NSCLC Group Research Articles

Clinical value of Hemoglobin in Combination with Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio as a Prognostic Factor in Advanced Lung Cancer

The absence of effective prognostic factors for assessing the survival outlook of patients with lung cancer has not significant improvement. Thus, this study aims to investigate the potential of a combination of serum haptoglobin (Hp), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) in blood as reliable prognostic markers for lung cancer patients. There were 62 lung cancer patients (male and female) at advanced stage (stage III and IV) with age mean (65.25) years, and 62 healthy participants with age mean 64.27 years. The levels of some hematological parameters were estimated by a hematology analyzer. Heptoglobin level was evaluated in serum by ELISA technology. There was significant increase in mean of haptoglobin, NLR, and PLR in SCLC (3.43 ±0.16, 2.47±0.88, and 221 ±23.21, respectively) and NSCLC groups (3.64 ±0.09, 3.68±1.3, and 210.26±12.6, respectively) compared with control group. Haptoglobin, NRL and PRL did not differ significantly between SCLC and NSCLC. The results indicate that the mean haptoglobin, NLR, and PLR were significantly increased in lung cancer group in contrast to controls and also showed a positive association with the severity of the disease, where they increased in patients at stage IV and receiving chemotherapy for 2 months. This makes them possible markers for prognostic advanced lung cancer and predictive responses to chemotherapy in lung cancer patients.

Machine learning prediction models for different stages of non-small cell lung cancer based on tongue and tumor marker: a pilot study

ObjectiveTo analyze the tongue feature of NSCLC at different stages, as well as the correlation between tongue feature and tumor marker, and investigate the feasibility of establishing prediction models for NSCLC at different stages based on tongue feature and tumor marker.MethodsTongue images were collected from non-advanced NSCLC patients (n = 109) and advanced NSCLC patients (n = 110), analyzed the tongue images to obtain tongue feature, and analyzed the correlation between tongue feature and tumor marker in different stages of NSCLC. On this basis, six classifiers, decision tree, logistic regression, SVM, random forest, naive bayes, and neural network, were used to establish prediction models for different stages of NSCLC based on tongue feature and tumor marker.ResultsThere were statistically significant differences in tongue feature between the non-advanced and advanced NSCLC groups. In the advanced NSCLC group, the number of indexes with statistically significant correlations between tongue feature and tumor marker was significantly higher than in the non-advanced NSCLC group, and the correlations were stronger. Support Vector Machine (SVM), decision tree, and logistic regression among the machine learning methods performed poorly in models with different stages of NSCLC. Neural network, random forest and naive bayes had better classification efficiency for the data set of tongue feature and tumor marker and baseline. The models’ classification accuracies were 0.767 ± 0.081, 0.718 ± 0.062, and 0.688 ± 0.070, respectively, and the AUCs were 0.793 ± 0.086, 0.779 ± 0.075, and 0.771 ± 0.072, respectively.ConclusionsThere were statistically significant differences in tongue feature between different stages of NSCLC, with advanced NSCLC tongue feature being more closely correlated with tumor marker. Due to the limited information, single data sources including baseline, tongue feature, and tumor marker cannot be used to identify the different stages of NSCLC in this pilot study. In addition to the logistic regression method, other machine learning methods, based on tumor marker and baseline data sets, can effectively improve the differential diagnosis efficiency of different stages of NSCLC by adding tongue image data, which requires further verification based on large sample studies in the future.

The Comparison of Serum Exosome Protein Profile in Diagnosis of NSCLC Patients.

A thorough study of the exosomal proteomic cargo may enable the identification of proteins that play an important role in cancer development. The aim of this study was to compare the protein profiles of the serum exosomes derived from non-small lung cancer (NSCLC) patients and healthy volunteers (control) using the high-performance liquid chromatography coupled to mass spectrometry (HPLC-MS) method to identify potentially new diagnostic and/or prognostic protein biomarkers. Proteins exclusively identified in NSCLC and control groups were analyzed using several bioinformatic tools and platforms (FunRich, Vesiclepedia, STRING, and TIMER2.0) to find key protein hubs involved in NSCLC progression and the acquisition of metastatic potential. This analysis revealed 150 NSCLC proteins, which are significantly involved in osmoregulation, cell-cell adhesion, cell motility, and differentiation. Among them, 3 proteins: Interleukin-34 (IL-34), HLA class II histocompatibility antigen, DM alpha chain (HLA-DMA), and HLA class II histocompatibility antigen, DO beta chain (HLA-DOB) were shown to be significantly involved in the cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs) infiltration processes. Additionally, detected proteins were analyzed according to the presence of lymph node metastasis, showing that differences in frequency of detection of protein FAM166B, killer cell immunoglobulin-like receptor 2DL1, and olfactory receptor 52R1 correlate with the N feature according to the TNM Classification of Malignant Tumors. These results prove their involvement in NSCLC lymph node spread and metastasis. However, this study requires further investigation.

