Background Tissue tumor mutational burden (TMB) has emerged as a potential biomarker predicting response to anti‐programmed cell death‐1 protein receptor (PD‐1)/programmed cell death‐1 protein ligand (PD‐L1) therapy, but few studies have explored using circulating tumor DNA (ctDNA) TMB in non‐small cell lung cancer (NSCLC). Materials and Methods A total of 136 patients with NSCLC with ctDNA testing were retrospectively evaluated from a single institution, along with a validation cohort from a second institution. ctDNA TMB was derived using the number of detected mutations over the DNA sequencing length. Results Higher ctDNA TMB was significantly correlated with smoking history (p < .05, chi‐squared test). Among patients treated with immune checkpoint inhibitors (n = 20), higher ctDNA TMB was significantly correlated with shorter progressive free survival (PFS) and overall survival (OS; 45 vs. 355 days; hazard ratio [HR], 5.6; 95% confidence interval [CI], 1.3–24.6; p < .01, and OS 106 days vs. not reached; HR, 6.0; 95% CI, 1.3–27.1; p < .01, respectively). In a small independent validation cohort (n = 12), there was a nonsignificant numerical difference for higher ctDNA TMB predicting shorter OS but not PFS. ctDNA TMB was not correlated with RECIST tumor burden estimation in the subset of patients treated with immune checkpoint blockade. Conclusion The findings indicate that higher ctDNA TMB, at the current commercial sequencing length, reflects worse clinical outcomes. Implications for Practice Biomarkers to identify patients who will respond to immune checkpoint blockade are critical. Tissue tumor mutational burden (TMB) has emerged as a viable biomarker to predict response to anti‐PD‐1/PD‐L1 therapy, but few studies have explored the meaning and potential clinical significance of noninvasive, blood‐based TMB. Here, we investigated circulating tumor DNA (ctDNA) TMB and present data demonstrating that current ctDNA TMB may reflect tumor burden and that ctDNA panels with a greater number of mutations may be necessary to more accurately reflect tissue TMB.

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Background: VeriStrat test is a serum assay which uses a mass spectrometry (MS)-based proteomic signature derived from machine learning. It is currently used as a prognostic marker for patients with nonsmall cell lung cancer (NSCLC) receiving chemotherapy. However, little is known about its role for NSCLC patients receiving immune checkpoint inhibitors (ICIs).Methods: This is a retrospective study that includes 47 patients with advanced stage NSCLC without an activating EGFR mutation, who underwent the VeriStrat test from 2016 to 2018. Spectra from blood samples were evaluated to assign patients into the VeriStrat 'Good' (VS-G) or VeriStrat 'Poor' (VS-P) risk group. The clinical outcomes of 32 patients who received programmed cell death 1 (PD-1) inhibitors nivolumab or pembrolizumab were analyzed by VeriStrat status. Results:The VS-G group demonstrated significantly higher progression-free survival (PFS) and overall survival (OS) compared to the VS-P group among overall NSCLC patients regardless of treatment (median PFS of 7.1 vs. 4.2 months, P=0.013, and median OS, not reached vs. 17.2 months, P=0.012). Among NSCLC patients treated with ICIs, VS-G classification was associated with significantly increased PFS in comparison to VS-P classification (median PFS of 6.2 vs. 3.0 months, P=0.012), while the differences in OS trended towards significance (median OS, not reached vs. 16.5 months P=0.076). Multivariate analysis showed that the VeriStrat status was significantly correlated with PFS and OS in NSCLC patients treated with ICIs (P=0.017, P=0.034, respectively).Conclusions: MS-based serum proteomic signature has potential as a biomarker for survival outcome in NSCLC patients receiving immunotherapy.

Spontaneous pneumomediastinum (SPM), a rare occurrence, is defined by the presence of extraluminal gas in the mediastinum in the absence of trauma or underlying parenchymal disease. It is usually benign and has been associated with the inhalation of marijuana, cocaine, and amphetamines. The breathing maneuvers along with cyclical vomiting have been postulated as the underlying etiology. We present a case of a 27-year-old previously healthy male who presented with sudden onset chest pain and was found to have marijuana-induced pneumomediastinum.

anti-tumor immunity play a major role in carcinogenesis of NSCLC. CD8 + CD28 À cytotoxic T (Tc) cells and CD4 + CD25 + FoxP3 + regulatory T (Treg) cells known as suppresor CD4+ T cells, have been shown to exist in tumor tissues and inhibits the anti-tumoral immune responses. Natural killer (NK) cells are cytokine producing innate lymphoid cells having cytotoxic capacity to kill tumor cells. In this study the prevalence of Treg cells and CD28 expressing Tc cells and cytotoxic functions were analyzed. Method: The study groups comprised patients with newly-diagnosed non-small cell lung cancer (NSCLC) (n¼46) with T1-3N0M0 NSCLC, none of whom had received preoperative chemotherapy and/or radiotherapy, and healthy subjects (n¼46). The prevalence of CD3 -CD16 + CD56 + NK cells, CD4 + CD25 + Foxp3 + regulatory (Treg) and CD8 + CD28 À T cells were analyzed by flow cytometry. Cytotoxic capacity of NK and CD8 + T cells were analyzed by CD107a degranulation assay. Result: NK and CD8 + CD28suppressor T cells were increased however percentage of activator CD8 + CD28 + T lymphocytes were significantly decreased in patients with NSCLC compared to healthy subjects (p¼0.002, p¼0.005, p¼0.000, p¼0.001, p¼0.001, p¼0.02 and p¼0.02, respectively). Although the cytotoxic activity of NK cells did not differ between the groups, CD107a expression was found increased in total CD8 + T cells in unstimulated and K562 stimulation (p¼0.001). Although the number of Treg cells are decreased in the NSCLC group but this is not statistically significant. No statistically signficant difference was found in terms of lymphocyte subsets and NK cells between the patients with early(T1) and late stages(T2-3). Conclusion: Our findings showed that suppressor CD8 + CD28 -T cell subset as well as NK cells were increased in patients with operable NSCLC. Increased CD8 + CD28 -T cells might cause supression of antitumour immunity and their prevalence might be useful to assess immunotherapy outcomes in patients. Although the number of NK cells increased significantly, the activity of NK cells did not show difference. Functional evaluation of cells has been found to be more important than cell populations.