Positive Epidermal Growth Factor Receptor Research Articles

The Association of the Epidermal Growth Factor Receptor (EGFR) Immunoexpression With Prognostic Parameters in Adenocarcinoma Patients Receiving Neoadjuvant Treatment.

The epidermal growth factor receptor (EGFR) expression is considered to play an essential role in the pathogenesis of colorectal adenocarcinoma. This study assessed the expression and predictive/prognostic value of EGFR expression in pre-op biopsy and post-op resection specimens in patients receiving neoadjuvant radiotherapy/neoadjuvant chemoradiotherapy (NRT/NCRT). Thirty-four consecutive patients were included in this study. The association between the prognostic features and EGFR immunohistochemical expression was analyzed in pre- (n=34) and post-treatment (n=22) tissue samples in cases with available tissue blocks. Of 34, 23 (67.6%) were men. The median age was 60.50 ± 10.69 (range, 31-84) years. EGFR expression was detected in 88.2% of biopsy specimens and in 91.2% of surgical specimens. There was only slight agreement between pre-op and post-op EGFR expression scores (kappa value 0.11). There was no significant correlation between pre-op and post-op EGFR expression scores (p>0.05). Although pre-op EGFR positivity and higher pre-op EGFR scores seemed to indicate a worse prognosis, this association between pre-op EGFR expression and overall survival (OS) or disease-specific survival (DSS) did not reach statistical significance (p>0.05). The only case with a post-op EGFR score of three who died of the disease experienced local recurrence and had distant metastasis. In conclusion, EGFR positivity in pre-op biopsy samples seems to be associated with shorter survival, and increased EGFR expression in post-treatment resection specimens predicts aggressive behavior in patients with rectal adenocarcinoma who received NRT/NCRT. However, due to the molecular heterogeneity, EGFR expression status should be evaluated in resection specimens rather than in pre-op biopsy samples for optimal prognosis prediction.

First-line Treatment with Furmonertinib Mesylate in Lung Adenocarcinoma Patient with EGFR Exon 20 Insertion Mutantion

With the continuous innovation of genomics, proteomics and molecular biological detection technology, the treatment of non-small cell lung cancer (NSCLC) has changed from traditional chemotherapy to immunotherapy and targeted therapy. Among them, molecular tumor markers targeting tyrosine kinase pathways play more important roles in clinical practice. For advanced NSCLC patients with positive epidermal growth factor receptor (EGFR) mutations, there are many first-line drugs on the market and they could bring significant efficacy, thus completely subverting the treatment pattern of advanced NSCLC. Common mutations of EGFR in Chinese patients are located on exons 19, 20 and 21, of which exons 19 and 21 mutations are the more common types. Besides, there is also a subtype of EGFR mutations, known as EGFR 20 exon insertion (EGFR 20ins) mutation. The authors summarized the treatment of a lung adenocarcinoma patient with EGFR 20ins mutation accepting Furmonertinib mesylate, in order to provide effective references for clinical diagnosis and treatment. .

Single-cell landscape of undifferentiated pleomorphic sarcoma.

Undifferentiated pleomorphic sarcoma (UPS) is a highly aggressive malignant soft tissue tumor with a poor prognosis; however, the identity and heterogeneity of tumor populations remain elusive. Here, eight major cell clusters were identified through the RNA sequencing of 79,569 individual cells of UPS. UPS originates from mesenchymal stem cells (MSCs) and features undifferentiated subclusters. UPS subclusters were predicted to exist in two bulk RNA datasets, and had a prognostic value in The Cancer Genome Atlas (TCGA) dataset. The functional heterogeneity of malignant UPS cells and the immune microenvironment were characterized. Additionally, the fused cells were innovatively detected by expressing both monocyte/macrophage markers and other subcluster-associated genes. Based on the ligand-receptor interaction analysis, cellular interactions with epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) were abundant. Furthermore, 73% of patients with UPS (48/66) showed positive EGFR expression, which was associated with a poor prognosis. EGFR blockade with cetuximab inhibited tumor growth in a patient-derived xenograft model. Our transcriptomic studies delineate the landscape of UPS intratumor heterogeneity and serve as a foundational resource for further discovery and therapeutic exploration.

