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Simple Summary: Systemic inflammation and changes in the inflammatory status are frequent features of lung cancer. There is a close interconnection between cancer development and the clinical, general, and inflammatory status of patients. In this paper, we evaluate a large panel of inflammatory indexes in patients who underwent lung resection for NSCLC lung cancer; we show that pre-operative inflammatory status strongly influences long-term prognosis in patients affected by NSCLC and undergoing surgery. 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. [ABSTRACT FROM AUTHOR]

Studies carried out in the last ten years have shown that the metabolites made up from the gut microbiota are essential for multiple functions, such as the correct development of the immune system of newborns, interception of pathogens, and nutritional enrichment of the diet. Therefore, it is not surprising that alteration of the gut microbiota is the starting point of gastrointestinal infection, obesity, type 2 diabetes, inflammatory bowel disease, colorectal cancer, and lung cancer. Diet changes and antibiotics are the major factors damaging the gut microbiota. Early exposure of the newborns to antibiotics may prevent their correct development of the immune system, exposing them to pathogen infections, allergies, and chronic inflammatory diseases. We already know much on how host genes, microbiota, and the environment interact, owing to experiments in several model animals, especially in mice; advances in molecular technology; microbiota transplantation; and comparative metagenomic analysis. However, much more remains to be known. Longitudinal studies on patients undergoing to therapy, along with the identification of bacteria prevalent in responding patients may provide valuable data for improving therapies. [ABSTRACT FROM AUTHOR]

Simple Summary: The role of autophagy in lung cancers is still controversial, mainly because the visualization of autophagy levels in patients remains challenging. One interesting approach consists of studying autophagy at the transcriptomic level. In this line, many transcriptomics analyses performed on autophagy genes focused on the discovery of new biomarkers to predict the efficiency of antitumor therapies. However, the majority of these studies were based on global transcriptomic analysis of the whole tumor microenvironment, and few investigations have been performed on malignant cells themselves. The goal of this study was not to determine another new predictive signature based on autophagy-related genes. Instead, we investigated the expression of autophagy genes to understand the involvement of this process in lung cancer homeostasis. Specifically, we discovered a new autophagy signature that correlates with the metabolic and immunogenic status of malignant cells, supporting the relationship between autophagy and tumor growth in lung cancer patients. Autophagy is a self-degradative mechanism involved in many biological processes, including cell death, survival, proliferation or migration. In tumors, autophagy plays an important role in tumorigenesis as well as cancer progression and resistance to therapies. Usually, a high level of autophagy in malignant cells has been associated with tumor progression and poor prognostic for patients. However, the investigation of autophagy levels in patients remains difficult, especially because quantification of autophagy proteins is challenging in the tumor microenvironment. In this study, we analyzed the expression of autophagy genes in non-small cell lung (NSCLC) cancer patients using public datasets and revealed an autophagy gene signature for proliferative and immune-checkpoint-expressed malignant cells in lung adenocarcinoma (LUAD). Analysis of autophagy-related gene expression profiles in tumor and adjacent tissues revealed differential signatures, namely signature A (23 genes) and signature B (12 genes). Signature B correlated with a bad prognosis and poor overall and disease-specific survival. Univariate and multivariate analyses revealed that this signature was an independent factor for prognosis. Moreover, patients with high expression of signature B exhibited more genes related to proliferation and fewer genes related to immune cells or immune response. The analysis of datasets from sorted fresh tumor cells or single cells revealed that signature B is predominantly represented in malignant cells, with poor expression in pan-immune population or in fibroblast or endothelial cells. Interestingly, autophagy was increased in malignant cells exhibiting high levels of signature B, which correlated with an elevated expression of genes involved in cell proliferation and immune checkpoint signaling. Taken together, our analysis reveals a novel autophagy-based signature to define the metabolic and immunogenic status of malignant cells in LUAD. [ABSTRACT FROM AUTHOR]

