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Introduction: Luteolin, a naturally occurring flavonoid compound, demonstrates promising anti-cancer properties. However, its mechanism against non-small-cell lung cancer (NSCLC) remains unknown. This study employed network pharmacology, molecular docking, molecular dynamics simulation (MDS), and in vitro experiments to investigate the potential mechanisms by which luteolin against NSCLC. Methods: Initially, the potential targets of luteolin and NSCLC-related targets were identified from public databases such as TCMSP, GeneCards, OMIM, DrugBank, and TTD. Subsequently, the protein-protein interaction (PPI) network screening and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted. The binding affinity and stability of luteolin with the core targets were assessed using molecular docking and MDS. Finally, the results were validated by in vitro experiments. Results: A total of 56 luteolin targets and 2145 NSCLC-related targets were identified. Six core targets, TP53, EGFR, AKT1, TNF, JUN, and CASP3, were screened via the PPI network. The GO and KEGG analyses indicated that luteolin's activity against NSCLC potentially involves PI3K-Akt, NF-kappa B, and other signaling pathways. Molecular docking revealed that luteolin had high binding affinity with the core targets. MDS confirmed the stable interaction between luteolin and key proteins TP53 and AKT1. in vitro , luteolin significantly inhibited the proliferation and migration of A549 cells, while also inducing apoptosis. In addition, luteolin downregulated the expression of p-Akt (Ser473), MDM2, and Bcl-2 but upregulated the expression of p53 and Bax, which was consistent with the effect of LY294002. Conclusion: Luteolin had a good anti-NSCLC effect, and the apoptosis-inducing effect might be related to the Akt/MDM2/p53 signaling pathway. [ABSTRACT FROM AUTHOR]

Background: Coronavirus disease (COVID)-19 can lead to chronic lung damage and respiratory issues, potentially increasing surgical difficulty and risk for patients with non-small-cell lung cancer (NSCLC). However, the impacts of a COVID-19 history on early outcomes in NSCLC patients remain controversial. Objectives: To evaluate the effect of COVID-19 history on early outcomes in NSCLC patients and identify high-risk groups undergoing radical resection based on the largest Chinese multi-center real-world data to date. Design: Multi-center retrospective cohort study. Methods: NSCLC patients with (POCVD group) or without (NCVD group) a history of COVID-19 who underwent radical surgery at six institutions from January 2022 to January 2024 were retrospectively reviewed from a prospectively maintained database. Propensity-score matching (PSM) was utilized to minimize patient selection bias. Results: Out of 7932 cases included, PSM resulted in 3021 cases per group. The two groups were comparable regarding the proportion of male patients (52.0% vs 51.6%) and those aged ⩾70 years (13.3% vs 13.8%). Although the two groups had comparable incidences of complications with Clavien-Dindo grades ⩾II (13.0% vs 14.4%, p = 0.117), the POCVD group had longer surgical durations (120.87 ± 40.23 min vs 110.74 ± 38.76 min, mean difference (95% confidence interval (CI) = 10.13 (8.138–12.122)) and higher rates of respiratory complications than the NCVD group. Subgroup logistic regression analysis indicated that patients aged ⩾70 years (odds ratio (OR) (95% CI) = 1.322 (1.022–1.876)) and those with a smoking history (OR (95% CI) = 1.235 (1.008–1.543)) had an increased risk of developing complications with Clavien-Dindo grades ⩾II. Further analysis confirmed that these high-risk patients experienced extended surgical durations, longer chest tube drainage, and prolonged postoperative hospital stay, along with increased postoperative respiratory complications following COVID-19. Conclusion: Generally, radical resection is safe for NSCLC patients with a COVID-19 history. However, these patients experienced prolonged surgical durations and a higher incidence of postoperative respiratory complications compared to those without a COVID-19 history. In addition, individuals aged ⩾70 years or with a smoking history faced elevated surgical risks following COVID-19. Plain language summary: Analyzing the impact of COVID-19 history on early outcomes and identifying high-risk groups among non-small cell lung cancer patients undergoing radical resection Aim and Purpose Research Question: Does a COVID-19 history affect the early outcomes of radical surgery (lobectomy/bi-lobectomy/pneumectomy) in patients with non-small cell lung cancer (NSCLC)? Hypothesis: Patients with a COVID-19 history face elevated surgical risks compared to those without. Objective: To understand how past COVID-19 infection impacts early outcomes in NSCLC patients undergoing surgery and to identify high-risk groups. Background Why This Study: COVID-19 can cause long-term lung damage, making surgery riskier for NSCLC. However, it's unclear how past COVID-19 infection affects NSCLC patients receiving surgery. Importance: The research helps to understand the additional risks for NSCLC patients with a COVID-19 history based on the largest cohort to date, aiming to improve their surgical outcomes. Method and Design Research Design: Multi-center retrospective cohort study. Methods and Participants: 7932 NSCLC patients undergoing radical surgery between January 2022 and January 2024 were included and divided into two groups: those with a COVID-19 history (POCVD group) and those without (NCVD group). Result and Importance Findings: 1. The POCVD group had longer surgical durations and higher rates of respiratory complications compared to the NCVD group. 2. The POCVD and NCVD groups were associated with a comparable incidence of postoperative complications with Clavien-Dindo grades ⩾II. 3. The elderly (aged ⩾70 years) and smokers were at higher risk for complications post-COVID-19. Implications: While surgery is generally safe for NSCLC patients with a COVID-19 history, they do face increased risks and complications. This highlights the need for special care and monitoring for older patients and those with smoking histories. Key Message: NSCLC patients with a COVID-19 history can safely undergo radical surgery, but they may experience longer surgical durations and more postoperative respiratory complications, especially the elderly and smokers. [ABSTRACT FROM AUTHOR]

Lung cancer, a common type of malignant neoplasm, has seen significant advancements in the treatment of lung adenocarcinoma (LUAD). However, the management of lung squamous cell carcinoma (LSCC) continues to pose challenges. Traditional treatment methods for LSCC encompass surgical resection, chemotherapy, and radiotherapy. The introduction of targeted therapy and immunotherapy has greatly benefited LSCC patients, but issues such as limited immune response rates and adverse reactions persist. Therefore, gaining a deeper comprehension of the underlying mechanisms holds immense importance. This review provides an in-depth overview of classical signaling pathways and therapeutic targets, including the PI3K signaling pathway, CDK4/6 pathway, FGFR1 pathway and EGFR pathway. Additionally, we delve into alternative signaling pathways and potential targets that could offer new therapeutic avenues for LSCC. Lastly, we summarize the latest advancements in targeted therapy combined with immune checkpoint blockade (ICB) therapy for LSCC and discuss the prospects and challenges in this field. [ABSTRACT FROM AUTHOR]

Lung cancer remains a significant health challenge, characterized by aberrant tissue growth within the pulmonary system. Early carcinogenic events often involve genomic instability and the emergence of a mutator phenotype. In this study, we aimed to explore the mutator phenotype in 89 patients diagnosed with non-small-cell lung cancer (NSCLC). RNA isolation from formalin-fixed paraffin-embedded (FFPE) tissue samples was performed using the Promega ReliaPrep RNA Miniprep System, facilitating gene amplification relevant to cancer through the Archer® FusionPlexComprehensiveThyroid and Lung (CTL) kit. Next-generation sequencing (NGS) on the Illumina NextSeq platform enabled comprehensive analysis of target areas. Utilizing Archer Analysis software, secondary analyses involving data cleansing, alignment, and variant/fusion identification were executed against the human reference genome hg19 (GRCh37). Expression patterns were visualized using HeatMap graphics. Our findings revealed a notable presence of KRAS gene mutations in approximately 20% of NSCLC patients. Among these mutations, the G12C variant was predominant at 50%, followed by G12V and G12D variants at 11.2% each. Notably, patients harboring the G12C variant responded favorably to sotorasib medication. These results underscore the importance of mutational profiling and targeted therapeutic approaches in managing NSCLC, particularly highlighting the promising efficacy of sotorasib in G12C-mutated cases. [ABSTRACT FROM AUTHOR]

We aimed to evaluate whether progression-directed radiation therapy (PDRT) can prolong the initiation of a subsequent systemic therapy regimen in a cohort of patients with oligoprogressive NSCLC. A retrospective analysis was conducted on NSCLC patients who underwent PDRT for extracranial oligoprogressive NSCLC, defined as limited (up to five) progressing lesions following initial complete, partial, or stable response to systemic therapy according to REC1ST 1.1 and/or PERCIST 1.0 criteria. Cox proportional hazard regressions were performed to identify factors influencing time to next treatment (TTNT), which was considered the primary endpoint. Forty patients were analyzed. First, second, and ≥3 lines of systemic therapy were administered in 22 (58.2%), 14 (27.2%), and 4 (14.6%) cases, respectively. The median total dose was 36 Gy (range: 12–60) in five fractions (1–10), with a median biological effective dose for tumor control (BED10) of 52 Gy (26.4–151.2). After a median follow-up of 11 months (2–50), PDRT delayed further systemic therapy in 32 (80.0%) treatments. Median TTNT was not reached at 8 months (1–47) with a one-year Kaplan–Meier estimate of 81.4% (95% CI: 75.0% to 87.8%). No >grade 3 adverse event was observed. On multivariate analysis, patients with ≥3 lines of systemic therapy and/or with larger CTV volumes did not benefit from PDRT. Despite the use of sub-ablative doses, our findings show that PDRT represents an effective, safe, and viable option for oligoprogressive NSCLC. Patients irradiated early during their systemic treatment course, with a low volume of disease and nonmetastatic oligoprogression, could derive substantial benefits from PDRT. [ABSTRACT FROM AUTHOR]