Durvalumab in Combination With Olaparib Versus Durvalumab Alone as Maintenance Therapy in Metastatic NSCLC: The Phase 2 ORION Study

IntroductionIncreased DNA damage triggered through poly (ADP-ribose) polymerase inhibition may modify tumor immunogenicity, sensitizing tumors to immunotherapy. ORION (NCT03775486) evaluated the combination of olaparib with durvalumab as maintenance therapy in patients with metastatic NSCLC. MethodsORION is a phase 2, randomized, multicenter, double-blind, international study. Patients with metastatic NSCLC (without activating EGFR or ALK aberrations) and Eastern Cooperative Oncology Group performance status of 0 or 1 were enrolled to receive initial therapy with durvalumab (1500 mg intravenously; every 3 wk) plus platinum-based chemotherapy for four cycles. Patients without disease progression were then randomized (1:1) to maintenance durvalumab (1500 mg; every 4 wk) plus either olaparib (300 mg orally) or placebo (both twice daily); randomization was stratified by objective response during initial therapy and tumor histologic type. The primary end point was investigator-assessed progression-free survival (PFS) (Response Evaluation Criteria in Solid Tumors version 1.1). ResultsBetween January 2019 and February 2020, 269 of 401 patients who received initial therapy were randomized. As of January 11, 2021 (median follow-up: 9.6 mo), median PFS was 7.2 months (95% confidence interval: 5.3–7.9) with durvalumab plus olaparib versus 5.3 months (3.7–5.8) with durvalumab plus placebo (hazard ratio = 0.76, 95% confidence interval: 0.57–1.02, p = 0.074). Safety findings were consistent with the known profiles of durvalumab and olaparib. Anemia was the most common adverse event (AE) with durvalumab plus olaparib (26.1% versus 8.2% with durvalumab plus placebo). The incidence of grade 3 or 4 AEs (34.3% versus 17.9%) and AEs leading to treatment discontinuation (10.4% versus 4.5%) was numerically higher with durvalumab plus olaparib versus durvalumab plus placebo. ConclusionsMaintenance therapy with durvalumab in combination with olaparib was not associated with a statistically significant improvement in PFS versus durvalumab alone, although numerical improvement was observed.

Glycoprofiling of early non-small cell lung cancer using lectin microarray technology

Abstract Objectives Non-small cell lung cancer (NSCLC) is one of the most common malignancies in the world with a high incidence and it lacks effective biomarkers for early-stage detection. In this investigation, we aimed to investigate the alterations in plasma glycans related to NSCLC and assess the possibility of plasma glycopatterns as potential biomarkers for the diagnosis of NSCLC. Methods First, plasma samples from 16 patients with early-stage lung adenocarcinoma (LUAD), 16 patients with early-stage Lung squamous cell carcinoma (LUSC), and 16 healthy volunteers, were selected for inclusion in this study to probe the difference in plasma glycopatterns using lectin microarrays. Then, the diagnostic effectiveness of the candidate lectins was evaluated using ROC. Results In contrast to the NL group, seven candidate lectins offered potential diagnostic utility in the NSCLC (LUAD and LUSC) group. F17AG was significantly altered in LUSC with an AUC of 0.818 (adj.P.Val<0.05) compared to NL samples. There were 20 differentially expressed lectins in the LUAD group compared to the NL group. Based on the AUC values (AUC>0.800) and the normalized fluorescence intensities of the lectins, we selected eight lectins, GAL2, PTL-1, GNA, SSA, LENTIL, CA, PHA-E, and MAA to perform logistic regression analysis, and found that the combination of these eight candidate lectins had high diagnostic potential. Conclusions The results of this study should help to distinguish between NSCLC and NL based on changes in plasma glycopatterns, which have a great deal of potential to be biomarkers for diagnosing NSCLC.

