Survival trends among patients with metastatic non-small cell lung cancer before and after the approval of immunotherapy in the United States: A Surveillance, Epidemiology, and End Results database-based study.

BACKGROUND: In 2015, the US Food and Drug Administration approved nivolumab as the first immunotherapy for patients with advanced non-small cell lung cancer (NSCLC). However, population-based survival benefit studies after the introduction of immunotherapy in lung cancer are lacking. This study examined overall survival (OS) and cancer-specific survival in patients with NSCLC in the pre immunotherapy and immunotherapy eras. METHODS: This study used the Surveillance, Epidemiology, and End Results database, which spanned 17 registries from 2000 to 2020. Two cohorts were delineated: preimmunotherapy (2010-2014) and immunotherapy (2015-2020), which coincided with nivolumab's approval. RESULTS: This study included 191,802 patients, 90,807 in the preimmunotherapy era and 100,995 in the immunotherapy era. OS was significantly higher in the immunotherapy era, as shown by Kaplan-Meier curves (1-year OS, 40.1% vs. 33.5%; 3-year OS, 17.8% vs. 11.7%; 5-year OS, 10.7% vs. 6.8%; median OS, 8 vs. 7 months; p < .001 by log-rank test). Similarly, cancer-specific survival improved in the immunotherapy era (1-year survival, 44.0% vs. 36.8%; 3-year survival, 21.7% vs. 14.4%; 5-year survival, 14.3% vs. 9.0%; median OS, 10 vs. 8 months; p < .001 by log-rank test). Survival rates were significantly better in the immunotherapy era, as confirmed by multivariate analysis with a Cox proportional hazards model after adjusting for age, sex, race, income, and geographical area (adjusted hazard ratio, 0.830; 95% CI, 0.821-0.840; p < .001). CONCLUSIONS: In summary, the survival rate of patients with metastatic NSCLC has improved since the introduction of immunotherapy.

Chemotherapy related changes in cfDNA levels in squamous non-small cell lung cancer: correlation with symptom scores and radiological responses.

Aim: There is limited data on prognostic value of baseline plasma cell free DNA (cfDNA) in advanced squamous non-small cell lung cancer (sq-NSCLC). This prospective observational study aimed to assess change in plasma cfDNA levels in locally-advanced/metastatic sq-NSCLC with chemotherapy and its correlation with symptom-scores and radiological-responses. Methods: Chemotherapy-naive patients with stages-IIIB/IIIC/IV sq-NSCLC (n = 59), smokers with chronic obstructive pulmonary disease [COPD, COPD-controls (CC); n = 27] and healthy-controls (n = 25) were enrolled. Respiratory symptom burden (RSB) and total symptom burden (TSB) were calculated from mean visual-analog-scores (VAS) of dyspnoea, cough, chest pain, hemoptysis RSB, anorexia and fatigue (all six for TSB). cfDNA was isolated from peripheral blood. All patients received platinum-doublet chemotherapy. RSB/TSB/cfDNA assessment and contrast-enhanced computed tomography (CECT)-thorax scans were done at baseline and post-chemotherapy. Results: At baseline, 13/59 (22%) sq-NSCLC, 3/27 (11%) CC and none (0%) healthy-controls had detectable cfDNA. All three CC were heavy smokers with no evidence of malignancy and undetectable cfDNA levels on repeat testing. In sq-NSCLC group, majority were males (95%), current-smokers (88%), heavy-smokers (70%), had metastatic disease (59%) with median age of 65 years. Eastern Co-operative Oncology Group (ECOG) performance status (PS) was 0-1 (56%) and 2 (42%). Median RSB- and TSB-scores were 9 [interquartile range (IQR) = 5-14] and 16 (IQR = 9-23), respectively. Of the 59 patients, 54 received ≥ 1 cycle while 27 underwent post-C4 evaluation with detectable cfDNA levels in 18/27 (66.7%). No baseline characteristic correlated with cfDNA detectability. Median overall survival (OS) and progression-free survival (PFS) were 262 days and 167 days, respectively. ECOG PS ≥ 2, RSB-score > 9 and TSB-score > 16 were all associated with worse OS and PFS as was cfDNA detectability [median OS = 97 days vs. 298 days and median PFS = 97 days vs. 197 days; P = 0.025; hazard ratio (HR) = 2.17]. Conclusions: Baseline cfDNA detectability is independently associated with poor OS and PFS in patients with advanced sq-NSCLC on chemotherapy.

