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Background Salvage surgery is performed for selected patients with relapses of locally advanced lung cancer after definitive chemoradiation therapy (CRT), and seems to be effective. To date, the feasibility of such salvage surgery, particularly anatomical pulmonary resection, has not been fully evaluated. To assess the feasibility of salvage surgery after definitive CRT, we compared clinical outcomes of surgery after definitive CRT to those of surgery after induction CRT. Methods Medical records of patients who underwent surgery from January 2000 to January 2018 were reviewed. We compared patients with salvage anatomical pulmonary resection after definitive CRT to patients with surgery after induction CRT in terms of perioperative and long-term outcomes. Results Twenty-three patients underwent salvage surgery after definitive CRT for locally advanced lung cancer (salvage group) and 36 underwent surgery after induction CRT for cN2-stage III non-small cell lung cancer (induction CRT group). The surgical procedures in the salvage group were 2 segmentectomies, 13 lobectomies, 1 bi-lobectomy and 7 pneumonectomies, and those in the induction CRT group were 34 lobectomies and 2 bi-lobectomies. There was no 30-day or 90-day mortality in either group. The 5-year overall survival was 44.7% for the salvage group and 58.6% for the induction CRT group. The 5-year progression-free interval was 42.2% for the salvage group and 47.7% for the induction CRT group. Conclusions Salvage anatomical pulmonary resection after definitive CRT for locally advanced lung cancer is feasible with acceptable morbidity and prognosis in highly selected patients.

Purpose The illness-death model (IDM) is a comprehensive approach to evaluate the relationship between relapse and death. This study aimed to illustrate the value of the IDM for identifying risk factors and evaluating predictive probabilities for relapse and death in patients with non–small cell lung cancer (NSCLC) in comparison with the disease-free survival (DFS) model.Materials and Methods We retrospectively analyzed 612 NSCLC patients who underwent a curative operation. Using the IDM, the risk factors and predictive probabilities for relapse, death without relapse, and death after relapse were simultaneously evaluated and compared to those obtained from a DFS model.Results The IDM provided more detailed risk factors according to the patient’s disease course, including relapse, death without relapse, and death after relapse, in patients with resected lung cancer. In the IDM, history of malignancy (other than lung cancer) was related to relapse and smoking history was associated with death without relapse; both were indistinguishable in the DFS model. In addition, the IDM was able to evaluate the predictive probability and risk factors for death after relapse; this information could not be obtained from the DFS model.Conclusion Compared to the DFS model, we found that the IDM provides more comprehensive information on transitions between states and disease stages and provides deeper insights with respect to understanding the disease process among lung cancer patients.

Purpose: Aim was to analyze demographic and tumor characteristics, treatment, and survival of patients with lung cancer younger than 40 years of age (U40) compared to older subgroups (41–70 and >70...

The Surveillance, Epidemiology and End Results (SEER) and the National Cancer Database (NCDB) are databases for cancer analysis that may be subject to error in data reporting. This study examined the rates and impact of discordant data for non-small cell lung cancer.NCDB and SEER were queried for non-small cell lung cancer pathologic tumor, node, metastasis data (NCDB) or "derived" data (SEER). Discordancy between descriptors with stage and impact of outlier data were analyzed.Incomplete staging was noted in 71.5% of the NCDB and 10.3% of SEER patients. A total of 174 829 patients from the NCDB and 117 114 from SEER were analyzed. The NCDB had 97 cases with ≥20 positive lymph nodes recorded vs 27 in SEER (P.001). Mean and median sampled lymph nodes were skewed with inclusion of these data points (P .001). The NCDB misclassified 0.99% tumors5 cm as stage I vs 0.04% in SEER (P.001). The NCDB misstaged positive lymph nodes as pathologic N0 (0.59%) or stage 0 or stage I (0.65%). The NCDB misclassified pathologic N1 as lower than stage II (0.91%) or N2 as lower than stage III (0.36%). The NCDB misclassified stage I with documentation of pathologic N1 or N3 disease (0.24%) or stage II with evidence of N2 or N3 disease (0.50%). The NCDB misclassified pathologic M1 as pathologic stageIV in 0.9% of cases and misclassified 19.8% of stage IV as pathologic M0. SEER collaborative staging had no discordance (P.001).The NCDB and SEER are 2 powerful cancer databases. However, the cumulative discordancy rate was 4.9% for the NCDB and 0.008% for SEER, with more misstaging and outliers in the NCDB.

Advances in biomarkers, targeted therapies, and immuno-oncology have transformed the clinical management of patients with advanced NSCLC. For oncogene-driven tumors, there are highly effective targeted therapies against EGFR, ALK, ROS1, BRAF, TRK, RET, and MET. In addition, investigational therapies for KRAS, NRG1, and HER2 have shown promising results and may become standard-of-care in the near future. In parallel, immune-checkpoint therapy has emerged as an indispensable treatment modality, especially for patients lacking actionable oncogenic drivers. While PD-L1 expression has shown modest predictive utility, biomarkers for immune-checkpoint inhibition in NSCLC have remained elusive and represent an area of active investigation. Given the growing importance of biomarkers, optimal utilization of small tissue biopsies and alternative genotyping methods using circulating cell-free DNA have become increasingly integrated into clinical practice. In this review, we will summarize the current landscape and emerging trends in precision medicine for patients with advanced NSCLC with a special focus on predictive biomarker testing.

HIV status may influence survival from non-small cell lung cancer (NSCLC). Among NSCLC patients in the Bronx, NY, we assessed (1) associations of CD4 count, CD4/CD8 ratio and HIV viral load (VL) with survival and (2) prognostic factors among persons living with HIV (PLWH). We compared survival from NSCLC diagnosis (2004-2017) between HIV-negative persons (HIV-, n=2,881) and PLWH (n=88) accounting for clinical and sociodemographic factors. HIV-survival was also compared with PLWH, dichotomized by CD4 (

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI), such as Erlotinib, have demonstrated remarkable efficacy in the treatment of non-small cell lung cancer (NSCLC) patients with mutated EGFR. However, the efficacy of EGFR-TKIs in wild-type (wt) EGFR tumours has been shown to be marginal. Methods that can sensitize Erlotinib to EGFR wild-type NSCLC remain rare. Herein, we developed a multifunctional superparamagnetic nanotheranostic agent as a novel strategy to potentiate Erlotinib to EGFR-wt NSCLCs. Our results demonstrate that the nanoparticles can co-escort Erlotinib and a vascular epithermal growth factor (VEGF) inhibitor, Bevacizumab (Bev), to EGFR-wt tumours. The nanotheranostic agent exhibits remarkable effects as an inhibitor of EGFR-wt tumour growth. Moreover, Bev normalizes the tumour embedded vessels, further promoting the therapeutic efficacy of Erlotinib. In addition, the tumour engagement of the nanoparticles and the vascular normalization could be tracked by magnetic resonance imaging (MRI). Collectively, our study, for the first time, demonstrated that elaborated nanoparticles could be employed as a robust tool to potentiate Erlotinib to EGFR-wt NSCLC, paving the way for imaging-guided nanotheranostics for refractory NSCLCs expressing EGFR wild-type genes.

