Diagnosis Of Non-small Cell Lung Cancer Research Articles

Economic burden of early-stage non-small-cell lung cancer: an assessment of healthcare resource utilization and medical costs.

Aim: To quantify the economic burden of early-stage non-small-cell lung cancer (NSCLC) among patients with and without adjuvant therapy. Methods: All-cause and NSCLC-related healthcare resource utilization and medical costs were assessed among patients with resected stage IB-IIIA NSCLC in the SEER-Medicare database (1 January2011-31 December2019), from NSCLC diagnosis to death, end of continuous enrollment, or end of data availability (whichever occurred first). Results: Patients receiving adjuvant therapy had the lowest mean NSCLC-related medical costs (adjuvant [n=1776]: $3738; neoadjuvant [n=56]: $5793; both [n=47]: $4818; surgery alone [n=3478]: $4892, per-person-per-month), driven by lower NSCLC-related hospitalization rates. Conclusion: Post-surgical management of early-stage NSCLC was associated with high economic burden. Adjuvant therapy was associated with numerically lower medical costs over surgical resection alone.

Association Between Demographic and Socioeconomic Factors and Diagnosis of Advanced Non-small Cell Lung Cancer: An Analysis of the National Cancer Database.

Introduction Lung cancer is a prevalent and potentially lethal cancer. The stage at initial presentation for diagnosis predicts mortality and helps to guide treatment options. Thus, it is critical to determine what factors impact the stage of cancer at diagnosis. This study sought to determine if certain socioeconomic and demographic factors are associated with receiving an early (Stage 0-I) or advanced (Stage IV) diagnosis of non-small cell lung cancer (NSCLC). Methods Using the National Cancer Database (NCDB), 1,149,539 patients were identified as having an NCDB Analytic Stage Group diagnosis of Stage 0-I (early) versus Stage IV (advanced) NSCLCbetween 2004 and 2018. Patients with early and delayed diagnoses were comparedbased on specific characteristics including sex, race, ethnicity, number of comorbid conditions, insurance status, median annual income, level of education, geographic location, and reporting facility. Using IBMSPSSStatistics for Windows, Version 28 (Released 2021; IBM Corp., Armonk, New York, United States), the data underwent analysis using binary multivariate logistic regression, chi-square analyses, and one-way ANOVA. Results Factors associated with an advanced diagnosis of NSCLC include being male, Black, Native American, or Hispanic. Compared to patients with at least one comorbid condition, those without comorbid conditions are more likely to present with advanced disease. Patients with private insurance, Medicaid, Medicare, or other government insurance are all less likely to present with advanced-stage cancer than patients without insurance. Compared to patients in the lowest median household income quartile, those in the second and fourth quartiles are diagnosed earlier. Patients living in areas where a higher proportion of residents lack a high school diploma are more likely to present with advanced NSCLC. Additionally, living in the Midwest and Western United States and presenting to Community Cancer programs are associated with advanced disease at initial presentation. Conclusions Factors that were associated with the advanced presentation of NSCLC included being male, Black, Native American, or Hispanic, having a lack of comorbid conditions or insurance, earning a lower median annual income, and living in a zip code where a higher proportion of residents lack a high school diploma. Additionally, residing in the Midwest and Western United States and seeking care at Community Cancer programs were associated with advanced disease at initial presentation. Understanding that certain socioeconomic and demographic factors impact the stage at initial diagnosis of NSCLC can allow for targeted intervention strategies aimed at the most at-risk individuals, areas, and facilities.

Upfront liquid next-generation sequencing in treatment-naïve advanced non-small cell lung cancer patients: A prospective randomised study in the Taiwanese health system