Management of oligometastatic and oligoprogressive epidermal growth factor receptor mutated non-small cell lung cancer patients: state of the art of a combined approach.

Recently, the development of targeted therapy approaches such as those based on tyrosine kinase inhibitor (TKI) greatly improved the clinical outcomes of patients affected by oncogene addicted advanced non-small cell lung cancer (NSCLC). Similarly, the improvement of radiation therapy techniques has permitted to deliver high radiation doses to a limited number of metastatic target lesions (oligopersistent or oligoprogressive), with limited high-dose normal tissue exposure that leads to low severe toxicity rates. The aim of this narrative review was to provide an overview of the currently established definition of oligometastatic and oligoprogressive disease, to define first line and subsequent lines targeted therapies and the role of consolidative non-invasive local ablative treatments (LATs) in these settings. The potential benefit of local treatment (LT) such as radiotherapy (RT) or surgery might be represented by an overall reduction of switching to subsequent systemic treatments lowering the risk of further systemic dissemination. Further randomized clinical trials will clarify the role of LT and their correct timing in relation to systemic targeted therapies.

Immunotherapeutic hydrogel for co-delivery of STAT3 siRNA liposomes and lidocaine hydrochloride for postoperative comprehensive management of NSCLC in a single application.

Despite standard treatment for non-small cell lung cancer (NSCLC) being surgical resection, cancer recurrence and complications, such as induction of malignant pleural effusion (MPE) and significant postoperative pain, usually result in treatment failure. In this study, an alginate-based hybrid hydrogel (SOG) is developed that can be injected into the resection surface of the lungs during surgery. Briefly, endoplasmic reticulum-modified liposomes (MSLs) pre-loaded with the signal transducer and activator of transcription 3 (STAT3) small interfering RNA and lidocaine hydrochloride are encapsulated in SOG. Once applied, MSLs strongly downregulated STAT3 expression in the tumor microenvironment, resulting in the apoptosis of lung cancer cells and polarization of tumor-associated macrophages towards the M1-like phenotype. Meanwhile, the release of lidocaine hydrochloride (LID) was beneficial for pain relief and natural killer cell activation. Our data demonstrated MSL@LID@SOG not only efficiently inhibited tumor growth but also potently improved the quality of life, including reduced MPE volume and pain relief in orthotopic NSCLC mouse models, even with a single administration. MSL@LID@SOG shows potential for comprehensive clinical management upon tumor resection in NSCLC, and may alter the treatment paradigms for other cancers.

The survival and cost-effectiveness analysis of adjunctive Chinese medicine therapy for patients with non-small cell lung cancer: a nationwide cohort study in Taiwan.

Introduction: Cancer, particularly lung cancer, is a significant global healthcare challenge. Non-Small Cell Lung Cancer (NSCLC) constitutes 85% of cases. Patients often seek alternative therapies like Chinese medicine alongside Western treatments. This study investigates the survival outcomes and cost-effectiveness of adjunctive Chinese medicine therapy for NSCLC patients in Taiwan. Methods: We utilized the National Health Insurance Research Database in a retrospective cohort study from 2000 to 2018, focusing on NSCLC patients diagnosed between 2007 and 2013. After propensity score matching 1:5 ratio, then compared patients with and without adjunctive Chinese medicine therapy. Survival outcomes, cost-effectiveness, and sensitivity analyses were conducted. Results: The study involved 43,122 NSCLC patients with 5.76% receiving adjunctive Chinese medicine. There is no significant associated between the risk of death and adjuvant Chinese medicine therapy until 181-365 days of adjuvant treatment could reduce the risk of death (HR = 0.88, 95% CI: 0.80-0.98). Cost-effectiveness analysis showed an incremental cost-effectiveness ratio of 880,908 NT$/year. Conclusion: Adjunctive Chinese medicine therapy, particularly when administered for 181-365 days, significantly reduced the mortality risk among stage IV NSCLC patients. The cost-effectiveness aligns with willingness-to-pay thresholds, indicating economic benefit.