OBJECTIVE Current guidelines primarily suggest resection of brain metastases (BMs) in patients with limited lesions. With a growing number of highly effective local and systemic treatment options, this view may be challenged. The purpose of this study was to evaluate the role of metastasectomy, disregarding BM count, in a comprehensive treatment setting. METHODS In this monocentric retrospective analysis, the authors included patients who underwent resection for at least 1 BM and collected demographic, clinical, and tumor-associated parameters. Prognostic factors for local control and overall survival (OS) were analyzed with the log-rank test and Cox proportional hazards analysis. RESULTS The authors analyzed 216 patients. One hundred twenty-nine (59.7%) patients were diagnosed with a single/solitary BM, whereas 64 (29.6%) patients had 2–3 BMs and the remaining 23 (10.6%) had more than 3 BMs. With resection of symptomatic BMs, a significant improvement in Karnofsky Performance Scale (KPS) was achieved (p < 0.001), thereby enabling adjuvant radiotherapy for 199 (92.1%) patients and systemic treatment for 119 (55.1%) patients. During follow-up, 83 (38.4%) patients experienced local recurrence. BM count did not significantly influence local control rates. By the time of analysis, 120 (55.6%) patients had died; the leading cause of death was systemic tumor progression. The mean (range) OS after surgery was 12.7 (0–88) months. In univariate analysis, the BM count did not influence OS (p = 0.844), but age < 65 years (p = 0.007), preoperative and postoperative KPS ≥ 70 (p = 0.002 and p = 0.005, respectively), systemic metastases other than BM (p = 0.004), adjuvant radiation therapy (p < 0.001), and adjuvant systemic treatment (p < 0.001) were prognostic factors. In regression analysis, the presence of extracranial metastases (HR 2.30, 95% CI 1.53–3.48, p < 0.001), adjuvant radiation therapy (HR 0.97, 95% CI 0.23–0.86, p = 0.016), and adjuvant systemic treatment (HR 0.37, 95% CI 0.25–0.55, p < 0.001) remained as independent factors for survival. CONCLUSIONS Surgery for symptomatic BM from non–small cell lung cancer may be indicated even for patients with multiple lesions in order to alleviate their neurological symptoms and to consequently facilitate further treatment.

Although preoperative immunotherapy is increasingly utilized for non-small cell lung cancer, there remains a paucity of robust clinical data on its safety and long-term survival. Our objective was to evaluate the perioperative outcomes and survival associated with immunotherapy followed by surgery for patients with non-small cell lung cancer.Outcomes of patients with non-small cell lung cancer who underwent lung resection after preoperative chemotherapy with or without radiation or immunotherapy (with or without chemotherapy or chemoradiation) in the National Cancer Database (2010 to 2017) were evaluated using Kaplan-Meier analysis, multivariable logistic regression, multivariable Cox proportional hazards analysis, and propensity score-matched analysis.From 2010 to 2017, 236 patients (2.2%) received immunotherapy and 10 715 patients received preoperative chemotherapy followed by surgery. There were no significant differences between the immunotherapy and preoperative chemotherapy groups with regard to margin positivity (8.5% [n = 20] vs 7.5% [n = 715], P = .98), 30-day readmission (4.2% [n = 10] vs 4.1% [n = 440], P = .87), and 30-day mortality (0.4% [n = 1] vs 2.4% [n = 253], P = .25). The immunotherapy and preoperative chemotherapy groups had similar overall survival (5-year survival 63% [95% confidence interval, 50% to 74%] vs 51% [95% confidence interval, 50% to 52%], log rank P = .06; multivariable adjusted hazard ratio 0.98; 95% confidence interval, 0.67 to 1.41; P = .90). A propensity score matched analysis of 344 patients, well matched by preoperative characteristics, showed no significant differences in short-term outcomes and overall survival (log rank P = 1.00) between the two groups.In this national analysis, preoperative immunotherapy followed by surgery for non-small cell lung cancer was found to be safe and feasible with similar short-term outcomes and overall survival when compared with preoperative chemotherapy followed by surgery.

Background: MicroRNAs can regulates tumor metastasis either as an oncomiR or suppressor miRNA. Here, we investigate the role of miR-224 in lymphatic metastasis of non-small-cell lung cancer (NSCLC). Methods: The expression of miR-224 was demonstrated by a validation cohort of 156 lung cancer patients (77 cases with lymphatic metastasis) by q-PCR. In vitro and in vivo experiments were performed to study the malignant phenotype after upregulation and inhibition of miR-224 expression. Furthermore, the direct target genes of miR-224 were determined by a luciferase reporter assay. Results: miR-224 was identified as a high expression miRNA in the tumor tissues with lymphatic metastasis) with an area under the receiver operating characteristic curve (AUC) of 0.57. Forced expression of miR-224 in H1299 cells promoted not only the cell viability, plate clone formation, migration and invasion in vitro, but also tumor growth and lung metastasis in vivo. Consistently, inhibition of miR-224 suppressed the malignant characters both in vitro and in vivo. Molecular mechanism research suggested that miR-422a targeted the ANGPTL1 as a novel tumor suppressor.Conclusions: The present study demonstrates that miR-224 is a potential marker for the prediction of lymphatic metastasis of NSCLC. And application of miR-224 may help for prophylactic intervention of NSCLC in clinical practice.

Clinical Practice Points • New metastatic sites in non-small cell lung cancer (NSCLC) patients have been shown to have the potential to transform into another histologic subtype that is different from the original histology of the patient while on treatment. • These histological transformations can indicate potential resistance mechanisms to current or prior treatments and can prompt a change in management in patients. • However, little is known about histologic transformations in NSCLC patients and what are the next steps in management. • New reports have shown that epidermal growth factor receptor tyrosine kinase inhibitors such as osimertinib can also lead to these histologic transformations in NSCLC cases and rarely to either large cell neuroendocrine carcinomas or small cell carcinoma. • This case highlights the important implications for these patients since the treatment plans are different and changes in prognosis and for clinicians to be aware of these possibilities and consider repeat biopsies and genomic testing to optimize treatment.