Background and Objectives: The burdened symptomatology accompanying advanced non-small-cell lung cancer (NSCLC) is associated with poor prognosis and lower quality of life (QoL). Although both chemotherapy and immunotherapy increase survival, they are still associated with reduced functionality due to their toxicity. This study aimed to estimate the QoL and symptom burden of NSCLC patients receiving second-line chemotherapy compared to patients receiving second-line immunotherapy. Materials and Methods: This comparative, prospective study, conducted from January 2020 to December 2021, included 111 NSCLC patients who were divided into two groups: 61 patients receiving second-line chemotherapy and 50 patients receiving second-line immunotherapy. Patients' QoL and symptom burden were estimated using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ C-30) (value range 0–100) from treatment cycle 1 to 6. Results: The QoL (mean score > 50) and functionality dimensions (mean score > 50) were moderate to good in both treatment groups, while the symptom burden did not appear to be a serious problem (mean score < 50). From cycle 3 to cycle 5, QoL was significantly better in the immunotherapy group. From cycle 3, the role and social functioning scores were higher in the immunotherapy group, while emotional and cognitive functioning were higher from cycle 2 (p <0.05). The chemotherapy group experienced higher levels of nausea/vomiting, constipation and financial difficulties in all the cycles (p < 0.05). Fatigue and appetite loss were significantly greater from cycle 2 and insomnia was significantly greater from cycle 3. On the contrary, the immunotherapy group experienced higher levels of diarrhea in cycles 5 and 6 (p < 0.05). Conclusions: Although both therapy groups did not report significantly impaired QoL and severe symptoms, it seems that QoL improved in the immunotherapy group, which reported a lower symptom burden compared to the chemotherapy group. [ABSTRACT FROM AUTHOR]

Background and objectives: Lung cancer is a common cancer, and its impact on public health is not only reflected in the 1 million deaths it causes annually but also in the significant implications it has on daily activities and quality of life, resulting in a considerable burden on healthcare systems. This review aims to determine the effects of pulmonary rehabilitation and pre- or post-surgical exercise in patients with lung cancer. Materials and methods: A systematic review with a meta-analysis of randomized controlled trials published between 2010 and 2024 was conducted; the search was carried out in PubMed, Cochrane Clinical Trial, SCOPUS, Science Direct, Web of Science, Scielo, and LILAC. Results: Pulmonary rehabilitation or exercise before surgery was associated with a greater 6 min walking distance (MD: 37.42, 95% CI: 9.68–65.1; p = 0.008); however, it had no implications on hospital stay (MD: −0.91, 95% CI: −1.88–0.055; p = 0.06). When the intervention was performed post-surgery, higher FEV1 (SMD: 0.62, 95% CI: 0.32–0.92; p = 0.0001) and improved 6 min walking distances (60.8, 95% CI: 20.96–100.6; p = 0.0033) were found compared to standard management. Conclusions: This review suggests that, depending on the timing of implementation, pulmonary rehabilitation or exercise could produce positive effects on certain clinical variables in lung cancer patients. [ABSTRACT FROM AUTHOR]

Background/Aim: Non-small-cell lung cancer (NSCLC) is the most frequently diagnosed malignancy and the first cause of cancer-related death. Thus, finding alternative therapeutic options is crucial. Drug repurposing offers therapeutic options in a simplified and affordable manner, especially to cancer patients in developing countries. Several drugs including antihistamines and beta-adrenergic receptor blockers (beta-blockers) display antiproliferative properties on cancer cells. Interestingly, NSCLC patients who had used either antihistamines or beta-blockers showed improved response to chemotherapy or reduced mortality in comparison to non-users of any of these drugs. However, combination therapy is gaining substantial interest in many cancers including non-EGFR mutated NSCLC. Here, we investigated the antineoplastic effect of the combination of the antihistamine loratadine, the beta-blocker nebivolol, and the tyrosine-kinase inhibitor gefitinib on NSCLC cell lines. Materials and Methods: A-549 and NCI-H1975 cell lines were used. The effect of nebivolol, gefitinib, and loratadine on the metabolic activity was studied using the MTT assay. The inhibitory concentrations (IC20 and IC50) were calculated and used in the drug-combination experiments. Apoptosis was investigated using flow cytometry; and cell survival using the colony formation assay. Results: The combination nebivolol-loratadine-gefitinib produced a significant synergistic effect on inhibiting the metabolic activity and colony formation, as well as on promoting apoptosis in both cell lines. Noteworthy, the effect on the cell line carrying the EGFR mutation (NCI-H1975) was very similar to the cell line that does not exhibit such mutation (A-549 cells). Conclusion: The nebivolol-gefitinib-loratadine combination may be a promising alternative for lung cancer treatment. [ABSTRACT FROM AUTHOR]

Echinoderm microtubule-associated protein 4 (EML4) - anaplastic lymphoma kinase (ALK) fusion gene detection is of great significance in personalized tumor treatment. With the development of EML4-ALK fusion variants detection, it is necessary to establish traceability to ensure the consistency and comparability of its detection results in clinical practice. The establishment of traceability relies on SI traceable reference materials (RMs) and potential reference measurement procedures (RMPs). In this study, a potential RMP for the quantitative detection of V1 and V3 fusion mutations and the reference type (ALK-ref, including wild type, V1 and V3 mutant type) based on reverse transcription dPCR (RT-dPCR) and EML4-ALK fusion gene RMs were established. The proposed potential RMP has high specificity, good inter-laboratory reproducibility (CV < 7.3%) and good linear relationship (0.92 < slope < 1.06, R2 ≧ 0.99). The limit of detection (LoD) of V1, V3, and ALK-ref are 2 copies/reaction, 2 copies/reaction, and 1 copy/reaction, respectively. Interlaboratory studies using the EML4-ALK RMs and potential RMP showed that participating laboratories can produce consistent copy concentrations of fusion variant and ALK-ref as well as the ratio of EML4-ALK/ALK-ref. The established potential RMP with high specificity and accuracy can be used to characterize the EML4-ALK RMs, and the potential RMP and RM are useful to establish the traceability of EML4-ALK fusion measurement to improve the comparability and consistency in clinical tests. [ABSTRACT FROM AUTHOR]

AbstractBackgroundObjectiveMethodsResultsConclusionsThe significance of local radiotherapy (RT) in advanced non-small-cell lung cancer (NSCLC) is well documented. However, the advent of immunotherapy has raised questions regarding the synergistic survival benefits or potential adverse effects.This study aimed to explore whether a combination of RT and systematic immune checkpoint inhibitors (ICIs) can improve the survival outcomes for NSCLC patients.Based on collected data patients who received RT were defined as the RT group, and those who had not for any site were defined as the non-RT group. Propensity score matching (PSM) was employed to mitigate bias. The primary endpoint was progression-free survival (PFS), with secondary endpoints including overall survival (OS) and treatment-related adverse events (AEs).Out of 709 patients (235 in RT group and 474 in non-RT group) were included, with 213 patients per group. The median PFS of the RT group was better than that of the non-RT group (13.8 months versus 9.5 months; p < 0.0001), although no superiority in median overall survival (OS) of the RT group was observed (p = 0.715). However, among the cohort of patients with ≤3 metastases, the median OS of the RT group improved significantly (HR = 0.60, [95% CI 0.44–0.83]; p = 0.004). Treatment-related AEs occurred in 94.5% of RT group patients and in 94.9% of non-RT group patients (p = 0.792), which indicated no observable increase in AEs from RT.These results demonstrate the tolerability of RT when administered along with immunotherapy, suggesting its potential to positively impact the survival outcomes of NSCLC patients. [ABSTRACT FROM AUTHOR]

AIM: This study aimed to explore the induction of ferroptosis in non-small-cell lung cancer （NSCLC） cells by tubeimoside II （TBMS II） and to elucidate the underlying molecular mechanisms. METHODS: H460 NSCLC cells were cultured in vitro. Cell survival rates were assessed by using MTT assays, and doses of TBMS II resulting in below 50% survival were selected for further experimentation. Cell migration was evaluated using Transwell assays and the effects of TBMS II on H460 cell proliferation were assessed by colony formation assays. Flow cytometry and fluorescence microscopy were used to assess changes in lipid peroxidation （lipid ROS）, and the levels of GSH, T-AOC, MDA, and Fe2+ were measured using commercial kits. Protein levels of GPX4, SLC7A11, FTH1, NCOA4, P62, and LC3 were examined using Western blot. Changes in mitochondrial structure were detected by transmission electron microscopy, and immunofluorescence was used to assess LC3 co-localization of FTH1 and NCOA4, as well as co-localization of LC3 and NCOA4 with lysosomes. RESULTS: Compared with the control group, TBMS II dose-dependently reduced H460 cell viability, migration, and clone formation, accompanied by the appearance of vacuoles within the cells. TBMS II treatment also led to decreased GSH and T-AOC levels, while increasing the cellular contents of MDA, indicating oxidative stress. Additionally, there was a decrease in the expression of the antioxidant proteins SLC7A11 and GPX4 in the cells, while lipid ROS and Fe2+ levels were increased in proportion to the TBMS II concentration. The ferroptosis inhibitor ferrostatin-1 reversed cell death caused by TBMS II, suggesting ferroptosis induction. Furthermore, increasing the TBMS II concentration resulted in an upregulation of the autophagy marker proteins LC3 II/LC3 I and P62, indicative of increased autophagy. TBMS II also affected mitochondrial morphology in the cells, as seen in reduced mitochondrial fluorescence intensity. Protein expression of NCOA4 increased with higher TBMS II concentrations, while that of FTH1 decreased. Co-localization of LC3 II with FTH1 and NCOA4, as well as the lysosomal association of LC3 II and FTH1, also increased in a dosedependent manner. CONCLUSION: TBMS II induces ferritinophagy in H460 cells, leading to decreased cell viability and increased ferroptosis. [ABSTRACT FROM AUTHOR]