Centipeda minima and 6-O-angeloylplenolin enhance the efficacy of immune checkpoint inhibitors in non-small cell lung cancer.

BACKGROUND: Chemotherapeutic agents including cisplatin, gemcitabine, and pemetrexed, significantly enhance the efficacy of immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC) by increasing PD-L1 expression and potentiating T cell cytotoxicity. However, the low response rate and adverse effects limit the application of chemotherapy/ICI combinations in patients. METHODS: We screened for medicinal herbs that could perturb PD-L1 expression and enhance T cell cytotoxicity in the presence of anti-PD-L1 antibody, and investigated the underlying mechanisms. RESULTS: We found that the aqueous extracts of Centipeda minima (CM) significantly enhanced the cancer cell-killing activity and granzyme B expression level of CD8+ T cells, in the presence of anti-PD-L1 antibody. Both CM and its active component 6-O-angeloylplenolin (6-OAP) upregulated PD-L1 expression by suppressing GSK-3ß-ß-TRCP-mediated ubiquitination and degradation. CM and 6-OAP significantly enhanced ICI-induced reduction of tumor burden and prolongation of overall survival of mice bearing NSCLC cells, accompanied by upregulation of PD-L1 and increase of CD8+ T cell infiltration. CM also exhibited anti-NSCLC activity in cells and in a patient-derived xenograft mouse model. CONCLUSIONS: These data demonstrated that the induced expression of PD-L1 and enhancement of CD8+ T cell cytotoxicity underlay the beneficial effects of 6-OAP-rich CM in NSCLCs, providing a clinically available and safe medicinal herb for combined use with ICIs to treat this deadly disease.

Quality of lymph node dissection and early recurrence in robotic versus thoracoscopic lobectomy for stage N1-2 non-small cell lung cancer: Eleven-year real-world data from a high-volume center.

BACKGROUND: The efficacy of lymph node dissection (LND) and oncological outcomes of robot-assisted (RL) versus video-assisted thoracoscopic lobectomy (VL) for non-small cell lung cancer (NSCLC) with nodal involvement remains controversial. This study aims to compare LND quality and early recurrence (ER) rate between RL and VL for stage N1-2 NSCLC patients based on eleven-year real-world data from a high-volume center. METHODS: Pathologic stage IIB-IIIB (T1-3N1-2) NSCLC patients undergoing RL or VL in Shanghai Chest Hospital from 2010 to 2021 were retrospectively reviewed from a prospectively maintained database. Propensity-score matching (PSM, 1:4 RL versus VL) was performed to mitigate baseline differences. LND quality was evaluated by adequate (≥16) LND and nodal upstaging rates. ER was defined as recurrence occurring within 24 months post-surgery. RESULTS: Out of 1578 cases reviewed, PSM yielded 200 RL and 800 VL cases. Without compromising perioperative outcomes, RL assessed more N1 and N2 LNs and N1 stations, and led to higher incidences of adequate LND (58.5 % vs. 42.0 %, p < 0.001) and nodal upstaging (p = 0.026), compared to VL. Notably, RL improved perioperative outcomes for patients undergoing adequate LND than VL. Finally, RL notably reduced ER rate (22.0 % vs. 29.6 %, p = 0.032), especially LN ER rate (15.0 % vs. 21.5 %, p = 0.041), and prolonged disease-free survival (DFS; hazard ratio = 0.837, p = 0.040) compared with VL. Further subgroup analysis of ER and DFS within the cN1-2-stage cohort verified this survival benefit. CONCLUSIONS: RL surpasses VL in enhancing LND quality, reducing ER rates, and improving perioperative outcomes when adequate LND is performed for stage N1-2 NSCLC patients.

Feasibility and Comparative Prognosis of Segmentectomy vs. Lobectomy in Centrally Located Small and Solid Dominant cN0 Non-Small Cell Lung Cancer.

