Advanced-stage Non-small Cell Lung Cancer Research Articles

The changing treatment landscape of EGFR-mutant non-small-cell lung cancer.

The discovery of the association between EGFR mutations and the efficacy of EGFR tyrosine-kinase inhibitors (TKIs) has revolutionized the treatment paradigm for patients with non-small-cell lung cancer (NSCLC). Currently, third-generation EGFR TKIs, which are often characterized by potent central nervous system penetrance, are the standard-of-care first-line treatment for advanced-stage EGFR-mutant NSCLC. Rational combinations of third-generation EGFR TKIs with anti-angiogenic drugs, chemotherapy, the EGFR-MET bispecific antibody amivantamab or local tumour ablation are being investigated as strategies to delay drug resistance and increase clinical benefit. Furthermore, EGFR TKIs are being evaluated in patients with early stage or locally advanced EGFR-mutant NSCLC, with the ambitious aim of achieving cancer cure. Despite the inevitable challenge of acquired resistance, emerging treatments such as new TKIs, antibody-drug conjugates, new immunotherapeutic approaches and targeted protein degraders have shown considerable promise in patients with progression of EGFR-mutant NSCLC on or after treatment with EGFR TKIs. In this Review, we describe the current first-line treatment options for EGFR-mutant NSCLC, provide an overview of the mechanisms of acquired resistance to third-generation EGFR TKIs and explore novel promising treatment strategies. We also highlight potential avenues for future research that are aimed at improving the survival outcomes of patients with this disease.

Gut metatranscriptomics based de novo assembly reveals microbial signatures predicting immunotherapy outcomes in non-small cell lung cancer.

Advanced-stage non-small cell lung cancer (NSCLC) poses treatment challenges, with immune checkpoint inhibitors (ICIs) as the main therapy. Emerging evidence suggests the gut microbiome significantly influences ICI efficacy. This study explores the link between the gut microbiome and ICI outcomes in NSCLC patients, using metatranscriptomic (MTR) signatures. We utilized a de novo assembly-based MTR analysis on fecal samples from 29 NSCLC patients undergoing ICI therapy, segmented according to progression-free survival (PFS) into long (> 6months) and short (≤ 6months) PFS groups. Through RNA sequencing, we employed the Trinity pipeline for assembly, MMSeqs2 for taxonomic classification, DESeq2 for differential expression (DE) analysis. We constructed Random Forest (RF), Support Vector Machine (SVM), and Extreme Gradient Boosting (XGBoost) machine learning (ML) algorithms and comprehensive microbial profiles. We detected no significant differences concerning alpha-diversity, but we revealed a biologically relevant separation between the two patient groups in beta-diversity. Actinomycetota was significantly overrepresented in patients with short PFS (vs long PFS, 36.7% vs. 5.4%, p < 0.001), as was Euryarchaeota (1.3% vs. 0.002%, p = 0.009), while Bacillota showed higher prevalence in the long PFS group (66.2% vs. 42.3%, p = 0.007), when comparing the abundance of corresponding RNA reads. Among the 120 significant DEGs identified, cluster analysis clearly separated a large set of genes more active in patients with short PFS and a smaller set of genes more active in long PFS patients. Protein Domain Families (PFAMs) were analyzed to identify pathways enriched in patient groups. Pathways related to DNA synthesis and Translesion were more enriched in short PFS patients, while metabolism-related pathways were more enriched in long PFS patients. E. coli-derived PFAMs dominated in patients with long PFS. RF, SVM and XGBoost ML models all confirmed the predictive power of our selected RNA-based microbial signature, with ROC AUCs all greater than 0.84. Multivariate Cox regression tested with clinical confounders PD-L1 expression and chemotherapy history underscored the influence of n = 6 key RNA biomarkers on PFS. According toML models specific gut microbiome MTR signatures' associate with ICI treated NSCLC outcomes. Specific gene clusters and taxa MTR gene expression might differentiate long vs shortPFS.