Machine learning-based radiomics strategy for prediction of acquired EGFR T790M mutation following treatment with EGFR-TKI in NSCLC

The epidermal growth factor receptor (EGFR) Thr790 Met (T790M) mutation is responsible for approximately half of the acquired resistance to EGFR-tyrosine kinase inhibitor (TKI) in non-small-cell lung cancer (NSCLC) patients. Identifying patients at diagnosis who are likely to develop this mutation after first- or second-generation EGFR-TKI treatment is crucial for better treatment outcomes. This study aims to develop and validate a radiomics-based machine learning (ML) approach to predict the T790M mutation in NSCLC patients at diagnosis. We collected retrospective data from 210 positive EGFR mutation NSCLC patients, extracting 1316 radiomics features from CT images. Using the LASSO algorithm, we selected 10 radiomics features and 2 clinical features most relevant to the mutations. We built models with 7 ML approaches and assessed their performance through the receiver operating characteristic (ROC) curve. The radiomics model and combined model, which integrated radiomics features and relevant clinical factors, achieved an area under the curve (AUC) of 0.80 (95% confidence interval [CI] 0.79–0.81) and 0.86 (0.87–0.88), respectively, in predicting the T790M mutation. Our study presents a convenient and noninvasive radiomics-based ML model for predicting this mutation at the time of diagnosis, aiding in targeted treatment planning for NSCLC patients with EGFR mutations.

Immunohistochemical analysis of epidermal growth factor receptor as a predictive biomarker in lung adenocarcinoma – A cross-sectional study of 33 cases on computed tomography-guided core needle biopsy specimens

Background: Lung cancer is the second most common cause of cancer in all ages and both genders and is the leading cause of cancer death. Two major groups of lung cancers are – small cell lung carcinoma (SCLC) and non-SCLC (NSCLC). Due to discovery of driver mutation such as epidermal growth factor receptor (EGFR) mutation in NSCLC, the paradigm of lung cancer therapy has shifted from cytotoxic platinum based therapy to tyrosine kinase inhibitor (TKI) therapy. In this study, we have analyzed EGFR expression in NSCLC by immunohistochemistry (IHC) and studied the response to TKI therapy in terms of progression free survival (PFS) and overall survival (OS). Aims and Objectives: In this study, we have retrospectively analyzed the EGFR overexpression in adenocarcinoma of lung in core needle biopsy (CNB) specimen by IHC analysis and correlated with the therapeutic response and survival rate (OS and PFS) in lung carcinoma patients. Materials and Methods: We have analyzed retrospectively EGFR expression in lung adenocarcinoma cases (computed tomography-guided CNB specimen) by IHC. In our study, we have used monoclonal primary antibodies against two most common EGFR mutations, that is, L858R point mutation and E 746–A 750 deletion. Results: Out of 33 cases, EGFR expression was seen in 28 cases. For EGFR expression assessment by IHC, both cytoplasmic and/or membranous staining taken into consideration. EGFR positivity was interpreted only when >10% tumor cells having 2+ or more intensely staining pattern. The response to TKI therapy in terms of PFS and OS was also studied. Conclusion: IHC analysis of EGFR mutation using specific antibodies has extremely high specificity with good sensitivity. Use of targeted therapy in the form of TKI in EGFR positive lung adenocarcinoma has high response rate and long duration of survival (PFS and OS) with acceptable toxicity profile in contrast to the conventional therapy.

Molecular analysis for EGFR, ALK, and ROS1 alterations in over 3000 Indian patients with non-small-cell lung cancer: A retrospective observational study

Background: Accurate molecular testing in non-small-cell lung cancer (NSCLC) is of paramount importance for treatment, prediction, and prognostication. Objectives: We aimed to comprehensively describe the clinicopathological and molecular profile of Indian patients with NSCLC with regard to alterations in the epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and c-ros oncogene 1 (ROS1). Materials and Methods: We conducted a retrospective analysis of lung tissue samples tested between January 2015 and December 2021 at the Metropolis Healthcare Limited global referral laboratory facility in Mumbai, Maharashtra, India. Testing was conducted for EGFR by real time reverse transcriptase polymerase chain reaction (RT-PCR) and Sanger sequencing, ALK by immunohistochemistry (IHC), ALK by fluorescence in situ hybridization (FISH), and c-ros oncogene 1 (ROS1) by FISH. We analyzed the positivity status and determined the trends in the results of the molecular targets in NSCLC cases. Results: Out of 3220 samples with malignancy, 1750 (54.3%) were tested for EGFR, out of which 510 (29.1%) were positive. The most common mutation detected was in exon 19 of EGFR (334/510, 65.5%), followed by exon 21 (164/510, 32.2%). A total of 1548 (48.1%) cases were tested for ALK by IHC, of which 125/1548 (8.1%) showed positivity, while among the 372/3220 (11.6%) cases tested for ALK by FISH, 29/372 (7.8%) were positive. In patients with squamous cell carcinoma, the ALK positivity rate by IHC was 5.3%. Of the 372 cases tested for ALK by FISH, 353 (94.9%) cases were tested for ALK by IHC as well; 98.9% concordance was observed for the positive cases. ROS1 testing was conducted in 370/3220 (11.5%) samples and showed a low positivity rate of 13/370 (3.5%). Conclusions: Indian patients with NSCLC have 29% EGFR positivity, 8.1% ALK positivity, and 3.5% ROS1 positivity, when tested with RT-PCR, IHC, and FISH, respectively. A detailed molecular analysis using next-generation sequencing (NGS) may help detect a higher number of molecular targets amenable to therapy.