BackgroundNext-generation sequencing (NGS) of plasma cell-free DNA identifies driver mutations in advanced non-small cell lung cancer (NSCLC) and may complement routine molecular evaluation. The utility of liquid NGS at the start of tumour workup is undetermined. MethodsThis is a randomised study of patients with suspected advanced NSCLC. All patients received blood liquid NGS testing at their first clinic visit and underwent standard histological diagnosis and tissue genotyping, encompassing polymerase chain reaction based methods for EGFR mutation, immunohistochemical (IHC) staining for ALK fusion and BRAF V600E mutation, and an IHC screening followed by confirmation using fluorescence in situ hybridization confirmation for ROS1 fusion. They were then randomly assigned to receive NGS results either after tissue genotyping (Group A) or as soon as possible after histological diagnosis of advanced NSCLC (Group B). The study measured time to start of systemic treatment as the primary endpoint and secondary endpoints included biomarker discovery rate, objective response rate (ORR), and progression-free survival (PFS). ResultsThis study enroled 180 patients with suspected advanced NSCLC, randomised into two groups. 63 patients in Group A and 59 in Group B with advanced NSCLC were confirmed as advanced NSCLC and analysed. Most had adenocarcinoma (Group A: 77.8%, Group B: 79.7%). The prevalence of EGFR mutations in the two groups was similar (Group A: 57.1%; Group B: 56.6%). Other driver alterations were rare. The median time to treatment was shorter in Group B (20 days) than in Group A (28 days). ORR and PFS did not differ between groups significantly. Liquid NGS had high concordance with tissue testing and identified driver mutations in 42.6% (20/47) of tissue-negative cases. ConclusionPerforming liquid NGS at the initial clinic visit for suspected advanced NSCLC identifies more patients suitable for targeted therapies and shortens time to the start of treatment.

Association between duration of smoking abstinence before non-small-cell lung cancer diagnosis and survival: a retrospective, pooled analysis of cohort studies

The association between duration of smoking abstinence before non-small-cell lung cancer (NSCLC) diagnosis and subsequent survival can influence public health messaging delivered in lung-cancer screening. We aimed to assess whether the duration of smoking abstinence before diagnosis of NSCLC is associated with improved survival. In this retrospective, pooled analysis of cohort studies, we used 26 cohorts participating in Clinical Outcomes Studies of the International Lung Cancer Consortium (COS-ILCCO) at 23 hospitals. 16 (62%) were from North America, six (23%) were from Europe, three (12%) were from Asia, and one (4%) was from South America. Patients enrolled were diagnosed between June 1, 1983, and Dec 31, 2019. Eligible patients had smoking data before NSCLC diagnosis, epidemiological data at diagnosis (obtained largely from patient questionnaires), and clinical information (retrieved from medical records). Kaplan-Meier curves and multivariable Cox models (ie, adjusted hazard ratios [aHRs]) were generated with individual, harmonised patient data from the consortium database. We estimated overall survival for all causes, measured in years from diagnosis date until the date of the last follow-up or death due to any cause and NSCLC-specific survival. Of 42 087 patients with NSCLC in the COS-ILCCO database, 21 893 (52·0%) of whom were male and 20 194 (48·0%) of whom were female, we excluded 4474 (10·6%) with missing data. Compared with current smokers (15 036 [40·0%] of 37 613), patients with 1-3 years of smoking abstinence before NSCLC diagnosis (2890 [7·7%]) had an overall survival aHR of 0·92 (95% CI 0·87-0·97), patients with 3-5 years of smoking abstinence (1114 [3·0%]) had an overall survival aHR of 0·90 (0·83-0·97), and patients with more than 5 years of smoking abstinence (10 841 [28·8%]) had an overall survival aHR of 0·90 (0·87-0·93). Improved NSCLC-specific survival was observed in 4301 (44%) of 9727 patients who had quit cigarette smoking and was significant at abstinence durations of more than 5 years (aHR 0·87, 95% CI 0·81-0·93). Results were consistent across age, sex, histology, and disease-stage distributions. In this large, pooled analysis of cohort studies across Asia, Europe, North America, and South America, overall survival was improved in patients with NSCLC whose duration of smoking abstinence before diagnosis was as short as 1 year. These findings suggest that quitting smoking can improve overall survival, even if NSCLC is diagnosed at a later lung-cancer screening visit. These findings also support the implementation of public health smoking cessation strategies at any time. The Alan B Brown Chair, The Posluns Family Fund, The Lusi Wong Fund, and the Princess Margaret Cancer Foundation.

The Relationship between Single Nucleotide Polymorphism of ERCC1 Gene and the Response to Platinum Based Chemotherapy in Egyptian Non-Small Cell Lung Cancer Patients