Changes in soluble PD-L1 levels in patients with advanced non-small cell lung cancer

Abstract Soluble programmed death-1 ligand (sPD-L1) in the serum of non-small cell lung cancer (NSCLC) patients is a crucial factor in disease prognosis and an indicator for immunotherapy response. This study aimed to evaluate changes in sPD-L1 levels in advanced NSCLC patients. Between May 2018 and October 2022, 80 patients with advanced-stage NSCLC and 30 healthy volunteers participated in a prospective study. The findings revealed a significant rise in sPD-L1 concentration in the lung cancer group compared to the normal control group (1.08 vs. 0.42, p &lt; 0.001). No apparent correlation was found between sPD-L1 concentration and membrane-bound programmed death-1 ligand (mPD-L1) expression. The optimal diagnostic threshold for sPD-L1 was set at 0.92 ng/mL, showing a sensitivity of 56.25% and specificity of 77.33%, with an area under the curve (AUC) of 0.743 (p = 0.001). Although increased sPD-L1 levels were prevalent in individuals with advanced age, prolonged disease duration, large tumor size, and finger clubbing, these associations did not reach statistical significance (p &gt; 0.05). In conclusion, sPD-L1 levels significantly increased in advanced NSCLC patients compared to controls (p &lt; 0.05), with no association observed with mPD-L1 (p = 0.304). The study suggests that sPD-L1 concentration can be a specific biomarker for guiding the diagnosis of advanced NSCLC, with a recommended cutoff value of 0.92 ng/mL, demonstrating a sensitivity of 56.25% and specificity of 77.33% (p = 0.001). Importantly, no apparent relationship was established between sPD-L1 levels and clinical or paraclinical characteristics in advanced NSCLC patients.

Neoadjuvant immune checkpoint inhibitor reduced recurrence in operable NSCLC patients with pathological complete response: a retrospective analysis

BackgroundThis study aimed to evaluate if neoadjuvant immune checkpoint inhibitor (ICI) plus chemotherapy (CT) reduced tumor recurrence after surgery than neoadjuvant CT alone in non–small cell lung cancer (NSCLC) patients with pathologic complete response (pCR).MethodsFrom January 1st 2019 to April 30th 2022, 16 NSCLC patients with pCR who received both neoadjuvant ICI and CT were designated as ICI/CT group. Another 8 patients, who received neoadjuvant CT alone, were designated as CT group. The tumor recurrence and patients’ survival status were analyzed.ResultsSquamous cell carcinoma was the predominant histology type in both groups. The CT group had higher percentage of patients who received adjuvant CT than the ICI/CT group (100% vs. 75%, p = 0.046). All patients had been followed up for at least 20 months. At 20 months after surgery, the ICI/CT group had a tumor recurrence rate of 6.25%, which was significantly lower than 37.5% recurrence rate of the CT group. One patient of the CT group died of gastrointestinal hemorrhage and severe anemia at 11 months after surgery, and no patient in the ICI/CT group died. During adjuvant therapy, the ICI/CT group had significantly lower risk of anemia (12.5% vs. 50%) than the CT group (p = 0.046).ConclusionThe study found that in NSCLC patients with pCR, neoadjuvant ICI reduced tumor recurrence rate. This indicated that like in advanced stage NSCLC, the ICI might bring similar long-term anti-tumor effect in operable NSCLC patients.

Unveiling the influence of tumor and immune signatures on immune checkpoint therapy in advanced lung cancer.

This study investigates the variability among patients with non-small cell lung cancer (NSCLC) in their responses to immune checkpoint inhibitors (ICIs). Recognizing that patients with advanced-stage NSCLC rarely qualify for surgical interventions, it becomes crucial to identify biomarkers that influence responses to ICI therapy. We conducted an analysis of single-cell transcriptomes from 33 lung cancer biopsy samples, with a particular focus on 14 core samples taken before the initiation of palliative ICI treatment. Our objective was to link tumor and immune cell profiles with patient responses to ICI. We discovered that ICI non-responders exhibited a higher presence of CD4+ regulatory T cells, resident memory T cells, and TH17 cells. This contrasts with the diverse activated CD8+ T cells found in responders. Furthermore, tumor cells in non-responders frequently showed heightened transcriptional activity in the NF-kB and STAT3 pathways, suggesting a potential inherent resistance to ICI therapy. Through the integration of immune cell profiles and tumor molecular signatures, we achieved an discriminative power (area under the curve [AUC]) exceeding 95% in identifying patient responses to ICI treatment. These results underscore the crucial importance of the interplay between tumor and immune microenvironment, including within metastatic sites, in affecting the effectiveness of ICIs in NSCLC.