Solitary lung adenocarcinoma: follow-up CT, pathological-molecular characteristics, and surgical prognosis for different morphological classifications

ObjectiveTo investigate the dynamic changes during follow-up computed tomography (CT), histological subtypes, gene mutation status, and surgical prognosis for different morphological presentations of solitary lung adenocarcinomas (SLADC).Materials and methodsThis retrospective study compared dynamic tumor changes and volume doubling time (VDT) in 228 patients with SLADC (morphological types I–IV) who had intermittent growth during follow-ups. The correlation between the morphological classification and histological subtypes, gene mutation status, and surgical prognosis was evaluated.ResultsAmong the 228 patients, 66 (28.9%) were classified as type I, 123 (53.9%) as type II, 16 (7%) as type III, and 23 (10.1%) as type IV. Type I had the shortest VDT (254 days), followed by types IV (381 days) and III (501 days), and then type II (993 days) (p < 0.05 each). Type I had a greater proportion of solid/micropapillary-predominant pattern than type II, and the lepidic-predominant pattern was more common in type II and III than in type I (p < 0.05 each). Furthermore, type II and IV SLADCs were correlated with positive epidermal growth factor receptor mutation (p < 0.05 each). Lastly, the Kaplan–Meier curves showed that the disease-free survival was longest for patients with type II tumors, followed by those with type III and IV tumors, and then those with type I tumors (p < 0.001 each).ConclusionA good understanding of the natural progression and pathological-molecular characteristics of different morphological SLADC types can help make accurate diagnoses, develop individual treatment strategies, and predict patient outcomes.Critical relevance statementA good understanding of the natural progression and pathological-molecular characteristics of different morphological solitary lung adenocarcinoma types can help make accurate diagnoses, develop individual treatment strategies, and predict patient outcomes.Key points• Type I–IV solitary lung adenocarcinomas exhibit varying natural progression on serial CT scans.• Morphological classification of solitary lung adenocarcinomas predicts histological subtype, gene status, and surgical prognosis.• This classification of solitary lung adenocarcinomas may help improve diagnostic, therapeutic, and prognosticating abilities.Graphical

BIOM-24. PREDICTION OF DISTANT RECURRENCE IN GLIOBLASTOMA PATIENTS TREATED WITH STANDARD THERAPY

Abstract BACKGROUND Infiltrative growth is a hallmark of glioblastoma (GBM) and is a major factor in therapeutic failure. We aimed to identify clinical and molecular factors associated with distance recurrence in glioblastoma patients treated with standard therapy (radiotherapy with concomitant and adjuvant temozolomide). METHODS Two prospective cohorts of consecutive, non-selected GBM patients administered standard therapy as primary treatment between year 2005-2016 (Cohort 1) and 2016-2021 (Cohort 2) at Rigshospitalet, Copenhagen were included. Distant recurrence was defined as a new contrast-enhancing tumor &amp;gt; 2 cm from the gross tumor volume. Clinical and molecular factors were screened for association with time to distant recurrence using univariate Cox regression analysis. The final model was generated employing multivariate analysis. RESULTS Cohort 1 and 2 included 628 and 395 patients, respectively. Out of the recurrence pattern evaluable patients, distant recurrence was observed in 117 patients (23%) in Cohort 1 and 73 patients (22%) in Cohort 2. PRELIMINARY RESULTS In Cohort 1, multivariate analysis showed that corticosteroid use, age, multifocal disease, ECOG performance status, and degree of tumor resection were not associated (p &amp;gt; 0.10) with distant recurrence. Two factors were independently associated with a higher likelihood of distant recurrence, namely non-methylated promoter of the MGMT gene (HR = 1.93; 95% CI:1.27-2.95; p = 0.002) and positive expression of Epidermal Growth Factor Receptor (EGFR) (HR = 3.70; 95% CI: 1.61-8.33; p = 0.002). In Cohort 2, the EGFR status was not available but the association of non-methylated MGMT with distant recurrence was validated (HR = 2.67; 95% CI: 1.62-4.42; p = 0.0001). CONCLUSION Non-methylated MGMT and positive EGFR expression were independent predictors of distant recurrence. Non-methylated MGMT was validated in Cohort 2 and can be used for risk stratification and to enrich clinical trials aiming at improved local or distant tumor control.