Abstract Background Lung cancer (LC) is the second most common cancer diagnosed in both males and females. There are two subtypes of LC. Non-small cell lung cancer (NSCLC) is the major one. Treatment options for NSCLC depends mainly on the stage at diagnosis. The majority of the patients are diagnosed at advanced stages at time of presentation. Therefore, chemotherapy and radiotherapy play the dominant role in treatment of advanced NSCLC. The most commonly used chemotherapy is platinum-based chemotherapy as cisplatin and carboplatin and third generation drugs as vinorelbine and gemcitabine. The efficacy of platinum-based chemotherapy is limited by chemoresistance. The excision repair cross complementation group 1(ERCC1) gene is a member of nucleotide excision repair pathway that plays a critical role in the DNA repair by removing DNA covalent helix-distorting adducts. Aim of the Work In this study investigated the relationship between single nucleotide polymorphism of ERCC1 rs11615 and the response to platinum-based chemotherapy in Egyptian NSCLC patients in order to prevent the non-necessary exposure to the toxic effect of chemotherapy. Patients and Methods This is a cross-sectional study conducted on 50 NSCLC patients who were recruited from the Oncology Clinic in Ain Shams University Hospitals; twenty of them were responders to platinumbased chemotherapy and the other 30 were non-responders according to RECIST criteria. All subjects underwent full medical history focusing on tobacco smoking and family history of cancers, thorough clinical examination, histological diagnosis of NSCLC and TNM classification, radiological studies: computed tomography of chest and abdomen and laboratory investigations in the form of: complete blood picture (CBC), liver function tests and kidney function tests. Detection of the ERCC1 (T/C) polymorphism by realtime PCR was done for both the responders' and the non-responders' groups. Results There was no significant statistical difference observed between the responders’ and nonresponders’ groups regarding the genotype frequencies nor the allelic frequency (p > 0.05). Conclusion The present study did not confirm the presence of significant association between the genotypic frequencies nor the allelic frequencies of the ERCC1 rs 11615 among the responders' and the non-responders' groups. Further studies with higher sample size are needed to clarify the association.

Association of Glutathione S-Transferase P1 (GSTP1) Gene Polymorphism with the Response to Platinum Based Chemotherapy in Patients with Non-Small Cell Lung Cancer

Abstract Background Lung cancer is one of the most commonly diagnosed cancers and despite therapeutic advances, mortality remains high. Platinum based chemotherapy remains the mainstay of adjuvant or first line chemotherapy in non small cell lung cancer (NSCLC) treatment, pathophysiological features along with genetic background significantly influence therapeutic efficacy of platinum-based chemotherapy. GSTP1 gene is a member of the cytosolic superfamily of glutathione-S-transferases, which is responsible for phase II detoxification enzymes that convert various reactive metabolites to more water-soluble and less harmful forms by conjugating them with glutathione. The genetic polymorphism GSTP1 rs1695 is associated with decreased substrate specific catalytic activity and the reduced enzyme activity which may reduces platinum detoxification, thus promoting better response rates to platinum-based chemotherapy. Aim of the Work In the present study was aimed to investigate the association of GSTP1 gene polymorphism with the response to platinum based chemotherapy in patients with NSCLC in order to prevent the non necessary exposure to the toxic effect of chemotherapy. Patients and Methods The study was a retrospective cross sectional study conducted on 50 NSCLC patients who were recruited from the Oncology clinic in Ain Shams University Hospitals, twenty of them were responders to platinum based chemotherapy and the other 30 were not responders according to RECIST criteria. All subjects underwent full medical history focusing on tobacco smoking and family history of cancers, thorough clinical examination, histological diagnosis of NSCLC and TNM classification, radiological studies: computed tomography of chest and abdomen and laboratory investigations in the form of: complete blood picture (CBC), liver function tests and kidney function tests. Detection of the GSTP1 rs1695 (A/G) polymorphism by real-time PCR was done for both the responders and the non responders group. Results There was no statistically significant difference between the responders’ and non responders’ groups regarding the genotypic distribution (p > 0.05). However, the G allele was significantly higher in the responders’ group compared to the non responders’ group with p value < 0.05. Conclusion The present study did not confirm the presence of significant association between the genotypic frequencies of the GSTP1 rs 1695 among the responders and the non responders group, but despite that it showed that the A allele was significantly higher in the non responders’ group compared to the responders’ group. However, the G allele was significantly higher in the responders’ group compared to the non responders’ group. Further studies with higher sample size are needed to clarify the association.

Estimation of disability free life expectancy in non small cell lung cancer based on real world data