Unveiling the influence of tumor and immune signatures on immune checkpoint therapy in advanced lung cancer

This study investigates the variability among patients with non-small cell lung cancer (NSCLC) in their responses to immune checkpoint inhibitors (ICIs). Recognizing that patients with advanced-stage NSCLC rarely qualify for surgical interventions, it becomes crucial to identify biomarkers that influence responses to ICI therapy. We conducted an analysis of single-cell transcriptomes from 33 lung cancer biopsy samples, with a particular focus on 14 core samples taken before the initiation of palliative ICI treatment. Our objective was to link tumor and immune cell profiles with patient responses to ICI. We discovered that ICI non-responders exhibited a higher presence of CD4+ regulatory T cells, resident memory T cells, and TH17 cells. This contrasts with the diverse activated CD8+ T cells found in responders. Furthermore, tumor cells in non-responders frequently showed heightened transcriptional activity in the NF-kB and STAT3 pathways, suggesting a potential inherent resistance to ICI therapy. Through the integration of immune cell profiles and tumor molecular signatures, we achieved an discriminative power (area under the curve [AUC]) exceeding 95% in identifying patient responses to ICI treatment. These results underscore the crucial importance of the interplay between tumor and immune microenvironment, including within metastatic sites, in affecting the effectiveness of ICIs in NSCLC.

Clinical value of comprehensive genomic profiling on clinical trial enrollment for patients with advanced solid tumors.

The use of biomarker testing to inform treatment decisions has emerged as a standard of care in multiple cancer types. However, the rates of patients with genomic testing results in hand to inform treatment decision-making remain variable. Here, we studied the impact of comprehensive genomic profiling (CGP) on clinical trial enrollment rates in patients with advanced-stage non-small cell lung, colorectal, breast, and prostate cancer using a real-world clinicogenomic database. On average, clinical trial enrollment in the therapy line immediately after CGP report receipt was 5.4%, which represents a 3.0 percentage point increase compared to therapy lines preceding CGP report receipt, supporting a meaningful association between CGP report availability and increased clinical trial enrollment.

Efficacy and Safety of MUC1 Antigen-Specific Vaccine as a Breakthrough Solution in the Treatment of Advanced Non-Small Cell Lung Cancer

Introduction: Non-Small Cell Lung Cancer (NSCLC) is the leading cause of death for cancer patients globally. Most of the patients are diagnosed in advanced stage that can only receive conventional chemotherapy with low overall survival and low progression-free survival outcomes. With the advancement of technology, researchers have discovered that antigen-specific vaccine could be utilized to fight tumor cells. MUC1 antigen-specific vaccine is a novel solution that has been proved to be specific and accurate against NSCLC. In this study, we would like to present current best evidences regarding the efficacy and safety of MUC1 antigen specific vaccine in battling NSCLC. Methods: Literature search was conducted on databases, namely PubMed, Scopus, Cochrane, Science Direct, EBSCOhost, and Google Scholar up to August 27th 2022. Our inclusion criteria include randomized controlled trials in patients with advanced stage NSCLC, given MUC1 antigen-specific vaccine as treatment, compared to placebo as control group, and measured the efficacy in terms of overall survival and progression-free survival, quality of life, and adverse events. Results and discussion: Six randomized controlled trials were included in this review. Overall, longer overall survival and progression-free survival is observed in all studies. However, significance differed from study to study. This could be attributed to different patient characteristics and chemotherapy regimens used. MUC1 antigen-specific vaccine is more effective in patients who received concurrent chemoradiotherapy, high sMUC1 and ANA level, and non-squamous tumor type. Minimum adverse events were reported and incidence is similar with the control group. No negative impact on quality of life was observed. Conclusion: MUC1 vaccine showed a promising impact on improving patients’ overall survival and progression-free survival while ensuring patient’s safety. However, further studies with larger sample size are recommended on more specific populations, for instance, patients with concurrent chemotherapy.

P2.11A.15 Gut Metatranscriptomics Predict Survival in Anti-PD Immunotherapy Treated Advanced-Stage Non-Small Cell Lung Cancer

P2.11A.15 Gut Metatranscriptomics Predict Survival in Anti-PD Immunotherapy Treated Advanced-Stage Non-Small Cell Lung Cancer