Immunotherapy strategies for EGFR-mutated advanced NSCLC after EGFR tyrosine-kinase inhibitors failure.

This study aimed to investigate the efficacy of immunotherapy, as monotherapy or in combination, comparing to chemotherapy with or without anti-angiogenesis for advanced non-small cell lung cancer (NSCLC) patients progressing to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs). We retrospectively analyzed patients with advanced NSCLC harboring EGFR mutations who received immune checkpoint inhibitors (ICI) and/or chemotherapy after EGFR-TKIs failure at Shanghai Chest Hospital between Aug 2016 and Oct 2022. According to the subsequent immunotherapy regimen, the patients were assigned to ICI monotherapy (IM), IO plus anti-angiogenesis (IA), ICI plus chemotherapy (IC), ICI plus chemotherapy plus anti-angiogenesis (ICA). Eligible patients undergoing standard chemotherapy were assigned to chemotherapy plus anti-angiogenesis (CA) and chemotherapy alone (CM). Efficacy was evaluated according to the RECIST 1.1version, and calculated the objective response rate (ORR) and disease control rate (DCR). Survival curves were plotted using the Kaplan-Meier method, and the median progression-free survival (PFS) was calculated. Differences among survival curves of the six groups were assessed using the log-rank test. A total of 237 advanced NSCLC patients with EGFR mutations were included in this study. Of the 160 patients who received immunotherapy, 57 received ICI monotherapy, 27 received ICI plus anti-angiogenesis therapy, 43 received ICI plus chemotherapy, and 33 received ICI plus anti-angiogenesis plus chemotherapy. 77 patients received standard chemotherapy, of which 30 received chemotherapy plus anti-angiogenesis and 47 received chemotherapy alone. Patients in ICA group showed significant longer PFS than IM (7.2 vs 1.9 months, P=0.011), IA (7.2 vs 4.8 months, P=0.009) and CM group (7.2 vs 4.4 months, P=0.005). There was no significant difference in PFS between the ICA and IC (7.2 vs 5.6 months, P=0.104) or CA (7.2 vs 6.7 months, P=0.959) group. Meanwhile, the ICA group showed the highest ORR and DCR (36.4% and 90.9%) compared to the other five groups. The IC group had a higher ORR than the IA and CA group (32.6% vs 7.4% vs 10.0%, respectively), but the DCR was comparable (79.1% vs 74.1% vs 76.7%, respectively). The ORR of the CM group was 6.4% and the DCR was 66.0%. IM group showed the lowest ORR and DCR (1.8% and 36.8%). Treatment-related adverse events (TRAEs) of grade 3 or worse occurred in 9 (27.3%) patients in the ICA group, 6 (20.0%) in the CA group, 7 (14.9%) in the CM group, 5 (11.6%) in the IC group, 5 (8.8%) in the IM group, and 2 (7.4%) in the IA group. NSCLC patients with positive EGFR mutations after EGFR-TKIs failure received subsequent immunotherapy plus anti-angiogenesis and chemotherapy are likely to have more benefits in ORR, DCR and mPFS.

Befotertinib: First Approval.

Befotertinib (Surmana®) is an orally administered, highly selective, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) being developed by Betta Pharmaceuticals and InventisBio for the treatment of non-small cell lung cancer (NSCLC). In May 2023, befotertinib was approved in China for the second-line treatment of patients with locally advanced or metastatic NSCLC who have received EGFR TKI therapy and have disease progression with positive EGFR T790M mutation. Befotertinib is under regulatory review for the first-line treatment of NSCLC in China. Clinical studies assessing befotertinib as an adjuvant therapy after surgery for early EGFR-mutant NSCLC (phaseIII) and in combination with icotinib for advanced or metastatic EGFR-mutant NSCLC (phaseII) are currently underway in China. This article summarizes the milestones in the development of befotertinib leading to this first approval for the second-line treatment of EGFR T790M-mutated locally advanced or metastatic NSCLC.

CT-based non-invasive identification of the most common gene mutation status in patients with non-small cell lung cancer.

Epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene homolog (KRAS) are mutually exclusive, and they are two important genes that are most prone to mutation in patients with non-small cell lung cancer. This retrospective study investigated the ability of radiomics to predict the mutation status of EGFR and KRAS in patients with non-small cell lung cancer (NSCLC) and guide precision medicine. Computed tomography images of 1045 NSCLC patients from five different institutions were collected, and 1204 imaging features were extracted. In the training set (EGFR: 678, KRAS: 246), Max-Relevance and Min-Redundancy and least absolute shrinkage and selection operator logistic regression were used to screen radiomics features. The combination of selected radiomics features and clinical factors was used to establish the combined models in identifying EGFR and KRAS mutation status, respectively, through stepwise logistic regression. Then, on two independent external validation sets (EGFR: 203/164, KRAS: 123/95), the performance of each model was evaluated separately, and then the overall performance of predicting the two mutation states was calculated. In the EGFR and KRAS groups, radiomics signatures comprised 14 and 10 radiomics features, respectively. They were mutually exclusive between the tumors with positive EGFR mutation and those with positive KRAS mutation in imaging phenotype. For the EGFR group, the area under the curve (AUC) of the combined model in the two validation sets was 0.871 (95% CI: 0.821-0.926) and 0.861 (95% CI: 0.802-0.911), respectively, whereas the AUC of the combined model in the two validation sets was 0.798 (95% CI: 0.739-0.850) and 0.778 (95% CI: 0.735-0.821), respectively, for the KRAS group. Considering both EGFR and KRAS, the overall precision, recall, and F1-score of the combined model in the two validation sets were 0.704, 0.844, and 0.768, as well as 0.754, 0.693, and 0.722, respectively. Our study demonstrates the potential of radiomics in the non-invasive identification of EGFR and KRAS mutation status, which may guide patients with non-small cell lung cancer to choose the most appropriate personalized treatment. This method can be used when biopsy will bring unacceptable risk to patients with NSCLC.

Deep learning based automated epidermal growth factor receptor and anaplastic lymphoma kinase status prediction of brain metastasis in non-small cell lung cancer.

The aim of this study was to investigate the feasibility of developing a deep learning (DL) algorithm for classifying brain metastases from non-small cell lung cancer (NSCLC) into epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) rearrangement groups and to compare the accuracy with classification based on semantic features on imaging. Data set of 117 patients was analysed from 2014 to 2018 out of which 33 patients were EGFR positive, 43 patients were ALK positive and 41 patients were negative for either mutation. Convolutional neural network (CNN) architecture efficient net was used to study the accuracy of classification using T1 weighted (T1W) magnetic resonance imaging (MRI) sequence, T2 weighted (T2W) MRI sequence, T1W post contrast (T1post) MRI sequence, fluid attenuated inversion recovery (FLAIR) MRI sequences. The dataset was divided into 80% training and 20% testing. The associations between mutation status and semantic features, specifically sex, smoking history, EGFR mutation and ALK rearrangement status, extracranial metastasis, performance status and imaging variables of brain metastasis were analysed using descriptive analysis [chi-square test (χ2)], univariate and multivariate logistic regression analysis assuming 95% confidence interval (CI). In this study of 117 patients, the analysis by semantic method showed 79.2% of the patients belonged to ALK positive were non-smokers as compared to double negative groups (P = 0.03). There was a 10-fold increase in ALK positivity as compared to EGFR positivity in ring enhancing lesions patients (P = 0.015) and there was also a 6.4-fold increase in ALK positivity as compared to double negative groups in meningeal involvement patients (P = 0.004). Using CNN Efficient Net DL model, the study achieved 76% accuracy in classifying ALK rearrangement and EGFR mutations without manual segmentation of metastatic lesions. Analysis of the manually segmented dataset resulted in improved accuracy of 89% through this model. Both semantic features and DL model showed comparable accuracy in classifying EGFR mutation and ALK rearrangement. Both methods can be clinically used to predict mutation status while biopsy or genetic testing is undertaken.

Clinicopathological Parameters and Biomarker Profile in a Cohort of Patients With Head and Neck Squamous Cell Carcinoma (HNSCC).

