Primary Non-small Cell Lung Cancer Research Articles

Single-Cell Profiling Comparisons of Tumor Microenvironment between Primary Advanced Lung Adenocarcinomas and Brain Metastases and Machine Learning Algorithms in Predicting Immunotherapeutic Responses.

Brain metastasis (BM) occurs commonly in patients with lung adenocarcinomas. Limited evidence indicates safety and efficacy of immunotherapy for this metastatic tumor, though immune checkpoint blockade has become the front-line treatment for primary advanced non-small cell lung cancer. We aim to comprehensively compare tumor microenvironments (TME) between primary tumors (PT) and BM at single-cell resolution. Single-cell RNA transcriptomics from tumor samples of PT (N = 23) and BM (N = 16) and bulk sequencing data were analyzed to explore potential differences in immunotherapeutic efficacy between PT and BM of lung adenocarcinomas. Multiple machine learning algorithms were used to develop and validate models that predict responses to immunotherapy using the external cohorts. We found obviously less infiltration of immune cells in BM than PT, characterized specifically by deletion of anti-cancer CD8+ Trm cells and more dysfunctional CD8+ Tem cells in BM tumors. Meanwhile, macrophages and dendritic cells within BM demonstrated more pro-tumoral and anti-inflammatory effects, represented by distinct distribution and function of SPP1+ and C1Qs+ tumor-associated microphages, and inhibited antigen presentation capacity and HLA-I gene expression, respectively. Besides, we also found the lack of inflammatory-like CAFs and enrichment of pericytes within BM tumors, which may be critical factors in shaping inhibitory TME. Cell communication analysis further revealed mechanisms of the immunosuppressive effects associated with the activation of some unfavorable pathways, such as TGFβ signaling, highlighting the important roles of stromal cells in the anti-inflammatory microenvironment, especially specific pericytes. Furthermore, pericyte-related genes were identified to optimally predict immunotherapeutic responses by machine learning models with great predictive performance. Overall, various factors contribute to the immunosuppressive TME within BM tumors, represented by the lack of critical anti-cancer immune cells. Meanwhile, pericytes may help shape the TME and targeting the associated mechanisms may enhance immunotherapy efficacy for BM tumors in patients with lung adenocarcinomas.

Expression of Her-2/NEU in Patients With Primary Non-small Cell Lung Cancer (Nsclc)

Introduction: Now a days immunohistochemistry and genomic testing for patient with Non- Small Cell Lung Cancer (NSCLC) is becoming new standard of care in clinical decision making. A renewed interest has been emerging on the human epidermal growth factor-2 (HER2) pathway. Aim of this present study was clinicopathological correlation of HER-2/neu expression by IHC in NSCLC. Method: This was a Cross sectional and observational study done at Sir Salimullah Medical College and National Institute of Disease of the Chest and Hospital (NIDCH) and other private hospitals in Dhaka city during July / 2014 to June / 2016. Adult of both gender with histologically diagnosed as a case of NSCLC was include in the study. Immunohistochemistry was done to see the positivity for HER/neu and clinical characteristics were observed. Result: A total 45 patients with NSCLC were enrolled in the study. Male was 77.8% (n=35) and female was 22.2% (n=10). The mean age was 55.67 (SD± 12) years and mean age of male was higher compared to female (57.54±11.64 years verses 49.1±11.38 years). Most of the male were smokers (71.1%) and female were nonsmokers (90%). 57.78% (n=26) of patients and 42.22% (n=19) of patients had adenocarcinoma and squamous cell carcinoma respectively. Most squamous cell carcinoma patients were elderly, had wasting and having higher TNM staging. Serum LDH level was higher with advance staging and grading. Only 8.89% (n=4) had HER-2/neu positive expression affected by male. Patients with HER 2/neu positive expression were relatively older (mean age 62.5±17.08). However, there were equal in histopathological categorization (50% SCC and 50% Adenocarcinoma). Mean LDH was slightly higher in HER-2 positive patients was compared to HER-2 negative patients (569.5±232.6 versus 469.7±181.8). Conclusion: About nine percent of patients having HER-2/neu positive was relatively older and had more high level of LDH. A large-scale study should be conducted in Bangladeshi population to characterize epidemiological, clinicopathological feature in patients with NSCLC with HER-2 expression. J Dhaka Med Coll. 2021; 29(1): 99-110

Genomic landscape and actionable mutations of brain metastases derived from non-small cell lung cancer: A systematic review.