Assessment of endobronchial chemotherapy in patients with bronchogenic carcinoma

Background Malignant airway obstruction is commonly found in patients with lung cancer and is associated with significant morbidity and mortality. Relieving malignant obstruction may improve symptoms, quality of life, and life expectancy. The aim of the present work is to determine the efficacy of endobronchial intratumoral injection of 5-Fluorouracil as a chemotherapeutic agent in palliative care for patients with inoperable nonsmall-cell lung cancer (NSCLC). Patients and methods A total of 30 patients diagnosed as inoperable advanced-stage NSCLC were included into this randomized prospective controlled comparative study and divided into two groups (group A: 15 patients received the conventional sessions of systemic chemotherapy only and group B: 15 patients received the conventional sessions of systemic chemotherapy in addition to two to three sessions of local endobronchial intratumoral chemotherapy using 5-fluorouracil). Patient characteristics, histology, airways infiltrated with the tumor, performance status, treatment cycles, complications, and therapeutic outcomes were evaluated. Tumor response was analyzed based on bronchoscopic evaluation performed on completion of the final treatment session. Results There was no significant difference in the total objective response between patients who used systemic chemotherapy alone for treatment of advanced NSCLC and those who used systemic chemotherapy in addition to sessions of local chemotherapy using 5-fluorouracil that was injected intratumorally through bronchoscopy in multiple sessions. Conclusion We concluded that endobronchial intratumoral chemotherapy using 5-fluorouracil is not an effective promising treatment approach for palliative treatment of patients with advanced malignant endobronchial NSCLC.

The American Cancer Society National Lung Cancer Roundtable strategic plan: Advancing comprehensive biomarker testing in non-small cell lung cancer.

Comprehensive biomarker testing is a crucial requirement for the optimal treatment of advanced-stage non-small cell lung cancer (NSCLC), with emerging relevance in the adjuvant treatment setting. To advance its goal of ensuring optimal therapy for persons diagnosed with lung cancer, the American Cancer Society National Lung Cancer Roundtable (ACS NLCRT) held The Summit on Optimizing Lung Cancer Biomarkers in Practice in September 2020 to align its partners toward the goal of ensuring comprehensive biomarker testing for all eligible patients with NSCLC. The ACS NLCRT's Strategic Plan for Advancing Comprehensive Biomarker Testing in NSCLC, a product of the summit, comprises actions to promote comprehensive biomarker testing for all eligible patients. The approach is multifaceted, including policy-level advocacy and the development and dissemination of targeted educational materials, clinical decision tools, and guides to patients, physicians, and payers aimed at ameliorating barriers to testing experienced by each of these groups. PLAIN LANGUAGE SUMMARY: The ACS NLCRT works to improve care for patients with lung cancer. The ACS NLCRT supports comprehensive biomarker testing as essential to determine treatment options for all eligible patients with non-small cell lung cancer. Many factors lead to some patients not receiving optimal biomarker testing. The ACS NLCRT held a collaborative summit and developed a strategic plan to achieve and promote comprehensive biomarker testing for all patients. These plans include developing educational materials and physician tools and advocating for national policies in support of biomarker testing.

Diagnosis, Treatment Patterns, and Outcomes in Real-World Patients with RET Fusion-Positive Non-small Cell Lung Cancer in China.

Epidemiological studies on non-small cell lung cancer (NSCLC) have noted RET fusions as an oncogenic driver. However, real-world data on RET biomarker testing and treatment patterns in China remain limited. This study aimed to examine demographics, clinical and molecular features, and RET testing and treatment patterns and outcomes in patients with RET fusion-positive NSCLC. Utilizing real-world data from the Chinese Multi-center Lung Cancer Precision Medicine Registry, this retrospective cohort study focused on Chinese patients diagnosed with RET fusion-positive NSCLC between January 1, 2016, and November 30, 2021. The cohort was divided into early-stage and advanced-stage subgroups. Demographics, clinical and molecular profiles, treatment received, and outcomes including real-world event free survival (rwEFS), real-world progression free survival (rwPFS), and overall survival (OS) were assessed. The study included 121 patients with RET fusion-positive NSCLC, comprising 80 early-stage and 58 advanced-stage patients. High biomarker testing rates were observed at diagnosis (75% for early-stage, 78% for advanced-stage). RET testing was often conducted via tissue samples (95.9%) and next-generation sequencing (89.3%). KIF5B (57.0%) and CCDC6 (20.7%) were the most common gene fusion partners. The most frequent oncogenic mutations were TP53 (15.7%) and EGFR (6.6%). Platinum-based chemotherapy was the most common first-line treatment among advanced-stage patients. Median rwPFS was 9.22months for advanced-stage patients on first-line chemotherapy, and median OS was 30.7months for all advanced-stage patients. The 2-year rwEFS rate for early-stage patients was 86.0%, with a median OS of 91.9months. The study observed high biomarker testing rates at initial diagnosis for early- and advanced-stage RET fusion-positive NSCLC patients in China. The heterogeneous treatment pattern of advanced patients suggests the need for more precise, evidence-based treatment to guide clinical decisions. Given the existing therapeutic regimens fall short of adequately addressing treatment needs, targeted therapies are essential to improve outcomes.

