Epidermal Growth Factor Receptor Mutation Rate Research Articles

Correlation of FDG PET/CT, tumor markers and Ki-67 index with EGFR mutation or positive ALK expression in patients with non-small cell lung cancer.

Epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) are the two most common druggable targets in non-small cell lung cancer (NSCLC). To investigate whether the EGFR mutation and ALK rearrangement could be predicted by the combination of FDG avidity, tumor markers and Ki-67 Index. A total of 168 newly diagnosed NSCLC patients who had undergone 18F-FDG PET/CT for staging were enrolled. PET/CT parameters of primary tumors including maximum standardized uptake value (pSUVmax), metabolic tumor volume (pMTV) and total lesion glycolysis (pTLG) were measured. Five serous tumor markers for lung cancer were recorded. Ki-67 labeling index was counted by immunohistochemical staining. EGFR mutation and ALK status were detected by ARMS-PCR and RT-PCR, respectively. Univariate and multivariate analyses were applied to identify the predictors of EGFR mutation and ALK positivity. EGFR mutation rate was 38.1% (64/168), which were found more frequently in female, ≤60 years old, non-smokers and adenocarcinoma patients, and were not related to lymph node involvements, distant metastases, stage and serum tumor markers. Low pSUVmax, pMTV, pTLG and Ki-67 were significantly associated with EGFR mutation. Logistic regression demonstrated that pSUVmax <6.75 and gender (female) were the independent factors affecting EGFR mutation, and the combination of them had a certain predictive value with the area under the curve of 0.784. ALK positive rate was 6.0% (10/168), all of them were adenocarcinoma patients, which were more common in non-smokers, low serum cytokeratin-19 fragment antigen (CYFRA21-1) and low Ki-67, and were not related to FDG activity. No independent factor for ALK positivity was found on Logistic regression. Low pSUVmax, rather than tumor markers or Ki-67, was correlated with EGFR mutation independently, which could be integrated with gender (female) to improve the identification for EGFR mutation in NSCLC patients.

The clinical, radiological, postoperative pathological, and genetic features of nodular lung adenocarcinoma: a real-world single-center data.

The preoperative differential diagnosis of nodular lung adenocarcinoma has long been a challenging issue for thoracic surgeons. This study aimed to explore differential diagnosis of nodular lung adenocarcinoma by comprehensively analyzing its clinical, computed tomography (CT) imaging, and postoperative pathological and genetic features. The clinical, CT imaging, and postoperative pathological features of different classifications of nodular lung adenocarcinoma were retrospectively analyzed through univariate and multivariate statistical methods. There were 132 patients with nodular lung adenocarcinoma enrolled. Firstly, compared with ground-glass nodular lung adenocarcinoma, solid nodular lung adenocarcinoma was more common in women [odds ratio (OR), 3.662; 95% confidence interval (CI): 1.066-12.577] and older adults (OR, 1.061; 95% CI: 1.007-1.119), and CT signs were mostly lobulation (OR, 4.957; 95% CI: 1.714-14.337) and spiculation (OR, 8.214; 95% CI: 2.740-24.621); the mean CT (CTm) value of solid nodular lung adenocarcinoma was significantly higher than that of ground-glass nodular lung adenocarcinoma, and the optimal diagnostic threshold was -267.5 Hounsfield units (HU). Secondly, the maximum diameter of nodule size (NSmax) of invasive adenocarcinoma (IAC) was significantly greater than that of minimally IAC (MIA; OR, 6.306; 95% CI: 1.191-33.400) or atypical adenomatous hyperplasia (AAH)/adenocarcinoma in situ (AIS; OR, 189.539; 95% CI: 4.720-7,610.476), and the optimal diagnostic threshold between IAC and MIA was 1.35 cm; the CTm value of IAC was significantly higher than that of MIA, and the optimal diagnostic threshold was -460.75 HU. Thirdly, lepidic-predominant adenocarcinoma (LPA) manifest more commonly as pure ground-glass nodule (pGGN; OR, 6.252; 95% CI: 1.429-27.358) or mixed ground-glass nodule (mGGN; OR, 4.224; 95% CI: 1.223-14.585). Moreover, the mutation rate of epidermal growth factor receptor (EGFR) in IAC was 70.69% (41/58). The EGFR mutation rates of mGGNs (OR, 8.794; 95% CI: 1.489-51.933) and solid nodules (SNs; OR, 12.912; 95% CI: 1.597-104.383) were significantly higher than that of pGGNs. Furthermore, compared with those of micropapillary-predominant adenocarcinoma (MPA), solid-predominant adenocarcinoma (SPA), or invasive mucinous adenocarcinoma (IMA), there were significantly higher EGFR mutation rates in acinar-predominant adenocarcinoma/papillary-predominant adenocarcinoma (APA/PPA; OR, 55.925; 95% CI: 4.045-773.284) and LPA (OR, 38.265; 95% CI: 2.307-634.596). Different classifications of nodular lung adenocarcinoma have their own clinicopathological and CT imaging features, and the latter is the main predictor.