Simple Summary: Incidence of lung carcinoids is rapidly increasing, but the correct management of these patients is still debated. Although their clinical behaviour differs from Non-Small Cell Lung Cancer, the same staging system is used for these tumors, even if it presents limitations in prognosis prediction and overlapping curves especially regarding sub-stages. For these reasons, in recent years, ad hoc scores have been constructed aiming to better stratify prognosis and indicate appropriate treatment options. In particular, a score including the node ration as nodal factor was proposed, although external validation was not possible. The aim of this study is to validate this score, for the possibility of identifying a specific class of patients that may benefit from specific follow-up schedules or post-operative treatments. Background: A prognostic score including T-dimension, age, histology and lymph node ratio was previously proposed in absence of an external validation dataset. The aim of the current study was to validate the proposed prognostic score using an independent dataset. Methods: Data of patients with lung carcinoids, who underwent surgical resection and lymphadenectomy in five institutions from 1 January 2005 to 31 December 2019, were retrospectively analyzed. Two risk groups were created based on the following data: age, histology, node ratio and pT for disease-free survival (DFS); age, sex, node ratio and pT for overall survival (OS). The previously proposed score was validated, identifying two groups of patients: a high risk (HRG) and low risk (LRG) group. Results: The final analysis was conducted on 283 patients. Regarding DFS, 230 (81.3%) patients were assigned to the LRG and 53 (18.7%) to the HRG. Considering OS, 268 (94.7%) were allocated in the LRG and 15 (5.3%) in the HRG. The 5-year DFS was 92.7% in the LRG vs. 67% in the HRG (p < 0.001) while the 5-year OS was 93.6% in the LRG vs. 86.2% in the HRG (p = 0.29) with clear curve separation. Conclusion: Our analysis confirmed the validity of the composite score for DFS in lung carcinoids. Regarding OS, statistical significance was not reached because of a low number of deaths and patients in the HRG. [ABSTRACT FROM AUTHOR]

Simple Summary: We propose that PFK1 promotes a positive feedback loop with PI3K/AKT and YAP/TAZ signaling pathways in cancer cells. Therefore, targeting PFK1 (or its product F-1,6-BP) could improve the efficacy of PI3K and YAP/TAZ inhibitors currently tested in clinical trials. To this aim, we suggest the use of citrate, which is a physiologic and potent inhibitor of PFK1. PI3K/AKT is one of the most frequently altered signaling pathways in human cancers, supporting the activation of many proteins sustaining cell metabolism, proliferation, and aggressiveness. Another important pathway frequently altered in cancer cells is the one regulating the YAP/TAZ transcriptional coactivators, which promote the expression of genes sustaining aerobic glycolysis (such as WNT, MYC, HIF-1), EMT, and drug resistance. Of note, the PI3K/AKT pathway can also regulate the YAP/TAZ one. Unfortunately, although PI3K and YAP inhibitors are currently tested in highly resistant cancers (both solid and hematologic ones), several resistance mechanisms may arise. Resistance mechanisms to PI3K inhibitors may involve the stimulation of alternative pathways (such as RAS, HER, IGFR/AKT), the inactivation of PTEN (the physiologic inhibitor of PI3K), and the expression of anti-apoptotic Bcl-xL and MCL1 proteins. Therefore, it is important to improve current therapeutic strategies to overcome these limitations. Here, we want to highlight how the glycolytic enzyme PFK1 (and its product F-1,6-BP) promotes the activation of both PI3K/AKT and YAP/TAZ pathways by several direct and indirect mechanisms. In turn, PI3K/AKT and YAP/TAZ can promote PFK1 activity and F-1,6-BP production in a positive feedback loop, thus sustaining the Warburg effect and drug resistance. Thus, we propose that the inhibition of PFK1 (and of its key activator PFK2/PFKFB3) could potentiate the sensitivity to PI3K and YAP inhibitors currently tested. Awaiting the development of non-toxic inhibitors of these enzymes, we propose to test the administration of citrate at a high dosage, because citrate is a physiologic inhibitor of both PFK1 and PFK2/PFKFB3. Consistently, in various cultured cancer cells (including melanoma, sarcoma, hematologic, and epithelial cancer cells), this "citrate strategy" efficiently inhibits the IGFR1/AKT pathway, promotes PTEN activity, reduces Bcl-xL and MCL1 expression, and increases sensitivity to standard chemotherapy. It also inhibits the development of sarcoma, pancreatic, mammary HER+ and lung RAS-driven tumors in mice without apparent toxicities. [ABSTRACT FROM AUTHOR]

