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The transformation from non‐small‐cell lung cancer (NSCLC) to small‐cell lung cancer (SCLC) is one of the mechanisms of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) resistance. Previous studies exhibited that the median transformation time was 17.8 months for NSCLC to SCLC. Here we introduced a case of lung adenocarcinoma (LADC) with EGFR19 exon deletion mutation in which the pathological transformation emerged only 1 month after lung cancer surgery and receiving EGFR‐TKI inhibitor. Eventually, the pathological examination confirmed the patient experienced a transformation from LADC to SCLC with EGFR, tumor protein p53 (TP53), RB transcriptional corepressor 1 (RB1), and SRY‐box transcription factor 2 (SOX2) mutation. Although the transformation of LADC with EGFR‐mutant into SCLC after targeted therapy was frequent, the pathological results of most patients were only biopsy specimens, which cannot rule out the existence of mixed pathological components of the primary tumor. In this case, the patient's postoperative pathology was sufficient to exclude the probability of mixed tumor components, confirming that the patient's pathological change was indeed transformation from LADC to SCLC. In addition, primary drug resistance in such a short time after surgery and osimertinib‐targeted therapy has not been reported before. We detected the molecular state of this patient before and after SCLC transformation through targeted gene capture and high‐throughput sequencing, and also found for the first time that the mutations of EGFR, TP53, RB1, and SOX2 continue to exist before and after transformation, but the mutation abundance is different. In our paper, the occurrence of small‐cell transformation is affected largely by these gene mutations. [ABSTRACT FROM AUTHOR]

Thoracoscopic lobectomy has become the preferred approach for surgical management of early stage lung cancer, but the potential higher operative costs limit its widespread use. Theoretically, higher direct costs may be significantly counterbalanced by lower indirect costs, resulting in lower overall costs for thoracoscopic than for open lobectomy. To support this hypothesis, we reviewed the literature until May 2020, analyzing all papers comparing the cost of thoracoscopic versus open lobectomy.A total of 20 studies provided the most applicable evidence to evaluate this issue. In all the studies apart from one, thoracoscopic lobectomy was associated with higher operative costs due to the increased use of disposable instruments, and prolonged operative time. By contrast, in 17 studies the increased operative costs were significantly offset by indirect costs which were lower in thoracoscopic than in open lobectomy due to fewer postoperative complications, faster recovery, and lower readmission rates. It translated into lower overall costs for thoracoscopic than for open lobectomy in 10 studies, similar costs in seven, and higher in three, despite the lower hospitalization costs. The low bed fees and high prices of disposable instruments in these three studies may explain the discordance. The careful use of disposable instruments, and the minimizing hospitalization costs can reduce the total costs of thoracoscopic lobectomy to levels similar or to below those of open lobectomy. The worry that video‐assisted thoracoscopic surgery lobectomy (VATSL) might be associated with an increased overal cost is thus not warranted, and should not be used as an excuse against the use of VATS in surgery for early stage lung cancers. [ABSTRACT FROM AUTHOR]

Background: Lung cancer is the leading cause of cancer‐related deaths. Although epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) are effective for advanced non‐small cell lung cancer (NSCLC) harboring EGFR mutations, some patients experience little or no response. The Glasgow prognostic score (GPS) is an inflammation‐related score based on C‐reactive protein (CRP) and albumin concentrations, and has prognostic value in various cancer settings. This study aimed to evaluate whether GPS could predict response of NSCLC to EGFR‐TKIs. Methods: This retrospective multicenter study evaluated patients with NSCLC harboring EGFR mutations who received EGFR‐TKI monotherapy from October 2006 to December 2016. GPS values were determined using CRP and albumin concentrations from before initiation of EGFR‐TKIs. The Kaplan‐Meier method and Cox proportional hazard models were used to evaluate progression‐free survival (PFS) and overall survival (OS). Results: In 214 patients, 141, 43, and two patients had GPS values of 0, 1, and 2, respectively. The GPS independently predicted the efficacy of EGFR‐TKIs; good GPS (0–1) conferred significantly better PFS (hazard ratio [HR]: 0.59, 95% confidence interval [CI]: 0.38–0.96, P = 0.03) and OS (HR: 0.56, 95% CI: 0.33–0.96, P = 0.03). Multivariate analysis confirmed that a good GPS (0–1) independently predicted good PFS and OS among patients who had PS of 0–1. Good GPS (0–1) independently predicted good OS among patients receiving treatment in first‐line settings. Conclusions: The GPS independently predicted the efficacy of EGFR‐TKIs for EGFR‐mutated NSCLC; however, further studies are needed to validate our findings. Key points: Significant findings of the study: Glasgow prognostic score (GPS) independently predicted the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) treatment for EGFR‐mutated NSCLC. What this study adds: The findings presented in this paper will help to identify patients who will be expected to experience limited or no response to EGFR‐TKI treatment by using GPS. [ABSTRACT FROM AUTHOR]

Background: Tumor with adjacent lobe invasion (T‐ALI) is an uncommon condition. Controversy still exists regarding the optimal resection of adjacent lobe invasion, and the prognostic value in relation to fissure integrity at the tumor invasion point. The aims of this paper were to evaluate the prognosis of T‐ALI with regard to fissure integrity, and type of resection. Methods: This was a retrospective multicenter study which included all consecutive patients with T‐ALI undergoing surgical treatment. Based on radiological, intraoperative and histological findings, T‐ALI patients were differentiated into two groups based on whether the fissure was complete (T‐ALI‐A group) or incomplete (T‐ALI‐D Group) at the level of tumor invasion point. Clinico‐pathological features and survival of two study groups were analyzed and compared. Results: Study population included 135 patients, of these 98 (72%) were included into T‐ALI‐A group, and 37 (38%) into T‐ALI‐D Group. T‐ALI‐D patients had better overall survival than T‐ALI‐A patients (63.9 ± 7.0 vs. 48.9 ± 3.9; respectively, P = 0.01) who presented with a higher incidence of lymph node involvement (35% vs. 4%; P = 0.004), and recurrence rate (43% vs. 16%; P = 0.01). At multivariable analysis, T‐ALI‐D (P = 0.01), pN0 stage (P = 0.0002), and pT≤5 cm (P = 0.0001) were favorable survival prognostic factors. Conclusions: T‐ALI‐D presented a better prognosis than T‐ALI‐A while extent of resection had no effect on survival. Thus, in patients with small T‐ALI‐D and without lymph node involvement, sublobar resection of adjacent lobe rather than lobectomy could be indicated. Key points: The extent of resection of adjacent lobe had no effect on survival while T‐ALI‐D, pN0 stage, and pT≤5 cm were significant prognostic factors.In patients with small T‐ALI‐D and without lymph node involvement, sublobar resection of adjacent lobe could be indicated as an alternative to lobectomy. [ABSTRACT FROM AUTHOR]

Background: Screening for anaplastic lymphoma kinase (ALK) rearranged non‐small cell lung cancer (NSCLC) is crucial for identifying patients eligible for targeted therapy. The FDA‐approved ALK (D5F3) immunohistochemistry (IHC) assay, used with the OptiView Amplification Kit, demonstrates excellent sensitivity and specificity in detecting these patients. However, the clinical significance of resulting focal positivity remains unclear, and ALK (D5F3) expression unrelated to ALK fusion is observed in some cases of neuroendocrine differentiation. This study aims to validate these findings with molecular testing and contribute to the accurate interpretation of ALK (D5F3) IHC results. Methods: A total of 1619 patients diagnosed with NSCLC and neuroendocrine carcinoma were evaluated using ALK (D5F3) IHC. For cases with strong but focal expression and those with diffuse strong positivity in neuroendocrine differentiation, ALK fluorescence in situ hybridization (FISH) and/or next‐generation sequencing (NGS) tests were performed. Results: Seven out of 1109 adenocarcinomas (0.6%) and six out of 289 squamous cell carcinomas (2.1%) exhibited strong focal ALK (D5F3) expression. Nine out of 209 neuroendocrine carcinomas (4.3%) showed homogeneously strong ALK (D5F3) expression. All these cases, including adenocarcinoma with neuroendocrine differentiation and combined small cell carcinoma, were negative for ALK fusions by FISH and/or NGS. Conclusion: This study demonstrates that strong but focal ALK (D5F3) immunostaining and strong expression in neuroendocrine differentiation may not indicate ALK fusion. By considering these findings, we can improve the accuracy of patient selection for targeted therapy by minimizing false‐positive interpretations of ALK (D5F3) staining. [ABSTRACT FROM AUTHOR]