To quantify the societal impact of disability in patients with non-small cell lung cancer (NSCLC), this study estimated the disability-free life expectancy (DFLE), loss-of-DFLE and explored their associations with quality-adjusted life expectancy (QALE) and loss-of-QALE. We interlinked national databases and applied a rolling-over algorithm to estimate the lifetime survival function for patients with NSCLC. Using the EuroQOL-5 Dimension (EQ-5D) and Barthel index (BI), we repeatedly measured the quality-of-life and disability functions of NSCLC patients who visited our hospital from 2011 to 2020. Age-, sex-matched referents were simulated from lifetables of the same calendar year of diagnosis. We categorized BI scores ≤ 70 as in need of long-term care and constructed linear mixed models to estimate the utility values and disability scores. We collected 960 cases and 3088 measurements. The proportions of measurements without disability at age 50–64 and in stage I–IIIa, 50–64 and stage IIIb–IV, 65–89 and stage I–IIIa and 65–89 and stage IIIb–IV were 97.3%, 89.3%, 94.8%,78.3%, corresponding to DFLEs of 15.3, 2.4, 6.8, 1.2 years and losses-of-DFLE of 8.1, 20.7, 4.0, 8.6 years, respectively, indicating that advanced stage had a stronger effect than old age. Survivors in advanced stages showed increased demands for assistance in almost all subitems. The DFLEs seemed to be approximate to the QALEs and the latter were shorter than the former due to discomfort and depression. From a societal perspective, future health technology assessment should consider the impact of lifetime duration of functional disability. Early diagnosis of NSCLC may decrease the burden of long-term care.

SDPS-39 AN UPDATED VALIDATION OF PREDICTIVE ALGORITHMS FOR BRAIN METASTASES IN NON-SMALL CELL LUNG CANCER: SYSTEMATIC REVIEW AND INDEPENDENT COHORTVALIDATION ANALYSIS

Abstract INTRODUCTION Many non-small cell lung cancer (NSCLC) patients eventually develop brain metastases (BM). Reliable risk stratification with predictive algorithms can lead to early intervention. Here, we evaluated the performance of published BM risk-stratification algorithms using an independent cohort of NSCLC patients. METHODS We evaluated statistical models predicting BM in NSCLC by systematically reviewing relevant studies and testing them on an independent cohort of NSCLC patients in electronic medical records (2011-2020) from Penn State Health. Patient data was randomly split into 70% training and 30% testing for modeling using L1-regularized logistic regression, and we assessed the models' performance using ROC analyses. RESULTS Out of 1,643 publications, 22 met our criteria, and 12 of those studies (527,258 patients) included variables consistently available in patient charts. Our validation cohort included 1,699 NSCLC patients, with a median age at diagnosis of 68 and 20.4% developing BM. Among feasible models, Zhang 2021 had the highest performance in our cohort (AUROC [95% CI]: 0.89 [0.85-0.93]) and was comprised of the following predictors: age at diagnosis; surgical, chemotherapy, and radiation status; T and N stage; histological grade; and number of organs with metastases. Within our independent cohort, logistic regression revealed that the most informative predictors were the number of organs with metastases (OR [95% CI]: 3.25 [2.70, 3.92]), age at NSCLC diagnosis (OR [95% CI]: 0.98 [0.96, 0.99]), N-stage 1 at diagnosis (OR [95% CI]: 1.83 [1.08, 3.11]), and non-carcinoid or -carcinoma histology (OR [95% CI]: 0.29 [0.10, 0.84]). CONCLUSION Our robust approach, including systematic review and one of the largest-to-date independent institutional datasets, proposes a clinically feasible, novel algorithm for stratifying NSCLC patients based on risk of developing BM. This work can inform pragmatic screening and surveillance guidelines to facilitate early detection of BM in NSCLC patients.

Comprehensive serum N-glycan profiling identifies a biomarker panel for early diagnosis of non-small-cell lung cancer.

Aberrant serum N-glycan profiles have been observed in multiple cancers including non-small-cell lung cancer (NSCLC), yet the potential of N-glycans in the early diagnosis of NSCLC remains to be determined. In this study, serum N-glycan profiles of 275 NSCLC patients and 309 healthy controls were characterized by MALDI-TOF-MS. The levels of serum N-glycans and N-glycosylation patterns were compared between NSCLC and control groups. In addition, a panel of N-glycan biomarkers for NSCLC diagnosis was established and validated using machine learning algorithms. As a result, a total of 54 N-glycan structures were identified in human serum. Compared with healthy controls, 29 serum N-glycans were increased or decreased in NSCLC patients. N-glycan abundance in different histological types or clinical stages of NSCLC presented differentiated changes. Furthermore, an optimal biomarker panel of eight N-glycans was constructed based on logistic regression, with an AUC of 0.86 in the validation set. Notably, this model also showed a desirable capacity in distinguishing early-stage patients from healthy controls (AUC=0.88). In conclusion, our work highlights the abnormal N-glycan profiles in NSCLC and provides supports potential application of N-glycan biomarker panel in clinical NSCLC detection.

