Targeted Therapies for EGFR Exon 20 Insertion Mutation in Non-Small-Cell Lung Cancer.

Non-small-cell lung cancer (NSCLC) frequently harbors mutations in the epidermal growth factor receptor (EGFR), with exon 20 insertions comprising 1-10% of these mutations. EGFR exon 20 insertions are less responsive to conventional tyrosine kinase inhibitors (TKIs), leading to the development of targeted agents. This review explores key therapeutic agents, such as Amivantamab, Mobocertinib, Poziotinib, Zipalertinib, and Sunvozertinib, which have shown promise in treating NSCLC with EGFR exon 20 insertions. Amivantamab, a bispecific antibody-targeting EGFR and c-MET, demonstrates significant efficacy, particularly when combined with chemotherapy. Mobocertinib, a TKI, selectively targets EGFR exon 20 mutations but faces limitations in efficacy. Poziotinib, another oral TKI, shows mixed results due to mutation-specific responses. Zipalertinib and Sunvozertinib have emerged as potent TKIs with promising clinical data. Despite these advances, challenges in overcoming resistance mutations and improving central nervous system penetration remain. Future research should focus on optimizing first-line combination therapies and enhancing diagnostic strategies for comprehensive mutation profiling.

Spine Metastasis Is Associated with the Development of Brain Metastasis in Non-Small-Cell Lung Cancer Patients.

Background and Objectives: The mechanisms involved in the development of brain metastasis (BM) remain elusive. Here, we investigated whether BM is associated with spine involvement in patients with non-small-cell lung cancer (NSCLC). Materials and Methods: A consecutive 902 patients with metastatic NSCLC were included from the Inha Lung Cancer Cohort. Patients with BM at diagnosis or subsequent BM development were evaluated for both spine involvement in NSCLC and anatomic proximity of BM to the cerebrospinal fluid (CSF) space. Results: At diagnosis, BM was found in 238 patients (26.4%) and bone metastasis was found in 393 patients (43.6%). In patients with bone metastasis, spine involvement was present in 280 patients. BM subsequently developed in 82 (28.9%) of 284 patients without BM at diagnosis. The presence of spine metastasis was associated with BM at diagnosis and subsequent BM development (adjusted odd ratios and 95% confidence intervals = 2.42 and 1.74-3.37, p < 0.001; 1.94 and 1.19-3.18, p = 0.008, respectively). Most patients with spine metastasis, either with BM at diagnosis or subsequent BM, showed BM lesions located adjacent (within 5mm) to the CSF space (93.8% of BM at the diagnosis, 100% of subsequent BM). Conclusions: These findings suggest that the presence of spine involvement is a risk factor for BM development in NSCLC patients with bone metastasis.

Anti-inflammatory properties of neutral lipids, glycolipids, and phospholipids isolated from Ammodytes personatus eggs in LPS-stimulated RAW264.7 cells.

In the present study, total lipids were extracted from Ammodytes personatus eggs and separated into neutral lipids, glycolipids, and phospholipids. The anti-inflammatory activity of the neutral lipids, glycolipids, and phospholipids was investigated in macrophages, as well as the fatty acid profiles of the lipids. Palmitic acid, oleic acid, docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA) were the primary fatty acids in the three fractionated lipids. Among the lipids, the phospholipids contained the highest concentration of polyunsaturated fatty acids (PUFAs), particularly DHA and EPA (31.89 and 16.93% of the total fatty acids, respectively). The anti-inflammatory effects of the three lipids isolated from A. personatus eggs were analyzed in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. The three lipids significantly reduced nitric oxide (NO) production and the mRNA expression of immune-associated genes in a dose-dependent manner. All lipids down-regulated the protein expression of phosphorylated NF-κB-p65 and MAPK (p38, JNK, and ERK1/2) signaling pathways, suggesting that they could inhibit cell signaling pathways by activating NF-κB and MAPK. The expression of CD40 and CD86 in LPS-stimulated RAW264.7 cells was also significantly decreased by A. personatus lipids. Consequently, the neutral lipids, glycolipids, and phospholipids from A. personatus eggs could serve as anti-inflammatory agents.

Monitoring Circulating Tumor DNA in Untreated Non-Small-Cell Lung Cancer Patients.

