UNASSIGNED: The Rearranged during Transfection (RET) gene represents a rare driver mutation in non-small cell lung cancer (NSCLC) occurring in only 1 %-2 % of cases, with implications in targeted carcinogenesis. Despite the significant efficacy demonstrated by immunotherapy in advanced NSCLC with wild-type driver genes, its validation in RET fusion-positive patients is yet to be established.
UNASSIGNED: This meta-analysis aims to systematically evaluate the effectiveness of immunotherapy in patients with RET fusion-positive NSCLC.
UNASSIGNED: and Methods: PubMed and Web of Science databases were systematically searched for relevant studies. Outcomes including objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were extracted for further analysis.
UNASSIGNED: Ten real-world evidence (RWE) studies involving 7145 patients were enrolled in this meta-analysis. In terms of tumor response, the pooled ORR and DCR were 24.0 % and 61.0 %, respectively. Regarding survival analysis, the pooled median PFS and median OS were 4.17 months [95 % confidence interval (CI): 3.40-5.02) and 17.22 months (95 % CI: 11.58-23.91)], respectively. Subgroup analyses showed that immunotherapies plus chemotherapy were superior to single-immunotherapy in terms of ORR, DCR, and median PFS, which were 43 % (95 % CI: 31%-55 %) vs. 17 % (95 % CI: 11%-25 %), 74 % (95 % CI: 60%-84 %) vs. 45 % (95 % CI: 31%-59 %) and 6.69 months (95 % CI: 4.91-8.93) vs. 2.96 months (95 % CI: 2.25-3.78), respectively.
UNASSIGNED: To date, RET fusions appear to be associated with poor response to immunotherapy in NSCLC patients, and immunotherapy combined with chemotherapy seems to offer greater clinical benefits than mono-immunotherapy.

UNASSIGNED: Radiotherapy (RT) can be used to reduce symptoms and maintain open airways for patients with non-small cell lung cancer when systemic treatment is not sufficient. For some patients, tumor control is not achieved due to radioresistance. Concurrent inhibition of epidermal growth factor receptors has been proposed as a strategy to overcome radioresistance but may increase toxicity. We performed a randomized trial to assess the efficacy, tolerance, and quality of life of concurrent erlotinib and palliative thoracic RT for patients with advanced non-small cell lung cancer.
UNASSIGNED: Patients were randomized 1:1 to RT alone (arm A) or in combination with erlotinib (arm B). A computed tomography (CT) scan at baseline and one at 4-12 weeks after inclusion was used to evaluate treatment response. Adverse events were registered during treatment and the subsequent 30 days. Health-related quality-of-life questionnaires were completed by the patients at baseline, weeks 2, 6, and 20.
UNASSIGNED: A total of 114 patients were included. Of the 74 patients with CT scans available for evaluation of treatment effect, there were no significant differences in tumor size reduction between the two groups: median 14.5% reduction in the control arm A and 17.0% in the erlotinib arm B (p = 0.68). Overall survival was not significantly different between the two treatment arms: 7.0 and 7.8 months in arm A and arm B, respectively (log-rank p = 0.32). There was no significant increase in adverse events in the experimental arm, other than what is expected from erlotinib treatment alone. Overall, patients reported similar quality of life in both treatment arms.
UNASSIGNED: Concurrent erlotinib and palliative thoracic RT for patients with advanced non-small cell lung cancer was well tolerated but did not improve the efficacy of the RT.
UNASSIGNED: ClinicalTrials.gov, identifier NCT02714530.

Homotypic cell-in-cell structures (hoCICs) are associated with tumor proliferation, invasion, and metastasis and is considered a promising prognostic marker in various cancers. However, the role of hoCICs in non-small cell lung cancer (NSCLC) remains unclear. Tumor tissue sections were obtained from 411 NSCLC patients. We analyzed the relationship between clinicopathological variables and the number of hoCICs. LASSO and multivariate Cox regression analysis were employed to identify prognostic factors for NSCLC. The impact of hoCICs on overall survival (OS) and disease-free survival (DFS) was assessed using the Kaplan-Meier curves and log-rank test. Prognostic models for OS and DFS were developed and validated using the C-index, time-dependent area under the curve (AUC), net reclassification improvement (NRI), integrated discrimination improvement (IDI), calibration curves and decision curve analysis (DCA). Among the cohort, 56% of patients had hoCICs while 44% did not. Notably, hoCICs were primarily found at the tumor invasion front. Male gender, smoking, squamous cell carcinoma, low differentiation, tumor size ≥ 3 cm, advanced TNM stage, lymph node metastasis, pleural invasion, vascular invasion, necrosis, P53 mutation, and high expression of Ki-67 were identified as relative risk factors for hoCICs. Furthermore, hoCICs was found to be a significant prognostic factor for both OS and DFS, with higher frequencies of hoCICs correlating with poorer outcomes. We constructed nomograms for predicting 1-, 3-, and 5-year OS and DFS based on hoCICs, and the calibration curves showed good agreement between the predicted and actual outcomes. The results of the C-index, time-dependent AUC, NRI, IDI, and DCA analyses demonstrated that incorporating hoCICs into the prognostic model significantly enhanced its predictive power and clinical applicability. HoCICs indicated independent perdictive value for OS and DFS in patients with NSCLC. Furthermore, the frequent localization of hoCICs at the tumor invasion front suggested a strong association between hoCICs and tumor invasion as well as metastasis.

