Epidermal Growth Factor Receptor Research Articles

Corrigendum to: Executive summary of the American Radium Society appropriate use criteria for brain metastases in epidermal growth factor receptor mutated-mutated and ALK-fusion non-small cell lung cancer

Corrigendum to: Executive summary of the American Radium Society appropriate use criteria for brain metastases in epidermal growth factor receptor mutated-mutated and ALK-fusion non-small cell lung cancer

Altered glycosylation in cancer: molecular functions and therapeutic potential

AbstractGlycosylation, a key mode of protein modification in living organisms, is critical in regulating various biological functions by influencing protein folding, transportation, and localization. Changes in glycosylation patterns are a significant feature of cancer, are associated with a range of pathological activities in cancer‐related processes, and serve as critical biomarkers providing new targets for cancer diagnosis and treatment. Glycoproteins like human epidermal growth factor receptor 2 (HER2) for breast cancer, alpha‐fetoprotein (AFP) for liver cancer, carcinoembryonic antigen (CEA) for colon cancer, and prostate‐specific antigen (PSA) for prostate cancer are all tumor biomarkers approved for clinical use. Here, we introduce the diversity of glycosylation structures and newly discovered glycosylation substrate—glycosylated RNA (glycoRNA). This article focuses primarily on tumor metastasis, immune evasion, metabolic reprogramming, aberrant ferroptosis responses, and cellular senescence to illustrate the role of glycosylation in cancer. Additionally, we summarize the clinical applications of protein glycosylation in cancer diagnostics, treatment, and multidrug resistance. We envision a promising future for the clinical applications of protein glycosylation.

Analytical and Clinical Validation of the Oncomine Dx Target Test to Assess HER2 Mutation Status in Tumor Tissue Samples From Patients With Non–Small Cell Lung Cancer Treated With Trastuzumab Deruxtecan in the DESTINY-Lung01 and DESTINY-Lung02 Studies

Context.— Trastuzumab deruxtecan (T-DXd), a human epidermal growth factor receptor 2 (HER2)–targeted therapy, has demonstrated durable anticancer activity in patients with advanced, metastatic HER2 (also known as ERBB2)–mutant (HER2m) non–small cell lung cancer (NSCLC) who have limited treatment options and poor prognosis. Objective.— To analytically validate and assess the clinical utility of the Oncomine Dx Target (ODxT) Test as a companion diagnostic to identify patients with HER2m NSCLC. Design.— Tumor samples from patients in DESTINY-Lung01 and DESTINY-Lung02 were retrospectively analyzed alongside commercially procured samples using the ODxT test and compared to the assays used for screening in these clinical trials. Results.— Positive percent agreement (PPA) and negative percent agreement (NPA) between the ODxT Test and TruSight Tumor 170 assay when testing DESTINY-Lung01 and commercially procured samples met prespecified thresholds (PPA and NPA ≥90%) for analytical accuracy (100% and 99.1%). The ODxT Test results were highly concordant with clinical trial assays (CTAs) used in DESTINY-Lung01 (PPA and NPA, 98.0% and 100%) and DESTINY-Lung02 (PPA and NPA, 96.7% and 100%) to identify activating HER2 mutations in tumor samples. Confirmed objective response rates were similar between patients with HER2m tumors identified by the ODxT Test and by CTAs in DESTINY-Lung01 (58.3% and 54.9%) and DESTINY-Lung02 (53.6% and 53.8%). Response duration was 12.0 and 9.3 months for patients identified by the ODxT Test and CTAs, respectively, in DESTINY-Lung01. Conclusions.— The ODxT Test detected HER2 mutations in NSCLC with high analytical and clinical accuracy and identified HER2m populations with response rates similar to populations identified by CTAs, supporting clinical utility of the ODxT Test to inform treatment decisions for HER2m NSCLC.

Integrating network pharmacology and bioinformatics to explore the mechanism of Xiaojian Zhongtang in treating major depressive disorder: An observational study.