In this article, a three-dimensional detection framework for detecting non-small cell lung cancer (NSCLC) in 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) images and guided by a multi-modality attention fusion is proposed. A total of 250 18F-FDG PET/CT scans between January 1, 2015 and December 31, 2019 of patients who had histopathologically proven NSCLC were acquired. A customized dual-path 3D CenterNet is used for NSCLC detection. Moreover, we propose a multi-modality attention module that adaptively refines the multi-modality feature map fusion. Since the 3D convolutional neural network (CNN) requires many graphic memories and sliding windows, a 384×384×32 patch size is designed and used for training and testing. Five-fold cross-validation is applied for this study. The sensitivity and false positive per scan (FPPS) obtained by our proposed method are 0.96 and 1.04, respectively. Our method significantly outperforms 3D CenterNet in terms of sensitivity (P =.031). This module demonstrates the potential to be implemented in other multi-modality applications. Our result performs competitively against other lung cancer detections. Furthermore, case studies show that the proposed method can detect difficult-to-diagnose NSCLCs. Our result shows the proposed method can help radiologists and medical physicists diagnose NSCLC.

Introduction Tobacco consumption and radon exposure are considered the first and second most common causes of lung cancer, respectively. The aim of this study was to analyze both whether selected genetic polymorphisms in loci that are in DNA repair pathways, are related to non-small-cell lung cancer (NSCLC) and whether they may modulate the association between residential radon exposure and lung cancer in both smokers and never smokers. Methods A multicentre, hospital-based, case–control study with 826 cases and 1201 controls was designed in a radon-prone area. Genotyping was determined in whole blood and residential radon exposure was measured in participants’ dwellings. Results Attending to tobacco exposure, the variant in the gene NBN (rs1805794) was associated with lung cancer in never smokers (OR 2.72; 95%1.44–5.2) and heavy smokers (OR 3.04; 95%CI 1.21–7.69). The polymorphism with the highest lung cancer association was OGG1 (rs125701), showing an OR of 8.04 (95%CI 1.64–58.29) for its homozygous variant genotype in heavy smokers. Attending to indoor radon exposure (>200 Bq/m3), rs1452584, for its homozygous variant genotype, showed the highest association (OR 3.04 (95%CI 1.15–8.48). Conclusion The genes analyzed seem to have no association with the fully adjusted model, but they might modulate lung cancer association when different categories of tobacco consumption are considered (i.e. heavy smokers). This association may similarly be elevated for those individuals having high indoor radon exposures, though at a minor extent.

Background: The fusion and rearrangement of the ALK gene of anaplastic lymphoma kinase is an important cause of a variety of cancers, including non-small cell lung cancer (NSCLC) and anaplastic large cell lymphoma (ALCL). Since crizotinib first came out, many ALK inhibitors have come out one after another, but the fatal flaw in each generation of ALK inhibitors is the body's resistance to drugs. Therefore, how to solve the problem of drug resistance has become an important bottleneck in the application and development of ALK inhibitors. This article briefly introduces the drug resistance of ALK inhibitors and the modified forms of ALK inhibitors, which provide a theoretical basis for solving the drug resistance of ALK inhibitors and the development of a new generation of ALK kinase inhibitors. Method: We use relevant databases to query relevant literature, and then screen and select based on the relevance and cutting edge of the content. We then summarize and analyze appropriate articles, integrate and classify relevant studies, and finally write articles based on topics. Result: This article starts with the problem of ALK resistance, first introduces the composition of ALK kinase, and then introduces the problem of resistance of ALK kinase inhibitors. Later, the structural modification to overcome ALK resistance was introduced, and finally, the method to overcome ALK resistance was introduced. Conclusion: This article summarizes the resistance pathways of ALK kinase inhibitors, and integrates the efforts made to overcome the structural modification of ALK resistance problems, and hopes to provide some inspiration for the development of the next generation of ALK kinase inhibitors.

Background: In advanced non-small-cell lung cancer, without activating mutations and with PD-L1≥50%, Pembrolizumab monotherapy is the therapeutic standard in Europe. Objective: To evaluate retrospectively the safety and efficacy of this drug and to investigate potential prognostic factors in daily clinical practice. Methods: From September 2017 to September 2019, 205 consecutive patients from 14 Italian Medical Oncology Units were enrolled in the study. Gender, Age (> or 90% or Results: At a median follow-up of 15.2 months, median progression-free and overall survival (mPFS and mOS) were 9.2 months (95% C.I., 4.8-13.5) and 15.9 months (95% C.I., not yet evaluable), respectively. Patients with Eastern Cooperative Oncology Group performance status (ECOG-PS) 2 had mPFS of 2.8 months (95% C.I., 2.1-3.4) and mOS of 3.9 months (95% C.I., 2.5-5.3). Patients with liver metastases at diagnosis had an mPFS of 3.2 months (95% C.I., 0.6-5.8) and an mOS of 6.0 months (95% C.I., 3.7-8.4). At multivariate analysis for OS gender, ECOG-PS 2, and presence of liver metastases were independent prognostic factors. Conclusion: Patients with ECOG-PS 2 derived little benefit from the use of first-line pembrolizumab. In patients with liver metastases, the association of pembrolizumab with platinum-based chemotherapy could be a better option than pembrolizumab alone.

The purpose of this study was to investigate the current status of diagnosis and treatment of Chinese patients with advanced non-small cell lung cancer (NSCLC) and the expert recommendation of the therapeutic regimens during the coronavirus disease 2019 (COVID-19) pandemic, and to analyze and summarize relevant rules.Under the planning and coordination of the Lung Cancer Group of the Chinese Thoracic Society, we performed an online questionnaire survey among experts in lung cancer and patients with NSCLC. Convenience sampling was adopted for questionnaire survey of experts, and random sampling was adopted for questionnaire survey of patients. After collecting and sorting out the questionnaire, a descriptive analysis of the data was performed.Within 24 h from the distribution of questionnaires to the deadline, a total of 808 and 321 valid questionnaires from patients and experts were collected across China, respectively. There were 83.81% of the experts performed moderately and strongly anti-tumor therapy for patients with NSCLC during the COVID-19 pandemic. 76.6% of patients mainly receive online public welfare treatment, and the patient satisfaction rate reached up to 64.97%. For driver gene-positive patients with advanced NSCLC and non-COVID-19, 82.87% of the experts recommended first-line simple targeted therapy, and 12.77% of the experts recommended targeted therapy with oral anti-angiogenic drugs. For patients who were unable to return to the hospital for treatment and showed resistance to the tyrosine kinase inhibitor (TKI) therapy, 92.21% of the experts recommended oral anti-angiogenic drugs as the third-line home-based therapy and above. For patients with advanced NSCLC combined with COVID-19, 98.76% and 95.95% of the experts recommended discontinuation of chemotherapy and immunotherapy, respectively.During COVID-19, most Chinese patients with NSCLC were still able to receive timely diagnosis and treatment either by online public welfare consultation or at nearby hospitals.

