A preliminary study on the diagnostic performance of the uPath PD-L1 (SP263) artificial intelligence (AI) algorithm in patients with NSCLC treated with PD-1/PD-L1 checkpoint blockade.

Objective: The uPath PD-L1 (SP263) is an AI-based platform designed to aid pathologists in identifying and quantifying PD-L1 positive tumor cells in non-small cell lung cancer (NSCLC) samples stained with the SP263 assay. Methods: In this preliminary study, we explored the diagnostic performance of the uPath PD-L1 algorithm in defining PD-L1 tumor proportion score (TPS) and predict clinical outcomes in a series of patients with advanced stage NSCLC treated with single agent PD-1/PD-L1 checkpoint blockade previously assessed with the SP263 assay in clinical practice. Results: 44 patients treated from August 2015 to January 2019 were included, with baseline PD-L1 TPS of ≥ 50%, 1-49% and < 1% in 38.6%, 25.0% and 36.4%, respectively. The median uPath PD-L1 score was 6 with a significant correlation with the baseline PD-L1 TPS (r: 0.83, p < 0.01). However, only 27 cases (61.4%) were scored within the same clinically relevant range of expression (≥ vs < 50%). In the study population the baseline PD-L1 TPS was not significantly associated with clinical outcomes, while the uPath PD-L1 score showed a good diagnostic ability for the risk of death at the ROC curve analysis [AUC: 0.81 (95%CI: 0.66-0.91), optimal cut-off of ≥ 3.2], resulting in 19 patients (43.2%) being u-Path low and 25 patients (56.8%) being uPath high. The objective response rate in uPath high and low was 51.6% and 25.0% (p = 0.1), respectively, although the uPath was significantly associated with overall survival (OS, HR 2.45, 95%CI: 1.19-5.05) and progression free survival (PFS, HR 3.04, 95%CI: 1.51-6.14). At the inverse probability of treatment weighting analysis used to balance baseline covariates, the uPath categories confirmed to be independently associated with OS and PFS. Conclusions: This preliminary analysis suggests that AI-based, digital pathology tools such as uPath PD-L1 (SP263) can be used to optimize already available biomarkers for immune-oncology treatment in patients with NSCLC.

Development and Portability of a Text Mining Algorithm for Capturing Disease Progression in Electronic Health Records of Patients With Stage IV Non-Small Cell Lung Cancer.

PURPOSE: The objective was to develop and evaluate the portability of a text mining algorithm for prospectively capturing disease progression in electronic health record (EHR) data of patients with metastatic non-small cell lung cancer (mNSCLC) treated with immunochemotherapy. METHODS: This study used EHR data from patients with mNSCLC receiving immunochemotherapy (between October 1, 2018, and December 31, 2022) in four Dutch hospitals. A text mining algorithm for capturing disease progression was developed in hospitals 1 and 2 and then transferred to hospitals 3 and 4 to evaluate portability. Performance metrics were calculated by comparing its outcomes with manual chart review. In addition, data were simulated to come available over time to assess performance in real-time applications. Median progression-free survival (PFS) was calculated using the Kaplan-Meier method to compare text mining with manual chart review. RESULTS: During development and portability, the text mining algorithm performed well in capturing disease progression, with all performance scores >90%. When real-time performance was simulated, the performance scores in all four hospitals exceeded 90% from week 15 after the start of follow-up. Although the exact progression dates varied in 46 patients of 157 patients with progressive disease, the number of patients labeled with progression too early (n = 24) and too late (n = 22) was well balanced with discrepancies ranging from -116 to 384 days. Nevertheless, the PFS curves constructed with text mining and manual chart review were highly similar for each hospital. CONCLUSION: In this study, an accurate text mining algorithm for capturing disease progression in the EHR data of patients with mNSCLC was developed. The algorithm was portable across different hospitals, and the performance over time was good, making this an interesting approach for prospective follow-up of multicenter cohorts.

Correlation of programmed death-ligand 1 expression in tumour cells between diagnostic small biopsies performed by radial EBUS and surgical specimens of peripheral lung cancer.

