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Tumor immunotherapy has been widely used in clinical treatment of various cancers. However, some patients of these cancers do not respond to immunotherapy effectively. And H. pylori infection has been considered to be related to the efficacy of immunotherapy. This review aims to summarize the different effects and mechanisms of H. pylori infection on immunotherapy in different kinds of cancers. We searched the relevant literature on H. pylori and tumor immunotherapy, and summarized to form a review. Generally, H. pylori infection plays a role in affecting kinds of cancers' development, besides gastric cancer. Current evidence suggests that H. pylori infection may reduce the efficacy of immunotherapy for colorectal cancer, non-small cell lung cancer and melanoma, but due to the lack of sufficient evidence, more data is needed to prove that. While for gastric cancer, the effects remain controversial. The H. pylori regulation effects and metabolisms involved in systematic related cancers should be paid attention to. Whether H. pylori should be eradicated when immunotherapy performed may be a critical consideration for some kinds of tumors. [ABSTRACT FROM AUTHOR]

Background: Adenocarcinoma with positive echinoderm microtubuleassociated protein-like 4 gene and anaplastic lymphoma kinase (EML4-ALK) gene fusion accounts for 3-7% of lung cancer cases and can be targeted with ALK tyrosine kinase inhibitors (TKIs). Second-generation TKIs are the standard of care for targeted populations, especially those with central nervous system (CNS) metastasis. However, most patients eventually experience disease progression because of drug resistance caused by multiple mechanisms, predominantly secondary mutations. Case description: We present a female advanced non-small cell lung cancer (NSCLC) case with positive EML4-ALK gene fusion, in which disease progression occurred in only 3 months after first-line treatment with alectinib. Two secondary mutations were detected by next-generation sequencing; one was V1180L located in exon 23, and the other was E803Q located in exon 14, which was a novel mutation that had never been reported. Ensartinib and ceritinib were administered as second-line and third-line treatments. However, the response to these TKIs was poor, and her overall survival was only 7 months. Conclusion: The secondary mutation E803Q located in exon 14 seems resistant to most second-generation ALK-TKIs. If there is an opportunity, the efficacy of the third-generation ALK-TKI loratinib should be tested. [ABSTRACT FROM AUTHOR]

Clinical staging in lung cancer has implications for treatment planning and prognosis. We sought to determine the rate of inaccurate clinical stage (relative to pathologic), identify risk factors for inaccuracy, and evaluate the association of inaccuracy on survival. We hypothesized that inaccurate staging was associated with poor survival. In this retrospective cohort study, adult patients who received surgical resection without neoadjuvant treatment for nonsmall cell lung cancer from 2004 to 2020 in the National Cancer Database were categorized by accuracy of clinical stage (relative to pathologic stage). Multivariate models were used to determine risk factors for inaccuracy. The association between inaccuracy and overall survival was also analyzed. We identified 255,598 patients with lung cancer, including 84,543 patients (33.1%) who were inaccurately staged. Stage inaccuracy was associated with higher tumor, node, metastasis stage (T-category 3: odds ratio [OR] = 1.2, 95% confidence interval [CI] 1.15-1.28; N-category 2: OR = 2.6, 95% CI 2.47-2.79), greater quantity of lymph nodes evaluated, and more extensive resection (extended lobectomy/bilobectomy: OR = 1.3, 95% CI 1.20-1.37; pneumonectomy: OR = 1.6, 95% CI 1.54-1.74). Patients undergoing robotic surgery were less likely to be inaccurately staged (OR = 0.89, 95% CI 0.852-0.939). Inaccurate staging was associated with worse overall survival (5-y 67.5% accurate versus 55.4% inaccurate, P < 0.001). Inaccurate staging was also associated with worse survival in a multivariate Cox model (hazard ratio [HR] = 1.3, 95% CI 1.29-1.33). Both "understaging" (path > clinical) and "overstaging" (clinical > path) were associated with inferior survival. Inaccurate clinical stage (relative to pathologic) occurs in one-third of patients receiving surgery for lung cancer. Inaccuracy is associated with poor survival. Quality improvement initiatives should focus on improving clinical staging accuracy. [ABSTRACT FROM AUTHOR]

Background: Previous clinical evidence has shown a correlation between pulmonary fibrosis (PF) and lung cancer (LC), but their causal relationship remains unknown. Methods: This study utilized a bidirectional two-sample Mendelian randomization (MR) approach to explore the causal relationship between PF and LC, including its subtypes. Genetic data were obtained from the IEU and FinnGen Genome-Wide Association Studies (GWAS). SNPs with genome-wide significance were selected, and analyses were conducted using Inverse-Variance Weighted (IVW), MR Egger, and Weighted Median methods. The IVW results for various subtypes of lung cancer and PF were used in a meta-analysis to investigate the overall causal effect between PF and lung cancer. Sensitivity analysis was used for both MR and meta-analysis to investigate the robustness of the results. Results: The bidirectional MR analysis showed no significant causal relationship between PF and overall, LC or its subtypes, except for SCLC, which had a significant positive association (OR = 1.29, 95% CI 1.07-1.57, p = 0.009). The meta-analysis results indicated no overall causal effect (OR = 1.067, 95% CI: 0.952-1.195, P = 0.265, I² = 57.3%). In the reverse MR analysis, NSCLC and LUSC showed significant associations with PF (OR = 1.12, 95% CI 1.01-1.23, p = 0.028 and OR = 1.04, 95% CI 1.01-1.08, p = 0.012, respectively), while the meta-analysis results indicated no significant causal effect (OR = 1.006, 95% CI: 0.973-1.040, P = 0.734, I² = 55.9%). Sensitivity analyses indicated no evidence of horizontal pleiotropy or significant heterogeneity. Conclusion: This study suggests a potential causal relationship between PF and SCLC, as well as between NSCLC and LUSC with PF. However, the overall causal relationship between PF and LC was not statistically significant, possibly due to individual variability and other influencing factors. Further research using data from diverse populations is needed to validate these findings. [ABSTRACT FROM AUTHOR]

Background: The most common form of therapy for nonsmall cell lung cancer (NSCLC) in early stage is surgery-based combination therapy, including radiotherapy and immunotherapy. However, postoperative radiotherapy (PORT) of cancer is correlated with increasing risk of second primary malignancy (SPM), especially young-onset cancer cases. The authors aimed to quantify the risks of SPM associated with PORT treatment for young-onset NSCLC in early stage. Methods: The authors screened for SPM that developed over 5 years since the diagnosis of NSCLC. Using the data from the Surveillance, Epidemiology, and End Results database, PORT-correlated risks were estimated with multivariate Logistic regression analysis. Moreover, Fine-Gray's competing risk regression analysis was used to calculate the cumulative incidence of SPMs. Results: Among the 30 308 young-onset NSCLC patients in early stage undergoing surgery, a total of 3728 patients have received PORT. Logistic regression analyses showed that PORT showed substantial correlation with elevated risks of second solid malignancies [relative risks (RR) =1.31; 95% CI: 1.17-1.46], lung cancer (RR=1.23; 95% CI: 1.07-1.42), breast cancer (RR=1.74; 95% CI: 1.16-2.74), and colon and rectum cancers (RR= 1.37; 95% CI: 1.07-2.06) as well as a negligible risk of second hematologic malignancies (RR =1.15; 95% CI: 0.82-1.67). The cumulative incidence of SPMs revealed similar findings. Higher RR was obtained in NSCLC patients aged 60-69 years (RR= 1.33), in white race (RR=1.36), diagnosed in 1975-2000 (RR =1.23) and 2001-2015 (RR =1.40), or diagnosed with lung adenocarcinoma (RR= 1.55). Conclusion: PORT for young-onset NSCLC in early stage was correlated with elevated risks of SPMs (lung cancer, breast cancer, as well as colon and rectum cancers), supporting the need for long-term surveillance of these patients. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) is an important causative factor of cervical cancer and is associated with nonsmall cell lung cancer (NSCLC). Merkel cell polyomavirus (MCPyV) is a rare and highly fatal cutaneous virus that can cause Merkel cell carcinoma (MCC). Although coinfection with oncogenic HPV and MCPyV may increase cancer risk, a definitive etiological link has not been established. Recently, genomic variation and genetic diversity in the MCPyV noncoding control region (NCCR) among ethnic groups has been reported. The current study aimed to provide accurate prevalence information on HPV and MCPyV infection/coinfection in NSCLC patients and to evaluate and confirm Korean MCPyV NCCR variant genotypes and sequences. DNA from 150 NSCLC tissues and 150 adjacent control tissues was assessed via polymerase chain reaction (PCR) targeting regions of the large T antigen (LT‐ag), viral capsid protein 1 (VP1), and NCCR. MCPyV was detected in 22.7% (34 of 150) of NSCLC tissues and 8.0% (12 of 150) of adjacent tissues from Korean patients. The incidence rates of HPV with and without MCPyV were 26.5% (nine of 34) and 12.9% (15 of 116). The MCPyV NCCR genotype prevalence in Korean patients was 21.3% (32 of 150) for subtype I and 6% (nine of 150) for subtype IIc. Subtype I, a predominant East Asian strain containing 25 bp tandem repeats, was most common in the MCPyV NCCR data set. Our results confirm that coinfection with other tumor‐associated viruses is not associated with NSCLC. Although the role of NCCR rearrangements in MCPyV infection remains unknown, future studies are warranted to determine the associations of MCPyV NCCR sequence rearrangements with specific diseases. [ABSTRACT FROM AUTHOR]