Brain metastases derived from non-small cell lung cancer (NSCLC) represent a significant clinical problem. We aim to characterize the genomic landscape of brain metastases derived from NSCLC and assess clinical actionability. We searched Embase, MEDLINE, Web of Science, and BIOSIS from inception to 18/19 May 2022. We extracted information on patient demographics, smoking status, genomic data, matched primary NSCLC, and programmed cell death ligand 1 expression. We found 72 included papers and data on 2346 patients. The most frequently mutated genes from our data were EGFR (n = 559), TP53 (n = 331), KRAS (n = 328), CDKN2A (n = 97), and STK11 (n = 72). Common missense mutations included EGFR L858R (n = 80) and KRAS G12C (n = 17). Brain metastases of ever versus never smokers had differing missense mutations in TP53 and EGFR, except for L858R and T790M in EGFR, which were seen in both subgroups. Of the top 10 frequently mutated genes that had primary NSCLC data, we found 37% of the specific mutations assessed to be discordant between the primary NSCLC and brain metastases. To our knowledge, this is the first systematic review to describe the genomic landscape of brain metastases derived from NSCLC. These results provide a comprehensive outline of frequently mutated genes and missense mutations that could be clinically actionable. These data also provide evidence of differing genomic landscapes between ever versus never smokers and primary NSCLC compared to the BM. This information could have important consequences for the selection and development of targeted drugs for these patients.

第二原发非小细胞肺癌患者的预后分析

第二原发非小细胞肺癌患者的预后分析

Theranostics application of tumor-initiating cell probe TiY in non-small cell lung cancer.

Background: Tumor-initiating cells (TIC) often elude conventional cancer treatment, which results in metastasis and cancer relapse. Recently, studies have begun to focus on the TIC population in tumors to provide better therapeutic options. Previously, we have reported the successful development of a TIC-specific probe TiY with the binding target as vimentin. While a low concentration of TiY showed a TIC visualization, at a high concentration, TiY induced selective toxicity onto TIC in vitro. In this study, we aim to assess TiY's applicability in theranostics purposes, from in vivo visualization to therapeutic effect toward TIC, in cancer mouse models. Methods: We performed cell experiments with the TIC line model derived from resected primary non-small cell lung cancer (NSCLC) patient tumor. The animal model studies were conducted in mice of NSCLC patient-derived xenograft (PDX). TiY was intravenously delivered into the mice models at different concentrations to assess its in vivo TIC-selective staining and therapeutic effect. Results: We demonstrated the TIC-selective identification and therapeutic effect of TiY in animal models. TiY treatment induced a significant ablation of the TIC population in the tumor, and further molecular study elucidated that the mechanism of TiY is through vimentin dynamics in TIC. Conclusion: The results underscore the applicability of TiY for cancer treatment by selectively targeting soluble vimentin in TIC.

Multiplex immunofluorescence and single-cell transcriptomic profiling reveal the spatial cell interaction networks in the non-small cell lung cancer microenvironment.