Antibody–drug conjugates (ADCs) represent an emerging class of targeted anticancer agents that have demonstrated impressive efficacy in numerous cancer types. In non-small cell lung cancer (NSCLC), ADCs have become a component of the treatment armamentarium for a subset of patients with metastatic disease. Emerging data suggest that some ADCs exhibit impressive activity even in central nervous system (CNS) metastases, a disease site that is difficult to treat and associated with poor prognosis. Herein, we describe and summarize the existing evidence surrounding ADCs in NSCLC with a focus on CNS activity. [ABSTRACT FROM AUTHOR]

Non-small-cell lung cancer (NSCLC) stands as a prevalent subtype of lung cancer, with circular RNAs emerging as key players in cancer development. This study elucidates the role of circRNA-CPA4 in NSCLC. Elevated circRNA-CPA4 expression in NSCLC lines was confirmed through qRT-PCR. Silencing circRNA-CPA4 with shRNA revealed, through CCK-8, colony formation, and flow cytometry assays, a notable constraint on proliferation and promotion of apoptosis in NSCLC cells. Subcellular localization analysis, RNA immunoprecipitation, and expression level assessments were employed to decipher the intricate interplay among miR-1183, circRNA-CPA4, and PDPK1. Results demonstrated heightened circRNA-CPA4 levels in NSCLC, and its knockdown curtailed NSCLC growth in vivo. Acting as a molecular sponge for miR-1183, circRNA-CPA4 regulated PDPK1 expression. Conversely, inhibiting miR-1183 counteracted the impact of circRNA-CPA4 silencing, reinstating NSCLC cell proliferation, and impeding apoptosis. Overall, this study unveils a novel mechanism: circRNA-CPA4 promotes PDPK1 expression by sequestering miR-1183, fostering NSCLC cell proliferation, and hindering apoptosis. [ABSTRACT FROM AUTHOR]

Programmed death receptor ligand 1 (PD-L1) tumor proportion score (TPS) and tumor mutational burden (TMB) are key predictive biomarkers for immune checkpoint inhibitor (ICI) efficacy in non-small-cell lung cancer (NSCLC). Data on their variation across multiple samples are limited. Patients with NSCLC and multiple PD-L1 TPS and/or TMB assessments were included. Clinicopathologic and genomic data were analyzed according to PD-L1 and TMB variation. In total, 402 PD-L1 sample pairs and 413 TMB sample pairs were included. Concordance between pairs was moderate for PD-L1 (ρ = 0.53, P < 0.0001) and high for TMB (ρ = 0.80, P < 0.0001). Shorter time between biopsies correlated with higher concordance in PD-L1, but not in TMB. Major increases (ΔTPS ≥ +50%) and decreases (ΔTPS ≤ −50%) in PD-L1 were observed in 9.7% and 8.0% of cases, respectively. PD-L1, but not TMB, decreased with intervening ICI (P = 0.02). Acquired copy number loss of CD274 , PDCD1LG2 , and JAK2 were associated with major decrease in PD-L1 (q < 0.05). Among patients with multiple PD-L1 assessments before ICI, cases where all samples had a PD-L1 ≥1%, compared to cases with at least one sample with PD-L1 <1% and another with PD-L1 ≥1%, achieved improved objective response rate and progression-free survival (PFS). Among patients with at least one PD-L1 <1% and one ≥1% before ICI, cases where the most proximal sample was PD-L1 ≥1% had longer median PFS compared to cases where the most proximal PD-L1 was <1%. Among patients with multiple TMB assessments before ICI, patients with a TMB ≥10 mut/Mb based on the most recent assessment, as compared to those with a TMB <10 mut/Mb, achieved improved PFS and overall survival to ICI; instead, no differences were observed when patients were categorized using the oldest TMB assessment. Despite intrapatient concordance in PD-L1 and TMB, variation in these biomarkers can influence ICI outcomes, warranting consideration for reassessment before ICI initiation when feasible. • Intrapatient paired PD-L1 TPS and TMB assessments have good concordance. • Variations in PD-L1 TPS and TMB with clinical implications may occur. • Intervening ICI therapy is associated with decrease in PD-L1 TPS. • Copy number loss in CD274 , PDCD1LG2 , and JAK2 genes are strongly associated with major decrease in PD-L1 TPS (−50% to −100%). • Variations in PD-L1 TPS and TMB have significant impact on outcomes to a subsequent ICI-based therapy. [ABSTRACT FROM AUTHOR]

Purpose: Given that left upper lobe and right upper and middle lobes share a similar anatomy, segmentectomy, such as upper division and lingulectomy, should yield identical oncological clearance to left upper lobectomy. We compared the prognosis of segmentectomy with that of lobectomy for early stage non-small-cell lung cancer (NSCLC) in the left upper lobe. Methods: We retrospectively examined 2115 patients who underwent segmentectomy or lobectomy for c-stage I (TNM 8th edition) NSCLC in the left upper lobe in 2010. We compared the oncological outcomes of segmentectomy (n = 483) and lobectomy (n = 483) using a propensity score matching analysis. Results: The 5-year recurrence-free and overall survival rates in the segmentectomy and lobectomy groups were comparable, irrespective of c-stage IA or IB. Subset analyses according to radiological tumor findings showed that segmentectomy yielded oncological outcomes comparable to those of lobectomy for non-pure solid tumors. In cases where the solid tumor exceeded 20 mm, segmentectomy showed a recurrence-free survival inferior to that of lobectomy (p = 0.028), despite an equivalent overall survival (p = 0.38). Conclusion: Segmentectomy may be an acceptable alternative to lobectomy with regard to the overall survival of patients with c-stage I NSCLC in the left upper lobe. [ABSTRACT FROM AUTHOR]

Objective Non-small-cell lung cancer (NSCLC) is a leading attributor to cancer deaths. High HDAC10 and low microRNA (miR)-223-5p levels have been observed in NSCLC. But their roles remain elusive. This study illustrated their roles in NSCLC cell ferroptosis and the mechanism. Methods HDAC10, miR-223-5p, and solute carrier family 7 member 11 (SLC7A11) levels in cells were determined by RT-qPCR. Iron ion content, reactive oxygen species (ROS), and glutathione (GSH) levels were tested using reagent kits, and levels of SLC7A11 and Acyl-CoA synthesis long chain family (ACSL4) were examined using Western blot. Chromatin immunoprecision was performed to analyze the enrichment of HDAC10 and acetylated lysine 9 of histone H3 (H3K9ac) on the miR-223-5p promoter. The targeted binding of miR-223-5p and SLC7A11 was analyzed by dual-luciferase assay. Joint experiments were designed to identify the role of miR-223-5p/SLC7A11 axis in HDAC10-regulated ferroptosis in NSCLC cells. Results HDAC10 was highly expressed in NSCLC cells. Silencing HDAC10 significantly reduced GSH and SLC7A11 levels, upregulated iron ion content, ROS levels, and ACSL4 expression, promoting cell ferroptosis. Mechanically, HDAC10 inhibited miR-223-5p expression through H3K9ac deacetylation of the miR-223-5p promoter, thereby targeting SLC7A11. The joint experimental results showed that overexpression of SLC7A11 or downregulation of miR-223-5p alleviated the promoting effect of silencing HDAC10 on ferroptosis in NSCLC cells. Conclusion HDAC10 inhibits miR-223-5p expression through H3K9ac deacetylation of the miR-223-5p promoter, thereby promoting SLC7A11 expression and inhibiting ferroptosis in NSCLC cells. [ABSTRACT FROM AUTHOR]

Background: CD155 is a transmembrane protein that inhibits antitumor immune response and represents a predictor of worse prognosis in non-small-cell lung cancer (NSCLC). However, it remains unexplored its association with clinical characteristics and genomic status of Latin American patients. This study characterizes the CD155 expression and its clinical implications in this population. Methods: Tissue biopsies from 86 patients with locally-advanced or metastatic NSCLC were assessed for CD155 protein expression, ALK rearrangements and EGFR mutations. Cutoff values for high CD155 expression (CD155high) were determined from receiver operating characteristic (ROC) curves according to 2-year survival. It was evaluated its association with clinicopathological features, median progression-free survival (mPFS) and overall survival (mOS). Results: the cutoff score for CD155high was 155 in the entire cohort and in patients without oncogenic alterations, and it was 110 in patients with oncogenic alterations. Eighty-four patients (97.7%) were CD155 positive, of which fifty-six (65.0%) had CD155high. EGFR L858R mutation related to lower CD155 IHC score than exon 19 deletion. Individuals with CD155high showed a shorter mOS (13.0 vs. 30.8 months; HR: 1.96 [95% CI, 1.15–3.35]; p = 0.014). Patients without oncogenic alterations having a CD155high displayed shorter mPFS (1.6 vs. 6.4 months, HR: 2.09 [95% CI, 1.06–4.20]; p = 0.034) and mOS (2.9 vs. 23.1 months; HR: 1.27 [95% CI, 1.07– 4.42]; p = 0.032). Patients with oncogenic alterations having CD155high only showed a trend to shorter mOS (26.3 vs. 52.0 months; HR: 2.39 [95% CI, 0.98–5.83]; p = 0.058). Conclusion: CD155high is a predictor of worse outcomes in patients with advanced NSCLC, predominantly among those without oncogenic alterations. CD155 could be a potential biomarker and a molecular target in patients with poor responses to current therapies. [ABSTRACT FROM AUTHOR]