OBJECTIVE: The reported impact of age on the effectiveness of emerging immunotherapies in patients with advanced non-small cell lung cancer (NSCLC) has been inconsistent in clinical trials, largely due to an underrepresentation of older individuals. This meta-analysis aimed to evaluate the efficacy of immune checkpoint inhibitor (ICI) in older patients with NSCLC.
METHODS: The literature up to April 2024 was reviewed to identify articles meeting the criteria for inclusion. Hazard ratios (HRs) for overall survival (OS) across various age groups were examined. The ratio of HR (RHR) was computed and combined for each study.
RESULTS: A preliminary search identified 118 articles, with 13 being phase II or III randomized clinical trials comparing the efficacy of nivolumab, avelumab, ipilimumab, pembrolizumab, atezolizumab, and chemotherapy with or without antiangiogenic therapy. The analysis revealed that the HR for OS was 0.75 (95 % CI: 0.70-0.80, P=0.080) in patients aged under 75 years and 0.87 (95 % CI: 0.74-1.01, P=0.913) in patients aged 75 years and older. The combined RHR for patients aged 75 years and above versus those aged under 75 years was 1.14 (95 % CI: 0.97-1.34, P=0.697). There was no significant difference in OS benefit between patients over 75 years and younger patients (P=0.105). Subgroup analyses indicated that the benefit of OS was consistent across all subgroups and age groups.
CONCLUSIONS: Our investigation found no significant differences in the efficacy of immunotherapy for patients with NSCLC aged 75 years and older compared to those under 75 years old. This suggests that the efficacy of immunotherapy against NSCLC is consistent across age groups.

UNASSIGNED: Almonertinib is an important third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) exhibiting high selectivity to EGFR-sensitizing and T790M-resistant mutations. Almonertinib resistance is a major obstacle in clinical use. Baicalein possesses antitumor properties, but its mechanism of antitumor action against almonertinib-resistant non-small cell lung cancer (NSCLC) remains unelucidated.
UNASSIGNED: CCK-8 assay was used to examine the survival rate of H1975/AR and HCC827/AR cells following treatment for 24 h with different concentrations of baicalein, almonertinib or their combination. The changes in colony formation ability, apoptosis, and intracellular reactive oxygen species (ROS) levels of the treated cells were analyzed using colony formation assay and flow cytometry. Western blotting was performed to detect the changes in protein expressions in the cells. The effects of pre-treatment with NAC on proliferation, apoptosis, and PI3K/Akt signaling pathway were observed in baicalein- and/or almonertinib-treated cells. A nude mouse model bearing subcutaneous HCC827/AR cell xenograft were treated with baicalein (20 mg/kg) or almonertinib (15 mg/kg), and the tumor volume and body mass changes was measured.
UNASSIGNED: Both baicalein and almonertinib represses the viability of HCC827/AR and H1975/AR cells in a concentration-dependent manner. Compared with baicalein or almonertinib alone, the combined application of the two drugs dramatically attenuates cell proliferation; triggers apoptosis; causes cleavage of Caspase-3, PARP, and Caspase-9; downregulates the protein expressions of p-PI3K and p-Akt; and significantly inhibits tumor growth in nude mice. Furthermore, baicalein combined with almonertinib results in massive accumulation of reactive oxygen species (ROS) and preincubation with N-acetyl-L-cysteine (ROS remover) prevents proliferation as well as inhibits apoptosis induction, with partial recovery of the decline of p-PI3K and p-Akt.
UNASSIGNED: The combination of baicalein and almonertinib can improve the antitumor activity in almonertinib-resistant NSCLC through the ROS-mediated PI3K/Akt pathway.

UNASSIGNED: The monocyte-to-lymphocyte ratio (MLR), a systemic inflammation biomarker, has been shown to predict patient outcomes in several types of cancer. This study aimed to determine the association between MLR and local control (LC) and cause-specific survival (CSS) rates in patients with non-small cell lung cancer (NSCLC) treated with stereotactic body radiation therapy (SBRT).
UNASSIGNED: The median age of the 194 included participants (144 men, 50 women) was 80 (range, 50-96) years. The median follow-up period was 19 (range, 1-108) months. The LC and CSS rates were calculated using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazard regression models were used to estimate the LC and CSS rates.
UNASSIGNED: Local recurrence was observed in 25 patients during the follow-up. Univariate Cox proportional hazards regression analysis revealed that MLR, performance status, and tumor diameter were significant factors for LC. Multivariate analysis showed MLR and tumor diameter as significant factors (p = 0.041 and 0.031, respectively). The 1- and 2-year LC rates for the lower and higher MLR groups were 97.5% and 97.5%, and 89.7% and 81.2%, respectively. During the follow-up period, 14 patients died due to NSCLC. Although MLR tended to predict CSS in univariate analysis (p = 0.086), none of the parameters was significant in predicting CSS. However, MLR as a continuous variable was a significant factor for CSS in the univariate analysis (p = 0.004).
UNASSIGNED: Our data suggest that MLR is correlated with LC and CSS rates in NSCLC patients treated with SBRT.