Validating the use of machine-learning cancer staging algorithms for Medicare cost analyses.

e13548 Background: Administrative claims provide valuable real-world insight into the care of cancer patients; however, claims data lacks cancer stage information. This limitation constrains research on the value of early diagnosis and treatment as well as on the costs and savings associated with increased cancer screening. In prior work, our team used the SEER-Medicare data to develop machine learning (ML) algorithms to stage non-small cell lung (NSCLC), colon (CC), and rectal (RC) cancer patients using clinical flags derived from claims data. These algorithms were 69% (RC), 78% (NSCLC), and 83% (CC) accurate at matching incident cancer patients with their SEER-recorded AJCC stage (SEER-stage) at diagnosis. This work sought to test whether these ML algorithms are sufficiently accurate for use in claim cost analyses. Methods: Incident NSCLC, CC, and RC patients were identified using 2016-2017 SEER-Medicare data and assigned a cancer stage using a claims-based predictive multinomial logistic regression model (R Statistical Software - v4.1.2 R Core Team 2021; nnet package - Venables and Ripley 2002). Patients’ cumulative medical and pharmacy costs were summarized for 12 months starting with patients’ index month. Patients’ Medicare index month was set equal to the month of their first claim with a cancer diagnosis. Patients’ SEER index month was set equal to the diagnosis month associated with their incident tumor record in SEER. Patients with each cancer type were then grouped two ways - by ML-stage and by SEER-stage. Median patient costs were compared between stage groups for each cancer type and differences tested for statistical significance using Wilcoxon Rank-Sum Testing. Results: For NSCLC and CC, raw differences in median 12-month claim costs between the ML- and SEER-stage cohorts were small (1%-4%). Cost differences for RC were higher (7%-17%). ML and SEER costs were not significantly different (p > 0.05) between later-stage cohorts (NSCLC stages 3 and 4, CC stages 2C/3 and 4, and RC stage 4); however, early-stage groups were always significantly different (p < 0.05). Conclusions: Although costs were not statistically equivalent across all stage groups, the similarity of ML and SEER costs across higher-stage cohorts and small raw differences in median costs for each NSCLC and CC group suggests that ML algorithms with higher accuracy may be used to develop costs from administrative data for stage shift modeling and cost tradeoff analyses. [Table: see text]

Abstract 2772: A novel bio-physical based CDA approach for evaluating lung cancer therapeutic responses

Abstract Background: Lung cancer is the world's highest mortality and incidence rate of malignancy, and the prognosis survival rate is significantly lower than other tumors. A novel bio-physics based multi (pan)-cancer test technology named Cancer Differentiation Analysis Technology (CDA) has been developed and investigated for evaluating and monitoring lung cancer therapeutic responses. Methods: A total of 686 patients diagnosed with different sub-types of lung cancer were included in this study. CDA levels were concurrently measured in peripheral blood obtained from 686 patients during the treatment. According to the response evaluation criteria in solid tumors (RECIST) 1.1 standard, the efficacy of 686 patients after treatment was evaluated, and the diagnostic efficacy of CDA technology was evaluated by receiver operating characteristic (ROC) curve. Results: Clinical pathological parameters of the patients are listed in Table 1. The higher the CDA value, the worse the curative effect. CDA value of lung cancer in CR (complete response) group was significantly lower than that in other 3 groups (p<0.05). CDA value of adenocarcinoma lung cancer in CR group were significantly lower than that in SD (stable disease) group (p<0.05). For non - metastatic lung cancer, CDA value in CR group was significantly lower than that in SD group (p<0.05) The receiver ROC analysis showed that the area under curve (AUC) of lung cancer group, NSCLC group, adenocarcinoma lung cancer group, were 0.756, 0.772, and 0.792, respectively. The AUC of early lung cancer group, and non - metastatic lung cancer group were 0.794, and 0.851. Conclusions: CDA appears to have the ability to predict and monitor therapeutic responses to lung cancer surgery and chemotherapy treatments. In most cases, the CDA of CR patients is low, and there is a good correlation between CDA and curative effect in early lung cancer. CDA could be a potential candidate for evaluating lung cancer, especially for early stage lung cancer therapeutic response. Citation Format: Junjie Wu, Zixiu Zou, Xuedong Du, Yue Lin, Xing Tang, Jie Chen, Lan Peng, Chris Yu. A novel bio-physical based CDA approach for evaluating lung cancer therapeutic responses [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2772.

Comparative study of clinico-radiological pattern of patients with small cell and non small cell lung cancer

Bronchogenic carcinoma is a malignant neoplasm of the lung arising from the epithelium of the bronchus. NSCLCs are a heterogeneous group, of which the most common subtypes are squamous cell carcinoma and adenocarcinoma. Squamous cell carcinomas are also predominantly linked to smoking. This study is planned to describe the clinical and radiological presentation of Small cell and Non-small cell lung cancer. The study included one hundred thirty patients admitted in various wards of hospital in chest Diseases and Tuberculosis & General Medicine department, at National institute of medical science & research, Jaipur between January, 2021 and December, 2021. Only those patients diagnosed as Primary lung cancer were included in this study. The present study included 130 proven cases of lung cancer. Two major histo-types of lung cancer SCLC and NSCLC were then correlated with their clinical and radiological features. 65 patients of each group were selected for study. Cough (with or without expectoration) was the common symptom (83.08%) observed in lung cancer patients. Chest pain was the next common symptom (80.77%) and had similar distribution in SCLC and NSCLC group patients. weight loss and Dyspnoea were the next common symptom observed.

