Metastatic Non-small Lung Cancer Research Articles

Impact of lung biomarker testing on out-of-pocket costs for metastatic non-small cell lung cancer.

11087 Background: Biomarker testing in metastatic non-small lung cancer (NSCLC) is critical for appropriate selection of therapy options. Claims-based datasets offer real-world information on the use and cost of biomarker testing across the United States. Methods: We used de-identified administrative claims data from Optum’s Clinformatics Data Mart Database (CDM) from 2013 to 2021 to assess for trends in biomarker testing. Eligible patients were adults with two or more lung cancer diagnosis codes and with two or more claims of a secondary malignant neoplasm. Patients were excluded if they had another primary cancer or did not have continuous insurance coverage twelve months prior and six months after diagnosis. We assessed claims-based out-of-pocket (OOP) costs associated with testing and treatment. Descriptive statistics were used to assess biomarker testing rates, and multivariable analyses (MVA) were performed to assess factors associated with testing. Results: A total of 4377 patients with metastatic NSCLC were eligible (mean age 60 years (SD: 8.33 years), 49.6% female, 76.7% former smokers). Testing rates within two months of diagnosis increased from 58.15% in 2013 to 69.96% in 2021. On MVA, biomarker testing was associated with younger age, being non-smokers, living in Mountain geographic region, or having point-of-service insurance plans. Biomarker testing was associated with a median OOP cost of $98 (IQR: $43.87-$306.58). Patients who underwent biomarker testing had a median total OOP cost of all services within 6 months of diagnosis of $3560.20 (IQR: $1538.37-$6199.44) compared to $1979.58 (IQR: $725.75-$4003.06) for those who did not undergo biomarker testing. Conclusions: Using claims data, we find that 70% of patients with metastatic NSCLC undergo biomarker testing within two months of diagnosis with metastatic disease. Most patients undergo biomarker testing early in their treatment course (0-60 days), suggesting that testing is appropriately being obtained early on in their treatment course, but this testing is associated with substantially higher overall OOP costs to patients.

CT-based nomogram for early identification of T790M resistance in metastatic non-small cell lung cancer before first-line epidermal growth factor receptor-tyrosine kinase inhibitors therapy

BackgroundTo evaluate the value of computed tomography (CT) radiomics in predicting the risk of developing epidermal growth factor receptor (EGFR) T790M resistance mutation for metastatic non-small lung cancer (NSCLC) patients before first-line EGFR-tyrosine kinase inhibitors (EGFR-TKIs) therapy.MethodsA total of 162 metastatic NSCLC patients were recruited and split into training and testing cohort. Radiomics features were extracted from tumor lesions on nonenhanced CT (NECT) and contrast-enhanced CT (CECT). Radiomics score (rad-score) of two CT scans was calculated respectively. A nomogram combining two CT scans was developed to evaluate T790M resistance within up to 14 months. Patients were followed up to calculate the time of T790M occurrence. Models were evaluated by area under the curve at receiver operating characteristic analysis (ROC-AUC), calibration curve, and decision curve analysis (DCA). The association of the nomogram with the time of T790M occurrence was evaluated by Kaplan–Meier survival analysis.ResultsThe nomogram constructed with the rad-score of NECT and CECT for predicting T790M resistance within 14 months achieved the highest ROC-AUCs of 0.828 and 0.853 in training and testing cohorts, respectively. The DCA showed that the nomogram was clinically useful. The Kaplan–Meier analysis showed that the occurrence time of T790M difference between the high- and low-risk groups distinguished by the rad-score was significant (p < 0.001).ConclusionsThe CT-based radiomics signature may provide prognostic information and improve pretreatment risk stratification in EGFR NSCLC patients before EGFR-TKIs therapy. The multimodal radiomics nomogram further improved the capability.Relevance statementRadiomics based on NECT and CECT images can effectively identify and stratify the risk of T790M resistance before the first-line TKIs treatment in metastatic non-small cell lung cancer patients.Key points• Early identification of the risk of T790M resistance before TKIs treatment is clinically relevant.• Multimodel radiomics nomogram holds potential to be a diagnostic tool.• It provided an imaging surrogate for identifying the pretreatment risk of T790M.Graphical

A Critical Review of the Prognostic and Predictive Implications of KRAS and STK11 Mutations and Co-Mutations in Metastatic Non-Small Lung Cancer.