BACKGROUND AND OBJECTIVE: Expression of programmed death-ligand 1 (PD-L1) in tumour cells (TCs) is predictive of immunotherapy efficacy in non-small cell lung cancer (NSCLC). Small biopsy samples collected by bronchoscopy are often used to diagnose peripheral lung cancer. It is questionable whether these small samples from radial endobronchial ultrasonography (r-EBUS) procedures are representative of PD-L1 expression in TCs. METHODS: We retrieved data of consecutive patients who had surgery for NSCLC and previous r-EBUS biopsy sampling, from 2017 to 2019 in our centre. PD-L1 expression in tumour cells was categorised as <1%, 1%-49% and ≥50%. PD-L1 expression was compared between r-EBUS samples and surgical specimens. RESULTS: Among 1026 patients who had r-EBUS, 521 had a diagnosis of lung cancer on r-EBUS sample. PD-L1 testing was indicated in 356 cases and results were considered contributive in 325 cases (91%). 82 patients with PD-L1 expression in r-EBUS samples had subsequent surgical resection of the nodule and were included in the study. PD-L1 expression was identical between r-EBUS samples and surgical specimens in 67% of cases, with kappa 0.44 (p<0.001). 82% of patients with PD-L1≥50% in surgical specimens were identified in r-EBUS samples. Nonetheless, 31% of patients with no PD-L1 expression in r-EBUS samples had some expression in surgical specimens. CONCLUSION: Small samples obtained by r-EBUS are adequate for assessment of PD-L1 expression in tumour cells, with moderate concordance compared to surgical specimens. Reassessment of PD-L1 expression in larger samples may be useful to guide therapy in patients with no PD-L1 expression in r-EBUS samples.

[Pulmonary sarcomatoid carcinoma:report of three cases].

Pulmonary sarcomatoid carcinoma (PSC) is a rare disease with strong aggressiveness, low response rates to treatment, short survival span and poor prognosis, belonging to a group of non-small cell lung carcinomas (NSCLC) that remains incompletely understood. Here, we presented three PSC cases with epidermal growth factor receptor (EGFR) L858R, BRAF V600E and ALK mutations respectively, described their clinical characteristics and conducted a review of literature, in order to improve its therapeutic level, which also provided evidence-based medical evidence for driver gene screening and molecular targeted drug application in PSC patients.

Detection of EGFR mutations in patients with suspected lung cancer using paired tissue-plasma testing: a prospective comparative study with plasma ddPCR assay.

Detecting EGFR mutations in plasma using droplet digital PCR (ddPCR) assay offers a promising diagnostic tool for lung cancer patients. The performance of plasma-based ddPCR assay relative to traditional EGFR mutation testing in tissue biopsies among Asian patients with suspected lung cancer remains underexplored. Consecutive patients admitted for diagnostic workup for suspected lung cancer were recruited. Peripheral blood samples were collected on the same day of tissue biopsies. Tissue samples were subjected to EGFR mutation analysis via real-time PCR, whereas plasma samples were processed for ddPCR assay to evaluate for EGFR mutation status. The tissue re-biopsy rate was 43.8% while 0.7% of patients failed blood taking. Despite repeat biopsy, 15.2% of patients could not achieve histological diagnosis. Of the 202 patients newly diagnosed with lung cancer, EGFR mutations were detected in 13.4% of plasma samples, compared to 44.3% in tissue samples. Plasma ddPCR for EGFR mutations detection were barely detectable in stages I and II non-small cell lung cancer (NSCLC), but the sensitivity was 25.0%, 56.3%, and 75.0% in stages III, IVA, and IVB NSCLC, respectively. Plasma EGFR mutations were highly specific among all stages of lung cancer. Concordance rates of plasma ddPCR assay also rose with more advanced stages, recorded at 41.9% for stages I and II, 71.9% for stage III, 86.3% for stage IV. In stage IV lung cancer, the false negative rate for the plasma ddPCR assay was 34.4%, whereas that for the tissue testing was 19.2% due to insufficient tissue samples. Plasma-based EGFR genotyping using ddPCR is a non-invasive method that offers early diagnosis and serves as a valuable adjunct to tissue-based testing for patients with advanced-stage lung cancer. However, its usefulness is limited in the context of early-stage lung cancer, indicating a need for further research to improve its accuracy in these patients.

The clinical value of combined detection of seven lung cancer-related autoantibodies in assisting the diagnosis of non-small-cell lung cancer.