Conventional immunohistochemistry technologies were limited by the inability to simultaneously detect multiple markers and the lack of identifying spatial relationships among cells, hindering understanding of the biological processes in cancer immunology. Tissue slices of primary tumours from 553 IA∼IIIB non-small cell lung cancer (NSCLC) cases were stained by multiplex immunofluorescence (mIF) assay for 10 markers, including CD4, CD38, CD20, FOXP3, CD66b, CD8, CD68, PD-L1, CD133 and CD163, evaluating the amounts of 26 phenotypes of cells in tumour nest and tumour stroma. StarDist depth learning model was utilised to determine the spatial location of cells based on mIF graphs. Single-cell RNA sequencing (scRNA-seq) on four primary NSCLC cases was conducted to investigate the putative cell interaction networks. Spatial proximity among CD20+ B cells, CD4+ T cells and CD38+ T cells (r2 =0.41) was observed, whereas the distribution of regulatory T cells was associated with decreased infiltration levels of CD20+ B cells and CD38+ T cells (r2 =-0.45). Univariate Cox analyses identified closer proximity between CD8+ T cells predicted longer disease-free survival (DFS). In contrast, closer proximity between CD133+ cancer stem cells (CSCs), longer distances between CD4+ T cells and CD20+ B cells, CD4+ T cells and neutrophils, and CD20+ B cells and neutrophils were correlated with dismal DFS. Data from scRNA-seq further showed that spatially adjacent N1-like neutrophils could boost the proliferation and activation of T and B lymphocytes, whereas spatially neighbouring M2-like macrophages showed negative effects. An immune-related risk score (IRRS) system aggregating robust quantitative and spatial prognosticators showed that high-IRRS patients had significantly worse DFS than low-IRRS ones (HR 2.72, 95% CI 1.87-3.94, p<.001). We developed a framework to analyse the cell interaction networks in tumour microenvironment, revealing the spatial architecture and intricate interplays between immune and tumour cells.

Treatment of unresectable stage III NSCLC: Real world cohort study and literature review

IntroductionUntil recently, the treatment for patients with locally advanced unresectable stage III non-small cell lung cancer (NSCLC) was combined chemoradiotherapy (CRT), delivered either concurrently (cCRT) or sequentially (sCRT). There is limited data on the outcomes and safety of CRT in a real-world setting. We conducted a real-world cohort analysis of our Leuven Lung Cancer Group (LLCG) experience with CRT for unresectable stage III NSCLC, prior to the era of consolidation treatment with immunotherapy. Patients and MethodsIn this observational, real-world monocentric cohort study, a total of 163 consecutive patients were included. They were diagnosed with unresectable stage III primary NSCLC and treated with CRT between January 1st, 2011, and December 31st, 2018. Patient and tumor characteristics, treatment patterns, toxicity, and primary outcome parameters such as PFS, OS and pattern of relapse were captured. ResultsCRT was concurrent in 108 patients, sequential in 55. Overall tolerability was good, with two thirds of patients without severe adverse events such as severe febrile neutropenia, ≥ grade 2 pneumonitis, or ≥ grade 3 esophagitis. All registered adverse events were more frequent in the cCRT group compared to the sCRT group. Median PFS was 13.2 months (95% CI 10.3–16.2), median OS was 23.3 months (95% CI 18.3–28.0), with a 47.5% survival rate at 2 years, and 29.4% at five years. Conclusions: This study provides a clinically relevant benchmark on the outcomes and toxicity of concurrent and sequential chemoradiotherapy in unresectable stage III NSCLC in a real-world setting in the pre-PACIFIC era.

Circular RNA Sec61 subunit alpha isoform 1 by competitive absorption of microRNA-513a-5p mediates peroxisomal biogenesis factor 5 expression and promotes the malignant phenotype of non-small cell lung cancer.

Circular RNAs (circRNAs) are functional RNAs in the development and metabolism of non-small cell lung cancer (NSCLC). Therein, this paper particularly elucidated the circRNA SEC61 subunit alpha isoform 1 (circSEC61A1) in NSCLC has not been fully elucidated. Clinical analysis of circSEC61A1 expression was performed on specimens collected from 51 patients with primary NSCLC, together with patients' survival. Cell experiments were performed after interfering with circSEC61A1, microRNA (miR)-513a-5p, and peroxisomal biogenesis factor 5 (PEX5) expression, respectively, and cell malignant phenotypes and aerobic glycolysis were evaluated, as well as epithelial-to-mesenchymal transition (EMT)-related markers and Wnt/β-catenin pathway. Xenografts experiments studied the performance of circSEC61A1 in vivo. The downstream molecules of circSEC61A1 were searched. Our data demonstrated that circSEC61A1 was upregulated in NSCLC patients, showing an association with poorer survival outcomes. In cell experiments, circSEC61A1 overexpression promoted NSCLC malignant phenotypes, glycolysis, EMT, and Wnt/β-catenin pathway activation, whereas circSEC61A1 underexpression did the opposite. Knockdown of circSEC61A1 limited tumor growth and metastasis. Furthermore, circSEC61A1 could regulate PEX5 expression through competitive absorption of miR-513a-5p. Generally, circSEC61A1 is a potential biomarker for NSCLC, and circSEC61A1 serves tumor-promoting action in the progression of NSCLC.