Squamous cell carcinoma (SCC) is the most common malignancy of the head and neck region, commonly termed as head and neck squamous cell carcinoma (HNSCC).Data related to biomarker expression in HNSCC are scarcely available, especially in our population. This study aimed to evaluate the association of immunohistochemical (IHC) expression of p16, epidermal growth factor receptor (EGFR), p27, and p53 in HNSCC with clinical and pathological parameters. This retrospective cross-sectional study was conducted at the Department of Histopathology, Liaquat National Hospital, Karachi, Pakistan from February 2017 to January 2022. A total of 308 cases of HNSCC with upfront surgical resection were included in the study. IHC analysis was performed for EGFR, p16, p27, and p53, and association with clinicopathological parameters was sought. p16, EGFR, and p53 positivity were noted in 22.1%, 18.8%, and 66.2% cases, respectively, whereas loss of p27 expression was seen in 14.3% cases of HNSCC. A significant association of p16 expression was observed with age, tumor size, tumor site, nodal metastasis, extranodal extension (ENE), and perineural invasion (PNI). Cases aged over 50 years were more significantly associated with positive p16. Similarly, cases with oral cavity SCC were more significantly associated with positive p16. HNSCC with larger tumor size, the presence of nodal metastasis, and ENE and PNI were associated with negative p16 expression. Similarly, a significant association of EGFR expression was observed with age, tumor size, tumor site, histological subtype, histological differentiation, nodal metastasis, ENE, and PNI (p < 0.05). Cases of HNSCC with age less than 50 years were associated with positive EGFR expression. Similarly, oral cavity and lip SCCs were associated with positive EGFR expression compared with other sites. Moreover, positive EGFR expression was significantly associated with nodal metastasis, ENE, moderate histological differentiation, and the presence of PNI. Loss of p27 expression was significantly associated with nodal stage and ENE; low nodal stage and absence of ENE were associated with p27 loss of expression, whereas no significant association was seen with other pathological parameters. Alternatively, a significant association of mutant-type p53 expression was noted with gender, nodal stage, and histological subtype. Females with HNSCC show a higher frequency of mutant-type p53 expression than males. Moreover, higher nodal stage (N2b and higher) and non-keratinizing SCCs were significantly associated with mutant-type p53 expression. Our study found a high expression of EGFR and mutant-type p53 expression in HNSCC. Conversely, p16 expression and loss of p27 expression were low. Moreover, EGFR and mutant-type p53 expression were associated with poor pathological parameters, whereas p16 expression was associated with better histological features.

The relation between epidermal growth factor receptor mutations profiles and smoking patterns in patients with lung adenocarcinoma: A cross‐sectional study

AbstractBackgroundNon‐small cell lung cancer (NSCLC) accounts for 85% of lung cancer cases, with smoking being a critical risk factor. The identification of NSCLC patients harboring epidermal growth factor receptor (EGFR) mutations, sensitized to tyrosine kinase inhibitors, has revolutionized treatment plans, resulting in improved clinical responses and reduced chemotherapy toxicity. This study aimed to assess the relationship between EGFR mutations and smoking patterns in patients diagnosed with lung adenocarcinoma referred to major pathologic laboratories.MethodsThis cross‐sectional study included 217 NSCLC patients aged above 18 years. Molecular abnormalities of the EGFR gene were analyzed by polymerase chain reaction amplification of exons 18–21 accompanied by Sanger sequencing. Then, the data were analyzed using the SPSS 26 software. Logistic regression analysis, χ2 test, and Mann–Whitney U test were used to evaluate the relation between EGFR mutations and smoking patterns.ResultsEGFR mutations were identified in 25.3% of patients, predominantly involving deletion in exon 19 (61.8%). For most of the mutant EGFR patients, the majority were nonsmokers (81.8%), and 52.7% were female patients. Besides, the median duration of smoking was 26 years and the median frequency of smoking was 23 pack‐years in the mutant EGFR group, both of which were lower compared to the wild mutant group. Moreover, female gender, current, and heavy smoking were significantly correlated with EGFR mutations based on the univariate logistic regression analysis (p: 0.004, 0.005, and 0.001, respectively).ConclusionsFemale gender and nonsmoker status were strongly associated with positive EGFR mutations. While guidelines traditionally recommended EGFR testing primarily for female nonsmokers with advanced NSCLC, our study in line with the recently published evidence has shown a significant prevalence of positive EGFR mutations among male patients and smokers. Therefore, routine mutation testing is suggested for all NSCLC patients. Considering the limited access to EGFR testing laboratories in developing countries, the results of such epidemiological surveys can assist oncologists in choosing the most suitable treatment plan.

Advanced Non-small Cell Lung Cancer: EGFR Mutation Analysis Using Pyrosequencing and the Fully Automated qPCR-Based IdyllaTM System.