198P Association between BTLA polymorphisms and NSCLC risk

Importance of immune checkpoints molecules in NSCLC was proven by the introduction of blockade of these receptors in routine treatment. B and T lymphocyte attenuator (BTLA) is another immune checkpoint molecule that regulates immune response. Our previous studies showed a significant association between BTLA gene variants and susceptibility to renal cell carcinoma and chronic lymphoblastic leukemia. The aim of this study was to verify the hypothesis that BTLA polymorphic variants are associated with susceptibility to NSCLC. Genomic DNA was isolated from the venous blood of 384 patients diagnosed with NSCLC and 475 controls. Using TaqMan probes we genotyped seven BTLA SNPs: rs1982809, rs1844089, rs9288952, rs9288953, rs2705511, rs2633582, and rs11921669 on ViiA 7 Real-Time PCR System. Statistical analysis of genotypes and alleles distributions for all investigated BTLA SNPs showed that SNP rs1982809 may be associated with susceptibility to NSCLC. In particular presence of G allele at rs1982809 (AG+GG genotypes) was more frequent in NSCLC group compared to controls (38.8% vs 45.3%, p=0.056). Allele distribution showed that the presence of allele G in rs1982809 significantly increases NSCLC risk (OR=1.25, p=0.046). For other studied SNPs in the overall analysis, we did not observe differences between NSCLC patients and controls. However, in the subgroup analysis we found that in patients with adenocarcinoma (AD) genotypes distribution of rs1982809 was significantly different between AD patients and controls (p=0.048). Moreover, we noticed the trend for overrepresentation of rs2705511[C] allele (AC+CC genotypes) in patients with AD compared to controls (43.4% vs 53%, p=0.079). After stratification by gender, we observed an association between the presence of rs9288953[T] and NSCLC susceptibility (p=0.004) in females. The global distributions of the haplotypes did not differ significantly between the cases and controls. However, we noticed that the global distribution of the haplotypes differs significantly between the never-smokers and smokers (p=0.0003). Results of our study show that rs1982809 in BTLA gene might be considered a low penetrating risk factor for NSCLC susceptibility in the Polish population.

Siglec15 facilitates the progression of non-small cell lung cancer and is correlated with spinal metastasis.

BackgroundNon-small cell lung cancer (NSCLC) frequently metastasizes to bone, leading to poor prognosis. Siglec15 has been identified as a newly discovered immune checkpoint and exists in a variety of tumors. However, the expression and function of Siglec15 in NSCLC and bone metastasis remains largely unclear.MethodsSiglec15 expression in NSCLC and the correlation between Siglec15 expression and the clinicopathological factors of patients with NSCLC were analyzed using The Cancer Genome Atlas (TCGA) dataset. Correlation analysis between Siglec15 and bone metastasis-related genes expression was based on the Molecular Signatures Database (MSigDB). Western blotting and immunohistochemistry were applied to detect Siglec15 expression in NSCLC and spinal metastasis. Human A549 and mouse CMT167 cells were transfected with Siglec15 siRNA to investigate its biological functions in NSCLC proliferation, migration, and invasion. The immune-related signaling pathways and correlations between Siglec15 and tumor-infiltrating immune cells and different immune checkpoints in the NSCLC tumor microenvironment (TME) were analyzed using Estimating Relative Subsets of RNA Transcripts (CIBERSORT) and gene set enrichment analysis (GSEA). To demonstrate Siglec15 in NSCLC cell-mediated T cell suppression and investigate the potential mechanism of Siglec15 silencing in antitumor immunity, we used a T cell killing assay in vitro and the high‑throughput sequencing approach.ResultsSiglec15 expression was positively associated with the tumor stage and lymph node metastasis, and was markedly up-regulated in NSCLC bone metastasis. Functionally, Siglec15 knockdown inhibited the proliferation, migration, and invasion of NSCLC cells (A549 and CMT167 cell lines). A total of eight kinds of tumor-infiltrating immune cells were found to have a strong association with the Siglec15 expression in NSCLC cases. The expression of previously discovered immune checkpoints was higher in the high Siglec15 expression NSCLC group. Furthermore, an in vitro T cell killing assay showed that the down-regulation of Siglec15 in tumor cells could enhance the antitumor immune responses of CD8+ T cells. High‑throughput sequencing revealed the potential molecular mechanisms underlying the Siglec15-mediated immunosuppression effect of tumor cells on immune cells.ConclusionsSiglec15 may be involved in the pathogenesis of spinal metastasis in NSCLC and provide a new potential therapeutic target for the treatment of NSCLC and bone metastasis.