Matched Analyses of Brain Metastases versus Primary Non-Small Cell Lung Cancer Reveal a Unique microRNA Signature.

Distant spreading of tumor cells to the central nervous system in non-small cell lung cancer (NSCLC) occurs frequently and poses major clinical issues due to limited treatment options. RNAs displaying differential expression in brain metastasis versus primary NSCLC may explain distant tumor growth and may potentially be used as therapeutic targets. In this study, we conducted systematic microRNA expression profiling from tissue biopsies of primary NSCLC and brain metastases from 25 patients. RNA analysis was performed using the nCounter Human v3 miRNA Expression Assay, NanoString technologies, followed by differential expression analysis and in silico target gene pathway analysis. We uncovered a panel of 11 microRNAs with differential expression and excellent diagnostic performance in brain metastasis versus primary NSCLC. Five microRNAs were upregulated in brain metastasis (miR-129-2-3p, miR-124-3p, miR-219a-2-3p, miR-219a-5p, and miR-9-5p) and six microRNAs were downregulated in brain metastasis (miR-142-3p, miR-150-5p, miR-199b-5p, miR-199a-3p, miR-199b-5p, and miR-199a-5p). The differentially expressed microRNAs were predicted to converge on distinct target gene networks originating from five to twelve core target genes. In conclusion, we uncovered a unique microRNA profile linked to two target gene networks. Our results highlight the potential of specific microRNAs as biomarkers for brain metastasis in NSCLC and indicate plausible mechanistic connections.

Prognostic Biomarkers after Radiotherapy for Nonsmall Cell Lung Cancer Based on Bioinformatics Analysis.

Radiotherapy is one of the main treatment modalities in nonsmall cell lung cancer (NSCLC). However, tumor radiosensitivity is influenced by intrinsic factors like genetic variations and extrinsic factors like tumor microenvironment. Consequently, we hope to develop novel biomarkers, so as to improve the response rate of radiotherapy and overcome resistance to radiotherapy in NSCLC. We investigate the difference genes of primary NSCLC patients before and after radiotherapy in GSE162945 dataset. Gene Ontology (GO), KEGG, Reactome, and GSEA were employed to represent the essential gene and biological function. It was found that most pathway genes clustered in extracellular matrix and ECM-receptor signal pathway. Additionally, TMT-based proteomics was used to survey the differential proteins present in the supernatant of H460 cells before or after irradiation with 2 Gy of γ-rays. And then we take the intersection between the proteomics of H460 cell and ECM-receptor signal pathway proteins of GSE162945 datasets. The data revealed that fibronectin 1 (FN1) and thrombin reactive protein 1 (THBS1) were upregulated after radiation in both datasets. Subsequently, survival analyses using the GEPIA web server demonstrated that FN1 and THBS1 had significant prognostic values (Logrank test P value < 0.05) for LUAD and LUSC. Our observations from this study suggest that FN1 and THBS1 might have potential to serve as novel biomarkers for predicting NSCLC tumor response to radiotherapy.

PARP-1 genetic polymorphism associated with radiation sensitivity of non-small cell lung cancer.

