Subgroup Of Non-small Cell Lung Cancer Research Articles

Peripheral Inflammation Featuring Eosinophilia or Neutrophilia Is Associated with the Survival and Infiltration of Eosinophils within the Tumor among Various Histological Subgroups of Patients with NSCLC.

Immune activation status determines non-small cell lung cancer (NSCLC) prognosis, with reported positive/negative associations for T helper type 2 (TH2) responses, including allergen-specific IgE and eosinophils. Our study seeks to explore the potential impact of these comorbid immune responses on the survival rates of patients with NSCLC. Our retrospective study used data from the Data Warehouse of the German Center for Lung Research (DZL) and Lung Biobank at Thoraxklinik Heidelberg. We estimated the association of blood eosinophilia and neutrophilia on survival rates in an inflammatory cohort of 3143 patients with NSCLC. We also tested sensitization to food and inhalants and high-sensitivity C-reactive protein (hs-CRP) in a comorbidity cohort of 212 patients with NSCLC. Finally, we estimated the infiltration of immune-relevant cells including eosinophils, T-cells, and mast cells in a tissue inflammatory sub-cohort of 60 patients with NSCLC. Sensitization to at least one food or inhalant (sIgE) was higher in patients with adenocarcinoma (adeno-LC) than the non-adenocarcinoma (non-adeno-LC). Furthermore, hs-CRP was higher in non-adeno-LC compared with adeno-LC. Peripheral inflammation, particularly eosinophilia and neutrophilia, was associated with poor survival outcomes in NSCLC with a clear difference between histological subgroups. Finally, blood eosinophilia was paralleled by significant eosinophil infiltration into the peritumoral tissue in the lung. This study provides novel perspectives on the crucial role of peripheral inflammation, featuring eosinophilia and neutrophilia, with overall survival, underscoring distinctions between NSCLC subgroups (adeno-LC vs. non-adeno-LC). Peripheral eosinophilia enhances eosinophil infiltration into tumors. This sheds light on the complex interplay between inflammation, eosinophil infiltration, and NSCLC prognosis among various histological subtypes. Further studies are required to underscore the role of eosinophils in NSCLC among different histological subgroups and their role in shaping the tumor microenvironment.

Molecular profiling METex14+ non-small cell lung cancer (NSCLC): Impact of histology

ObjectivesMET exon 14 skipping alterations (METex14+) represent a heterogeneous subgroup of non-small cell lung cancer (NSCLC) with distinct biological and genomic features. We characterized this heterogeneity in a large cohort, integrating genomic and transcriptomic profiling with clinical outcomes, to elucidate the histologic and molecular traits and survival patterns of METex14+ NSCLC. Materials and methodsNSCLC tissue samples (n = 28,739) underwent DNA-based next-generation sequencing (592 genes, NextSeq) or whole-exome sequencing (NovaSeq), RNA-sequencing including whole transcriptome sequencing (WTS, NovaSeq), and PD-L1 IHC (Dako 22C3) at Caris Life Sciences. Immune cell fractions were estimated from bulk RNA sequencing (quanTIseq). Real-world survival data (mOS) was calculated from insurance claims. Statistical analyses employed Chi-square, Fisher’s exact, or Mann-Whitney U and log-rank tests and were corrected for hypothesis testing where applicable. ResultsA total of 711 METex14+ cases were detected. Of 575 cases of defined histology, 77 (13.6 %) were squamous (Sq), 474 (82.3 %) were nSq (non-squamous), and 24 (4.1 %) were adenosquamous. Mutations in POT1 and BRCA2 were enriched, and amplifications in MDM2, HMGA2, CDK4, and MET were common in METex14+ tumors. TMB-high and TP53 mutated tumors were reduced in METex14+ independent of histology. KEAP1 (2.1 vs 14.7 %) and STK11 mutations (0.8 vs 17.1 %) were reduced only in METex14+ nSq (vs METex14+ Sq, q < 0.05). While the prevalence of PD-L1 high tumors was enriched in METex14+ independent of histology, T-cell inflamed tumors were enriched only in nSq METex14+. B-cells and CD8+ T-cells (1.07–1.43-fold) were enriched in nSq METex14+, and dendritic cells (0.32 fold) were reduced only in METex14+ Sq. METex14+ tumors had a modest improvement in mOS compared to METex14- tumors (mOS = 22.9 m vs 18.6 m, HR = 0.914, p = 0.04). Moreover, METex14+ tumors who received immunotherapy (IO) had a modest improvement in survival (mOS = 27.5 m vs 21.8 m; HR = 0.803, p = 0.03) compared to those who did not receive IO. METex14+ nSq tumors were associated with improved mOS compared to METex14+ Sq tumors (mOS = 27.7 vs 8.9 m, HR = 0.493, p < 0.0001). ConclusionMETex14+ alterations are a heterogeneous subgroup of NSCLC. Our analysis reveals that METex14+ nSq exhibit improved survival compared to METex14+ Sq. The distinct genomic and transcriptomic variations across histologies warrant clinical consideration.

