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Introduction: In real-world practice, most non-small cell lung cancer (NSCLC) patients receiving combined immunochemotherapy are exposed to short-course corticosteroids following immune checkpoint inhibitor (ICI) infusion to prevent chemotherapy-related adverse events. However, whether this early short-course corticosteroid use prevents immune-related adverse events (irAEs) remains unknown. Methods: Between January 1st, 2015, and December 31st, 2020, NSCLC patients who received at least one cycle of ICI with or without chemotherapy were enrolled. Early short-course corticosteroids were defined as corticosteroids administered following ICI injection and before chemotherapy on the same day and no longer than 3 days afterward. The patients were categorized as either "corticosteroid group" or "non-corticosteroid group" depending on their exposure to early short-course corticosteroid. The frequencies of irAEs requiring systemic corticosteroid use and irAEs leading to ICI discontinuation were compared between the two groups, and exploratory survival analyses were performed. Results: Among 252 eligible patients, 137 patients were categorized as "corticosteroid group" and 115 patients as "non-corticosteroid group." The corticosteroid group enriched patients in the first-line setting (n = 75, 54.7%), compared to the non-corticosteroid group (n = 28, 24.3%). Thirty patients (21.9%) in the corticosteroid group and 35 patients (30.4%) in the non-corticosteroid group developed irAEs requiring systemic corticosteroid use (odds ratio [OR], 0.64; 95% confidence interval [CI], 0.35–1.18; p = 0.15). Eight patients (5.8%) in the corticosteroid group, as compared with 18 patients (15.7%) in the non-corticosteroid group, permanently discontinued ICI due to irAEs (OR, 0.34; 95% CI, 0.12–0.85; p = 0.013). Conclusion: Early short-course corticosteroids following each ICI injection may reduce the rate of irAEs that lead to ICIs discontinuation, warranting further investigation of its prophylactic use to mitigate clinically significant irAEs. [ABSTRACT FROM AUTHOR]

Background: Patients with advanced epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma (LAD) inevitably experience drug resistance following treatment with EGFR-tyrosine kinase inhibitors (TKIs). Objectives: We aimed to analyze the effect of primary tumor consolidative therapy (PTCT) on patients treated with first-line osimertinib. Design and methods: This retrospective cohort study was conducted in patients with advanced stage III or stage IV LAD with EGFR-sensitizing mutations (exon 19 deletion or L858R mutation) with disease control after first-line osimertinib. A curative dose of primary tumor radiotherapy or primary tumor resection was classified as PTCT. We compared the progression-free survival (PFS) and overall survival (OS) of patients with and without PTCT. Results: This study included 106 patients with a median age of 61.0 years, and of those, 42% were male and 73.6% were never-smokers. Exon 19 deletion was observed in 67.9%, 30.2% had a programmed cell death ligand 1 (PD-L1) tumor proportion score <1%, 33.0% had brain metastasis, and 40.6% had oligometastasis. In all, 53 (50%) patients underwent PTCT. Patients who underwent PTCT demonstrated significantly better PFS [30.3 (95% confidence interval (CI), 24.1–36.4) versus 18.2 (95% CI, 16.1–20.2) months; p = 0.005] and OS [not reached versus 36.7 (95% CI, 32.5–40.9) months; p = 0.005] than patients who did not. A multivariate analysis showed that PTCT was an independent factor associated with better PFS [hazard ratio (HR), 0.22; 95% CI, 0.10–0.49; p < 0.001] and OS [HR, 0.10; 95% CI, 0.01–0.82; p = 0.032]. The PFS benefits of PTCT were consistent across subgroups, and the HR tended to be lower in patients aged <65 years, males, smokers, stage IVB disease, L858R, PD-L1 expression ⩾1%, non-oligometastasis, and brain metastasis. Conclusion: Of the patients with advanced EGFR -mutant LAD, those who underwent PTCT had a significantly better survival outcome than those who did not. The survival benefits were consistent across different subgroups. [ABSTRACT FROM AUTHOR]