Background: The relationship between the combination of platelet count and neutrophil‐lymphocyte ratio (COP‐NLR) and prognosis in patients with advanced non‐small cell lung cancer (NSCLC) treated with immune checkpoint inhibitor (ICI) combination therapy with chemotherapy remains unclear. Thus, we investigated prognostic factors, including the COP‐NLR, to identify patients who could benefit from the therapeutic efficacy of ICI combination therapy for advanced NSCLC. Furthermore, we evaluated the relationship between the COP‐NLR score during ICI combination therapy and treatment response. Methods: We conducted a retrospective cohort study of 88 patients with NSCLC who initially received ICI combination therapy. The primary outcome was overall survival (OS). The prognostic factors were extracted using the Cox proportional hazards model. The relationship between COP‐NLR score at 3 weeks after starting ICI combination therapy and a good response (complete response [CR] and partial response [PR]) to treatment was analyzed using the chi‐square test. Results: The median OS was 15.7 months. In the multivariable analysis, Eastern Cooperative Oncology Group Performance Status (ECOG PS) 2, distant metastatic sites ≥2, and baseline COP‐NLR scores of 1, 2 were extracted as significant poor prognostic factors. The proportion of patients with CR and PR in the 3‐week COP‐NLR score of 0 group was significantly higher than that in scores of 1, 2 group. Conclusions: Baseline COP‐NLR, ECOG PS, and number of distant metastatic sites were prognostic factors in patients with NSCLC with ICI combination therapy. A lower 3‐week COP‐NLR was associated with a good response to treatment. [ABSTRACT FROM AUTHOR]

Background: Methyltransferase 3 (METTL3) accelerates N6‐methyladenosine (m6A) modifications and affects cancer progression, including non‐small‐cell lung cancer (NSCLC). In this study, we aimed to explore the regulatory mechanisms of METTL3 underling NSCLC. Methods: Immunohistochemical assay, quantitative real‐time polymerase chain reaction (qRT‐PCR) assay, and western blot assay were conducted for gene expression. MTT assay and colony formation assay were performed to explore cell proliferation capacity. Cell apoptosis and THP‐1 cell polarization were estimated by flow cytometry analysis. Cell migration and invasion capacities were evaluated by transwell assay. Methylated RNA immunoprecipitation assay, dual‐luciferase reporter assay, actinomycin D treatment and RIP assay were performed to analyze the relationships of METTL3, insulin‐like growth factor 2 mRNA binding protein 1 (IGF2BP1), and transient receptor potential cation channel subfamily V member 1 (TRPV1). The functions of METTL3 and TRPV1 in vivo were investigated through establishing the murine xenograft model. Results: TRPV1 expression was upregulated in NSCLC and related poor prognosis. TRPV1 silencing inhibited NSCLC cell growth and metastasis, induced NSCLC cell apoptosis, and repressed M2 macrophage polarization. The results showed that METTL3 and IGF2BP1 could regulate TRPV1 expression through m6A methylation modification. Moreover, METTL3 deficiency inhibited NSCLC cell growth, metastasis, and M2 macrophage polarization and facilitated NSCLC cell apoptosis, while TRPV1 overexpression restored the impacts. In addition, METTL3 knockdown restrained tumor growth in vivo via regulating TRPV1 expression. Conclusion: METTL3 bound to IGF2BP1 and enhanced IGF2BP1's m6A recognition of TRPV1 mRNA, thereby promoting NSCLC cell growth and metastasis, and inhibiting M2 macrophage polarization. [ABSTRACT FROM AUTHOR]

This meta‐analysis aimed to evaluate the feasibility and oncological outcomes between video‐assisted thoracic surgery (VATS) and thoracotomy for non–small cell lung cancer (NSCLC) patients with pathologic N2 (pN2) disease. Data for analysis included short‐term outcomes and long‐term outcomes. We calculated the weighted mean differences (WMDs) for continuous data and the results of overall survival (OS) and disease free survival (DFS) were pooled using the hazard ratios (HRs) with 95% confidence intervals (CIs). Heterogeneity was assessed using the Q‐test and I2‐test. Sensitivity analysis was performed to further examine the stability of pooled HRs and WMDs. In the pooled analyses of 10 eligible studies, results showed that VATS for NSCLC patients with pN2 disease yielded significantly less blood loss (WMD = −61.43; 95% confidence intervals [CI], [−87.69, −35.18]; p < 0.001), less post‐operation hospital stay (WMD, −1.62; 95% CI, [−2.96, −0.28]; p = 0.02), and comparable operation time (WMD, −8.32; 95% CI, [−23.88, 7.23]; p = 0.29), post‐operation complication rate (risk ratio [RR], 0.95; 95% CI, [0.78, 1.15]; p = 0.59), chest tube duration to thoracotomy (WMD, −0.64; 95% CI, [−1.45, 0.17]; p = 0.12), extent of lymph node dissection (WMD, −1.46; 95% CI, [−3.87, 0.95]; p = 0.23) and 1‐year OS (HR, 1.30; 95% CI, [0.96, 1.76]; p = 0.09) than thoracotomy. However, VATS may improve 3‐year OS (HR, 1.26; 95% CI, [1.12, 1.42]; p = 0.0002) and yield comparable 1‐year DFS (HR, 1.14; 95% CI, [0.89, 1.46]; p = 0.32) and 3‐year DFS (HR, 1.03; 95% CI, [0.88, 1.22]; p = 0.70) for NSCLC patients with pN2 disease than thoracotomy. VATS could yield less surgical trauma and improve post‐operative recovery than thoracotomy. Moreover, VATS may improve the oncological outcomes of those patients. [ABSTRACT FROM AUTHOR]

The ALK gene encodes a transmembrane tyrosine kinase receptor. ALK is physiologically expressed in the nervous system during embryogenesis, but its expression decreases postnatally. ALK first emerged in the field of oncology in 1994 when it was identified to fuse to NPM1 in anaplastic large‐cell lymphoma. Since then, ALK has been associated with other types of cancers, including non‐small‐cell lung cancer (NSCLC). More than 19 different ALK fusion partners have been discovered in NSCLC, including EML4, KIF5B, KLC1, and TPR. Most of these ALK fusions in NSCLC patients respond well to the ALK inhibitor, crizotinib. In this paper, we reviewed fusion partner genes with ALK, detection methods for ALK‐rearrangement (ALK‐R), and the ALK‐tyrosine kinase inhibitor, crizotinib, used in NSCLC patients. [ABSTRACT FROM AUTHOR]

This paper analyzed the results of a modified and simpler technique for distinguishing the intersegmental border during lung segmentectomy surgery. From January 2013 to December 2015, 539 patients with screening‐detected lung nodules <2 cm in maximum diameter underwent anatomic segmentectomy. With the guidance of preoperative three‐dimensional computed tomography bronchography and angiography, the bronchus, artery, and intrasegmental vein of the targeted segment could be precisely dissected under unilateral differential ventilation, and then intersegmental demarcation was confirmed by the modified inflation‐deflation method. The demarcation presented by this method was highly coincident with the real intersegmental border. Dissection along the border between the collapsed and inflated segments using either electrocautery or staples was safe, with almost no air leak or bleeding. This technique is a simple and effective alternative to previously described intersegmental border marking methods. [ABSTRACT FROM AUTHOR]

Objectives: Pretreatment biomarkers are needed to identify patients with non‐small‐cell lung cancer (NSCLC) likely to have worse survival. This ensures that only patients with a real chance of benefit receive immune checkpoint inhibitor (ICI) treatment. In this study, we examined the associations of baseline nutritional and inflammatory biomarkers with overall survival in a real‐world cohort of NSCLC patients who received ICIs. Materials and Methods: We used prospectively collected data from the OncoLifeS data biobank. The cohort included 500 advanced‐stage NSCLC patients treated with ICIs from May 2015 to June 2021. Biomarkers were evaluated within 2 weeks before ICI treatment: neutrophil‐to‐lymphocyte ratio, C‐reactive protein (CRP), Glasgow prognostic score, CRP/albumin ratio (CAR), prognostic nutritional index (PNI), and advanced lung cancer inflammation index. For each biomarker, low‐ and high‐risk groups were defined using literature‐based cut‐offs. Adjusted hazard ratios (aHRs) and 95% confidence intervals (95% CIs) were estimated using adjusted survival analysis. Results: Most patients were male (60.8%), the mean baseline age was 65 ± 9 years, and 88% had stage IV disease. For each biomarker, low‐risk patients had better overall survival (all, p < 0.001), with CAR and PNI showing the strongest associations. In multivariable analyses a combined CAR/PNI risk score had a stronger association with overall survival (aHR 3.09, 95% CI 2.36–4.06) than CAR alone (aHR 2.22, 95% CI 1.79–2.76) or PNI alone (aHR 2.09, 95% CI 1.66–2.61). Conclusion: These results highlight the potential value of nutritional and inflammatory biomarkers, in particular CAR and PNI, in identifying NSCLC patients with highest mortality risk before starting ICI treatment. [ABSTRACT FROM AUTHOR]