Purpose: To establish recommended phase II dose (RP2D) in phase I and evaluate safety and efficacy of abivertinib in patients with EGFR Thr790Met point mutation (T790M)-positive(+) non–small cell lung cancer (NSCLC) with disease progression from prior EGFR inhibitors in phase II. Patients and Methods: This multicenter, open-label study included 367 adult Chinese patients. Abivertinib at doses of 50 mg twice a day to 350 mg twice a day was evaluated in phase I in continual 28-day cycles, and the RP2D of 300 mg twice a day was used in phase II in continual 21-day cycles. Primary endpoints include RP2D in phase I and objective response rate (ORR) at RP2D in phase II. Results: The RP2D of 300 mg twice a day for abivertinib was established based on pharmacokinetics, efficacy, and safety profiles across doses in phase I. In phase II, 227 patients received RP2D for a median treatment duration of 24.6 weeks (0.43–129). Among 209 response–evaluable patients, confirmed ORR was 52.2% [109/209; 95% confidence interval (CI): 45.2–59.1]. Disease control rate (DCR) was 88.0% (184/209; 95% CI: 82.9–92.1). The median duration of response (DoR) and progression-free survival (PFS) was 8.5 months (95% CI: 6.1–9.2) and 7.5 months (95% CI: 6.0–8.8), respectively. The median overall survival (OS) was 24.9 months [95% CI: 22.4–not reachable (NR)]. All (227/227) patients reported at least 1 adverse event (AE), with 96.9% (220/227) of treatment-related AEs. Treatment-related serious AEs were reported in 13.7% (31/227) of patients. Death was reported in 4.4% (10/227) of patients, and none was deemed as treatment-related. Conclusions: Abivertinib of 300 mg twice a day demonstrated favorable clinical efficacy with manageable side effects in patients with EGFR T790M+ NSCLC.

Background: This study investigated the efficacy and complications of microwave ablation in combination with chemotherapy in treating peripheral IIIB-IV nonsmall cell lung cancer (NSCLC). Materials...

Background: The optimal treatment (Tx) for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients (pts) with brain metastasis (BM) remains to be determined. Methods: A retrospective review was conducted on 77 NSCLC pts with synchronous BM who underwent first-line EGFR-TKI Tx (gefitinib: 46, erlotinib: 11, afatinib: 20). The outcomes of pts were analyzed according to the clinicopathological characteristics including local Tx modalities.Results: Fifty-nine pts underwent local Tx for BM (gamma knife surgery (GKS): 37, whole brain radiotherapy (WBRT): 18, others: 4) concurrently or sequentially with EGFR-TKI. Pts treated with TKI alone showed significantly lower incidence of central nervous system (CNS) symptoms (p=0.006), with a tendency toward a smaller number of BM lesions compared with those who received local treatment. The median progression-free survival (PFS) and overall survival (OS) after the initiation of EGFR-TKI for all pts were 9 and 19 months, respectively. In 60 pts with follow-up brain imaging, the median intracranial PFS was 15 months. Pts with EGFR exon 19 deletion (n=42) had a significantly longer median OS than those with L858R mutation (n=25) or other mutations (n=10) (23 vs. 17 months, p=0.010). Other clinical characteristics, including CNS symptoms (p=0.410), number of BM (p=0.709), and the use of local Tx (p=0.834), were not associated with OS, as well as PFS. In terms of the local optimal treatment modality, no difference was found between GKS and WBRT in the OS and PFS.Conclusions: This study suggests that EGFR-TKI may result in a favorable outcome in NSCLC pts with synchronous BM, especially in deletion 19 mutant, regardless of the extent of BM lesions or local Tx modalities. Pts with asymptomatic BM can be treated with EGFR-TKI and careful surveillance.

LncRNA ELF3-AS1 has been characterized as an oncogenic lncRNA in bladder cancer and oral cancer, whereas its role in non-small cell lung cancer (NSCLC) is unknown. In this study, the authors observed that ELF3-AS1 was upregulated in NSCLC tissues in comparison with that in paired nontumor tissues collected from 68 NSCLC patients. High expression levels of ELF3-AS1 predicted the poor survival of NSCLC patients. Expression levels of miR-212 were inversely and significantly correlated with the expression levels of ELF3-AS1 across NSCLC tissue samples. In NSCLC cells, overexpression of ELF3-AS1 led to downregulated miR-212 and increased methylation of miR-212 gene. In addition, overexpression of ELF3-AS1 inhibited the role of miR-212 in suppressing cancer cell invasion and migration. Therefore, ELF3-AS1 is upregulated in NSCLC and promotes cancer cell invasion and migration by downregulating miR-212 through methylation.

Lung cancer (LC) is the leading cause of cancer-related deaths worldwide, with high morbidity and mortality. Non-small cell lung cancer (NSCLC) is a major pathological type of LC and accounts for more than 80% of all cases. Circular RNAs (circRNAs) are a large class of non-coding RNAs (ncRNAs) with covalently closed-loop structures, a high abundance, and tissue-specific expression patterns. They participate in various pathophysiological processes by regulating complex gene networks involved in proliferation, apoptosis, migration, and epithelial-to-mesenchymal transition (EMT), as well as metastasis. A growing number of studies have revealed that the dysregulation of circRNAs contributes to many aspects of cancer progression, such as its occurrence, metastasis, and recurrence, suggesting their great potential as efficient and specific biomarkers in the diagnosis, prognosis, and therapeutic targeting of NSCLC. In this review, we systematically elucidate the characteristics, biogenesis, and functions of circRNAs and focus on their molecular mechanisms in NSCLC progression. Moreover, we highlight their clinical implications in NSCLC treatment., Graphical Abstract, In this review, Liu et al. systematically summarize the biological characteristics, biogenesis, and functions of circRNAs and focus on their mechanisms in non-small cell lung cancer (NSCLC) progression. Moreover, the authors also highlight the potential of circRNAs as diagnostic and prognostic biomarkers and therapeutic targets for NSCLC.