Background: Emphysema is generally considered a poor prognostic factor for patients with nonsmall cell lung cancer; however, whether the poor prognosis is due to highly malignant tumors or emphysema itself remains unclear. This study was designed to determine the prognostic value of emphysema in patients with early-stage nonsmall cell lung cancer. Methods: A total of 721 patients with clinical stage IA nonsmall cell lung cancer who underwent complete resection between April 2007 and December 2018 were retrospectively analyzed regarding clinicopathological findings and prognosis related to emphysema. Results: The emphysematous and normal lung groups comprised 197 and 524 patients, respectively. Compared with the normal lung group, lymphatic invasion (23.9% vs. 14.1%, P = 0.003), vascular invasion (37.6% vs. 17.2%, P < 0.001), and pleural invasion (18.8% vs. 10.9%, P = 0.006) were observed more frequently in the emphysema group. Additionally, the 5-year overall survival rate was lower (77.1% vs. 91.4%, P < 0.001), and the cumulative incidence of other causes of death was higher in the emphysema group (14.0% vs. 3.50%, P < 0.001). Multivariable Cox regression analysis of overall survival revealed that emphysema (vs. normal lung, hazard ratio 2.02, P = 0.0052), age > 70 years (vs. < 70 years, hazard ratio 4.03, P < 0.001), and SUVmax > 1.8 (vs. ≤ 1.8, hazard ratio 2.20, P = 0.0043) were independent prognostic factors. Conclusions: Early-stage nonsmall cell lung cancer with emphysema has a tendency for the development of highly malignant tumors. Additionally, emphysema itself may have an impact on poor prognosis. [ABSTRACT FROM AUTHOR]

In a large academic medical center, processes for ordering and receiving biomarker testing to inform cancer treatment in non–small cell lung cancer varied by whether tests were conducted internally or externally. Lack of standardization in biomarker testing processes, despite the availability of electronic health record solutions, contributes to clinician burden and may increase risk of delays in receipt of testing results; therefore, efforts to streamline ordering processes may benefit health systems. [ABSTRACT FROM AUTHOR]

Background and Aims: Lung cancer is ranked as the second most prevalent form of cancer worldwide. Nonsmall cell lung cancer (NSCLC) represents the predominant histological subtype. Research suggests that one‐third of lung cancer patients also experiencing depression. Antidepressants play an indispensable role in the management of NSCLC. Despite significant advancements in treatment, lung cancer patients still face a high mortality rate. Major depressive disorder (MDD) and related antidepressants involved in treatment efficacy and prognosis of NSCLC. However, there has been a lack of screening and analysis regarding genes and networks associated with both NSCLC and MDD. Methods: To investigate the correlation between MDD and NSCLC, our discovery and validation analysis included four datasets from the Gene Expression Omnibus database from NSCLC or MDD. Differential gene expression (DEGs) analysis, GO and KEGG Pathway, and protein‐protein interaction network analyzes to identify hub genes, networks, and associated observations link between MDD and NSCLC. Results: The analysis of two datasets yielded a total of 84 downregulated and 52 upregulated DEGs. Pathway enrichment analyzes indicated that co‐upregulated genes were enriched in the regulation of positive regulation of cellular development, collagen‐containing extracellular matrix (ECM), cytokine binding, and axon guidance. We identified 20 key genes, which were further analyzed using the MCODE plugin to identify two core subnetworks. The integration of functionally similar genes provided valuable insights into the potential involvement of these hub genes in diverse biological processes including angiogenesis humoral immune response regulation inflammatory response organization ECM network. Conclusion: We have identified a total of 136 DEGs that participate in multiple biological signaling pathways. A total of 20 hub genes have demonstrated robust associations, potentially indicating novel diagnostic and therapeutic targets for both diseases. [ABSTRACT FROM AUTHOR]

Purpose: Although the treatment of nonsmall cell lung cancer (NSCLC) has rapidly progressed recently, there is little evidence of treatment for patients with symptomatic brain metastases (BM) and poor performance status (PS). However, in symptomatic BM patients, appropriate upfront intracranial treatment can often lead to rapid improvement in PS and effective systemic therapy. Thus, this study investigated the prognostic factors for the survival of poor PS NSCLC patients with synchronous BM. Methods: Data of patients with BM and Karnofsky PS (KPS) ≤70 at the first diagnosis of NSCLC who were treated in our hospital between January 2017 and December 2021 were reviewed. Patient survival was compared among patients stratified by type of first-line regimen of systemic treatment. Correlations between patient characteristics and survival were examined. Results: Fifty patients receiving aggressive treatment were enrolled. The median survival times for tyrosine kinase inhibitor (TKI), immune checkpoint inhibitor (ICI), and chemotherapy alone groups were 19 (95 % confidence interval [CI], 2.8–68.5), 19 (3.0–62.0), and 13 (1.2–24.8) months, respectively. Survival in the TKI and ICI groups was significantly longer than in the chemotherapy alone group (p = 0.046, TKI vs. chemo; p = 0.022, ICI vs. chemo; p = 0.023). Both sex and type of systemic treatment correlated to survival time on univariate analysis. Chemotherapy alone for systemic treatment [p = 0.034; hazard ratio (HR), 0.44 (0.20–0.94)] remained significant for predicting overall survival in the multivariate analysis. Conclusion: Even in patients with poor PS and BM at the initial diagnosis of NSCLC, the ICI group had a survival time comparable to that of the TKI group when combined with tailor-made intracranial treatment. There is a subgroup in the patient population that was previously considered unsuitable for ICI, whose PS improves with individualized intracranial treatment, and who may benefit from immunotherapy.

Percutaneous lung ablation is increasingly used in the treatment of lung malignancies with good outcomes, but recurrence is commonly reported in ablation of lesions size larger than 3 cm. We report a 50-year-old female with a 9 cm nonsmall cell lung cancer involving the right upper lobe and apical chest wall causing severe neuropathic shoulder pain and significantly disturbing her daily activities. CT-guided percutaneous cryoablation was performed using a 4-phase protocol with complete eradication of the tumor. Follow-up imaging showed no evidence of recurrence 6 months after the procedure. The neuropathic pain was significantly improved after the procedure, and she was pain-free until her death due to metastatic disease elsewhere. To our knowledge, this is the first case of successful cryoablation for an exceptionally large lesion.

Background: Definitive concurrent chemoradiotherapy (CCRT) followed by maintenance therapy with immune checkpoint inhibitors offers the best chance of cure for patients with stage III non-small cell lung cancer (NSCLC). A significant challenge in this regimen is the occurrence of acute severe lymphopenia (ASL), which can compromise treatment efficacy. Currently, there are no effective strategies for preventing and treating ASL. Shenglin decoction (SLD), a traditional Chinese herbal medicine formulation, has demonstrated preliminary efficacy in mitigating ASL. However, robust evidence from clinical trials and a clear understanding of its mechanism of action are still needed. This study aims to comprehensively assess the efficacy, safety, and underlying mechanisms of SLD in the prevention of ASL. Methods: This prospective, dual-center, open-label, randomized controlled trial will enroll 140 stage III NSCLC patients. Participants will be randomly allocated in a 1:1 ratio to a control group or an experimental group. Both groups will undergo definitive CCRT. Alongside the commencement of CCRT, the experimental group will receive an additional oral SLD intervention for a duration of three months. The primary outcome is the incidence rate of ASL, defined as the proportion of patients who experience at least one instance of a total lymphocyte count falling below 0.5 × 10^9 cells/L within 3 months of initiating CCRT treatment. Additionally, 16S rRNA gene sequencing analysis of fecal samples to assess gut microbiota, as well as metabolomic analysis of fecal/blood samples, will be conducted to explore potential mechanisms. Discussion: This study protocol aims to rigorously evaluate the efficacy and safety of SLD, as well as elucidate its mechanism of action in preventing ASL. Successful outcomes could establish SLD as an evidence-based intervention for ASL prevention in NSCLC patients undergoing CCRT. [ABSTRACT FROM AUTHOR]

Introduction: This meta‐analysis sought to investigate the effect of neoadjuvant chemotherapy (NACT) combined with surgery in patients with nonsmall cell lung cancer (NSCLC). Methods: With time span from January 2010 to December 2022, PubMed, Web of Science and Embase, China National Knowledge Infrastructure, and WanFang databases were searched for randomized controlled trials on comparison between NACT combined with surgery and surgery alone in patients with NSCLC. Then a meta‐analysis was performed in accordance with Preferred Reporting Items for Systematic reviews and Meta‐Analyses (PRISMA) guidelines. Results: A total of 1511 studies were retrieved and 12 were finally included. Meta‐analysis results showed that compared with surgery alone, a combination of NACT and surgery was associated with higher treatment response rate (odds ratio, OR = 2.459, 95% confidence interval, CI [1.785, 3.388], P < 0.001), 1‐year survival rate (OR = 2.185, 95% CI [1.608, 2.970], P < 0.001), and 3‐year survival rate (OR = 2.195, 95% CI [1.568, 3.073], P < 0.001) and lower levels of intraoperative blood loss (standardized mean difference, SMD = −0.932, 95% CI [−1.588, −0.275], P = 0.005) and length of hospital stay (SMD = −0.481, 95% CI [−0.933, −0.028], P = 0.037). Conclusion: NACT combined with surgery is superior to surgery alone in the treatment of NSCLC and can promote postoperative recovery. Collectively, such combination is a safe and effective treatment for patients with NSCLC. [ABSTRACT FROM AUTHOR]