Unlike the better-studied aberrant epigenome in the tumor, the clinicopathologic impact of DNA methylation in the tumor microenvironment (TME), especially the contribution from cancer-associated fibroblasts (CAFs), remains elusive. CAFs exhibit profound patient-to-patient tumorigenic heterogeneity. We asked whether such heterogeneity may be exploited to quantify the level of TME malignancy. We developed a robust and efficient methylome/transcriptome co-analytical system for CAFs and paired normal fibroblasts (NFs) from non-small-cell lung cancer patients. We found 14,781 CpG sites of CAF/NF differential methylation, of which 3,707 sites showed higher methylation changes in ever-smokers than in nonsmokers. Concomitant CAF/NF differential gene expression analysis pointed to a subset of 54 smoking-associated CpG sites with strong methylation-regulated gene expression. A methylation index that summarizes the [beta] values of these CpGs was built for NF/CAF discrimination (MIND) with high sensitivity and specificity. The potential of MIND in detecting premalignancy across individual patients was shown. MIND succeeded in predicting tumor recurrence in multiple lung cancer cohorts without reliance on patient survival data, suggesting that the malignancy level of TME may be effectively graded by this index. Precision TME grading may provide additional pathological information to guide cancer prognosis and open up more options in personalized medicine., Introduction The multistep process of tumor development accompanies the coevolution of the tumor microenvironment (TME) that engages critical participants during tumorigenesis through direct and indirect interaction with tumors (1, 2). [...]

Background: Studies comparing the effectiveness of either adjuvant oral uracil‐tegafur (UFT) or intravenous chemotherapy on early‐stage (stage I and II) non‐small cell lung cancer (NSCLC) patients treated with complete surgical treatment remain limited. Methods: From January 2011 to December 2017, patients with early‐stage NSCLC (defined as tumor size >3 cm without mediastinal lymph node involvement or any distant metastasis) receiving either adjuvant oral UFT or intravenous chemotherapy after surgical resection were identified from the Taiwan Cancer Registry. Overall survival (OS) and relapse‐free survival (RFS) were the primary and secondary outcomes, respectively. Propensity matching was used for controlling confounders. Results: A total of 840 patients receiving adjuvant therapy after surgery (including 595 oral UFT and 245 intravenous chemotherapy) were enrolled. Before matching, patients using oral UFT had significantly longer OS (HR: 0.69, 95% CI: 0.49–0.98, p = 0.0387) and RFS (HR: 0.79, 95% CI: 0.61–0.97, p = 0.0392) than those with intravenous chemotherapy. A matched cohort of 352 patients was created using 1:1 propensity score‐matching. In the Cox regression analysis, the UFT and the matched chemotherapy groups had similar OS (HR: 0.80, 95% CI: 0.48–1.32, p = 0.3753) and RFS (HR: 0.98, 95% CI: 0.72–1.34, p = 0.9149). Among subgroup analysis, oral UFT use was associated with longer RFS among the subgroups of non‐drinker (HR: 0.66, 95% CI: 0.34–0.99, p = 0.0478) and patients with stage IB disease (HR: 0.67, 95% CI: 0.42–0.97, p = 0.0341). Conclusions: This population‐based study in the real‐world setting of Taiwan demonstrates comparable effectiveness between oral UFT and intravenous chemotherapy in terms of clinical outcomes for early‐stage NSCLC patients after surgery. [ABSTRACT FROM AUTHOR]