Abstract 783: Early impact assessment of in-house EGFR testing for NSCLC in Kenya

Abstract Introduction: Quality of life and survival among non-small cell lung cancer (NSCLC) patients have improved in the last two decades owing mainly to use of tyrosine kinase inhibitors (TKIs) and other targeted therapies. Low and middle-income countries (LMICs) especially in Africa, are lagging in realizing these benefits largely due to hurdles in molecular testing. In addition, quality histology and molecular data from LMICs is deficient. The aim of this study is to assess the immediate impact of improved access to epidermal growth factor receptor (EGFR) testing in Kenya, and to establish a long term-lung cancer data base. Methods: Staring mid-June 2023, an in-house PCR-based method was adopted for EGFR testing of NSCLC in order to side step the challenges of out-of-country send outs which was until then, the only option for EGFR testing. Further, a sponsored access program was created. From prospectively accrued samples, we performed a before-and-after assessment of the number of NSCLC cases intercepted, cost and turnaround times (TAT) as measures of impact. Demographic, histopathology, and EGFR mutation profiles were analyzed in comparison to Asia, USA and European data. Whole slide histology scanned images are made to compliment the database. Results: Over the four-month period, 62 NSCLC cases were accrued, median age at diagnosis was 63 with a range of 24 - 93. The male to female ratio was 1: 1.5. Adenocarcinomas comprised 89%, squamous cell carcinoma 5% and 3% were not classifiable. Metastatic disease was reported in 14 (22%) with the brain being the commonest site. EGFR mutations were identified in 16 (25%) with exon 19 deletions and L858R mutations constituting 94% of them. Monthly requisitions for EGFR have increased 3-fold, and the average TAT has been halved to 7 days. Conclusion: Similarities between our data and global patterns are noted; median age is in the seventh decade, NSCLC is more common in women, and so are the rates of EGFR mutations, adenocarcinomas are the predominant type, and there are high rates of brain metastasis at diagnosis. EGFR mutation rates appear to be higher than USA and European data but lower than Asian data. In-house and sponsored testing has had an immediate impact in reduction of costs and TAT and increased requisitions. Assessment of access to targeted therapy, clinical outcome, survival, expansion of molecular profiling beyond EGFR, and build-up of the database including virtual histology images for exploring artificial intelligence algorithms are our next steps. Citation Format: Allan Njau, Samuel Nguku, Joseph Abuodha. Early impact assessment of in-house EGFR testing for NSCLC in Kenya [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 783.

Clinical impact of pleural fluid carcinoembryonic antigen on therapeutic strategy and efficacy in lung adenocarcinoma patients with malignant pleural effusion.

Epidermal growth factor receptor (EGFR) mutation is important in determining the treatment strategy for advanced lung cancer patients with malignant pleural effusion (MPE). Contrary to serum carcinoembryonic antigen (S-CEA) levels, the associations between pleural fluid CEA (PF-CEA) levels and EGFR mutation status as well as between PF-CEA levels and treatment efficacy have rarely been investigated in lung adenocarcinoma patients with MPE. This retrospective study enrolled lung adenocarcinoma patients with MPE and available PF-CEA levels and EGFR mutation results. The patients were categorized based on PF-CEA levels: < 10 ng/mL, 10-100 ng/mL, 100-500 ng/mL, and ≥ 500 ng/mL. The association between PF-CEA levels and EGFR mutation status as well as their therapeutic impact on overall survival was compared among the four groups. This study included 188 patients. PF-CEA level was found to be an independent predictor of EGFR mutation but not S-CEA level. The EGFR mutation rates were higher as the PF-CEA levels increased, regardless of cytology results or sample types. Among EGFR-mutant lung adenocarcinoma patients receiving EGFR-tyrosine kinase inhibitor (TKI) treatment, those with high PF-CEA levels had significantly better survival outcomes than those with low PF-CEA levels. High PF-CEA levels were associated with high EGFR mutation rate and may lead to a favorable clinical outcome of EGFR-TKI treatment in EGFR-mutant lung adenocarcinoma patients with MPE. These findings highlight the importance of actively investigating EGFR mutation detection in patients with suspected MPE and elevated PF-CEA levels despite negative cytology results.