BACKGROUND: This retrospective study aimed to investigate treatment patterns and outcomes in patients with NSCLC harboring EGFR20ins in China. EGFR20ins mutations are associated with poor responses to EGFR-TKIs, and limited real-world data exist regarding the efficacy of various treatment modalities.
METHODS: In this retrospective, single-center study, treatment outcomes, including PFS and ORR, were evaluated for different treatment regimens based on imaging assessments. The impact of mutation heterogeneity on treatment efficacy was also explored.
RESULTS: Data from 302 patients diagnosed with NSCLC with EGFR20ins were analyzed. EGFR-TKI monotherapy demonstrated suboptimal PFS compared to platinum-based chemotherapy in the first-line setting (3.00 m vs. 6.83 m, HR = 3.674, 95%CI = 2.48-5.44, p < 0.001). Platinum plus pemetrexed plus bevacizumab combination therapy showed improved PFS and ORR compared to platinum plus pemetrexed (7.50m vs. 5.43 m, HR = 0.593, 95%CI = 0.383-0.918, p = 0.019). In later-line treatments, monotherapy with EGFR-TKIs or ICIs exhibited suboptimal efficacy. The specific EGFR20ins subtype, A763_Y764insFQEA, showed favorable responses to EGFR-TKIs in real-world settings.
CONCLUSIONS: This large-scale real-world study provides valuable insights into the treatment patterns and outcomes of NSCLC patients with EGFR20ins mutations in China. These findings contribute to the understanding of EGFR20ins treatment and provide real-world benchmark for future clinical trials and drug development.

Immune checkpoint inhibitor (ICI) therapy, which targets programmed cell death protein 1, has demonstrated enhanced survival outcomes in numerous patients with cancer. Historically, individuals with autoimmune diseases have been excluded from clinical trials involving cancer immunotherapies due to concerns about the potential worsening of their underlying autoimmune conditions. In the present case report, a patient with non-small cell lung cancer and bullous pemphigoid (BP) who underwent treatment with the ICI pembrolizumab is described. In this specific clinical case, no severe exacerbation of the underlying autoimmune disease was observed. Contrarily, the patient not only tolerated pembrolizumab well but also experienced amelioration of the BP lesions after the treatment. This case challenges the conventional exclusion criteria for ICI therapy in patients with autoimmune diseases, suggesting the potential safety and efficacy of such treatments in this specific population. However, further investigations and larger-scale studies are warranted to validate these findings and provide a more comprehensive understanding of the implications of ICI therapy in patients with autoimmune comorbidities.

Extracellular vesicles (EVs) are nanoscale lipid bilayer vesicles released during cell activation, cellular damage, or apoptosis. They carry nucleic acids, proteins, and lipids facilitating intercellular communication and activate signaling pathways in target cells. In non-small cell lung cancer (NSCLC), EVs may contribute to tumor growth and metastasis by modulating immune responses, facilitating epithelial-mesenchymal transition, and promoting angiogenesis, while potentially contributing to resistance to chemotherapy drugs. EVs in liquid biopsies serve as non-invasive biomarkers for early cancer detection and diagnosis. Due to their small size, inherent molecular transport properties, and excellent biocompatibility, EVs also act as natural drug delivery vehicles in NSCLC therapy.

BACKGROUND: Although sublobar resection (wedge resection [Wed] or segmentectomy [Seg]) has become a standard operative procedure for clinical stages IA1 and IA2 non-small cell lung cancer (NSCLC) in Japan, the impact of this procedure on the prognosis and postoperative complications in real-world clinical practice is unknown.
METHODS: This study retrospectively analyzed risk factors for a poor prognosis and postoperative complications of 470 patients with clinical stage ≤ IA2 NSCLC who underwent surgery from 2012 to 2021.
RESULTS: Among the patients with a consolidation-to-tumor ratio (CTR) higher than 0.5, the 5-year relapse-free survival (RFS) rate was significantly lower in the Wed group (72.1%) than in the Seg (85.8%) and Lob (86.8%) groups (p < 0.01), but the difference between the Seg and Lob groups was not significant. Among patients with a CTR of 0.5 or lower, the 5-year RFS rate did not differ significantly among the three groups. Multivariable analysis of RFS showed that the prognosis was significantly worse in the Wed group than in the Lob group (hazard ratio, 2.83; p < 0.01), but the difference between the Wed and Seg groups or the between Seg and Lob groups was not significant. Multivariable analysis of postoperative complications showed a significantly lower risk in the Wed group than in the Seg group (odds ratio, 0.31; p < 0.01).
CONCLUSIONS: Seg could become the standard operative procedure for clinical stages IA1 and IA2 NSCLC patients. Wed is suggested to be an option for patients with a CTR of 0.5 or lower and has the advantage of avoiding postoperative complications.