The Kirsten rat sarcoma viral oncogene homolog (KRAS) and serine/threonine kinase 11 (STK11) co-mutations are associated with the diverse phenotypic and heterogeneous oncogenic subtypes in non-small cell lung cancer (NSCLC). Due to extensive mixed evidence, there needs to be a review of the recent KRAS and STK11 mutation literature to better understand the potential clinical applications of these genomic biomarkers in the current treatment landscape. This critical review highlights the clinical studies that have elucidated the potential prognostic and predictive implications of KRAS mutations, STK11 mutations, or KRAS/STK11 co-mutations when treating metastatic NSCLC across various types of treatments (e.g., immune checkpoint inhibitors [ICIs]). Overall, KRAS mutations are associated with poor prognoses and have been determined to be a valid but weak prognostic biomarker among patients diagnosed with NSCLC. KRAS mutations in NSCLC have shown mixed results as a predictive clinical biomarker for immune checkpoint inhibitor treatment. Overall, the studies in this review demonstrate that STK11 mutations are prognostic and show mixed results as predictive biomarkers for ICI therapy. However, KRAS/STK11 co-mutations may predict primary resistance to ICI. Prospective KRAS/STK11-biomarker-driven randomized trials are needed to assess the predictive effect of various treatments on the outcomes for patients with metastatic NSCLC, as the majority of the published KRAS analyses are retrospective and hypothesis-generating in nature.

MT13 In-House Versus Send-out Next Generation Sequencing Testing for Metastatic Non-Small Cell Lung Cancer Patients. a Budget Impact Analysis

Next generation sequencing (NGS) is used to identify genetic markers of disease, making it important for personalized cancer treatment. NGS testing can occur in external laboratories (send-out) or in the hospital (in-house). We analyzed the impact on hospital budgets if they invested in increased in-house testing for metastatic non-small lung cancer (mNSCLC).

Les patients ALK et ROS1 : quelle séquence ?

Crizotinib, an inhibitor of ALK tyrosine kinase activity (ALKi), available as an oral compound is more efficient and better tolerated than chemotherapy, in first-line setting treatment of patients with metastatic non-small lung cancer with ALK rearrangement (NSCLC ALK+). A resistance occurs systematically. In one-third of cases such resistance comes from the emergence of clones with a resistance mutation in ALK gene sequence, while in half of the cases some bypass pathways become hyper-activated, when one third of cases consists of a brain progression. The new generation ALKi (ceritinib, alectinib, brigatinib, lorlatinib, ensartinib) show good efficacy for resistance to crizotinib. Alectinib and brigatinib, two second-generation ALKi, and lorlatinib, a third generation ALKi, all showed their superiority as compared with crizotinib, in first line setting treatment, in terms of progression-free survival, survival without brain progression and control of brain disease, in large phase 3 trials. Alectinib and brigatinib thus became the standard of care in frontline. Lorlatinib, is very efficient in first-line setting either and might become a new treatment option. Crizotinib remains the reference treatment in advanced NSCLC ROS1+. The treatment at relapse upon crizotinib in such NSCLC ROS1+ patients is not currently consensual.1877-1203/© 2022 SPLF. Published by Elsevier Masson SAS. All rights reserved.

EP08.02-040 Dacomitinib Induced Febrile Neutropenia: a Rare Serious Adverse Event

Dacomitinib, a second-generation oral irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, has improved overall survival in metastatic non-small lung cancer patients harbouring EGFR mutations. The common adverse reactions associated with dacomitinib are diarrhoea and dermatological toxicities while severe febrile neutropenia has not been reported in literature.

Impact of the Nuclear Envelope on Malignant Transformation, Motility, and Survival of Lung Cancer Cells.