Rapid and reliable testing for clinically actionable EGFR mutations in non-small cell lung cancer using the IdyllaTM platform: a real-world two-center experience in Greece

ABSTRACT Background Limited information exists on epidermal growth factor receptor (EGFR) molecular epidemiology in Greece. Next-generation sequencing (NGS) is the recommended method for EGFR genotyping in NSCLC. The Idylla Biocartis platform is a fully automated system for actionable EGFR mutation detection. Research design and methods We describe the prevalence of EGFR mutations in NSCLC patients in two high-volume clinical centers in Greece and compare key methods used for their determination. Eight hundred and fifty-seven FFPE samples from NSCLC patients were tested for EGFR mutations at University of Crete (UoC; n = 324) and at Evangelismos Hospital, Athens (Evangelismos; n = 503). Results The prevalence of EGFR mutations was 11.1% in the whole cohort (11.5% in non-squamous). The detection rate was 11.0% by NGS, 9.8% by Sanger and 11.3% by Idylla for the whole cohort (12.0% in non-squamous). The agreement between Idylla and Sanger was 93.2%. A targetable EGFR mutation was detected in 10.0% using tissue NGS alone, and in 16.0% using concurrent Idylla ctEGFR testing. Conclusion The frequency of EGFR mutations was as expected for a Caucasian population. The Idylla EGFR test performance is comparable to reference methods and with a shorter TAT. Adding a concurrent plasma Idylla test to tissue NGS testing increases the detection rate of EGFR mutations in NSCLC.

Analysis of EGFR Gene Mutations in Lung Adenocarcinoma in Karamay, Xinjiang

Abstract Objective To investigate the mutation types and mutation rate of the epidermal growth factor receptor (EGFR) gene in patients with lung adenocarcinoma and the clinical features of lung adenocarcinoma with EGFR gene mutations in Karamay, Xinjiang, China. Methods Paraffin-embedded tissue samples of adenocarcinoma patients were collected in the Karamay Central Hospital from March 2016 to June 2019, and mutations in exon 18–21 of the EGFR gene were detected by the allele-specific amplification polymerase chain reaction (Amplification Refractory Mutation System–PCR) method. The relationships between the mutation types, mutation incidence, and clinical features were analyzed. Results Of the 170 patients with lung adenocarcinoma, 83 had EGFR mutations. The total mutation rate of EGFR in patients with lung adenocarcinoma was 48.8%, which included mutations in exons 18 (1.2% [2/170]), 19 (19.4% [33/170]), 20 (2.4% [4/170]), and 21 (20.6% [35/170]). Intriguingly, there was a case with 9 mutations in exons 20 and 21. The mutations in exon 19 of EGFR resulted in the deletion of codons 746 to 750. The main mutation in exon 21 was L858R (91.4% [32/35]). There was no significant difference in exons 19 and 21 mutation rates (P &gt; 0.05). The mutation rate of EGFR in female patients was significantly higher than that in male patients (P &lt; 0.05) but had no correlation with the age, smoking status, and clinical stage of patients with non–small cell lung cancer (P &gt; 0.05). The EGFR mutation rate may be related to the degree of tumor differentiation. Conclusion Among patients with lung adenocarcinoma in Kelamayi (city in Xinjiang), EGFR mutations were more frequently detected in female patients, and the main sites of mutations were exons 19 and 21.

Correlation between carcinoembryonic antigen (CEA) expression and EGFR mutations in non-small-cell lung cancer: a meta-analysis.

The purpose of this meta-analysis was to investigate the relationship between serum carcinoembryonic antigen (CEA) expression and epidermal growth factor receptor (EGFR) mutation status in non-small cell lung cancer (NSCLC). Databases such as PubMed, Cochrane, EMBASE and Google Scholar were systematically searched to identify studies assessing the association of serum CEA expression with EGFR mutations. Across 19 studies, 4168 patients were included between CEA expression and EGFR mutations odds ratio (OR) conjoint analysis of correlations. Compared with CEA-negative NSCLC, CEA-positive tumors had an increased EGFR mutation rate (OR = 1.85, 95% confidence interval: 1.48-2.32, P < 0.00001). This association was observed in both stage IIIB/IV patients (OR = 1.60, 95% CI: 1.18-2.15, P = 0.002) and stage I-IIIA (OR = 1.67, 95% CI: 1.01-2.77, P = 0.05) patients. In addition, CEA expression was associated with exon 19 (OR = 1.97, 95% CI: 1.25-3.11, P = 0.003) and exon 21 (OR = 1.51, 95% CI: 1.07-2.12, P = 0.02) EGFR mutations. In ADC pathological type had also showed the correlation (OR = 1.84, 95% CI: 1.31-2.57, P = 0.0004). This meta-analysis indicated that serum CEA expression was associated with EGFR mutations in NSCLC patients. The results of this study suggest that CEA level may play a predictive role in the EGFR mutation status of NSCLC patients. Detecting serum CEA expression levels can give a good suggestion to those patients who are confused about whether to undergo EGFR mutation tests. Moreover, it may help better plan of the follow-up treatment.

Liquid biopsy in clinical outcomes and detection of T790M mutation in metastatic non-small cell lung cancer after progression to EGFR-TKI.