Aim: Evaluate the clinical value of lung-cancer-related autoantibodies (CAGE, GAGE7, GBU4-5, MAGEA1, P53, PGP9.5, SOX2) in auxiliary diagnosis of non-small-cell lung cancer (NSCLC).Methods: We detected the concentrations of above 7 antibodies and lung cancer markers (CEA, NSE, CYFRE21-1) and drew area under the receiver characteristic curve of 316 patients.Results: The concentrations of CAGE, GBU4-5, MAGEA1, P53, PGP9.5 and SOX2 of significantly higher than other groups (p < 0.01). The sensitivity of different stages and pathological types of NSCLC consistent. Among them, the sensitivity of combined-detection in diagnosing adenocarcinoma and squamous cell carcinoma significantly better than CEA, NSE and CYFRA21-1.Conclusion: The combined detection has better efficacy in assisting the diagnosis of NSCLC and has certain clinical promotion and application value.

[Box: see text].

Non-small-cell lung cancer.

Non-small-cell lung cancer (NSCLC) is one of the most frequent cancer types and is responsible for the majority of cancer-related deaths worldwide. The management of NSCLC has improved considerably, especially in the past 10 years. The systematic screening of populations at risk with low-dose CT, the implementation of novel surgical and radiotherapeutic techniques and a deeper biological understanding of NSCLC that has led to innovative systemic treatment options have improved the prognosis of patients with NSCLC. In non-metastatic NSCLC, the combination of various perioperative strategies and adjuvant immunotherapy in locally advanced disease seem to enhance cure rates. In metastatic NSCLC, the implementation of novel drugs might prolong disease control together with preserving quality of life. The further development of predictive clinical and genetic markers will be essential for the next steps in individualized treatment concepts.

[Advances in Diagnosis and Targeted Therapy of G719X/L861Q/S768I Mutant 
Non-small Cell Lung Cancer].

Lung cancer accounts for the highest proportion of cancer deaths in the world and poses a great threat to human health. About 30% to 40% of non-small cell lung cancer (NSCLC) is caused by point mutations, exon insertion and exon deletion of the epidermal growth factor receptor (EGFR). In addition to the common exon 19 deletion mutation and exon 21 L858R mutation, exon 18 G719X mutation, exon 21 L861Q mutation and exon 20 S768I mutation are the most important rare mutations. At present, the diagnostic methods for major rare mutations are mainly next-generation sequencing (NGS), digital polymerase chain reaction (dPCR), droplet digital PCR (ddPCR), etc. Regarding the targeted therapy of G719X/L861Q/S768I mutant NSCLC, the first generation EGFR-tyrosine kinase inhibitors (TKIs) have poor efficacy, while the second and third generation EGFR-TKIs have similar efficacy. The novel third generation EGFR-TKIs and combination therapy show a good therapeutic prospect. This article summarized the progress in the diagnosis and targeted therapy of G719X/L861Q/S768I mutant NSCLC, so as to provide reference for subsequent clinical drug use and research.
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Acyl-coenzyme a binding protein (ACBP) - a risk factor for cancer diagnosis and an inhibitor of immunosurveillance.

BACKGROUND: The plasma concentrations of acyl coenzyme A binding protein (ACBP, also known as diazepam-binding inhibitor, DBI, or 'endozepine') increase with age and obesity, two parameters that are also amongst the most important risk factors for cancer. METHODS: We measured ACBP/DBI in the plasma from cancer-free individuals, high-risk patients like the carriers of TP53 or BRCA1/2 mutations, and non-syndromic healthy subjects who later developed cancer. In mice, the neutralization of ACBP/DBI was used in models of non-small cell lung cancer (NSCLC) and breast cancer development and as a combination treatment with chemoimmunotherapy (chemotherapy + PD-1 blockade) in the context of NSCLC and sarcomas. The anticancer T cell response upon ACBP/DBI neutralization was characterized by flow cytometry and single-cell RNA sequencing. RESULTS: Circulating levels of ACBP/DBI were higher in patients with genetic cancer predisposition (BRCA1/2 or TP53 germline mutations) than in matched controls. In non-syndromic cases, high ACBP/DBI levels were predictive of future cancer development, and especially elevated in patients who later developed lung cancer. In preclinical models, ACBP/DBI neutralization slowed down breast cancer and NSCLC development and enhanced the efficacy of chemoimmunotherapy in NSCLC and sarcoma models. When combined with chemoimmunotherapy, the neutralizing monoclonal antibody against ACBP/DBI reduced the frequency of regulatory T cells in the tumor bed, modulated the immune checkpoint profile, and increased activation markers. CONCLUSION: These findings suggest that ACBP/DBI acts as an endogenous immune suppressor. We conclude that elevation of ACBP/DBI constitutes a risk factor for the development of cancer and that ACBP/DBI is an actionable target for improving cancer immunosurveillance.