Spatial profiling of non-small cell lung cancer provides insights into tumorigenesis and immunotherapy response

Lung cancer is the second most common cancer worldwide and a leading cause of cancer-related deaths. Despite advances in targeted therapy and immunotherapy, the prognosis remains unfavorable, especially in metastatic cases. This study aims to identify molecular changes in non-small cell lung cancer (NSCLC) patients based on their response to treatment. Using tumor and matched immune cell rich peritumoral tissues, we perform a retrospective, comprehensive spatial transcriptomic analysis of a proven malignant NSCLC sample treated with immune checkpoint inhibitor (ICI). In addition to T cells, other immune cell types, such as B cells and macrophages, were also activated in responders to ICI treatment. In particular, B cells and B cell-mediated immunity pathways are consistently found to be activated. Analysis of the histologic subgroup (lung squamous cell carcinoma, LUSC; lung adenocarcinoma, LUAD) of NSCLC also confirms activation of B cell mediated immunity. Analysis of B cell subtypes shows that B cell subtypes were more activated in immune cell-rich tissues near tumor tissue. Furthermore, increased expression of B cell immunity-related genes is associated with better prognosis. These findings provide insight into predicting ICI treatment responses and identifying appropriate candidates for immunotherapy in NSCLC patients.

Exploring the safety and efficacy of GT201 as a first-in-class autologous tumor-infiltrating lymphocyte monotherapy in advanced solid tumors.

2547 Background: GT201, featuring a membrane bound IL-15 stably expressed on tumor-infiltrating lymphocytes (TIL), aims to augment TIL persistence and function as well as ameliorate immune suppression within the tumor microenvironment, offering potential for durable responses in advanced solid tumor patients. We present data from 7 patients enrolled in an open-label, single-arm, multicenter clinical study (NCT05729399), investigating the safety profile and efficiency trend of GT201 therapy. Methods: The GT201 phase 1 trial is designed with the primary endpoint of DLT evaluation and the secondary endpoint of measuring preliminary efficacy parameters including overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), duration of response (DOR, and overall survival (OS) following the RECIST v1.1. Results: As of January 22, 2024, a cohort of 7 pts has been enrolled in the study, with a median age of 48 and a median of 3 prior lines of therapy. Among these patients, 1 pt has a history of bone metastases, 2 pts have a history of liver metastases, and 1 pt has a history of brain metastases. Following the standard FC lymphodepletion, pts underwent infusion with GT201 at doses ≥ 5x109 total viable cells. Five pts subsequently received IL-2 as part of the treatment protocol. Treatment-related AEs were observed in ≥ 50% of pts with no grade≥3 AEs. Grade ≥ 3 AEs related to FC lymphodepleting chemotherapy and IL-2 included decreased lymphocyte count, decreased neutrophil count, and decreased white blood cell count, pyrexia and increased heart rate. Notably, all grade ≥3 AEs were either recovered or downgraded to grade ≤ 2 within 14 days. Among the 7 response-evaluable patients across various indications, including Non-Small-Cell-Lung Cancer (NSCLC), melanoma malignant, cervical cancer, and ovarian cancer, 3 patients (42.9%) achieved a confirmed partial response (PR), and 2 patients (28.6%) demonstrated stable disease (SD) as their best response. Notably, among the NSCLC subgroup, disease control (SD ≥ 24 weeks or any PR) was observed in all 3 pts (3/3, 100 %). GT201 cells can be detected in all patients receiving treatment, indicated by both staining IL15RA protein on peripheral T cells and measuring the transgene copy number in peripheral white blood cells. GT201 cells expanded robustly in patients and persist in peripheral blood beyond at least 6 months post cell infusion. Conclusions: In patients with heavily pretreated advanced or metastatic solid tumor, GT201, when infused after FC lymphodepletion and followed by high dose IL-2, exhibits a manageable safety profile. Notably, GT201 has demonstrated a favorable clinical profile in NSCLC, with an encouraging objective response rate, response durability, and no GT201-treatment related grade≥3 AEs. Clinical trial information: NCT05729399 .

