EGFR Mutation Rate Research Articles

Prognostic implications, genomic and immune characteristics of lung adenocarcinoma with lepidic growth pattern

AimsConflicting data were provided regarding the prognostic impact and genomic features of lung adenocarcinoma (LUAD) with lepidic growth pattern (LP+A). Delineation of the genomic and immune characteristics of LP+A could...

Liquid-based cytology specimens for next-generation sequencing in lung adenocarcinoma: challenges and evaluation of targeted therapy

BackgroundTo explore challenges of liquid-based cytology (LBC) specimens for next-generation sequencing (NGS) in lung adenocarcinoma and evaluate the efficacy of targeted therapy.MethodsA retrospective analysis was conducted on the NGS test of 357 cases of advanced lung adenocarcinoma LBC specimens and compared with results of histological specimens to assess the consistency. The impact of tumor cellularity on NGS test results was evaluated. The utility of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) was collected. Clinical efficacy evaluation was performed and survival curve analysis was conducted using the Kaplan-Meier method.ResultsThere were 275 TKI-naive and 82 TKI-treated specimens, the mutation rates of cancer-related genes detected in both groups were similar (86.2% vs. 86.6%). The EGFR mutation rate in the TKI treated group was higher than that in the TKI-naive group (69.5% > 54.9%, P = 0.019). There was no significant difference in the EGFR mutation frequency among different tumor cellularity in the TKI-naive group. However, in the TKI treated group, the frequency of EGFR sensitizing mutation and T790M resistance mutation in specimens with < 20% tumor cellularity was significantly lower than that in specimens with ≥ 20% tumor cellularity. Among 22 cases with matched histological specimens, 72.7% (16/22) of LBC specimens were completely consistent with results of histological specimens. Among 92 patients with EGFR-mutant lung adenocarcinoma treated with EGFR-TKIs in the two cohorts, 88 cases experienced progression, and the median progression-free survival (PFS) was 12.1 months.ConclusionsCytological specimens are important sources for gene detection of advanced lung adenocarcinoma. When using LBC specimens for molecular testing, it is recommended to fully evaluate the tumor cellularity of the specimens.

Correlation between common driver gene variations and clinicopathological typing in lung adenocarcinoma

Objective: To correlate the common driver gene variations in primary lung adenocarcinoma with their clinical characteristics and histopathological subtypes. Methods: There were 4 995 cases of primary lung adenocarcinoma diagnosed at Weifang People's Hospital of Shandong Province from January 2015 to December 2021 which were retrospectively analyzed. Among them 1 983 cases were evaluated for their histopathological subtype; 3 012 were analyzed for the correlation of their histopathological subtypes and corresponding driver gene variations, including invasive non-mucinous adenocarcinoma (INMA) and invasive mucinous adenocarcinoma (IMA), and morphologically, poorly-differentiated, moderately-differentiated and well-differentiated adenocarcinomas. Next-generation sequencing was used to detect variations in EGFR, KRAS, ALK, RET, ROS1, MET, HER2, or BRAF driver genes. Results: There were 2 384 males and 2 611 females. EGFR and ALK variations were more commonly found in female patients aged 60 years or older, with EGFR mutation rate in clinical stage Ⅰ (25.80%) significantly higher than in other stages (P<0.05). KRAS mutations were more commonly detected in male smokers aged 60 years or older, HER2 mutations were more commonly in patients younger than 60 years, and RET mutations were more commonly in non-smokers (all P<0.05). No correlation was found between ROS1, MET, and BRAF gene variations and their clinical characteristics (P>0.05). For the histopathological subtypes, among the 1 899 cases of acinar adenocarcinoma, EGFR mutation rate was the highest (67.30%) compared to the other genes. Exon 21 L858R and exon 19 del were the main mutation sites in IMA and INMA, with a higher mutation rate at exon 20 T790M (11.63%) in micropapillary adenocarcinoma. In IMA, KRAS had the highest overall mutation rate (43.80%), with statistically significant difference in mutation rates of exon 2 G12D and exon 2 G12V in acinar adenocarcinoma, solid, and IMA (P<0.05). KRAS mutation at various sites were higher in poorly differentiated groups compared to moderately- and well-differentiated groups (P<0.05). HER2 mutations were more commonly observed in acinar adenocarcinoma, papillary, and micropapillary adenocarcinoma of INMA. BRAF mutation was higher in micropapillary adenocarcinoma compared with other types (P<0.05). Conclusions: Variations in EGFR, ALK, KRAS, HER2, and RET in primary lung adenocarcinoma are associated with patients' age, smoking history, and clinical stage, and driver gene mutations vary among different histopathological subtypes. EGFR mutations are predominant in INMA, while KRAS mutations are predominant in IMA.