Liquid biopsy (LB) is used to detect epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) and has been demonstrated to have prognostic and predictive value. To associate the rates of EGFR and T790M mutations detected by LB during disease progression after first- or second-generation EGFR-TKIs with clinical characteristics and survival outcomes. From January 2018 to December 2021, 295 patients with advanced EGFR mutant (EGFRm) NSCLC treated with first- or second-generation EGFR-TKIs were retrospectively analyzed. LB was collected at the time of progression. The frequency of EGFRT790M mutations, overall survival (OS), and the clinical characteristics associated with LB positivity were determined. The prevalence of EGFRT790M mutation detected using LB was 44%. In patients with negative vs. positive LB, the median OS was 45.0 months vs. 25.0 months (p= 0.0001), respectively. Patients with a T790M mutation receiving osimertinib had a median OS of 44 months (95% CI [33.05-54.99]). Clinical characteristics associated with positive LB at progression extra-thoracic involvement, > 3 metastatic sites, and bone metastases. Our findings showed that LB positivity was associated with worse survival outcomes and specific clinical characteristics. This study also confirmed the feasibility and detection rate of T790M mutation in a Latin American population.

Feasibility analysis of rapid gene detection using intraoperative frozen tissues: comparison of intraoperative frozen tissues with paraffin-embedded tissues in epidermal growth factor receptor gene mutation detection of lung adenocarcinoma.

Epidermal growth factor receptor (EGFR) is the driver gene with the highest frequency of mutations in lung adenocarcinoma and can guide the development of targeted therapies. The detection of routine gene mutations must be performed after the preparation of paraffin samples in a standard polymerase chain reaction (PCR) laboratory, which is time-consuming. The Idylla™ EGFR fully automatic PCR system for rapid detection requires no special detection environment and completes the process in only 2.5h. It has been applied to tissues embedded in paraffin. The Idylla™ EGFR automated PCR system was used to detect EGFR gene mutations in intraoperative frozen fresh tissues and paraffin-embedded tissues from 47 enrolled patients with lung adenocarcinoma. The gold standard amplification refractory mutation system (ARMS) method for gene mutation detection was used for verification, and the concordance between the three detection results was compared, to investigate the feasibility of detecting rapid gene mutations in intraoperative frozen samples. The EGFR mutation rate in 47 fresh samples of lung adenocarcinoma was 61.7% (29/47), which is consistent with the mutation level of lung adenocarcinoma in the Asian population (38.8-64.0%). The concordance rate between the Idylla™ frozen tissues and paraffin-embedded tissues was 91.4% (43/47) when compared to the ARMS method, while the coincidence rate between the two methods was 93.6% (44/47). The three methods had a total consistency rate of 89.4% (42/47). The Idylla™ EGFR fully automatic PCR system directly detects EGFR mutations in fresh tissues. The operation is simple, the detection time is short, and the accuracy is high. The detection time is reduced to 1/4-1/3 of the original time while meeting clinical standards for detecting the gene status of patients, thus saving crucial time for individualized and accurate treatment of patients. The method has promising clinical application prospects.

Investigation of EGFR and ALK mutation frequency and treatment results in advanced non-small cell lung cancer.

Lung cancer has opened a new era in cancer treatment by elucidating the tumor's molecular structure and identifying the targetable mutations. Identifying the targeted mutations in lung cancer constitutes one of the main steps of treatment planning. The frequency of EGFR (epidermal growth factor receptor gene) and ALK (anaplastic lymphoma kinase gene) mutations in non-small cell lung cancer (NSCLC) also varies in populations depending on ethnicity, gender, smoking, and histopathological subtype. In general, limited data are available regarding the frequency and regional distribution of these mutations in the Turkish population. Our study aimed to determine the frequency of EGFR and ALK mutations in patients with advanced-stage NSCLC and compare the clinical characteristics, treatment, and survival results of cases with mutations with the group without mutations. In our study, 593 patients with advanced-stage NSCLC diagnosis and mutational analyses were evaluated retrospectively. Demographic characteristics, tumor stages (tumor, node, metastasis, TNM), EGFR and ALK analysis results, treatments applied, and survival of the cases were recorded. EGFR analysis, exon 18, 19, 20, and 21 mutations were studied with real-time PCR (RT-PCR) Rotor-Gene system from patients' samples. For ALK analysis, the ALK Break Apart kit (Zytovision GmbH; Germany) was used with the fluorescent in situ hybridization (FISH) method. In our study, EGFR mutation was detected in 63 patients (10.6%) and ALK mutation in 19 patients (3.2%) out of 593 patients. EGFR mutation was observed more frequently in women and non-smokers (P = 0.001, P = 0.003). No correlation was found between the presence of EGFR mutation and metastases regions and recurrence (P > 0.05). ALK mutation was observed more frequently in non-smokers and females (P = 0.001, P = 0.003). Patients with ALK mutations were younger than other groups (P = 0.003). There was also no significant relationship between ALK mutation and metastates regions and recurrence after treatment (P > 0.05). Patients with EGFR or ALK mutations had a longer life span than other cases (P = 0.474). Those who had ALK mutations and received targeted therapy had a longer average life expectancy (P < 0.05). No difference was observed in those who had EGFR mutations and received targeted treatment in terms of survival (P > 0.05). In our study, conducted in the Aegean region of Turkey, the positivity rates of EGFR and ALK mutations were found to be at similar rates with the Caucasian race across the world. EGFR mutation was more common in women, non-smokers, and patients with adenocarcinoma histology. ALK mutation was also detected more frequently in younger patients, women, and non-smokers. Patients with EGFR and ALK mutations had a longer life expectancy than those without the mutation. It was observed that testing patients diagnosed with advanced-stage NSCLC for genetic mutations of the tumor in the first step of the treatment and initiating treatment in patients with mutations provided a significant survival advantage.