Diagnostic value of microRNA-200 expression in peripheral blood-derived extracellular vesicles in early-stage non-small cell lung cancer.

OBJECTIVE: This study assessed the diagnostic value of microRNA-200 (miR-200) expression in peripheral blood-derived extracellular vesicles (EVs) in early-stage non-small cell lung cancer (NSCLC). METHODS: This study retrospectively analyzed 100 healthy volunteers (the control group) receiving physical examinations, 168 early-stage NSCLC patients (the NSCLC group), and 128 patients with benign lung nodules (the benign group). The basic and clinical data of participants were obtained, including age, sex, smoking history, carbohydrate antigen 242 (CA242), carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), forced expiratory volume in 1 s, maximal voluntary ventilation, forced vital capacity, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and miR-200 expression. The correlation of miR-200 expression in peripheral blood-derived EVs with CA242, CEA, and CA199 was analyzed, and the diagnostic value of peripheral blood-derived EV miR-200 for early-stage NSCLC was assessed. The risk factors of early-stage NSCLC development were also determined. RESULTS: Age, the percentage of patients with smoking history, CA242, CEA, CA199, IL-6, and TNF-α levels, and miR-200 expression in peripheral blood-derived EVs were significantly higher in the NSCLC group than in the benign and control groups. Lung disease patients with high miR-200 expression in peripheral blood-derived EVs comprised a higher percentage of patients with smoking history and mixed lesions and had higher CA242, CEA, CA199, and TNF-α levels than those with low miR-200 expression in peripheral blood-derived EVs. In lung diseases, miR-200 expression in peripheral blood-derived EVs was significantly and positively correlated with CA242, CEA, and CA199. Peripheral blood-derived EV miR-200 combined with CA242, CEA and CA199 had higher diagnostic value (area under the curve = 0.942) than single detection, along with higher specificity, and high expression of peripheral blood-derived EV miR-200 was an independent risk factor for early-stage NSCLC. CONCLUSION: Peripheral blood-derived EV miR-200 expression in patients with lung diseases is closely correlated with CA242, CEA, and CA199, and high expression of peripheral blood-derived EV miR-200 is an independent risk factor for early-stage NSCLC and is of high clinical diagnostic value for early-stage NSCLC.

Beyond biomarkers: Exploring the diverse potential of a novel phosphoprotein in lung cancer management.

In addressing the challenges of lung cancer, attention has increasingly turned to molecular diagnostics and targeted therapies, with nucleolin (NCL) assuming a pivotal role, especially in non-small cell lung cancer. The aberrant activity and cellular distribution of NCL act as crucial biomarkers for early detection and treatment monitoring, showing a strong correlation with disease progression and patient prognosis. Elevated NCL levels signal advanced disease and poorer outcomes, underscoring its significance in evaluating disease severity and therapeutic response. Strategies targeting the molecular interactions of NCL have spurred innovative approaches to inhibit tumour growth, overcome drug resistance and improve treatment efficacy. These advancements are paving the way for personalized therapies tailored to the unique molecular profiles of patients' tumours. Consequently, NCL stands at the forefront of lung cancer management, symbolizing the move towards more precise and individualized oncology care, and marking substantial progress in therapeutic development.

Detection of serum SNHG22 and its correlation with prognosis of non-small cell lung cancer.