FDA analysis of immune checkpoint inhibitors in combination with vascular endothelial growth factor tyrosine kinase inhibitors in the second-line treatment of patients with advanced non-small cell lung cancer.

8595 Background: Immune checkpoint inhibitors (ICIs) targeting PD-(L)1 in combination with platinum-based chemotherapy is standard first-line therapy for patients with advanced non-small cell lung cancer (NSCLC). The majority of these patients progress and there remains a high unmet medical need in the second-line setting given the limited FDA approved available therapies. The ICI plus vascular endothelial growth factor tyrosine kinase inhibitor (VEGF TKI) combination, successful across several tumor types, was studied in NSCLC as a potential treatment option. Methods: The FDA identified 3 randomized trials conducted between June 2019 and August 2023, comparing the combination regimen ICI plus VEGF TKI to docetaxel in patients with advanced NSCLC who had progressed on both platinum-based chemotherapy and an ICI. All 3 trials were publicly reported to have not met their primary endpoint. Topline results for key efficacy and safety outcomes from each of the 3 trials were provided by the commercial sponsors. Results: 1317 total patients across 3 trials (LEAP-008, SAPPHIRE and CONTACT-01) were randomized to receive either an ICI plus VEGF TKI or docetaxel. The results are presented (Table). Efficacy parameters demonstrated similar results across trials between arms. There was no clear signal that the combination is more effective than single agent docetaxel. Safety parameters across trials consistently demonstrated higher rates of toxicity with the combination. Conclusions: ICI plus oral VEGF TKI combinations have not demonstrated an advantage over docetaxel in randomized trials of patients with advanced NSCLC. In 2 of the 3 trials, response rate data did not demonstrate superior efficacy compared to docetaxel. Additionally, any observed PFS benefit was small in magnitude. The relatively low efficacy, in combination with the additive toxicity of the regimen, may curtail a potential OS benefit. There remains a high unmet medical need in this patient population and further analysis is necessary to explore potential NSCLC subgroups which may derive benefit. [Table: see text]

Genome-Wide Methylation Analysis in Two Wild-Type Non-Small Cell Lung Cancer Subgroups with Negative and High PD-L1 Expression.

We conducted a pilot study to analyze the differential methylation status of 20 primary acinar adenocarcinomas of the lungs. These adenocarcinomas had to be wild type in mutation analysis and had either high (TPS > 50%; n = 10) or negative (TPS < 1%; n = 10) PD-L1 status to be integrated into our study. To examine the methylation of 866,895 specific sites, we utilized the Illumina Infinium EPIC bead chip array. Both hypermethylation and hypomethylation play significant roles in tumor development, progression, and metastasis. They also impact the formation of the tumor microenvironment, which plays a decisive role in tumor differentiation, epigenetics, dissemination, and immune evasion. The gained methylation patterns were correlated with PD-L1 expression. Our analysis has identified distinct methylation patterns in lung adenocarcinomas with high and negative PD-L1 expression. After analyzing the correlation between the methylation results of genes and promoters with their pathobiology, we found that tumors with high expression of PD-L1 tend to exhibit oncogenic effects through hypermethylation. On the other hand, tumors with negative PD-L1 expression show loss of their suppressor functions through hypomethylation. The suppressor functions of hypermethylated genes and promoters are ineffective compared to simultaneously activated dominant oncogenic mechanisms. The tumor microenvironment supports tumor growth in both groups.