Circulating tumor DNA (ctDNA) has been utilized to monitor the clinical course of patients of non-small-cell lung cancer (NSCLC) who receive therapies targeting druggable mutations. However, despite providing valuable information on how NSCLC would naturally progress, the clinical utility of ctDNA for clinical-course monitoring and prediction of treatment-naïve NSCLC patients without druggable mutations remain unknown. We longitudinally followed a total of 12 treatment-naïve NSCLC patients, who did not harbor EGFR and ALK mutations, by collecting clinical information, radiological data, and plasma samples. Changes in ctDNA levels and tumor burden (TB) were compared with each other. New metastasis development, volume doubling time (VDT), and overall survival (OS) were analyzed regarding ctDNA detection at diagnosis. ctDNA was detected in the plasma of seven (58.3%) patients. Changes in ctDNA levels correlated with those in TB in a substantial fraction (57.1%) of patients and was also associated with brain metastasis, tumor necrosis, or pneumonia in other patients. All patients with ctDNA detection developed new metastasis during follow-ups in the organs that had been devoid of metastasis at diagnosis. The patients without ctDNA detection did not develop new metastasis (median duration of follow-ups: 9.8 months). In addition, patients with ctDNA detection had shorter VDT (p = 0.039) and worse OS (p = 0.019) than those without ctDNA detection. The natural course of NSCLC progression can be monitored by measuring ctDNA levels. Detection of ctDNA at diagnosis can predict development of new metastasis, rapid tumor growth and poor survival of NSCLC patients.

Immunomodulatory Activities of Ammodytes personatus Egg Lipid in RAW264.7 Cells.

Ammodytes personatus, known as the Pacific sand lance, thrives in cold areas of the North Pacific. In this study, the total lipid was extracted from A. personatus eggs and the fatty acid composition was determined using gas chromatography (GC)-flame ionization detection (FID). The results showed that the extracted lipid contained high content of polyunsaturated fatty acids (PUFAs). The immunomodulatory activities of the A. personatus lipid were investigated using rodent macrophages. First, immune enhancement was analyzed, and the A. personatus lipid significantly and dose-dependently increased the NO production in RAW264.7 cells, and this lipid also regulated the transcription of immune-associated genes in RAW264.7 cells by activating the NF-κB and MAPK pathways. Additionally, flow cytometry revealed that this lipid stimulated phagocytosis. Conversely, the anti-inflammatory activity of the A. personatus lipid was also analyzed and the results showed significantly decreased NO production and gene expression in a dose-dependent manner in LPS-stimulated RAW264.7 cells. In addition, the A. personatus lipid suppressed the LPS-induced phosphorylation of proteins related to the NF-κB and MAPK pathways in LPS-stimulated RAW264.7 cells. Further, flow cytometry demonstrated the lipid-regulated anti-inflammatory activity via inhibition of CD86 expression. The results indicate that A. personatus egg lipid is a potential source of immunomodulation.

A Rare Case of Fatal Endobronchial Mucormycosis Masquerading as Endobronchial Tuberculosis.

Pulmonary mucormycosis is a relatively rare but often fatal opportunistic fungal infection that occurs mostly in immunocompromised patients. Endobronchial mucormycosis, a distinct clinical form of pulmonary mucormycosis, is very rare, and only a few cases have been reported. The most common bronchoscopic findings in patients with endobronchial mucormycosis are stenosis, erythematous mucosa and airway obstruction. Here, we present a case of fatal endobronchial mucormycosis mimicking actively caseating endobronchial tuberculosis in a young diabetic patient living in a country with an intermediate tuberculosis burden.

Feasibility of Bronchial Washing Fluid-Based Approach to Early-Stage Lung Cancer Diagnosis.

A blood-based approach such as circulating tumor DNA remains challenging in diagnosis for early-stage disease. Bronchial washing (BW) is a minimally invasive procedure that yields fluids that may contain tumor DNA. Therefore, we prospectively enrolled 12 patients with early-stage non-small cell lung cancer without endoscopically visible tumors. Somatic mutations were analyzed using ultra-deep next-generation sequencing in 48 paired specimens (primary tumor tissue, normal tissue, BW supernatant, and BW precipitate). In primary tumors, 130 missense mutations/indels (5-16 per patient) and 20 driver mutations (0-3 per patient) were found. Concordance of driver mutations between BW fluids and primary tumors was 95.0%. The allele frequencies for missense mutations/indels in BW supernatants significantly correlated with those in primary tumors and were higher than those in BW precipitates. These findings suggest that BW supernatants are reflective of tumor-associated mutations and could be used for early-stage lung cancer diagnosis.