OBJECTIVES: This study aimed to determine the feasibility of segmentectomy in patients with central, whole tumor size ≤2 cm and radiologically solid-dominant cN0 non-small cell lung cancer (NSCLC). METHODS: We retrospectively reviewed 1240 patients who underwent lobectomy or segmentectomy for small and radiologically solid-dominant cN0 NSCLC between January 2010 and December 2022. The inclusion criteria encompassed centrally located tumors defined as tumors located in the inner two-thirds of the pulmonary parenchyma. Propensity score matching was applied to balance the baseline characteristics. RESULTS: Among the 299 eligible patients, no significant differences in recurrence-free survival (RFS) and overall survival (OS) were observed between the segmentectomy (n = 121) and lobectomy (n = 178) groups (P = .794 and .577, respectively). After propensity score matching, no significant differences in hilar and mediastinal lymph node upstaging were found among the 93 matched patients (P = 1.00) and locoregional recurrence was comparable between those who underwent segmentectomy (n = 4) and lobectomy (n = 4). RFS and OS did not significantly differ between the two groups (P = .700 and .870, respectively). Propensity score-adjusted multivariable Cox analysis for RFS and OS indicated that segmentectomy was not an independent prognostic factor (RFS: hazard ratio, 0.89; 95% confidence interval, 0.43-1.85; P = .755; OS: hazard ratio, 1.09; 95% confidence interval, 0.38-3.14; P = .860). CONCLUSIONS: Segmentectomy may be a viable treatment option with local control and prognosis comparable to that of lobectomy in appropriately selected patients with central, small (≤2 cm), and radiologically solid-dominant NSCLC.

Is the burden of metastatic lymph node stations a prognostic factor in patients with resected lung cancer?

OBJECTIVES: The burden of metastatic lymph node (LN) stations might reflect a distinct N subcategory with a more aggressive biology and behaviour than the traditional N classification. METHODS: Between 2008 and 2018, we analyzed 1236 patients with pN1/2 lung cancer. Survival was analyzed based on LN station metastasis, determining the optimal threshold for the number of metastatic LN stations that provided additional prognostic information. N prognostic subgrouping was performed using thresholds for the number of metastatic LN stations with the maximum chi-square log-rank value, and validated at each pT-stage. RESULTS: Survival showed stepwise statistical deterioration with an increase in the number of metastatic LN stations., Threshold values for the number of metastatic LN stations were determined and N prognostic subgroupswas created as sN-alpha; one LN station metastases (n = 632), sN-beta; two-three LN stations metastases (n = 505), and sN-gamma; ≥4 LN stations metastasis (n = 99). The 5-year survival rate was 57.7% for sN-alpha, 39.2% for sN-beta, and 12.7% for sN-gamma (chi-square log rank = 97.906, p < 0.001). A clear tendency of survival deterioration was observed from sN-alpha to sN-gamma in the same pT stage, except for pT4 stage. Multivariate analysis showed that age (p < 0.001), sex (p = 0.002), tumour histology (p < 0.001), IASLC-proposed N subclassification (p < 0.001), and sN prognostic subgroups (p < 0.001) were independent risk factors for survival. CONCLUSION: The burden of metastatic LN stations is an independent prognostic factor for survival in patients with lung cancer. It could provide additional prognostic information to the N classification.

EGFR-mutated lung adenocarcinoma with choroidal oligometastasis during treatment with gefitinib: a case report.

The patient was a 74-year-old woman who was diagnosed with lung adenocarcinoma, clinical Stage IIIA. Induction chemoradiation was performed followed by right upper lobectomy and lymph node dissection. Because of positive pleural effusion cytology, which was proven after surgery, the patient was diagnosed with pathological Stage IVA with EGFR L858R mutation. At 17 months after the administration of gefitinib, left choroidal metastasis appeared. Stereotactic irradiation and ruthenium small-beam radiation were effective; however, the metastatic lesion showed regrowth 7 months after these treatments. Because the patient's choroidal oligometastasis was resistant to conservative therapy, left ophthalmectomy was performed. EGFR mutations (L858R and E709K) were detected in the resected choroidal tumor. The patient continued to take gefitinib. However, a neoplastic lesion developed on the optic nerve adjacent to the resected posterior eye segment. The lesion was treated with stereotactic radiation, gefitinib was switched to afatinib 30 mg, and the patient remains alive and disease free for 11 months.

Risk factors and prognostic analysis of right ventricular dysfunction after lung resection for NSCLC.