Real-world data analysis of first-line targeted therapy for patients with non-small cell lung cancer with different EGFR mutation status in a tertiary care hospital.

e20586 Background: Lung cancer is still the malignant tumor with the highest incidence and mortality rate in the world, of which non-small cell lung cancer (NSCLC) accounts for about 85%. The EGFR mutation rate in Asians is 30%-60%, with exon 19 deletion mutations and exon 21 L858R point mutations accounting for about 90% of EGFR mutations, which are the classic EGFR mutation types. The two have significant differences in clinical characteristics, and some clinical trials have shown differences in efficacy between different subgroups, but whether they exist in the real world needs to be further confirmed. Meanwhile, the efficacy of first-line targeted therapy in patients with coexisting mutant NSCLC harboring different EGFR classical mutations and whether there is a difference in different subgroups has not been conclusively determined. Methods: To collect general clinical data and their genetic test reports of NSCLC patients diagnosed with gene mutations who attended the Affiliated Hospital of North Sichuan Medical College from January 2019 to December 2021 for follow-up, with a follow-up date of June 30,2023, as the end date. Kaplan-Meier survival analysis and log-rank test were applied to compare:1)the median PFS in different subgroups of patients with no co-mutation classic EGFR mutation;2)the median PFS in patients with co-mutation classic EGRR mutation and no co-mutation classic EGFR mutation;3)the median PFS in different subgroups of patients with no co-mutation 19-Del/L858R and with co-mutation 19-Del/L858Rpatients;4)median PFS of patients between co-mutated 19-Del and L858R subgroups. Results: The median PFS of 19Del was significantly better than that of L858R in different subgroups of EGFR classical mutations (14.0 months vs. 8.1 months, p = 0.004 &lt; 0.05). The median PFS of EGFR classical mutation was significantly better than that of EGFR classical mutation with co-mutation,11.1months vs. 5.8 months, respectively, p &lt; 0.001. In different subgroups,19Del median PFS was superior to 19Del co-mutation (14.0 months vs. 6.1 months, p = 0.001 &lt; 0.05),and L858R median PFS was superior to L858R co-mutation (8.1 months vs. 5.8 months, p = 0.449 &gt; 0.05). 19Del co-mutation and L858R co-mutation median PFS were not observed in the analysis of the same simple 19del first-line targeted therapy survival benefit was significantly better than the similar survival benefit of L858R, whose median PFS was 6.1 months vs. 5.8 months, respectively, p = 0.449&gt;0.05, the difference was not statistically significant. Conclusions: The survival benefit of first-line targeted therapy for 19Del in the real world is superior to that of L858R, while the clinical benefit of first-line targeted therapy is poor for classical mutations in EGFR with co-mutations, and combinations with other therapeutic modalities should be considered.

Prevalence of EGFR Mutations in Patients With Resected Stages I to III NSCLC: Results From the EARLY-EGFR Study

IntroductionThere is limited literature on the prevalence of EGFR mutations in early stage NSCLC. EARLY-EGFR (NCT04742192), a cross-sectional study, determined the prevalence of EGFR mutations in early stage NSCLC. MethodsThis noninterventional, real-world study enrolled consecutive patients with resected stages IA to IIIB (American Joint Committee on Cancer eighth edition) NSCLC from 14 countries across Asia, Latin America, and the Middle East and Africa. The primary end point was prevalence of EGFR mutations and secondary end points included prevalence of EGFR mutation subtypes and treatment patterns. ResultsOf 601 patients (median [range] age: 62.0 [30.0–86.0] y) enrolled, 52.7% were females and 64.2% were nonsmokers. Most had stages IA to IB NSCLC (64.1%) and adenocarcinoma (98.7%). Overall prevalence of EGFR mutations was 51.0%; most reported exon 19 deletions (48.5%) followed by exon 21 L858R mutations (34.0%). Women had a higher EGFR mutation rate than men (64.0% versus 36.4%). Compared with no EGFR mutations, patients with EGFR mutations were more likely to be nonsmokers (35.1% versus 60.9%) and have stage I NSCLC than stages II and III NSCLC (54.8% versus 47.3% and 35.6%). Systemic adjuvant therapy was planned in 33.8% of the patients with stages IB to IIIB disease and adjuvant chemoradiotherapy in 6.8%. Age above or equal to 60 years, females, and Asians were found to have a significantly (p < 0.05) higher odds of EGFR mutations, whereas smoking history and stage III disease had lower odds of EGFR mutations. ConclusionsThe EARLY-EGFR study provides an overview of EGFR mutations and subtype prevalence in patients with early stage NSCLC. The study highlights the limited adherence to treatment guidelines suggesting an unmet need for improved adjuvant therapy.