Prognostic impact of a new score using neutrophil-to-lymphocyte ratios in the serum and malignant pleural effusion in lung cancer patients.

BACKGROUNDS: Various studies have reported that the neutrophil-to-lymphocyte ratio in the serum (sNLR) may serve as a cost-effective and useful prognostic factor in patients with various cancer types. However, no study has reported the prognostic impact of the NLR in malignant pleural effusion (MPE). To address this gap, we investigated the clinical impact of NLR as a prognostic factor in MPE (mNLR) and a new scoring system that use NLRs in the serum and MPE (smNLR score) in lung cancer patients. METHODS: We retrospectively reviewed all of the patients who were diagnosed with lung cancer and who presented with pleural effusion. To maintain the quality of the study, only patients with malignant cells in the pleural fluid or tissue were included. The patients were classified into three smNLR score groups, and clinical variables were investigated for their correlation with survival. RESULTS: In all, 158 patients were classified into three smNLR score groups as follows: 84 (53.2%) had a score of 0, 58 (36.7%) had a score of 1, and 16 (10.1%) had a score of 2. In a univariate analysis, high sNLR, mNLR, and increments of the smNLR score were associated with shorter overall survival (p < 0.001, p = 0.004, and p < 0.001, respectively); moreover, age, Eastern Cooperative Oncology Group performance status (ECOG PS), histology, M stage, hemoglobin level, albumin level, and calcium level were significant prognostic factors. A multivariable analysis confirmed that ECOG PS (p < 0.001), histology (p = 0.001), and smNLR score (p < 0.012) were independent predictors of overall survival. CONCLUSIONS: The new smNLR score is a useful and cost-effective prognostic factor in lung cancer patients with MPE. Although further studies are required to generalize our results, this information will benefit clinicians and patients in determining the most appropriate therapy for patients with MPE.

Minimal Pleural Effusion in Small Cell Lung Cancer: Proportion, Mechanisms, and Prognostic Effect.

PURPOSE: To determine the frequency and investigate possible mechanisms and prognostic relevance of minimal (<10-mm thickness) pleural effusion in patients with small cell lung cancer (SCLC). MATERIALS AND METHODS: The single-center retrospective study was approved by the institutional review board of the hospital, and informed consent was waived by the patients. A cohort of 360 consecutive patients diagnosed with SCLC by using histologic analysis was enrolled in this study. Based on the status of pleural effusion on chest computed tomographic (CT) scans at diagnosis, patients were classified into three groups: no pleural effusion, minimal pleural effusion, and malignant pleural effusion. Eighteen variables related to patient, environment, stage, and treatment were included in the final model as potential confounders. RESULTS: Minimal pleural effusion was present in 74 patients (20.6%) and malignant pleural effusion in 83 patients (23.0%). Median survival was significantly different in patients with no, minimal, or malignant pleural effusion (median survival, 11.2, 5.93, and 4.83 months, respectively; P < .001, log-rank test). In the fully adjusted final model, patients with minimal pleural effusion had a significantly increased risk of death compared with those with no pleural effusion (adjusted hazard ratio, 1.454 [95% confidence interval: 1.012, 2.090]; P = .001). The prognostic effect was significant in patients with stage I-III disease (adjusted hazard ratio, 2.751 [95% confidence interval: 1.586, 4.773]; P < .001), but it disappeared in stage IV disease. An indirect mechanism representing mediastinal lymphadenopathy was responsible for the accumulation in all but one patient with minimal pleural effusion. CONCLUSIONS: Minimal pleural effusion is a common clinical finding in staging SCLC. Its presence is associated with worse survival in patients and should be considered when CT scans are interpreted.

Deep learning-radiomics integrated noninvasive detection of epidermal growth factor receptor mutations in non-small cell lung cancer patients.