Simple Summary: Enhanced Recovery Pathways (ERP) have been scarcely assessed in lung cancer surgery. We performed a two-step audit for our experience: the first dealing with our initial experience focusing on patients undergoing segmentectomies and lobectomies, the second including all subsequent consecutive patients undergoing all kind of lung resections for NSCLC. The first step aimed at auditing results of ERP on occurrence of postoperative complications and at assessing which ERP components were associated with improved short-term outcomes. We also audited late results by assessing long-term survival of patients in the first step of our study. The second step aimed at auditing on large-scale short-term results of the ERP in a real-life setting. In total, 166 patients were included in the first period. No postoperative death occurred. The overall adverse events rate was 30%. In multivariate analyzes, the only element associated with reduced adverse postoperative events was chest tube withdrawal within POD2. The 1-, 3- and 5-year survival rates were 97%, 86.1%, and 76.3%, respectively. In the second period, 1077 patients were included; 11 patients died during the postoperative period. The overall postoperative adverse event rate was 30.3%. Thoracoscore independently predicted postoperative death, the occurrence of complications (all-kind, minor, major, or respiratory ones). We conclude that compliance to ERP procedures and early chest tube removal are associated with reduced postoperative events in patients with lung resection surgery. Thoracoscore is a useful tool in predicting mortality and postoperative adverse events. Introduction: In spite of increasing diffusion, Enhanced Recovery Pathways (ERP) have been scarcely assessed in large scale programs of lung cancer surgery. The aim of this study was auditing our practice. Methods: A two-step audit program was established: the first dealing with our initial ERP experience in patients undergoing non-extended anatomical segmentectomies and lobectomies, the second including all consecutive patients undergoing all kind of lung resections for NSCLC. The first step aimed at auditing results of ERP on occurrence of postoperative complications and at assessing which ERP components are associated with improved short-term outcomes. We also audited late results by assessing long-term survival of patients in the first step of our study. The second step aimed at auditing on large-scale short-term results of the ERP in a real-life setting. Results: Over a one-year period, 166 patients were included. The median number of ERP procedures per patient was three (IQR 3–4). No postoperative death occurred. The overall adverse events rate was 30%. In multivariate analyzes, the only element associated with reduced adverse postoperative events was chest tube withdrawal within POD2 (OR = 0.21, 95% CI (0.10–0.46)). The 1-, 3-, and 5-year survival rates were 97%, 86.1%, and 76.3%, respectively. In the second period, 1077 patients were included in our ERP; 11 patients died during the postoperative period or within 30 days of operation (1.02%). The overall postoperative adverse event rate was 30.3%, major complication occurring in 134 (12.4%), and minor ones in 192 (17.8%). Respiratory complications occurred in 64 (5.9%). Thoracoscore independently predicted postoperative death, the occurrence of complications (all-kind, minor, major, or respiratory ones). Conclusions: Compliance to ERP procedures and early chest tube removal are associated with reduced postoperative events in patients with lung resection surgery. In a large setting scale, ERP can be applied with satisfactory results in terms of mortality and morbidity. Thoracoscore is a useful tool in predicting mortality and postoperative adverse events. [ABSTRACT FROM AUTHOR]