Purpose We develop a deep learning (DL) radiomics model and integrate it with circulating tumor cell (CTC) counts as a clinically useful prognostic marker for predicting recurrence outcomes of early-stage non-small cell lung cancer (ES-NSCLC) patients treated with stereotactic body radiation therapy (SBRT). Methods and Materials A cohort of 421 NSCLC patients was used to train a DL model for gleaning informative imaging features from computed tomography (CT) data. The learned imaging features were optimized on a cohort of 98 ES-NSCLC patients treated with SBRT for predicting individual patient recurrence risks by building DL models on CT data and clinical measures. These DL models were validated on the third cohort of 60 ES-NSCLC patients treated with SBRT to predict recurrent risks and stratify patients into subgroups with distinct outcomes in conjunction with CTC counts. Results The DL model obtained a concordance-index of 0.880 (95% confidence interval: 0.879, 0.881). Patient subgroups with low and high DL risk scores had significantly different recurrence outcomes (p = 3.5e-04). The integration of DL risk scores and CTC measures identified 4 subgroups of patients with significantly different risks of recurrence (χ2= 20.11, p=1.6e-04). Patients with positive CTC measures post-SBRT were associated with increased risks of recurrence that were significantly different from patients with negative CTC measures (χ2= 4.03, p=0.0447). Conclusion In this first-ever study integrating DL radiomics models and CTC counts, our results suggested that this integration improves patient stratification compared with either imagining data or CTC measures alone in predicting recurrence outcomes for patients treated with SBRT for ES-NSCLC.

PURPOSE Insertion mutations in Erb-b2 receptor tyrosine kinase 2 gene ( ERBB2 or HER2) exon 20 occur in 2%-5% of non–small-cell lung cancers (NSCLCs) and function as an oncogenic driver. Poziotinib, a tyrosine kinase inhibitor, was evaluated in previously treated patients with NSCLC with HER2 exon 20 insertions. METHODS ZENITH20, a multicenter, multicohort, open-label phase II study, evaluated poziotinib in patients with advanced or metastatic NSCLC. In cohort 2, patients received poziotinib (16 mg) once daily. The primary end point was objective response rate evaluated by independent review committee (RECIST v1.1); secondary outcome measures were disease control rate, duration of response, progression-free survival, and safety and tolerability. Quality of life was assessed. RESULTS Between October 2017 and March 2021, 90 patients with a median of two prior lines of therapy (range, 1-6) were treated. With a median follow-up of 9.0 months, objective response rate was 27.8% (95% CI, 18.9 to 38.2); 25 of 90 patients achieved a partial response. Disease control rate was 70.0% (95% CI, 59.4 to 79.2). Most patients (74%) had tumor reduction (median reduction 22%). Median progression-free survival was 5.5 months (95% CI, 3.9 to 5.8); median duration of response was 5.1 months (95% CI, 4.2 to 5.5). Clinical benefit was seen regardless of lines and types of prior therapy, presence of central nervous system metastasis, and types of HER2 mutations. Grade 3 or higher treatment-related adverse events included rash (48.9%), diarrhea (25.6%), and stomatitis (24.4%). Most patients had poziotinib dose reductions (76.7%), with median relative dose intensity of 71.5%. Permanent treatment discontinuation because of treatment-related adverse events occurred in 13.3% of patients. CONCLUSION Poziotinib demonstrates antitumor activity in previously treated patients with HER2 exon 20 insertion NSCLC.

Aim: This study aimed to access the efficacy of plasma small nucleolar RNAs in early diagnosis of non-small-cell lung cancer (NSCLC). Methods: SNORD83A was selected based on databases and further verified in 48 paired formalin-fixed, paraffin-embedded tissues, as well as in plasma from 150 NSCLC patients and 150 healthy donors. The diagnostic efficiency of plasma SNORD83A, as well as in combination with carcinoembryonic antigen, was determined by receiver operating characteristic analysis. Results: SNORD83A was significantly increased not only in tissues but also in plasma from NSCLC patients compared with those from healthy donors. Plasma SNORD83A was able to act as a diagnostic biomarker for NSCLC. The diagnostic efficiency of carcinoembryonic antigen was also significantly elevated for early-stage NSCLC when combined with SNORD83A. Conclusion: SNORD83A can serve as a diagnostic biomarker for NSCLC.

Objective To define the relationship between the duration of smoking cessation and post-operative complications for patients with lung cancer undergoing surgical treatment. Background Smoking increases the risk of post-operative morbidity and mortality in patients with lung cancer undergoing surgical treatment. While smoking cessation before surgery can mitigate these risks, the ideal duration of pre-operative smoking cessation remains unclear. Methods Using a uniquely compiled Veterans Health Administration (VHA) dataset, we performed a retrospective cohort study of patients with clinical stage I non-small cell lung cancer (NSCLC) undergoing surgical treatment between 2006 and 2016. We characterized the relationship between duration of pre-operative smoking cessation and risk of post-operative complications or mortality within 30-days using multivariable restricted cubic spline functions. Results The study included a total of 9509 patients, of whom 6168 (64.9%) were smoking at the time of lung cancer diagnosis. Among them, only 662 (10.7%) patients stopped smoking prior to surgery. Longer duration between smoking cessation and surgery was associated with lower odds of major complication or mortality (aOR for every additional week, 0.919; 95% CI, 0.850-0.993; P = 0.03). Compared to non-smokers, patients who quit at least 3 weeks before surgery had similar odds of major complication (aOR, 1.005; 95% CI, 0.702-1.437; P = 0.98) whereas those who quit within 3 weeks of surgery had significantly higher odds of major complication (aOR, 1.698; 95% CI, 1.203-2.396; P = 0.003). Conclusion Smoking cessation at least 3 weeks prior to the surgical treatment of lung cancer is associated with reduced morbidity and mortality. Providers should aggressively encourage smoking cessation in the pre-operative period, since it can disproportionately impact outcomes in early-stage lung cancer.