Background: To elucidate the treatment and surgery outcomes with or without perioperative therapies in Japanese patients with clinical stage III non‐small cell lung cancer (NSCLC) in real‐world settings. Methods: We performed subset analyses of the SOLUTION study, a multicenter, noninterventional, observational study of Japanese patients diagnosed with clinical stage III NSCLC, for those who started first‐line treatment (surgery±perioperative therapy) between January 2013 and December 2014 (study registration: UMIN000031385). Follow‐up data were obtained using medical records from diagnosis to March 1, 2018. Results: Of 149 eligible patients, 67 underwent surgery alone (median age 71 years) and 82 underwent surgery+perioperative therapy (median age 63 years). Lung resection was performed in 137 patients and the others underwent exploratory thoracotomy or other procedures. Perioperative therapies included adjuvant therapy only (n = 41), neoadjuvant therapy only (n = 24), and neoadjuvant+adjuvant therapy (n = 17). The median overall survival (OS) and 3‐year OS rate were 29.3 months and 44.0%, respectively, in patients who underwent surgery alone, and not reached and 61.1%, respectively, in patients who underwent surgery+perioperative therapy. The 3‐year progression‐free survival (PFS) and disease‐free survival (DFS) rates were 42.4% and 47.1%, respectively, in patients who underwent surgery+perioperative therapy and 28.5% and 28.9%, respectively, in patients who underwent surgery alone. In multivariable Cox regression, perioperative therapy was associated with improved OS (hazard ratio [95% confidence interval] 0.49 [0.29–0.81]), PFS (0.62 [0.39–0.96]), and DFS (0.62 [0.39–0.97]) versus surgery alone. Conclusions: Our study suggested that perioperative therapy may be associated with better survival among patients undergoing surgical treatment of clinical stage III NSCLC. [ABSTRACT FROM AUTHOR]

Background: In patients with non‐small cell lung cancer (NSCLC), interstitial lung abnormalities (ILA) have been linked to mortality and can be identified on computed tomography (CT) scans. In the present study we aimed to evaluate the predictive value of automatically quantified ILA based on the Fleischner Society definition in patients with stage I NSCLC. Methods: We retrospectively reviewed 948 patients with pathological stage I NSCLC who underwent pulmonary resection between April 2009 and October 2022. A commercially available deep learning‐based automated quantification program for ILA was used to evaluate the preoperative CT data. The Fleischner Society definition, quantitative results, and interdisciplinary discussion led to the division of patients into normal and ILA groups. The sum of the fibrotic and nonfibrotic ILA components constituted the total ILA component and more than 5%. Results: Of the 948 patients with stage I NSCLC, 99 (10.4%) patients had ILA. Shorter overall survival and recurrence‐free survival was associated with the presence of ILA. After controlling for confounding variables, the presence of ILA remained significant for increased risk of death (hazard ratio [HR] = 3.09; 95% confidence interval [CI]: 1.91–5.00; p < 0.001) and the presence of ILA remained significant for increased recurrence (HR = 1.96; 95% CI: 1.16–3.30; p = 0.012). Conclusions: The automated CT quantification of ILA, based on the Fleischner Society definition, was significantly linked to poorer survival and recurrence in patients with stage I NSCLC. [ABSTRACT FROM AUTHOR]

Background: To identify independent factors of cognitive frailty (CF) and construct a nomogram to predict cognitive frailty risk in patients with lung cancer receiving drug therapy. Methods: In this cross‐sectional study, patients with lung cancer undergoing drug therapy from October 2022 to July 2023 were enrolled. The data collected includes general demographic characteristics, clinical data characteristics and assessment of tools for cognitive frailty and other factors. Logistic regression was harnessed to determine the influencing factors, R software was used to establish a nomogram model to predict the risk of cognitive frailty. The enhanced bootstrap method was employed for internal verification of the model. The performance of the nomogram was evaluated by using calibration curves, the area under the receiver operating characteristic curve, and decision curve analysis. Results: A total of 372 patients were recruited, with a cognitive frailty prevalence of 56.2%. Age, education background, diabetes mellitus, insomnia, sarcopenia, and nutrition status were identified as independent factors. Then, a nomogram model was constructed and patients were classified into high‐ and low‐risk groups with a cutoff value of 0.552. The internal validation results revealed good concordance, calibration and discrimination. The decision curve analysis presented prominent clinical utility. Conclusions: The prevalence of cognitive frailty was higher in lung cancer patients receiving drug therapy. The nomogram could identify the risk of cognitive frailty intuitively and simply in patients with lung cancer, so as to provide references for early screening and intervention for cognitive frailty at the early phases of drug treatment. [ABSTRACT FROM AUTHOR]

Background: The effective therapeutic approach is still an unmet need for patients diagnosed with both lung cancer and interstitial lung disease (ILD). This is primarily due to the possible risk of ILD exacerbation caused by surgery or radiotherapy. The current study aimed to investigate the efficacy and safety of local ablative therapy (LAT) for this specific population. Methods: Consecutive patients with non-small cell lung cancer (NSCLC) and ILD who received LAT between January 2018 and August 2022 were enrolled, and propensity score matching (PSM) was utilized to match the non-ILD group. The primary endpoint was recurrence-free survival (RFS), and secondary endpoints included overall survival (OS), adverse events (AEs) and hospital length of stay (HLOS). Results: The PSM algorithm yielded matched pairs in the ILD group (n = 25) and non-ILD group (n = 72) at a ratio of 1:3. There were no statistically significant differences in RFS (median 16.4 vs. 18 months; HR = 1.452, p = 0.259) and OS (median: not reached vs. 47.9 months; HR = 1.096, p = 0.884) between the two groups. Meanwhile, no acute exacerbation of ILD was observed in the ILD group. However, the incidence of pneumothorax, especially pneumothorax requiring chest tube drainage, was significantly higher (36.0% vs. 11.2%, p = 0.005) among patients with NSCLC and co-existing ILD, which resulted in longer HLOS (p = 0.045). Conclusion: Although ILD was associated with a higher incidence of pneumothorax, the efficacy of LAT for NSCLC patients with ILD was comparable to those without ILD, suggesting that LAT might be a reliable and effective treatment option for this population, particularly in the early stage. [ABSTRACT FROM AUTHOR]

Segmentectomy is a widely adopted surgical procedure, however, experiences of tailoring the intersegmental border have rarely been reported. This paper investigates the strategy and results of tailoring complex demarcation during lung segmentectomy surgery. Because intersegmental demarcation can be divided into plane or curved types according to the location and stereo shape of a segment, a one‐size‐fits‐all method for tailoring the intersegmental demarcation is obviously unreasonable. For tailoring a complex segmentectomy with two or more curved borders, tips including good exposure of the intersegmental demarcation, sharp‐blunt combined dissection skill, "work‐plane" extension, and "gate" opening techniques all contribute to an accurate segmentectomy. This technique, based on anatomical characteristics, can provide a cutting surface with a greater physiological shape and less curling of the edge, and should be recommended as a general standard method for tailoring complex demarcation. [ABSTRACT FROM AUTHOR]

Background: Numerous studies have characterized the gut microbiome (GM) in lung cancer (LC). Yet, the causality between GM and LC and its subtypes remain uncharacterized. Methods: Two‐sample Mendelian randomization (MR) was designed to investigate the causal relationship between the GM and LC and its subtypes, using publicly available summary data of genome‐wide association studies. The researchers ran two groups of MR analyses, including the genome‐wide statistical significance threshold (5 × 10−8) and the locus‐wide significance level (1 × 10−5). Results: Using MR analysis, we ascertained 42 groups of GM that are intimately linked to LC and its subtypes at the locus‐wide significance level. Of the 42 groups, 12 were in LC, nine in non‐small cell lung cancer (NSCLC), six in small cell lung cancer (SCLC), two in lung adenocarcinomas, and 13 in lung squamous carcinomas. After false discovery rate correction, we still found a remarkable causal interaction between the Eubacterium ruminantium group and SCLC. Moreover, five groups of GM closely linked to LC and its subtypes were recognised at the genome‐wide statistical significance threshold. This finding included one group each in LC, NSCLC and SCLC, two groups in lung adenocarcinoma and none in lung squamous carcinoma. None of the foregoing findings were heterogeneous or horizontal pleiotropy. Reverse MR revealed that genetic susceptibility to LC and its subtypes caused significant changes in three groups of GM. Conclusion: Our findings substantiate the causality between GM and LC and its subtypes. This study offers fresh insights into the function of GM in mediating the progression of LC. [ABSTRACT FROM AUTHOR]