Objectives: Lung cancer is the leading cause of cancer death, and 80-85% of all lung cancer cases are non-small cell lung cancer (NSCLC). Surgical resection is the standard treatment for early-stage NSCLC. However, lung resection, a surgical procedure, can result in complications and increased mortality. Recent studies have shown a significant correlation between complications after lung resection and right ventricular dysfunction. Methods: Transthoracic echocardiography-derived right ventricular-pulmonary artery coupling (RV-PAC) was utilized to assess right ventricular function in these patients. Multivariate logistic regression analysis was also conducted to assess risk factors independently associated with RV-PA uncoupling. The 3- and 5-year cumulative survival rates were estimated with Kaplan-Meier curves, and differences between groups were analyzed using the Mantel-Cox log-rank test. Results: RV-PA uncoupling was defined as a TAPSE/PASP value < 0.67 mm/mm Hg according to spline analysis. The results of multivariable logistic regression analysis indicated that diabetes is an independent risk factor for right ventricular dysfunction after lung resection in patients with NSCLC. Kaplan-Meier analysis revealed a significant decrease in the survival rate of patients with RV-PA uncoupling at both the 3-year follow-up (73% vs 40%, p < 0.001) and 5-year follow-up (64% vs 37%, p < 0.001). Conclusions: After lung resection for NSCLC, the patient's right ventricular function predicts prognosis. Patients with right ventricular dysfunction, particularly those with diabetes mellitus, have a worse prognosis. It is crucial to actively prevent and correct risk factors to reduce the mortality rate in these patients.

A case of complete pathological response after comprehensive treatment in a patient with pulmonary adenocarcinoma with synchronous solitary brain metastasis.

Systemic chemotherapy is the standard treatment for non-small cell lung cancer with distant metastases. However, additional local treatment for brain and thoracic lesions is recommended for patients with synchronous solitary brain metastases (SSBM). We report the case of a 71-year-old male diagnosed with pulmonary adenocarcinoma and SSBM. Pathological examination of the brain metastasis showed positive immunostaining for programmed cell death ligand 1 expression. After four cycles of chemotherapy with immune checkpoint inhibitors, right upper lobectomy with ND2a-1 was performed. Pathological examination revealed complete pathological response, and this patient is expected to experience long-term survival.

Circulating tumor DNA to guide diagnosis and treatment of localized and locally advanced non-small cell lung cancer.

Liquid biopsy is a minimally invasive method for biomarkers detection in body fluids, particularly in blood, which offers an elevated and growing number of clinical applications in oncology. As a result of the improvement in the techniques for DNA analysis, above all next-generation sequencing (NGS) assays, circulating tumor DNA (ctDNA) has become the most informing tumor-derived material for most types of cancer, including non-small cell lung cancer (NSCLC). Although ctDNA concentration is higher in patients with advanced tumors, it can be detected even in patients with early-stage disease. Therefore, numerous clinical applications of ctDNA in the management of early-stage lung cancer are emerging, such as lung cancer screening, the identification of minimal residual disease (MRD), and the prediction of relapse before radiologic progression. Moreover, a high number of clinical trials are ongoing to better define the impact of ctDNA evaluation in this setting. Aim of this review is to offer a comprehensive overview of the most relevant implementations in using ctDNA for the management of early-stage lung cancer, addressing available data, technical aspects, limitations, and future perspectives.

Modulating the gut microbiome in non-small cell lung cancer: Challenges and opportunities.

Despite the efficacy of immunotherapy in non-small cell lung cancer (NSCLC), the majority of the patients experience relapse with limited subsequent treatment options. Preclinical studies of various epithelial tumors, such as melanoma and NSCLC, have shown that harnessing the gut microbiome resulted in improvement of therapeutic responses to immunotherapy. Is this review, we summarize the role of microbiome, including lung and gut microbiome in the context of NSCLC, provide overview of the mechanisms of microbiome in efficacy and toxicity of chemotherapies and immunotherapies, and address current ongoing clinical trials for NSCLC including fecal microbiota transplantation (FMT) and live biotherapeutic products (LBPs).

A meta-analysis of liquid biopsy versus tumor histology for detecting EGFR mutations in non-small cell lung cancer.