AIM: To investigate the effects of sodium selenite (SS) on viability, migration and angiogenesis of human non-small-cell lung cancer (NSCLC) H520 and A549 cells. METHODS: The H520 cells, A549 cells, and human umbilical vein endothelial cells (HUVEC) were divided into control group (0 μmol/L SS), low dose group (5 μmol/L SS), middle dose group (10 μmol/L SS), and high dose group (20 μmol/L SS). Cell viability was assessed using the CCK-8 assay, and the half-maximal inhibitory concentration (IC50) was calculated. Cell migration and invasion abilities were determined through wound healing and Transwell assays. The regulatory effects of SS on angiogenesis, vasculogenic mimicry and "mosaic" vascular formation between HUVEC and NSCLC cells were detected using vessel forming assays. The expression of vascular endothelial growth factor (VEGF) in the supernatant of lung cancer cells in each group was detected using chemiluminescence. RT-qPCR was used to assess the mRNA expression of VEGF, vascular endothelial growth factor receptor 2 (VEGFR2) and angiotensin II (Ang II). Western blot was used to examine the protein levels of VEGF, p-PI3K, and p-Akt in H520 and A549 cells. RESULTS : The IC50 values of SS to HUVEC, A549 cells and H520 cells for 48 h were 6. 762, 9. 003 and 7. 356 μmol/L, respectively. Compared with control group, the wound healing rate was significantly decreased in each group treated with SS for 48 h (p<0. 01). In HUVEC, the number of migrating cells in middle dose and high dose groups decreased (p<0. 01), whereas in lung cancer cells, the number of migrating cells in each group decreased after SS treatment (p<0. 01). The mRNA expression levels of VEGF, VEGFR2 and Ang II were lower in high-dose SS group than those in control group (p<0. 05 or p<0. 01). In H520 cells, compared with control group, the protein levels of VEGF, p-PI3K and p-Akt in SS treatment groups were significantly decreased (p<0. 05 or p< 0. 01). CONCLUSION: Sodium selenite inhibits the viability and migration of HUVEC, H520 cells and A549 cells, and inhibits the formation of vasculogenic mimicry and mosaic vessels in NSCLC cells. This mechanism may be related to the inhibition of PI3K-Akt signaling pathway activation and regulation of VEGF. [ABSTRACT FROM AUTHOR]

OBJECTIVES Invasive mucinous adenocarcinoma exhibits distinct prognostic outcomes compared to non-mucinous adenocarcinoma (ADC). This study investigated and compared the clinical outcomes and prognostic factors of invasive mucinous and non-mucinous ADC patients. METHODS This retrospective study included patients who underwent curative surgery for ADC between 2011 and 2021. Patient characteristics were balanced using propensity score matching. Cumulative incidence was analysed to evaluate cancer recurrence incidence, and the Kaplan–Meier method was used to calculate overall survival (OS) for each group. RESULTS A total of 6101 patients were included. After matching, the non-mucinous group and mucinous groups comprised 798 and 408 patients, respectively. The patients in the mucinous group had a lower recurrence incidence than those in the non-mucinous group (P  = 0.014). The recurrence incidence in the mucinous group was between those of grades 1 (P  = 0.011) and 2 (P  = 0.012) and the OS rates were comparable to those of grades 2 (P  = 0.6) and 3 (P  = 0.2). Multivariable analysis revealed that the maximal standardized uptake value [hazard ratio (HR): 1.13, P  = 0.11] and progressed pathological stages (pStage II, HR: 3.9, P  = 0.028; pStage III, HR: 8.33, P  = 0.038) served as adverse prognostic factors for the mucinous group. CONCLUSIONS Patients with mucinous ADC demonstrated lower recurrence incidence and similar OS rates compared to those with non-mucinous ADC. The recurrence incidence of mucinous ADC was between those of International Association for the Study of Lung Cancer grades 1 and 2, with the OS rates comparable to those of grades 2 and 3. CLINICAL REGISTRATION NUMBER None. [ABSTRACT FROM AUTHOR]

Since the initial US FDA approval of an immune checkpoint inhibitor (ICI) for the treatment of non-oncogene-driven non-small-cell lung cancer (NSCLC) nine years ago, this therapeutic strategy has been cemented as a crucial component of treatment for most of these patients. However, there is a clear efficacy–effectiveness gap whereby patients in the 'real world' seem to have more modest clinical outcomes compared to those enrolled in landmark clinical trials. This gap may be driven by the under-representation of important patient populations, including populations defined by clinical or molecular characteristics. In this review, we summarize the data outlining the evidence of ICIs in patients with poor Eastern Cooperative Oncology Group performance status (ECOG PS), underlying autoimmune disease (AID), older age, active brain metastases (BMs), and molecular aberrations such as EGFR mutations, ALK fusions, BRAF mutations and ROS1 fusions. [ABSTRACT FROM AUTHOR]

Non‐small‐cell lung cancer (NSCLC) accounts for the majority of lung cancer cases worldwide, with a significant proportion of patients harbouring actionable oncogenic alterations. Among these alterations, the ROS1 rearrangement represents a distinct subset with therapeutic implications. Here, we present the case of a 52‐year‐old man diagnosed with advanced NSCLC harbouring the ROS1 fusion gene. Despite the initial poor response to conventional chemotherapy, the patient exhibited an exceptional and sustained response to crizotinib, with a progression‐free survival of 94 months and complete metabolic response on PET scan. This case underscores the importance of molecular profiling in guiding treatment decisions and highlights the efficacy of targeted therapies for ROS1‐positive NSCLC. [ABSTRACT FROM AUTHOR]

Introduction: Artificial intelligence image recognition has applications in clinical practice. The purpose of this study was to develop an automated image classification model for lung cancer cytology using a deep learning convolutional neural network (DCNN). Methods: Liquid-based cytology samples from 8 normal parenchymal (N), 22 adenocarcinoma (ADC), and 15 squamous cell carcinoma (SQCC) surgical specimens were prepared, and 45 Papanicolaou-stained slides were scanned using whole-slide imaging. The final dataset of 9,141 patches consisted of 2,737 N, 4,756 ADC, and 1,648 SQCC samples. Densenet-121 was used as the DCNN to classify N versus malignant (ADC+SQCC) and ADC versus SQCC images. AdamW optimizer and 5-fold cross-validation were used in the training. Results: For malignancy prediction, the sensitivity, specificity, and accuracy were 0.97, 0.85, and 0.94, respectively, in the patch-level classification, and 0.92, 0.88, and 0.91, respectively, in the case-level classification. For SQCC prediction, the sensitivity, specificity, and accuracy were 0.86, 0.91, and 0.90, respectively, in the patch-level classification and 0.73, 0.82, and 0.78, respectively, in the case-level classification. Conclusion: The DCNN model performed excellently in predicting malignancy and histological types of lung cancer. This model may be useful for predicting cytopathological diagnosis in clinical situations by reinforcing training. [ABSTRACT FROM AUTHOR]

A 73-year-old man with lung squamous cell carcinoma was administered carboplatin + nab-paclitaxel + pembrolizumab for four cycles. Subsequently, he presented with multiple purpuras on his extremities, joint swelling on his fingers, abdominal pain, and diarrhea, accompanied by acute kidney injury (AKI), increased proteinuria, hematuria, and elevated C-reactive protein levels. Skin biopsy showed leukocytoclastic vasculitis as well as IgA and C3 deposition in the vessel walls. Based on these findings, the patient was diagnosed with IgA vasculitis as an immune-related adverse event (irAE) induced by carboplatin + nab-paclitaxel + pembrolizumab. After discontinuation of pembrolizumab and glucocorticoids, the symptoms immediately resolved. Regular monitoring of skin, blood tests, and urinalysis are necessary, and the possibility of irAE IgA vasculitis should be considered in cases of purpura and AKI during treatment with immune checkpoint inhibitors. [ABSTRACT FROM AUTHOR]

Background and Objective: The aim of this study is to evaluate the effectiveness of apparent diffusion coefficient (ADC) values in predicting pathologic subtypes and grade in non-small-cell lung cancer (NSCLC). Materials and Methods: From January 2018 to March 2020, 48 surgically diagnosed NSCLC cases were included in this study. To obtain ADC values, ADC maps were constructed, and a region of interest was put on the tumor. The values were measured three times from different places of the lesion, and the mean value of these measurements was recorded. All MRI scans were evaluated by two radiologists in consensus. Results: A total of 14 cases were squamous cell cancer, 32 cases were adenocarcinoma, and 2 cases were large cell carcinoma. The mean ADC values of adenocarcinoma, squamous cell carcinoma, and large cell cancer were 1.51 ± 0.19 × 10−3 mm2/s, 1.32 ± 0.15 × 10−3 mm2/s, and 1.39 ± 0.25 × 10−3 mm2/s, respectively. There were 11 grade 1, 27 grade 2, and 10 grade 3 NSCLC cases. The mean ADC value was 1.44 ± 0.14 × 10−3 mm2/s in grade 1 tumors, 1.25 ± 0.10 × 10−3 mm2/s in grade 2 tumors, and 1.07 ± 0.15 × 10−3 mm2/s in grade 3 tumors. The cut-off value to discriminate grade 2 from grade 1 tumors was 1.31 ± 0.11 × 10−3 mm2/s (85% sensitivity, 75% specificity). The cut-off value to discriminate grade 3 from grade 2 tumors was 1.11 ± 0.15 × 10−3 mm2/s (87% sensitivity, 69% specificity). Conclusions: ADC values can accurately predict NSCLC histopathologic subtypes and tumor grade. [ABSTRACT FROM AUTHOR]