Simple Summary: Surgery is the mainstay treatment of non-small-cell lung cancer, but its impact on survival beyond 15 years has never been reported so far. We studied retrospectively clinical characteristics and short and long-term survival of a single-institution patient population whose baseline data were prospectively collected. All patients underwent major lung resection between June 2001 and December 2002. Vital status was obtained by checking INSEE database and verifying if reported as "non-death" by the hospital administrative database and direct phone interviews with patients of families. A total of 345 patients were analyzed; 15-year and 20-year overall survival rates were 12.2% and 5.7%, respectively. At univariate analysis, predictors of worse survivals were increasing age at surgery, lower BMI, weight loss, higher baseline C-reactive protein, pathological stage, and, among patients with adenocarcinoma, higher grade. Increasing age, cumulative smoking, lower BMI, and pathological stage were independent predictors of long-term survival at Cox multivariate analysis. We conclude that very-long-term survivals can be achieved after surgery of NSCLC, and factors classically predicting 5- and 10-years survival also determines longer outcomes suggesting that both initial tumor aggressiveness and host characteristics act beyond the period usually taken into account in oncology. Surgery is the mainstay treatment of non-small-cell lung cancer (NSCLC), but its impact on very-long-term survival (beyond 15 years) has never been evaluated. Methods: All patients operated on for major lung resection (Jun. 2001–Dec. 2002) for NSCL in the Thoracic Surgery Department at Paris-Hôtel-Dieu-University-Hospital were included. Patients' characteristics were prospectively collected. Vital status was obtained by checking INSEE database and verifying if reported as "non-death" by the hospital administrative database and direct phone interviews with patients of families. Results: 345 patients were included. The 15- and 20-year survival rates were 12.2% and 5.7%, respectively. At univariate analysis, predictors of worse survivals were: increasing age at surgery (p = 0.0042), lower BMI (p = 0.009), weight loss (p = 0.0034), higher CRP (p = 0.049), pathological stage (p = 0.00000042), and, among patients with adenocarcinoma, higher grade (p = 0.028). Increasing age (p = 0.004), cumulative smoking (p = 0.045), lower BMI (0.046) and pathological stage (p = 0.0026), were independent predictors of long-term survival at Cox multivariate analysis. In another model, increasing age (p = 0.013), lower BMI (p = 0.02), chronic bronchitis (p = 0.03), lower FEV1% (p = 0.00019), higher GOLD class of COPD (p = 0.0079), and pathological stage (p = 0.000024), were identified as independent risk factors. Conclusions: Very-long-term survivals could be achieved after surgery of NSCLC, and factors classically predicting 5- and 10-years survival also determined longer outcomes suggesting that both initial tumor aggressiveness and host's characteristics act beyond the period usually taken into account in oncology. [ABSTRACT FROM AUTHOR]

Currently, the clinical impact of cell therapy after a myocardial infarction (MI) is limited by low cell engraftment due to low cell retention, cell death in inflammatory and poor angiogenic infarcted areas, secondary migration. Cells interact with their microenvironment through integrin mechanoreceptors that control their survival/apoptosis/differentiation/migration and proliferation. The association of cells with a three-dimensional material may be a way to improve interactions with their integrins, and thus outcomes, especially if preparations are epicardially applied. In this review, we will focus on the rationale for using collagen as a polymer backbone for tissue engineering of a contractile tissue. Contractilities are reported for natural but not synthetic polymers and for naturals only for: collagen/gelatin/decellularized-tissue/fibrin/Matrigel™ and for different material states: hydrogels/gels/solids. To achieve a thick/long-term contractile tissue and for cell transfer, solid porous compliant scaffolds are superior to hydrogels or gels. Classical methods to produce solid scaffolds: electrospinning/freeze-drying/3D-printing/solvent-casting and methods to reinforce and/or maintain scaffold properties by reticulations are reported. We also highlight the possibility of improving integrin interaction between cells and their associated collagen by its functionalizing with the RGD-peptide. Using a contractile patch that can be applied epicardially may be a way of improving ventricular remodeling and limiting secondary cell migration. [ABSTRACT FROM AUTHOR]

Simple Summary: It is commonly believed that obesity increases the risk of cancers and lowers the possibility of cure of patients with proven cancers. In recent years, this traditional view has been challenged by the hypothesis of an 'obesity paradox', which refers to a better prognosis in obese patients with some specific cancers, compared to normal/underweight patients. In this study, we assessed, in a nationwide dataset, the prognostic role of preoperative BMI on postoperative outcomes in patients undergoing curative lung resection for non-small-cell lung cancer (NSCLC) and found that BMI is a strong and independent predictor of long-term survival. Obesity could have a protective effect in patients with lung cancer. We assessed the prognostic role of preoperative BMI on survival in patients who underwent lung resection for NSCLC. A total of 54,631 consecutive patients with resectable lung cancer within a 15-year period were extracted from Epithor (the French Society of Thoracic and Cardiovascular Surgery database). Patient subgroups were defined according to body mass index (BMI): underweight (BMI < 18.5 kg/m2), normal weight (18.5 ≤ BMI < 25 kg/m2), overweight (25 ≤ BMI < 30 kg/m2), and obese (BMI ≥ 30 kg/m2). Underweight was associated with lower survival (unadjusted HRs 1.24 (1.16–1.33)) compared to normal weight, whereas overweight and obesity were associated with improved survival (0.95 (0.92–0.98) and 0.88 (0.84–0.92), respectively). The impact of BMI was confirmed when stratifying for sex or Charlson comorbidities index (CCI). Among patients with obesity, a higher BMI was associated with improved survival. After adjusting for period of study, age, sex, WHO performance status, CCI, side of tumor, extent of resection, histologic type, and stage of disease, the HRs for underweight, overweight, and obesity were 1.51 (1.41–1.63), 0.84 (0.81–0.87), and 0.80 (0.76–0.84), respectively. BMI is a strong and independent predictor of survival in patients undergoing surgery for NSCLC. [ABSTRACT FROM AUTHOR]