Epidermal growth factor receptor (EGFR) mutation status is of a major clinical significance in non-small cell lung cancer (NSCLC) management, as it guides therapeutic decision making to target patients for a better response to therapy. This implicates the introduction of EGFR mutation analysis as the standard of care for Moroccan NSCLC patients, which in itself entails the implementation of targeted methods for routine EGFR mutation analysis in our laboratories. In this study, we aimed to present 2 targeted methods for EGFR mutation identification and to determine the prevalence and spectrum of EGFR mutations in NSCLC Moroccan patients. A retrospective investigation of a cohort of 340 patients was undertaken to analyze somatic EGFR mutations in exons 18 to 21 using pyrosequencing and the IdyllaTM system. Of the enrolled patients, 70.9% were males and 29.1% were females. Predominately, 92% of cases had adenocarcinoma, and 53.7% of patients self-reported a history of smoking. Overall, 73 patients (21.7%) harbored an EGFR mutation, the most prevalent of which were the exon 19 deletions (53.4%) followed by exon 21 substitutions (31%). Exon 18 mutations and exon 20 alterations occurred in 8.1% and 6.7% of the positive EGFR mutation cases, respectively. Of the analyzed cases, all of the EGFR-mutated patients had adenocarcinoma. EGFR mutation prevalence was significantly higher in females (females vs males: 38.4% vs 14.5%, P < .001) and non-smokers (non-smokers vs non-smokers: 36% vs 10.3%, P < .001). The featured pyrosequencing and the IdyllaTM system are targeted methods endowed with high sensitivity and specificity as well as other compelling characteristics which make them great options for routine EGFR mutation testing for advanced NSCLC patients. These findings underline the imperious need for implementing quick and efficient targeted methods for routine EGFR mutation testing among NSCLC patients, which is particularly useful in determining patients who are more likely to benefit from targeted therapy.

PET/CT standardized uptake value and EGFR expression predicts treatment failure in nasopharyngeal carcinoma

ObjectiveThis study inventively combines epidermal growth factor receptor (EGFR) expression of the primary lesion and standardized uptake value (SUV) of positron emission tomography and computed tomography (PET/CT) to predict the prognosis of nasopharyngeal carcinoma (NPC). This study aimed to evaluate the predictive efficacy of maximum standard uptake value (SUVmax) and EGFR for treatment failure in patients with NPC.MethodsThis retrospective study reviewed the results of EGFR expression and pretreatment 18F-FDG PET/CT of 313 patients with NPC. Time-dependent receiver operator characteristics was used for analyzing results and selecting the optimal cutoff values. Cox regression was used to screen out multiple risk factors. Cumulative survival rate was calculated by Kaplan–Meier.ResultsThe selected cutoff value of SUVmax-T was 8.5. The patients were categorized into four groups according to EGFR expression and SUVmax-T. There were significant differences in the 3-year local recurrence-free survival (LRFS) (p = 0.0083), locoregional relapse-free survival (LRRFS) (p = 0.0077), distant metastasis-free survival (DMFS) (p = 0.013), and progression-free survival (PFS) (p = 0.0018) among the four groups. Patients in the EGFR-positive and SUVmax-T > 8.5 group had the worst survival, while patients in the EGFR-negative and SUVmax-T ≤ 8.5 group had the best prognosis. Subsequently, patients with only positive EGFR expression or high SUVmax-T were classified as the middle-risk group. There were also a significant difference in 3-year overall survival among the three risk groups (p = 0.034). SUVmax-T was associated with regional recurrence-free survival and LRRFS in multivariate analysis, whereas EGFR was an independent prognostic factor for LRRFS, DMFS, and PFS.ConclusionThe combination of SUVmax-T and EGFR expression can refine prognosis and indicate clinical therapy.

Heterogeneity and Clinical Effect of Epidermal Growth Factor Receptor in Primary Lung and Brain Metastases of Nonsmall Cell Lung Cancer

IntroductionThis study aimed to analyze the heterogeneity in epidermal growth factor receptor (EGFR) gene mutation and its impact on clinical outcomes in primary tumor and corresponding brain metastasis (BM) in nonsmall cell lung cancer (NSCLC). Materials and methodsPrimary pulmonary tumors and paired BMs of 27 NSCLC patients were surgically removed. All brain lesions were histologically confirmed as metastatic NSCLC. EGFR gene mutation status was detected by using amplification refraction mutation system. McNemar test was performed to compare EGFR mutation status between lung primary tumors and metastatic brain tumors and Kappa test was performed to quantify the agreement between the two. ResultsOf the 27 patients, nine cases were found to have EGFR mutations in BMs and 10 had a positive EGFR mutation status in primary lung tumor tissue. The rate of consistency of the matched tumor was 24/27 (88.9%). Among the three cases presenting EGFR mutational heterogeneity, two patients harbored an EGFR mutation in the primary tumor but not in the BMs; meanwhile, the last patient demonstrated the opposite pattern. Compared to patients with consistent EGFR mutations, patients with inconsistent mutations showed better outcomes. Further analysis revealed that the two patients whose EGFR mutant-type primary tumor progressed to wild-type cerebral metastatic tumor had longer overall survival than the patient whose EGFR wild-type primary tumor progressed to mutant-type brain metastatic tumor. ConclusionsHeterogeneity of EGFR mutation status was observed between primary NSCLC and paired BM. Patients possessing a wild-type EGFR mutation in BM might have better outcomes, especially those with transition from mutant to wild-type.