Impact of concurrent medications on clinical outcomes of cancer patients treated with immune checkpoint inhibitors: analysis of Health Insurance Review and Assessment data

PurposeMedications regulating immune homeostasis and gut microbiota could affect the efficacy of immune checkpoint inhibitors (ICIs). This study aimed to investigate the impact of concurrent medications on the clinical outcomes of patients with cancer receiving ICI therapy in South Korea.MethodsWe identified patients newly treated with ICI for non-small cell lung cancer (NSCLC), urothelial carcinoma (UC), and malignant melanoma (MM) between August 2017 and June 2020 from a nationwide database in Korea. The effect of concurrent antibiotics (ATBs), corticosteroids (CSs), proton-pump inhibitors (PPIs), and opioids prescribed within 30 days before ICI initiation on the treatment duration and survival was assessed.ResultsIn all, 8870 patients were included in the ICI cohort (NSCLC, 7,128; UC, 960; MM, 782). The patients were prescribed ATBs (33.8%), CSs (47.8%), PPIs (28.5%), and opioids (53.1%) at the baseline. The median overall survival durations were 11.1, 12.2, and 22.1 months in NSCLC, UC, and MM subgroups, respectively, since starting the ICI mostly as second-line (NSCLC and UC) and first-line (MM) therapy. Early progression was observed in 34.2% of the patients. Opioids and CS were strongly associated with poor survival across all cancer types. A high number of concurrent medications was associated with early progression and short survival. Opioid and CS use was associated with poor prognosis in all patients treated with ICIs. However, ATBs and PPIs had a cancer-specific effect on survival.ConclusionA high number of concurrent medications was associated with poor clinical outcomes.

Targeted Therapy of Advanced Non-Small Cell Lung Cancer

Lung cancer is the leading cause of cancer death in Republic of Korea. After their initial diagnosis, only 10-20% of patients with advanced non-small cell lung cancer (NSCLC) survive for 5 years of longer. Given enormous advances in therapeutics such as novel targeted therapies and immunotherapies, survival rates are improving for advanced patients with NSCLC; 5-year survival rates range from 15% to 50%, contingent upon the biomarker. Detection of the specific molecular alteration as biomarker is thus crucial for identifying subgroups of NSCLC that contain therpapeutically targetable oncogenic drivers. This review examines the process of diagnosing lung adenocarcinoma with dominant biomarkers in order to customize treatment with appropriate targeted therapy.

The Effects of Drug Exposure and Single Nucleotide Polymorphisms on Aaptinib-Induced Severe Toxicities in Solid Tumors.

In this prospective study, plasma APA concentrations were quantified using liquid chromatography with tandem mass spectrometry, and 57 germline mutations were genotyped in 126 advanced solid tumor patients receiving 250 mg daily APA, a vascular endothelial growth factor receptor II inhibitor. The correlation between drug exposure, genetic factors, and the toxicity profile was analyzed. Non-small cell lung cancer (NSCLC) was more prone to APA-related toxicities and plasma concentrations of APA, and its main metabolite M1-1 could be associated with high-grade adverse events (AEs) (P < 0.01; M1-1, P < 0.01) and high-grade antiangiogenetic toxicities (APA, P = 0.034; P < 0.05), including hypertension, proteinuria, and hand-foot syndrome, in the subgroup of NSCLC. Besides, CYP2C9 rs34532201 TT carriers tended to have higher levels of APA (P < 0.001) and M1-1 (P < 0.01), whereas CYP2C9 rs1936968 GG carriers were predisposed to higher levels of M1-1 (P < 0.01). Plasma APA and M1-1 exposures were able to predict severe AEs in NSCLC patients. Dose optimization and drug exposure monitoring might need consideration in NSCLC patients with CYP2C9 rs34532201 TT and rs1936968 GG. Apatinib is an anti-VEGFR2 inhibitor for the treatment of multiple cancers. Though substantial in response, apatinib-induced toxicity has been a critical issue that is worth clinical surveillance. Few data on the role of drug exposure and genetic factors in apatinib-induced toxicity are available. Our study demonstrated a distinct drug-exposure relationship in NSCLC but not other tumors and provided invaluable evidence of drug exposure levels and single nucleotide polymorphisms as predictive biomarkers in apatinib-induced severe toxicities.