GABA(A) Receptor Activation Drives GABARAP-Nix Mediated Autophagy to Radiation-Sensitize Primary and Brain-Metastatic Lung Adenocarcinoma Tumors.

In non-small cell lung cancer (NSCLC) treatment, radiotherapy responses are not durable and toxicity limits therapy. We find that AM-101, a synthetic benzodiazepine activator of GABA(A) receptor, impairs the viability and clonogenicity of both primary and brain-metastatic NSCLC cells. Employing a human-relevant ex vivo 'chip', AM-101 is as efficacious as docetaxel, a chemotherapeutic used with radiotherapy for advanced-stage NSCLC. In vivo, AM-101 potentiates radiation, including conferring a significant survival benefit to mice bearing NSCLC intracranial tumors generated using a patient-derived metastatic line. GABA(A) receptor activation stimulates a selective-autophagic response via the multimerization of GABA(A) receptor-associated protein, GABARAP, the stabilization of mitochondrial receptor Nix, and the utilization of ubiquitin-binding protein p62. A high-affinity peptide disrupting Nix binding to GABARAP inhibits AM-101 cytotoxicity. This supports a model of GABA(A) receptor activation driving a GABARAP-Nix multimerization axis that triggers autophagy. In patients receiving radiotherapy, GABA(A) receptor activation may improve tumor control while allowing radiation dose de-intensification to reduce toxicity.

A preliminary study on the diagnostic performance of the uPath PD-L1 (SP263) artificial intelligence (AI) algorithm in patients with NSCLC treated with PD-1/PD-L1 checkpoint blockade.

The uPath PD-L1 (SP263) is an AI-based platform designed to aid pathologists in identifying and quantifying PD-L1 positive tumor cells in non-small cell lung cancer (NSCLC) samples stained with the SP263 assay. In this preliminary study, we explored the diagnostic performance of the uPath PD-L1 algorithm in defining PD-L1 tumor proportion score (TPS) and predict clinical outcomes in a series of patients with advanced stage NSCLC treated with single agent PD-1/PD-L1 checkpoint blockade previously assessed with the SP263 assay in clinical practice. 44 patients treated from August 2015 to January 2019 were included, with baseline PD-L1 TPS of ≥ 50%, 1-49% and < 1% in 38.6%, 25.0% and 36.4%, respectively. The median uPath PD-L1 score was 6 with a significant correlation with the baseline PD-L1 TPS (r: 0.83, p < 0.01). However, only 27 cases (61.4%) were scored within the same clinically relevant range of expression (≥ vs < 50%). In the study population the baseline PD-L1 TPS was not significantly associated with clinical outcomes, while the uPath PD-L1 score showed a good diagnostic ability for the risk of death at the ROC curve analysis [AUC: 0.81 (95%CI: 0.66-0.91), optimal cut-off of ≥ 3.2], resulting in 19 patients (43.2%) being u-Path low and 25 patients (56.8%) being uPath high. The objective response rate in uPath high and low was 51.6% and 25.0% (p = 0.1), respectively, although the uPath was significantly associated with overall survival (OS, HR 2.45, 95%CI: 1.19-5.05) and progression free survival (PFS, HR 3.04, 95%CI: 1.51-6.14). At the inverse probability of treatment weighting analysis used to balance baseline covariates, the uPath categories confirmed to be independently associated with OS and PFS. This preliminary analysis suggests that AI-based, digital pathology tools such as uPath PD-L1 (SP263) can be used to optimize already available biomarkers for immune-oncology treatment in patients with NSCLC.

Preliminary experience of surgery after neoadjuvant immunotherapy combined with chemotherapy for stage-IIIB non-small cell lung cancer.