BACKGROUND: Lung cancer accounts for a significant proportion of cancer-related deaths in China, with the majority of the cases being classified as non-small cell lung cancer (NSCLC). The study aimed to investigate the expression of serum SNHG22 in patients with NSCLC, and its molecular mechanism and prognostic potential in NSCLC. METHODS: Admitted 125 NSCLC patients were selected for the study, along with 125 healthy individuals in the same period. The levels of SNHG22 and miR-128-3p were quantified via RT-qPCR. Correlations between the SNHG22 level and the pathological characteristics of the NSCLC patients were investigated through the application of the chi-square test. The targeting relationship between SNHG22 and miR-128-3p was predicted by online database and confirmed by luciferase activity. The prognostic ability of SNHG22 in NSCLC was assessed by Kaplan-Meier curves and multivariate Cox analysis. RESULTS: SNHG22 was upregulated in NSCLC and directly targeted miR-128-3p. The rate of overall survival is lower in patients with high-SNHG22 group compared to those with low-SNHG22 group. Silencing SNHG22 impaired the functionality of cells, which was restored by miR-128-3p inhibitor. SNHG22 stands as an independent predictor of poor prognosis in NSCLC patients. CONCLUSION: The overexpression of SNHG22 in NSCLC is related to lymph node metastasis, TNM stage and patient survival, which is expected to be a prognostic predictor of NSCLC patients.

Advances in early detection of non-small cell lung cancer: A comprehensive review.

BACKGROUND: Lung cancer has the highest mortality rate among malignancies globally. In addition, due to the growing number of smokers there is considerable concern over its growth. Early detection is an essential step towards reducing complications in this regard and helps to ensure the most effective treatment, reduce health care costs, and increase survival rates. AIMS: To define the most efficient and cost-effective method of early detection in clinical practice. MATERIALS AND METHODS: We collected the Information used to write this review by searching papers through PUBMED that were published from 2021 to 2024, mainly systematic reviews, meta-analyses and clinical-trials. We also included other older but notable papers that we found essential and valuable for understanding. RESULTS: EB-OCT has a varied sensitivity and specificity-an average of 94.3% and 89.9 for each. On the other hand, detecting biomarkers via liquid biopsy carries an average sensitivity of 91.4% for RNA molecules detection, and 97% for combined methylated DNA panels. Moreover, CTCs detection did not prove to have a significant role as a screening method due to the rarity of CTCs in the bloodstream thus the need for more blood samples and for enrichment techniques. DISCUSSION: Although low-dose CT scan (LDCT) is the current golden standard screening procedure, it is accompanied by a highly false positive rate. In comparison to other radiological screening methods, Endobronchial optical coherence tomography (EB-OCT) has shown a noticeable advantage with a significant degree of accuracy in distinguishing between subtypes of non-small cell lung cancer. Moreover, numerous biomarkers, including RNA molecules, circulating tumor cells, CTCs, and methylated DNA, have been studied in the literature. Many of these biomarkers have a specific high sensitivity and specificity, making them potential candidates for future early detection approaches. CONCLUSION: LDCT is still the golden standard and the only recommended screening procedure for its high sensitivity and specificity and proven cost-effectiveness. Nevertheless, the notable false positive results acquired during the LDCT examination caused a presumed concern, which drives researchers to investigate better screening procedures and approaches, particularly with the rise of the AI era or by combining two methods in a well-studied screening program like LDCT and liquid biopsy. we suggest conducting more clinical studies on larger populations with a clear demographical target and adopting approaches for combining one of these new methods with LDCT to decrease false-positive cases in early detection.

Combination of circulating tumor cells and 18F-FDG PET/CT for precision diagnosis in patients with non-small cell lung cancer.