Nuclear pore complexes (NPCs) selectively mediate all nucleocytoplasmic transport and engage in fundamental cell‐physiological processes. It is hypothesized that NPCs are critical for malignant transformation and survival of lung cancer cells, and test the hypothesis in lowly and highly metastatic non‐small human lung cancer cells (NSCLCs). It is shown that malignant transformation is paralleled by an increased NPCs density, and a balanced pathological weakening of the physiological stringency of the NPC barrier. Pharmacological interference using barrier‐breaking compounds collapses the stringency. Concomitantly, it induces drastic overall structural changes of NSCLCs, terminating their migration. Moreover, the degree of malignancy is found to be paralleled by substantially decreased lamin A/C levels. The latter provides crucial structural and mechanical stability to the nucleus, and interacts with NPCs, cytoskeleton, and nucleoskeleton for cell maintenance, survival, and motility. The recent study reveals the physiological importance of the NPC barrier stringency for mechanical and structural resilience of normal cell nuclei. Hence, reduced lamin A/C levels in conjunction with controlled pathological weakening of the NPC barrier stringency may facilitate deformability of NSCLCs during the metastasis steps. Modulation of the NPC barrier presents a potential strategy for suppressing the malignant phenotype or enhancing the effectiveness of currently existing chemotherapeutics.

Comparison of Different EGFR Gene Mutation Status in Patients with Metastatic Non-Small Lung Cancer After First-Line EGFR-TKIs Therapy and Analyzing Its Relationship with Efficacy and Prognosis.

PurposeThe purpose of this study is to compare the different EGFR mutation status in patients with metastatic non-small cell lung cancer (NSCLC) after first-line EGFR-TKIs therapy and analyze its relationship with efficacy and prognosis.Patients and MethodsThis study retrospectively analyzed the data of patients with metastatic NSCLC harboring EGFR mutation in the Affiliated Tumor Hospital of Guangxi Medical University from June 2016 to December 2020. Samples were collected before treatment and at the time of disease progression after first-line EGFR-TKIs therapy. Amplification refractory mutation system (ARMS) PCR and next-generation sequencing (NGS) were used to detect EGFR mutation. ORR, DCR, and PFS of different EGFR mutation groups were compared.ResultsThe EGFR mutation rate of re-biopsy was 60.23%. The inconsistency rate of EGFR mutations in the same and different simple types was 72.22% (26/36) and 92.31% (48/52), respectively. Alterations in terms of EGFR mutations were divided into four groups: Group A: EGFR-sensitive mutation negative and T790M negative (39.77%); Group B: EGFR-sensitive mutation positive and T790M negative (18.19%); Group C: EGFR-sensitive mutation negative and T790M positive (36.36%); Group D: EGFR-sensitive mutation positive and T790M positive (5.68%). The differences between the four groups in ORR and DCR were not statistically significant (P>0.05). The median PFS of all patients was 10.65 months. PFS of Group A, B, C, and D was 12.26, 7.96, 10.55, and 13.81 months, respectively, with statistical significance (Log rank P = 0.014).ConclusionEGFR mutation status in metastatic NSCLC patients receiving the first- and second-generation TKIs after disease progression show diversity. Monitoring the EGFR mutation changes is of great importance for subsequent clinical decision-making and exploring the underlying mechanisms of acquired resistance.

Capmatinib improves insulin sensitivity and inflammation in palmitate-treated C2C12 myocytes through the PPARδ/p38-dependent pathway