This study focused on a novel strategy that combines deep learning and radiomics to predict epidermal growth factor receptor (EGFR) mutations in patients with non-small cell lung cancer (NSCLC) using computed tomography (CT). A total of 1280 patients with NSCLC who underwent contrast-enhanced CT scans and EGFR mutation testing before treatment were selected for the final study. Regions of interest were segmented from the CT images to extract radiomics features and obtain tumor images. These tumor images were input into a convolutional neural network model to extract 512 image features, which were combined with radiographic features and clinical data to predict the EGFR mutation. The generalization performance of the model was evaluated using external institutional data. The internal and external datasets contained 324 and 130 EGFR mutants, respectively. Sex, height, weight, smoking history, and clinical stage were significantly different between the EGFR-mutant patient groups. The EGFR mutations were predicted by combining the radiomics and clinical features, and an external validation dataset yielded an area under the curve (AUC) value of 0.7038. The model utilized 1280 tumor images, radiomics features, and clinical characteristics as input data and exhibited an AUC of approximately 0.81 and 0.78 during the primary cohort and external validation, respectively. These results indicate the feasibility of integrating radiomics analysis with deep learning for predicting EGFR mutations. CT-image-based genetic testing is a simple EGFR mutation prediction method, which can improve the prognosis of NSCLC patients and help establish personalized treatment strategies.

Real-World Outcomes of Crizotinib in ROS1-Rearranged Advanced Non-Small-Cell Lung Cancer.

Real-world data on the use and outcomes of crizotinib in ROS1-rearranged non-small-cell lung cancer (NSCLC) are limited. This study aims to analyze the real-world efficacy of crizotinib in South Korea and explore the utilization of liquid biopsies that implement next-generation sequencing (NGS) using cell-free total nucleic acids. In this prospective multicenter cohort study, 40 patients with ROS1-rearranged NSCLC, either starting or already on crizotinib, were enrolled. Patients had a median age of 61 years, with 32.5% presenting brain/central nervous system (CNS) metastases at treatment initiation. At the data cutoff, 48.0% were still in treatment; four continued with it even after disease progression due to the clinical benefits. The objective response rate was 70.0%, with a median duration of response of 27.8 months. The median progression-free survival was 24.1 months, while the median overall survival was not reached. Adverse events occurred in 90.0% of patients, primarily with elevated transaminases, yet these were mostly manageable. The NGS assay detected a CD74-ROS1 fusion in 2 of the 14 patients at treatment initiation and identified emerging mutations, such as ROS1 G2032R, ROS1 D2033N, and KRAS G12D, during disease progression. These findings confirm crizotinib's sustained clinical efficacy and safety in a real-world context, which was characterized by a higher elderly population and higher rates of brain/CNS metastases. The study highlights the clinical relevance of liquid biopsy for detecting resistance mechanisms, suggesting its value in personalized treatment strategies.

Effect of whole-brain radiotherapy with platinum-based chemotherapy in non-small cell lung cancer patients with multiple metastases including brain metastases.

Current guidelines recommend that cytotoxic chemotherapy be considered first in non-small cell lung cancer (NSCLC) patients with multiple metastases, and whole-brain radiotherapy (WBRT) is not initially recommended even if brain metastases are present. However, cytotoxic chemotherapeutic agents are less effective in brain metastases due to poor blood-brain barrier permeability. We investigated the effect of WBRT in combination with cytotoxic chemotherapy on survival in NSCLC patients who were EGFR, ALK, and PD-L1 negative, had an ECOG PS of 2, and had multiple metastases including brain metastases. From January 2005 to December 2018, histologically confirmed NSCLC patients who were EGFR, ALK, and PD-L1 negative, had an ECOG PS of 2, and had multiple metastases including brain metastases were included in this study. Patients were classified into two groups based on receiving WBRT prior to or concurrently with administration of first-line chemotherapeutic agents or receiving chemotherapy only. We compared intracranial progression-free survival (iPFS) and overall survival (OS). Of the 240 NSCLC patients with brain metastases at diagnosis and an ECOG PS of 2, 67 patients were EGFR, ALK, and PD-L1 negative with multiple metastases including brain metastases. Among those patients, 43 (64.2%) received WBRT prior to or concurrently with platinum-based chemotherapy. Patients who received WBRT prior to or concurrently with chemotherapy had better iPFS (7.7 months [4.8-10.6] vs. 3.5 months [2.1-4.9], p = 0.009) and OS (10.8 months [5.9-15.7] vs. 6.1 months [1.9-10.3], p = 0.038) than those who did not receive WBRT. In multivariate analyses, WBRT was significantly associated with iPFS (HR: 1.94 and 95% CI 1.11-3.40, p = 0.020) and OS (HR: 1.92 and 95% CI 1.08-3.42, p = 0.027). In NSCLC patients who are EGFR, ALK, and PD-L1 negative, have an ECOG PS of 2, and have multiple metastases including brain metastases, WBRT prior to or concurrently with chemotherapy could improve iPFS and OS. Therefore, the combination of WBRT with cytotoxic chemotherapy should be considered in these patients.