Correlation Analysis of Ki67 Expression and EGFR Mutation on the Risk of Recurrence and Metastasis in Postoperative Patients with Stage I Lung Adenocarcinoma

The prognosis of stage I non-small cell lung cancer (NSCLC) is generally good. However, some of the stage I NSCLC patients still may have early recurrence and metastasis, and there is no standard method to screen this part of the population. The aim of this study is to investigate the relationship between Ki67 expression as well as epidermal growth factor receptor (EGFR) mutation and the risk of recurrence in postoperative patients with stage I lung adenocarcinoma. We retrospectively enrolled 118 postoperative patients with stage I lung adenocarcinoma. EGFR mutation was tested using amplification refractory mutation system polymerase chain reaction (ARMS-PCR) , and Ki67 level was detected by immunohistochemistry (IHC), followed by the collection of the patients' clinical characteristics. Kaplan-Meier method, Log-rank test, and Cox proportional hazards regression model were used for the prognostic statistical analysis. Among the 118 patients, the rate of high Ki67 expression was 43.22% (51/118), which is related to gender, smoking status, surgical method, differentiation degree, and postoperative stage (P<0.05). Meanwhile, EGFR mutation rate was 61.02% (72/118), of which EGFR exon 19 deletion mutation rate was 19.49% (23/118), and the EGFR exon 21 L858R mutation rate was 41.53% (49/118). However, Ki67 expression was not associated with EGFR mutation status (χ2=1.412, P=0.235). Survival analysis showed that high Ki67 expression was inversely associated with disease-free survival (DFS) and overall survival (OS) in stage I lung adenocarcinoma (P<0.05), but EGFR mutation status was not significantly associated with DFS and OS (P>0.05). In the subgroup analysis, the DFS of the EGFR exon 19 deletion group was significantly decreased compared with the EGFR exon 21 L858R mutation group (P=0.031), but there was no significant difference in OS (P=0.308). Multivariate analysis showed that there was statistical significance between Ki67 expression (P=0.001) and DFS in stage I lung adenocarcinoma; Ki67 expression (P=0.03) and gender (P=0.015) were associated with OS in stage I lung adenocarcinoma. Ki67 expression is an independent influencing factor for postoperative recurrence and OS of stage I lung adenocarcinoma and it is not significantly associated with EGFR mutation. There is no significant difference between EGFR mutation status and the prognostis of stage I lung adenocarcinoma. However, the prognosis differed in EGFR mutation types; the patients with EGFR exon 19 deletion are at higher risk of recurrence than EGFR exon 21 L858R mutation.

High rate of epidermal growth factor receptor-mutated primary lung cancer in patients with primary breast cancer.

BackgroundWith increased survival in breast cancer, resulting from advances in treatment, patients incur the possibility of subsequent primary malignancies, especially lung cancer. The aim of this study was to assess the frequency of CT-detected pulmonary ground-glass nodules and lung cancer following breast cancer diagnosis, the associations between breast cancer and lung cancer, the pathological features of double primary cancer, and the status of epidermal growth factor receptor (EGFR) mutations in second primary lung cancer.MethodsClinical data from more than 9000 individuals who were diagnosed with primary breast cancer at Jiangsu Province Hospital (Jiangsu, China) between January 2008 and December 2021 were retrospectively analyzed.ResultsOf the 9179 patients, 6512 underwent diagnostic CT, 55 (0.8%) were diagnosed with a second primary lung cancer, which accounted for approximately 18.4% of the pulmonary ground-glass nodules (GGNs) detected. The incidence was higher than in the general female population (standardized incidence ratio 1.4 [95% confidence interval (CI): 1.25-1.55]). Patients who experienced a second primary lung cancer exhibited a significantly higher rate of EGFR mutation (78.5%) than those with lung adenocarcinoma alone, with most exhibiting low-grade malignancy, older age, estrogen receptor negativity, low Ki67, and no lymph node metastasis.ConclusionsBreast cancer patients, especially those with low-grade malignancy, were at high risk for developing primary lung cancer. For isolated GGN in patients with high-risk factors, clinicians should insist on close follow-up. Furthermore, EGFR may play an important role in primary lung adenocarcinomas and breast cancer.

Economic Analysis of Tissue-First, Plasma-First, and Complementary NGS Approaches for Treatment-Naïve Metastatic Lung Adenocarcinoma.