OBJECTIVE: To assess the consistency of liquid biopsy and histologic analysis for detecting epidermal growth factor receptor (EGFR) gene mutations in patients with advanced non-small cell lung cancer (NSCLC). METHODS: The PubMed, Cochrane Library, and CNKI et al. databases were searched to collect studies comparing liquid biopsy and histopathologic specimens. The EGFR mutation status was extracted from the studies, and meta-analysis was carried out using Stata 12.0 software. RESULTS: We included 22 studies of 3359 NSCLC patients. In the meta-analysis, eight papers with a sample size of size <150 had an OR of 45, indicating that liquid biopsy had high sensitivity for detecting EGFR mutations. In addition, seven papers with a sample size ≥150, with an OR of 70, reported that liquid biopsy was highly susceptible to detecting EGFR mutations. The pooled diagnostic effect size of 6 for literature that included the T790M mutation was smaller than that of 69 for literature that did not include the T790M mutation, and I2 >50 %, showing that literature that did not include the T790M mutation was more heterogeneous. The combined diagnostic effect size of 34 in the exon 19 group was smaller than that in the group with no exon 19, with an I2>50 %. There was substantial heterogeneity in both the exon 19 group and the non-exon 19 group. The group with the L858R mutation had a greater diagnostic effect size of 28, lower I2, and less heterogeneity than the group without the L858R mutation. The exon 21 group had a larger pooled diagnostic effect size of 66, a smaller I2, and less heterogeneity than the group without exon 21. CONCLUSION: Liquid biopsy and histologic analysis have high concordance for detecting EGFR mutations in NSCLC. Liquid biopsy can provide an alternative technology for individualized treatment and monitoring of minimal residual disease (MRD) in advanced NSCLC patients with EGFR tyrosine kinase inhibitor-sensitive and drug resistance (T790M) mutations.

Comparison of early postoperative patient-reported outcomes after multiportal robotic-assisted thoracoscopic surgery and uniportal video-assisted thoracoscopic surgery for non-small cell lung cancer.

INTRODUCTION: We aimed to compare early postoperative patient-reported outcomes between multiportal robotic-assisted thoracoscopic surgery (M-RATS) and uniportal video-assisted thoracoscopic surgery (U-VATS) for non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: Symptom severity and functional status were measured using the Perioperative Symptom Assessment for Lung Surgery at pre-surgery, during postoperative hospitalisation, and within 4 weeks of discharge. A propensity score-matched (PSM) analysis of patients with NSCLC who were treated with M-RATS and U-VATS was performed. The symptom severity and daily functional status presented as proportion of moderate-to-severe scores on a 0-10-point scale, were compared using a generalised estimation equation model. RESULTS: We enrolled 762 patients with NSCLC from a prospective cohort (CN-PRO-Lung 3), including 151 and 611 who underwent M-RATS and U-VATS, respectively, before PSM analysis. After 1:1 PSM, two groups of 148 patients each were created. Pain severity (P = 0.019) and activity limitation (P = 0.001) during hospitalisation were higher in the M-RATS group. However, no significant differences existed post-discharge in pain (P = 0.383), cough (P = 0.677), shortness of breath (P = 0.526), disturbed sleep (P = 0.525), drowsiness (P = 0.304), fatigue (P = 0.153), distress (P = 0.893), walking difficulty (P = 0.242), or activity limitation (P = 0.513). M-RATS caused less intraoperative blood loss (P = 0.013), more stations of dissected lymph nodes (P = 0.001), more numbers of dissected lymph nodes (P = 0.001), and less tube drainage on the first postoperative day (P = 0.003) than U-VATS. CONCLUSION: M-RATS and U-VATS achieved comparable symptom burden and functional impairment after discharge. However, compared to U-VATS, M-RATS was associated with more severe pain and activity limitation in the short postoperative period. TRIAL REGISTRATION NUMBER: ChiCTR2000033016.

CCL2 promotes EGFR-TKIs resistance in non-small cell lung cancer via the AKT-EMT pathway.