Integrated models of blood protein and metabolite enhance the diagnostic accuracy for Non-Small Cell Lung Cancer

BackgroundFor early screening and diagnosis of non-small cell lung cancer (NSCLC), a robust model based on plasma proteomics and metabolomics is required for accurate and accessible non-invasive detection. Here we aim to combine TMT-LC-MS/MS and machine-learning algorithms to establish models with high specificity and sensitivity, and summarize a generalized model building scheme.MethodsTMT-LC-MS/MS was used to discover the differentially expressed proteins (DEPs) in the plasma of NSCLC patients. Plasma proteomics-guided metabolites were selected for clinical evaluation in 110 NSCLC patients who were going to receive therapies, 108 benign pulmonary diseases (BPD) patients, and 100 healthy controls (HC). The data were randomly split into training set and test set in a ratio of 80:20. Three supervised learning algorithms were applied to the training set for models fitting. The best performance models were evaluated with the test data set.ResultsDifferential plasma proteomics and metabolic pathways analyses revealed that the majority of DEPs in NSCLC were enriched in the pathways of complement and coagulation cascades, cholesterol and bile acids metabolism. Moreover, 10 DEPs, 14 amino acids, 15 bile acids, as well as 6 classic tumor biomarkers in blood were quantified using clinically validated assays. Finally, we obtained a high-performance screening model using logistic regression algorithm with AUC of 0.96, sensitivity of 92%, and specificity of 89%, and a diagnostic model with AUC of 0.871, sensitivity of 86%, and specificity of 78%. In the test set, the screening model achieved accuracy of 90%, sensitivity of 91%, and specificity of 90%, and the diagnostic model achieved accuracy of 82%, sensitivity of 77%, and specificity of 86%.ConclusionsIntegrated analysis of DEPs, amino acid, and bile acid features based on plasma proteomics-guided metabolite profiling, together with classical tumor biomarkers, provided a much more accurate detection model for screening and differential diagnosis of NSCLC. In addition, this new mathematical modeling based on plasma proteomics-guided metabolite profiling will be used for evaluation of therapeutic efficacy and long-term recurrence prediction of NSCLC.

Multimodal prehabilitation in patients with non-small cell lung cancer undergoing anatomical resection: protocol of a non-randomised feasibility study

BackgroundThe preoperative period can be used to enhance a patient’s functional capacity with multimodal prehabilitation and consequently improve and fasten postoperative recovery. Especially, non-small cell lung cancer (NSCLC) surgical patients may benefit from this intervention, since the affected and resected organ is an essential part of the cardiorespiratory fitness. Drafting a prehabilitation programme is challenging, since many disciplines are involved, and time between diagnosis of NSCLC and surgery is limited. We designed a multimodal prehabilitation programme prior to NSCLC surgery and aimed to conduct a study to assess feasibility and indicative evidence of efficacy of this programme. Publication of this protocol may help other healthcare facilities to implement such a programme.MethodsThe multimodal prehabilitation programme consists of an exercise programme, nutritional support, psychological support, smoking cessation, patient empowerment and respiratory optimisation. In two Dutch teaching hospitals, 40 adult patients with proven or suspected NSCLC will be included. In a non-randomised fashion, 20 patients follow the multimodal prehabilitation programme, and 20 will be assessed in the control group, according to patient preference. Assessments will take place at four time points: baseline, the week before surgery, 6 weeks postoperatively and 3 months postoperatively. Feasibility and indicative evidence of efficacy of the prehabilitation programme will be assessed as primary outcomes.DiscussionSince the time between diagnosis of NSCLC and surgery is limited, it is a challenge to implement a prehabilitation programme. This study will assess whether this is feasible, and evidence of efficacy can be found. The non-randomised fashion of the study might result in a selection and confounding bias. However, the control group may help putting the results of the prehabilitation group in perspective. By publishing this protocol, we aim to facilitate others to evaluate and implement a multimodal prehabilitation programme for surgical NSCLC patients.Trial registrationThe current study is registered as NL8080 in the Netherlands Trial Register on the 10th of October 2019, https://www.trialregister.nl/trial/8080. Secondary identifiers: CCMO (Central Committee on Research Involving Human Subjects) number NL70578.015.19, reference number of the Medical Ethical Review Committee of Máxima MC W19.045.

Advances in Genomic Data and Biomarkers: Revolutionizing NSCLC Diagnosis and Treatment.