PURPOSE: To investigate the value of 2-deoxy-18f-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) and circulating tumor cells (CTCs) for the differential diagnosis of patients with benign lung diseases and those with NSCLC. To explore the phenotypic heterogeneity of CTCs and their correlation with FDG uptake in patients with Stage I-IV NSCLC. METHODS: Blood specimens from patients with benign lung diseases and patients with primary NSCLC were collected for the detection of CTCs and their subtypes (epithelial, mixed, and mesenchymal) and analyzed for 18F-FDG PET/CT tumor metabolic parameters, including the maximum standardized uptake value (SUVmax), standard uptake value (SUL), metabolic tumor volume of primary lesion (MTV), total lesion glycolysis of primary lesion (TLG). Clinical data including age, gender, smoking history, tumor size, TNM stage and pathology type were also collected. The value of the two method alone and in combination for the differential diagnosis of benign and malignant was comparatively analyzed. Finally, the differences in CTC and its subtypes in different stages of NSCLC were compared, and FDG metabolic parameters were correlated with CTC subtypes. RESULTS: There were a total of 65 patients with pulmonary diseases, including 12 patients with benign pulmonary diseases and 53 patients with NSCLC. The mean age was 67 ± 10 (38-89 years), 27 were females and 38 were males. 31 (22 males and 9 females) had a long history of smoking. The mean size of the largest diameter of all single lesions was 36 ± 22 mm with a range of 10-108 mm. Seven out of 12 benign diseases were inflammatory granulomatous lesions and 5 were inflammatory pseudotumours. Twenty-four out of 53 NSCLC were adenocarcinomas and 29 were squamous carcinomas. Twelve out of 53 patients with NSCLC were in Stage I, 10 were in Stage II, 17 were in Stage III and 14 were in Stage IV. SUVmax, SUL, MTV, TLG, total CTCs, epithelial CTCs, and mixed CTCs were all valuable in the differential diagnosis of benign and malignant. TLG combined with mixed CTCs was statistically different from all other diagnostic methods (p < 0.05) and higher than any other diagnostic criteria. In the differential diagnosis of benign and Stage I NSCLC, only total CTC (Z = -2.188 p = 0.039) and mixed CTCs (Z = -3.020 p = 0.014) had certain diagnostic efficacy, and there was no statistical difference between them (p = 0.480). Only mesenchymal CTCs differed in Stage I-IV NSCLC, with a higher number of those who developed distant metastases than those who had non-distant metastases. Epithelial CTCs correlated with SUVmax (r = 0.333, p = 0.015) and SUL (r = 0.374, p = 0.006). Mmesenchymal CTCs correlated with MTV (r = 0.342, p = 0.018) and TLG (r = 0.319, p = 0.02). Further subgroup analyses revealed epithelial CTCs were correlated with SUVmax (r = 0.543, p = 0.009) and SUL (r = 0.552, p = 0.008), and the total CTCs was correlated with SUVmax (r = 0.622, p = 0.003), SUL (r = 0.652, p = 0.003), MTV (r = 0.460, p = 0.031), and TLG (r = 0.472, p = 0.027) in the early group (Stage I-II). Only mesenchymal CTCs was associated with MTV (r = 0.369, p = 0.041), and TLG (r = 0.415, p = 0.02) in the intermediate-late group (Stage III-IV). CONCLUSION: Both FDG PET metabolic parameters and CTCs demonstrated diagnostic value for NSCLC, and combining TLG with mixed CTCs could enhance their diagnostic efficacy. The total CTCs and mixed CTCs showed greater diagnostic value than FDG PET in distinguishing benign lesions from Stage I NSCLC. In NSCLC patients, the epithelial CTCs exhibited a positive correlation with SUVmax and SUL, while mesenchymal CTCs correlated with MTV, and TLG. Besides, epithelial CTCs showed stronger correlations with SUVmax and SUL, and total CTCs showed stronger correlations with SUVmax, SUL, MTV, and TLG in Stage I-II NSCLC. Only mesenchymal CTCs in Stage III-IV NSCLC showed correlations with MTV and TLG. Stage IV NSCLC cases displayed a higher number of mesenchymal CTCs.

Clinical utility of ctDNA by amplicon based next generation sequencing in first line non small cell lung cancer patients.

The assessment of ctDNA has emerged as a minimally invasive avenue for molecular diagnosis and real-time tracking of tumor progression in NSCLC. However, the evaluation of ctDNA by amplicon-based NGS has been not endorsed by all the healthcare systems and remains to be fully integrated into clinical routine practice. To compare tissue single-gene with plasma multiplexed testing, we retrospectively evaluated 120 plasma samples from 12 consecutive patients with advanced non-squamous NSCLC who were part of a prospective study enrolling treatment-naïve patients and in which tissue samples were evaluated using a single-gene testing approach. While the plasma ctDNA detection of EGFR and BRAF mutations had an acceptable level of concordance with the archival tissue (85%), discordance was seen in all the patients in whom ALK alterations were only detected in tissue samples. Among six responders and six non-responders, early ctDNA mutant allelic frequency (MAF) reduction seemed to predict radiologic responses and longer survival, whereas increasing MAF values with the emergence of co-mutations like BRAFV600E, KRASG12V or TP53M237I seemed to be an early indicator of molecular and radiologic progression. This report using an amplicon-based NGS assay on ctDNA underscores the real-life need for plasma and tissue genotyping as complementary tools in the diagnostic and therapeutic decision-making process.