Liquid biopsy for detecting epidermal growth factor receptor mutation among patients with non-small cell lung cancer treated with afatinib: a multicenter prospective study

BackgroundThis study aimed to determine the effectiveness of liquid biopsy in detecting epidermal growth factor receptor (EGFR) mutations at diagnosis, disease progression, and intermediate stages.MethodsThis prospective, multicenter, observational study included 30 patients with non-small cell lung cancer treated with afatinib, harboring a major EGFR mutation confirmed by tumor tissue biopsy. We collected blood samples for liquid biopsy at diagnosis, intermediate stage, and progressive disease. Tissue and liquid biopsies were examined using Cobas ® EGFR Mutation Test v2.ResultsLiquid biopsy detected EGFR mutations in 63.6% of the patients at diagnosis. The presence of metastasis in the extrathoracic, brain, and adrenal glands correlated positively with the detection of EGFR mutations. Patients with positive EGFR mutations at diagnosis had significantly shorter overall and progression-free survival than patients with negative EGFR mutations. Four of the 18 patients (22.2%) who reached progressive disease had positive EGFR T790M mutations. Three of 10 patients (30.0%) with progressive disease were positive and negative for T790M using tumor re-biopsy and liquid biopsy, respectively. The results of EGFR mutation by tissue re-biopsy were the same as those of liquid biopsy in the three patients who were positive for significant EGFR mutations but negative for the T790M mutation using liquid biopsy at progressing disease. Only two patients were positive for major EGFR mutations at intermediate levels.ConclusionsLiquid biopsy can be a prognostic factor in EGFR-tyrosine kinase inhibitor treatments at diagnosis. Tumor re-biopsy can be omitted in patients with positive EGFR mutations by liquid biopsy at PD.

A novel ligand-modified nanocomposite microparticles improved efficiency of quercetin and paclitaxel delivery in the non-small cell lung cancer

Chemotherapy is the first choice for the treatment of cancer but it is still limited by insufficient kill efficiency and drug resistance. These problems urgently need to be overcome in a way that minimizes damage to the body. In this study, we designed the nanocomposite microparticles (NMPs) modified by cetuximab (Cet) and loaded anti-tumor agents- quercetin (QUE) and paclitaxel (PTX)- for eliciting specific drugs homing and enhancing the killing efficiency of chemotherapy drugs (P/Q@CNMPs). Physicochemical characteristics results presented that P/Q@CNMPs have a suitable aerodynamic diameter and uniform morphology that could meet the requirements of particles deposition in the lung. And it also had the characteristics of sustained-release and pH-responsive which could release the agents in the right place and has a continuous effect. In vitro and in vivo analysis results presented that P/Q@CNMPs have the accuracy targeting ability and killing effect on non-small cell lung cancer (NSCLC) which express positive epidermal growth factor receptor (EGFR) on the membrane. Furthermore, this system also has low toxicity and good biocompatibility. These results demonstrated that P/Q@CNMPs could be a potential intelligent targeting strategy used for chemo-resistant NSCLC therapies.

Prognostic Impact of Low-Level p53 Expression on Brain Astrocytomas Immunopositive for Epidermal Growth Factor Receptor.

Although the expression of p53 and epidermal growth factor receptor (EGFR) is associated with therapeutic resistance and patient outcomes in many malignancies, the relationship in astrocytomas is unclear. This study aims to correlate p53 and EGFR expression in brain astrocytomas with overall patient survival. Eighty-two patients with astrocytomas were enrolled in the study. Semi-quantitative p53 and EGFR immunohistochemical staining was measured in tumor specimens. The mean follow-up after astrocytoma surgery was 18.46 months. The overall survival rate was 83%. Survival was reduced in EGFR-positive patients compared with survival in EGFR-negative patients (p < 0.05). However, no significant differences in survival were detected between patients with high and low p53 expression. In patients with low p53 expression, positive EGFR staining was associated with significantly worse survival compared with patients with negative EGFR staining (log-rank test: p < 0.001). Survival rates in positive and negative EGFR groups with high p53 protein expression were similar (log-rank test: p = 0.919). The IC50 of an EGFR inhibitor was higher in GBM cells with high p53 protein expression compared with the IC50 in cells with low p53 expression. Combined EGFR and p53 expression may have prognostic significance in astrocytomas.