Real-World Study of Osimertinib in Korean Patients with Epidermal Growth Factor Receptor T790M Mutation-Positive Non-Small Cell Lung Cancer.

PURPOSE: Although osimertinib is the standard-of-care treatment of epidermal growth factor receptor (EGFR) T790M mutation-positive non-small cell lung cancer, real-world evidence on the efficacy of osimertinib is not enough to reflect the complexity of the entire course of treatment. Herein, we report on the use of osimertinib in patients with EGFR T790M mutation-positive non-small cell lung cancer who had previously received EGFR tyrosine kinase inhibitor (TKI) treatment in Korea. MATERIALS AND METHODS: Patients with confirmed EGFR T790M after disease progression of prior EGFR-TKI were enrolled and administered osimertinib 80 mg daily. The primary effectiveness outcome was progression-free survival, with time-to-treatment discontinuation, treatment and adverse effects leading to treatment discontinuation, and overall survival being the secondary endpoints. RESULTS: A total of 558 individuals were enrolled, and 55.2% had investigator-assessed responses. The median progression-free survival was 14.2 months (95% confidence interval [CI], 13.0 to 16.4), and the median time-to-treatment discontinuation was 15.0 months (95% CI, 14.1 to 15.9). The median overall survival was 36.7 months (95% CI, 30.9 to not reached). The benefit with osimertinib was consistent regardless of the age, sex, smoking history, and primary EGFR mutation subtype. However, hepatic metastases at the time of diagnosis, the presence of plasma EGFR T790M, and the shorter duration of prior EGFR-TKI treatment were poor predictors of osimertinib treatment. Ten patients (1.8%), including three with pneumonitis, had to discontinue osimertinib due to severe adverse effects. CONCLUSION: Osimertinib demonstrated its clinical effectiveness and survival benefit for EGFR T790M mutation-positive in Korean patients with no new safety signals.

The effect of Epstein-Barr virus viremia on the progression to severe COVID-19.

ABSTRACT: Epstein-Barr virus (EBV) is frequently reactivated by coronavirus 2019 (COVID-19), and a high incidence of EBV viremia has been reported in patients with severe COVID-19. However, the impact of EBV viremia on progression to severe COVID-19 is unclear. Therefore, we conducted a study to evaluate the effect of EBV on COVID-19 progression.We investigated EBV viremia at the time of admission in COVID-19 patients hospitalized between February 1, 2020, and April 11, 2021. A cross-sectional study was performed to compare the severity of COVID-19 according to the presence or absence of EBV viremia. However, since it is difficult to analyze the influence of EBV viremia on COVID-19 progression with cross-sectional studies, a retrospective cohort study, limited to patients with mild COVID-19, was additionally conducted to observe progression to severe COVID-19 according to the presence or absence of EBV viremia.Two hundred sixty-nine COVID-19 patients were tested for EBV viremia. In a cross-sectional study that included patients with both mild and severe COVID-19, the EBV viremia group had more severe pneumonia than the EBV-negative group. However, in the cohort study limited to mild cases (N = 213), EBV viremia was not associated with COVID-19 progression.COVID-19 severity may affect EBV viremia; however, there was no evidence that EBV viremia was a factor in exacerbating pneumonia in patients with mild COVID-19.

Association Between Vitamin D Level and Respiratory Symptoms in Patients with Stable Chronic Obstructive Pulmonary Disease.