Non-small cell lung cancer (NSCLC) is a significant public health concern with high mortality rates. Recent advancements in genomic data, bioinformatics tools, and the utilization of biomarkers have improved the possibilities for early diagnosis, effective treatment, and follow-up in NSCLC. Biomarkers play a crucial role in precision medicine by providing measurable indicators of disease characteristics, enabling tailored treatment strategies. The integration of big data and artificial intelligence (AI) further enhances the potential for personalized medicine through advanced biomarker analysis. However, challenges remain in the impact of new biomarkers on mortality and treatment efficacy due to limited evidence. Data analysis, interpretation, and the adoption of precision medicine approaches in clinical practice pose additional challenges and emphasize the integration of biomarkers with advanced technologies such as genomic data analysis and artificial intelligence (AI), which enhance the potential of precision medicine in NSCLC. Despite these obstacles, the integration of biomarkers into precision medicine has shown promising results in NSCLC, improving patient outcomes and enabling targeted therapies. Continued research and advancements in biomarker discovery, utilization, and evidence generation are necessary to overcome these challenges and further enhance the efficacy of precision medicine. Addressing these obstacles will contribute to the continued improvement of patient outcomes in non-small cell lung cancer.

First-line osimertinib for patients with EGFR-mutated advanced non-small cell lung cancer: efficacy and safety during the COVID-19 pandemic.

The FLAURA trial demonstrated improved overall survival (OS) with first-line osimertinib for patients with epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer (NSCLC). We studied the efficacy and safety of osimertinib in a cohort treated during the coronavirus disease 2019 (COVID-19) pandemic. Patients diagnosed with EGFR-mutated advanced NSCLC between 11 March 2020 to 31 December 2021 who received first-line osimertinib in British Columbia, Canada were identified retrospectively. Kaplan-Meier curves of OS and progression-free survival (PFS) from the start of osimertinib were plotted. The associations of baseline characteristics with PFS, and development of pneumonitis or dose reductions due to toxicity with OS were evaluated with hazard ratios estimated using univariable and multivariable Cox models. The cohort comprised 231 individuals. 58.7% of patients with de novo advanced NSCLC were initially diagnosed after presentation to the Emergency Room. At osimertinib initiation, 31.6% were aged ≥75 years and 45.5% had an Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2. Median PFS and OS were 18.0 months [95% confidence interval (CI): 16.1-26.2] and 25.4 months (95% CI: 20.3-not reached), respectively. On multivariable analysis, age ≥75 years (vs. <75), ECOG PS 2/3 (vs. 0/1), ECOG PS 4 (vs. 0/1), current smokers (vs. never smokers), programmed death ligand 1 (PD-L1) expression ≥50% (vs. <1%), and L858R mutation (vs. exon 19 deletion) were associated with shorter PFS. Among 110 patients who progressed, 33.6% received subsequent therapy. A proportion of 16.5% of the cohort developed grade ≥3 adverse events. Pneumonitis from osimertinib (3.9% incidence) was weakly associated with shorter OS (hazard ratio: 2.59, 95% CI: 0.94-7.12, P=0.066); dose reductions were not associated with worse OS. 10.8% of patients developed COVID-19. In a cohort receiving first-line osimertinib during the COVID-19 pandemic, ECOG PS ≥2 was observed in nearly half of patients at treatment initiation contributing to a median OS shorter than in FLAURA. The incidence of severe adverse events was low and dose reduction for drug toxicity did not impact OS. Identifying and reducing barriers to the diagnosis of NSCLC during the COVID-19 pandemic are required.

OPTIMIZATION OF MOLECULAR GENETIC DIAGNOSTICS OF PATIENTS WITH ADVANCED NON-SMALL CELL LUNG CANCER BY INTRODUCING ROS1 TESTING IN THE REPUBLIC OF KAZAKHSTAN