Prognostic Factors in Patients with Metastatic Spinal Cord Compression Secondary to Lung Cancer-A Retrospective UK Single-Centre Study.

Metastatic spinal cord compression (MSCC) is a severe complication of cancer that can lead to irreversible neurological impairment, necessitating prompt recognition and intervention. This retrospective, single-centre study aimed to determine the prognostic factors and survival rates among patients presenting with MSCC secondary to lung cancer. We identified 74 patients with epidural metastases-related spinal cord compression and a history of lung cancer through the electronic database of Medway Maritime Hospital in the United Kingdom (UK), spanning the period from April 2016 to September 2021. Among them, 39 were below 55 years old, while 35 were aged 55 years or older; 24 patients were diagnosed with small cell lung cancer (SCLC), and 50 patients had non-small cell lung cancer (NSCLC). The median overall survival (OS) was 5.5 months, with 52 out of 74 patients dying within 6 months of diagnosis with MSCC. For the entire cohort, the statistically significant variables on multi-variate analysis were cancer type (NSCLC had improved OS), the number of involved vertebrae (one to two vertebrae involvement had improved OS), and the time taken to develop motor deficits (≤10 days to develop motor deficits had worsened OS). For the NSCLC cohort, the statistically significant variables on multivariate analysis were molecular alterations (patients with epidermal growth factor receptor (EGFR) mutation), pre-treatment ambulatory status, Eastern Cooperative Oncology Group (ECOG) performance status, and the time taken to develop motor deficits. Within the entire cohort, patients diagnosed with NSCLC and spinal metastases affecting one to two vertebrae exhibited enhanced OS. Within the NSCLC subgroup, those with EGFR mutations who were ambulatory and possessed an ECOG performance status of 1-2 demonstrated improved OS. In both the entire cohort and the NSCLC subgroup, the development of motor deficits within a period of ≤10 days was associated with poor OS.

Investigations of the distant metastatic non-small cell lung cancer without local lymph node involvement: Real world data from a large database.

This study aimed to investigate the presentations and survival outcomes of the distant metastatic non-small cell lung cancer (NSCLC) without lymph node involvement to obtain a clearer picture of this special subgroup of metastatic NSCLC. A least absolute shrinkage and selection operator (LASSO) penalized Cox regression analysis was used to select the prognostic variables. A nomogram and corresponding risk-classifying systems were constructed. The C-index and calibration curves were used to evaluate the performance of the model. Overall survival (OS) curves were plotted using the Kaplan-Meier method, and the log-rank test was used to compare OS differences between groups. Propensity score matching (PSM) was performed to reduce bias. A total of 12 610 NSCLC patients with M1 category (N0 group: 3045 cases; N1-3 group: 9565 cases) were included. Regarding the N0 group, multivariate analysis demonstrated that age, sex, race, surgery, grade, tumor size, and M category were independent prognostic factors. A nomogram and corresponding risk-classifying systems were formulated. Favorable validation results were obtained from the C-index, calibration curves, and survival comparisons. Survival curves demonstrated that N0 NSCLC patients had better survival than N1-3 NSCLC patients both before and after PSM. Furthermore, the survival of resected N0M1 patients was superior to that of those without surgery. In this study, a prognostic nomogram and risk-classifying systems designed for the T1-4N0M1 NSCLC patients showed acceptable performance. Primary lung tumor resection might be a feasible treatment for this population subset. Additionally, we proposed that lymph node stage might have a place in the forthcoming tumor-node-metastasis (TNM)staging proposal for NSCLC patients with M1 category.

Phase I trial of KN046, a novel bispecific antibody targeting PD-L1 and CTLA-4 in patients with advanced solid tumors

BackgroundKN046 is a novel bispecific antibody targeting programmed death ligand 1 (PD-L1) and cytotoxic T lymphocyte-associated protein 4 (CTLA-4). This multicenter phase I trial investigated the safety, tolerability, pharmacokinetics (PK),...