ROS1 rearrangements are considered rare in non-small-cell lung cancer (NSCLC). This retrospective real-world study aimed to evaluate first-line treatment with crizotinib, a tyrosine kinase inhibitor (TKI) standard of care vs. new generation ROS1 anti-cancer agents. Forty-nine ROS1-expressing NSCLC patients, diagnosed with advanced metastatic disease, were included. Molecular profiling using either FISH/CISH or NGS was performed on tissue samples. Twenty-eight patients were treated with crizotinib, while fourteen patients were administered newer drugs (entrectinib, repotrectinib) and seven patients received platinum-doublet chemotherapy in a first-line setting. Overall response rate and disease control rate for the crizotinib and entrectinb/repotrectinib cohort were 68% and 82% vs. 86% and 93%, respectively. Median progression free survival was 1.6 years (95% CI 1.15–2.215) for the crizotinib treatment vs. 2.35 years for the entrectinib/repotrectinib cohort (95% CI 1.19–3.52). Central nervous system progression was noted in 20% and 25% of the crizotinib and entrectinib/repotrectinib cohorts, respectively. This multi-center study presents real-world treatment patterns of ROS1 NSCLC population, indicating that crizotinib exhibited comparable results to entrectinib/repotrectinib in a first-line setting, although both response rate and survival was numerically longer with treatment with newer agents. [ABSTRACT FROM AUTHOR]

In advanced non-squamous non-small-cell lung cancer (NSCLC), routine testing with next-generation sequencing (NGS) is recommended to identify actionable genomic alterations (AGAs). The therapeutic implications of repeated NGS testing on synchronous and metachronous tumors are unclear. Between February 2017 and October 2020, NSCLC samples from a single institution were reflex-tested using a targeted 15-gene NGS panel (TruSight Tumor 15, Illumina). Thirty-eight patients were identified with multiple NGS results from 82 samples: 11% were from single unifocal, 51% were from synchronous, and 38% were from metachronous tumors. Changes in EGFR, KRAS, PI3KCA, and TP53 variants were found in 22 patients' samples (58%). No changes were seen with longitudinal testing of multiple samples from single unifocal tumors, while changes were observed in 60% of synchronous and 71% of metachronous tumors. Of these, 26% of patients had AGA differences between samples. Acknowledging the limited sample size, a significant difference in overall survival was observed between synchronous separate primaries and metastasis. Repeat NGS testing of synchronous and metachronous NSCLC tumors may identify differing variants in >50% of patients. These changes may reflect separate primary lung carcinomas, tumor heterogeneity among intrapulmonary metastases, and clonal evolution. NGS testing of multiple tumors may enhance the identification of therapeutic targets for treatment decisions. [ABSTRACT FROM AUTHOR]

Background: Radiomics provided opportunities to quantify the tumor phenotype non-invasively. This study extracted contrast-enhanced computed tomography (CECT) radiomic signatures and evaluated clinical features of bone metastasis in non-small-cell lung cancer (NSCLC). With the combination of the revealed radiomics and clinical features, the predictive modeling on bone metastasis in NSCLC was established. Methods: A total of 318 patients with NSCLC at the Tianjin Medical University Cancer Institute & Hospital was enrolled between January 2009 and December 2019, which included a feature-learning cohort (n = 223) and a validation cohort (n = 95). We trained a radiomics model in 318 CECT images from feature-learning cohort to extract the radiomics features of bone metastasis in NSCLC. The Kruskal-Wallis and the least absolute shrinkage and selection operator regression (LASSO) were used to select bone metastasis-related features and construct the CT radiomics score (Rad-score). Multivariate logistic regression was performed with the combination of the Rad-score and clinical data. A predictive nomogram was subsequently developed. Results: Radiomics models using CECT scans were significant on bone metastasis prediction in NSCLC. Model performance was enhanced with each information into the model. The radiomics nomogram achieved an AUC of 0.745 (95% confidence interval [CI]: 0.68,0.80) on predicting bone metastasis in the training set and an AUC of 0.808(95% confidence interval [CI]: 0.71,0.88) in the validation set. Conclusion: The revealed invisible image features were of significance on guiding bone metastasis prediction in NSCLC. Based on the combination of the image features and clinical characteristics, the predictive nomogram was established. Such nomogram can be used for the auxiliary screening of bone metastasis in NSCLC. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study is to assess the impact of physical activity on both therapeutic efficacy and immune-related adverse events (irAEs) during immunotherapy for non-small cell lung cancer (NSCLC). Methods: Physical activity was divided into three groups: light physical activity (LPA), moderate physical activity (MPA), and vigorous physical activity (VPA) for laboratory indexes, efficacy, and irAEs. A multivariate logistic regression was employed to analyze the relationship between sedentary behavior with efficacy and irAEs. Results: The study included 121 patients. The three levels of physical activity were not significantly associated with efficacy or irAEs. However, noteworthy disparities were observed in base-hemoglobin levels (F = 3.4, P = 0.037) and base-lymphocyte levels (χ2 = 6.13, P = 0.047) among the three groups. After treatment, we identified statistically significant variations in albumin levels (P = 0.012) and lymphocyte counts (P = 0.035). Furthermore, a negative correlation emerged between pre-treatment sedentary behavior duration and immune-efficacy (β: −0.005, P = 0.027). Conclusions: In summary, within the cohort of NSCLC patients undergoing single immunotherapy or a combination of immunotherapy and chemotherapy, physical activity is closely related to immune and inflammatory indicators in patients, and prolonged sitting will reduce the therapeutic effect. [ABSTRACT FROM AUTHOR]

Background and Objectives: Lung cancer is the leading cause of cancer-related deaths. Spread through air spaces (STAS) is an adverse prognostic factor that has become increasingly known in recent years. This study aims to investigate the impact of STAS presence on overall survival (OS) and disease-free survival (DFS) in patients with surgically resected stage IA-IIIA lung cancer and to identify clinicopathological features associated with STAS. Materials and Methods: This research involved 311 lung cancer surgery patients. The relationship between the presence of STAS in the patients' surgical pathology and OS and DFS values was examined. Clinicopathological features associated with the presence of STAS were determined. Results: There were 103 (33%) STAS-positive patients. Adenocarcinoma histological subtype, perineural invasion (PNI), and lymphovascular invasion (LVI) were significantly correlated with being STAS positive. STAS significantly predicted DFS and OS. One-year and five-year DFS rates were significantly lower in the STAS-positive group compared to the STAS-negative group (65% vs. 88%, 29% vs. 62%, respectively, p ≤ 0.001). Similarly, one-year and five-year OS rates were significantly lower in the STAS-positive group compared to the STAS-negative group (92% vs. 94%, 54% vs. 88%, respectively, p ≤ 0.001). In multivariate analysis, STAS was found to be an independent prognostic factor for both DFS and OS (HR: 3.2 (95%CI: 2.1–4.8) and 3.1 (95%CI: 1.7–5.5), p < 0.001 and <0.001, respectively). Conclusions: In our study, STAS was found to be an independent prognostic biomarker in operated stage IA-IIIA lung cancer patients. It may be a beneficial pathological biomarker in predicting the survival of patients and managing their treatments. [ABSTRACT FROM AUTHOR]

Recent advancements in targeted therapies for non-small-cell lung cancer (NSCLC), specifically focusing on epidermal growth factor receptor (EGFR) mutations, have revolutionized treatment strategies. Osimertinib, an approved therapy for metastatic NSCLC with EGFR mutations, highlights remarkable efficacy but also harbors the potential for severe adverse events, whose rarity or lack of precedence may mask their criticality. This article delves into the exploration of adverse events linked to osimertinib, shedding light on a rare yet life-threatening occurrence: severe myelosuppression. A case study detailing a patient with EGFR-mutated NSCLC exhibiting a robust treatment response but experiencing severe myelosuppression following osimertinib initiation is presented. Immediate discontinuation of osimertinib alongside concurrent blood transfusions facilitated toxicity recovery, prompting a successful reduction in myelosuppression severity upon re-administration at a lowered dosage. [ABSTRACT FROM AUTHOR]