BackgroundTo compare the testing costs and testing turnaround times of tissue-first, plasma-first, and complementary next-generation sequencing (NGS) approaches in patients with treatment-naïve metastatic lung adenocarcinoma.Materials and MethodsWe developed a decision tree model to compare three different approaches. Patients were entered into the model upon cancer diagnosis and those with both insufficient tissue specimens and negative liquid-based NGS were subjected to tissue re-biopsy. Actionable gene alterations with the U.S. Food and Drug Administration (FDA)-approved therapies included epidermal growth factor receptor (EGFR) mutation, anaplastic lymphoma kinase (ALK) gene rearrangement, ROS proto-oncogene 1 (ROS1) rearrangement, B-Raf proto-oncogene (BRAF) V600E mutation, rearranged during transfection (RET) gene rearrangement, mesenchymal-epithelial transition factor (MET) mutation, neurotrophic tyrosine receptor kinase (NTRK) gene rearrangement, K-Ras proto-oncogene (KRAS) G12C mutation, and human epidermal growth factor receptor 2 (HER2) mutation. Model outcomes were testing costs, testing turnaround times, and monetary losses taking both cost and time into consideration. We presented base-case results using probabilistic analysis. Stacked one-way and three-way sensitivity analyses were also performed.ResultsIn terms of testing costs, tissue-first approach incurred US$2,354($1,963–$2,779) and was the most cost-efficient strategy. Complementary approach testing turnaround time (days) of 12.7 (10.8 to 14.9) was found as the least time-consuming strategy. Tissue-first, complementary, and plasma-first approaches resulted in monetary losses in USD of $4,745 ($4,010–$5,480), $6,778 ($5,923–$7,600), and $7,006 ($6,047–$7,964) respectively, and identified the same percentage of patients with appropriate FDA-approved therapies. Costs for liquid-based NGS, EGFR mutation rates, and quantity of tissue specimens were the major determinants in minimizing monetary loss. Plasma-first approach would be the preferable strategy if its testing price was reduced in USD to $818, $1,343, and $1,869 for populations with EGFR mutation rates of 30%, 45%, and 60% respectively.ConclusionThe tissue-first approach is currently the best strategy in minimizing monetary loss. The complementary approach is an alternative for populations with a low EGFR mutation rate. The plasma-first approach becomes increasingly preferable as EGFR mutation rates gradually increase.

Prognostic Significance of PD-L1 Expression and Standardized Uptake Values in the Primary Lesions of Stage IV Adenocarcinoma Lung Cancer.

BackgroundThis study evaluated the prognostic ability of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) in patients with stage IV adenocarcinoma lung cancer to detect protein death-ligand 1 (PD-L1) expression levels.MethodsIn total, 86 patients with stage IV adenocarcinoma lung cancer underwent 18F-FDG PET/CT imaging and PD-L1 expression evaluation before treatment from February 2019 to November 2020 at Bach Mai Hospital, Hanoi, Vietnam. The assessed patient characteristics in this study included sex, age, smoking status, epidermal growth factor receptor (EGFR) mutation, PD-L1 expression level, survival status, tumor, node, and metastasis (TNM) stage, and metastasis locations.ResultsThe average age was 62.23 ± 9.51 years, and men and women represented 67.4% and 32.6% of the population, respectively. The EGFR mutation rate was 36%. PD-L1 expression was negative (detected in <1% of the tumor) in 40.7% of cases and positive in 59.3% of cases (detected in 1–49% of the tumor in 32.6%; detected in ≥50% of the tumor in 26.7%). The mean maximum standardized uptake value (SUVmax) was 11.09 ± 3.94. SUVmax was significantly higher in PD-L1–positive tumors than in PD-L1–negative tumors (12.24 ± 4.01 and 9.43 ± 3.22, respectively; p = 0.001). Receiver operating characteristic curve analysis revealed an area under the curve of SUVmax was 0.681 (95% confidence interval 0.570–0.793, p = 0.004). Compared with PD-L1–negative cases, SUVmax was significantly different in all PD-L1–positive cases (p = 0.001), weakly PD-L1–positive cases (1–49%, p = 0.005), and strongly PD-L1–positive cases (≥50%, p = 0.003). PD-L1 expression levels were significantly associated with SUVmax (p = 0.001), tumor size (p = 0.022), and EGFR mutation status (p = 0.045).ConclusionsSUVmax in the primary lesions was able to predict PD-L1 expression and may play a role in predicting PD-L1 immunotherapy efficacy in patients with stage IV lung adenocarcinoma.