Evolution of the Targeted Therapy Landscape for Cholangiocarcinoma: Is Cholangiocarcinoma the 'NSCLC' of GI Oncology?

In the past two decades, molecular targeted therapy has revolutionized the treatment landscape of several malignancies. Lethal malignancies such as non-small cell lung cancer (NSCLC) have become a model for precision-matched immune- and gene-targeted therapies. Multiple small subgroups of NSCLC defined by their genomic aberrations are now recognized; remarkably, taken together, almost 70% of NSCLCs now have a druggable anomaly. Cholangiocarcinoma (CCA) is a rare tumor with a poor prognosis. Novel molecular alterations have been recently identified in patients with CCA, and the potential for targeted therapy is being realized. In 2019, a fibroblast growth factor receptor 2 (FGFR2) inhibitor, pemigatinib, was the first approved targeted therapy for patients with locally advanced or metastatic intrahepatic CCA who had FGFR2 gene fusions or rearrangement. More regulatory approvals for matched targeted therapies as second-line or subsequent treatments in advanced CCA followed, including additional drugs that target FGFR2 gene fusion/rearrangement. Recent tumor-agnostic approvals include (but are not limited to) drugs that target mutations/rearrangements in the following genes and are hence applicable to CCA: isocitrate dehydrogenase 1 (IDH1); neurotrophic tropomyosin-receptor kinase (NTRK); the V600E mutation of the BRAF gene (BRAFV600E); and high tumor mutational burden, high microsatellite instability, and gene mismatch repair-deficient (TMB-H/MSI-H/dMMR) tumors. Ongoing trials investigate HER2, RET, and non-BRAFV600E mutations in CCA and improvements in the efficacy and safety of new targeted treatments. This review aims to present the current status of molecularly matched targeted therapy for advanced CCA.

Toripalimab plus chemotherapy vs. chemotherapy in patients with advanced non-small-cell lung cancer: A cost-effectiveness analysis.

Background: The potency and safety of toripalimab combination with chemotherapy (TC) as the first-line therapy for advanced non-small cell lung cancer (NSCLC) have been demonstrated in the CHOICE-01 study. Our research explored whether TC was cost-effective compared to chemotherapy alone from the Chinese payer perspective. Materials and methods: Clinical parameters were obtained from a randomized, multicenter, registrational, placebo-controlled, double-blind, phase III trial. Standard fee databases and previously published literature were used to determine costs and utilities. A Markov model with three mutually exclusive health statuses (progression-free survival (PFS), disease progression, and death) was used to predict the disease course. The costs and utilities were discounted at 5% per annum. The main endpoints of the model included cost, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER). Univariate and probabilistic sensitivity analyses were performed to investigate the uncertainty. Subgroup analyses were performed to verify the cost-effectiveness of TC in patients with squamous and non-squamous cancer. Results: TC combination therapy yielded an incremental 0.54 QALYs with an incremental cost of $11,777, compared to chemotherapy, giving rise to ICERs of $21,811.76/QALY. Probabilistic sensitivity analysis revealed that TC was not favorable at 1 time GDP per capita. With a prespecified willingness-to-pay threshold (WTP) of three times the GDP per capita, combined treatment had a 100% probability of being cost-effective and had substantial cost-effectiveness in advanced NSCLC. Probabilistic sensitivity analyses showed that TC was more likely to be accepted with a WTP threshold higher than $22,195 in NSCLC. Univariate sensitivity analysis showed that the utility of PFS state, crossover proportions of the chemotherapy arm, cost per cycle of pemetrexed treatment, and discount rate were the dominant influencing factors. Subgroup analyses found that in patients with squamous NSCLC, the ICER was $14,966.09/QALY. In the non-squamous NSCLC, ICER raised to $23,836.27/QALY. ICERs were sensitive to the variance of the PFS state utility. TC was more likely to be accepted when WTP increases exceeded $14,908 in the squamous NSCLC subgroup and $23,409 in the non-squamous NSCLC subgroup. Conclusion: From the perspective of the Chinese healthcare system, TC may be cost-effective in individuals with previously untreated advanced NSCLC at the prespecified WTP threshold compared to chemotherapy, and more significant in individuals with squamous NSCLC, which will provide evidence for clinicians to make the best decisions in general clinical practice.