Clonal expansion of shared T cell receptors reveals the existence of immune commonality among different lesions of synchronous multiple primary lung cancer

The increase in the detection rate of synchronous multiple primary lung cancer (MPLC) has posed remarkable clinical challenges due to the limited understanding of its pathogenesis and molecular features. Here, comprehensive comparisons of genomic and immunologic features between MPLC and solitary lung cancer nodule (SN), as well as different lesions of the same patient, were performed. Compared with SN, MPLC displayed a lower rate of EGFR mutation but higher rates of BRAF, MAP2K1, and MTOR mutation, which function exactly in the upstream and downstream of the same signaling pathway. Considerable heterogeneity in T cell receptor (TCR) repertoire exists among not only different patients but also among different lesions of the same patient. Invasive lesions of MPLC exhibited significantly higher TCR diversity and lower TCR expansion than those of SN. Intriguingly, different lesions of the same patient always shared a certain proportion of TCR clonotypes. Significant clonal expansion could be observed in shared TCR clonotypes, particularly in those existing in all lesions of the same patient. In conclusion, this study provided evidences of the distinctive mutational landscape, activation of oncogenic signaling pathways, and TCR repertoire in MPLC as compared with SN. The significant clonal expansion of shared TCR clonotypes demonstrated the existence of immune commonality among different lesions of the same patient and shed new light on the individually tailored precision therapy for MPLC.

High-efficiency EGFR genotyping using cell-free DNA in bronchial washing fluid.

EGFR mutation testing is required for treatment of lung adenocarcinoma using epidermal growth factor receptor-tyrosine kinase inhibitor. However, the amounts of tumor tissue or tumor cells obtained by bronchoscopy are often insufficient. Bronchial washing fluid, obtained by lavage with saline after tumor biopsy or brushing, and the supernatant of bronchial washing fluid are thought to contain cell-free DNA that would be potentially applicable for EGFR testing. From among patients with suspected adenocarcinoma or non-small cell lung carcinoma diagnosed from biopsy or surgical specimens at the University of Tsukuba Hospital between 2015 and 2019, cell-free DNAs from 80 specimens of supernatant of bronchial washing fluid (50 with EGFR mutation and 30 with wild type EGFR) and 8 blood serum samples were examined for EGFR mutation using droplet digital PCR. Among the 50 patients harboring EGFR mutation, the rate of positivity for cell-free DNA extracted from supernatant of bronchial washing fluid was 80% (40/50). In nine of the EGFR mutation-positive cases, tumor cells were not detected by either biopsy or cytology, but the mutation was detected in four cases (4/9, 44%). Comparison of the cell-free DNA mutation detection rate between supernatant of bronchial washing fluid and blood serum in six cases showed that mutations were detected from the former in all cases (6/6, 100%), but from the latter in only one case (1/6, 17%). Using supernatant of bronchial washing fluid samples, the detection rate of EGFR mutation was high, and EGFR mutations were detectable even when no tumor cells had been detectable by biopsy or cytology. Supernatant of bronchial washing fluid might be an effective sample source for EGFR mutation testing.

Targeted next-generation sequencing of 491 lung cancers in clinical practice: Implications for future detection strategy and targeted therapy

Although lung cancer remains the most common cause of global cancer-related mortality, the identification of oncogenic driver alterations and the development of targeted drugs has dramatically altered the therapeutic landscape. In this retrospective study, we found that 97.7% samples carried at least one mutation in the 25 genes tested in our cohort. 53.6% samples were positive for EGFR mutations, followed by TP53 (41.1%), KRAS (11.8%), ERBB2 (4.3%). EGFR mutations were mainly found in female adenocarcinomas, while TP53 was mainly found in male non-adenocarcinomas. Significant differences can be found in the mutation rate of EGFR (60.9% vs 11.9%), KRAS (12.2% vs 25.0%), STK11 (1.5% vs 11.9%), FGFR3 (2.4% vs 0.0%) and ERBB4 (1.2% vs 6.1%) between adenocarcinoma in our cohort and TCGA-LUAD data (all p < 0.001). What's more, we found that the mutation of EGFR increased significantly from adenocarcinomas in situ (AIS, 21.4%) to microinvasive adenocarcinomas (MIA, 52.4%) and invasive adenocarcinomas (IA, 61.1%), while the mutation of ERBB2 dropped markedly from AIS (21.4%) to MIA (9.5%) and IA (4.1%). At last, comparations between targeted NGS and ARMS-based single gene test in the detection of EGFR showed a 94.6% consistence. In conclusion, targeted NGS can provide a comprehensive mutational profile of lung cancer. Considering the high mutation rate of EGFR in NSCLC of Asian populations, a specialized detection strategy should be conducted.

Survival analysis of patients with advanced non-small cell lung cancer receiving EGFR-TKI treatment of Yunnan in southwestern China: a real-world study.