Using a Polygenic Risk Score to Improve the Risk Prediction of Non-Small Cell Lung Cancer in Taiwan.

PURPOSE: Low-dose computed tomography (LDCT) can help reducing lung cancer mortality. In Taiwan, the existing screening criteria revolve around smoking habits and family history of lung cancer. The role of genetic variation in non-small cell lung cancer (NSCLC) development is increasingly recognized. In this study, we aimed to investigate the potential benefits of polygenic risk scores (PRSs) in predicting NSCLC and enhancing the effectiveness of screening programs. METHODS: We conducted a retrospective cohort study that included participants without prior diagnosis of lung cancer and later received LDCT for lung cancer screening. Genetic data for these participants were obtained from the project of Taiwan Precision Medicine Initiative. We adopted the model of genome-wide association study-derived PRS calculation using 19 susceptibility loci associated with the risk of NSCLC as reported by Dai et al. RESULTS: We studied a total of 2,287 participants (1,197 male, 1,090 female). More female participants developed NSCLC during the follow-up period (4.4% v 2.5%, P = .015). The only risk factor of NSCLC diagnosis among male participants was age. Among female participants, independent risk factors of NSCLC diagnosis were age (adjusted hazard ratio [aHR], 1.08 [95% CI, 1.04 to 1.11]), a family history of lung cancer (aHR, 3.21 [95% CI, 1.78 to 5.77]), and PRS fourth quartile (aHR, 2.97 [95% CI, 1.25 to 7.07]). We used the receiver operating characteristics to show an AUC value of 0.741 for the conventional model. With the further incorporation of PRS, the AUC rose to 0.778. CONCLUSION: The evaluation of PRS for NSCLC prediction holds promise for enhancing the effectiveness of lung cancer screening in Taiwan especially in women. By incorporating genetic information, screening criteria can be tailored to identify individuals at higher risks of NSCLC.

Comparison of methods for cancer stem cell detection in prognosis of early stages NSCLC.

BACKGROUND: Despite advances in diagnosis and treatment in lung cancer, therapies still fail to improve patient management due to resistance mechanisms and relapses. As Cancer stem cells (CSCs) directly contribute to tumor growth and therapeutic resistance, their clinical detection represents a major challenge. However specific and additional CSC markers lack. Thus, our aim was to achieve selective detection of CSCs with specific glycan patterns and assess the CSCs burden to predict the risk of relapse in NSCLC tumors. METHODS: The lung CSCs detection and sorting with a lectin MIX were assessed and compared to CD133 in vitro. Then, its putative role as CSC biomarker was evaluated in vivo and its clinical significance on 221 NSCLC patients. RESULTS: We showed a significant CSCs enrichment in the MIX+ sorted fraction compared to CD133+ cells and confirmed its high tumorigenic capacity. The MIX prognostic value on the overall survival from early stages patients was validated suggesting its potential for detecting CSCs directly linked to tumor aggressiveness. CONCLUSION: The MIX could be more relevant for detecting and sorting CSCs than CD133. Moreover, its prognosis value could enable clinicians to better classify early-stage patients at high risk of relapse in order to tailor therapeutic decisions.

Clinical Utility of Circulating Tumor DNA for Detecting Lung Cancer Mutations by Targeted Next-Generation Sequencing With Insufficient Tumor Samples.