About 70% of non-small cell lung cancer (NSCLC) patients require radiotherapy. However, due to the difference in radiation sensitivity, the treatment outcome may differ for the same pathology and choice of treatment. Poly (ADP-ribose) polymerase 1 (PARP-1) is a key gene responsible for DNA repair and is involved in base excision repair as well as repair of single strand break induced by ionizing radiation and oxidative damage. In order to investigate the relationship between PARP-1 gene polymorphism and radiation sensitivity in NSCLC, we collected 141 primary NSCLC patients undergoing three-dimensional conformal radiotherapy. For each case, the gross tumor volumes (GTV) before radiation and that after 40Gy radiation were measured to calculate the tumor regression rate. TaqMan real-time polymerase chain reaction was performed to genotype the single-nucleotide polymorphisms (SNPs). Genotype frequencies for PARP-1 genotypes were 14.2% for C/C, 44.7% for C/G and 41.1% for G/G. The average tumor regression rate after 40Gy radiation therapy was 35.1% ± 0.192. Tumor regression rate of mid-term RT of C/C genotype was 44.6% ± 0.170, which was higher than that of genotype C/G and G/G (32.4% ± 0.196 and 34.8% ± 0.188, respectively) with statistical significance (F = 3.169 p = 0.045). The higher tumor regression rate in patients with C/C genotype suggested that G allele was a protective factor against radiation therapy. Using the median tumor regression rate of 34%, we divided the entire cohort into two groups, and found that the frequency distribution of PARP-1 gene rs3219073 had significant difference between these two groups (p < 0.05). These results showed that PARP-1 gene polymorphism may affect patient radiation sensitivity and predict the efficacy of radiotherapy. It therefore presents an opportunity for developing new therapeutic targets to improve radiotherapy outcome.

Heterogeneity and Clinical Effect of Epidermal Growth Factor Receptor in Primary Lung and Brain Metastases of Nonsmall Cell Lung Cancer

IntroductionThis study aimed to analyze the heterogeneity in epidermal growth factor receptor (EGFR) gene mutation and its impact on clinical outcomes in primary tumor and corresponding brain metastasis (BM) in nonsmall cell lung cancer (NSCLC). Materials and methodsPrimary pulmonary tumors and paired BMs of 27 NSCLC patients were surgically removed. All brain lesions were histologically confirmed as metastatic NSCLC. EGFR gene mutation status was detected by using amplification refraction mutation system. McNemar test was performed to compare EGFR mutation status between lung primary tumors and metastatic brain tumors and Kappa test was performed to quantify the agreement between the two. ResultsOf the 27 patients, nine cases were found to have EGFR mutations in BMs and 10 had a positive EGFR mutation status in primary lung tumor tissue. The rate of consistency of the matched tumor was 24/27 (88.9%). Among the three cases presenting EGFR mutational heterogeneity, two patients harbored an EGFR mutation in the primary tumor but not in the BMs; meanwhile, the last patient demonstrated the opposite pattern. Compared to patients with consistent EGFR mutations, patients with inconsistent mutations showed better outcomes. Further analysis revealed that the two patients whose EGFR mutant-type primary tumor progressed to wild-type cerebral metastatic tumor had longer overall survival than the patient whose EGFR wild-type primary tumor progressed to mutant-type brain metastatic tumor. ConclusionsHeterogeneity of EGFR mutation status was observed between primary NSCLC and paired BM. Patients possessing a wild-type EGFR mutation in BM might have better outcomes, especially those with transition from mutant to wild-type.

A Pilot Analysis of Circulating cfRNA Transcripts for the Detection of Lung Cancer.

Lung cancers are the leading cause of cancer-related deaths worldwide. Studies have shown that non-small cell lung cancer (NSCLC), which constitutes the majority of lung cancers, is significantly more responsive to early-stage interventions. However, the early stages are often asymptomatic, and current diagnostic methods are limited in their precision and safety. The cell-free RNAs (cfRNAs) circulating in plasma (liquid biopsies) offer a non-invasive detection of spatial and temporal changes occurring in primary tumors since the early stages. To address gaps in the current cfRNA knowledge base, we conducted a pilot study for the comprehensive analysis of transcriptome-wide changes in plasma cfRNA in NSCLC patients. Total cfRNA was extracted from archived plasma collected from NSCLC patients (N = 12), cancer-free former smokers (N = 12), and non-smoking healthy volunteers (N = 12). Plasma cfRNA expression levels were quantified by using a tagmentation-based library preparation and sequencing. The comparisons of cfRNA expression levels between patients and the two control groups revealed a total of 2357 differentially expressed cfRNAs enriched in 123 pathways. Of these, 251 transcripts were previously reported in primary NSCLCs. A small subset of genes (N = 5) was validated in an independent sample (N = 50) using qRT-PCR. Our study provides a framework for developing blood-based assays for the early detection of NSCLC and warrants further validation.