The microbiome is known to play a significant role in cancer biology; however, few studies have elucidated its relationship with Nonsmall Cell Lung Cancer (NSCLC) patient outcomes. We hypothesized that there are specific microorganisms that are closely related with NSCLC patient survival. Total of 647 NSCLC (Adenocarcinoma and Squamous Cell Carcinoma combined) patients in The Cancer Genome Atlas (TCGA) were analyzed using the R software. A Volcano Plot was analyzed with the patients divided into Short and Long Survivors by overall survival of 0.9 years, and we found that a bacterium Rothia was significantly abundant in Short Survivors, and Blastococcus, Leptospira, and Haematobacter in Long Survivors, but presence of Rothia alone was associated with overall survival. The age, race, subtype, and sex were not significantly different by the presence of Rothia in NSCLC. Unexpectedly, Rothia-positive NSCLC was associated with less cell proliferation by gene set enrichment analysis, Mki67 expression, proliferation score, with less fraction altered and homologous recombination deficiency, and with high infiltration of stromal cells, indicating favorable oncological characteristics. Further, Rothia-positive tumors were associated with significantly higher infiltration of CD8 T cells, CD4 T cells, Monocytes, and NK cells, and high interferon-gamma response, T-cell receptor richness, cytolytic activity, indicating favorable tumor immune microenvironment. NSCLC with Rothia was associated with worse survival but also with favorable oncological characteristics such as less cell proliferation and favorable tumor immune microenvironment. We cannot help but speculate that Rothia in NSCLC is associated with mortality unrelated to oncological characteristics. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant chemoimmunotherapy (NACI) is promising for resectable nonsmall cell lung cancer (NSCLC), but predictive biomarkers are still lacking. The authors aimed to develop a model based on pretreatment parameters to predict major pathological response (MPR) for such an approach. Methods: The authors enrolled operable NSCLC treated with NACI between March 2020 and May 2023 and then collected baseline clinical-pathology data and routine laboratory examinations before treatment. The efficacy and safety data of this cohort was reported and variables were screened by Logistic and Lasso regression and nomogram was developed. In addition, receiver operating characteristic curves, calibration curves, and decision curve analysis were used to assess its power. Finally, internal crossvalidation and external validation was performed to assess the power of the model. Results: In total, 206 eligible patients were recruited in this study and 53.4% (110/206) patients achieved MPR. Using multivariate analysis, the predictive model was constructed by seven variables, prothrombin time (PT), neutrophil percentage (NEUT%), large platelet ratio (P-LCR), eosinophil percentage (EOS%), smoking, pathological type, and programmed death ligand-1 (PD-L1) expression finally. The model had good discrimination, with area under the receiver operating characteristic curve (AUC) of 0.775, 0.746, and 0.835 for all datasets, cross-validation, and external validation, respectively. The calibration curves showed good consistency, and decision curve analysis indicated its potential value in clinical practice. Conclusion: This real world study revealed favorable efficacy in operable NSCLC treated with NACI. The proposed model based on multiple clinically accessible parameters could effectively predict MPR probability and could be a powerful tool in personalized medication. [ABSTRACT FROM AUTHOR]

The theophylline derivative d17 is a candidate drug for nonsmall cell lung cancer (NSCLC) treatment previously developed by our group. However, it has the limitations of inadequate bioavailability, poor targeting, and insignificant therapeutic effect. Chemo-photodynamic synergistic therapy is a promising method of synergistic antitumor therapy. Herein, d17 and photosensitizer chlorin e6 (Ce6) were loaded into nanoparticles (NPs) via supramolecular self-assembly, which are self-assembled through π–π stacking and hydrogen bond interactions to form nanospheres with a size of about 85 nm and a surface charge of −33 mV. Compared with free Ce6, the d17–Ce6 NPs have good hydrophilicity and stability and can effectively accumulate in NSCLC tumor tissues due to the enhancement and retention effect. More significantly, the d17–Ce6 NPs can synergistically inhibit tumor growth compared with other treatment groups with no obvious toxicity. Taken together, the d17–Ce6 NPs may be an effective carrier-free nanodrug for the chemo-photodynamic synergistic treatment of NSCLC. [ABSTRACT FROM AUTHOR]

Claudin‐6 (CLDN6) has been extensively studied in different tumors to date. However, in the case of nonsmall cell lung cancer (NSCLC), CLDN6 has a largely unknown role and molecular mechanism. We detected the expression of CLDN6 in NSCLC tissues and cells using reverse transcription‐quantitative polymerase chain reaction (PCR) and western blot assays. A gain‐of‐function experiment was performed to evaluate the biological effects of CLDN6 on NSCLC cell behaviors. Methylation‐specific PCR was utilized to detect the DNA methylation of CLDN6 gene promoter region. The interaction of CLDN6 and receptor interacting protein 1 (RIP1) was determined by coimmunoprecipitation assay. Furthermore, the modulation of CLDN6 on RIP1/apoptosis signal‐regulating kinase 1 (ASK1)/c‐Jun N‐terminal kinase (JNK) axis was confirmed. The results showed that in NSCLC tissues and cells, CLDN6 expression level was declined, and was associated with a high level of DNA methylation. CLDN6 overexpression suppressed the viability, invasion, migration, and promoted cell apoptosis. Besides, the enhanced expression of CLDN6 reduced the glycolysis and the dysfunction of mitochondrial respiration of NSCLC cells. Mechanistic investigation confirmed that CLDN6 interacted with RIP1 and inhibited cellular biological function of NSCLC cells via RIP1/ASK1/JNK axis. Besides, CLDN6 overexpression inhibited tumor growth in vivo. In conclusion, CLDN6 inhibited NSCLC cell proliferation through inactivating aerobic glycolysis via the RIP1/ASK1/JNK axis. Highlight: Low expression of CLDN6 and was associated with a high level of DNA methylation in NSCLC tissues and cell lines.CLDN6 interacted with RIP1 and inhibited promoted RIP1 expression.CLDN6 inhibited progression of NSCLC cells by inactivating aerobic glycolysis via the RIP1/ASK1/JNK axis. [ABSTRACT FROM AUTHOR]

Background: Studies of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in resectable non-small-cell lung cancer (NSCLC) have been conducted. The purpose of our study was to evaluate the benefits of osimertinib as neoadjuvant therapy for resectable EGFR-mutated NSCLC. Method: This retrospective study evaluated patients with EGFRmutations in exon 19 or 21 who received targeted therapy with osimertinib (80 mg per day) before surgery between January 2019 and October 2023 in Henan Cancer Hospital. Results: Twenty patients were evaluated, all of whom underwent surgery. The rate of R0 resection was 100% (20/20). The objective response rate was 80% (16/ 20), and the disease control rate was 95% (19/20). Postoperative pathological analysis showed a 25% (5/20) major pathological response rate and 15% (3/20) pathological complete response rate. In total, 25% (5/20) developed adverse events (AEs), and the rate of grades 3--4 AEs was 10% (2/20). One patient experienced a grade 3 skin rash, and 1 patient experienced grade 3 diarrhea. Conclusion: Osimertinib as neoadjuvant therapy for resectable EGFR-mutated NSCLC is safe and well tolerated. Osimertinib has the potential to improve the radical resection rate and prognosis. [ABSTRACT FROM AUTHOR]

Introduction: The efficacy of second-line immune checkpoint inhibitor (ICI) therapy is limited in non-small cell lung cancer (NSCLC) patients with ≤ 49% PDL1 expression. Although chemoimmunotherapy is a promising strategy, platinum-based chemotherapy followed by ICI monotherapy is often used to avoid synergistic adverse events. However, predictors of the efficacy of ICI monotherapy after platinum-based chemotherapy in NSCLC with ≤ 49% PD-L1 expression remain scarce. Methods: This multicenter retrospective study evaluated 54 advanced or recurrent NSCLC patients with ≤ 49% PD-L1 expression who were treated with second-line ICI monotherapy following disease progression on first-line platinum-based chemotherapy at nine hospitals in Japan. The impact of response to platinum-based chemotherapy on the efficacy of subsequent ICI monotherapy was investigated. Results: The response to first-line platinum-based chemotherapy was divided into two groups: the non-progressive disease (PD) group, which included patients who did not experience disease progression after four cycles of chemotherapy, and the PD group, which included patients who showed initial PD or could not maintain disease control during the four cycles of chemotherapy and switched to second-line ICI monotherapy. Among the 54 patients, 32 and 22 were classified into the non-PD and PD groups, respectively. The non-PD group showed better response rates (p = 0.038) and longer overall survival (OS) with ICI monotherapy (p = 0.023) than the PD group. Multivariate analysis identified that maintaining a non-PD status after four cycles of chemotherapy was an independent prognostic factor for ICI monotherapy (p = 0.046). Moreover, patients with a modified Glasgow Prognostic Score (mGPS) of 0 showed a tendency for longer OS with ICI monotherapy (p = 0.079), and there was a significant correlation between maintaining non-PD after four cycles of chemotherapy and an mGPS of 0 (p = 0.045). Conclusion: Maintaining a non-PD status after four cycles of platinum-based chemotherapy was a predictor of OS after second-line ICI monotherapy. These findings will help physicians select the most suitable treatment option for NSCLC patients who were treated with platinum-based chemotherapy and switched to second-line treatment. Those who experienced early PD during platinum-based chemotherapy should not be treated with ICI monotherapy in the secondline setting. [ABSTRACT FROM AUTHOR]