Background: Non‐small cell lung cancer (NSCLC) is often diagnosed at an advanced stage. Clinical trials have demonstrated that first‐line immunotherapy alone or in combination with chemotherapy improves overall survival. However, reports of survival outcomes in real‐world settings are limited. We assessed survival in advanced NSCLC patients treated with immunotherapy alone or in combination with chemotherapy in first‐ or second‐line at the Windsor Regional Cancer Program (WRCP) and compared it to existing literature. Methods: We included patients diagnosed with stage IV NSCLC from January 2015 to December 2020 and treated with first‐line chemoimmunotherapy (ChemoImmuno1), chemotherapy followed by immunotherapy (Chemo1), or immunotherapy followed by chemotherapy (Immno1) in our survival analysis. Patients with oncogene‐addicted mutations were excluded. Results: There were 160 patients of which 41.5% were female. Mean age was 68 years. Median overall survival from time of diagnosis was 474 days (95% CI: 249, 949) with an estimated 5‐year survival of 11.1% (95% CI: 4.5, 21.3). Median OS in ChemoImmuno1 was 9.6 months, in Chemo1 was 19.2 months from time of diagnosis and 10.5 months from time of initiation of immunotherapy, and in Immuno1 was 18.4 months, respectively. Estimated survival at three years from time of diagnosis for ChemoImmuno1 was 17.6% and for Immuno1 was 17.9%. For Chemo1, from diagnosis it was 20.1% and from second‐line therapy it was 15.4%. Survival outcomes were comparable to clinical trials and other studies. Conclusion: Real‐world survival outcomes of immunotherapy for advanced NSCLC are comparable to the existing literature in this single center study. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the clinicopathological features and prognostic indicators of primary pulmonary adenoid cystic carcinoma (PACC). Methods: Clinical data were collected from 64 primary PACC patients and analyzed retrospectively at the Tianjin Medical University General Hospital, the West China Hospital of Sichuan University, the First Affiliated Hospital of Guangxi Medical University, and the Bishan Hospital of Chongqing Medical University from January 2003 to August 2023. The 64 patients (28 males and 36 females) were aged from 20 to 73 years, with a median age of 49 years and an average age of 49.3 years. Results: Immunohistochemical staining showed that the tumors expressed CK7, S‐100 protein, CK5/6, CD117, and p63. Seven patients underwent fluorescence in situ hybridization (FISH) testing and three were found to have myeloblastosis (MYB) gene translocation. In total, 53 patients underwent surgery, among whom 31 received only surgery and 22 received both surgery and postoperative chemoradiotherapy. In addition, 10 patients received chemoradiotherapy only, while one patient underwent treatment with traditional Chinese medicine. The overall survival rates in the first, third, and fifth years were 98.4%, 95.3%, and 87.5%, respectively. Conclusion: Prognostic analysis revealed that age, tumor size, lymph node metastasis status, margin status, and choice of treatment modality significantly influenced the patients' prognosis. [ABSTRACT FROM AUTHOR]

Background: Venous thromboembolism (VTE) increases the risk of death or adverse outcomes in patients with lung cancer. Therefore, early identification and treatment of high‐risk groups of VTE have been the research focus. In this systematic review, the risk assessment tools of VTE in patients with lung cancer were systematically analyzed and evaluated to provide a reference for VTE management. Methods: Relevant studies were retrieved from major English databases (The Cochrane Library, Embase, Web of Science, PubMed, Scopus, Medline) and Chinese databases (China National Knowledge Infrastructure [CNKI] and WanFang Data) until July 2023 and extracted by two researchers. This systematic review was registered at PROSPERO (no. CRD42023409748). Results: Finally, two prospective cohort studies and four retrospective cohort studies were included from 2019. There was a high risk of bias in all included studies according to the Prediction Model Risk of Bias Assessment tool (PROBAST). In the included studies, Cox and logistic regression were used to construct models. The area under the receiver operating characteristic curve (AUC) of the model ranged from 0.670 to 0.904, and the number of predictors ranged from 4 to 11. The D‐dimer index was included in five studies, but significant differences existed in optimal cutoff values from 0.0005 mg/L to 2.06 mg/L. Then, three studies validated the model externally, two studies only validated the model internally, and only one study validated the model using a combination of internal and external validation. Conclusion: VTE risk prediction models for patients with lung cancer have received attention for no more than 5 years. The included model shows a good predictive effect and may help identify the risk population of VTE at an early stage. In the future, it is necessary to improve data modeling and statistical analysis methods, develop predictive models with good performance and low risk of bias, and focus on external validation and recalibration of models. [ABSTRACT FROM AUTHOR]

This paper reports a case of high-grade fetal lung adenocarcinoma with particularly aggressive clinical and biological features in a 57-year-old man. Our patient first underwent neoadjuvant chemotherapy followed by surgery, and was then treated with adjuvant chemotherapy. Next, he had radiotherapy on the mediastinal region and prophylactic whole brain radiation therapy ( WBRT). Following radiotherapy treatment, the patient started maintenance therapy with a somatostatin analogue. After 58 months of follow-up he is asymptomatic and disease free. [ABSTRACT FROM AUTHOR]

Drug‐related pneumonitis (DRP) caused by epidermal growth factor receptor (EGFR)‐tyrosine kinase inhibitors (TKIs) is a fatal adverse event in patients with EGFR‐mutant non‐small cell lung cancer (NSCLC). The diagnosis of DRP is based on radiological findings, the temporal association of presentation with the initiation of a systemic therapeutic agent, and the exclusion of other likely causes. Here we report a case in which severe adenoviral pneumonia mimicking DRP occurred during treatment with osimertinib, and osimertinib was successfully resumed after recovery from adenoviral pneumonia. [ABSTRACT FROM AUTHOR]

The rearranged during transfection (RET) gene is one of the receptor tyrosine kinases and cell‐surface molecules responsible for transmitting signals that regulate cell growth and differentiation. In non‐small cell lung cancer (NSCLC), RET fusion is a rare driver gene alteration associated with a poor prognosis. Fortunately, two selective RET inhibitors (sRETi), namely pralsetinib and selpercatinib, have been approved for treating RET fusion NSCLC due to their remarkable efficacy and safety profiles. These inhibitors have shown the ability to overcome resistance to multikinase inhibitors (MKIs). Furthermore, ongoing clinical trials are investigating several second‐generation sRETis that are specifically designed to target solvent front mutations, which pose a challenge for first‐generation sRETis. The effective screening of patients is the first crucial step in the clinical application of RET‐targeted therapy. Currently, four methods are widely used for detecting gene rearrangements: next‐generation sequencing (NGS), reverse transcription‐polymerase chain reaction (RT‐PCR), fluorescence in situ hybridization (FISH), and immunohistochemistry (IHC). Each of these methods has its advantages and limitations. To streamline the clinical workflow and improve diagnostic and treatment strategies for RET fusion NSCLC, our expert group has reached a consensus. Our objective is to maximize the clinical benefit for patients and promote standardized approaches to RET fusion screening and therapy. [ABSTRACT FROM AUTHOR]

Background: To develop a radiomics model based on chest computed tomography (CT) for the prediction of a pathological complete response (pCR) after neoadjuvant or conversion chemoimmunotherapy (CIT) in patients with non‐small cell lung cancer (NSCLC). Methods: Patients with stage IB–III NSCLC who received neoadjuvant or conversion CIT between September 2019 and July 2021 at Hunan Cancer Hospital, Xiangya Hospital, and Union Hospital were retrospectively collected. The least absolute shrinkage and selection operator (LASSO) were used to screen features. Then, model 1 (five radiomics features before CIT), model 2 (four radiomics features after CIT and before surgery) and model 3 were constructed for the prediction of pCR. Model 3 included all nine features of model 1 and 2 and was later named the neoadjuvant chemoimmunotherapy‐related pathological response prediction model (NACIP). Results: This study included 110 patients: 77 in the training set and 33 in the validation set. Thirty‐nine (35.5%) patients achieved a pCR. Model 1 showed area under the curve (AUC) = 0.65, 64% accuracy, 71% specificity, and 50% sensitivity, while model 2 displayed AUC = 0.81, 73% accuracy, 62% specificity, and 92% sensitivity. In comparison, NACIP yielded a good predictive value, with an AUC of 0.85, 81% accuracy, 81% specificity, and 83% sensitivity in the validation set. Conclusion: NACIP may be a potential model for the early prediction of pCR in patients with NSCLC treated with neoadjuvant/conversion CIT. [ABSTRACT FROM AUTHOR]