Sequential bronchoplastic lobectomies in complex treatment for synchronous bilateral multiple primary non-small cell lung cancer: a rare clinical case

Today, lung cancer (LC) occupies a special place in the oncological general morbidity among the male population both in Russia and in foreign countries. Despite modern diagnostic capabilities provided for modern physicians, steadily frequent cases of triggering and exclusion are more common in patients older than 60–65 years. Surgery is the main treatment for early-stage non-small cell lung cancer (NSCLC), but as the disease progresses, unfortunately, its effectiveness decreases. The strategy of diagnosing and treating patients with one NSCLC has been developed and worked out for a long time and does not cause any difficulties, but in the presence of two or more tumors, especially when they are located in both lungs, the correct choice of therapy is determined by many additional factors. This article describes the rare use of extended bronchoplastic upper lobectomy as a surgical component of the complex treatment of a patient with bilateral synchronous NSCLC. Based on our own observational data, it can be claimed that the use of modern therapeutic principles in combination with surgical intervention allows achieving satisfactory long-term results in the treatment of patients with primary multiple NSCLC.The interest of the presented observation is based on the fact that it contains a description of a rare and unique application of sequential extended bronchoplastic upper lobectomy as a surgical component of the complex treatment of a patient with bilateral synchronous NSCLC, which we have not found analogues in the literature. We have shown that the consistent use of modern therapeutic modalities makes it possible to achieve satisfactory long-term results in the treatment of a locally advanced disease.

RBIO-02. ACTIVATION OF GABAA RECEPTORS WITH A NON-TOXIC, BRAIN PENETRANT SMALL MOLECULE SENSITIZES LUNG ADENOCARCINOMA PRIMARY AND BRAIN METASTATIC TUMOR CELLS TO RADIATION VIA AUTOPHAGY INDUCTION

Abstract Most advanced-stage non-small cell lung cancer (NSCLC) patients have brain metastases that render a dismal prognosis. Treatment of metastatic brain lesions from NSCLC and other tumor types include radiation as part of a multimodal treatment regimen. Challenges in the application of radiotherapy include overcoming radiation resistance and reducing associated co-morbidities. Non-toxic therapeutics capable of sensitizing tumors to radiation are needed to improve survival and mitigate radiation side-effects. Many CNS and solid systemic tumors express ligand-gated ion channels, which may contribute to tumor growth. Leveraging ion channels is therefore a potential way of diminishing the spread of cancer. We find that NSCLC and its brain metastases express subunits of the type-A GABA-gated chloride channel or GABAA receptor. Importantly, patient-derived NSCLC cells have functional GABAA receptors. We identified a brain penetrant, small molecule activator of GABAA receptors (AMLAL-101), which alone impairs the viability of both primary NSCLC cells and brain metastatic cells. In addition, AMLAL-101 combined with radiation is a highly potent inducer of NSCLC cell death and clonogenic arrest. Using a human ex vivo model of NSCLC-on-chip, we assessed the efficacy and toxicity of AMLAL-101 relative to Docetaxel, an antimicrotubular agent used in treating advanced NSCLC. AMLAL-101 is as potent as Docetaxel but does not exhibit its toxic side effects. AMLAL-101 also potentiates radiation in vivo, significantly reducing lung adenocarcinoma xenograft tumor growth in mice, equivalent to docetaxel plus radiation. Mechanistically, AMLAL-101 activates GABAA receptors in NSCLC and synergizes with radiation by inducing an autophagic response that includes: (i) stabilization of Beclin-1, BNIP3L/NIX, and GABARAP; (ii) ATG7 upregulation; and (iii) utilization of ubiquitin-binding protein p62. Activating GABAA receptors in NSCLC and other tumor types may improve radiation efficacy and mitigate its toxic side effects in treating brain metastases.

Real-World Evidence of Health Outcomes Related to Lung Stereotactic Body Radiation Therapy in Brazil.