Patients with EGFR mutations who have advanced-stage non-small cell lung cancer (NSCLC) already receive tyrosine kinase inhibitors (TKIs) as the standard first-line therapy. Notably, Yunnan is a regional high incidence area of lung cancer in the highlands with a high rate of rare EGFR mutations. Overall, lung cancer patients in Xuanwei may present a distinct subgroup globally. Recent studies suggested that the NSCLC cohort in Xuanwei harbored a significantly higher uncommon mutation rate. However, little was known about the clinicopathological features and treatment efficacy of EGFR-TKI in Yunnan NSCLC patients. This study aimed to investigate the clinical impact of histologic type on the survival outcomes of patients with stage IIIB and IV NSCLC receiving EGFR-TKI treatment of Yunnan in southwestern China. In this retrospective study, we enrolled advanced NSCLC patients (IIIB-IV) with EGFR mutations who were first diagnosed and treated at Yunnan Cancer hospital from January 2016 to December 2019. Sociodemographics, lifestyle, survival, and clinicopathological characteristics of the patients were collected. The Kaplan-Meier method was used to assess the OS and PFS of patients. An analysis of prognostic factors was conducted using Cox regression. A total of 468 eligible patients were included. The median progression-free survival (PFS) and overall survival(OS) were 11.30(95% CI, 10.12-12.48) months and 30.30(95% CI, 26.24-34.36) months. Based on survival analysis among all the patients,females(HR=0.815;95% CI:0.671-0.989; P=0.017), Xuanwei origin (HR=0.776; 95% CI: 0.609-0.989; P=0.040), sample types(HR=0.780; 95% CI: 0.642-0.947; P=0.012) had a longer PFS. Multivariable analysis showed that only the sample type was an independent factor on median PFS with EGFR-TKI therapy. Patients less than 60 years old (HR=1.433; 95% CI:1.134-1.812, P=0.003)had better OS, but objectives with BMI≥24kg/m2(HR=0.653; 95% CI: 0.500-0.864; P=0.002), females(HR=0.776; 95% CI:0.613-0.982; P=0.035)and patients with tissue sample type (HR=0.760; 95% CI:0.600-.0961; P=0.022) had better OS. Notably, subgroup analysis of our study also found that PFS was significantly better in patients with G719X, L861Q, S768I, G719X+L861Q, and G719X+S768I in Xuanwei than classical mutation ones, including 19-Del and L858R (median 22.7 vs. 12.0 months, HR=0.523, P=0.010), while PFS was inferior in patients with rare mutations of EGFR in non-Xuanwei than the classical mutation ones (median 5.10 vs. 11.10 months, HR=1.760, P=0.015). NSCLC patients in Yunnan displayed a unique EGFR mutation profile, especially a higher prevalence of EGFR uncommon and compound mutations subtype. This study indicates prognostic factors of NSCLC treated with EGFR-TKI in Yunan and Xuanwei. This study will provide new clinical evidence for EGFR-TKI-targeted therapy in patients with rare EGFR mutations in China and worldwide. More researchs were needed for NSCLC EGFR-TKI therapy and medical insurance policy-making in Yunnan, Xuanwei area and uncommon especially.

Proteomics-based clustering of lung adenocarcinoma identifies three subtypes with significantly different clinical and molecular features.

Lung adenocarcinoma (LUAD) is a predominant subtype of lung cancer. Although molecular classification of LUAD has been widely explored, proteomics-based subtyping of LUAD remains scarce. We proposed a subtyping method for LUAD based on the expression profiles of 500 proteins with the largest expression variability across LUAD. Furthermore, we comprehensively compared molecular and clinical features among the LUAD subtypes. Consensus clustering identified three subtypes of LUAD, namely MtE, DrE, and StE. We demonstrated this subtyping method to be reproducible by analyzing two independent LUAD cohorts. MtE was characterized by high enrichment of metabolic pathways, high EGFR mutation rate, low stemness, proliferation, invasion, metastasis and inflammation signatures, favorable prognosis; DrE was characterized by high enrichment of DNA repair pathways, high TP53 mutation rate, and high levels of genomic instability, stemness, proliferation, and intratumor heterogeneity (ITH); and StE was characterized by high enrichment of stroma-related pathways, high KRAS mutation rate, and low levels of genomic instability. The proteomics-based clustering analysis identified three LUAD subtypes with significantly different molecular and clinical properties. The novel subtyping method offers new perspectives on the cancer biology and holds promise in improving the clinical management of LUAD.

Correlation exploration among CT imaging, pathology and genotype of pulmonary ground-glass opacity.