Despite advances, malignant pleural mesothelioma (MPM) remains a challenging disease in terms of diagnosis, treatment, and overall management. Herein, we analyzed, in a large-scale single-center cohort, the characteristics and perioperative course of patients undergoing surgical diagnosis of MPM. We identified a total of 514 consecutive patients, 71.4% male and 28.6% female, with mean age 71.3 +/− 13.6 years. Most exhibited pleural, respiratory, or general symptoms and American Society of Anesthesiologists (ASA) score was ≥3 in 68.3% of cases. Thoracoscopy was the most frequent approach (92.0%) and short open thoracotomy was performed in the remaining patients. Pleurodesis was simultaneously performed in 74.3% of cases. Diagnostic failure led to redo surgery in 3.7% of patients. Non-epithelioid histology was found in 19.5% of MPMs and was significantly more frequent in right-sided MPM (p = 0.04), and in patients without history of cancer (p = 0.03), or pleural nodules at thoracoscopy (p = 0.01). Minor only or major complications occurred in respectively 7.8% and 3.6% of cases. They were more frequent in patients ≥ 70 years (p = 0.05) and Performance Status > 2 (p = 0.05). The mean hospital stay was 7.5 days. The 30-day and 90-day early mortality rates were 2.3% and 6.4%, respectively. Surgical diagnosis of MPM is a reliable procedure but is associated with significant morbidity and hospital-stay duration. [ABSTRACT FROM AUTHOR]

Simple Summary: Lung cancer continues to be one of the leading cause of cancer-related deaths. In multimodality management of non-small cell lung cancer, surgery remains the mainstay, and in particular, pneumonectomy remains the only possible surgical procedure in patients with centrally located lesions. However, despite improvements in technique and perioperative management, it continues to be associated with significant postoperative mortality. Thus, identifying patients at high postoperative risk is of paramount importance to select surgical candidates, but identifying patients more likely to achieve definitive cure after surgery is at least as important. Among all the evaluated parameters, we found that being sarcopenic at both psoas and parietal muscles is an independent negative prognostic factor of overall survival. The whole muscular area had the best predictive value among all of the tested factors evaluating sarcopenia. 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. [ABSTRACT FROM AUTHOR]

Hypothesizing that pulmonary artery diameter is a marker of subclinical pulmonary hypertension, we assessed its impact on postoperative outcome in patients requiring pneumonectomy. Morphometric, clinical, and laboratory data were retrospectively retrieved from files of 294 consecutive patients treated by pneumonectomy for malignancy (289 NSCLC). Pulmonary artery was measured at bifurcation level on CT scan and normalized by body surface area. Median normalized pulmonary artery diameter (cut-off for analyses) was 14 mm/m2. Postoperatively, 46 patients required re-do intubation and 30 had acute respiratory distress syndrome (ARDS). Multivariate analysis showed that Charlson Comorbidity Index >5 (p = 0.0009, OR 3.8 [1.76–8.22]), right side of pneumonectomy (p = 0.013, OR 2.37 [1.20–4.71]), and higher normalized pulmonary artery diameter (p = 0.029, OR 2.16 [1.08–4.33]) were independent predictors of re-do intubation, while Charlson Comorbidity Index >5 (p = 0.018, OR 2.55 [1.17–5.59]) and higher normalized pulmonary artery diameter (p = 0.028, OR = 2.52 [1.10–5.77]) were independently associated with occurrence of ARDS. Post-operative mortality was 8.5%. Higher normalized pulmonary artery diameter, (p = 0.026, OR 3.39 [1.15–9.95]), right side of pneumonectomy (p = 0.0074, OR 4.11 [1.46–11.56]), and Charlson Comorbidity Index >5 (p = 0.0011, OR 5.56 [1.99–15.54]) were independent predictors of postoperative death. We conclude that pre-operative normalized pulmonary artery diameter predicts the risk of re-do intubation, ARDS and mortality in patients undergoing pneumonectomy for cancer. [ABSTRACT FROM AUTHOR]