Stereotactic body radiation therapy (SBRT) is an effective option for patients with both early-stage and oligometastatic non-small-cell lung cancer (NSCLC). However, data from Latin America are limited. Therefore, the aim of this study was to investigate the real-world outcomes of applying SBRT for lung lesions in a Brazilian institution. This study investigated a consecutive cohort of patients treated with SBRT for lung lesions (primary and metastasis). The study primary outcome was local control rates per lesion. Secondary outcomes included progression-free survival (PFS), overall survival (OS), and toxicity. Between 2015 and 2019, a total of 216 patients received SBRT and were included in the study. The median follow-up was 24.5 months (5-70), primary NSCLC corresponded to 70% (n = 151) and nonprimary lung lesions to 30% (n = 65), respectively. Stage I NSCLC represented 56% (85 of 151) of the NSCLC cohort. The average number of fractions and total dose prescribed was 5 (3-10)/59 Gy (50-62 Gy). For stage I NSCLC (all lesions treated with a biologically effective dose [10] > 100 Gy), 2-year local control, OS, and PFS were 93.4%, 81.6%, and 80.7%, respectively. For stage IV lesions, if biologically effective dose (10) > 100 Gy or < 100 Gy, 2-year local control was 95.8/86.4% (P = .03), 2-year-OS was 81.6/60.5% (P = .006), and 2-year PFS was 38.9/17.9% (P = .10). Late toxicity was observed in 16.2% (n = 35) of the total cases. Our results indicate that SBRT is effective (high local control and acceptable toxicity) for treating malignant lung lesions in a real-world scenario in Latin America.

Quantitative Proteomics Indicate Radical Removal of Non-Small Cell Lung Cancer and Predict Outcome.

Non-small cell lung cancer (NSCLC) is associated with low survival rates, often due to late diagnosis and lack of personalized medicine. Diagnosing and monitoring NSCLC using blood samples has lately gained interest due to its less invasive nature. In the present study, plasma was collected at three timepoints and analyzed using proximity extension assay technology and quantitative real-time polymerase chain reaction in patients with primary NSCLC stages IA-IIIA undergoing surgery. Results were adjusted for patient demographics, tumor, node, metastasis (TNM) stage, and multiple testing. Major histocompatibility (MHC) class 1 polypeptide-related sequence A/B (MIC-A/B) and tumor necrosis factor ligand superfamily member 6 (FASLG) were significantly increased post-surgery, suggesting radical removal of cancerous cells. Levels of hepatocyte growth factor (HGF) initially increased postoperatively but were later lowered, potentially indicating radical removal of malignant cells. The levels of FASLG in patients who later died or had a relapse of NSCLC were lower at all three timepoints compared to surviving patients without relapse, indicating that FASLG may be used as a prognostic biomarker. The biomarkers were confirmed using microarray data. In conclusion, quantitative proteomics could be used for NSCLC identification but may also provide information on radical surgical removal of NSCLC and post-surgical prognosis.

Immune cell-lipoprotein imbalance as a marker for early diagnosis of non-small cell lung cancer metastasis.

The underlying molecular mechanisms and evolutionary patterns of lung cancer metastasis remain unclear, resulting in a lack of effective indicators for early diagnosis of metastasis. We retrospectively analyzed 117 patients with primary non-small cell lung cancer (NSCLC) admitted to Tongji Hospital of Tongji University in 2021, of which 93 patients with tumor metastasis were set as the metastasis group. 24 patients without metastasis were set as the non-metastasis group. The differences of each index in the two groups of patients and the expression levels in different TNM stages were compared. This study intends to evaluate the diagnostic value and net clinical benefit of common blood-related indicators Neutrophil/lymphocyte (NLR), lymphocyte/monocyte (LMR), High density lipoprotein/neutrophil (HNR), High density lipoprotein/monocyte (HMR) and combined assays in NSCLC metastasis for the early diagnosis of patients with NSCLC metastasis. It was found that the level of NLR was higher in metastatic NSCLC than non-metastatic, but the level of LMR, HNR and HMR was lower. The levels of NLR, LMR, HNR and HMR in patients with different TNM stages showed that NLR levels increased with TNM stage, while LMR, HNR and HMR levels decreased. The threshold probability range of the 4 combined tests was greater and the overall clinical benefit rate was higher compared to the individual tests. Our findings suggest that NLR, LMR, HNR and HMR have better diagnostic value for NSCLC metastasis. This study provides a clinical basis for investigating the mechanisms by which immune cells and lipid metabolism-related proteins remodel the microenvironment prior to NSCLC metastasis.