Introduction: This systematic review and network meta-analysis(NMA) was designed to compare the long-term outcomes of pembrolizumab monotherapy and pembrolizumab plus chemotherapy as first-line therapy for metastatic non-small-cell lung cancer(NSCLC). Materials and Methods: Four databases(Medline, Embase, Web of Science and CENTRAL were searched published from establishment of database to August 17, 2023, for articles studying pembrolizumab monotherapy or pembrolizumab plus chemotherapy for non-small cell lung cancer (NSCLC). Network meta-analyses of progression-free survival(PFS), overall survival(OS), objective response rate (ORR), treatment-related adverse events(trAEs) and immune-related adverse events(irAEs) were performed. Results: A total of five studies were considered for NMA. This NMA includes a cohort of 2878 patients diagnosed with advanced NSCLC. Among them, 791 patients received pembrolizumab monotherapy, 1337 patients received chemotherapy, and 748 patients received pembrolizumab plus chemotherapy. The IPDformKM software was utilized to reconstruct Kaplan-Meier curves for OS and PFS, offering a lucid and intuitive depiction of oncological outcomes. For patients who have high levels of programmed death-ligand 1(PD-L1) expression (≥50%), pembrolizumab plus chemotherapy was more effective than using pembrolizumab alone as first-line therapy in terms of PFS (median survival time: 10.41 months versus 7.41 months, HR: 0.81, 95%CI 0.67 to 0.97, P=0.02) and ORR (RR:1.74, 95% CI: 1.25-2.43). Nevertheless, there was no statistically significant difference observed between the two groups in terms of OS (median survival time: 22.54 months versus 22.62 months, HR: 0.89, 95%CI 0.73 to 1.08, P=0.24). Furthermore, pembrolizumab plus chemotherapy provided a more advantageous long-term survival advantage in terms of OS (median survival time: 20.88 months versus 13.60 months, HR: 0.77, 95%CI: 0.62 to 0.95, P=0.015) compared to pembrolizumab monotherapy in patients with low PD-L1 expression levels (1% to 49%). With regards to safety, there was no statistically significant disparity between the two groups in relation to any irAEs (RD=0.02, 95% CI: -0.12 to 0.16) or Grade≥ 3 irAEs (RD=0.01, 95% CI: -0.10 to 0.12). Nevertheless, pembrolizumab plus chemotherapy exhibited a greater likelihood of encountering any trAEs (RD=0.23, 95% CI: 0.17 to 0.30) and Grade≥ 3 trAEs (RD=0.28, 95% CI: 0.21 to 0.35) in comparison to pembrolizumab monotherapy. Conclusions: The present network meta-analysis reported comparative longterm outcomes of pembrolizumab plus chemotherapy versus pembrolizumab monotherapy as first-line therapy for metastatic non-small-cell lung cancer. Pembrolizumab plus chemotherapy led to improved PFS and ORR in patients with advanced NSCLC who had a PD-L1 expression level of 50% or above. However, there was no noticeable benefit in terms of OS when pembrolizumab was paired with chemotherapy compared to utilizing pembrolizumab alone. In addition, pembrolizumab plus chemotherapy offered a greater long-term survival benefit in terms of OS when compared to utilizing pembrolizumab alone in patients with PD-L1 expression levels ranging from 1% to 49%. Furthermore, the increased effectiveness of pembrolizumab plus chemotherapy was accompanied by an increase in adverse side effects. [ABSTRACT FROM AUTHOR]

Background: The identification of cancer driver genes from sequencing data has been crucial in deepening our understanding of tumor biology and expanding targeted therapy options. However, apart from the most commonly altered genes, the mechanisms underlying the contribution of other mutations to cancer acquisition remain understudied. Leveraging on our whole-exome sequencing of the largest Asian lung adenocarcinoma (LUAD) cohort (n = 302), we now functionally assess the mechanistic role of a novel driver, PARP4. Methods: In vitro and in vivo tumorigenicity assays were used to study the functional effects of PARP4 loss and mutation in multiple lung cancer cell lines. Interactomics analysis by quantitative mass spectrometry was conducted to identify PARP4's interaction partners. Transcriptomic data from cell lines and patient tumors were used to investigate splicing alterations. Results: PARP4 depletion or mutation (I1039T) promotes the tumorigenicity of KRAS- or EGFR-driven lung cancer cells. Disruption of the vault complex, with which PARP4 is commonly associated, did not alter tumorigenicity, indicating that PARP4's tumor suppressive activity is mediated independently. The splicing regulator hnRNPM is a potentially novel PARP4 interaction partner, the loss of which likewise promotes tumor formation. hnRNPM loss results in splicing perturbations, with a propensity for dysregulated intronic splicing that was similarly observed in PARP4 knockdown cells and in LUAD cohort patients with PARP4 copy number loss. Conclusions: PARP4 is a novel modulator of lung adenocarcinoma, where its tumor suppressive activity is mediated not through the vault complex—unlike conventionally thought, but in association with its novel interaction partner hnRNPM, thus suggesting a role for splicing dysregulation in LUAD tumorigenesis. [ABSTRACT FROM AUTHOR]

Tissue-resident memory T cells (TRM) are a specialized subset of long-lived memory T cells that reside in peripheral tissues. However, the impact of TRM-related immunosurveillance on the tumor-immune microenvironment (TIME) and tumor progression across various non-small-cell lung cancer (NSCLC) patient populations is yet to be elucidated. Our comprehensive analysis of multiple independent single-cell and bulk RNA-seq datasets of patient NSCLC samples generated reliable, unique TRM signatures, through which we inferred the abundance of TRM in NSCLC. We discovered that TRM abundance is consistently positively correlated with CD4+ T helper 1 cells, M1 macrophages, and resting dendritic cells in the TIME. In addition, TRM signatures are strongly associated with immune checkpoint and stimulatory genes and the prognosis of NSCLC patients. A TRM-based machine learning model to predict patient survival was validated and an 18-gene risk score was further developed to effectively stratify patients into low-risk and high-risk categories, wherein patients with high-risk scores had significantly lower overall survival than patients with low-risk. The prognostic value of the risk score was independently validated by the Cancer Genome Atlas Program (TCGA) dataset and multiple independent NSCLC patient datasets. Notably, low-risk NSCLC patients with higher TRM infiltration exhibited enhanced T-cell immunity, nature killer cell activation, and other TIME immune responses related pathways, indicating a more active immune profile benefitting from immunotherapy. However, the TRM signature revealed low TRM abundance and a lack of prognostic association among lung squamous cell carcinoma patients in contrast to adenocarcinoma, indicating that the two NSCLC subtypes are driven by distinct TIMEs. Altogether, this study provides valuable insights into the complex interactions between TRM and TIME and their impact on NSCLC patient prognosis. The development of a simplified 18-gene risk score provides a practical prognostic marker for risk stratification. [ABSTRACT FROM AUTHOR]

The emergence of targeted therapies in non-small-cell lung cancer (NSCLC), including inhibitors of epidermal growth factor receptor (EGFR) tyrosine kinase, has increased the need for robust companion diagnostic tests. Nowadays, detection of actionable variants in exons 18–21 of the EGFR gene by qPCR and direct DNA sequencing is often replaced by next-generation sequencing (NGS). In this study, we evaluated the diagnostic usefulness of targeted NGS for druggable EGFR variants testing in clinical NSCLC material previously analyzed by the IVD-certified qPCR test with respect to DNA reference material. We tested 59 NSCLC tissue and cytology specimens for EGFR variants using the NGS 'TruSight Tumor 15' assay (Illumina) and the qPCR 'cobas EGFR mutation test v2' (Roche Diagnostics). The sensitivity and specificity of targeted NGS assay were evaluated using the biosynthetic and biological DNA reference material with known allelic frequencies (VAF) of EGFR variants. NGS demonstrated a sufficient lower detection limit for diagnostic applications (VAF < 5%) in DNA reference material; all EGFR variants were correctly identified. NGS showed high repeatability of VAF assessment between runs (CV% from 0.02 to 3.98). In clinical material, the overall concordance between NGS and qPCR was 76.14% (Cohen's Kappa = 0.5933). The majority of discordant results concerned false-positive detection of EGFR exon 20 insertions by qPCR. A total of 9 out of 59 (15%) clinical samples showed discordant results for one or more EGFR variants in both assays. Additionally, we observed TP53 to be a frequently co-mutated gene in EGFR-positive NSCLC patients. In conclusion, targeted NGS showed a number of superior features over qPCR in EGFR variant detection (exact identification of variants, calculation of allelic frequency, high analytical sensitivity), which might enhance the basic diagnostic report. [ABSTRACT FROM AUTHOR]

Third-generation tyrosine kinase inhibitors are the first-line gold standard in treating advanced non-small-cell lung cancer bearing common EGFR mutations, but data documenting clinical efficacy in uncommon mutations are currently limited. In this paper, we describe the case of a patient bearing uncommon compound EGFR mutations in exon 20, who experienced a near-complete response to third-line Osimertinib, with metabolic complete response of pulmonary, nodal and ostheolytic lesions. This radiological assessment corresponded to an ECOG PS improvement (from three to one) and a substantial clinical benefit for the patients. Out of two mutations, S768I was associated with poor response to third-generation TKI and V774M had unknown clinical significance, highlighting the complexity of the correct management of these kinds of mutations. We reviewed the literature to document the up-to-date preclinical and clinical data concerning third-generation tyrosine kinase inhibitors for the treatment of patients bearing uncommon EGFR mutations. [ABSTRACT FROM AUTHOR]

Objective: To compare the uniportal and multiportal video-assisted thoracoscopic surgery (VATS) in patients with nonsmall- cell lung cancer (NSCLC). Methods: Medical records of 128 patients with NSCLC who underwent surgical treatment in the First School of Clinical Medicine, Southern Medical University from August 2020 to February 2022 were retrospectively analyzed. There were 60 patients who underwent uniportal VATS (UVATS group) and 68 patients underwent multiportal VATS (MVATS group). The relevant indexes, complications, postoperative pain levels and quality of life, recurrence, metastases and survival between the two groups were compared. Results: UVATS was associated with longer operation time and higher intraoperative blood loss compared to MVATS (P<0.05). The postoperative drainage volume, and the visual analogue scale (VAS) scores at 24 and 72 hours were lower in the UVATS group compared to the MVATS group, while the chest tube retention time and hospitalization time were shorter than those in the MVATS group (P<0.05). The quality of life at six months after surgery in the UVATS group was significantly higher than that in the MVATS group (P<0.05). Conclusions: UVATS and MVATS have similar outcomes in patients with NSCLC. Although UVATS surgery takes longer and is associated with more interoperative bleeding, it can reduce postoperative pain, shorten postoperative recovery time, and help further improve the quality of life of patients after surgery. [ABSTRACT FROM AUTHOR]