Relevance: Currently, molecular diagnosis in NSCLC in Kazakhstan includes detection of EGFR, ALK driver mutations status, and PD-L1-status, but not ROS1, what limits the access of patients with this driver mutation to vital therapy.&#x0D; The study aimed to optimize the methods of molecular genetic diagnosis of patients with NSCLC by introducing ROS1 testing in the Republic of Kazakhstan.&#x0D; Methods: The biopsy and surgical material of non-small cell lung cancer (NSCLC) fixed in 10% buffered formalin was studied. After the initial morphological diagnosis of adenocarcinoma, EGFR, and ALK mutation status determination, EGFR, and ALK-negative tumor assays were sent for further determination of ROS1 mutation status. First, we performed immunohistochemistry (IHC) using the Ventana BenchMark Ultra platform using the ROS1 antibody (SP283) and the OptiView DAB Detection Kit imaging system. After that, samples with positive and doubtful IHC results were sent for RT-PCR (reverse transcriptase polymerase chain reaction) to confirm the ROS1 mutation status.&#x0D; Results: A total of 99 tumor samples from patients with EGFR-negative and ALK-negative lung adenocarcinoma were studied by IHC from January 01 till September 30, 2022. The results of IHC staining were assessed as: 0 (negative) – 59 samples, 1+ (negative) – 25 samples, 2+ (doubtful) – 12 samples, 3+ (positive) – 3 samples. Cases with ≥70% immunostaining were considered positive. Samples with an IHC stain score of 2+ (doubtful), 3+ (positive), and a few samples of 1+ were sent for confirmation by PCR.&#x0D; Overall, 22 samples were tested using RT-PCR, and results were considered as follows:1 (4%) – positive, 13 (59%) – negative, 8 (37%) -– invalid.&#x0D; Conclusion: A large proportion of positive and questionable results were obtained when determining ROS1 mutation status using IHC, and a large proportion of invalid results during subsequent RT-PCR testing. Choosing methods for nationwide ROS1 implementation, one should evaluate the economics of the methods to be implemented and compare them with a standard validated FISH method.

Analysis of Diagnostic Value of CTC and CTDNA in Early Lung Cancer.

This paper is the exploration and analysis of the diagnostic value of circulating tumor cells (CTC) and circulating tumor deoxyribonucleic acid (ctDNA) in early non-small cell lung cancer (NSCLC).A total of 125 NSCLC patients that hospitalized from March 2019 to December 2020 were selected, of which 64 subjects with stage I-II were listed as the early-stage group, and 61 patients with stage III-IV were classified as the intermediate-advanced group; In addition, 47 patients with benign pulmonary nodules hospitalized within same period were selected as a group of benign pulmonary nodules, and 50 healthy subjects were enrolled as a control group. The levels of CTC and ctDNA, serum tumor markers carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), cytokeratin 21-1 (CYFRA21-1) and gastrin-releasing peptide precursor (pro-GRP) were detected. The diagnostic value of CTC and ctDNA in early NSCLC patients was analyzed by ROC curve. The area under the curve of CTC count for early-stage lung cancer was 0. 949 (P=0. 000, 95%CI: 0. 918-0. 980), and ctDNA was 0. 914 (P=0. 000, 95%CI: 0. 866~0. 963). There were significant differences in CTC count and ctDNA among subjects in each group (P<0. 05). CTC count and ctDNA of the early and intermediate-advanced group were remarkably higher than those of the control group and group of benign pulmonary nodules (P<0. 05), and CTC count and ctDNA of patients in the middle-late group were critically higher than those in the early-stage group (P<0. 05). There were significant differences in serum CEA, NSE, CYFRA21-1 and pro-GRP levels among all groups (P<0. 05). The results showed that CTC and ctDNA in NSCLC patients were significantly positively correlated with CEA, NSE, CYFRA21-1 and pro-GRP (P<0. 05). Peripheral blood CTC and ctDNA levels are significantly increased in NSCLC patients. They are positively correlated with serum tumor markers CEA, NSE, CYFRA21-1 and pro-GRP levels, and are related to tumor progression. CTC and ctDNA have high value in the clinical diagnosis of early NSCLC.

OPTIMIZATION OF MOLECULAR GENETIC DIAGNOSTICS OF PATIENTS WITH ADVANCED NON-SMALL CELL LUNG CANCER BY INTRODUCING ROS1 TESTING IN THE REPUBLIC OF KAZAKHSTAN