Objective: We conducted this paper to decipher the efficacy of the combined chemotherapy of zoledronic acid and pamidronate in treating bone metastases from nonsmall cell lung cancer (NSCLC) and the effects on pain stress and bone metabolic indices. Methods: Patients with bone metastases from NSCLC were allocated into Group A and Group B. Patients in the Group A were administrated with pamidronate combined chemotherapy and patients in the Group B were administrated with zoledronic acid combined chemotherapy. The efficacy, pain symptom scores, quality of life scores, serum inflammatory factor, serum bone metabolic indices, serum pain stress indicators, and the occurrence of adverse effects were compared in patients of the two groups. Results: The total effective rate of treatment was higher in the Group B than in the Group A. After treatment, reduced Numerical Rating Scale scores and elevated Karnofsky Performance Score score, reduced serum levels of N‐terminal mid‐fragment of osteocalcin, N‐terminal propeptide of type I procollagen, bone‐specific alkaline phosphatase, and type I collagen hydroxyl terminal peptide β special sequence, reduced serum levels of C‐reactive protein, procalcitonin, tumor necrosis factor‐α, and interleukin‐6, as well as decreased levels of bradykinin, substance P, neuropeptide Y, and β‐endorphin were found in the Group B versus the Group A. No notable difference was witnessed in the rate of adverse reactions between the Group A and the Group B. Conclusion: Zoledronic acid combined with chemotherapy can effectively treat bone metastases of NSCLC and improve pain stress and bone metabolic status, which has value that can be promoted and applied in clinical treatment. [ABSTRACT FROM AUTHOR]

Background: Protein-1 (PD-1) and programmed cell death 1 ligand 1 (PD-L1) therapy have become an important treatment approach for patients with advanced nonsmall cell lung cancer (NSCLC), but primary or secondary resistance remains a challenge for some patients. PD-1/PD-L1 combined with anti-angiogenic drugs (AAs) in NSCLC patients have potential synergistic effects, and the survival benefit may vary based on a treatment order. To investigate the efficacy of PD-1/PD-L1 combined with AAs as the treatment for patients with advanced NSCLC. Materials and Methods: We comprehensively searched EMBASE, PubMed, Web of Science, CNKI, VIP, and Wanfang databases from January 2017 to September 2022. The Cochrane risk bias tool evaluated the quality of included randomized clinical trials. Newcastle-Ottawa-Scale score was used to evaluate the quality of retrospective studies. Publication bias was evaluated by funnel plot, Begg's test, and Egger's test. Results: Seventeen articles were finally selected, involving 5182 patients. Meta-analysis results showed that PD1/PD-L1 combined with AAs therapy significantly improved progression-free survival (PFS) (hazard ratio [HR] = 0.61, 95% confidence interval [CI]: 0.50-0.75, P < 0.00001), overall survival (OS) (HR = 0.79, 95% CI: 0.71-0.88, P < 0.00001), and objective response rate (ORR) (risk ratio = 0.88, 95% CI: 0.81-0.96, P = 0.004), with the statistically significant difference. The sensitivity analysis demonstrated the robustness of the PFS, ORR, and OS. Conclusion: The combination of PD-1/PD-L1 inhibitors with AAs in treating advanced patients has exhibited notable therapeutic advantages when contrasted with monotherapy. Specifically, the administration of PD-1/PD-L1 inhibitors in conjunction with AAs, or sequential treatment involving PD-1/PD-L1 followed by AAs, has shown enhanced therapeutic efficacy in this patient population. [ABSTRACT FROM AUTHOR]

C–C chemokine receptor 5 (CCR5) plays a crucial role in the regulation of immune cell activation and migration as well as the progression of many cancers. We performed an in silico analysis using public data resources and found that the lung cancer patients with higher CCR5 expression had a notably better overall survival than those with lower CCR5 expression patients and CCR5 expression level is positive correlated with the infiltration of immune cells, such as B, CD8+ T and CD4+ T cells, in both lung adenocarcinoma and lung squamous cell cancer. In the present study, we investigated the association between the promoter polymorphism of CCR5 and nonsmall cell lung cancer (NSCLC). A case‒control study of 449 NSCLC patients and 516 controls of Chinese Han population was conducted, along with polymorphism detection using a sequencing method. A dual‐luciferase reporter assay system was used to analyse the transcriptional activity of CCR5 promoter variations. Our results showed that the frequency of rs1799987‐AA was significantly higher in the NSCLC group than in the controls in recessive model (p =.007, OR = 1.66 95% confidence interval [CI]: 1.14–2.40, adjusted by sex and age); the G allele showed a significant associated with NSCLC in dominant model (p =.003, OR = 1.64, 95%CI: 1.18–2.28, adjusted by sex and age). Compared with haplotype H1 rs2227010–rs2734648–rs1799987–rs1799988–rs1800023–rs1800024: A‐T‐G‐T‐G‐C, haplotype H5: A‐G‐G‐T‐G‐C increased the risk of NSCLC by over 10‐fold (p <.0001, OR = 16.09, 95%CI: 5.37–48.20, adjusted by sex and age) and notably depressed the transcriptional activity of the CCR5 promoter in 293T, A549, H1299 and HeLa cells. In conclusion, CCR5 promoter polymorphisms are significantly associated with NSCLC by affecting the transcriptional activity of the CCR5 promoter. [ABSTRACT FROM AUTHOR]

Background: Several deletion and insertion subtypes occur in exon 19 of the epidermal growth factor receptor (EGFR) gene, collectively called exon 19 deletions (del19), and are one of the common EGFR mutations in nonsmall cell lung cancer (NSCLC). Previous studies have shown that del19 subtypes might influence the response to tyrosine kinase inhibitors (TKIs), but their findings have been inconsistent. Therefore, this study aimed to evaluate the impact of del19 subtypes in an Asian population and provide additional evidence on this issue. Materials and Methods: NSCLC patients treated at Chang Gung Medical Hospitals between 2011 and 2018 were retrospectively reviewed. Their clinicopathological characteristics, clinical tumor response, progression-free survival (PFS), and overall survival (OS) were collected. PFS was evaluated among different del19 subtypes and EGFR-TKIs. Results: This study included 164 patients with NSCLC carrying an EGFR del19 mutation who had detailed information about their del19 subtype and were treated with frontline EGFR-TKIs (39 with afatinib and 125 with gefitinib/erlotinib). In this cohort, del19 subtypes did not influence PFS and OS based on different classifications, including start codon of deletion, the number of deleted nucleotides, or pure deletion versus mixed deletion/ insertion/substitution. In addition, afatinib generally showed better PFS than gefitinib/erlotinib, particularly and significantly for patients with the p. E746&lowbar;A750 mutation, a common 15 nucleotide deletion, or a pure deletion without insertion/substitution. Conclusion: In this study, del19 subtypes did not influence PFS and OS with EGFR-TKIs. Afatinib showed better activity than first-generation TKIs and should be preferred for patients with del19 mutations. [ABSTRACT FROM AUTHOR]

Introduction: Regulator of G protein signalling 1 (RGS1) closely regulates malignant phenotypes and tumour immunity in several cancers, while its clinical value in nonsmall cell lung cancer (NSCLC) is by far rarely reported. Consequently, this study aimed to explore the linkage of blood RGS1 with clinical features and prognosis in surgical NSCLC patients. Methods: Two‐hundred and ten surgical NSCLC patients were consecutively enrolled in this study, whose RGS1 in peripheral blood mononuclear cells was determined before treatment via reverse transcriptional‐quantitative polymerase chain reaction. Additionally, the blood RGS1 was also collected from 30 healthy controls (HCs). Results: Blood RGS1 was increased in NSCLC patients compared with HCs (P < 0.001). Elevated blood RGS1 was related to lymph node (LYN) metastasis (P = 0.001), higher tumour‐nodes‐metastasis (TNM) stage (P = 0.004), neoadjuvant chemotherapy administration (P = 0.044), shortened accumulative disease‐free survival (DFS) (P = 0.008) and overall survival (OS) (P = 0.013) in NSCLC patients. A multivariate Cox's regression analysis showed that blood RGS1 high expression could independently reflect shortened DFS (hazard ratio = 1.499, P = 0.023), whereas it could not independently predict OS (P > 0.050). Furthermore, blood RGS1 high expression was associated with shortened OS (P = 0.020) in patients with neoadjuvant therapy and with worse DFS (P = 0.028) and OS (P = 0.026) in patients with adjuvant therapy, while blood RGS1 was not linked with DFS or OS in patients without neoadjuvant or adjuvant therapy (all P > 0.050). Conclusion: Elevated blood RGS1 correlates with LYN metastasis, neoadjuvant chemotherapy administration, worse DFS and OS, which might serve as a useful prognostic biomarker for surgical NSCLC patients. [ABSTRACT FROM AUTHOR]