To analyse the clinical features, imaging manifestation, pathological typing and genetic testing results of patients undergoing surgery for ground-glass opacity (GGO) nodules, and explore the reasonable diagnosis and treatment program for GGO patients as to provide the basis for the establishment of GGO treatment process. This study is an exploratory study. 465 cases with GGO confirmed by HRCT, undergoing surgery and approved by pathologic diagnosis in Shanghai pulmonary hospital were enrolled in this study. All the patients with GGO were cases with single lesion. The relationship between the clinical, imaging, pathological and molecular biological data of single GGO were statistically studied. (1) Among 465 cases, the median age was 58 years and females were 315 (67.7%); there were 397 (85.4%) non-smoking, and 354 cases (76.1%) had no clinical symptoms. There were 33 cases of benign and 432 cases of malignant GGO. Significant differences were observed on the size, vacuole sign, pleural indentation and blood vessel sign of GGO between two groups (p < 0.05). Of 230 mGGO, there were no AAH, 13 cases of AIS, 25 cases of MIA and 173 cases of invasive adenocarcinoma. The probability of solid nodules in invasive adenocarcinoma was higher than that in micro invasive carcinoma, and the difference was statistically significant (p < 0.05). 360 cases were followed up with the average follow-up time of 6.05 months, and GGO of 34 cases (9.4%) increased. (2) In 428 adenocarcinoma samples approved by pathologic diagnosis, there were 262 (61.2%) lesions of EGFR mutation, 14 (3.3%) lesions of KRAS mutation, 1 (0.2%) lesion of Braf mutation, 9 (2.1%) lesions of EML4-ALK gene fusion and 2 (0.5%) lesions of ROS1 fusion. The detection rate of gene mutation in mGGO was higher than that of pGGO. During the follow-up period, genetic testing results of 32 GGO showed that EGFR mutation rate was 53.1%, ALK positive rate of 6.3%, KRAS mutation rate of 3.1% and no ros1 and BRAF gene mutation. No statistically significant difference was observed in comparison with unchanged GGO. (3) EGFR mutation rate of invasive adenocarcinoma was the highest (168/228, 73.7%), mainly in the 19Del and L858R point mutations. No KRAS mutation was found in atypical adenoma hyperplasia. No significant difference was observed on the mutation rate of KRAS between different types of GGO (p = 0.811). EML4-ALK fusion gene was mainly detected in invasive adenocarcinoma (7/9). GGO tends to occur in young, non-smoking women. The size of GGO is related to the degree of malignancy. Pleural depression sign, vacuole sign and vascular cluster sign are all characteristic images of malignant GGO. pGGO and mGGO reflect the pathological development of GGO. During the follow-up, it is found that GGO increases and solid components appear, which is the indication of surgical resection. The detection rate of EGFR mutations in mGGO and invasive adenocarcinoma is high. pGGO has heterogeneity in imaging, pathology and molecular biology. Heterogeneity research helps to formulate correct individualized diagnosis and treatment plans.

Stromal micropapillary pattern and CD44s expression predict worse outcome in lung adenocarcinomas with micropapillary pattern

ObjectivesThis study aims to investigate the clinicopathologic characteristics of lung adenocarcinoma with micropapillary pattern (MPP) and the expression of CD44s and CD44v6 in MPP. MethodsA total of 202 patients diagnosed with primary lung adenocarcinoma with MPP were included. We estimated the proportion of MPP in each tumor tissue and divided MPP into aerogenous micropapillary pattern (AMP) and stromal micropapillary pattern (SMP). The expression of CD44s and CD44v6 was estimated by immunohistochemical staining. Clinicopathologic data were collected from the patients’ medical records. We also collected patients’ follow-up data and used PFS (progression-free survival) as a survival indicator. ResultsLung adenocarcinoma with MPP had a high risk of pleural invasion, lymph node metastasis, in advanced TNM stage, and a high rate of EGFR mutation. The presence of SMP indicated a higher rate of pleural invasion, lymphovascular invasion, lymph node metastasis, and a worse PFS compared with pure AMP. We found high expression of CD44s in micropapillary, especially in AMP, while the absence of CD44s expression indicated shorter survival, which was an independent unfavorable factor for PFS. ConclusionsLung adenocarcinoma with micropapillary pattern indicated an unfavorable prognosis, which had two different pattens, AMP and SMP. SMP indicated a worse survival than AMP, and was an independent unfavorable factor for PFS. So, AMP/SMP subclassification is necessary to evaluate patient’s prognosis. Furthermore, the absent expression of CD44s in micropapillary indicated shorter survival, especially in patients with EGFR mutation. Herein, CD44s may be a biological marker for micropapillary lung adenocarcinoma.