Relevance: Currently, molecular diagnosis in NSCLC in Kazakhstan includes detection of EGFR, ALK driver mutations status, and PD-L1-status, but not ROS1, what limits the access of patients with this driver mutation to vital therapy.&#x0D; The study aimed to optimize the methods of molecular genetic diagnosis of patients with NSCLC by introducing ROS1 testing in the Republic of Kazakhstan.&#x0D; Methods: The biopsy and surgical material of non-small cell lung cancer (NSCLC) fixed in 10% buffered formalin was studied. After the initial morphological diagnosis of adenocarcinoma, EGFR, and ALK mutation status determination, EGFR, and ALK-negative tumor assays were sent for further determination of ROS1 mutation status. First, we performed immunohistochemistry (IHC) using the Ventana BenchMark Ultra platform using the ROS1 antibody (SP283) and the OptiView DAB Detection Kit imaging system. After that, samples with positive and doubtful IHC results were sent for RT-PCR (reverse transcriptase polymerase chain reaction) to confirm the ROS1 mutation status.&#x0D; Results: A total of 99 tumor samples from patients with EGFR-negative and ALK-negative lung adenocarcinoma were studied by IHC from January 01 till September 30, 2022. The results of IHC staining were assessed as: 0 (negative) – 59 samples, 1+ (negative) – 25 samples, 2+ (doubtful) – 12 samples, 3+ (positive) – 3 samples. Cases with ≥70% immunostaining were considered positive. Samples with an IHC stain score of 2+ (doubtful), 3+ (positive), and a few samples of 1+ were sent for confirmation by PCR.&#x0D; Overall, 22 samples were tested using RT-PCR, and results were considered as follows:1 (4%) – positive, 13 (59%) – negative, 8 (37%) -– invalid.&#x0D; Conclusion: A large proportion of positive and questionable results were obtained when determining ROS1 mutation status using IHC, and a large proportion of invalid results during subsequent RT-PCR testing. Choosing methods for nationwide ROS1 implementation, one should evaluate the economics of the methods to be implemented and compare them with a standard validated FISH method.

Updated Interpretation of the NCCN Clinical Practice Guidelines (Version 3. 2023) for Non-small Cell Lung Cancer

Lung cancer is the malignant tumor with the highest morbidity and mortality in China. Non-small cell lung cancer (NSCLC) is the main pathological subtype of lung cancer. On April 13, 2023, the National Comprehensive Cancer Network (NCCN) released the third edition of the 2023 NCCN Oncology Clinical Practice Guidelines: Non-small Cell Lung Cancer, which reflects the latest advances in international lung cancer research. This article will interpret the main updated contents of the new edition of the guidelines, and compare it with the third edition of the NCCN guidelines in 2022, so as to provide references about the diagnosis and treatment of NSCLC for clinical medical personnel in China. .

Clinical implications of the concentration of alveolar nitric oxide in non-small cell lung cancer.

Clinical implications of the concentration of alveolar nitric oxide in non-small cell lung cancer.

Expression Pattern and Prognostic Analysis of Branched-Chain Amino Acid Catabolism-Related Genes in Non-Small Cell Lung Cancer.

The purpose of our study is to analyze the expression pattern and prognostic value of catabolism-related enzymes of branched-chain amino acids (BCAAs) in non-small cell lung cancer (NSCLC). Differential expression analysis, mutation, copy number variation (CNV), methylation analysis, and survival analysis of BCAAs catabolism-related enzymes in NSCLC were performed using the Cancer Genome Atlas (TCGA) database. Six and seven differentially expressed genes were obtained in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), respectively. IL4I1 was located at the core regulatory nodes in the gene co-expression networks of both LUAD and LUSC. The AOX1 mutation rate was the highest in both LUAD and LUSC. For CNV, IL4I1 was up-regulated in both LUAD and LUSC with an increase in copy number, whereas AOX1 and ALDH2 were differentially regulated in the two subtypes of lung cancer. In patients with NSCLC, high expression of IL4I1 was associated with lower overall survival (OS), and low expression of ALDH2 predicted shorter disease-free survival (DFS). ALDH2 expression was related with LUSC survival. This study explored the biomarkers of BCAAs catabolism related to the prognosis of NSCLC, which provided a theoretical foundation to guide the clinical diagnosis and treatment of NSCLC.

Clinical application of liquid biopsy based on circulating tumor DNA in non-small cell lung cancer.

Lung cancer is a widely occurring and deadly malignancy, with high prevalence rates in China and across the globe. Specifically, non-small cell lung cancer (NSCLC) represents about 85% of all lung cancer cases. The 5-year disease-free survival rate after surgery for stage IB-IIIB NSCLC patients (disease-free survival, DFS) has notably declined from 73% to 13%. Early detection of abnormal cancer molecules and subsequent personalized treatment plans are the most effective ways to address this problem. Liquid biopsy, surprisingly, enables safe, accurate, non-invasive, and dynamic tracking of disease progression. Among the various modalities, circulating tumor DNA (ctDNA) is the most commonly used liquid biopsy modality. ctDNA serves as a credible "liquid biopsy" diagnostic tool that, to a certain extent, overcomes tumor heterogeneity and harbors genetic mutations in malignancies, thereby providing early information on tumor genetic alterations. Despite considerable academic interest in the clinical significance of ctDNA, consensus on its utility remains lacking. In this review, we assess the role of ctDNA testing in the diagnosis and management of NSCLC as a reference for clinical intervention in this disease. Lastly, we examine future directions to optimize ctDNA for personalized therapy.