Concurrent Administration of Immune Checkpoint Inhibitors and Stereotactic Radiosurgery is Not Associated with an Increased Risk of Radiation Necrosis: An International Multicenter Study of 657 Patients

<h3>Purpose/Objective(s)</h3> Stereotactic radiosurgery (SRS) and immune checkpoint inhibitors (ICI) are highly effective treatments for brain metastases (BrM), particularly when these therapies are administered concurrently. However, there are limited data reporting the risk of radiation necrosis (RN) in this setting. <h3>Materials/Methods</h3> Patients with BrM from primary non-small cell lung cancer, renal cell carcinoma, or melanoma treated with SRS and ICI were considered. Recursive partitioning analysis (RPA) was utilized for model development, and a loop of potential models was analyzed, with the highest-fidelity model selected. <h3>Results</h3> Six hundred fifty-seven patients with 4,182 BrM across 11 international institutions were analyzed. Rates of RN and symptomatic RN (SRN) for all patients were 10% and 6.8%, respectively. The highest-fidelity models consistently identified V12 Gy as the dominant variable predictive of RN. Three risk groups were identified using V12 Gy: (1) < 12 cm³; (2) 20 cm³ ≤ V12 Gy ≥ 12 cm³; (3) > 20 cm³. Odds ratios for RN and SRN with cases of V12 Gy ≥ 12 cm³ compared with < 12 cm³ were 3.05 (<i>p</i> < 0.001) and 3.72 (<i>p</i> < 0.001), respectively. Rates of RN and SRN are presented in the table below. Concurrent ICI use rates were equivalent among these resulting groups, and the addition of concurrent ICI use did not improve the model's fidelity. Using RPA, 80% of the highest-fidelity models failed to incorporate concurrent ICI as a predictive variable. Even after exclusion of V12 Gy as a candidate variable, concurrent ICI remained unused in 85% of the highest-fidelity models. These models yielded 94% accuracy for the validation set and 92% accuracy for the test set. <h3>Conclusion</h3> Utilization of SRS and ICI results in a low risk of RN and SRN. This risk is not increased when ICI and SRS are administered concurrently. Therefore, ICI can safely be administered within 4-weeks of SRS. In patients receiving SRS and ICI, three risk groups based on V12 Gy were identified, which clinicians may consider to further reduce rates of RN.

Lung resection surgery in Jehovah’s Witness patients: a 20-year single-center experience

BackgroundThe paucity of literature on surgical outcomes of Jehovah’s Witness (JW) patients undergoing lung resection suggests some patients with operable lung cancers may be denied resection. The aim of this study is to better understand perioperative outcomes and long-term cancer survival of JW patients undergoing lung resection.MethodsAll pulmonary resections in JW patients at one institution from 2000 through 2020 were examined. Demographics, comorbidities, operative parameters, and perioperative outcomes were reviewed. Among operations performed for primary non-small cell lung cancer (NSCLC), details regarding staging, extent of resection, additional therapies, recurrence, and survival were abstracted.ResultsSeventeen lung resections were performed in fourteen patients. There were nine anatomic resections and eight wedge resections. Fourteen resections (82%) were approached thoracoscopically, of which 3 of 6 anatomic resections were converted to thoracotomy as compared to 1 of 8 wedge resections. There was one (6%) perioperative death. Ten resections in 8 patients were performed for primary pulmonary malignancies, and two patients underwent procedures for recurrent disease. Median survival for resected NSCLCs (N = 7) was 65 months. Three of 6 patients who survived the immediate perioperative period underwent additional procedures: 2 pulmonary wedge resections for diagnosis and one pleural biopsy.ConclusionsThis series of JW patients undergoing lung resections demonstrates that resections for cancer and inflammatory etiologies can be performed safely in the setting of both primary and re-operative procedures.