A large interindividual variability has been observed in anti Programmed cell Death 1 (anti-PD1) therapies efficacy. The aim of this study is to assess the correlation of soluble PD-1 (sPD-1), soluble Programmed cell Death Ligand 1 (sPD-L1), Vascular Endothelial Growth Factor A (VEGFA), soluble CD40 ligand (sCD40L) and soluble CD44 (sCD44), with survival in nivolumab-treated metastatic non-small cell lung cancer (NSCLC) patients. Plasma biomarkers were assayed at baseline and after two cycles of nivolumab. A cut-off of positivity for sPD-1, sPD-L1 and sCD40L expressions was defined as a plasma level above the lower limit of quantification. Baseline sPD-1 and sPD-L1 levels were subsequently analyzed in a control group of EGFR-mutated (Epidermal Growth Factor Receptor) NSCLC patients. Association between survival and biomarkers was investigated using Cox proportional hazard regression model. Eighty-seven patients were included (51 nivolumab-treated patients, 36 in EGFR-mutated group). In nivolumab group, baseline sPD-1, sPD-L1 and sCD40L were positive for 15(29.4%), 27(52.9%) and 18(50%) patients, respectively. We defined a composite criteria (sCombo) corresponding to sPD-1 and/or sPD-L1 positivity for each patient. In nivolumab group, baseline sCombo positivity was associated with shorter median progression-free survival (PFS) (78 days 95%CI (55–109) vs. 658 days (222-not reached); HR: 4.12 (1.95–8.71), p = 0.0002) and OS (HR: 3.99(1.63–9.80), p = 0.003). In multivariate analysis, baseline sCombo independently correlated with PFS (HR: 2.66 (1.17–6.08), p = 0.02) but not OS. In EGFR-mutated group, all patients were baseline sCombo positive; therefore this factor was not associated with survival. After two cycles of nivolumab, an increased or stable sPD-1 level independently correlated with longer PFS (HR: 0.49, 95%CI (0.30–0.80), p = 0.004) and OS (HR: 0.39, 95%CI (0.21–0.71), p = 0.002). VEGFA, sCD40L and sCD44 did not correlate with survival. We propose a composite biomarker using sPD-1and sPDL-1 to predict nivolumab efficacy in NSCLC patients. A larger validation study is warranted. [ABSTRACT FROM AUTHOR]

Lower pre-surgery Body Mass Index (BMI) and low muscle mass impact negatively long-term survival of non-small cell lung cancer (NSCLC). We investigated their influence on survival after major lung resection for NSCLC. Methods: A retrospective analysis of a prospectively collected database was made on 304 consecutive patients. Results: Underweight, normal, overweight and obese patients represented 7.6%, 51.6%, 28.6%, and 12.6% of the pre-disease population. Weight loss and gain were recorded in 44.4% and 5% of patients, respectively. Low muscle mass was more frequently associated with BMI < 25 kg/m2 (p < 0.000001). Overall survival was positively affected by pre-disease (p = 0.036) and pre-surgery (p = 0.017) BMI > 25 kg/m2, and, even more, in case of BMI > 25 kg/m2 and increasing weight (p = 0.012). Long-term outcome was negatively influenced by low muscle mass (p = 0.042) and weight loss (p = 0.0052) as well as age (p = 0.017), ASA categories (p = 0.025), extent of resection (p = 0.0001), pleural invasion (p = 0.0012) and higher pathologic stage (p < 0.0001). Three stepwise multivariable models confirmed the independent favorable prognostic value of higher pre-disease (RR 0.66[0.49–0.89], p = 0.006) and pre-surgery BMI (RR 0.72[0.54–0.98], p = 0.034), and the absence of low muscle mass (RR 0.56[0.37–0.87], p = 0.0091). Conclusions: Body reserves assessed by simple clinical markers impact survival of surgically treated NSCLC. Strategies improving body fat and muscular mass before surgery should be considered. [ABSTRACT FROM AUTHOR]