Major depressive disorder (MDD) is a common mental illness. The traditional Chinese medicine compound Xiaojian Zhongtang (XJZT) has a good therapeutic effect on MDD, but the specific mechanism is not clear. The aim of this study is to explore the molecular mechanism of XJZT in the treatment of MDD through network pharmacology and bioinformatics. The traditional Chinese medicine system pharmacology database was used to screen the chemical components and targets of XJZT, while the online Mendelian inheritance in man, DisGeNET, Genecards, and therapeutic target database databases were used to collect MDD targets and identify the intersection targets of XJZT and MDD. A "drugs-components-targets" network was constructed using the Cytoscape platform, and the STRING was used for protein-protein interaction analysis of intersecting targets. Gene Ontology and Kyoto encyclopedia of genes and genomes analysis of intersecting targets was performed using the DAVID database. Obtain serum and brain transcriptome datasets of MDD from the gene expression omnibus database, and perform differentially expressed genes, weighted gene co-expression network analysis, gene set enrichment analysis, and receiver operating characteristic analysis. A total of 127 chemical components and 767 targets were obtained from XJZT, among which quercetin, kaempferol, and maltose are the core chemical components, and 1728 MDD targets were screened out, with 77 intersecting targets between XJZT and MDD. These targets mainly involve AGE-RAGE signaling pathway in diabetic complexes, epidermal growth factor receptor tyrosine kinase inhibitor resistance, and HIF-1 signaling pathway, and these core targets have strong binding activity with core components. In addition, 1166 differentially expressed genes were identified in the MDD serum transcriptome dataset, and weighted gene co-expression network analysis identified the most relevant gene modules (1269 genes), among which RAC-alpha serine/threonine-protein kinase (AKT1), D(4) dopamine receptor (DRD4), and kynurenine 3-monooxygenase (KMO) were target genes for the treatment of MDD with XJZT, these 3 genes are mainly related to the ubiquitin-mediated proteolysis, arachidonic acid (AA) metabolism, and Huntington disease pathways, and the expression of AKT1, DRD4, and KMO was also found in the MDD brain transcriptome dataset, which is significantly correlated with the occurrence of MDD. We have identified 3 key targets for XJZT treatment of MDD, including AKT1, KMO, and DRD4, and they can be regulated by the key components of XJZT, including quercetin, maltose, and kaempferol. This provides valuable insights for the early clinical diagnosis and development of therapeutic drugs for MDD.

Oral cancer in young adults: incidence, risk factors, prognosis, and molecular biomarkers

Oral cavity squamous cell carcinoma (OCSCC) predominantly affects the tongue and the floor of the mouth, primarily in patients over 50 years of age. Incidence and mortality rates vary significantly worldwide, influenced by geographic areas and demographic characteristics. Epidemiological studies revealed an increase in incidence of OCSCC among young adults (YA) <44 years old. This narrative review, provides updated information on the incidence, risk factors, and prognosis of YA-OCSCC using data published from 2018 to 2023 from different geographic locations. The studies indicate that the incidence of YA-OCSCC in Asia is approximately twice that in the US and that the incidence is strongly linked to risk factors such as betel quid chewing, tobacco use, and high alcohol consumption. The prognosis for YA-OCSCC, compared to that in older patients, shows similar or better overall survival, even in cases with relapses, but worse 5-year disease-free survival, despite receiving similar treatments. Consequently, a concerted effort is crucial to raise awareness about the cessation of tobacco and areca nut use, alcohol control, and the promotion of healthy lifestyle behaviors. Recent molecular data on YA-OCSCC suggests a potential profile characterized by epidermal growth factor receptor overexpression, low tumor mutation burden and an attenuated immune response. Upon confirmation in larger cohorts of YA-OCSCC patients from different geographical areas, the validated markers could aid in selecting tailored treatments.

Repurposing Antiviral Drugs as Potential Anti-EGFR Agents in NSCLC: A Structure-Based Screening and Molecular Dynamics Analysis.