ALK-driven NSCLC: A narrative review - Part I

ABSTRACT Anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC) is a molecularly distinct subgroup of oncogene-addicted NSCLC, accounting for 3-5% of cases. These are mainly genomic rearrangements resulting in a fusion oncoprotein, thus causing persistent constitutive signaling. Recent developments and approvals of various generations of ALK inhibitors have revamped the therapeutic and prognostic landscape of this disease entity. For the preparation of this review, we searched various databases such as PubMed, Embase, and Scopus, using the keywords “ALK,” “ALK crizotinib,” “Oncogene NSCLC,” and “Alectinib,” and we finally included 46 articles. In this review, we describe the molecular biology and pathologic and clinical characteristics of ALK-rearranged NSCLC. The detection methods, therapeutic strategies, and trials will be discussed in the next part of this biomarker review series.

Concurrent classic driver oncogenes mutation with ROS1 rearrangement predicts superior clinical outcome in NSCLC patients.

There is high mortality rate and poor prognosis in lung cancer, especially non-small-cell lung cancer (NSCLC). Recent study showed that concurrent classic driver oncogene mutation with ROS1 rearrangement was found in NSCLC patients. However, whether this would affect the development and prognosis of NSCLC is still unclear. To explore the clinical characteristics and prognosis of NSCLC patients harboring concurrent classic driver oncogene mutation with ROS1 rearrangement. A retrospective study was conducted on 220 patients diagnosed with NSCLC. All samples were screened for EGFR and KRAS using amplification-refractory mutation system assay, and for ALK, ROS1 using RT-PCR. The clinical characteristics and clinical outcomes of concurrent gene alterations with ROS1 rearrangement were analyzed. In 220 patients, 12 (5.45%) were ROS1 rearrangement, who tend to be younger, non-smokers. The mutation rates of EGFR, KRAS, ALK and ROS1 in NSCLC were 28.64%, 1.82%, 3.64% and 5.45%, respectively. ROS1 rearrangement was identified to co-occur in 5 (2.27%) NSCLC patients. ROS1/EGFR co-alterations were found in 3.17% of NSCLC patients, 16.67% of ROS1-positive NSCLC patients. Concomitant ROS1/ALK rearrangement constituted 37.50% in ALK-positive patients, and 25.00% in ROS1-positive patients. SDC4-ROS1 was the most common fusion partner in concurrent ROS1 rearrangement patients. The median overall survival of NSCLC with concurrent ROS1 rearrangement group and single ROS1 rearrangement group were 25 months and 14 months. Concurrent driver oncogenes mutation with ROS1 rearrangement defines a unique subgroup of NSCLC. Patients with concomitant ROS1 rearrangement might have a better prognosis.

Stage IV non-small cell lung cancer among young individuals: Incidence, presentations, and survival outcomes of conventional therapies.

There is a paucity of data published on the clinicopathological features and prognosis of stage IV non-small cell lung cancer (NSCLC) patients aged ≤45 years. Herein, we evaluated a large clinical series in an effort to provide a clearer picture of this population. The least absolute shrinkage and selection operator (LASSO)-penalized Cox regression model was performed to identify prognostic factors for NSCLC among individuals aged ≤45 years. The Kaplan-Meier method with log-rank test was used to compare overall survival (OS) differences between groups. Competing risk analysis with the Fine-Gray test was used to analyze cancer-specific survival (CSS) differences. Propensity score matching (PSM) was used to minimize selection bias. Incidence-rate analyses, including 588,680 NSCLC cases (stage IV, 233,881; age ≤ 45 years stage IV, 5,483; and age > 45 years stage IV, 228,398) from 2004 to 2015, showed that the incidence of stage IV NSCLC among young individuals decreased over the years. In comparative analyses of clinical features and survival outcomes, a total of 48,607 eligible stage IV cases (age ≤ 45 years stage IV, 1,390; age > 45 years stage IV, 47,217) were included. The results showed that although patients in the young cohort were more likely to be diagnosed at advanced stages, they were also more likely to receive aggressive treatments. In addition, the survival rates of the young patients were superior to those of the older patients both before and after PSM. Stage IV NSCLC patients aged ≤45 years comprise a relatively small but special NSCLC subgroup. Although this population had better survival outcomes than older patients, these patients deserve more attention due to their young age and the significant socioeconomic implications.