Circular RNA (circRNA) was an important modulator and potential molecular target of nonsmall cell lung cancer (NSCLC). CircSATB2 was reported to be upregulated in NSCLC. However, the role and mechanism of circSATB2 in NSCLC progression remain to be illustrated. The RNA and protein expression was detected by quantitative real‐time polymerase chain reaction, western blot, and immunohistochemistry assay. Cell counting kit‐8, cell colony formation, and 5‐ethynyl‐2′‐deoxyuridine assays were applied to assess cell growth. The migrated and invaded cells were examined by transwell assay. Flow cytometry was performed to measure apoptotic cells. The interaction among circSATB2, microRNA‐150‐5p (miR‐150‐5p), and tripartite motif‐containing protein 66 (TRIM66) was identified by dual‐luciferase reporter assay and RNA immunoprecipitation assay. An in vivo experiment was conducted to investigate the effect of circSATB2 on tumor growth. CircSATB2 expression was highly expressed in NSCLC tissues and cell lines. CircSATB2 and TRIM66 silencing both suppressed NSCLC cell growth, migration, and invasion whereas promoted NSCLC cell apoptosis. CircSATB2 acted as a molecular sponge for miR‐150‐5p, and miR‐150‐5p interacted with the 3′ untranslated region (3′UTR) of TRIM66. Moreover, circSATB2 knockdown‐induced effects were partly reversed by TRIM66 overexpression in NSCLC cells. Besides, cirSATB2 expression was negatively correlated with miR‐150‐5p level and positively correlated with TRIM66 level in NSCLC tumor tissues. CircSATB2 knockdown blocked xenograft tumor growth in vivo. In summary, this study verified that circSATB2 stimulated NSCLC cell malignant behaviors by miR‐150‐5p/TRIM66 pathway, providing a possible circRNA‐targeted therapy for NSCLC. Highlights: CircSATB2 silencing inhibited nonsmall cell lung cancer (NSCLC) progression.Circ_SATB2 acted as a sponge for miR‐150‐5p to regulate TRIM66 expression in NSCLC cells.CircSATB2/miR‐150‐5p/TRIM66 signal axis existed in the pathogenesis of NSCLC. [ABSTRACT FROM AUTHOR]

Background: Currently, the value of induction chemoimmunotherapy before chemoradiotherapy (CRT) in unresectable stage III non-small cell lung cancer (NSCLC) has not been explored. This study was designed to explore the efficacy and safety of induction chemoimmunotherapy in patients with unresectable stage III NSCLC. Methods: Unresectable stage III NSCLC patients who received CRT with or without induction chemoimmunotherapy between August 2014 and December 2021 were retrospectively enrolled. Progression-free survival (PFS) and overall survival (OS) were assessed from the initiation of treatment and estimated by the Kaplan-Meier method. The potential factors affecting PFS and OS were analyzed by univariate and multivariate Cox regression models. One-to-one propensity score matching (PSM) was used to further minimize confounding. Results: A total of 279 consecutive patients were enrolled, with 53 (19.0%) receiving induction chemoimmunotherapy followed by CRT (I-CRT group), and the remaining 226 (81.0%) receiving CRT alone (CRT group). After PSM, the median PFS was 24.8 months in the I-CRT group vs. 13.3 months in the CRT group (P=0.035). The median OS was not reached (NR) vs. 36.6 months ((P=0.142). The incidence of treatment-related adverse events (TRAEs) was similar in both groups, except that the incidence of hematological toxicity was higher in the I-CRT group (77.1% vs. 58.3%, P=0.049). Compared to induction chemotherapy, induction chemoimmunotherapy demonstrated a superior objective response rate (60.4% vs. 22.2%, P<0.001) and further prolonged PFS (median NR vs. 13.2 months, P=0.009) and OS (median NR vs. 25.9 months, P=0.106) without increasing the incidence of TRAEs in patients receiving concurrent chemoradiotherapy. Conclusion: Induction chemoimmunotherapy is safe and may improve outcomes of CRT in patients with unresectable stage III NSCLC. Moreover, induction chemoimmunotherapy may further improve treatment response and survival outcomes compared to induction chemotherapy before cCRT. [ABSTRACT FROM AUTHOR]

Background Neoadjuvant immunochemotherapy is currently being tested in pivotal trials for stage I to III nonsmall cell lung cancer (NSCLC). The impact of immunochemotherapy in patients with oligometastatic disease (OMD) remains undefined. This study aimed to compare the outcomes of radical treatment after the neoadjuvant course of immunochemotherapy versus chemotherapy. Methods We retrospectively analyzed patients with OMD who were treated with immunochemotherapy or chemotherapy combined with local ablation of metastases and radical primary tumor resection between 2017 and 2021. Group A included eight patients with immunochemotherapy; Group B included seven patients with chemotherapy. Descriptive statistical analysis included the characteristics of the patients, tumors, and outcomes. Results There was no difference in postoperative morbidity rates between the groups (p = 0.626). The 30-day mortality in both groups was 0%. The median overall survival for Group A was not reached, with a median follow-up time of 25 (range: 13–35) months; the median overall survival for Group B was 26 (range: 5–53) months. In Group A, all patients remained alive; in contrast, in Group B, four patients died (p = 0.026). There was no local thoracic recurrence in either group. In Group B, the recurrent disease was identified significantly more often (12.5 vs. 85.75%; p = 0.009). The rates of complete and major pathologic response were 37.5 and 0% in Group A and 42.85 and 14.25% in Group B, respectively. Conclusion Despite the small patient number and short-term results, the progression-free and overall survival in patients with OMD after local therapy for metastases and primary tumor resection following a neoadjuvant course of immunochemotherapy might be promising compared with chemotherapy. [ABSTRACT FROM AUTHOR]

Background: The eighth edition of nodal classification is defined only by the anatomical location of metastatic lymph nodes and has limited prognostic discrimination power. The authors aimed to evaluate the prognostic significance and discriminatory capability of the number of metastatic lymph nodes (nN) in resected nonsmall cell lung cancer. Materials and methods: Patients with stage IA to IIIB resected nonsmall cell lung cancer between 1 January 2009 and 31 December 2013 were analyzed as a Chinese cohort. The optimal thresholds for the nN classification were determined by the X-tile. The receiver operating characteristic curve, net reclassification improvement and standardized net benefit calculated by decision curve analysis was estimated to quantify the nN classification's performance in prognostic stratification. External validation in the surveillance, epidemiology, and end results database was performed to test the robustness of the nN classification. Results: Both cohorts showed a stepwise prognosis deterioration with increasing nN. One to three, four to six, and more than six were selected as optimal thresholds of nN classification in the Chinese cohort, which included 4432 patients, then validated in the SEER cohort (n=28 022 patients). Multivariate Cox analysis showed the nN classification was an independent predictive factor for overall survival in both cohorts (Chinese cohort and SEER cohort: N0 vs. N1-3, P< 0.001; N0 vs. N3-6, P <0.001; N0 vs. N>6, P<0.001). And prognostic discriminatory capability was improved in the nN classification compared with location-based N classification [5-year NRI score, 0.106 (95% CI: 0.049-0.132) and 5-year time-independent AUC, 0.593 (95% CI: 0.560-0.625) vs. 0.554 (95% CI: 0.520-0.588), P<0.001]. [ABSTRACT FROM AUTHOR]

Non-small Cell Lung Cancer (NCLC) is the predominant form of lung cancer, representing the primary cause of cancer-related mortality on a global scale. In recent decades, significant research has been conducted on tumor angiogenesis in treating NCLC, owing to its pivotal role in advancing cancer. Numerous anti-angiogenic pharmaceuticals, including Recombinant Endostatin (RE), have undergone extensive assessment in preclinical and clinical settings, yielding varied outcomes that frequently fall short of expectations. Nevertheless, there is a growing fascination with RE owing to its capacity to induce a circulatory normalizing window, thereby potentially enhancing the therapeutic effectiveness of the conventional treatment for NCLC. This work aimed to assess the potential benefits of RE in enhancing the effectiveness and safety of Platinumbased Radiotherapy (PRT) when administered through intravenous and pulmonary infusions for patients with stage IIIA/B-NCLC. This paper presents a comprehensive review of both experimental and clinical investigations that have examined the combined administration of REPRT as a therapeutic approach for NCLC treatment. Out of the total sample size of 14 individuals who were assessed, the treatment's combined effectiveness is 77.6%. This percentage indicates a substantial proportion of positive results about the therapeutic intervention. The disease control rate, encompassing patients who display complete or partial responses, exhibits a noteworthy rise of 89.6%. The results underscores the effectiveness of RE-PRT in successfully arresting or reversing the advancement of the NCLC [ABSTRACT FROM AUTHOR]

Abstract Introduction This meta‐analysis sought to investigate the effect of neoadjuvant chemotherapy (NACT) combined with surgery in patients with nonsmall cell lung cancer (NSCLC). Methods With time span from January 2010 to December 2022, PubMed, Web of Science and Embase, China National Knowledge Infrastructure, and WanFang databases were searched for randomized controlled trials on comparison between NACT combined with surgery and surgery alone in patients with NSCLC. Then a meta‐analysis was performed in accordance with Preferred Reporting Items for Systematic reviews and Meta‐Analyses (PRISMA) guidelines. Results A total of 1511 studies were retrieved and 12 were finally included. Meta‐analysis results showed that compared with surgery alone, a combination of NACT and surgery was associated with higher treatment response rate (odds ratio, OR = 2.459, 95% confidence interval, CI [1.785, 3.388], P

Abstract Background There is no well‐established late‐line treatment for advanced nonsquamous non‐small cell lung cancer (NSCLC). Therefore, we retrospectively determined the efficacy and safety of platinum rechallenge with paclitaxel‐carboplatin and bevacizumab in patients with nonsquamous NSCLC as a late‐line therapy in a clinical setting. Methods Thirty patients with nonsquamous NSCLC who received paclitaxel‐carboplatin with bevacizumab therapy as a late‐line treatment at Sendai Kousei Hospital (Miyagi, Japan) between December 2011 and December 2021 were enrolled into the study. The efficacy and safety of this treatment were evaluated. The patients were further categorized into responders and nonresponders, and predictive factors of treatment response were estimated. Results The median progression‐free survival (PFS) was 6.3 (range, 4.9–6.8) months, and the median overall survival (OS) was 11.8 (range, 7.2–17.2) months. There were no significant differences in PFS and OS between patients with and those without epidermal growth factor receptor mutations. In the univariate analyses of this study, responders were younger than nonresponders (p = 0.012). No fatal adverse events were reported. Conclusions With the increase in the number of treatment options in recent years, the sequence of treatments and overall therapeutic strategy are becoming increasingly important. Thus, platinum rechallenge with paclitaxel‐carboplatin and bevacizumab, a late‐line treatment for patients with nonsquamous NSCLC, may be an effective therapeutic option.

