the basis of this network and how the complex interplay between these respiratory disorders affects the clinical decision-making process.

Introduction : Landscape of Extensive Stage (ES)-SCLC treatment has been unchanged over the years. Chemotherapy, mostly based on cisplatin and etoposide, remained the standard-of-care for patients with ES-SCLC for almost 40 years. Recently, immune check points inhibitors have emerged marking a turning point for ES-SCLC treatment Areas covered : Aim of the paper is to discuss ICIs impact on ES-SCLC treatment algorithms, review current clinical trials, and explore future perspectives. Expert opinion : A growing body of evidence supports ICI-containing regimens as a new mainstay of ES-SCLC treatment. Whether subgroups of SCLC patients may have greater survival benefits from ICIs treatment needs to be better defined. Understanding the impact of tumor microenvironment and identifying reliable predictive and/or prognostic biomarkers will be fundamental to move toward a personalized treatment approach leading to improved survival.

Lung cancer still represents the leading cause of cancer-related death, globally. Likewise, malnutrition and inactivity represent a major risk for loss of functional pulmonary capacities influencing overall lung cancer severity. Therefore, the adhesion to an appropriate health lifestyle is crucial in the management of lung cancer patients despite the subtype of cancer. This review aims to summarize the available knowledge about dietary approaches as well as physical activity as the major factors that decrease the risk towards lung cancer, and improve the response to therapies. We discuss the most significant dietary schemes positively associated to body composition and prognosis of lung cancer and the main molecular processes regulated by specific diet schemes, functional foods and physical activity, i.e., inflammation and oxidative stress. Finally, we report evidence demonstrating that dysbiosis of lung and/or gut microbiome, as well as their interconnection (the gut-lung axis), are strictly related to dietary patterns and regular physical activity playing a key role in lung cancer formation and progression, opening to the avenue of modulating the microbiome as coadjuvant therapy. Altogether, the evidence reported in this review highlights the necessity to consider non-pharmacological interventions (nutrition and physical activity) as effective adjunctive strategies in the management of lung cancer.

Background: Programmed death-ligand 1 (PD-L1) expression on cancer cells is a clinically important biomarker to select patients with non-small cell lung cancer (NSCLC) for treatment with programmed death-1/PD-L1 inhibitors. Clinical trials of immunotherapy in patients with NSCLC have required histologic evidence for PD-L1 testing; in clinical practice, cytologic samples commonly are acquired in patients with advanced disease., Research Question: This study aims to investigate whether endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) samples are adequate for PD-L1 testing in NSCLC., Study Design and Methods: This study investigates the sampling adequacy of EBUS-TBNA for PD-L1 testing when compared with other methods. Furthermore, the relationship between clinicopathologic characteristics and PD-L1 expression in the study population have been examined. Five hundred seventy-seven NSCLC specimens were analyzed from consecutive patients with NSCLC across six centers in the United Kingdom and one center in the United States between January 2015 and December 2016., Results: In the EBUS-TBNA group (189 specimens), the overall percentage of patients with successful PD-L1 testing was 94.7%. There was no significant difference in sampling adequacy with other methods of tissue acquisition. Older patients had higher failure rates of PD-L1 testing (OR, 1.06; P = .008). In multivariate analysis, advanced N-stage (P = .048) and presence of brain metastasis (P < .001) were associated with high PD-L1 expression., Interpretation: This large multicenter study shows that EBUS-TBNA provides samples adequate for PD-L1 testing and that advanced N stage and the presence of brain metastasis are associated with high PD-L1 expression., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Viral infections are frequent among patients with thoracic malignancies prompted by dysregulation of innate and adaptative immune response. Clinical symptoms and radiological findings of both viral pneumonia and lung adenocarcinoma may overlap resulting in diagnostic and clinical  challenges.We present the case of a women admitted to our department presenting with an acute manifestation of coronavirus OC43 pneumonia with underlying undiagnosed lung adenocarcinoma.