BACKGROUND: Circulating tumor deoxyribonucleic acid (ctDNA) is increasingly applied in clinical practice. This study aimed to explore clinical utility of a minimal invasive and sensitive way of ctDNA for next-generation sequencing in non-small cell lung cancer (NSCLC) with inadequate tumor samples. METHODS: Targeted DNA sequencing was performed on tissue biopsies and matched plasma samples from 60 patients with NSCLC. RESULTS: A total of 13 driving genes were detected in 60 matched tissue DNA (tDNA) and ctDNA samples. Overall concordance rate was 75.47%, with 77.55% sensitivity and 50% specificity. Epidermal growth factor receptor (EGFR) mutations were the most common in both tDNA and ctDNA samples. Among other mutated genes were tumor protein p53 (TP53), erb-b2 receptor tyrosine kinase 2 (ERBB2), anaplastic lymphoma kinase (ALK), cyclin-dependent kinase inhibitor 2A (CDKN2A), ros proto-oncogene 1, and receptor tyrosine kinase (ROS1). Mutations in b-raf proto-oncogene, serine/threonine kinase (BRAF), cluster of differentiation 274 (CD274), neurotrophin receptor tyrosine kinase 1 (NTRK1), and rearranged during transfection (RET) occurred only in plasma. The majority of mutations in both samples were single-nucleotide variants. Deletions were found in EGFR, BRAF, and TP53 in ctDNA, whereas in tDNA, deletions were only found in EGFR. In ALK, single nucleic acid-site amplification occurred simultaneously in tissue and plasma, but insertions and copy number variations were detected only in plasma. CONCLUSIONS: Identifying ctDNA mutations by targeted sequencing in plasma is feasible, showing the clinical value of ctDNA-targeted sequencing in NSCLC patients when tumor tissue sampling is insufficient or even impossible.

Validation of Non-Small Cell Lung Cancer Clinical Insights Using a Generalized Oncology Natural Language Processing Model.

PURPOSE: Limited studies have used natural language processing (NLP) in the context of non-small cell lung cancer (NSCLC). This study aimed to validate the application of an NLP model to an NSCLC cohort by extracting NSCLC concepts from free-text medical notes and converting them to structured, interpretable data. METHODS: Patients with a lung neoplasm, NSCLC histology, and treatment information in their notes were selected from a repository of over 27 million patients. From these, 200 were randomly selected for this study with the longest and the most recent note included for each patient. An NLP model developed and validated on a large solid and blood cancer oncology cohort was applied to this NSCLC cohort. Two certified tumor registrars and a curator abstracted concepts from the notes: neoplasm, histology, stage, TNM values, and metastasis sites. This manually abstracted gold standard was compared with the NLP model output. Precision and recall scores were calculated. RESULTS: The NLP model extracted the NSCLC concepts with excellent precision and recall with the following scores, respectively: Lung neoplasm 100% and 100%, NSCLC histology 99% and 88%, histology correctly linked to neoplasm 98% and 79%, stage value 98.8% and 92%, stage TNM value 93% and 98%, and metastasis site 97% and 89%. High precision is related to a low number of false positives, and therefore, extracted concepts are likely accurate. High recall indicates that the model captured most of the desired concepts. CONCLUSION: This study validates that Optum's oncology NLP model has high precision and recall with clinical real-world data and is a reliable model to support research studies and clinical trials. This validation study shows that our nonspecific solid tumor and blood cancer oncology model is generalizable to successfully extract clinical information from specific cancer cohorts.

Applications of CT-based radiomics for the prediction of immune checkpoint markers and immunotherapeutic outcomes in non-small cell lung cancer.

In recent years, there has been significant research interest in the field of immunotherapy for non-small cell lung cancer (NSCLC) within the academic community. Given the observed variations in individual responses, despite similarities in histopathologic type, immunohistochemical index, TNM stage, or mutation status, the identification of a reliable biomarker for early prediction of therapeutic responses is of utmost importance. Conventional medical imaging techniques primarily focus on macroscopic tumor monitoring, which may no longer adequately fulfill the requirements of clinical diagnosis and treatment. CT (computerized tomography) or PEF/CT-based radiomics has the potential to investigate the molecular-level biological attributes of tumors, such as PD-1/PD-L1 expression and tumor mutation burden, which offers a novel approach to assess the effectiveness of immunotherapy and forecast patient prognosis. The utilization of cutting-edge radiological imaging techniques, including radiomics, PET/CT, machine learning, and artificial intelligence, demonstrates significant potential in predicting diagnosis, treatment response, immunosuppressive characteristics, and immune-related adverse events. The current review highlights that CT scan-based radiomics is a reliable and feasible way to predict the benefits of immunotherapy in patients with advanced NSCLC.