Differentiation of brain metastases originating from lung and breast cancers using apparent diffusion coefficient histogram analysis and the relation of histogram parameters with Ki-67.

A fast, reliable and non-invasive method is required in differentiating brain metastases (BMs) originating from lung cancer (LC) and breast cancer (BC). The aims of this study were to assess the role of histogram analysis of apparent diffusion coefficient (ADC) maps in differentiating BMs originated from LC and BC, and then to investigate further the association of ADC histogram parameters with Ki-67 index in BMs. A total of 55 patients (LC, N = 40; BC, N = 15) with BMs histopathologically confirmed were enrolled in the study. The LC group was divided into small-cell lung cancer (SCLC; N = 15) and non-small-cell lung cancer (NSCLC; N = 25) groups. ADC histogram parameters (ADCmax, ADCmean, ADCmin, ADCmedian, ADC10, ADC25, ADC75 and ADC90, skewness, kurtosis and entropy) were derived from ADC maps. Mann-Whitney U-test, independent samples t-test, receiver operating characteristic (ROC) analysis and Spearman correlation analysis were used for statistical assessment. ADC histogram parameters did not show significant differences between LC and BC groups (p > 0.05). Subgroup analysis showed that various ADC histogram parameters were found to be statistically lower in the SCLC group compared to the NSCLC and BC groups (p < 0.05). ROC analysis showed that ADCmean and ADC10 for differentiating SCLC BMs from NSCLC, and ADC25 for differentiating SCLC BMs from BC achieved optimal diagnostic performances. Various histogram parameters were found to be significantly correlated with Ki-67 (p < 0.05). Histogram analysis of ADC maps may reflect tumoural proliferation potential in BMs and can be useful in differentiating SCLC BMs from NSCLC and BC BMs.

Molecular Identification and Genetic Characterization of Early-Stage Multiple Primary Lung Cancer by Large-Panel Next-Generation Sequencing Analysis.

ObjectiveThe incidence of early stage multiple primary lung cancer (MPLC) has been increasing in recent years, while the ideal strategy for its diagnosis and treatment remains controversial. The present study conducted genomic analysis to identify a new molecular classification method for accurately predicting the diagnosis and therapy for patients with early stage MPLC.MethodsA total of 240 tissue samples from 203 patients with multiple-non-small-cell lung cancers (NSCLCs) (n = 30), early stage single-NSCLC (Group A, n = 94), and advanced-stage NSCLC (Group B, n = 79) were subjected to targeted multigene panel sequencing.ResultsThirty patients for whom next-generation sequencing was performed on >1 tumor were identified, yielding 45 tumor pairs. The frequencies of EGFR, TP53, RBM10, ERBB2, and CDKN2A mutations exhibited significant differences between early and advanced-stage NSCLCs. The prevalence of the EGFR L858R mutation in early stage NSCLC was remarkably higher than that in advanced-stage NSCLC (P = 0.047). The molecular method classified tumor pairs into 26 definite MPLC tumors and four intrapulmonary metastasis (IM) tumors. A high rate of discordance in driver genetic alterations was found in the different tumor lesions of MPLC patients. The prospective Martini histologic prediction of MPLC was discordant with the molecular method for three patients (16.7%), particularly in the prediction of IM (91.7% discordant).ConclusionsComprehensive molecular evaluation allows the unambiguous delineation of clonal relationships among tumors. In comparison, the Martini and Melamed criteria have notable limitations in the recognition of IM. Our results support the adoption of a large panel to supplement histology for strongly discriminating NSCLC clonal relationships in clinical practice.

Impact of ALK Rearrangement on Venous and Arterial Thrombotic Risk in NSCLC.