Capmatinib (CAP) has been used to treat metastatic non-small lung cancer (NSCL) and suppress inflammation. It causes hypoglycemia in NSCL patients. Therefore, it is expected that CAP improves inflammation-mediated insulin resistance due to its anti-inflammatory effect. However, the impacts of CAP on insulin signaling in skeletal muscle cells have not yet been fully elucidated. Herein, we investigated the effect of CAP on insulin resistance in palmitate-treated C2C12 myocytes and explored the related molecular mechanisms. We found that treatment of C2C12 myocytes with CAP reversed palmitate-induced impairment of insulin signaling and glucose uptake. CAP treatment ameliorated phosphorylation of inflammatory markers, including NFκB and IκB, in palmitate-treated C2C12 myocytes. Further, it augmented PPARδ expression and suppressed palmitate-induced p38 phosphorylation in a dose-dependent manner. siRNA-mediated suppression of PPARδ abolished the effects of CAP on palmitate-induced insulin resistance and inflammation as well as p38 phosphorylation. Therefore, it has been shown that CAP treatment ameliorates insulin resistance in palmitate-treated C2C12 myocytes via PPARδ/p38 signaling-mediated suppression of inflammation. These results may represent a novel therapeutic approach that could halt insulin resistance and type 2 diabetes.

Comparison of Resistance Spectra after First and Second Line Osimertinib Treatment Detected by Liquid Biopsy.

Simple SummarySince the recent approval of osimertinib, a third generation tyrosine kinase inhibitor (TKI) targeting EGFR in non-small cell lung cancer (NSCLC), tracing the resistance mechanisms that yield to failure of osimertinib has become of interest. As the spectrum of osimertinib-resistance related genomic alterations appears significantly more diverse compared to first and second generation TKI, comprehensive, and preferably non-invasive molecular diagnostic methods are required for the detection of resistance mechanisms. In this study, we present molecular results of 56 NSCLC patients during disease progression on first and second line osimertinib treatment using a hybrid capture (HC) next generation sequencing (NGS) based liquid biopsy approach. We show examples of polyclonal resistance development which leads to the presence of multiple resistance mechanisms in the same patient, and highlight the clinical utility of HC NGS over single gene testing.Since 2009, several first, second, and third generation EGFR tyrosine kinase inhibitors (TKI) have been approved for targeted treatment of EGFR mutated metastatic non-small lung cancer (NSCLC). A vast majority of patients is improving quickly on treatment; however, resistance is inevitable and typically occurs after one year for TKI of the first and second generation. Osimertinib, a third generation TKI, has recently been approved for first line treatment in the palliative setting and is expected to become approved for the adjuvant setting as well. Progression-free survival (PFS) under osimertinib is superior to its predecessors but its spectrum of resistance alterations appears significantly more diverse compared to first and second generation EGFR TKI. As resistance mechanisms to osimertinib are therapeutically targetable in some cases, it is important to comprehensively test for molecular alterations in the relapse scenario. Liquid biopsy may be advantageous over tissue analysis as it has the potential to represent tumor heterogeneity and clonal diversification. We have previously shown high concordance of hybrid capture (HC) based next generation sequencing (NGS) in liquid biopsy versus solid tumor biopsies. In this study, we now present real-word data from 56 patients with metastatic NSCLC that were tested by liquid biopsy at the time of disease progression on mostly second line treated osimertinib treatment. We present examples of single and multiple TKI resistance mechanisms, including mutations in multiple pathways, copy number changes and rare fusions of RET, ALK, FGFR3 and BRAF. In addition, we present the added value of HC based NGS to reveal polyclonal resistance development at the DNA level encoding multiple EGFR C797S and PIK3CA mutations.

Moving beyond epidermal growth factor receptor resistance in metastatic non-small cell lung cancer - a drug development perspective.

Epidermal Growth Factor Receptor (EGFR) mutations are the most common targetable oncogenic driver mutation in metastatic non-small lung cancer (NSCLC). There have been significant advances in the management of metastatic EGFR-mutant NSCLC from the advent of first and second generation EGFR inhibitors to, more recently, the third-generation inhibitor osimertinib. Osimeritinib is now established as first-line therapy on the basis of improved outcomes compared to first and second generation agents. However, despite excellent initial response rates, responses may not be durable due to the development of acquired resistance. Understanding these mechanisms of resistance is critical to the development of rational drug and drug combinations capable of circumventing them. We discuss the major mechanisms of resistance to first, second and third generation EGFR TKIs. The potential of drug combinations utilising chemotherapy, immunotherapy and anti-angiogenic drugs are explored. We examine strategies to aid drug development, including circulating tumour DNA and novel trial designs.