Acquired resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs) represents a primary cause of treatment failure in non-small cell lung cancer (NSCLC) patients. Chemokine (C-C motif) ligand 2 (CCL2) is recently found to play a pivotal role in determining anti-cancer treatment response. However, the role and mechanism of CCL2 in the development of EGFR-TKIs resistance have not been fully elucidated. In the present study, we focus on the function of CCL2 in the development of acquired resistance to EGFR-TKIs in NSCLC cells. Our results show that CCL2 is aberrantly upregulated in EGFR-TKIs-resistant NSCLC cells and that CCL2 overexpression significantly diminishes sensitivity to EGFR-TKIs. Conversely, CCL2 suppression by CCL2 synthesis inhibitor, bindarit, or CCL2 knockdown can reverse this resistance. CCL2 upregulation can also lead to enhanced migration and increased expressions of epithelial-mesenchymal transition (EMT) markers in EGFR-TKI-resistant NSCLC cells, which could also be rescued by CCL2 knockdown or inhibition. Furthermore, our findings suggest that CCL2-dependent EGFR-TKIs resistance involves the AKT-EMT signaling pathway; inhibition of this pathway effectively attenuates CCL2-induced cell migration and EMT marker expression. In summary, CCL2 promotes the development of acquired EGFR-TKIs resistance and EMT while activating AKT signaling in NSCLC. These insights suggest a promising avenue for the development of CCL2-targeted therapies that prevent EGFR-TKIs resistance in NSCLC.

Efficacy of uniportal versus multiportal video-assisted thoracoscopic lobectomy for non-small cell lung cancer: A retrospective analysis.

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

The Interplay of Malignancy and Endocarditis: A Report of a Rare Case of Marantic Endocarditis in Metastatic Lung Adenocarcinoma.

Endocarditis involves inflammation of the inner layer of the heart, known as the endocardium. This condition typically presents with vegetation, with bacteria and fungi usually being the primary culprits. It is divided into two main categories based on its cause: infectious endocarditis and noninfectious endocarditis (NIE). Most cases of NIE are associated with malignancies, most of which are adenocarcinomas of the pancreas and lungs. We present the case of a 63-year-old man with recently diagnosed stage 3 non-small cell lung cancer and a previous history of thrombosis to the renal and popliteal arteries alongside an extensive cardiovascular history who presented with blurry vision secondary to multiple acute ischemic strokes, initially thought to be a consequence of septic emboli due to bacterial endocarditis; however, further workup revealed otherwise, illustrating the complex relationship between malignancy and endocarditis and its ramification.

CD161+CD127+CD8+ T cell subsets can predict the efficacy of anti-PD-1 immunotherapy in non-small cell lung cancer with diabetes mellitus.

The role of CD161+CD127+CD8+ T cells in non-small cell lung cancer (NSCLC) patients with diabetes remains unexplored. This study determined the prevalence, phenotype, and function of CD8+ T cell subsets in NSCLC with diabetes. We recruited NSCLC patients (n = 436) treated with anti-PD-1 immunotherapy as first-line treatment. The progression-free survival (PFS), overall survival (OS), T cells infiltration, and peripheral blood immunological characteristics were analyzed in NSCLC patients with or without diabetes. NSCLC patients with diabetes exhibited shorter PFS and OS (p = 0.0069 and p = 0.012, respectively) and significantly lower CD8+ T cells infiltration. Mass cytometry by time-of-flight (CyTOF) showed a higher percentage of CD161+CD127+CD8+ T cells among CD8+T cells in NSCLC with diabetes before anti-PD-1 treatment (p = 0.0071) than that in NSCLC without diabetes and this trend continued after anti-PD-1 treatment (p = 0.0393). Flow cytometry and multiple-immunofluorescence confirmed that NSCLC with diabetes had significantly higher CD161+CD127+CD8+ T cells to CD8+T cells ratios than NSCLC patients without diabetes. The RNA-sequencing analysis revealed immune-cytotoxic genes were reduced in the CD161+CD127+CD8+ T cell subset compared to CD161+CD127-CD8+ T cells in NSCLC with diabetes. CD161+CD127+CD8+ T cells exhibited more T cell-exhausted phenotypes in NSCLC with diabetes. NSCLC patients with diabetes with ≥ 6.3% CD161+CD127+CD8+ T cells to CD8+T cells ratios showed worse PFS. These findings indicate that diabetes is a risk factor for NSCLC patients who undergo anti-PD-1 immunotherapy.CD161+CD127+CD8+ T cells could be a key indicator of a poor prognosis in NSCLC with diabetes. Our findings would help in advancing anti-PD-1 therapy in NSCLC patients with diabetes.