Purpose: Vitamin D insufficiency or deficiency is prevalent in patients with chronic obstructive pulmonary disease (COPD). However, the association between vitamin D levels and respiratory symptoms in patients with stable COPD has not been fully investigated. This study evaluated the association between vitamin D levels and respiratory symptoms in patients with stable COPD. Patients and Methods: Patients with COPD who had their serum 25-hydroxyvitamin D (25-OH vitamin D) level measured within 6 months of spirometry between January 2016 and April 2020 were retrospectively included. Respiratory symptoms were assessed using the modified Medical Research Council (mMRC) scale and COPD assessment test (CAT) score. Results: Of the 329 included patients, 193, 88, and 48 were categorized as having vitamin D deficiency (<20 ng/mL), insufficiency (20-29 ng/mL), and sufficiency (≥30 ng/mL), respectively. The mean serum 25-OH vitamin D level of each group was 13.45 ng/mL, 24.61 ng/mL, and 38.90 ng/mL, respectively. Patients with vitamin D insufficiency/deficiency showed higher CAT scores than those with vitamin D sufficiency (p = 0.004). In multivariable adjusted models, vitamin D insufficiency/deficiency was significantly associated with a CAT score of 10 or more (adjusted odds ratio [aOR] = 2.41, 95% confidence interval [CI] = 1.20-4.82, p = 0.013) and mMRC ≥ 2 (aOR = 2.39, 95% CI = 1.08-5.32, p = 0.032). Among CAT items, the amount of phlegm (p = 0.008), chest tightness (p = 0.030), breathlessness walking upstairs (p < 0.001), home activity limitations (p = 0.002), and lack of energy (p = 0.003) were significantly associated with vitamin D insufficiency/deficiency after adjustment for age, sex, body mass index, smoking history, Charlson comorbidity index, post-bronchodilator forced expiratory volume in 1 second, and season of blood draw. Conclusion: Vitamin D insufficiency/deficiency were associated with worse respiratory symptoms in patients with stable COPD.

Heterogeneous radiological response to chemotherapy is associated with poor prognosis in advanced non-small-cell lung cancer.

BACKGROUND: A heterogeneous radiological response is frequently observed in cancer patients and could reflect tumor heterogeneity. We investigated the prognostic impact of heterogeneous radiological responses in patients with advanced non-small-cell lung cancer (NSCLC) who received platinum-based chemotherapy. METHODS: The treatment response according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria was evaluated in 212 patients with advanced NSCLC who received platinum-based chemotherapy. Patients with partial response (PR) or stable disease (SD) were classified into "PR homo," "PR hetero," "SD homo," and "SD hetero" by the presence of a heterogeneous radiological response, and survival was compared between groups. We also compared survival based on the presence of metabolic responses in lesions with heterogeneous radiological responses. RESULTS: Fifty-two patients (24.5%) were classified as PR, 112 patients (52.8%) as SD, and 48 patients (22.7%) as progressive disease (PD). There was no significant difference in progression-free survival (PFS) and overall survival (OS) between the PR homo and PR hetero groups. The SD homo group had a longer PFS and OS than the SD hetero group. In the SD hetero group, patients with increased maximum standardized uptake value (SUVmax) in lesions with heterogeneous radiological responses had a shorter PFS than those with a stable SUVmax. CONCLUSIONS: The presence of lesions with radiological heterogeneity was associated with disease progression and poor prognosis in the SD group. Patients with heterogeneous radiological responses require careful monitoring.

Anti-inflammatory activities of the mixture of strawberry and rice powder as materials of fermented rice cake on RAW264.7 macrophage cells and mouse models.

Rice cake is a traditional food in Korea, and is made by rice alone, or with other grain powder. To improve the health benefits of fermented rice cake, the rice powder was supplemented with strawberry powder. Anti-inflammatory activities of the mixture of strawberry and rice powder were evaluated. Treatment with the mixture significantly decreased the production of nitric oxide (NO). The mixture of strawberry and rice powder in the ratio 10: 90 effectively and dose-dependently reduced the immune-associated genes iNOS, IL-1ß, IL-6, COX-2, and TNF-α. Furthermore, carrageenan-injected mice were used to study the anti-inflammatory effect of the mixture. Pre-oral administration of the mixture of strawberry and rice powder at doses of 50 and 100 mg/kg BW significantly reduced paw edema induced by carrageenan. These results suggest that for fermented rice cake production and processing, the strawberry and rice powder mixture may be a potential source of anti-inflammatory activity.

The clinical impact of three validated PD-L1 immunohistochemistry assays as a prognostic factor in small cell lung cancer.