A 46-year-old man was referred to our centre with blurring of vision in both eyes (BE) since 1 month and breathlessness for last 1 week. He was an active smoker with 13.6 pack-years of exposure. Ocular examination revealed a best-corrected visual acuity of 20/60 and 20/80 in right and left eye

PURPOSE: Non-small cell lung cancer (NSCLC), the most prevalent subtype of lung cancer, tends to metastasize to the brain. Between 10-60% of NSCLCs harbor an activating mutation in the epidermal growth factor receptor (EGFR), which may be targeted with selective EGFR inhibitors. However, due to a high discordance rate between the molecular profile of the primary tumor and the brain metastases (BMs), identifying an individual patient’s EGFR status of the BMs necessitates tissue diagnosis via an invasive surgical procedure. We employed a deep learning (DL) method with the aim of noninvasive detection of the EGFR mutation status in NSCLC BM. METHODS: We retrospectively collected clinical, radiological, and pathological-molecular data of all the NSCLC patients who had been diagnosed with BMs and underwent resection of their BM during 2006-2019. The study population was then divided into 2 groups based upon EGFR mutational status. We further employed a DL technique to classify the 2 groups according to their preoperative magnetic resonance imaging features. Finally, we established the accuracy of our model in predicting EGFR mutation status of BM of NSCLC. RESULTS: Fifty-nine patients were included in the study, 16 patients harbored EGFR mutations. Our model predicted mutational status with mean accuracy of 89.8%, sensitivity of 68.7%, specificity of 97.7%, and a receiver operating characteristic curve )ROC( value of 0.91 across the 5 validation datasets.CONCLUSION: DL based noninvasive molecular characterization is feasible, has high accuracy and should be further validated in large prospective cohorts.

Objectives This study aimed to evaluate the cost-effectiveness, from a US commercial payer perspective, of cemiplimab versus other first-line treatments for advanced non-small cell lung cancer with programmed death-ligand 1 expression ≥50%. Methods A 30-year “partitioned survival” model was constructed. Overall survival and progression-free survival were estimated by applying time-varying hazard ratios from a network meta-analysis of randomized clinical trials. Overall survival and progression-free survival were estimated from EMPOWER-Lung 1 (cemiplimab monotherapy vs chemotherapy) and KEYNOTE-024 and KEYNOTE-042 (pembrolizumab monotherapy vs chemotherapy). Drug acquisition costs were based on published 2020 US list prices. A 3% discount rate was applied to life-years, quality-adjusted life-years (QALYs), and costs. A deterministic analysis was performed on the base case; 1-way sensitivity and probabilistic sensitivity analyses assessed model and parameter uncertainties. Results Cemiplimab was associated with increased time in the “preprogression” (13.08 vs 7.90 and 6.08 months) and “postprogression” (47.30 vs 29.49 and 14.78 months) health states versus pembrolizumab and chemotherapy, respectively. Compared with pembrolizumab and chemotherapy, cemiplimab generated 1.00 (95% CI −0.266 to 2.440) and 1.78 (95% CI 0.607-3.20) incremental QALYs, respectively, with incremental cost-effectiveness ratios of $68 254 and $89 219 per QALY for cemiplimab versus pembrolizumab and cemiplimab versus chemotherapy, respectively. The probability of cemiplimab being cost-effective at a willingness-to-pay threshold of $100 000 to $150 000 per QALY was 62% to 76% versus pembrolizumab and 56% to 84% versus chemotherapy. Conclusions Findings suggest that cemiplimab, versus pembrolizumab or versus chemotherapy, is a cost-effective first-line treatment option for advanced non-small cell lung cancer with programmed death-ligand 1 expression ≥50%.

BACKGROUND: The treatment landscape for advanced nonsmall cell lung cancer (NSCLC) has evolved from 2015 onward, since the introduction of immune checkpoint inhibitors (ICIs). Considering this shif...

The association of hospital volume with outcomes has been assessed previously for patients with non-small cell lung cancer (NSCLC), but there are limited data on the cumulative effect of travel burden and hospital volume on treatment decisions and survival outcomes. We used the National Cancer Database to evaluate this relationship in early-stage NSCLC.Outcomes of interest were compared between 2 propensity-matched groups with stage I NSCLC: patients in the bottom quartile of distance travelled who underwent surgery at low-volume centers (Local) and those in the top quartile of distance travelled who received surgery at high-volume centers (Distant). Outcomes included type of resection (anatomic or nonanatomic), time to resection (or ≥8 weeks), number of lymph nodes examined (or ≥10 nodes) and R0 resection.We identified 3325 Local patients who travelled 2.3 miles (interquartile range [IQR]: 1.4-3.3 miles) to centers that treated 10.5 (IQR: 6.5-16.5) stage I NSCLCs/year and 3361 Distant patients who travelled 40.0 miles (IQR: 29.1-63.4 miles) to centers treating 56.9 (IQR: 40.1-84.7) stage I NSCLCs/year. Local patients were less likely to receive surgery8 weeks post-diagnosis, have ≥10 lymph nodes examined during surgery, and undergo an R0 resection (all P.01). Distant patients had shorter hospital stays and superior median survival, both P.01.Patients travelling longer distances to high-volume centers receive better and more timely surgical care, leading to shorter hospital stays and improved survival outcomes. Regionalization of lung cancer care by improving travel support to larger treatment facilities may help improve early-stage NSCLC outcomes.

NEKs are proteins that are involved in various cell processes and play important roles in the formation and development of cancer. However, few studies have examined the role of NEKs in the development of non-small-cell lung carcinoma (NSCLC). To address this problem, the Oncomine, UALCAN, and the Human Protein Atlas databases were used to analyze differential NEK expression and its clinicopathological parameters, while the Kaplan-Meier, cBioPortal, GEPIA, and DAVID databases were used to analyze survival, gene mutations, similar genes, and biological enrichments. The rate of NEK family gene mutation was high (>50%) in patients with NSCLC, in which NEK2/4/6/8/ was overexpressed and significantly correlated with tumor stage and nodal metastasis status. In addition, the high expression of NEK2/3mRNA was significantly associated with poor prognosis in patients with NSCLC, while high expression of NEK1/4/6/7/8/9/10/11mRNA was associated with good prognosis. In summary, these results suggest that NEK2/4/6/8 may be a potential prognostic biomarker for the survival of patients with NSCLC.