We performed a systematic review and meta-analysis to assess the efficacy of EGFR-tyrosine kinase inhibitors (TKI) retreatment in advanced/metastatic non-small-cell lung cancer (NSCLC) patients. We systematically searched PubMed, Embase, Cochrane databases, ASCO, and ESMO websites for studies evaluating EGFR-TKI retreatment in advanced/metastatic NSCLC patients. All analyses were performed using R software (v.4.2.2). We included 19 studies (9 CTs and 10 retrospective cohorts) with a total of 886 patients. In a pooled analysis of all patients during retreatment with TKI, median OS was 11.7 months (95% confidence interval [CI] 10.2–13.4 months) and PFS was 3.2 months (95% CI 2.5–3.9 months). ORR was 15% (95% CI 10–21%) and DCR was 61% (95% CI 53–67%). The subanalysis by generation of TKI in the rechallenge period revealed a slightly better ORR for patients on 3rd generation TKI (p = 0.05). Some limitations include the high heterogeneity of some of the analyses and inability to perform certain subanalyses. Our results unequivocally support the benefit of EGFR-TKI rechallenge in EGFR-mutated NSCLC patients progressing on TKI treatment after a TKI-free interval. These findings may be especially valuable in areas where access to novel therapeutic drugs and clinical trials is limited. [ABSTRACT FROM AUTHOR]

Objectives: Non‐small‐cell lung carcinoma (NSCLC) is the most prevalent and lethal form of lung cancer. The need for biomarker‐informed stratification of targeted therapies has underpinned the need to uncover the underlying properties of the tumor microenvironment (TME) through high‐plex quantitative assays. Methods: In this study, we profiled resected NSCLC tissues from 102 patients by targeted spatial proteomics of 78 proteins across tumor, immune activation, immune cell typing, immune‐oncology, drug targets, cell death and PI3K/AKT modules to identify the tumor and stromal signatures associated with overall survival (OS). Results: Survival analysis revealed that stromal CD56 (HR = 0.384, P = 0.06) and tumoral TIM3 (HR = 0.703, P = 0.05) were associated with better survival in univariate Cox models. In contrast, after adjusting for stage, BCLXL (HR = 2.093, P = 0.02) and cleaved caspase 9 (HR = 1.575, P = 0.1) negatively influenced survival. Delta testing indicated the protective effect of TIM‐3 (HR = 0.614, P = 0.04) on OS. In multivariate analysis, CD56 (HR = 0.172, P = 0.001) was associated with better survival in the stroma, while B7.H3 (HR = 1.72, P = 0.008) was linked to poorer survival in the tumor. Conclusions: Deciphering the TME using high‐plex spatially resolved methods is giving us new insights into compartmentalised tumor and stromal protein signatures associated with clinical endpoints in NSCLC. [ABSTRACT FROM AUTHOR]

Introduction. Inflammation is known to be related to the development, spread, prognosis, and treatment response in cancer patients. Our study aimed to evaluate the correlation between inflammation indices and positron emission tomography-computed tomography (PET/CT) parameters and investigate their relationship with progression-free survival (PFS) and overall survival (OS) in patients diagnosed with stage-IV non-small cell lung cancer (NSCLC). Material and methods. Demographic, clinicopathological, laboratory, and PET/CT data of 179 patients diagnosed with stage-IV NSCLC who presented to the Oncology Department of Dicle University, Faculty of Medicine between 2010-2020 were retrieved from patient files and the hospital database system. Results. The median age at diagnosis was 64 (27-87) years. All patients included in the study had NSCLC: 72.6% had adenocarcinoma, 21.2% had squamous cell carcinoma, and 6.1% had other histological types. Of the 78 patients who were subjected to molecular analysis, 26 (33.3%) were EGFR-mutation positive. During the 10-month median follow-up, median first-line PFS was 6 months (95% CI 5.00-6.99), and median OS was 10 months (95% CI 7.8-12.1). The multivariate analysis performed for first-line PFS determined hemoglobin (HR = 1.01; 95% CI 1.003-1.02; p = 0.005) and PET total lesion glycolysis (TLG) (HR = 1.002; 95% CI 1.001-1.003; p = 0.003) values as independent prognostic factors. The multivariate analysis for OS determined positive EGFR mutation status (HR = 0.385; 95% CI 0.213-0.696; p = 0,014) and performance status (HR = 1.88; 95% CI 1.092-3.238; p = 0,008) as independent prognostic factors. Conclusions. Our study determined the hemoglobin level and PET TLG from PET/CT parameters to be independent prognostic factors for PFS, and performance status and EGFR mutation positivity to be independent prognostic factors for OS. [ABSTRACT FROM AUTHOR]

The emergence of acquired resistance to EGFR-tyrosine kinase inhibitors (TKIs) is almost inevitable even after a remarkable clinical response. Secondary mutations such as T790M and C797S are responsible for the resistance to 1st/2nd-generation (1/2G) TKIs and 3G TKIs, respectively. To overcome both the T790M and C797S mutations, novel 4G EGFR-TKIs are now under early clinical development. In this study, we evaluated the efficacy of a 4G EGFR-TKI in the treatment of lung cancer with EGFR mutation as well as explored resistance mechanisms to a 4G TKI. First, we compared the efficacies of seven TKIs including a 4G TKI, BI4020, against Ba/F3 cell models that simulate resistant tumors after front-line osimertinib treatment failure because of a secondary mutation. We also established acquired resistant cells to BI4020 by chronic drug exposure. Ba/F3 cells with an osimertinib-resistant secondary mutation were refractory to all 3G TKIs tested (alflutinib, lazertinib, rezivertinib, almonertinib, and befotertinib). BI4020 inhibited the growth of C797S-positive cells; however, it was not effective against L718Q-positive cells. Erlotinib was active against all Ba/F3 cells tested. In the analysis of resistance mechanisms of BI4020-resistant (BIR) cells, none harbored secondary EGFR mutations. HCC827BIR cells had MET gene amplification and were sensitive to a combination of capmatinib (MET-TKI) and BI4020. HCC4006BIR and H1975BIR cells exhibited epithelial-to-mesenchymal transition. This study suggests that erlotinib may be more suitable than 4G TKIs to overcome secondary mutations after front-line osimertinib. We found that off-target mechanisms that cause resistance to earlier-generation TKIs will also cause resistance to 4G TKIs. [ABSTRACT FROM AUTHOR]

Lung cancer is the leading cause of global cancer-related deaths. Platinum-based chemotherapy is the first-line treatment for the most common type of lung cancer, i.e., non-small-cell lung cancer (NSCLC), but its therapeutic efficiency is limited by chemotherapeutic resistance. Therefore, it is vital to develop effective therapeutic modalities that bypass the common molecular mechanisms associated with chemotherapeutic resistance. Ferroptosis is a form of nonapoptotic regulated cell death characterized by iron-dependent lipid peroxidation (LPO). Ferroptosis is crucial for the proper therapeutic efficacy of lung cancer-associated chemotherapies. If targeted as a novel therapeutic mechanism, ferroptosis modulators present new opportunities for increasing the therapeutic efficacy of lung cancer chemotherapy. Emerging studies have revealed that the pharmacological induction of ferroptosis using natural compounds boosts the efficacy of chemotherapy in lung cancer or drugresistant cancer. In this review, we first discuss chemotherapeutic resistance (or chemoresistance) in lung cancer and introduce the core mechanisms behind ferroptosis. Then, we comprehensively summarize the small-molecule compounds sourced from traditional medicines that may boost the antitumor activity of current chemotherapeutic agents and overcome chemotherapeutic resistance in NSCLC. Cumulatively, we suggest that traditional medicines with ferroptosis-related anticancer activity could serve as a starting point to overcome chemotherapeutic resistance in NSCLC by inducing ferroptosis, highlighting new potential therapeutic regimens used to overcome chemoresistance in NSCLC. [ABSTRACT FROM AUTHOR]

Cancer immunotherapy in the form of immune checkpoint inhibitors has led to a dramatic increase in the survival of patients with lung cancer across all stages. Over the past decade, the field has experienced rapid maturation; however, several challenges continue to complicate patient management. This review aims to highlight the data that led to this dramatic shift in practice as well as to focus on key challenges. These include determining the optimal therapy duration, managing frail patients or those with brain metastases, addressing the challenges posed by immune-related adverse events, and defining the various patterns of clinical and radiological responses to immunotherapy. [ABSTRACT FROM AUTHOR]

OBJECTIVES In patients with oligometastatic non-small-cell lung cancer (NSCLC), systemic therapy in combination with local ablative treatment of the primary tumour and all metastatic sites is associated with improved prognosis. For patient selection and treatment allocation, further knowledge about the molecular characteristics of the oligometastatic state is necessary. Here, we performed a genetic characterization of primary NSCLC and corresponding brain metastases (BM). METHODS We retrospectively identified patients with oligometastatic NSCLC and synchronous (<3 months) or metachronous (>3 months) BM who underwent surgical resection of both primary tumour and BM. Mutation profiling of formalin-fixed paraffin-embedded tumour cell blocks was performed by targeted next-generation sequencing using the Oncomine Focus Assay panel. RESULTS Sequencing was successful in 46 paired samples. An oncogenic alteration was present in 31 primary tumours (67.4%) and 40 BM (86.9%). The alteration of the primary tumours was preserved in the corresponding BM in 29 out of 31 cases (93.5%). The most prevalent oncogenic driver in both primary tumours and BM was a KRAS (Kirsten rat sarcoma viral oncogene) mutation (s  = 21). In 16 patients (34.8%), the BM harboured additional oncogenic alterations. The presence of a private genetic alteration in the BM was an independent predictor of shorter overall survival. CONCLUSIONS In oligometastatic NSCLC, BM retain the main genetic alterations of the primary tumours. Patients may profit from targeted inhibition of mutated KRAS. Additional private genetic alterations in the BM are dismal. [ABSTRACT FROM AUTHOR]