Clinical venous thromboembolism (VTE) risk prediction scores, such as the Khorana Risk Score, perform poorly in NSCLC, possibly because the tumor molecular subtype is omitted. Previous studies suggest a possible increased VTE risk in ALK-rearranged NSCLC, but data are conflicting. We performed a retrospective cohort study of patientswith advanced-stage NSCLC diagnosed between 2009 and 2019. Multivariable, time-to-event analyses modeling the risk of first venous or arterial thrombosis in ALK and non-ALK NSCLC groups, controlling for covariates known to impact thrombosis risk (15 in VTE model and 17 in arterial thrombosis model), were performed using Cox proportional hazards regression and competing-risks regression. Multivariable negative binomial regression modeled the total VTE rate. A total of 422 patients with ALK-rearranged and 385 patients with non-ALK-rearranged NSCLC were included. Patientswith an ALK rearrangement were younger, had better performance status, and had lower rates of most thrombotic risk factors but had significantly higher rates of initial VTE (42.7% versus 28.6%, p < 0.0001), recurrent VTE (13.5% versus 3.1%, p < 0.0001), and similar rates of arterial thrombosis (5.0% versus 4.4%, p = 0.71) compared with non-ALK NSCLC. VTE risk attributable to ALK was significant (Coxmodel: hazard ratio 3.70, [95% confidence interval [CI]: 2.51-5.44, p < 0.001], competing risks: subhazard ratio 3.91 [95% CI: 2.55-5.99, p < 0.001]). Negative binomial modeling revealed higher VTE rates in patients with an ALK rearrangement (incidence rate ratio 2.47 [95% CI: 1.72-3.55, p < 0.001]). The OR for recurrent VTE was 4.85 (95% CI: 2.60-9.52, p < 0.001). Arterial thrombosis risk attributable to ALK was significant (Cox model: hazard ratio 3.15 [95%CI: 1.18-8.37, p= 0.021], competing risks: subhazard ratio 2.80 [95% CI: 1.06-7.43, p= 0.038]). In time-to-event analyses controlling for thrombosis risk factors, the ALK rearrangement conferred a fourfold increase in VTE risk and a threefold increase in arterial thrombosis risk in NSCLC. These patients may benefit from pharmacologic thromboprophylaxis.

Diagnostic Accuracy of Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration (EBUS-TBNA) in Real Life.

Background: EBUS-TBNA is an integral tool in the diagnosis and staging of lung cancer and other diseases involving mediastinal lymphadenopathy. Most studies attesting to the performance of EBUS-TBNA are prospective analyses performed under strict protocols. The objective of our study was to compare the accuracy of EBUS-TBNA to surgery in diagnosing hilar and mediastinal pathologies in a tertiary hospital, staffed by pulmonologists with and without formal interventional pulmonary training.Methods: We retrospectively analyzed subjects who underwent EBUS-TBNA followed by a confirmatory surgical procedure from January 2012 to December 2018. The primary outcome was to evaluate the accuracy of EBUS-TBNA in the diagnosis of all mediastinal disease. Secondary analyses determined the accuracy of EBUS-TBNA in cancer, NSCLC, and non-malignant lesions individually.Results: One hundred and forty-three subjects had an EBUS-TBNA procedure followed by surgery. EBUS-TBNA for all pathologies had an accuracy of 81.2% (CI 95% 73.8–87.4) and sensitivity of 55.1% (CI 95% 41.5–68.3). The accuracy and sensitivity of individual groups were: cancer (81.7, 48.8%), NSCLC (84, 48.3%), and non-malignancy (78.9, 60%). The NSCLC group had 15 false negatives and 5 (33.3%) of them were due to non-sampling of EBUS accessible nodes. Missed sampling led to a change in the final staging in 8.6% of NSCLC subjects.Conclusion: The accuracy of EBUS-TBNA across all groups was comparable to those reported previously. However, the sensitivity was comparatively lower. This was primarily due to the large number of EBUS-TBNA accessible lymph nodes that were not sampled. This data highlights the need for guidelines outlining the best sampling approach and lymph node selection.

Prognostic Value of Neutrophil to Lymphocyte Ratio and Platelet to Lymphocyte Ratio in Lung Cancer

Numerous studies determined that the neutrophil/lymphocyte (NLR) and platelet/lymphocyte ratios (PLR) had prognostic value in several cancer types. This study aimed to evaluate the relationship between NLR and PLR values with the survival time of lung cancer patients. Patients diagnosed with lung cancer between January 2014 and December 2016, were retrospectively evaluated. Demographic characteristics, disease stages, laboratory parameters recorded, and the relationship of NLR and PLR values with the survival time and the disease stage evaluated. NLR and PLR were categorized into two groups. SPSS 17.0 software package was used for the statistical analysis. ROC analysis, Student T-test, Chi-square, and Mann-Whitney U test were used. Mean age of 62±8 years were included in the study. In the NSCLC group, the average NLR and PLR values were 4±3.35 and 194.6±144.4 respectively. Regarding the NSCLC group, the overall survival time was shorter in the subgroup with an NLR &gt;3.43 (13.1 months) compared to the subgroup with an NLR ≤3.43 (24.3 months). The mean survival time was shorter in the group with a PLR &gt; 136.9 compared to the group with a PLR ≤136.9 (15.9 and 24.6 months respectively). Subgroups consisting of survivors and non-survivors in the NSCLC group showed a statistically significant difference considering neutrophil and lymphocyte count, CRP, NLR, and PLR values (p&lt;0.05). As NLR and PLR values are easily accessible, they have an essential role in the prognosis of lung cancer as well as other cancer types.