Background Knowledge regarding cognitive problems in metastatic non-small cell lung cancer (mNSCLC) is limited. Such problems may include both patient-reported cognitive concerns and demonstrable cognitive impairment. Greater understanding of these outcomes is needed to inform rehabilitation strategies for these difficulties. We aimed to identify the frequency of cognitive problems and associated factors in patients with mNSCLC. Methods In this cross-sectional study, adults with mNSCLC completed validated neuropsychological tests and self-report questionnaires measuring cognitive concerns, neurobehavioral concerns, depression, demoralization, illness intrusiveness, self-esteem, and physical symptoms. Cognitive impairment (performance based) was defined according to International Cancer and Cognition Task Force criteria. Clinically significant cognitive concerns were defined by a score ≥1.5 SD below the normative mean on the Functional Assessment of Cancer Therapy-Cognitive Function Perceived Cognitive Impairment (FACT-Cog PCI). Univariate and multivariate logistic regression analyses were performed to identify associated factors. Results Of 238 patients approached, 77 participated (median age: 62 years; range: 37-82). Brain metastases were present in 41 patients (53%), and 23 (29%) received cranial irradiation. Cognitive impairment and cognitive concerns were present in 31 (40%) and 20 patients (26%), respectively. Cognitive impairment and cognitive concerns co-occurred in 10 patients (13%), but their severity was unrelated. Cognitive impairment was associated with cranial irradiation (odds ratio [OR] = 2.89; P = .04), whereas cognitive concerns were associated with greater illness intrusiveness (OR = 1.04; P = .03) and lower self-esteem (OR = 0.86; P = .03). Conclusions Cognitive impairment and cognitive concerns are both common in patients with mNSCLC but are not necessarily related, and their risk factors differ. The association of illness intrusiveness and self-esteem with cognitive concerns can inform therapeutic interventions in this population.

PURPOSE To investigate the efficacy of gefitinib as an adjuvant therapy for non–small-cell lung cancer patients with EGFR mutation. PATIENTS AND METHODS IMPACT (WJOG6410L; University Hospital Medical Information Network Clinical Trials Registry: UMIN000006252 ), a randomized, open-label, phase III study, included patients with completely resected pathologic stage II-III non–small-cell lung cancer harboring EGFR mutations (exon 19 deletion or L858R) during September 2011 to December 2015. Patients were randomly assigned to receive gefitinib (250 mg once daily) for 24 months or cisplatin (80 mg/m2 on day 1) plus vinorelbine (25 mg/m2 on days 1 and 8; cis/vin) once every 3 weeks for four cycles. The primary end point was disease-free survival (DFS). RESULTS Overall, 234 patients were randomly assigned. Among 232 eligible patients (116 each; excluding two who withdrew consent), the median DFS was 35.9 and 25.1 months in the gefitinib and cis/vin groups, respectively. However, Kaplan-Meier curves crossed around 4 years after surgery with no statistically significant difference (stratified log-rank P = .63; hazard ratio by stratified Cox proportional hazards model = 0.92; 95% CI, 0.67 to 1.28). Overall survival (OS) was also not different (stratified log-rank P = .89; hazard ratio = 1.03; 95% CI, 0.65 to 1.65), with the 5-year OS rates being 78.0% and 74.6% in the gefitinib and cis/vin groups, respectively. Treatment-related deaths occurred in 0 and three patients in the gefitinib and cis/vin groups, respectively. CONCLUSION Although adjuvant gefitinib appeared to prevent early relapse, it did not prolong DFS or OS. However, similar DFS and OS may justify adjuvant gefitinib in the selected patient subsets, especially those deemed ineligible for platinum-doublet adjuvant therapy; however, this was not a noninferiority trial.

Purpose Metachronous brain-only oligorecurrence in patients with non–small cell lung cancer (NSCLC) is a rare event with favorable prognosis, but the clinical outcome has not been fully determined. We retrospectively analyzed clinical outcomes and prognostic factors in metachronous brain-only oligorecurrence in patients with NSCLC who underwent definitive treatment.Materials and Methods We reviewed 4,437 NSCLC patients without oncogenic driver mutations who underwent definitive treatment between 2008 and 2018. Among them, we identified 327 patients who developed 1 to 5 brain metastases with or without systemic metastasis. Of the 327 patients, 71 had metachronous brain-only oligorecurrence without extracranial progression and were treated with local therapy to the brain. Overall survival (OS), progression-free survival (PFS), and prognostic factors affecting OS were analyzed.Results The median OS was 38.9 months (95% confidence interval [CI], 21.8 to 56.1 months) in 71 patients. The 2-year OS rate was 67.8% and the 5-year OS rate was 33.1%. The median PFS was 25.5 months (95% CI, 12.2 to 14.4 months). The longest surviving patient had a survival period of 115 months. Through multivariate analysis, Eastern Cooperative Oncology Group ≥ 1 (hazard ratio, 5.33; p=0.005) was associated with poor survival. There was no significant difference in OS between patients with local therapy and those with local plus systemic therapy (18.5 months vs. 34.7 months, p=0.815).Conclusion Metachronous brain-only oligorecurrence NSCLC patients who underwent definitive treatment experienced long-term survival with local therapy, highlighting the unique patient population. The role of systemic chemotherapy in this patient population requires further investigation.

The FDA approved capmatinib and tepotinib on May 6, 2020, and February 3, 2021, respectively. Capmatinib is indicated for patients with metastatic non–small cell lung cancer (mNSCLC) whose tumors have a mutation leading to mesenchymal–epithelial transition (MET) exon 14 skipping as detected by an FDA-approved test. Tepotinib is indicated for mNSCLC harboring MET exon 14 skipping alterations. The approvals were based on trials GEOMETRY mono-1 (capmatinib) and VISION (tepotinib). In GEOMETRY mono-1, overall response rate (ORR) per Blinded Independent Review Committee (BIRC) was 68% [95% confidence interval (CI), 48–84] with median duration of response (DoR) 12.6 months (95% CI, 5.5–25.3) in 28 treatment-naïve patients and 41% (95% CI: 29, 53) with median DoR 9.7 months (95% CI, 5.5–13) in 69 previously treated patients with NSCLC with mutations leading to MET exon 14 skipping. In VISION, ORR per BIRC was 43% (95% CI: 32, 56) with median DoR 10.8 months (95% CI, 6.9–not estimable) in 69 treatment-naïve patients and 43% (95% CI, 33–55) with median DoR 11.1 months (95% CI, 9.5–18.5) in 83 previously-treated patients with NSCLC harboring MET exon 14 alterations. These are the first two therapies to be FDA approved specifically for patients with metastatic NSCLC with MET exon 14 skipping.