Non-small-cell lung cancer (NSCLC) frequently harbors mutations in the epidermal growth factor receptor (EGFR), with exon 20 insertions comprising 1–10% of these mutations. EGFR exon 20 insertions are less responsive to conventional tyrosine kinase inhibitors (TKIs), leading to the development of targeted agents. This review explores key therapeutic agents, such as Amivantamab, Mobocertinib, Poziotinib, Zipalertinib, and Sunvozertinib, which have shown promise in treating NSCLC with EGFR exon 20 insertions. Amivantamab, a bispecific antibody-targeting EGFR and c-MET, demonstrates significant efficacy, particularly when combined with chemotherapy. Mobocertinib, a TKI, selectively targets EGFR exon 20 mutations but faces limitations in efficacy. Poziotinib, another oral TKI, shows mixed results due to mutation-specific responses. Zipalertinib and Sunvozertinib have emerged as potent TKIs with promising clinical data. Despite these advances, challenges in overcoming resistance mutations and improving central nervous system penetration remain. Future research should focus on optimizing first-line combination therapies and enhancing diagnostic strategies for comprehensive mutation profiling. [ABSTRACT FROM AUTHOR]

• CircMYBL1 suppressed acquired resistance to osimertinib in non-small-cell lung cancer cells. • The results suggest that circMYBL1 could play an important role in facilitating growth and metastasis in susceptible cells. • In-silico analysis and the results show that the target genes of circMYBL1 are involved in tumor growth and metastasis. Circular RNAs (circRNAs) play an important role in the development of acquired resistance to many anticancer drugs. We developed the Non-Small-Cell Lung Cancer (NSCLC) cell lines with acquired resistance to osimertinib, a third-generation of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), and evaluated the different expression profiles of circRNAs in osimertinib-sensitive and -resistant NSCLC cell lines using RNA sequencing (RNA-Seq). The expression of selected differentially expressed circRNAs was verified using quantitative real-time PCR (qRT-PCR) in paired osimertinib-sensitive and -resistant NSCLC cell lines, and in plasma samples of osimertinib-sensitive and -resistant NSCLC patients. We found that circMYBL1(has_circ_0136924) was downregulated after acquired resistance to osimertinib, inhibiting circMYBL1 expression facilitated the proliferation, migration, and invasion in osimertinib-sensitive NSCLC cells. CircMYBL1 may be a novel molecular biomarker and therapeutic target for osimertinib-resistant NSCLC. [ABSTRACT FROM AUTHOR]

TP53 comutation is related to poor prognosis of non‐small cell lung cancer. However, there is limited study focusing on the structural influence of TP53 mutation on third‐generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) treatment. We retrospectively analyzed the clinical and molecular data of patients treated with third‐generation EGFR‐TKIs in two independent cohorts. A total of 117 patients from the Sun Yat‐sen University Cancer Center (SYSUCC) and 141 patients from the American Association for Cancer Research Project GENIE database were included. In the SYSUCC cohort, TP53 comutations were found in 59 patients (50.4%) and were associated with poor median progress‐free survival (mPFS) and median overall survival (mOS). The additional subtype analysis found that TP53 mutation in the alpha‐helix region had shorter mOS compared with those with TP53 mutations in other regions in the SYSUCC cohort (mOS, 12.2 vs. 21.7 months; p = 0.027). Similar findings were confirmed in the GENIE cohort. Specifically, the presence of TP53 mutation in the alpha‐helix region was an independent negative predictive factor for PFS [hazard ratio (HR) 2.05(1.01–4.18), p = 0.048] and OS [HR 3.62(1.60–8.17), p = 0.002] in the SYSUCC cohort. TP53 mutation in alpha‐helix region was related to inferior clinical outcomes in patients treated with third‐generation EGFR‐TKIs. [ABSTRACT FROM AUTHOR]

(1) Background: Non-small-cell lung cancer (NSCLC) represents a significant global health challenge, contributing to numerous cancer deaths. Despite advances in diagnostics and therapy, identifying reliable biomarkers for prognosis and therapeutic stratification remains difficult. Toll-like receptors (TLRs), crucial for innate immunity, now show potential as contributors to cancer development and progression. This study aims to investigate the role of TLR expression as potential biomarkers in the development and progression of NSCLC. (2) Materials and Methods: The study was conducted on 89 patients diagnosed with NSCLC and 40 healthy volunteers, for whom the prevalence of TLR2, TLR3, TLR4, TLR7, TLR8, and TLR9 was assessed on selected subpopulations of T and B lymphocytes in the peripheral blood of recruited patients along with the assessment of their serum concentration. (3) Result: Our study showed several significant changes in NSCLC patients at the beginning of the study. This resulted in a 5-year follow-up of changes in selected TLRs in recruited patients. Due to the high mortality rate of NSCLC patients, only 16 patients survived the 5 years. (4) Conclusions: The results suggest that TLRs may constitute real biomarker molecules that may be used for future prognostic purposes in NSCLC. However, further validation through prospective clinical and functional studies is necessary to confirm their clinical utility. These conclusions may lead to better risk stratification and tailored interventions, benefiting NSCLC patients and bringing medicine closer to precision. [ABSTRACT FROM AUTHOR]

Background: Circular RNAs (circRNAs), one of the major contents of exosomes, have been shown to participate in the occurrence and progression of cancers. The role and the diagnostic potential of exosome-transported circRNAs in non-small-cell lung cancer (NSCLC) remain largely unknown. Methods: The NSCLC-associated exosomal circ_0061407 and circ_0008103 were screened by circRNA microarray. The role of circ_0061407 and circ_0008103 in NSCLC was examined in vitro and in vivo. The encapsulation of the two circRNAs into exosomes and the transport to recipient cells were observed by confocal microscopy. The effects of exosome-transported circ_0061407 and circ_0008103 on recipient cells were investigated using a co-culture device. Bioinformatics analyses were performed to predict the mechanisms by which circ_0061407 and circ_0008103 affected NSCLC. The quantitative polymerase chain reaction was used to quantify the exosome-containing circ_0061407 and circ_0008103 in the serum samples of healthy, pneumonia, benign lung tumours, and NSCLC. The diagnostic efficacy was evaluated using receiver operating characteristic curves. Results: The levels of circ_0061407 and circ_0008103 within exosomes were down-regulated in the serum of patients with NSCLC. The up-regulation of circ_0061407 and circ_0008103 inhibited the proliferation, migration/invasion, cloning formation of NSCLC cells in vitro and inhibited lung tumour growth in vivo. Circ_0061407 and circ_0008103 were observed to be packaged in exosomes and transported to recipient cells, where they inhibited the proliferation, migration/invasion, and cloning formation abilities of the recipient cells. Moreover, circ_0061407 and circ_0008103 might be involved in the progression of NSCLC by interacting with microRNAs and proteins. Additionally, lower serum exosomal circ_0061407 and circ_0008103 levels were associated with advanced pathological staging and distant metastasis. Conclusions: This study identified two novel exosome-transported circRNAs (circ_0061407 and circ_0008103) associated with NSCLC. These findings may provide additional insights into the development of NSCLC and potential diagnostic biomarkers for NSCLC. [ABSTRACT FROM AUTHOR]

N6 -methyladenosine (m6 A) denotes the addition of a methyl group to the sixth nitrogen atom of adenosine, a common occurrence in eukaryotic RNA. The m6 A modifications govern RNA splicing, translocation, stability, and translation into proteins. The RNA methyltransferases, like methyltransferase-like protein 3(METTL3), METTL14, and Wilms' tumor 1-associated protein (WTAP), are responsible for these modifications, while the removal process involves demethylases, specifically fat mass and obesity-associated protein (FTO) and ALKB homolog 5(ALKBH5). Recognition of these modifications is facilitated by m6 A-binding proteins, such as YTH family proteins and insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs). The m6 A modification regulators are involved in the onset and progression of non-small-cell lung cancer through multiple mechanisms. This review concentrates on the biological functions and molecular mechanisms of m6 A modification-related regulatory factors in the malignant progression of non-small-cell lung cancer. [ABSTRACT FROM AUTHOR]

Lung cancer is the most common cause of cancer death. The mainstay treatment for non-small-cell lung cancer (NSCLC), particularly in the early stages, is surgical resection. Traditionally, lobectomy has been considered the gold-standard technique. Sublobar resection includes segmentectomy and wedge resection. Compared to lobectomy, these procedures have been viewed as a compromise procedure, reserved for those with poor cardiopulmonary function or who are poor surgical candidates for other reasons. However, with the advances in imaging and surgical techniques, the subject of sublobar resection as a curative treatment is being revisited. Many studies have now shown segmentectomy to be equivalent to lobectomy in patients with small (<2.0 cm), peripheral NSCLC. However, there is a mix of evidence when it comes to wedge resection and its suitability as a curative procedure. At this time, until more data can be found, segmentectomy should be considered before wedge resection for patients with early-stage NSCLC. [ABSTRACT FROM AUTHOR]