Objectives: A definitive diagnosis of pulmonary sarcomatoid carcinoma cannot be made with small biopsies. In clinical practice, a diagnosis of advanced non-small-cell lung cancer with spindle cell and/or giant cell carcinoma (NSCLCsg), or possible sarcomatoid carcinoma, is acceptable. Therefore, we aimed to investigate the treatment patterns and outcomes of advanced NSCLCsg. Materials and methods: Between 01 January 2012 and 01 April 2021, patients with pathologically proven advanced NSCLCsg were enrolled. The choice of treatment was based on clinician discretion. Results: In all, 101 patients with advanced NSCLCsg were enrolled. In total, 77 (76.2%) patients received at least one line of systemic therapy; 44 patients (43.1%) had received platinum doublet chemotherapy; 27 (26.7%) patients had been treated with targeted therapies; and 23 patients (22.8%) had been given an immune checkpoint inhibitor (ICI). The median overall survival (OS) was 6.3 months [95% confidence interval (CI): 3.6–9.0 months]. Excluding patients without systemic therapy, patients who had received an ICI had better OS (median: 18.2 months) than those who had not (median 3.8 months, log-rank test p = 0.002). No significant difference in OS was detected between patients who had or had not received platinum doublet chemotherapy (log-rank test p = 0.279), or targeted therapy (log-rank test p = 0.416). Having received any systemic therapy [hazard ratio (HR): 0.33, 95% CI: 0.18–0.61, p < 0.0001) and ICI (HR: 0.38, 95% CI: 0.19–0.78, p = 0.008) were independent factors for better OS. Patients with programmed death ligand-1 (PD-L1) expression ⩾50% had better OS than those with PD-L1 expression <50% (HR: 0.51, 95%: 0.30–0.86, p = 0.012). Conclusion: Although advanced NSCLCsg has a poor survival outcome, our results showed that ICI may prolong OS in patients with advanced NSCLCsg. Further prospective studies are warranted to gain more understanding of the role of ICI in this specific patient population. [ABSTRACT FROM AUTHOR]

Background: Microorganisms of tuberculosis (TB) are frequently difficult to identify from the airway specimen; therefore, lung biopsy for further histologic and microbiologic study is required. Endobronchial ultrasound-guided transbronchial biopsy (EBUS-TBB) is used for the diagnosis of pulmonary malignancy, but is rarely in the TB population. The purpose of this study was to verify the effectiveness and safety of EBUS-TBB with histologic study and tissue culture in the diagnosis of sputum smear-negative pulmonary TB. Methods: Patients who underwent EBUS-TBB with histologic study and TB tissue culture for clinically suspected, but sputum smear-negative pulmonary TB from January 2016 to December 2018, were included. The accuracy of each diagnostic modality was calculated, respectively. Factors that might influence the positive rate of TB culture (washing fluid and tissue specimen) were also evaluated. Results: One hundred sixty-one patients who underwent EBUS-TBB for clinically suspected, but sputum smear-negative pulmonary TB, were enrolled, and 43 of them were finally diagnosed as having pulmonary TB. The sensitivity of washing fluid (a combination of smear, culture, and polymerase chain reaction for TB) and tissue specimen (a combination of pathology and tissue culture) via EBUS-TBB for TB diagnosis were 48.8 and 55.8%, respectively. The sensitivity for TB diagnosis would be elevated to 67.4% when both washing fluid and tissue specimens are used. The positive TB culture rate would not statistically increase with a combination of tissue specimens and washing fluid. Univariate analysis revealed that TB microorganisms would be more easily cultivated when lesions had an abscess or cavity on the computed tomography (CT) image (presence vs. absence; 62.5 vs. 26.3%, p = 0.022), heterogeneous echogenicity on the EBUS finding (heterogeneous vs. homogeneous; 93.3 vs. 21.4%, p = 0.001), or a necrotic pattern via histologic study (presence vs. absence; 70.6 vs. 30.8%, p = 0.013). Heterogeneous echogenicity in the EBUS finding was the independent predictor according to the results of multivariate analysis. None of our patients encountered major adverse events or received further intensive care after EBUS-TBB. Conclusion: Endobronchial ultrasound-guided transbronchial biopsy is safe and effective for use in diagnosing sputum smear-negative pulmonary TB. EBUS echoic feature is also a predictor of the positive TB culture rate in pulmonary TB. However, tissue culture via EBUS-TBB has little effect in improving the positive TB culture rate. [ABSTRACT FROM AUTHOR]