RADIOTHERAPY FOR THE TREATMENT OF LOCALLY ADVANCED NON SMALL CELL LUNG CANCER

In this literature review we analyze the effectiveness of radiotherapy (as an independent method and in combination with surgery and chemotherapy) in the treatment of locally advanced non-small cell lung cancer. The postoperative adjuvant radiotherapy can increase overall survival and reduce the frequency of local recurrences in IIIA / N2 stage of NSCLC, however, its positive effect can be offset by the damage to surrounding structures. Modern high-tech equipment, improved planning systems, methods radiation doses delivery, and the fractionation regimen can improve the outcomes of radiation therapy. No bimodal treatment has shown advantages over other combinations. Some improvement in survival was noted in a number of studies using three-modal treatment, but it was also associated with an increase in the proportion of postoperative complications, especially after pneumonectomies. The heterogeneity of the IIIA / N2 NSCLC group and criteria for their operability present certain difficulties for a correct comparison of the treatment results, which requires further discussion. In most studies, insufficient attention has been paid to the influence of multimodal treatment on the quality of life of patients, which, taking into account comparable results of treatment, can be crucial in determining indications and contraindications.

Correlation of cell-free circulating DNA, RNA, and PD-L1 from plasma with clinical response in patients with metastatic lung and breast cancers.

11550 Background: There is an unmet need to evaluate tumor response by other means than radiology tests. Changes in gene expression, allele-fractions of mutations, PDL-1 expression and levels of cell free DNA [DNA] or RNA [RNA] in plasma might be useful for monitoring disease state and predicting outcome to anti-tumoral therapy. Methods: We measured serial levels of plasma DNA/RNA in metastatic patients (pts) with NSCLC and breast cancers undergoing treatment and correlated them with response (CR/PR/SD/PD) seen by CT scans. We also monitored PD-L1 expression in NSCLC pts treated with immunotherapy. DNA/RNA were extracted from plasma. RNA was reverse transcribed with random primers to cDNA. Levels of DNA/RNA were determined by RT-qPCR. Results: 52 pts were enrolled (28 breast/24 NSCLC). Breast group: 39% (11/28) were Caucasian (NHW) and 36% (10/28) Hispanic (H). 20 pts completed first two cycles of therapy: 2 pts had PR and showed no change (NC) or decrease (DEC) in levels of DNA/RNA. 11pts achieved SD, 9 had NC levels of DNA/RNA. Pts with PD: 5/6 underwent significant increase (INC) in DNA/RNA levels. Overall, among breast pts, there was an 84% (16/19) agreement between response and levels of DNA/RNA. These were correlated with one another ( r = 0.7002, p&lt; 0.0001). NSCLC group: 71% (16/24) were NHW and 25% (6/24) H. Non-SQCC were 87% (21/24). 20 pts had CT scans. One pt had PR with DEC levels of DNA/RNA. 10 pts achieved SD, all showed DEC or NC levels of DNA/RNA. 8 pts had PD, 6 of them had INC in DNA/RNA levels even 7 weeks prior to PD. Among NSCLC pts, there was a 90% (17/19) agreement in response and levels of DNA/RNA. These were correlated with one another ( r= 0.6231, p&lt; 0.0001). In 5 pts PD-L1 expression remained stable when CT scans showed SD or PR. Conclusions: There is a strong correlation between clinical responses with changes in plasma levels of DNA/RNA in pts with NSCLC (90%) and breast cancer (84%). Some of these were documented weeks before imaging was done. cfRNA is as effective as cfDNA as predictive tool for response. Plasma PDL-1 expression is a new tool to monitor immunotherapy response.

P2.01-004 The Methylation Profiling of Multiple Tumor Suppressor Genes in Plasma Cell-Free DNA of Patients with NSCLC vs Benign Tumors