The genomic landscape and prognostic significance of 11.q.13 amplification in breast, head &amp; neck, and lung cancer.

e18037 Background: The 11.q.13 (11q) chromosomal band is amplified in many cancers and is associated with poor outcomes in Head &amp; Neck (HN) cancer. The 11q amplicon contains several putative oncogenes, but it’s unclear which amplified genes drive clinical outcomes. We compared the genomic landscape and prognostic significance of 11q amplification in Breast (BC), HN, and non-small cell lung cancer (NSCLC) tumors and identify genes whose expression may be driving clinical outcomes. Methods: DNA (592 genes or WES)/RNA (WTS) sequencing was performed for BC (N = 6,967), HN (N = 2,337), and NSCLC (N = 13,433) tumors submitted to Caris Life Sciences (Phoenix, AZ). 11q amplification (CNA) was defined as tumors with concurrent copy number amplification with copies of FGF3, FGF4, FGF19, and CCND1. Non-amplified tumors (copy number normal, CNN) were defined as a &lt; 4 copies for all four genes. Her2/Neu (+: ≥3+ and &gt; 10%) and HR (ER or PR+: ≥1+ and ≥1%) expression was tested by IHC. tests were applied as appropriate, with P-values adjusted for multiple comparisons. Real-world overall survival (OS) data was obtained from insurance claims, and Kaplan-Meier estimates were calculated for a molecularly defined subset of tumors. 11q genes that were two-fold over expressed in CNA vs CNN were further investigated. The hazard ratio (HR) was calculated for subgroups stratified by median expression of 11q genes. The genes with the five largest HRs (worse OS for CNA, p &lt; .05) were identified as potential driver genes. Results: 11q CNA was observed in 10% of BC, 12% of HN, and 3% of NSCLC. 11q CNA rates were enriched in HR+ BC (HR+/HER2-: 17%, HR+/HER2+: 19%) as compared to HR- tumors (HR-/HER2+: 6%, TNBC: 3%, p &lt; .05). TP53 mutations were less frequent in CNA BC (32 vs 53% CNN) but more frequent in CNA HN (91 vs 52%) and NSCLC (89 vs 66%, p &lt; .05 all). In NSCLC, CNA tumors had a lower rate of EGFR (4.3 vs 12%), KRAS (6.7 vs 28%) and STK11 (5.7 vs 13%) mutations ( p &lt; .05). Over 34 gene were amplified as compared to CNN ( &gt; 3% increase, p &lt; .05), including FGFR3 (11 vs 0.2%) and PDCD1 (10 vs 0). MEN1 (5 vs 0%) was the only 11q gene amplified. CNA was associated with worse OS in HR-/HER2+ (HR 6.3 [2.6-15.5], p = .001), while no difference in OS was observed in BC (HR 1.0 [.9-1.1], p = .62). Compared to CNN, CNA had worse OS in HN (HR 1.5 [1.3-1.7], p &lt; .001) and NSCLC (HR 1.3 [1.2-1.4], p &lt; .001). Stratification by 11q gene expression identified DHCR7, GAL, ANO1, MRPL21, and FADD as the strongest predictors of OS in HN tumors, while GAL, MYEOV, MRPL21, OVOL1, and DHCR7 were strongest in NSCLC (HR: 1.3-1.2). Conclusions: 11q CNA shows differential association with key driver mutations across cancer types that provides new insight to patient subpopulations harboring these alterations. Co-amplification of non-11q genes in NSCLC suggests a unique mechanism of genome instability. The role of DHCR7 and GAL as predictors of clinical outcomes in HN and NSCLC CNA tumors warrants further investigation.

Afatinib for the Treatment of NSCLC with Uncommon EGFR Mutations: A Narrative Review.

Afatinib, the world's first irreversible ErbB family (containing four different cancer cell epidermal growth factor receptors, including EGFR, HER2, ErbB3, and ErbB4) inhibitor, is a second-generation oral epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). It can be used as a first-line treatment for locally advanced or metastatic non-small-cell lung cancer (NSCLC) with an EGFR-sensitive mutation or for patients with locally advanced or metastatic squamous lung cancer whose disease progresses during or after platinum-containing chemotherapy. Currently, with the use of third-generation EGFR-TKIs, afatinib is no longer clinically indicated as the first choice for patients with NSCLC who have EGFR-sensitive mutations. However, afatinib showed a considerable inhibitory effect in NSCLC patients with uncommon EGFR mutations (G719X, S768I, and L861Q) according to a combined post hoc analysis of the LUX-Lung2/3/6 trials. With the development of genetic testing technology, the detection rate of uncommon EGFR mutations is increasing. The aim of this paper is to describe in detail the sensitivity of rare EGFR mutations to afatinib and to provide information and a reference for those suffering from advanced NSCLC who have uncommon EGFR mutations.