Clinical significance of epidermal growth factor receptor mutations in resected stage IA non-small cell lung cancer

Background: Epidermal growth factor receptor (EGFR) gene mutation is a known predictor of the response to EGFR tyrosine kinase inhibitors. However, detecting EGFR mutations is a potential challenge because of the ground-glass opacity component, and its prognostic value for stage IA lung adenocarcinoma remains controversial. This study aimed to investigate the associations between EGFR mutation status, clinicopathological characteristics, and prognosis in surgically resected stage IA non-small cell lung cancer (NSCLC). Materials and Methods: We retrospectively examined the data of patients who underwent surgical resection for lung cancer between 2004 and 2014. The clinical data, imaging characteristics of nodules, surgical approaches, and outcomes were analyzed. Results: A total of 429 patients (female, n = 303; male, n = 126) with surgically resected stage IA NSCLC were analyzed and 343 were nonsmokers. The EGFR mutation rate was 48.3% (n = 207). Of the patients, 192 (44.8%) had stage IA1, 165 (38.5%) had stage IA2, and 72 (16.8%) had stage IA3 NSCLC. In the analysis of the correlations between clinicopathological features and EGFR status, older age (P = 0.032), nonsmoking history (P = 0.039), and pathological stage (P < 0.05) were related to EGFR mutation. Patients with stage IA2 NSCLC had a higher positive expression of EGFR than patients with stages IA1 and IA3. The 5-year overall survival rates and disease-free survival rates were better in the EGFR mutation group; however, the difference was not statistically significant. Conclusion: EGFR mutations are common in older and nonsmoking patients with stage IA NSCLC. Further separate analyses of EGFR gene mutations and pathological stage could improve the diagnostic performance and predict patients with unavailable EGFR gene testing who may benefit from targeted drug treatment.

Computed tomography-guided lung biopsy for molecular tests: a meta-analysis.

IntroductionComputed tomography (CT)-guided lung biopsy has been widely used for molecular testing.AimTo evaluate the potential clinical effectiveness of computed tomography (CT)-guided lung biopsy in molecular tests.Material and methodsWe searched the related studies from the PubMed, Embase, and Cochrane Library until July 2021. The endpoints included adequacy rates for molecular tests, positive rates of epidermal growth factor receptor (EGFR) mutations, anaplastic lymphoma kinase (ALK) translocation, and Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations.ResultsInitially, we were able to identify 1783 potentially relevant studies, among which only 12 were ultimately included in the present meta-analysis. All the studies were retrospective in nature. A total of 2559 patients underwent CT-guided lung biopsy and 1414 of them received molecular testing. We found that the pooled adequacy rate for molecular tests, positive rate of EGFR mutations, and positive rate of ALK translocation were 95%, 49%, and 7%, respectively. Significant heterogeneity was detected in the endpoints of adequacy rate for molecular tests (I2 = 86.2%) and positive rate of EGFR mutations (I2 = 77.7%). We did not identify any variables that could significantly influence the adequacy rate for molecular tests and positive rate of EGFR mutations. A high risk of publication bias was also found in the endpoint of adequacy rate for molecular tests.ConclusionsCT-guided lung biopsy can serve as an effective method to provide sufficient lung cancer samples for molecular testing. The EGFR gene was found to be the most frequently mutated during the analysis.

A Hospital-Based Study of EGFR and ALK Mutations in Patients with Lung Adenocarcinoma in Odisha

Background: Patients with advanced non-small cell lung cancer (NSCLC) have considerably benefited from the molecular identification of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) mutations and subsequent targeted therapy against these biomarkers. Few studies have been undertaken in the Indian population on the analysis of both EGFR and ALK mutations in lung adenocarcinoma cases. Aim and Objectives: The aim of this study was to determine the prevalence of EGFR and ALK mutations in lung adenocarcinoma patients, as well as to link mutational status with age, sex, and smoking history. Materials and Methods: This single hospital-based retrospective study was conducted at the Department of Medical Oncology, Acharya Harihar Post Graduate Institute of Cancer, Cuttack, on histologically proven lung adenocarcinoma cases over a duration of two years from 01.08.2019 to 31.07.2021. Results: Out of a total of 164 cases, males comprised 89 (54.26%) of the 164 lung adenocarcinoma cases, while females comprised 75 (45.73%). EGFR mutations were found in 42 (26.75%) of the patients. In 9 cases, the ALK gene rearrangement was also determined to be positive (5.66%). In terms of EGFR and ALK mutations, there was no statistically significant relationship between patient age and gender. (P-value &lt; 0.05). In our research, we found a link between nonsmokers and EGFR and ALK mutations. (P-value &lt;0.05). The deletion of exon 19 (76.19%) was the most prevalent mutation, followed by the exon 21 L858R mutation (14.28%). Conclusion: This study was found to have a significantly higher rate of EGFR and ALK mutation in the Indian population with adenocarcinoma of lung compared to Western populations. To get the maximum benefit from targeted therapies, all patients of adenocarcinoma of the lung should have mutational testing for EGFR and ALK as part of a broad molecular pannel.

Differential diagnosis of multiple primary lung cancers and intra-lung metastasis of lung cancer by multiple gene detection.

Differential diagnosis of multiple primary lung cancers and intra-lung metastasis of lung cancer by multiple gene detection.