DIAGNOSTIC CAPABILITIES OF FINE NEEDLE ASPIRATION OF LYMPH NODES METASTASES OF PRIMARY PULMONARY LYMPHOEPITHELIAL CARCINOMAS

Introduction. Primary pulmonary lymphoepithelial carcinoma is a poorly differentiated squamous cell carcinoma admixed with variable amounts of lymphoplasmacytic infiltrate, frequently associated with EBV. It is a rare cancer and have a better prognosis than other non-small cell lung cancer. The tumor can mimic metastatic non-keratinizing SCC of the naso-pharynx, poorly differentiated non-small cell carcinoma and NUT carcinoma arising in the lung, and non-Hodgkin lymphomas. Materials and methods. A 75-year-old man presented with peripheral mass of left lower lobe, maximal diameter was 5.1 cm, involving lingula and medial pleura, with mediastinal, and retroperitoneal lymphadenopathy revealed by computer tomography. Fine needle aspiration-EBUS was performed from hilar and interlobar lymph nodes. Papanicolaou smears and cell blocks were prepared. Additional CT-guided cor-needle biopsy and FNA were performed from lung lesion later. Results. A few large malignant epithelial cells, consistent with non-small lung cancer, were found on a background of lymphocytes in fine-needle aspiration from lymph nodes. Immunostain results: Pan-CK (AE1/AE3), p63 and Ki67 were positive in malignant cells, leukocyte common antigen (CD45) was positive in lymphocytes (negative in tumor cells), and negative markers were TTF1, chromogranin and synaptophysin. Cytological diagnosis was metastatic non-small lung cancer, favor squamous cell carcinoma. Biopsy and aspiration from left lung showed syncytial groups of large malignant epithelial cells with scant cytoplasm and prominent nucleoli on a background of prominent inflammatory infiltrate,consistent with lymphoepithelial carcinoma. Conclusion. It is impossible to correctly diagnose metastasis of lymphoepithelial carcinoma in lymph node by FNA only without FNA or biopsy of primary lesion, because cytological features and immunostains are identical to non-keratinizing squamous cell carcinoma.

Prognostic value of HLA-I homozygosity in patients with non-small cell lung cancer treated with single agent immunotherapy

BackgroundWe aimed to assess the impact of genomic human leukocyte antigen (HLA)-I/II homozygosity on the survival benefit of patients with unresectable locally advanced, metastatic non-small lung cancer treated by single-agent...

301MO Genomic HLA as a predictive biomarker for survival among non-small cell lung cancer patient treated with single agent immunotherapy

We aimed to assess the role of genomic HLA-I/II homozygosity in the overall survival benefit in patients with unresectable locally advanced, metastatic non-small lung cancer treated by single agent PD1/PDL1 inhibitors...

Early palliative care of non-small cell lung cancer in the context of immunotherapy.

The most common cause of mortality due to malignant neoplasms in the general population around the world is lung cancer. In the last 10 years, there has been an enormous improvement in the treatment of this disease, mainly due to the immunotherapy that activates the immune system to fight cancer. Patients with metastatic non-small cell lung cancer are a special group of patients requiring not only cancer treatment but also considerable support in the treatment of cancer-related problems, as well as comorbidities. Early palliative care is important in this area. In addition, there is certain evidence that medicines most commonly administered in palliative care may lower the efficacy of immunotherapy. The present review article compares information on the prolonging of life after early hospice care, which has become the foundation of current standards of management in patients with metastatic lung cancer, and reports of decreased efficacy of the immunotherapy due to the administration of major palliative care medications.