Alterations of adipose tissue occurring in obesity have been recognized as a major risk factor for several cancers. The relationship between adipose tissue and lung cancer, which is the main cancer-related cause of death worldwide, still requires investigation. Perturbations in the adipokine system are likely to interfere with inter-organ crosstalk in lung cancer, which may influence the lung tumor microenvironment. Adiponectin (Acrp30) expression is deregulated in several cancer types. Acrp30 circulates as oligomers with a Low (LMW), Medium (MMW), and High Molecular Weight (HMW), with the latter mediating the main biological effects. Acrp30 acts through AdipoR1 and AdipoR2 receptors. T-cadherin has been described as a non-signaling receptor. This study's aim was to investigate the regulation of serum Acrp30 and its receptors in sample tissue from non-small cell lung cancer (NSCLC) patients. We recruited 72 NSCLC patients and 60 healthy controls, whom we evaluated in terms of their Acpr30 levels and oligomeric profile. In addition, the expression of AdipoRs in tissues from lung cancer specimens was also measured and compared to coupled healthy lung samples. Our findings show a significant reduction of total Acrp30 levels in NSCLC patients compared to normal subjects, with a specific down-regulation of HMW oligomers. Acrp30 expression was lower in lung adenocarcinoma than other subtypes, regardless of other factors. A significantly higher expression of AdipoR1 was observed, while no differences in R2 and a lower expression of T-cadherin were found in lung cancer specimens compared to normal healthy lung tissues. Involvement of the Acrp30 system in lung cancer may provide new insight into the interaction between adipose tissue and lung and sheds light on its potential ability to influence the lung tumor microenvironment.

Testicular carcinoma recurrences represent a rare finding (1-6% in non-seminomatous germ cell tumours). However, cases of recurrence have been described many years later. We report a case of late recurrence of embryonic testicular carcinoma, after 26 years, with pulmonary metastases. Following evidence of increase of alpha-fetoprotein (AFP), the patient underwent a total body computed tomography scan that exhibited two pulmonary nodules, one in upper left lobe and other in left hilar region with multiple mediastinal and retrocrural lymph node enlargements All consolidations showed increased sugar uptake value at PET CT. Biopsies of lung consolidations confirmed diagnosis of recurrence of testicular carcinoma.

Objective: Preoperative functional evaluation is central to optimizing the identification of patients with non-small cell lung cancer (NSCLC) who are candidates for surgery. The minute ventilation/carbon dioxide output (VE/VCO2) slope has proven to be a predictor of surgical complications and mortality. Pulmonary rehabilitation programs (PRPs) could influence short-term outcomes in patients with COPD undergoing lung resection. Our objective was to evaluate the effects of a PRP on the VE/VCO2 slope in a cohort of patients with COPD undergoing lung resection for NSCLC., Methods: We retrospectively evaluated 25 consecutive patients with COPD participating in a three-week high-intensity PRP prior to undergoing lung surgery for NSCLC, between December of 2015 and January of 2017. Patients underwent complete functional assessment, including spirometry, DLCO measurement, and cardiopulmonary exercise testing., Results: There were no significant differences between the mean pre- and post-PRP values (% of predicted) for FEV1 (61.5 ± 22.0% vs. 62.0 ± 21.1%) and DLCO (67.2 ± 18.1% vs. 67.5 ± 13.2%). Conversely, there were significant improvements in the mean peak oxygen uptake (from 14.7 ± 2.5 to 18.2 ± 2.7 mL/kg per min; p < 0.001) and VE/VCO2 slope (from 32.0 ± 2.8 to 30.1 ± 4.0; p < 0.01)., Conclusions: Our results indicate that a high-intensity PRP can improve ventilatory efficiency in patients with COPD undergoing lung resection for NSCLC. Further comprehensive prospective studies are required to corroborate these preliminary results.

Manipulation of the immune response is a game changer in lung cancer treatment, revolutionizing management. PD1 and CTLA4 are dynamically expressed on different T cell subsets that can either disrupt or sustain tumor growth. Monoclonal antibodies (MoAbs) against PD1/PDL1 and CTLA4 have shown that inhibitory signals can be impaired, blocking T cell activation and function. MoAbs, used as both single-agents or in combination with standard therapy for the treatment of advanced non-small cell lung cancer (NSCLC), have exhibited advantages in terms of overall survival and response rate; nivolumab, pembrolizumab, atezolizumab and more recently, durvalumab, have already been approved for lung cancer treatment and more compounds are in the pipeline. A better understanding of signaling elicited by these antibodies on T cell subsets, as well as identification of biological determinants of sensitivity, resistance and correlates of efficacy, will help to define the mechanisms of antitumor responses. In addition, the relevance of T regulatory cells (Treg) involved in immune responses in cancer is attracting increasing interest. A major challenge for future research is to understand why a durable response to immune checkpoint inhibitors (ICIs) occurs only in subsets of patients and the mechanisms of resistance after an initial response. This review will explore current understanding and future direction of research on ICI treatment in lung cancer and the impact of tumor immune microenvironment n influencing clinical responses.