Abstract Introduction Regulator of G protein signalling 1 (RGS1) closely regulates malignant phenotypes and tumour immunity in several cancers, while its clinical value in nonsmall cell lung cancer (NSCLC) is by far rarely reported. Consequently, this study aimed to explore the linkage of blood RGS1 with clinical features and prognosis in surgical NSCLC patients. Methods Two‐hundred and ten surgical NSCLC patients were consecutively enrolled in this study, whose RGS1 in peripheral blood mononuclear cells was determined before treatment via reverse transcriptional‐quantitative polymerase chain reaction. Additionally, the blood RGS1 was also collected from 30 healthy controls (HCs). Results Blood RGS1 was increased in NSCLC patients compared with HCs (P 0.050). Furthermore, blood RGS1 high expression was associated with shortened OS (P = 0.020) in patients with neoadjuvant therapy and with worse DFS (P = 0.028) and OS (P = 0.026) in patients with adjuvant therapy, while blood RGS1 was not linked with DFS or OS in patients without neoadjuvant or adjuvant therapy (all P > 0.050). Conclusion Elevated blood RGS1 correlates with LYN metastasis, neoadjuvant chemotherapy administration, worse DFS and OS, which might serve as a useful prognostic biomarker for surgical NSCLC patients.

The phenomenon of histological transformation has been widely reported in advanced non-small cell lung cancer (NSCLC) with EGFR mutations following the failure of EGFR-TKI treatment. Recent evidence suggests that similar histological changes can also occur in advanced NSCLC without driver gene mutations after developing resistance to immunotherapy. In this review, it was found that 66.7% of cases with immunotherapy-induced histological transformation were classified as lung squamous cell carcinoma (LSCC), while histological conversion into lung adenocarcinoma (LUAD) without EGFR or ALK gene mutations has rarely been reported. There have been sporadic reports on the occurrence of mutual transformation between LUAD and LSCC. The histological conversion from NSCLC into small cell lung cancer (SCLC) appears to be significantly underestimated, likely due to the infrequency of re-biopsy following the development of immunotherapy resistance. Several studies have reported a close association between the transformation and mutations at TP53 and the RB1 splice site, as well as the loss of an FBXW7 mutation. However, the exact mechanisms underlying this conversion remain unclear. Currently, there is a lack of guidelines for the management of transformed SCLC from NSCLC following immunotherapy, with chemotherapy being the most commonly employed treatment approach. [ABSTRACT FROM AUTHOR]

Sarcomatoid lung cancer has mainly been described in case series and single institution reviews. Although often associated with a poor prognosis, the overall survival compared to other forms of nonsmall cell lung cancer (NSCLC) is unknown. We hypothesize that sarcomatoid lung cancers have worse overall survival relative to other forms of NSCLC. In this retrospective cohort study, we identified adult patients with nonmetastatic NSCLC from 2004 to 2018 in the National Cancer Database. Patients were categorized by histology as sarcomatoid, adenocarcinoma, or squamous cell carcinoma. We compared clinical and demographic characteristics between the groups. The primary outcome of overall survival was analyzed using Kaplan-Meier analysis. Multivariable Cox analysis was used to analyze factors associated with overall survival in sarcomatoid patients undergoing surgery. Among 1,259,109 patients with lung cancer, there were 5223 (0.4%) sarcomatoid cancers. Sarcomatoid patients were more likely to be male, of Hispanic ethnicity, have fewer comorbidities, and receive treatment at an academic program. Despite higher cT- and M-stages, patients with sarcomatoid cancer were more likely to undergo surgical resection in multivariate analysis (odds ratio = 1.8 [confidence interval 1.60-2.11]; P < 0.001). Among nonmetastatic patients, overall survival was lower for sarcomatoid cancer relative to other histologies in Kaplan-Meier analysis (median survival sarcomatoid 17.6 mo versus nonsarcomatoid 31.5 mo, P < 0.001). This National Cancer Database study confirms the findings of smaller studies that sarcomatoid cancer is associated with inferior overall survival compared to other NSCLCs. Given the inferior prognosis, further studies regarding optimal staging practices are appropriate. [ABSTRACT FROM AUTHOR]

Background: There is no well‐established late‐line treatment for advanced nonsquamous non‐small cell lung cancer (NSCLC). Therefore, we retrospectively determined the efficacy and safety of platinum rechallenge with paclitaxel‐carboplatin and bevacizumab in patients with nonsquamous NSCLC as a late‐line therapy in a clinical setting. Methods: Thirty patients with nonsquamous NSCLC who received paclitaxel‐carboplatin with bevacizumab therapy as a late‐line treatment at Sendai Kousei Hospital (Miyagi, Japan) between December 2011 and December 2021 were enrolled into the study. The efficacy and safety of this treatment were evaluated. The patients were further categorized into responders and nonresponders, and predictive factors of treatment response were estimated. Results: The median progression‐free survival (PFS) was 6.3 (range, 4.9–6.8) months, and the median overall survival (OS) was 11.8 (range, 7.2–17.2) months. There were no significant differences in PFS and OS between patients with and those without epidermal growth factor receptor mutations. In the univariate analyses of this study, responders were younger than nonresponders (p = 0.012). No fatal adverse events were reported. Conclusions: With the increase in the number of treatment options in recent years, the sequence of treatments and overall therapeutic strategy are becoming increasingly important. Thus, platinum rechallenge with paclitaxel‐carboplatin and bevacizumab, a late‐line treatment for patients with nonsquamous NSCLC, may be an effective therapeutic option. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant chemoimmunotherapy is an important therapeutic modality for resectable nonsmall cell lung cancer (NSCLC). The roles of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio in predicting the efficacy and prognosis of patients with resectable NSCLC receiving neoadjuvant chemoimmunotherapy remain uncertain. This study aimed to explore the association of baseline and preoperative NLR, platelet-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio with the treatment response and survival of patients with resectable NSCLC treated with neoadjuvant chemoimmunotherapy. Materials and methods: Data of patients with resectable NSCLC treated with neoadjuvant chemoimmunotherapy between May 2019 and July 2022 at our institute, were retrospectively analyzed. Peripheral blood cell counts were obtained at baseline and before surgery. Data that may affect treatment efficacy were also collected and analyzed, including age, sex, BMI, cumulative smoking exposure, pathological type, clinical stage, PD-L1 tumor proportion score, immune checkpoint inhibitors, dosage of neoadjuvant therapy, duration from final therapy to surgery, and baseline and preoperative oncological markers. The present work has been reported in compliance with REporting recommendations for tumor MARKer prognostic studies (REMARK) criteria and guidelines (Supplemental Digital Content 1, http://links.lww.com/JS9/A860). Results: A total of 116 patients were included in the study. Univariate logistic regression analysis showed that a higher baseline NLR (P =0.001) and preoperative NLR (P=0.001) were associated with a lower incidence of pathological complete response (pCR) following neoadjuvant therapy. Multivariate analysis indicated that a lower incidence of pCR was achieved in the high baseline NLR group (P= 0.014). Higher baseline NLR (P=0.021), preoperative NLR (P= 0.004) and higher preoperative CEA levels (P=0.059) were associated with shorter disease-free survival (DFS). Multivariate Cox proportional hazard regression analyses showed that shorter DFS was achieved in the high preoperative NLR group (P =0.033). Conclusion: In patients with resectable NSCLC treated with neoadjuvant chemoimmunotherapy, a higher baseline NLR was associated with a lower incidence of pCR, and a higher preoperative NLR was associated with a shorter DFS. However, a future prospective study with a large sample size and long-term follow-up is needed to verify the predictive value of NLR in these patients. [ABSTRACT FROM AUTHOR]