Aim: This study aimed to investigate the prognostic value of peripheral naive and memory CD8+ and CD4+ T cells and other immune cells in patients with oligometastatic non-small-cell lung cancer (NSCLC) undergoing radiotherapy (RT). Methods: A total of 142 patients with oligometastatic NSCLC treated with RT were enrolled, and their blood samples were collected within 3 days before RT. Immune cells were identified by flow cytometry. Results: Patients with high levels of naive CD8+ T cells had longer overall survival (p = 0.004) and progression-free survival (p = 0.001) than those with low levels of naive CD8+ T cells. Multivariate analyses revealed that naive CD8+ T cells were independently correlated with overall survival (p = 0.019) and progression-free survival (p = 0.024). Conclusion: The results suggest that peripheral naive CD8+ T cells may be an independent prognostic indicator for patients with oligometastatic NSCLC undergoing RT.

Background Calf circumference (CC), the greatest girth of the lower leg, is a simple tool for assessing sarcopenia. Its significance in patients with resectable non‐small‐cell lung cancer (NSCLC) is unknown. Methods A total of 684 NSCLC patients who underwent surgery were included in the present study. The relationship between parameters of sarcopenia [i.e. the CC and skeletal mass index (SMI)] and the short‐term and long‐term outcomes was retrospectively analysed. Results The median CC (34.5 cm for men and 32.0 cm for women) was selected as the cut‐off value of the CC for the analysis in this study, and the patients were classified into the smaller CC (SC) and normal CC (NC) groups. The mean age of the SC group was significantly older than that of the NC group (70.8 vs. 65.8 years, P

Background/Aim. Lung cancer is one of the most com-mon cancer types worldwide. More than 70% of patients are diagnosed with lung cancer in the advanced stages of the disease, with limited therapeutic options based on cytological and histopathological material. The value of cytology in diagnosing and subtyping non-small cell lung cancer (NSCLC) is very important for modern personalized therapies. The aim of this study was to find out the concordance between cytological and histopathological diagnosis of NSCLC and the accuracy, sensitivity, specificity, and the positive and negative predictive value of cytology in diagnosing lung cancer. Methods. A two-year retrospective study included 169 patients with cytological diagnosis of NSCLC, who, at the same time, had small biopsy and surgical specimens for histopathological diagnoses confirmation that were compared with cytological one. Histopathological diagnosis on surgical specimens was the golden standard for evaluation concordance to the cytological diagnosis of NSCLC and evaluation accuracy, specificity, sensitivity, and the positive and negative prognostic value of cytology as a diagnostic method for detecting lung cancer. Results. This study included 129 (76.3%) male and 40 (23.7%) female patients, aged between 39 and 83, with the average of 62.53 ? 7.6. There was no statistically significant difference between the ages of different genders (p = 0.207). The most frequent diagnosis among cytological diagnoses was NSCLC in 99 (58.58%) patients. Concordance between cytological and histopathological diagnoses of surgical specimens was 61.48%. There was no statistically significant difference between cytological diagnoses and histopathological diagnoses of small biopsies specimens (p = 0.856). The sensitivity, specificity, positive and negative prognostic value, and accuracy of cytology as a diagnostic method of lung cancer were 94.98%, 98.60%, 95.72%, 98.35%, and 97.71%, respectively. Conclusion. Cytological diagnosis of NSCLC is accurate, with high sensitivity, specificity, and benefits for patients. Most patients are diagnosed with advanced cancer when there is no surgical therapy option, and the only available diagnostic material is a small biopsy sampled during bronchoscopy.

Circulating tumor DNA (ctDNA) has demonstrated great potential as a noninvasive biomarker to assess minimal residual disease (MRD) and profile tumor genotypes in patients with non‐small‐cell lung cancer (NSCLC). However, little is known about its dynamics during and after tumor resection, or its potential for predicting clinical outcomes. Here, we applied a targeted‐capture high‐throughput sequencing approach to profile ctDNA at various disease milestones and assessed its predictive value in patients with early‐stage and locally advanced NSCLC. We prospectively enrolled 33 consecutive patients with stage IA to IIIB NSCLC undergoing curative‐intent tumor resection (median follow‐up: 26.2 months). From 21 patients, we serially collected 96 plasma samples before surgery, during surgery, 1–2 weeks postsurgery, and during follow‐up. Deep next‐generation sequencing using unique molecular identifiers was performed to identify and quantify tumor‐specific mutations in ctDNA. Twelve patients (57%) had detectable mutations in ctDNA before tumor resection. Both ctDNA detection rates and ctDNA concentrations were significantly higher in plasma obtained during surgery compared with presurgical specimens (57% versus 19% ctDNA detection rate, and 12.47 versus 6.64 ng·mL−1, respectively). Four patients (19%) remained ctDNA‐positive at 1–2 weeks after surgery, with all of them (100%) experiencing disease progression at later time points. In contrast, only 4 out of 12 ctDNA‐negative patients (33%) after surgery experienced relapse during follow‐up. Positive ctDNA in early postoperative plasma samples was associated with shorter progression‐free survival (P = 0.013) and overall survival (P = 0.004). Our findings suggest that, in early‐stage and locally advanced NSCLC, intraoperative plasma sampling results in high ctDNA detection rates and that ctDNA positivity early after resection identifies patients at risk for relapse., ctDNA profiling in plasma revealed higher levels and detection rates of ctDNA during tumor resection as compared to pretreatment time points in patients with early‐stage or locally advanced NSCLC. Moreover, patients testing positive for ctDNA immediately after tumor resection had worse clinical outcomes than patients with undetectable ctDNA. Our research highlights the role of ctDNA assessment for guiding treatment in patients with respectable NSCLC.

Aim: To describe initial treatment patterns and survival of patients diagnosed with non-small-cell lung cancer (NSCLC) in Denmark, before immune checkpoint inhibitor and later-generation tyrosine kinase inhibitor use. Patients & methods: Adults diagnosed with incident NSCLC (2005–2015; follow-up: 2016). Initial treatments and overall survival (OS) are reported. Results: 31,939 NSCLC patients (51.6% stage IV) were included. Increasing use of curative radiotherapy/chemoradiation for stage I, II/IIIA and IIIB NSCLC coincided with improved 2-year OS. Systemic anticancer therapy use increased for patients with stage IV non-squamous NSCLC (53.0–60.6%) but not squamous NSCLC (44.9–47.3%). 1-year OS improved in patients with stage IV non-squamous NSCLC (23–31%) but not squamous NSCLC (22–25%). Conclusion: Trends indicated improved OS as treatments evolved between 2005 and 2015, but the effect was limited to 1-year OS in stage IV disease.