Analysis of EGFR gene mutation in patients with Non-Small cell lung cancer in Hue Central Hospital

ABSTRACT Objective: To analyze the EGFR mutation index on the cancer blocs of the patients with non - small cell lung cancer (NSCLC) at the Department of Pathology - Hue Central Hospital. Subjects and methods: A prospective, cross-sectional descriptive study of 227 patients with advanced, metastatic non - small cell lung cancer who were mutated in the EGFR gene. The study were carried out on the cancer parrafin blocs stored in Pathology Department, Hue Central Hospital. Results: Mean age 58.29 ± 9.36 years old, male/female ratio 1.58. Histopathology is mainly adenocarcinoma: 96%, squamous epithelium: 0.9%, large cell: 3.1%. EGFR mutation rate positive 38.3%, negative: 61.7%. The rate of positive EGFR mutations in women: (53.4%) is higher than in men: (28.8%). The rate of positive EGFR mutations in the smoking group: (24.4%), insignificant smoking: (32.8%), the non - smoking group (56.6%). The cases of patients carrying mutations in EGFR gene have 50.6% of LREA deletion mutations in exon 19; 40.23% are L858R substitution mutations in exon 21; 3.45% are G719X mutations and 2.3% are G719S mutations in exon 18; 1.14% are Q787 mutations in exon 20; 1.14% are double mutations S768I + V769L in exon 20 and T790M + L858R in exons 20 and 21. Conclusion: The rate of EGFR gene mutation in NSCLC patients was 38.3%, higher in women than in men and especially high in non - smokers or non - smokers, the difference was statistically significant with p. &lt; 0.05. The most common TKI - sensitive mutations include deletion mutations in exon 19 and substitution mutations in exon 21 (accounting for more than 90%), a percentage less than 5% are mutations. Keywords: EGFR, gene mutation, lung cancer.

Epidermal Growth Factor Receptor Mutation Status and the Impact on Clinical Outcomes in Patients with Non-Small Cell Lung Cancer.

Epidermal growth factor receptor (EGFR) mutation status differs according to ethnicity, gender, smoking history, and histology types. The present study aimed to evaluate EGFR mutation status in patients with non-small cell lung cancer (NSCLC) and further explore its association with clinical characteristics and prognosis in advanced NSCLC patients (Stage IIIB-IV). 238 NSCLC patients were enrolled in this study from October 2016 through December 2019. Patient characteristics and clinical data including age, gender, smoking history, histology types, tumor stage, survival status, and time were collected via electronic medical record system or telephone. 21 somatic mutations which spanned exons 18-21 of EGFR were detected using the amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) method, followed by analysis of links to clinical characteristics, progression-free survival (PFS) and overall survival (OS). 103 patients were detected harboring EGFR mutations among the 238 cases tested (43.3%), and exons 19 and 21 were the highest mutation frequencies, with 20.6% and 19.3% respectively. The EGFR mutation rate was much higher in female versus male (57.4% vs 31.5%, p <0.001), in non-smokers compared to smokers (56.8% vs 25.9%, p <0.001), and in those with adenocarcinoma than other histology types (48.3% vs 3.7%, p <0.001). For patients in advanced stage, median PFS was 11 months in patients harboring EGFR mutations, versus 4 months in patients with wild type EGFR (p <0.001); median OS was 24 versus 12 months (p <0.001). Never smoking (p = 0.042) and adenocarcinoma (p = 0.007) were independent favorable factors for EGFR mutations. Our data strengthen the findings of high prevalence of EGFR mutations in Asian patients with NSCLC. Mutations are prevalent in those patients who are female, adenocarcinoma, and have never smoked. Moreover, advanced EGFR mutation-positive patients have better PFS and OS than those with wild type EGFR.

31P EGFR mutation rate and spectrum in Ukrainian patients with advanced NSCLC: Relation to gender and PD-L1 expression

31P EGFR mutation rate and spectrum in Ukrainian patients with advanced NSCLC: Relation to gender and PD-L1 expression

Application of the WHO Classification of Thoracic Tumors (2021) grading system in invasive pulmonary adenocarcinoma and its correlation with the targeted genes' variations