Background and Aims: Nonsmall cell lung cancer accounts for over 85% of lung cancer incidences worldwide, and often has a poor prognosis. Proteasome inhibitors, such as bortezomib, have previously demonstrated evidence in preclinical and clinical models in the treatment of NSCLC both alone and as part of chemotherapeutic regimens. Methods: Five databases were searched from inception to February 2023 to identify published clinical trial data and ongoing clinical trials on the use of proteasome inhibitors in treatment of NSCLC with a comprehensive search strategy. Results: This review examines the clinical evidence from 21 completed and published phase I and II trials studying the use of bortezomib monotherapy and combination therapy in the treatment of NSCLC. Bortezomib/docetaxel combination resulted in longer median time‐to‐progression (TTP), median duration of response, median duration of disease control and median progression‐free survival (PFS) than bortezomib monotherapy, with concurrent administration having greater 6‐month PFS and median overall survival (OS) than sequential administration. Bortezomib/vorinostat with chemotherapy was well tolerated and effective. Bortezomib/gemcitabine/carboplatin, bortezomib/bevacizumab/carboplatin and bortezomib/paclitaxel/carboplatin combinations showed promising results and were of further investigational value. Conclusion: Bortezomib showed some clinical promise in combination therapy but not monotherapy. It also demonstrated a manageable side effect profile. Combination regimens are of further investigation value in Phase II trials. [ABSTRACT FROM AUTHOR]

The presence of brain metastases (BM) is a negative prognostic factor for patients with advanced nonsmall cell lung cancer (NSCLC). Their incidence seems to be higher in patients with oncogene‐driven tumours, especially those with EGFR‐mutated or ALK‐rearranged tumours. Although targeted treatments demonstrate significant efficacy regarding BM, they only apply to a minority of NSCLC patients. On the other hand, systemic therapies for nononcogenic‐driven NSCLC with BM have shown limited clinical benefit. In recent years, immunotherapy alone or combined with chemotherapy has been adopted as a new standard of care in first‐line therapy. This approach seems to be beneficial to patients with BM in terms of efficacy and toxicity. Combined immune checkpoint inhibition as well as the combination of immunotherapy and radiation therapy show promising results with significant, but overall acceptable toxicity. A pragmatic approach of allowing enrolment of patients with untreated or symptomatic BM in randomised trials evaluating immune checkpoint inhibitors strategies, possibly coupled with central nervous system‐related endpoints may be needed to generate data to refine treatment for this patient population. [ABSTRACT FROM AUTHOR]

Purpose: The accuracy of dose calculation is the prerequisite for CyberKnife (CK) to implement precise stereotactic body radiotherapy (SBRT). In this study, CK-MLC treatment planning for early-stage non-small cell lung cancer (NSCLC) were compared using finite-size pencil beam (FSPB) algorithm, FSPB with lateral scaling option (FSPB_LS) and Monte Carlo (MC) algorithms, respectively. We concentrated on the enhancement of accuracy with the FSPB_LS algorithm over the conventional FSPB algorithm and the dose consistency with the MC algorithm.Methods: In this study, 54 cases of NSCLC were subdivided into central lung cancer (CLC, n=26) and ultra-central lung cancer (UCLC, n=28). For each patient, we used the FSPB algorithm to generate a treatment plan. Then the dose was recalculated using FSPB_LS and MC dose algorithms based on the plans computed using the FSPB algorithm. The resultant plans were assessed by calculating the mean value of pertinent comparative parameters, including PTV prescription isodose, conformity index (CI), homogeneity index (HI), and dose-volume statistics of organs at risk (OARs).Results: In this study, most dose parameters of PTV and OARs demonstrated a trend of MC > FSPB_LS > FSPB. The FSPB_LS algorithm aligns better with the dose parameters of the target compared to the MC algorithm, which is particularly evident in UCLC. However, the FSPB algorithm significantly underestimated the does of the target. Regarding the OARs in CLC, differences in dose parameters were observed between FSPB and FSPB_LS for V10 of the contralateral lung, as well as between FSPB and MC for mean dose (Dmean) of the contralateral lung and maximum dose (Dmax) of the aorta, exhibiting statistical differences. There were no statistically significant differences observed between FSPB_LS and MC for the OARs. However, the average dose deviation between FSPB_LS and MC algorithms for OARs ranged from 2.79% to 11.93%. No significant dose differences were observed among the three algorithms in UCLC.Conclusion: For CLC, the FSPB_LS algorithm exhibited good consistency with the MC algorithm in PTV and demonstrated a significant improvement in accuracy when compared to the traditional FSPB algorithm. However, the FSPB_LS algorithm and the MC algorithm showed a significant dose deviation in OARs of CLC. In the case of UCLC, FSPB_LS showed better consistency with the MC algorithm than observed in CLC. Notwithstanding, UCLC’s OARs were highly sensitive to radiation dose and could result in potentially serious adverse reactions. Consequently, it is advisable to use the MC algorithm for dose calculation in both CLC and UCLC, while the application of FSPB_LS algorithm should be carefully considered. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) are widely used for the treatment of various types of cancer. One of the possible immune-related adverse effects of ICI is pneumonitis, which is a life-threatening condition that can present as a variety of radiographic patterns, so it can be difficult to differentiate from infectious cases of pneumonia based on radiological findings alone. We present a rare case of miliary tuberculosis (M. tuberculosis) in a patient receiving programmed death-1 (PD-1) inhibitor therapy mimicking autoimmune pneumonitis and possible pathophysiological mechanisms of this unexpected event. We presented a 52-year-old patient with stage IV non-small-cell lung carcinoma (NSCLC) who was admitted to the hospital with radiological and clinical signs of pneumonitis caused by immunotherapy—Pembrolizumab. During hospitalization, she was clinically, laboratory, and microbiologically processed and her diagnosis of M. tuberculosis was confirmed. Initial treatment started with corticosteroids as a pneumonitis treatment, and because there was no adequate response, and the diagnosis of tuberculosis was confirmed, treatment with a four-regimen antituberculotic drug started. On a control, CT scan regression in distribution and number of changes in lungs occurred. After a while, patient died due to hepatic failure. There are not many reported cases of pulmonary tuberculosis in patients receiving immunotherapy; to our knowledge, no cases of M. tuberculosis in a patient with lung cancer were described. Since there is a different approach to the treatment of tuberculosis and pneumonitis, we presented our dilemmas and literature review in this article. A multidisciplinary approach (oncologist, radiologist, microbiologist, etc.) is essential in a case like this. [ABSTRACT FROM AUTHOR]

Abstract Background and Aims Nonsmall cell lung cancer accounts for over 85% of lung cancer incidences worldwide, and often has a poor prognosis. Proteasome inhibitors, such as bortezomib, have previously demonstrated evidence in preclinical and clinical models in the treatment of NSCLC both alone and as part of chemotherapeutic regimens. Methods Five databases were searched from inception to February 2023 to identify published clinical trial data and ongoing clinical trials on the use of proteasome inhibitors in treatment of NSCLC with a comprehensive search strategy. Results This review examines the clinical evidence from 21 completed and published phase I and II trials studying the use of bortezomib monotherapy and combination therapy in the treatment of NSCLC. Bortezomib/docetaxel combination resulted in longer median time‐to‐progression (TTP), median duration of response, median duration of disease control and median progression‐free survival (PFS) than bortezomib monotherapy, with concurrent administration having greater 6‐month PFS and median overall survival (OS) than sequential administration. Bortezomib/vorinostat with chemotherapy was well tolerated and effective. Bortezomib/gemcitabine/carboplatin, bortezomib/bevacizumab/carboplatin and bortezomib/paclitaxel/carboplatin combinations showed promising results and were of further investigational value. Conclusion Bortezomib showed some clinical promise in combination therapy but not monotherapy. It also demonstrated a manageable side effect profile. Combination regimens are of further investigation value in Phase II trials.

Malignant pleural and peritoneal effusion are common clinical manifestations in advanced malignant tumors, associated with a poor prognosis. This article presents a case of advanced lung adenocarcinoma with ROS1 rearrangement, characterized by persistent malignant pleural and peritoneal effusion. The patient received combined therapy of Crizotinib and Anlotinib, resulting in a significant reduction and even disappearance of the malignant effusion. Exploratory use of this treatment approach improved the patient's quality of life and holds potential for extending overall survival. However, given the single case report nature, the efficacy of this regimen in treating advanced ROS1-rearranged lung adenocarcinoma should be considered as a supplementary strategy, warranting further validation through multicenter clinical data. [ABSTRACT FROM AUTHOR]

Background: Nonsmall cell lung cancer (NSCLC) is the main type of lung cancer, accounting for approximately 85%. Berberine (BBR), a commonly used traditional Chinese medicine, has been reported to exhibit a potential antitumor effect in various cancers. In this research, we explored the function of BBR and its underlying mechanisms in the development of NSCLC. Methods: Cell Counting Kit‐8 (CCK‐8), 5‐ethynyl‐20‐deoxyuridine (EdU), colony formation assays, flow cytometry, and transwell invasion assay were employed to determine cell growth, the apoptotic rate, cell invasion of NSCLC cells, respectively. Western blot was applied for detecting the protein expression of c‐Myc, matrix metalloprotease 9 (MMP9), kinesin family member 20A (KIF20A), cyclin E2 (CCNE2), and phosphatidylinositol‐3‐kinase/protein kinase B (PI3K/AKT) pathway‐related proteins. Glycolysis was evaluated by detecting glucose consumption, lactate production, and adenosine triphosphate/adenosine diphosphate (ATP/ADP) ratio with the matched kits. Real‐time quantitative polymerase chain reaction (RT‐qPCR) was conducted to analyze the level of KIF20A and CCNE2. Tumor model was established to evaluate the function of BBR on tumor growth in NSCLC in vivo. In addition, immunohistochemistry assay was employed to detect the level of KIF20A, CCNE2, c‐Myc, and MMP9 in mice tissues. Results: BBR exhibited suppressive effects on the progression of NSCLC, as evidenced by inhibiting cell growth, invasion, glycolysis, and facilitating cell apoptosis in H1299 and A549 cells. KIF20A and CCNE2 were upregulated in NSCLC tissues and cells. Moreover, BBR treatment significantly decreased the expression of KIF20A and CCNE2. KIF20A or CCNE2 downregulation could repress cell proliferation, invasion, glycolysis, and induce cell apoptosis in both H1299 and A549 cells. The inhibition effects of BBR treatment on cell proliferation, invasion, glycolysis, and promotion effect on cell apoptosis were rescued by KIF20A or CCNE2 overexpression in NSCLC cells. The inactivation of PI3K/AKT pathway caused by BBR treatment in H1299 and A549 cells was restored by KIF20A or CCNE2 upregulation. In vivo experiments also demonstrated that BBR treatment could repress tumor growth by regulating KIF20A and CCNE2 and inactivating the PI3K/AKT pathway. Conclusion: BBR treatment showed the suppressive impact on the progression of NSCLC by targeting KIF20A and CCNE2, thereby inhibiting the activation of the PI3K/AKT pathway. [ABSTRACT FROM AUTHOR]