BACKGROUND: Evidence of the clinical impact of programmed death-ligand 1 (PD-L1) expression in small cell lung cancer (SCLC) is scarce and conflicting, even though atezolizumab became the first PD-L1 inhibitor approved by the US Food and Drug Administration (FDA) in recent years for the initial treatment of extensive-stage (ES)-SCLC. METHODS: We investigated PD-L1 expression in SCLC tumors using the three validated PD-L1 immunohistochemistry (IHC) assays (SP263, SP142, and 22C3) and assessed the correlation between PD-L1 expression and clinicopathological factors to determine the prognostic value of PD-L1 expression. The three PD-L1 IHC analyses were prospectively used to assess tumor samples of patients with SCLC at diagnosis. RESULTS: Of the total of 59 patients, 47 patients received the active treatment beyond platinum-based chemotherapy at our institution. PD-L1 expression was positive in 39.0% with SP263, 37.3% with SP142, and 22.0% with 22C3. In a univariate analysis, the positive result of at least one of the three PD-L1 assays and the positive result of the SP142 assay were associated with longer overall survival (OS). A multivariable analysis confirmed that performance status, stage, and the SP142 assay were independent predictors of OS. In subgroup analysis, these results revealed more significant prognostic factors in ES than in limited-stage (LS). In patients with SCLC, especially those with ES, the expression of the SP142 assay is a significant independent prognostic factor. CONCLUSIONS: Although these results need to be further validated in larger cohorts, this information will benefit clinicians and patients in determining the immunotherapy for patients with ES-SCLC.

Abdominal lymph node metastasis by lymphatic spread through the thoracic duct in patients with non-small-cell lung cancer.

BACKGROUND: Abdominal lymph node metastasis (ALNM) is common in patients with metastatic non-small-cell lung cancer (NSCLC). However, its mechanism of spread remains to be elucidated. We investigated whether thoracic duct has the role as a pathway for ALNM in NSCLC using clinical data. METHODS: We classified ALNM into subgroups by their location and evaluated its prevalence and association with clinical characteristics in 892 patients with metastatic NSCLC. The abdominal lymph nodes were classified into direct or indirect groups depending on whether they drain directly into the trunk (intestinal trunk or lumbar trunks) connected to the cisterna chyli. RESULTS: One hundred-five patients (11.8%) had ALNM. The paraaortic lymph node was most commonly involved, followed by the aortocaval, left gastric, paracaval, and celiac lymph nodes. After grouping the patients by location of ALNM, 56 patients (53.3%) with ALNM were in the "direct only" group, only seven patients (6.7%) were in the "indirect only" group, and 42 patients (40.0%) were in "both" groups. In patients whose intrathoracic lesions were limited to the right thorax, there was a significantly lower prevalence of ALNM (3.4% vs. 14.3%, p < 0.001). On multivariate logistic regression analysis of clinical variables, higher N category was associated with increased risk of ALNM. CONCLUSIONS: This study suggests that the thoracic duct is one of the potential routes of lymphatic spread to the abdominal lymph nodes. Clinicians should assess for the presence of ALNM during staging work-up and follow-up for NSCLC patients with intrathoracic lesion in left thorax and with high N category.

A Preliminary Study on the Prognostic Impact of Neutrophil to Lymphocyte Ratio of the Bronchoalveolar Lavage Fluid in Patients with Lung Cancer.

The cumulative results indicate that the neutrophil to lymphocyte ratio of peripheral blood (pbNLR) is a useful prognostic factor in patients with various cancers. In contrast to peripheral blood, the bronchoalveolar lavage (BAL) fluid is in direct contact with the lung lesion. However, no study has reported on the clinical utility of the NLR of BAL fluid (bNLR) for patients with lung cancer. To investigate the clinical utility of the bNLR as a prognostic factor in patients with lung cancer, we conducted a retrospective review of the prospectively collected data. A total of 45 patients were classified into high bNLR (n = 29) and low bNLR (n = 16) groups. A high pbNLR and high bNLR were associated with a shorter overall survival (p < 0.001 and p = 0.011, respectively). A multivariable analysis confirmed that ECOG PS (p = 0.023), M stage (p = 0.035), pbNLR (p = 0.008), and bNLR (p = 0.0160) were independent predictors of overall survival. Similar to the pbNLR, a high bNLR value was associated with a poor prognosis in patients with lung cancer. Although further studies are required to apply our results clinically, this is the first study to show the clinical value of the bNLR in patients with lung cancer.