More and more patients with small cell lung cancer (SCLC) have received surgical treatment in the last 20 years. This meta‐analysis compared whether surgical treatment can bring greater survival benefits to patients with stage I–III SCLC compared with chemotherapy, radiotherapy and chemoradiotherapy. Pubmed, Embase, Web of Science, Cochrane library database, and ClinicalTrials were searched for relevant articles. The main outcomes were overall survival (OS), reported as hazard ratios (HRs), and 95% confidence intervals (CIs). A total of 19 articles containing 30 185 patients (3940 patients receiving surgical treatment and 26 245 patients receiving nonsurgical treatment) were included in this study. Surgical resection significantly improved OS when compared to nonsurgical treatment in retrospective studies (HR: 0.55, 95% CI: 0.47–0.64, p < 0.01). In the subgroup analysis for retrospective studies, surgical resection was associated with superior OS in stage I (HR: 0.42, 95% CI: 0.24–0.71, p < 0.01), stage II (HR: 0.61, 95% CI: 0.52–0.73, p < 0.01), and stage III diseases (HR: 0.66, 95% CI: 0.51–0.86, p < 0.01). Sublobar resection resulted in worse OS than a lobectomy (HR: 0.78,95% CI: 0.60–1.00, p < 0.01) for patients undergoing surgical resection. Compared with nonsurgical treatment, surgical treatment can indeed bring more significant survival benefits to patients with stage I–III SCLC, and lobectomy can bring longer survival compared with sublobectomy. More prospective studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Background: Evidence on the influence of programmed death‐ligand 1 (PD‐L1) expression on the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) in EGFR‐mutant non‐small cell lung cancer (NSCLC) patients is at variance. Methods: A single‐center retrospective study was conducted to evaluate the influence of PD‐L1 expression on the efficacy of EGFR‐TKIs for NSCLC patients with EGFR mutation. Clinical information was retrieved from electronic medical records. The patients were divided into three subgroups according to PD‐L1 expression level: PD‐L1 < 1% (negative), PD‐L1 1%–49% and PD‐L1 ≥ 50%. The clinicopathological features, overall response rate (ORR), progression‐free survival (PFS) and comutation information were collected and compared between the three subgroups. Results: A total of 117 patients were included. For PD‐L1 < 1%, PD‐L1 1%–49% and PD‐L1 ≥ 50% group, there were 39 (33.3%), 51 (43.5%) and 27 (23.0%) patients respectively, and the ORR was 43.2%, 64.0%, and 51.9%, respectively (p = 0.162), and the median progression‐free survival (mPFS) was 22.0 months (95% CI: 14.0–29.9 months), 15.4 months (95% CI: 8.9–21.8 months) and 13.0 months (95% CI: 10.6–15.3 months), respectively (log‐rank, p = 0.01). The mPFS was negatively correlated with PD‐L1 expression level (r = −0.264, p = 0.041) and PD‐L1 expression was an independent risk factor for worse PFS of EGFR‐TKIs in multivariate Cox regression. Patients with concurrent TP53 mutation had shorter PFS (p = 0.039) and the patients harboring both mutant TP53 and positive PD‐L1 had the shortest PFS (p = 0.006). Conclusions: The efficacy of EGFR‐TKIs was influenced by the baseline PD‐L1 expression. Higher PD‐L1 expression was associated with shorter PFS. The combined indicators of TP53 and PD‐L1 identified subgroups showing divergent benefits from EGFR‐TKIs. [ABSTRACT FROM AUTHOR]

Background: Along with the improvement of lung cancer screening implementation, the identification of interstitial lung abnormality (ILA) is increasing. Currently, there is a limited description of the oncogenic status and ILA subtypes among newly diagnosed non‐small cell lung cancer (NSCLC) patients with ILA in the Chinese population. This study aimed to investigate the prevalence, characteristics, oncogenic status and factors associated with overall survival (OS) among NSCLC patients with ILA. Methods: A total of 765 newly diagnosed NSCLC cases at our hospital were reviewed and ILA was diagnosed according to the criteria of the Fleischner Society. The characteristics, clinical pathological features and OS of NSCLC patients with ILA were retrospectively analyzed. Results: Of the 765 patients included in the study, 101 (13.2%) cases experienced ILA at the time of NSCLC diagnosis. Multivariate analysis revealed that ILA was more likely to be detected in NSCLC patients who were age ≥60 (OR 2.404, p = 0.001), male gender (OR 2.476, p = 0.004), and EGFR wild‐type (OR 2.035, p = 0.007). Additionally, according to the multivariate Cox model, the presence of ILA in NSCLC patients was significantly associated with a shorter OS period than those without ILA (751 days vs. 445 days, HR 0.6, p = 0.001). Following analysis, it was determined that OS in patients with usual interstitial pneumonia (UIP) was shorter than in those without UIP (HR 1.82, p = 0.037). Conclusion: ILA is a common comorbidity among newly diagnosed NSCLC patients. We found that patients with EGFR wild‐type NSCLC were more likely to develop ILA. The presence of ILA, especially UIP, was significantly associated with poor NSCLC prognosis. [ABSTRACT FROM AUTHOR]

Background: Lung cancer has significantly higher incidence and mortality rates worldwide. In this study, we analyzed the metabolic profiles of non‐small cell lung cancer (NSCLC) patients and constructed prediction models for smokers and nonsmokers with internal validation. Methods: Plasma was collected from all patients enrolled for metabolic profiling by liquid chromatography–tandem mass spectrometry (LC–MS/MS). The total population was divided into two groups according to smoking or not. Statistical analysis of metabolites was performed separately for each group and prediction models were constructed. Results: A total of 1723 patients (1109 NSCLC patients and 614 healthy controls) were enrolled from the affiliated hospital during 2018 to 2021. After grouping by smoking history, each group was statistically analyzed and prediction models were constructed, which resulted in eight indicators (propionylcarnitine, arginine, citrulline, etc.) significantly associated with lung cancer risk for smokers and eight indicators (dodecanoylcarnitine, hydroxybutyrylcarnitine, asparagine, etc.) for nonsmokers (p < 0.05). The smoker model indicated an AUC of 0.860 in the training set and 0.850 in the validation set. The nonsmoker model showed an AUC of 0.783 in the training set and 0.762 in the validation set. Further calibration tests for both models indicated excellent goodness‐of‐fit results. Conclusions: In this study, we found a series of metabolites significantly associated with lung cancer incidence and constructed respectively prediction models for NSCLC risk in smokers and nonsmokers, with internal validation to confirm the efficiency to discriminate lung cancer risk in both smoking and nonsmoking states. [ABSTRACT FROM AUTHOR]

Background: Previous trials suggest that older adults with non‐small cell lung cancer (NSCLC) derive benefit from platinum doublet combination therapy, but its superiority is controversial. Although geriatric assessment variables are used to assess the individual risk of severe toxicity and clinical outcomes in older patients, the standard first‐line treatment is still debated. Therefore, we aimed to identify the risk factors for clinical outcomes in older patients with NSCLC. Methods: Patients aged ≥75 years with advanced NSCLC treated at any of 24 National Hospital Organization institutions completed a pre‐first‐line chemotherapy assessment, including patient characteristics, treatment variables, laboratory test values, and geriatric assessment variables. We evaluated whether these variables were the risk factors for progression‐free survival (PFS) and overall survival (OS). Results: A total of 148 patients with advanced NSCLC were treated with combination therapy (n = 90) or monotherapy (n = 58). Median PFS was 5.3 months and OS was 13.6 months. We identified that hypoalbuminemia (hazard ratio [HR] 2.570, 95% confidence interval [CI]: 1.117–5.913, p = 0.0264) was a risk factor for PFS and monotherapy (HR 1.590, 95% CI: 1.070–2.361, p = 0.0217), lactate dehydrogenase (HR 3.682, 95% CI: 1.013–13.39, p = 0.0478), and high C‐reactive protein (HR 2.038, 95% CI: 1.141–3.642, p = 0.0161) were risk factors for OS. The median OS was significantly longer in patients treated with combination therapy than in those who received monotherapy (16.5 months vs. 10.3 months; HR 0.684, 95% CI: 0.470–0.995, p = 0.0453). Discussion: Platinum doublet combination therapy may be beneficial in older patients with NSCLC. Identification of risk factors will assist in the development of a personalized treatment strategy. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to assess the response prediction and prognostic values of different peripheral blood cell biomarkers for advanced lung adenocarcinoma (LUAD) patients receiving first‐line therapy. Methods: Patients diagnosed with advanced LUAD as well as healthy controls and patients with benign pulmonary diseases were collected in this retrospective study. Propensity score matching (PSM) was performed in a 1:1 ratio. Survival state was estimated by the Kaplan–Meier method and the Cox proportional hazard model was used to assess the prognostic factors. Results: Compared with the control groups, the level of peripheral blood leucocyte, neutrophil, monocyte, platelet, and neutrophil to lymphocyte ratio, monocyte to lymphocyte ratio, platelet to lymphocyte ratio, and systemic inflammation response index (SIRI) were higher in LUAD patients (all p < 0.001). Some inflammatory markers decreased at the time of optimal response and then increased again as the disease progressed. Multivariate analysis revealed that SIRI and lactate dehydrogenase (LDH) were independent prognostic factors no matter before or after PSM analysis. Area under the curve (AUC) of SIRI and LDH were 0.625 (p < 0.001) and 0.596 (p = 0.008), respectively. When SIRI and LDH were combined, the AUC reached 0.649 (p < 0.001). Conclusions: Pretreatment SIRI was an independent prognostic factor of progression free survival (PFS) in advanced LUAD patients. Dynamic monitoring of inflammatory index changes could help to predict therapeutic efficacy. The combination of SIRI and LDH is expected to be a promising clinically accessible biomarker in the future. [ABSTRACT FROM AUTHOR]