Nonsmall cell lung cancer (NSCLC) is treated by various therapies such as surgical intervention, radiotherapy, chemotherapy, molecular targeted therapy, and immunotherapy. Currently, molecular targeted therapy, including epidermal growth factor receptor (EGFR) inhibitors and Anaplastic Lymphoma Kinase (ALK) and Kirsten Rat Sarcoma viral Oncogene (KRAS) inhibitors, has received much attention and improved the prognosis of NSCLC. Nevertheless, the terminal point of molecular targeted drugs is resistance. Drug resistance has been classified into oligoprogression and extensive progression based on the tumor lesion progression after drug resistance. There is extensive research demonstrating that local therapy (surgical resection, radiotherapy, and thermal ablation) can prolong the survival of patients with drug resistance. This review is intended to determine the efficacy of image‐guided thermal ablation in patients with NSCLC with EGFR mutation. [ABSTRACT FROM AUTHOR]

Nonsmall cell lung cancer (NSCLC) accounts for approximately 80%–85% of all lung cancer patients. Gossypin, a flavonoid contained in Hibiscus vitifolius, has been reported as a potential anticancer agent. However, the effect of gossypin on NSCLC has not been elucidated. Herein, we evaluated the anticancer effects and investigated the molecular mechanisms of gossypin in NSCLC cell line, A549. We treated A549 cells with gossypin at different concentrations and performed cell viability and colony formation assays. As a result, gossypin inhibited cell proliferation. phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) is known to be involved in cancer cell growth. Additionally, p-PI3K/p-Akt reduces p21 expression, resulting in cell cycle progression. Therefore, the effects of gossypin on the expression of PI3K, Akt, and p21 were investigated via Western blot analysis. Gossypin inhibited p-PI3K/p-Akt and induced p21 expression. Also, gossypin induced the sub-G1 phase, which exhibits DNA fragmentation, indicating apoptosis. To corroborate these results, apoptosis and the expression of caspase-3 and poly ADP-ribose polymerase (PARP) were evaluated in gossypin-treated cells. Results showed that gossypin cleaved caspase-3 and PARP to induce apoptosis. Our study findings indicate a possible therapeutic effect of gossypin in NSCLC. [ABSTRACT FROM AUTHOR]

Objective: Mean lung dose (MLD) and percent of total lung (TL) volume that receive a dose greater than 20 Gy (V20) have been the most validated parameters in the prediction of radiation pneumonitis (RP). However, these parameters present mean values of TL parenchyma and predict the right and the left lung as a unique functional organ unit, not take into account the difference in function and dose density between the lungs. Furthermore, there have been very limited data evaluating ipsilateral lung dosimetric constraints in addition to TL parameters to predict RP in non-small cell lung cancer (NSCLC) patients treated with radiochemotherapy (RCT). Methods: Between 2010 and 2017, clinical-radiological findings of NSCLC patients treated with RCT were evaluated in terms of RP, retrospectively. MLD, V20, and V30 values of ipsilateral lung were assessed from dose-volume histogram and registered. The primary endpoint was to assess the relation between ipsilateral lung dose constraints and RP risk. Results: There were 75 patients. There was =Grade 2 RP in 33 cases (%44). In univariate analysis, ipsilateral MLD, ipsilateral V20, ipsilateral V30, and TL V30 were found to be significant. Ipsilateral MLD and PTV were found to be the independent risk factors for RP. Cutoff values for RP risk were determined as 18Gy, 35%, and 28% for ipsilateral MLD, ipsilateral V20, and ipsilateral V30, respectively. Predictive values for ipsilateral MLD and ipsilateral V20 were higher than TL. Conclusions: In NSCLC patients treated with RCT, MLD, V20, and V30 values of ipsilateral lung parameters might increase the predictability of RP risk in addition to TL parameters. Advances in Knowledge: Cutoff values for RP risk were determined as 18Gy, 35%, and 28% for ipsilateral MLD, ipsilateral V20, and ipsilateral V30, respectively. Predictive values for ipsilateral MLD and ipsilateral V20 were higher than TL. [ABSTRACT FROM AUTHOR]

Background/aim: Oligometastatic disease for nonsmall cell lung cancer (NSCLC) patients is generally thought to represent a better prognosis with a quieter biology, limited number of disease sites and long-term disease control. In this study, we aimed to determine the efficacy of radical treatment options for patients with oligometastatic NSCLC. Materials and methods: This retrospective trial included totally 134 patients with oligometastatic NSCLC. The presence of oncodriver mutation, tumor stages and nodal status, the number of metastases and involved metastatic site, treatment of primary tumor and oligometastasis, response rate, overall survival (OS) and progression-free survival (PFS) were evaluated. Results: Of 134 patients 66.4% were defined as adenocarcinoma, 26.1% were squamous cell carcinoma and 7.5% of patients were in other histology. Based on the treatment of primary tumor, in 36 patients (26.9%) curative surgery has undergone, in addition, 19 (14.2%) patients were received chemotherapy, 73 (54.5%) were treated with chemoradiotherapy, while immunotherapy and targeted therapy were used in 1 (0.7%) and 2 (1.4%), respectively. The preferred treatment for oligometastatic lesions were SBRT in 72.4% of patients, surgery in 10.5%, and both SBRT and surgery in 17.1% of patients. At the median follow up of 31.3 months (range: 9.5-48.5), the median PFS and OS times were 17 and 24.4 months, respectively. Moreover, OS-2 after progression was also 7.2 months. Conclusion: Based on our real-life experience, we demonstrated a significant correlation between good response to first treatment and survival in oligometastatic disease, we also understand that local ablative treatment modalities prolong and also delay both OS and PFS in oligometastatic NSCLC patients OS-2. [ABSTRACT FROM AUTHOR]

Background Standard cervical mediastinoscopy (SCM) has traditionally been considered the reference standard for grading mediastinal involvement in lung cancer. The objective of this research is to evaluate the impact of surgeon experience and patient-related restrictions on the adequacy of mediastinal lymph node (LN) sampling. Additionally, we aim to assess the effectiveness of PET/computed tomography (CT) in comparison to ECM (extended cervical mediastinoscopy), particularly in identifying metastases in the aortopulmonary window (APW) LN. Methods This prospective cohort study involved sixty individuals diagnosed with nonsmall cell lung cancer (NSCLC). The participants underwent fine needle transthoracic aspiration biopsy or bronchoscopy and subsequently had ECM performed. All participants underwent various diagnostic procedures, including thoracic CT, posteroanterior chest radiograph, pulmonary function tests, PET/CT, electrocardiography, cranial magnetic resonance imaging, and laboratory investigations. Results In terms of our outcomes, we evaluated the specificity, positive predictive value (PPV), sensitivity, negative predictive value (NPV), and accuracy of ECM. The results for ECM were as follows specificity of 100.0%, PPV of 100.0%, sensitivity of 78.3%, NPV of 88.1%, and accuracy of 91.7%. For PET/CT, the results were: a specificity of 90.5%, PPV of 75.0%, sensitivity of 57.1%, NPV of 80.9%, and accuracy of 78.3%. Conclusion The ECM procedure is highly beneficial in identifying APW LN metastasis in individuals diagnosed with nonsmall cell lung cancer. It exhibits a favorable NPV and efficiency. Moreover, it can be easily performed by a team with the necessary experience. [ABSTRACT FROM AUTHOR]

Advances in biomarker‐driven therapies for patients with nonsmall cell lung cancer (NSCLC) both provide opportunities to improve the treatment (and thus outcomes) for patients and pose new challenges for equitable care delivery. Over the last decade, the continuing development of new biomarker‐driven therapies and evolving indications for their use have intensified the importance of interdisciplinary communication and coordination for patients with or suspected to have lung cancer. Multidisciplinary teams are challenged with completing comprehensive and timely biomarker testing and navigating the constantly evolving evidence base for a complex and time‐sensitive disease. This guide provides context for the current state of comprehensive biomarker testing for NSCLC, reviews how biomarker testing integrates within the diagnostic continuum for patients, and illustrates best practices and common pitfalls that influence the success and timeliness of biomarker testing using a series of case scenarios. [ABSTRACT FROM AUTHOR]