Previously, stage-IIIB non-small cell lung cancer (NSCLC) has been considered inoperable. In recent years, neoadjuvant immunotherapy has shown encouraging efficacy in the treatment of advanced stage NSCLC in several trials. However, the effectiveness and safety of neoadjuvant immunotherapy in treating stage-IIIB NSCLC are still unknown. Therefore, we conducted this retrospective study to examine the outcomes of surgery after neoadjuvant immunotherapy combined with chemotherapy for stage-IIIB NSCLC. Thirty patients with stage-IIIB NSCLC who were treated at the Department of Thoracic Surgery of Renji Hospital from January 2019 to September 2021 were analyzed retrospectively. Neoadjuvant immunotherapy combined with chemotherapy was administered prior to surgery. The curative effect was evaluated by imaging and pathological examinations. The objective response rate (ORR) and disease control rate (DCR) of the patients after neoadjuvant therapy evaluated by imaging studies were 70% and 86.7%, respectively. Of the 30 patients, 19 (63%) underwent surgical resection, in which all achieved a complete R0 resection. The median operative time was 168 minutes (range, 75-295 minutes), and the average intraoperative blood loss was 215.3±258.4 mL. The median postoperative hospital stay was 8 days (range, 4-59 days). The major pathological response (MPR) rate was 73.7% (14/19), and the pathological complete response rate was 47.4% (9/19); 2/30 patients (6.7%) had postoperative complications, including two who developed bronchopleural fistulas and one mortality, from a postoperative pulmonary infection. The treatment-related adverse reactions were mainly grades 1-2. Only two patients had grade 3 anemia, and no grade 4 adverse reactions were observed. Neoadjuvant immunotherapy and chemotherapy combined with surgery in patients with stage-IIIB NSCLC is safe and feasible. The patient outcomes and optimal number of neoadjuvant treatment cycles need to be explored and studied further.

‘Plasma first’ approach for detecting epidermal growth factor receptor mutation in advanced non-small cell lung carcinoma

IntroductionThe treatment approach for recently diagnosed advanced non-small cell lung cancer (NSCLC) with EGFR mutations primarily relies on confirming the tissue diagnosis as non-squamous NSCLC. This routine clinical practice of tissue diagnosis imposes several barriers and delays in turnaround time (TAT) for biomarker testing, significantly delaying the time to treatment. The objective of this study is to investigate the ‘plasma first’ approach for detection of EGFR mutation in advanced stage treatment naïve NSCLC patients.MethodsWe prospectively collected blood samples of treatment naïve patients with clinical and radiological suspicion of advanced stage NSCLC prior to obtaining tissue biopsy. Plasma cfDNA was tested for EGFR mutation using two different methods. We compared the sensitivity and TAT of liquid biopsy with tissue biopsy.ResultsIn total, we analyzed plasma cell-free DNA (cfDNA) of 236 patients suspected of having advanced NSCLC for EGFR mutations. We observed a notably shorter turnaround time (TAT) of 3 days, which was significantly quicker compared to the 12-day TAT for tissue biopsy (p < 0.05). The ddPCR method had a sensitivity of 82.8%, which was higher than 66.34% sensitivity of ARMS-PCR. The current study also highlights that there is no significant difference in the clinical outcome of the patients whether treated based on liquid biopsy only or tissue biopsy (median progression-free survival of 11.56 vs. 11.9 months; p = 0.94).ConclusionsUtilizing a ‘plasma first’ strategy, given its shorter turnaround time, strong positive concordance and comparable outcomes to tissue biopsy, emerges as a highly specific and reliable method for detecting EGFR mutations in advanced-stage NSCLC.

Impact of preoperative inflammatory indices and postoperative pneumonia on postoperative atrial fibrillation in patients with non-small cell lung cancer: a retrospective study