Objectives: Aberrantly expressed circular RNAs (circRNAs) have been detected in many types of tumors. Hence, they are currently investigated as candidate biomarkers for diagnostic and potential targets for therapy in cancers. The objective of this study was to assess the expression profile of circRNA in lung adenocarcinoma (LUAD). Methods: This study included 14 pairs of postoperative lung adenocarcinoma specimens, including cancer tissues and matched adjacent tissues. Second‐generation sequencing was applied to the specimens to determine the circRNA expression in them among the 5242 distinct circRNAs detected. Results: We identified a total of 18 significantly dysregulated circRNAs in the LUAD tissues: upregulation in four and downregulation in 14. ROC (The receiver operating characteristic curve) further suggested that hsa_circ_0120106, has_circ_0007342, has_circ_0005937, and circRNA_0000826 could potentially be used as biomarkers in the diagnosis of LUAD. Furthermore, study of the circRNA–microRNA (miRNA)–messenger RNA (mRNA) revealed interactions between the 18 dysregulated circRNA and several cancer‐related miRNAs. Finally, a further Kyoto Encyclopedia of Genes and Genomes analysis showed that the cell cycle phase transition, p53 signaling pathway, AMP‐activated protein kinase (AMPK) relative signaling pathway, and so on were key putative pathways in the process of LUAD. Conclusions: These findings demonstrated the correlation between abnormality in circRNA expression and LUAD, which lays the foundation of making CircRNAs candidate biomarkers in the diagnosis of LUAD. [ABSTRACT FROM AUTHOR]

Objective: Cuproptosis‐related genes are closely related to lung adenocarcinoma (LUAD), which can be analyzed via the analysis of long noncoding RNA (lncRNA). To date, the clinical significance and function of cuproptosis‐related lncRNAs are still not well elucidated. Further analysis of cuproptosis‐related prognostic lncRNAs is of great significance for the treatment, diagnosis, and prognosis of LUAD. Methods: In this study, a multiple machine learning (ML)‐based computational approach was proposed for the identification of the cuproptosis‐related lncRNAs signature (CRlncSig) via comprehensive analysis of cuproptosis, lncRNAs, and clinical characteristics. The proposed approach integrated multiple ML algorithms (least absolute shrinkage and selection operator regression analysis, univariate and multivariate Cox regression) to effectively identify the CRlncSig. Results: Based on the proposed approach, the CRlncSig was identified from the 3450 cuproptosis‐related lncRNAs, which consist of 13 lncRNAs (CDKN2A‐DT, FAM66C, FAM83A‐AS1, AL359232.1, FRMD6‐AS1, AC027237.4, AC023090.1, AL157888.1, AL627443.3, AC026355.2, AC008957.1, AP000346.1, and GLIS2‐AS1). Conclusions: The CRlncSig could well predict the prognosis of different LUAD patients, which is different from other clinical features. Moreover, the CRlncSig was proved to be an effective indicator of patient survival via functional characterization analysis, which is relevant to cancer progression and immune infiltration. Furthermore, the results of RT‐PCR assay indicated that the expression level of FAM83A‐AS1 and AC026355.2 in A549 and H1975 cells (LUAD) was significantly higher than that in BEAS‐2B cells (normal lung epithelial). [ABSTRACT FROM AUTHOR]

The most common driver gene mutation in patients with non‐small‐cell lung cancer (NSCLC) is an epidermal growth factor receptor (EGFR) mutation. With the introduction of EGFR‐tyrosine kinase inhibitors, the treatment prospects and prognosis of NSCLC patients with EGFR‐sensitive mutations have significantly improved. Nonetheless, therapies targeting NSCLC are still associated with a risk of primary or secondary nonclassical drug resistance mutations. In recent years, the research and methodology have led to the continuous discovery of new drugs and drug resistance targets. These explorations have also resulted in continuously discovering new drugs. Consequently, rapid advancements have been made to overcome NSCLC drug resistance. This study aimed to review the current dilemma of targeted therapy for EGFR mutation‐positive NSCLC and the coping strategies for these difficulties. [ABSTRACT FROM AUTHOR]

Metastasis is the major cause of cancer‐related death of cancer patients. Epithelial‐mesenchymal transition (EMT) is one critical process during the cascade of tumor metastasis. EMT is a developmental program exploited by cancer cells to transition from epithelial state to mesenchymal state and confers metastatic properties as well as treatment resistance. Finding factors to inhibit EMT will greatly improve the prognosis patients. Spermatogenesis associated 2 (SPATA2) was originally isolated from human testis and proved playing a role in spermatogenesis. To date, however, the role of SPATA2 in oncogenesis is unknown. In the current study, by mining the public database and validating in a cohort of collected non–small cell lung cancer (NSCLC) specimens, we uncovered that the expression of SPATA2 positively correlated with the prognosis of patients and was an independent prognosis marker in NSCLC. Functional studies proved that ectopic overexpression of SPATA2 inhibited EMT resulting in impaired motility and invasiveness properties in vitro and metastasis in vivo, and increased radiosensitivity in NSCLC. Mechanistic investigation showed that SPATA2 could suppress the β‐catenin signaling via attenuating DVL1 ubiquitination to achieve the functions. Taken together, the current study revealed an inhibitory role of SPATA2 on EMT and that SPATA2 could be a potential target for therapy of NSCLC. [ABSTRACT FROM AUTHOR]

Background: Circular RNAs (circRNAs) have been reported to play roles in lung cancer development. The purpose of this work was to explore the function and mechanism of circ_0043256 in lung cancer tumorigenesis. Methods: Quantitative real‐time polymerase chain reaction (qRT‐PCR) and western blot were used for the detection of the levels of genes and proteins. Cell growth, angiogenesis ability, migration, and invasion were analyzed by using 5‐ethynyl‐2′‐deoxyuridine (EdU) assay, flow cytometry, tube formation assay, transwell assay, and murine xenograft model, respectively. The target between miR‐1206 and circ_0043256 or Krüppel‐like factor 2 (KLF2) was verified by dual‐luciferase reporter assay. Results: Circ_0043256 was a stable circRNA, which was found to be decreased in lung cancer tissues and cells. Functionally, forced expression of circ_0043256 suppressed lung cancer cell growth, angiopoiesis, migration, and invasion. Mechanistically, circ_0043256 directly bound to miR‐1206 and miR‐1206 targeted KLF2, circ_0043256 could regulate KLF2 expression via absorbing miR‐1206. Rescue assay showed that miR‐1206 overexpression reversed the anticancer effects of circ_0043256 on lung cancer cells. Moreover, inhibition of miR‐1206 could suppress the malignant phenotypes of lung cancer cells, which was attenuated by KLF2 knockdown. Pre‐clinically, lentivirus‐mediated circ_0043256 overexpression impeded lung cancer growth in nude mice. Conclusion: Forced expression of circ_0043256 could impede the tumorigenesis of lung cancer via miR‐1206/KLF2 axis, indicating a potential therapeutic approach for lung cancer. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors (ICIs) have become one important therapeutic strategy for advanced non-small-cell lung cancer (NSCLC). It remains imperative to identify reliable and convenient biomarkers to predict both the efficacy and toxicity of immunotherapy, and tumor-associated autoantibodies (TAAbs) are recognized as one of the promising candidates for this. Patients and Methods: This study enrolled 97 advanced NSCLC patients with ICIbased immunotherapy treatment, who were divided into a training cohort (n = 48) and a validation cohort (n = 49), and measured for the serum level of 35 TAAbs. According to the statistical association between the serum positivity and clinical outcome of each TAAb in the training cohort, a TAAb panel was developed to predict the progression-free survival (PFS), and further examined in the validation cohort and in different subgroups. Similarly, another TAAb panel was derived to predict the occurrence of immune-related adverse events (irAEs). Results: In the training cohort, a 7-TAAb panel composed of p53, CAGE, MAGEA4, GAGE7, UTP14A, IMP2, and PSMC1 TAAbs was derived to predict PFS (median PFS [mPFS] 9.9 vs. 4.3 months, p = 0.043). The statistical association between the panel positivity and longer PFS was confirmed in the validation cohort (mPFS 11.1 vs. 4.8 months, p = 0.015) and in different subgroups of patients. Moreover, another 4-TAAb panel of BRCA2, MAGEA4, ZNF768, and PARP TAAbs was developed to predict the occurrence of irAEs, showing higher risk in panel-positive patients (71.43% vs. 28.91%, p = 0.0046). Conclusions: Collectively, our study developed and validated two TAAb panels as valuable prognostic biomarkers for immunotherapy. [ABSTRACT FROM AUTHOR]

Background: With the widespread use of alectinib in patients with anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC), its cardiotoxicity has gradually emerged, including new-onset sinus bradycardia (SB). However, the incidence, timing, severity, and risk factors of alectinib-induced bradycardia remain unknown. Methods: From January 2020 to June 2022, 93 patients with ALK-positive NSCLC treated with alectinib were enrolled in this retrospective analysis. These patients had heart rate (HR) recorded before and after alectinib administration. By reviewing electronic medical records and follow-up, the HR changes of patients during medication were recorded. The potential risk factors associated with alectinib-induced SB were explored. Results: According to an HR cut-off of 60 beats per minute (bpm), 47 patients (50.54%) experienced at least one recorded bradycardia. The mean HR of total participants before alectinib administration was 78.32 (standard deviation [SD], 9.48) and after was 64.88 (SD, 12.21). The median maximum change in HR (range) for all patients was 11 (-55, +4) bpm. For the bradycardia subgroup, the HR of most patients (76.60%) hovered around 50-60 bpm, and 61.70% of SB occurred within 3 months after alectinib administration. Multivariate analysis indicated that baseline HR (odds ratio [OR] 0.86, 95% confidence interval [CI] 0.79-0.93, p < 0.001) and history of hypertension (OR 13.71, 95% CI 2.49-76.38, p = 0.003) were independent risk factors for alectinib-related bradycardia. Conclusions: Alectinib-induced bradycardia had a high incidence, appeared relatively early, and was reversible by dose reduction or withdrawal. [ABSTRACT FROM AUTHOR]