Relationship between molecular changes in epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) mutations in lung adenocarcinoma*

Abstract Objective This study aimed to analyze the relationship between the mutations in epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) and their impact on the prognosis and treatment of lung adenocarcinoma. Methods A total of 158 cases of lung adenocarcinoma reported between January 2007 and January 2014 were retrospectively analyzed. These tumors were resected using radical pneumonectomy and underwent pathology-based diagnosis at our institution (Inner Mongolia People’s Hospital, Hohhot, China). The tissue sections were evaluated using the updated World Health Organization classification of lung adenocarcinomas (2015 version), with each histological component recorded in 5% increments. The histological subtypes were classified, and any surviving cases were followed up. The reverse transcription-polymerase chain reaction (RT-PCR) and direct DNA sequencing were used to evaluate mutations in exons 18, 19, 20, and 21 in the EGFR gene, and the echinoderm microtubule-associated protein-like 4 gene-ALK variant (EML4-ALK) fusions were detected using sequencing. Results Our cohort included 25 patients with pre-invasive adenocarcinoma, 13 patients with lepidic, 66 patients with acinar, 13 patients with papillary, and 25 patients with solid infiltrative adenocarcinoma with the remaining cases presenting with a variety of pathological subtypes. The prognosis of each histological subtype was different with the 5-year disease-free survival and 5-year overall survival (OS) of pre-invasion adenocarcinoma at 100%; the 5-year OS of lepidic, acinar, and papillary adenocarcinoma patients was only 84.6%, 72.7%, and 76.9%, respectively. The 5-year OS of solid and mucinous adenocarcinomas were 32.0% and 36.4%, respectively. EGFR mutation was detected in 69 cases with a mutation rate of 43.7% and majority of these mutations were found in exons 19 (50.6%) and 21 (37.9%), with women and non-smokers shown to experience a higher mutation rate (P &lt; 0.05). However, histological subtype analysis showed that EGFR mutations were primarily found in adenocarcinomas. Most of these mutations were found in lepidic (53.8%) or acinar adenocarcinomas (50.0%), whereas these mutations were rare in both solid (28.0%) and mucinous adenocarcinoma (27.2%). The fusion mutation rate in the EML4-ALK gene was 5.69%, and was most common in young, nonsmoking patients (P &lt; 0.05). Conclusion The prognosis of patients in each lung adenocarcinoma subtype is different, and these outcomes are likely related to mutations in the EGFR and EML4-ALK genes. EGFR mutation rates are higher in lepidic and acinar adenocarcinomas, whereas EML4-ALK gene fusion mutations are more common in solid and mucinous adenocarcinoma. EGFR mutations are more common in female and non-smoking patients, whereas EML4-ALK fusions are more common in young, non-smoking patients.

Analysis of the Relationship Between the Quality of Small Biopsy Specimens of Non-small Cell Lung Cancer and the Mutation Rate of EGFR Gene

背景与目的表皮生长因子受体（epidermal growth factor receptor, EGFR）是非小细胞肺癌（non-small cell lung cancer, NSCLC）患者中突变率最高的基因，准确检测出其突变类型有助于指导患者接受靶向药物治疗从而延长患者生存期。为了得到准确的检查结果，基因检测平台对标本质量有一定要求。已有文献报道标本的肿瘤细胞数量及其比例等会影响EGFR基因突变检出率，本研究旨在分析NSCLC小活检标本质量与突变扩增系统（amplification refractory mutation system, ARMS）法检测EGFR基因突变检出率的关系。方法收集299例小活检肺腺癌病例的临床特征、在显微镜下评估切片的肿瘤细胞数量及比例、标本提取的DNA浓度、EGFR基因突变检测结果，分析标本质量与EGFR基因突变检出率的关系。结果肿瘤细胞数≤500组与 > 500组EGFR基因突变阳性率分别为40.7%（11/27）、43.8%（119/272），两者间无统计学差异（P=0.764）。DNA浓度≤20.4 ng/μL组及 > 20.4 ng/μL组的基因突变阳性率分别为42.7%（64/150）、44.3%（66/149），两者间无统计学差异（P=0.776）。肿瘤细胞比例≤30%及 > 30%组的阳性率分别为29.4%（20/68）、47.6%（110/231），两者间存在统计学差异（P=0.008）。多因素Logistic分析显示男性、甲状腺转录因子1（thyroid transcription factor-1, TTF-1）阴性、有吸烟史及肿瘤细胞比例 < 30%是影响EGFR基因突变低检出率的主要因素。结论在达到检测的最低要求后，肿瘤细胞比例仍可影响EGFR基因突变检出率。有必要在基因检测切片后再次评估最后一张切片的肿瘤细胞比例，对于肿瘤细胞比例过低的标本，建议通过显微切割等方法富集肿瘤细胞，提高其肿瘤细胞比例，得出更准确的检测结果。对于无法进行肿瘤细胞富集的标本，可行循环肿瘤DNA（circulating tumor DNA, ctDNA）检测作为补充，若结果仍为阴性才需考虑再次活检获取足够的肿瘤标本进行分子检测。