BackgroundThis study aimed to evaluate the impact of preoperative inflammatory indices and postoperative pneumonia (POP) on postoperative atrial fibrillation (POAF) in non–small cell lung cancer (NSCLC) patients.MethodsAll consecutive patients who underwent pulmonary resection at our hospital (January 2016-October 2019) were enrolled. Preoperative inflammatory indices, demographic data, surgical details, and postoperative conditions were analyzed. Univariate and multivariate analyses of risk factors associated with POAF were also conducted.ResultsAmong the 382 patients included in the study, 32 (8.38%) developed POAF. Compared to non-POAF patients, POAF patients had greater incidence of POP (P = 0.09). Approximately 31 patients (96.9%) developed atrial fibrillation within three days after surgery. The POAF group had a significantly greater mean age (68.94 years) than did the non-POAF group (63 years) (P = 0.002). Additionally, compared to non-POAF patients, POAF patients exhibited an increased number of resected mediastinal lymph nodes (P < 0.001) and mediastinal lymph node stations (P < 0.001).The POAF group also had a greater intraoperative blood volume (P = 0.006), longer surgical duration (P = 0.022), and greater drainage volume (P = 0.003). IA/B stage (P < 0.001) and IIIA/B stage(P < 0.001), and lobectomy resection (P = 0.008) and wedge resection (P = 0.023) were also associated with POAF. Compared to those in the non-POAF group, the POAF group had longer postoperative hospital stays (10.54 days vs. 9 days; P = 0.001) and longer drainage times (7 days vs. 5 days; P = 0.004). Multivariate analysis revealed age, POP, and stage IIIA/B as independent influencing factors of POAF in NSCLC patients.ConclusionPreoperative inflammatory indices were not significantly associated with POAF, but age, POP, and stage IIIA/B were identified as independent influencing factors. Advanced-stage NSCLC patients may have a greater susceptibility to POAF than early-stage patients, although further validation is needed. Additionally, POAF was linked to a longer postoperative hospital stay.

The association of nutritional and inflammatory biomarkers with overall survival in patients with non-small-cell lung cancer treated with immune checkpoint inhibitors.

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. 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. 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). 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.

Next-generation sequencing as a valuable tool for mutational spectrum in advanced-stage NSCLC patients.

Lung cancer remains one of the most threatening malignancies, ranking as the second most diagnosed cancer, and it continues to be the leading cause of cancer-related deaths worldwide. Challenges persist with late diagnosis and the high mutational burden characteristic of lung cancer. Our study focuses on identifying the mutational spectrum of a cohort of advanced-stage non-small cell lung cancer (NSCLC) patients using a minimally invasive method through blood collection. To analyze the mutational landscape of these patients, we employed plasma DNA for the next-generation sequencing (NGS) cancer panel Ion Torrent, which contains 50 of the most mutated genes in lung cancer. All protocols for extraction, quality and quantity control, and library preparation follow the manufacturer's rules. Bioinformatics analysis was performed to select pathogenic mutations versus non-pathogenic-benign ones. This approach is particularly valuable for patients in advanced stages (III and IV, n=10) of lung adenocarcinoma and lung squamous cell carcinoma, who lack surgical options and limited therapeutic avenues. The comprehensive sequencing analysis revealed that nine of the ten lung cancer patients carried a TP53 mutation. Also, several other mutations exist in various cases, showing heterogeneous profiling. Our findings demonstrate the potential of liquid biopsies in providing crucial genetic insights that can guide personalized treatment strategies, improving the management and outcomes for patients with advanced lung cancer.

Comparison of treatment outcome between first-line combination immunotherapy (anti-PD-L1 or anti-PD1) with or without chemotherapy and chemotherapy alone in advanced non-small cell lung cancer patients in tertiary care hospital.

Despite promising outcomes of first-line immunotherapy with or without chemotherapy in advanced non-small cell lung cancer (NSCLC), limited accessibility due to reimbursement was remain the problem in low to middle income countries. This study aimed to evaluate real-world effectiveness of immunotherapy in patients with advanced NSCLC in Northern Thailand. A retrospective, single-centered cohort, was conducted. Patients with advanced NSCLC who underwent PD-L1 testing (excluding EGFR and ALK mutations) and were treated with immunotherapy or without chemotherapy or chemotherapy alone were included. The primary end point was progression-free survival (PFS). The secondary endpoints were overall survival (OS), objective response rate (ORR), and adverse events. A total of 123 patients, of which 21 patients received immunotherapy-based regimen and 102 patients received chemotherapy alone. The median PFS was 11.9 months in immunotherapy-based group compared to 5.93 months in the chemotherapy group, with a. hazard ratio (HR) of 0.4 (95% confidence interval [CI], 0.23 to 0.68; p = 0.001). Similarly, the median OS was 26.68 months in the immunotherapy-based group and 11.21 months in the chemotherapy group, with HR of 0.42 (95% CI 0.22-0.8; p = 0.009). ORRs were significantly higher in the immunotherapy-based group, with 65% of patients showing a response compared to 32% in the chemotherapy group (p = 0.006). The result of this real-world study in patients with advanced stage NSCLC indicate that first-line immunotherapy-based regimen was associated with significantly greater PFS, OS, and ORR with a safety profile consistent with pivotal studies.