The therapeutic scenario for elderly patients with advanced NSCLC has been limited to radiotherapy and chemotherapy. Recently, a novel therapeutic approach based on targeting the immune-checkpoints has showed noteworthy results in advanced NSCLC. PD1/PD-L1 pathway is co-opted by tumor cells through the expression of PD-L1 on the tumor cell surface and on cells within the microenvironment, leading to suppression of anti-tumor cytolytic T-cell activity by the tumor. The success of immune-checkpoints inhibitors in clinical trials led to rapid approval by the FDA and EMA. Currently, data regarding efficacy and safety of ICIs in older subjects is limited by the poor number of elderly recruited in clinical trials. Careful assessment and management of comorbidities is essential to achieve better outcomes and limit the immune related adverse events in elderly NSCLC patients.

Lung cancer is the leading cause of cancer-related death worldwide and majority of patients are diagnosed in advanced/metastatic disease stage. Sites of distant metastases mainly include contralateral lung, lymph nodes, brain, bones, adrenal glands and liver; skeletal muscles metastases (SMMs) are less common. Psoas muscle and diaphragm metastases are mainly found during autopsy, as their involvement commonly is asymptomatic. We report a case of a 60-year-old female, suffering from non-small cell lung cancer (NSCLC), with refractory lower back pain, as expression of malignant psoas syndrome (MPS). MPS is a rare and difficult-to-treat cancer-pain syndrome, unresponsive to majority of analgesic therapy, related to psoas muscle metastasis; it is usually caused by different tumors such as uterus, ovary, bladder, prostate, colon-rectum, lymphoma, melanoma and sarcoma and represents an uncommon finding in NSCLC patients.

Background: Tracheobronchial malignant stenosis is a life-threatening condition which may cause recurrent infections due to lung atelectasis. Despite immunotherapy is less toxic than standard chemotherapy, recurrent lung infections may represent a challenge for this treatment. We report a clinical case of a patient with metastatic squamous cell carcinoma suffering from pulmonary infections due to central airway obstruction who underwent endoscopic recanalization followed by immunotherapy., Case Presentation: A 64 year-old man was referred to our attention for the management of metastatic squamous cell carcinoma obstructing the right main bronchus with recurrent pulmonary infections. Patient exhibited strong positive PD-L1 expression (> 50%). Advanced disease stage contraindicated surgical treatment. Although therapy with immune check point inhibitors was indicated as first-line treatment, recurrent pulmonary infections made it unfeasible. Therefore, we planned a combined approach including endoscopic recanalization of central airway in order to resolve lung atelectasis, and lung infection followed by immunotherapy treatment with pembrolizumab in order to avoid local and systemic disease progression., Conclusions: At 16-week follow-up, the patient was alive in stable disease with improvement of clinical condition and no signs of lung infection.

Cancers have the ability to disrupt immune response by interfering with adaptive immunity. Blocking checkpoint pathways has become a target for pharmacological research in lung cancer with particular focus on peptides PD-1 and CTLA-4. A number of immune check-point inhibitors (ICIs) targeting both PD-1 and CTLA-4 pathways are under investigation within clinical trials, of which Nivolumab, Pembrolizumab and Atezolizumab have already been approved for lung cancer treatment by both FDA and EMA. Employed as single-agents in current practice for the treatment of advanced non-small cell lung cancer (NSCLC) ICIs have exhibited advantages in terms of overall survival and response rate with some responses being durable. Evaluating combinations of different inhibitors, dosing and sequencing within a multimodal therapy approach, together with better management of toxicity represents a new challenge for future research of therapy targeting immune check-points., (Copyright © 2018 Elsevier Ltd. All rights reserved.)