Radiolabeled EGFR TKI as predictive imaging biomarkers in NSCLC patients - an overview.

Non-small cell lung cancer (NSCLC) has one of the highest cancer-related mortality rates worldwide. In a subgroup of NSCLC, tumor growth is driven by epidermal growth factor receptors (EGFR) that harbor an activating mutation. These patients are best treated with EGFR tyrosine kinase inhibitors (EGFR TKI). Identifying the EGFR mutational status on a tumor biopsy or a liquid biopsy using tumor DNA sequencing techniques is the current approach to predict tumor response on EGFR TKI therapy. However, due to difficulty in reaching tumor sites, and varying inter- and intralesional tumor heterogeneity, biopsies are not always possible or representative of all tumor lesions, highlighting the need for alternative biomarkers that predict tumor response. Positron emission tomography (PET) studies using EGFR TKI-based tracers have shown that EGFR mutational status could be identified, and that tracer uptake could potentially be used as a biomarker for tumor response. However, despite their likely predictive and monitoring value, the EGFR TKI-PET biomarkers are not yet qualified to be used in the routine clinical practice. In this review, we will discuss the currently investigated EGFR-directed PET biomarkers, elaborate on the typical biomarker development process, and describe how the advances, challenges, and opportunities of EGFR PET biomarkers relate to this process on their way to qualification for routine clinical practice.

EP08.01-051 Clinical Characterization and Outcomes of Non Small Cell Lung Cancer with HER2 Alterations in the Era of Immunotherapy

HER2-altered Non Small Cell Lung Cancer (NSCLC) is a rare subgroup (2-4%) of NSCLC. Previous studies, using small cohorts, report poor outcomes and shorter survival in HER2-altered NSCLC compared to the other subtypes of NSCLC. However, most studies were done before immunotherapy is used as the first-line therapy in stage IV NSCLC. The detailed outcomes of those patients treated under the most recent guidelines are largely unknown.

Parameters of Dual-layer Spectral Detector CT Could be Used to Differentiate Non-Small Cell Lung Cancer from Small Cell Lung Cancer.

Differentiating non-small cell lung cancer (NSCLC) from small cell lung cancer (SCLC) remains a substantial challenge. This study aimed at evaluating the performance of dual-layer spectral detector CT (DLCT) in differentiating NSCLC from SCLC. Spectral images of 247 cancer patients confirmed by pathology were retrospectively analyzed in both the arterial phase (AP) and the venous phase (VP), including 197 cases of NSCLC and 50 cases of SCLC. Effective atomic number (Z-eff), Spectral CT-Mono Energetic (MonoE [40keV~90keV]), iodine density (ID) and thoracic aorta iodine density (IDaorta) in contrast-enhanced images were measured and compared between the SCLC and NSCLC subgroups of tumors. The slope of the spectral curve (λ, interval of 10 keV) and normalized iodine density (NID) were also calculated between the SCLC and NSCLC. Through the statistical analysis, the diagnostic efficiency of each spectral parameter was calculated, and the difference in their efficiency was analyzed. Both in NSCLS and SCLC, all parameters in VP were significantly higher than those in AP (p<0.001), except for λ90. There were significant differences in all spectral parameters between NSCLS and SCLC, both in AP and VP (p < 0.001). Except for VP-λ90, there was no significant difference in ROC curves of all spectral parameters. VP-NID exhibited the best diagnostic performance with an AUC value of 0.917 (95%[CI]: 0.870~0.965), sensitivity and specificity of 92.9% and 80%, and a diagnostic threshold of 0.217. All parameters of DLCT have high diagnostic efficiency in differentiating NSCLC from SCLC except for VP-λ90, and VP-NID has the highest diagnostic efficiency.