Chemotherapy (CT) and immunotherapy (IO) act synergically in the treatment of non-small cell lung cancer (NSCLC). However, the molecular basis of such interaction is poorly understood. The aim of this review was to explore the mechanisms of CT to potentiate the immune system and, consequently, the action of IO. The most up-todate knowledge concerning the interaction of CT and IO in NSCLC was reviewed and a bibliographic search was made in PubMed/Medline database, using the mentioned keywords, with preference given to recently published articles in English. In addition to the direct cytotoxic effect, CT affects the immune system leading indirectly to cell death. The immune response triggered by PD-1 inhibition is enhanced by the cytotoxic immunogenic effects of CT. This potentiation phenomenon occurs due to an increase in effector cells relatively to regulatory cells, inhibition of myeloid derived suppressor cells, increased potential for cross-presentation by dendritic cells after the death of tumor cells or blocking the STAT6 pathway to increase dendritic cell activity. In conclusion, the effects of CT on the immune system work in synergy with the actions of IO, transforming "cold" tumors into "hot" tumors, which are more visible to the immune system. [ABSTRACT FROM AUTHOR]

Background: COVID‐19 incidence is high in patients with cancer. The fatality rate was high for the Delta variant, necessitating infection prevention by vaccination. This study evaluated the safety of a SARS‐CoV‐2 vaccine in patients with advanced lung cancer receiving anticancer therapy. Methods: We prospectively enrolled patients receiving anticancer drugs for advanced lung cancer and planning SARS‐CoV‐2 vaccination. Early side effects within 7 days of vaccination were evaluated using patient‐reported outcome (PRO) surveys. Chi‐square test and multivariate logistic regression analyses were used. Results: Post‐vaccination PROs were collected from 406 patients (252 were males). The mean age was 72 years. Treatment at the time of initial vaccination included chemotherapy, immune checkpoint inhibitors (ICI), a combination of chemotherapy and ICI, targeted therapy including tyrosine kinase inhibitors, and others in 115, 93, 45, 147, and six cases, respectively. The vaccines administered were BNT162b2 and mRNA273 in 361 and three cases, respectively and unknown in 42 cases. A total of 16.1% of patients developed fever (38°C) after the second mRNA vaccination (95% confidence interval: 12.6%–20.1%). This rate is comparable to data previously reported in 120 patients and slightly higher than that of healthy participants of the BNT162b2 study. Patients receiving treatment with cytotoxic anticancer agents were more likely to have high fever. Multivariate analysis showed no correlation between fever frequency and patient background. No serious initial adverse events due to vaccination were observed. Conclusions: Anti‐SARS‐CoV‐2 mRNA vaccination is safe; however, post‐vaccination fever is more common in patients undergoing lung cancer treatment than in healthy individuals. [ABSTRACT FROM AUTHOR]

Background: Interstitial lung abnormalities (ILAs) are known to be a risk of drug‐induced pneumonitis. However, there are few reports on the relationship between ILAs and immune checkpoint inhibitor‐related interstitial lung disease (ICI‐ILD). We retrospectively investigated the clinical significance of ILAs in patients with non‐small cell lung cancer (NSCLC) receiving ICIs. Methods: We defined ILAs as nondependent abnormalities affecting more than 5% of any lung zone, including ground‐glass or diffuse centrilobular nodularities, traction bronchiectasis, honeycombing, and nonemphysematous cysts. Early‐onset ICI‐ILD was defined as developing within 3 months after the initiation of ICI administration. Results: Of 264 patients with advanced NSCLC, 57 patients (21.6%) had ILAs (43 fibrotic and 14 nonfibrotic ILAs). The difference between the incidence of ICI‐ILD in patients with or without ILAs was not significant. Of 193 patients treated by ICI monotherapy, 18 (9.3%) developed early‐onset ICI‐ILD. Among patients receiving ICI monotherapy, the incidence of early‐onset ICI‐ILD was significantly higher in patients with than in patients without nonfibrotic ILAs. Conclusion: The presence of nonfibrotic ILAs is a significant risk for early‐onset ICI‐ILD in patients with NSCLC undergoing ICI monotherapy. Clinicians should be aware of ILAs, especially nonfibrotic ILAs, before administering ICIs to lung cancer patients. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitor (ICI) combined with chemotherapy is one of the standards of care for advanced non–small cell lung cancer (NSCLC) without driver mutations. However, the biomarker of combination therapy is still unknown. Although previous studies have confirmed that low allele frequency adjusted blood‐based tumor mutational burden (LAF‐bTMB) is associated with the efficacy of ICI monotherapy, there has been no report on the correlation between the efficacy of LAF‐bTMB and ICI combined chemotherapy. This study aimed to explore whether LAF‐bTMB can be used as a predictive biomarker for the efficacy of immunotherapy combined with chemotherapy in advanced NSCLC. Methods: This study enrolled patients diagnosed with advanced NSCLC and who received ICI combined with chemotherapy for first‐line therapy from May 2020 to December 2021 at Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Clinical information, treatment information, survival data, and peripheral blood samples of every patient before treatment were collected. Next‐generation sequencing was performed on plasma samples to estimate bTMB and LAF‐bTMB. Results: A total of 42 patients with NSCLC were enrolled. In this cohort, 19 patients achieved partial response (PR), and the objective response rate (ORR) was 45.2%. The median progression‐free survival (PFS) of all patients was 13.4 months (95% CI, 7.49–19.72). Both PFS and the overall survival (OS) were significantly longer in the responder (R) group than in the non‐responder (NR) group (median PFS, 16.4 months vs. 7.2 months, p = 0.028; median OS, NE vs. 9.3 months, p = 0.016). There was no significant difference in bTMB and LAF‐BTMB between the R and NR group. The ORR of patients with LAF‐bTMB≤8muts/Mb was significantly higher than that of patients with LAF‐bTMB >8muts/Mb (ORR, 61% vs. 26%, respectively, p = 0.033). When LAF‐bTMB ≤8muts/Mb or > 20muts/Mb, ORR was significantly higher than that of patients with LAF‐bTMB between 8 and 20muts/Mb (ORR were 57% and 21%, p = 0.047). No correlation has been found between LAF‐bTMB and PFS or OS. Conclusions: This study confirmed that neither bTMB nor LAF‐bTMB is feasible as a potential predictor of first‐line immunochemotherapy for advanced NSCLC. More suitable biomarkers need to be explored to screen patients with better efficacy of immunotherapy combined with chemotherapy in the future. [ABSTRACT FROM AUTHOR]

Background: Although the utility of segmentectomy for early‐stage non‐small cell lung cancer (NSCLC) has been reported, the adaptation criterion for segmentectomy is unclear. Methods: In total, 171 NSCLC patients who underwent segmentectomy or lobectomy with a consolidation tumor diameter on computed tomography of ≤20 mm were analyzed. Results: Consolidation diameter (p = 0.01), consolidation to tumor ratio (CTR) (p < 0.01), maximum standardized uptake value (SUVmax) (p < 0.01), and segmentectomy (p = 0.01) were significantly different upon univariate analysis among patients stratified by recurrence. Positive correlations were observed between the consolidation diameter on CT and CEA (correlation coefficient; r = 0.19, p = 0.01), SUVmax (r = 0.48, p < 0.01), and CTR (r = 0.83, p < 0.01). Because there was a significant correlation among the consolidation diameter of tumors on CT, CTR, and SUVmax in this study, we integrated these factors into one. Consolidation, CTR, and SUVmax (hazard ratio [HR]: 3.77, 95% confidence interval [CI]: 1.35–11.29, p = 0.01) and segmentectomy (HR: 0.24, 95% CI: 0.03–0.90, p = 0.03) were risk factors for recurrence in a multivariate analysis. There was a significant difference between the segmentectomy and lobectomy groups (5‐year relapse‐free survival [RFS] 96.5% vs. 80.7%, p = 0.02). Conclusions: Consolidation tumor diameter on CT, CTR, and SUVmax is a risk factor for recurrence. These results suggest that for patients with small‐sized early stage NSCLC, this combined factor is important for determining the indication for segmentectomy. [ABSTRACT FROM AUTHOR]