LBA14 - Genomic HLA heterozygosity as a predictive marker for survival in lung cancer patients post immunotherapy

BackgroundWe aimed to assess the role of genomic HLA-I/II heterozygosity in the overall survival benefit in patients with unresectable locally advanced, metastatic non-small lung cancer treated by PD1/L1 inhibitors. MethodsWe collected blood from 170 advanced lung cancer patients treated with immunotherapy at two major oncology centres in Western Australia. High quality DNA was extracted from white blood cells and used for HLA-I/II typing. Information of tumour PDL1 status, pre-treatment neutrophil to lymphocyte ratio (NLR) and sex were identified. Each of those variables were correlated independently then in a multivariate analysis with OS. Correlation between HLA heterozygosity and response was assessed using Fisher exact. Patients with reduced or stable disease for 6 or more months were considered as responders. ResultsOur data matured for 146 patients treated with anti-PD1/L1 therapy. We found that heterozygosity at all HLA-I loci had a favorable statistical trend towards better OS(HR = 0.5,P=0.06). However, heterozygosity at all HLA-II loci was not associated with OS(HR = 0.91,P=0.76). While response rate was higher amongst heterozygous patients especially at HLA-I (53.4% vs 45.6%), it was not statistically significant. NLR>5 was associated with statistically significant worse survival (HR = 2.22,P=0.009). This effect was driven by the patients with PDL1≥50% (HR = 3.86, P = 0.01 vs HR = 0.7, P = 0.5 for patients with PDL1<50%). Similarly, the effect of sex was seen mainly among patients with PDL1≥50%, with men more likely to have better OS than women (HR = 0.36, P = 0.06 vs HR = 1.1, P = 0.89 in the group of patients with PDL1<50%). A multivariate analysis showed that all three variables to be statistically significant predictors of survival.TableLBA14TableVariableHR(95% CI)P valueSex1.9(1.1-3.5)0.028NRLD(≥5vs<5)7.1(1.8-27.3)0.004Homozygosity at ≥ 1 HLA-I0.3(0.8-0.9)0.039 ConclusionsOur analysis suggest that OS among advanced lung cancer patients treated with immunotherapy is more likely to be influenced by homozygosity at HLA-I loci. Women with PDL1≥50%, NLR>5 and homozygous at ≥ 1 HLA-I locus possibly carries the worse prognosis when treated with immunotherapy alone and might benefit from treatment escalation. Editorial acknowledgementA/Prof Elin Gray, Edith Cowan University, Western Australia. Legal entity responsible for the studySouth Metropolitan Health Service - WA Health. FundingFiona Stanley Hospital (FSH) and Sir Charles Gairdner Hospital (SCGH) DisclosureAll authors have declared no conflicts of interest.

First-line pembrolizumab in programmed death ligand 1 positive non-small cell lung cancer

In these past few years, immune checkpoint inhibitors (ICI) in locally advanced or metastatic non-small cell lung cancer (NSCLC) have fundamentally changed the prognosis for some patients.

Neutrophils lymphocyte ratio role in predicting response to checkpoint inhibitors in metastatic non-small lung cancer.

e20646 Background: There have been numerous advances in the management of metastatic lung cancer, including targeted therapy against certain mutations in cancer cells and later developing immune therapy with check point inhibitors.From the pre-immune therapy era, a simple blood test allowing the calculation of the neutrophil-to-lymphocyte ratio (NLR) was established as a strong prognostic marker associated with worse overall survival (OS) in several tumor types including non-small cell lung cancer (NSCLC). Methods: We have retrospectively reviewed electronic medical records for patients with Metastatic NSCLC whom received at least one dose of Checkpoint Inhibitors from January 2014 till January 2019 in Van Eslander Cancer Center.The analysis was done using SPSS v. 25.0 and a p-value of 0.05 or less was considered to indicate statistical significance. A univariant analysis was done using Student’s t-test, the Mann-Whitney U test and the chi-squared test. Survival analysis was conducted using Kaplan Meier methodology as well as Cox proportional hazards models. Results: There were 80 patients with metastatic NSCLC received at least one dose of a checkpoint inhibitor. Median age was 63.9 ± 9.3; Males were 45%; Whites were 62.5%. 67.5% of patient had adenocarcinoma and 24% had squamous cell carcinoma. Twenty patients had brain metastasis (25%) and nineteen patients had liver metastasis (24.6%). Eleven patients (13.8%) had PDL-1 greater than 50% and 11 patients (13.8%) had PDL-1 between 1%-50% and 22 patients (27.5%) had negative PD-L1 status. 18.8% received immunotherapy as a first-line treatment and 65% got immunotherapy on their second line and 16.3% had immunotherapy as the third line of treatment or more. Sixty-one patients (76.2%) received Nivolumab and nineteen patients (23.8%) received pembrolizumab. Mean duration of immunotherapy was 13.7 months ± 20.7. Mean NLR was 6.1 ± 5. Patient with NLR &gt; 5:1 had statistically significant higher progression-free survival (PFS) 27.5 months compared to 12 months P = 0.02. Also, Patients with baseline NLR &gt; 5:1 had a trend toward higher median overall survival (OS) but was not statistically significant 41 months compared to 12 months P = 0.08. Conclusions: Our data showed similar finding to Bagley et al and other retrospective analysis from multiple institutes showing that NLR could be a good predictor of response to checkpoint inhibitors And a cutoff of NLR higher than 5.1 was associated with statistically significant better PFS and a trend towards a better OS.

