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.

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.

UNASSIGNED: Anlotinib and apatinib, both vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs), are clinically established in the treatment of advanced non-small cell lung cancer (NSCLC) in China, with anlotinib emerging as a standard treatment strategy. This study was conducted to evaluate the efficacy and safety of apatinib and anlotinib, and to compare their differences in treating patients with advanced NSCLC.
UNASSIGNED: We retrospectively analyzed the data of patients with advanced NSCLC treated with apatinib or anlotinib at a hospital in Eastern China from January 2017 to December 2021. The primary endpoint was progression-free survival (PFS), while secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety profile.
UNASSIGNED: A total of 145 patients were included in this study. Median PFS (mPFS) was 3.53 months for the apatinib group and 5.3 months for the anlotinib group (HR = 0.59, 95% CI: 0.41-0.84; P = 0.004), and median OS (mOS) was 7.6 months versus 15.6 months (HR = 0.68, 95% CI: 0.46-1.00; P = 0.048), which all showed significant differences after adjusting for confounders (P < 0.05). Subgroup analysis revealed that the presence or absence of bone metastases significantly influenced PFS in both treatment groups. The ORR was 3.03% in the anlotinib group versus 10.13% in the apatinib group (P = 0.12), the DCR was 72.73% versus 51.90% (P = 0.21). No unanticipated adverse events (AEs) were observed. The incidence of grade 3-4 AEs was significantly higher in the apatinib group (31.65% vs 13.64%, P < 0.05).
UNASSIGNED: Anlotinib demonstrated greater efficacy and safety compared to apatinib in the treatment of advanced NSCLC, particularly in patients with bone metastases and EGFR(-).

Lung cancer is the leading cause of cancer mortality worldwide. Fortunately, the advent of precision medicine, which includes targeted therapy and immunotherapy, offers hope. However, identifying specific mutations is imperative before initiating precise medications. Traditional methods, such as real-time PCR examination of individual mutations, are time-consuming. Contemporary techniques, such as tissue- and plasma-based next-generation sequencing (NGS), allow comprehensive genome analysis concurrently. Notably, plasma-based NGS has a shorter turnaround time (TAT) and thus a shorter time-to-treatment (TTT). In this case report, we demonstrate the benefits of plasma-based NGS before pathological diagnosis in a patient with image-suspected non-small cell lung cancer (NSCLC). An 82-year-old Taiwanese woman presented with lower back pain persisting for one month and left-sided weakness for two weeks. Whole-body computed tomography (CT) revealed lesions suspicious for brain and bone metastases, along with a mass consistent with a primary tumor in the left upper lobe, indicative of advanced NSCLC with T4N3M1c staging. The patient underwent a bronchoscopic biopsy on Day 0, and the preliminary report that came out on Day 1 was suggestive of metastatic NSCLC. Blood was also collected for plasma-based NGS on Day 0. The patient was Coronavirus disease 2019-positive and was treated with molnupiravir on Day 6. On Day 7, pathology confirmed pulmonary adenocarcinoma, and the results of plasma-based NGS included EGFR L858R mutation. The patient was started on targeted therapy (afatinib) on Day 9. Unfortunately, the patient died of hypoxic respiratory failure on Day 26, a complication of underlying viral infection. Plasma-based NGS offers a rapid and efficient means of mutation detection in NSCLC, streamlining treatment initiation and potentially improving the negative emotions of patients. Its utility, particularly in regions with a high prevalence of specific mutations, such as EGFR alterations in East Asian populations, highlights its relevance in guiding personalized therapy decisions.

Introduction: One of the most important prognostic factors in non-small cell lung cancer (NSCLC), a condition with a high mortality rate, is the presence of mediastinal lymph node metastases alongside distant metastases. The aim of this study was to evaluate the prognostic value of selected parameters of N2 stage NSCLC with a special focus on lymph node ratio (LNR). Material: The study included 163 patients (61 women and 102 men) operated on due to NSCLC, postoperatively diagnosed as stage N2. The age of the patients ranged from 38 to 82 years (mean age: 62.4 years). The effects of the following factors on clinical data and survival rate were assessed: N1 stage, total number of all metastatic nodes, LNR and LNR N2 ratios, and the presence of skip, single- or multistation metastases. Results: Univariate analysis showed patient survival to be correlated with LNR and LNR N2 ratios, single/multistation metastases, and the number of nodes involved in metastasis. A multivariate model based on patient clinical data found nicotine dependence (p = 0.013), LNR > 0.26 (p = 0.004), and Charlson Comorbidity Index (CCI) value > 3 (p = 0.014) to be independent adverse prognostic factors in this group. Conclusions: LNR ratio is a significant cancer disease-derived independent prognostic factor for patients with postoperative N2 stage NSCLC. In addition, smoking and comorbidities also appear to have prognostic value.