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH), a rare condition, is characterized by pathological proliferation of neuroendocrine cells. Some of them are localized to the airway mucosa, and others locally infiltrate to form tumorlets and nodules. Here, we present a patient with lung adenocarcinoma accompanied by DIPNECH, making the latter difficult to distinguish from multiple pulmonary metastases. The patient, a 72‐year‐old Japanese woman, was diagnosed as having stage IVA lung adenocarcinoma because she had multiple nodules in both lungs. Mutation of epidermal growth factor receptor gene having been found in the primary tumor, treatment with osimertinib was started. This resulted in shrinkage of the primary tumor, but not the multiple pulmonary nodules. To determine whether these lung nodules were indeed lung metastases, we performed right upper lobectomy with lymphadenectomy and wedge resection of the right lower lobe. On pathological examination, the primary tumor was diagnosed as invasive adenocarcinoma, whereas the multiple pulmonary nodules were diagnosed as DIPNECH manifesting as tumorlets. Therefore, the final diagnosis was stage IA1 lung adenocarcinoma accompanied by DINPECH. The patient had no recurrences 1 year after the operation without any additional treatment. This is a rare case of lung adenocarcinoma accompanied by DIPNECH presenting as multiple pulmonary nodules. DIPNECH should be included in the differential diagnosis of multiple pulmonary nodules. [ABSTRACT FROM AUTHOR]

With the in‐depth understanding of programmed cell death 1 ligand 1 (PD‐L1) in non‐small cell lung cancer (NSCLC), PD‐L1 has become a vital immunotherapy target and a significant biomarker. The clinical utility of detecting PD‐L1 by immunohistochemistry or next‐generation sequencing has been written into guidelines. However, the application of these methods is limited in some circumstances where the biopsy size is small or not accessible, or a dynamic monitor is needed. Radiomics can noninvasively, in real‐time, and quantitatively analyze medical images to reflect deeper information about diseases. Since radiomics was proposed in 2012, it has been widely used in disease diagnosis and differential diagnosis, tumor staging and grading, gene and protein phenotype prediction, treatment plan decision‐making, efficacy evaluation, and prognosis prediction. To explore the feasibility of the clinical application of radiomics in predicting PD‐L1 expression, immunotherapy response, and long‐term prognosis, we comprehensively reviewed and summarized recently published works in NSCLC. In conclusion, radiomics is expected to be a companion to the whole immunotherapy process. [ABSTRACT FROM AUTHOR]

Background: To investigate the independent risk factors of poor short‐term outcomes in patients with lung cancer‐associated acute ischemic stroke (LCAIS) and use them to develop an index of prognosis LCAIS (pLCAIS) which could help clinicians identify patients at high risk for poor short‐term outcomes. Methods: We retrospectively enrolled patients with lung cancer‐associated acute ischemic stroke and employed the 90D modified Rankin cale (mRS) to divide them into two groups: good outcomes (score 0–2) and poor outcomes (score 3–6). Propensity score matching (PSM) was used to remove confounding factors, and multivariable logistic regression analysis was used to analyze the independent risk factors of pLCAIS. The receiver operating characteristic (ROC) and area under the ROC curve (AUC) developed a multiple model combining the independent risk factors of pLCAIS. Results: A total of 172 patients were included: 67 (38.9%) with good outcomes and 105 (61.1%) with poor outcomes. After using PSM, there were 33 cases in each group. The results showed that patients with poor short‐term outcomes were significantly higher in D‐dimer (OR = 1.001, 95% CI: 1.000–1.002, p = 0.048), CRP (OR = 1.078, 95% CI: 1.008–1.153, p = 0.028), and neutrophil count (OR = 14.673, 95% CI: 1.802–19.500, p = 0.012). The ROC curve, used to assess the diagnostic ability of binary classifiers, showed that the product of these three independent risk factors showed high sensitivity and specificity. Conclusion: In this study, we have identified three independent risk factors associated with poor short‐term outcomes in pLCAIS: higher NC, CRP, and D‐dimer levels. These findings may be helpful for clinicians in identifying poor short‐term outcomes patients. [ABSTRACT FROM AUTHOR]

Background: Endobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA) is used to evaluate hilar/interlobar/lobar lymph nodes. This study aimed to assess the clinical utility of EBUS‐TBNA for station 10/11/12 lymph nodes (LNs) in patients with primary lung cancer. Methods: This was a retrospective analysis of a prospectively collected database of patients with primary lung cancer who underwent EBUS‐TBNA for station 10/11/12 LNs from January 2015 to December 2019. Patients with benign results from EBUS‐TBNA who did not undergo surgical sampling/clinical follow‐up or who received radiotherapy/chemotherapy were excluded. Results: The analyses were conducted on 889 LNs from 797 patients. The overall diagnostic sensitivity, specificity, accuracy, negative predictive value (NPV), and positive predictive value of EBUS‐TBNA were 95.7, 100, 97.3, 93.2, and 100%, respectively. Diagnostic sensitivity was significantly lower for LNs <10 mm than ≥10 mm in size (90.1% vs. 97.8%; p < 0.001). There was no significant difference in diagnostic performance according to the nodal station (10 vs. 11/12) and left‐ versus right‐sided LNs. The diagnostic sensitivity (100 vs. 95.5%; p = 0.221) and specificity (100 vs. 100%) of N3 LNs was not significantly different from those of N1 LNs. In this study, eight (8/91, 8.8%) patients with cN1 NSCLC received neoadjuvant treatment based on the results of EBUS‐TBNA. Conclusion: EBUS‐TBNA accurately evaluates station 10/11/12 LNs of both N1 and N3 disease. The diagnostic performances of EBUS‐TBNA for station 10/11/12 LNs seem to be comparable to those of EBUS‐TBNA for mediastinal LNs. [ABSTRACT FROM AUTHOR]

Background Hospitalization expenses for the therapy of lung cancer are not only a direct economic burden on patients, but also the focus of medical insurance departments. Therefore, the method for classifying and analyzing lung cancer hospitalization expenses so as to predict reasonable medical cost has become an issue of common interest for both hospitals and insurance institutions. Methods A C5.0 algorithm is adopted to analyze factors influencing hospitalization expenses of 731 lung cancer patients. A C5.0 algorithm is a data mining method used to classify calculation. Results Increasing the number of input variables leads to variation in the importance of different variables, but length of stay ( LOS), major therapy, and medicine cost are the three variables of greater importance. They are important factors that affect the hospitalization cost of lung cancer patients. In all three calculations, the classification accuracy rate of training and testing partition sets reached 84% and above. The classification accuracy rate reached over 95% after addition of the cost variables. Conclusion The classification rules are proven to be in accordance with actual clinical practice. The model established by the research can also be applied to other diseases in the screening and analysis of disease hospitalization costs according to selected feature variables. [ABSTRACT FROM AUTHOR]

The safety of neoadjuvant chemoimmunotherapy before surgery in patients with non–small cell lung cancer (NSCLC) remains unclear in the perioperative stage. We describe a case of a 63‐year‐old man with IIIC stage NSCLC who received neoadjuvant chemoimmunotherapy and radical lobectomy. After the second cycle of pembrolizumab and chemotherapy (paclitaxel + carboplatin), the patient was diagnosed with immunologic enterocolitis and relieved by glucocorticoid therapy. Radical lobectomy of the right upper lobe was then performed. On postoperative day 4 (POD 4), the patient suddenly suffered suffocated wheezing during sleep. Interstitial lung disease was, therefore, identified by chest computed tomography scan. Glucocorticoids and mechanical ventilation were applied and the symptoms were relieved. On POD 10, the patient developed a bronchial fistula and underwent emergent repair surgery. This is the first case of multi‐organs, multi‐time point immune‐related adverse events (irAE) in perioperative NSCLC patients who received neoadjuvant chemoimmunotherapy. Clinicians should be on high alert for signs of irAEs in neoadjuvant chemoimmunotherapy patients, promptly requiring multidisciplinary management. [ABSTRACT FROM AUTHOR]

Background: To investigate the impact of station 3A lymph node dissection (LND) on overall survival (OS) and disease‐free survival (DFS) in completely resected right‐side non‐small‐cell lung cancer (NSCLC) patients. Methods: A total of 1661 cases with completely resected right‐side NSCLC were included. Propensity score matching (PSM) was performed to minimize selection bias, and a logistic regression model was conducted to investigate the risk factors associated with station 3A lymph node metastasis (LNM). The Kaplan–Meier method and Cox proportional hazards model were used to evaluate the impact of station 3A LND on survival. Results: For the entire cohort, 503 patients (30.3%) underwent station 3A LND. Of those, 11.3% (57/503) presented station 3A LNM. Univariate and multivariate logistic analyses showed that station 10 LNM, tumor location, and the number of resected lymph nodes were independent risk factors associated with station 3A LNM. Before PSM, patients with station 3A LND had worse 5‐year OS (p = 0.002) and DFS (p = 0.011), and more drainage on postoperative day 1 (p = 0.041) than those without. After PSM, however, station 3A LND was not associated with the 5‐year OS (65.7% vs. 63.6%, p = 0.432) or DFS (57.4% vs. 56.0%, p = 0.437). The multivariate analysis further confirmed that station 3A LND was not a prognostic factor (OS, p = 0.361; DFS, p = 0.447). Conclusions: Station 3A LND could not improve long‐term outcomes and it was unnecessary to dissect station 3A lymph nodes during surgery of right‐side NSCLC. [ABSTRACT FROM AUTHOR]