Prognostic significance of gamma-glutamyl transferase in patients with metastatic non-small cell lung cancer

ABSTRACTBackground: The prognostic significance of serum gamma-glutamyl transferase (GGT) level at diagnosis in patients with metastatic non-small lung cancer (NSCLC) is not clear. We aimed to assess the relationship between serum GGT level and overall survival (OS) and progression-free survival (PFS) in this patient population.Methods: Data of patients with metastatic NSCLC who were admitted to the medical oncology clinic of our hospital during April 2013–December 2017 were retrospectively analyzed. Patients were divided into two groups based on GGT levels, normal and high (as defined by normal reference levels), and then compared.Results: Significant differences between the high and normal GGT level groups were found regarding female sex, Eastern Cooperative Oncology Group performance score, weight loss at the time of diagnosis, and lactate dehydrogenase level (p < 0.05). The high GGT group had a shorter median OS (11.5 vs. 3.4 months, p < 0.001) and PFS (7.8 vs. 3.0 months, p = 0.001). High GGT level is an independent risk factor for OS (hazard ratio [HR] 2.270; 95% confidence interval [CI], 1.398–3.686; p < 0.001) and PFS (HR 2.489; 95% CI, 1.323–4.684; p = 0.005).Conclusions: High serum GGT level is an independent prognostic factor for OS and PFS in metastatic NSCLC patients.

Genotype change and mechanism of drug resistance of metastatic non-small cell lung cancer

Objective To investigate the difference of genotype between primary tumor and metastatic tumor and the mechanism of chemoresistance in metastatic non-small cell lung cancer (NSCLC). Methods The mRNA expression level of frequently mutated genes in primary and metastatic tumors was detected by quantitive real-time quantitative polymerase chain reaction (Real-time PCR). Real-time PCR was applied to the primary tumor (P1), culture-expanded P5 and P10 cells. Scratch and Transwell migration assays were performed to study the migration ability. Cells in different groups were treated with chemotherapeutics. The difference of high frequency mutated gene was detected after three generations. Scratch assays and Transwell migration assays were performed to study the migration ability. Results The Real-time PCR results showed that the RB1 expression (0.72±0.05, (P=0.013) in primary tumor decreased and the expression of RB1 (0.75±0.02, P=0.004) and p53 (0.23±0.07, P=0.021) in metastatic tumor decreased also. After expanded, cultured cells didn’t show difference in the results of Real-time PCR, Transwell migration assay and scratch assay. When exposed to chemotherapy drugs, the expression of KRAS (3.43±0.31, P=0.002) increased in primary tumor, phosphatase and tensin homologue deleted on chromosome ten (PTEN) (0.43±0.25, P= 0.015) expression decreased significantly and migration capability was enhanced (P=0.048, 0.011). Conclusion The gene mutation in primary tumor was different with metastatic tumor of NSCLC, which occurred during the invasive process. Cancer cells could produce chemoresistance through inducing novel mutation. Key words: Non-small cell lung cancer; Metastatic tumor; Gene mutation; Chemoresistance