Objective: To investigate the applicability of the 2021 WHO classification of thoracic tumors' new grading system for invasive pulmonary adenocarcinoma (IPA) with different clinical stages and its correlation with the characteristics of targeted genes' variation. Methods: A total of 2 467 patients with surgically resected primary IPA in Shanghai Pulmonary Hospital, Shanghai, China from September to December 2020 were retrospectively analyzed. Eligible cases were graded using the new grading system of IPA of the 2021 WHO classification of thoracic tumors. The clinicopathological data and targeted-gene abnormality were collected. The utility of new grading system of IPA in different clinical stages was investigated. The correlation of clinicopathological features and targeted-gene abnormality in different grades of IPA were compared. Results: All 2 311 cases of IPA were included. There were 2 046 cases of stage Ⅰ IPA (88.5%), 169 cases of stage Ⅱ (7.3%), and 96 cases of stage Ⅲ (4.2%). According to the new classification system of IPA, 186 cases (9.1%), 1 413 cases (69.1%) and 447 cases (21.8%) of stage-Ⅰ adenocarcinoma were classified as Grade 1, Grade 2 and Grade 3, respectively. However, there were no Grade 1 adenocarcinomas in stages Ⅱ and Ⅲ cases. Among stage-Ⅱ and Ⅲ IPA cases, there were 38 Grade 2 cases (22.5%) and 131 Grade 3 cases (77.5%), and 3 Grade 2 cases (3.1%) and 93 Grade 3 cases (96.9%), respectively. In stage-Ⅰ cases, no tumor cells spreading through airspace (STAS), vascular invasion or pleural invasion was found in Grade 1 of IPA, while the positive rates of STAS in Grade 2 and 3 IPA cases were 11.3% (159/1 413) and 73.2% (327/447), respectively. There was a significant difference among the three grades (P<0.01). Similarly, the rates of vascular and pleural invasion in Grade 3 IPA cases were 21.3% (95/447) and 75.8% (339/447), respectively, which were significantly higher than those of 1.3% (19/1 413) and 3.0% (42/1 413) in Grade 2 (P<0.01). EGFR mutational rates in Grades 1, 2 and 3 IPA were 65.7% (94/143), 76.4% (984/1 288) and 51.3% (216/421), respectively. The differences among the three grades were statistically significant (P<0.01). No fusion genes were detected in Grade 1 IPA, while the positive rates of ROS1 and ALK fusion genes in Grade 3 were 2.4% (10/421) and 8.3% (35/421), respectively, which were significantly higher than that of 0.5% (7/1 288) and 1.6% (20/1 288) in Grade 2 (P<0.01). In stage-Ⅱ cases, only EGFR mutation rate in Grade 2 adenocarcinoma (31/37, 83.8%) was higher than that in Grade 3 adenocarcinoma (71/123, 57.7%; P<0.01). However, the correlation between the new grade system of IPA and the distribution characteristics of targeted-gene variation cannot be evaluated in stage Ⅲ cases. Conclusions: The new grading system for IPA is mainly applicable to clinical stage-Ⅰ patients. Tumor grades of IPA are strongly correlated with the high-risk factors of prognosis and the distribution features of therapeutic targets. It is of great significance and clinical value to manage postoperative patients with early-stage IPA.

Application of the Novel Grading System of Invasive Pulmonary Adenocarcinoma in a Real Diagnostic Scenario: A Brief Report of 9353 Cases

IntroductionThe International Association for the Study of Lung Cancer proposed a novel grading system of invasive pulmonary adenocarcinoma (IPA), but the application of this grading system and its genotypic characterization in the real diagnostic scenario has never been reported. MethodsWe prospectively collected and analyzed the clinicopathological and genotypic features of a cohort of 9353 consecutive patients with resected IPA, including 7134 patients with detection of common driver mutation. ResultsIn the entire cohort, 3 (0.3%) of lepidic, 1207 (19.0%) of acinar, and 126 (23.6%) of papillary predominant IPAs were diagnosed as grade 3. In chronological order, an evident downtrend of the proportion of grade 2 was observed in chronological order. Conversely, the diagnostic ratio of grade 1 (8.0%–14.5%) and grade 3 (27.9%–32.3%) experienced a gradual rise. EGFR mutation was more frequently detected in grade 2 (77.5%) and grade 1 (69.7%) IPA than grade 3 (53.7%, p < 0.001), whereas the mutation rates of KRAS, BRAF, ALK, and ROS1 were higher in grade 3 IPA. More importantly, the rate of EGFR mutation gradually fell as the proportion of high-grade components increased, to 24.3% in IPA with more than 90% high-grade components. ConclusionsThe grading system for IPA could be applied to stratify patients with different clinicopathological and genotypic features in a real diagnostic scenario.

Lung cancer in Asian Indian females: Identification of disease-specific characteristics and outcome measures over a 12-year period.

Globally, the incidence of lung cancer amongst women appears to be increasing. We aimed to compare the socio-epidemiological and clinical characteristics of lung cancer amongst men and women from a large cohort at a tertiary care hospital in Northern India. Records of patients diagnosed with lung cancer between January 2008 and March 2020 were reviewed. Baseline epidemiological data, clinical characteristics, histologic profiles, treatment administered, and survival were compared between males and females. A total of 2054 male and 438 female patients were included in analysis. Compared to males, female patients were younger [median age, 56 vs. 60 years, P < 0.001)], less likely to be working, less educated beyond secondary level and less likely to be smokers (29.1% vs. 84.9%, P < 0.0001). No difference in baseline performance status was observed. Females were more frequently diagnosed with adenocarcinoma (54.2% vs. 30.2%, P = <0.0001), stage IV disease (70.8% vs. 63%, P = 0.001), and had higher rate of EGFR mutation (37.2% vs. 21.5%, P < 0.0001). There was no difference in the proportion of females receiving cancer-specific therapy. Multivariate Cox proportional hazards model revealed higher progression-free survival [median 9.17 vs. 7.23 months; P = 0.007] and overall survival [median 13.80 vs. 9.10 months respectively, P = 0.001] amongst females compared to males. Amongst a large cohort of lung cancer, females demonstrated several distinct and characteristic demographics as well as disease-related features, especially better survival outcomes.