Effective discrimination between lung cancer and benign tumors is a common clinical problem in the differential diagnosis of solitary pulmonary nodules. While most solitary pulmonary nodules are benign, around 20% of cases represent an early stage lung cancer. The presence of cell-free DNA (cfDNA) in plasma of lung cancer patients demonstrates promising diagnostic implications and could be considered as an auxiliary tool in the differential diagnosis of solitary pulmonary nodules by evaluating cancer-specific biomarkers, such as hypermethylated tumor DNA fragments. We developed a simultaneous methylation profiling of 21 distinct tumor suppressor genes (TSGs) in plasma cfDNA using MS-MLPA assay. The methylation profiling of 21 TSGs in plasma cfDNA of 32 resectable NSCLC (I-IIIa) patients and 8 subjects with benign lung nodules (hamartoma, fibrosis, granuloma) was performed using optimized MS-MLPA assay. 25/32 (78%) NSCLC and 8/8 (100%) benign-nodule cfDNA samples presented at least one TSG methylation, however the number of hypermethylated TSGs was much higher in NSCLC group. APC (frequency 18% samples), MLH1 (18%), ATM (13.6%), DAPK1 (13.6%), HIC 1 (13.6%), and RARβ (9%) were the most frequently methylated genes in NSCLC, while TIMP3 (75%), MLH1 (25%) and TP73 (37.5%) – in benign patients. The optimized MS-MLPA assay allowed simultaneous detection of multiple methylated TSGs in plasma cfDNA. The MS-MLPA showed good performance in samples with diverse cfDNA concentrations suggesting that methylation detection rate depends on the methylated DNA content in a sample. The study is on-going. The groups are to be extended and other benign lung pathologies evaluated.

MiRSNPs of miR1274 and miR3202 Genes that Target MeCP2 and DNMT3b Are Associated with Lung Cancer Risk: A Study Conducted on MassARRAY Genotyping.

Genetic variants of miRNAs that target DNMTs and MBDs involved in DNA methylation were scanned with current databases, and 35 miRSNPs in 22 miRNA genes were identified. The aim of the study was to determine the association between these variants of miRNA genes and lung cancer (LC). DNA samples were isolated from blood samples and genotyped using a Sequenom MassARRAY System. An association between the rs188912830 gene variant of miR3202 that targets the MeCP2 protein and LC was indicated in both subtypes. The presence of the C-allele in patients with LC and its subtypes was significantly lower, and the absence of the C-allele was determined to increase the risk of LC by 7,429-times compared to the presence (p=0,010). The rs318039 gene variant of miR1274 that targets DNMT3b was found to be associated with LC subtypes. When allele distributions were compared, the numbers of individuals with the C-allele were significantly lower in the NSCLC and SCLC groups. No significant associations were found for the rs72563729 variant of the miR200b gene that targets DNMT3a or for the rs145416750 variant of the miR513c gene that targets TRDMT1. The other 33 variants were found to be ancestral genotypes. Consequently, rs188912830 and rs318039 variations were associated with LC subtypes. Importantly, this study is the first to indicate the functional characterisation of miRSNPs of genes that target DNA methylation.

Impairments after curative intent treatment for non-small cell lung cancer: A comparison with age and gender-matched healthy controls

BackgroundThe aim of this study was to compare measures of exercise capacity, health-related quality of life (HRQoL), muscle force, lung function and feelings of anxiety and depression in people after curative intent treatment for NSCLC with age and gender-matched healthy controls. MethodsThis cross-sectional study included 23 participants (68 ± 10yr; 16 females), 6–10 weeks after lobectomy for NSCLC or, for those who received adjuvant chemotherapy, 4–8 weeks after their last cycle. The study also included 20 age and gender-matched healthy controls (69 ± 5yr; 13 females). All participants underwent measurements of exercise capacity (cycle-ergometry test [CPET] and 6-min walk test [6MWT]), HRQoL (Short-Form 36 general health survey [SF-36]), handgrip force, quadriceps torque, lung function and feelings of anxiety and depression. ResultsWhen compared with data collected in healthy controls, those in the NSCLC group demonstrated impairments in the peak rate of oxygen consumption (15 ± 3 versus 24 ± 7 ml kg−1·min−1; p < 0.001) and maximum work rate (75 ± 25 versus 127 ± 51Watts; p < 0.001) measured during the CPET, and 6-min walk distance (494 ± 77 versus 649 ± 61 m; p < 0.001). Similarly, impairments were demonstrated in all domains of the SF-36 (p < 0.01 for all), isometric handgrip force (28 ± 7 versus 34 ± 10 kg; p = 0.02), and all measures of lung function (p ≤ 0.001 for all). A higher score for depression was also seen (3.0 ± 2.5 versus 1.5 ± 1.6; p = 0.03). There was no difference between the groups in isometric quadriceps torque or feelings of anxiety. ConclusionsAfter curative intent treatment for NSCLC, compared to healthy controls, impairments were demonstrated in laboratory and field-based measures of exercise capacity, HRQoL, isometric handgrip force and lung function. Although people after curative intent treatment for NSCLC reported greater feelings of depression, these levels were below those considered clinically relevant. These findings suggest that people after curative intent treatment for NSCLC may benefit from rehabilitative strategies to optimise exercise capacity and HRQoL.