One of the problems resulting from recurrent hyperactivated or mutant epidermal growth factor receptors (EGFR) in non-small cell lung cancer (NSCLC) is therapeutic resistance. Consequently, this leads to increased expressionof oncogenicproteins and reduces the efficacy of EGFR tyrosine kinase inhibitors (TKIs). This study assessed antiviral drug efficacy as potential anti-EGFR agentsfor NSCLC. We used structure-based virtual screening to evaluate 66 antiviral drugs thoroughly. The top 6 antiviral drugs exhibiting impressive binding energies (i.e. surpassing a threshold of -8.5 kcalmol-1) were identified. Subsequent bioactivity analysis and ADMET profiling were performed to select the most promising candidates, followed by a molecular dynamic simulation. Among the selected antiviral regimens, dolutegravir demonstrated the highest docking score (-9.8 kcalmol-1), followed by rilpivirine and ensitrelvir, surpassing other candidates and our reference EGFR TKI. Further molecular dynamics simulations revealed promising dynamic interactions of dolutegravir, ensitrelvir, and rilpivirine with the EGFR target as compared with afatinib. Our findings highlight the repositioning potential of antiviral drugs for anti-EGFR drug discovery, supported by their robust docking scores, ADMET profiles, dynamic interactions, and binding free energies. The results open up new avenues for advanced NSCLC therapy. Further in vitro investigations are warranted to evaluate their efficacy and safety.

PEARL: A Phase Ib/II Biomarker Study of Adding Radiation Therapy to Pembrolizumab Before Neoadjuvant Chemotherapy in Human Epidermal Growth Factor Receptor 2–Negative Breast Cancer

PURPOSE To assess safety and immune biomarkers after preoperative radiation therapy (RT) and anti-PD1 therapy in breast cancer. MATERIALS AND METHODS A phase I/IIb trial of pembrolizumab with RT was conducted in patients with triple-negative breast cancer (TNBC) and hormone receptor–positive/human epidermal growth factor receptor 2–negative (HR+/HER2–) breast cancer. All received pembrolizumab followed by a second cycle + RT (anti-PD1/RT) of 24 Gy/three daily fractions delivered to the breast tumor and then neoadjuvant chemotherapy (NAC). Blood and tumor biopsies were obtained at baseline, after anti-PD1, and after anti–PD-RT. Coprimary end points were safety and change in tumor-infiltrating lymphocytes (TILs). Secondary end points were pathologic complete response (pCR), residual cancer burden (RCB) rates, and event-free survival (EFS). RESULTS Sixty-six patients with stage I-III breast cancer (54 TNBC, 12 HR+/HER2–) were enrolled. The median follow-up was 32 months. Safety end point was met. Incidence of grade ≥3 toxicities was 41%. The pCR rate was 59.2%, 33.3%, and 54.5% for the TNBC, HR+/HER2–, and entire cohort, respectively. A total of 77.8% of TNBC and 41.6% of HR+/HER2– had a near pCR (RCB 0-1). The 3-year EFS was 80%. In the entire cohort, PD-L1 expression increased after anti-PD1 (median Combined Positive Score [CPS], 7.49-23.20; 95% CI, –41.88 to –6.30; P = .044) and anti-PD1/RT (median CPS, 7.49-23.41; 95% CI, –41.88 to –6.30; P = .009), compared with baseline. In TNBC, adding RT to anti-PD1 significantly decreased TILs (28.9%-17.1%; 95% CI, 2.46 to 21.09; P = .014). Baseline TILs correlated with PD-L1 expression and TNF-a. CONCLUSION Preoperative RT with pembrolizumab is safe and results in high pCR rates and 3-year EFS, despite the lack of pembrolizumab during NAC. PD-L1 and TILs may be predictive biomarkers for preoperative anti-PD1/RT response. Reduction in TILs after adding RT to anti-PD1 highlights the importance of treatment sequencing.

EGFRVIII and EGFR targeted chimeric antigen receptor T cell therapy in glioblastoma.

Glioblastoma is the most common primary brain tumor. Although there have been significant advances in surgical techniques, chemo and immunotherapies, and radiation therapy, outcomes continue to be devastating for these patients with minimal improvements in survival. Chimeric antigen receptor T cell therapy is a revolutionary approach that is a new pillar in the treatment of cancer. CAR T cell therapy has produced remarkable results in hematological malignancies; however, multiple limitations currently prevent it from being a first-line therapy, especially for solid tumors. Epidermal growth factor receptor is classically amplified in glioblastoma, and a variant, EGFR variant III, is expressed on glioblastoma, making it an exciting potential target for CAR T cell therapy. Although preclinical has exciting potential, clinical data has been heterogeneous. In this review, we assess the state of field of EGFR-targeted CAR T cells.

The Correlation between Immunohistochemistry and In Situ Hybridization for the Assessment of Human Epidermal Growth Factor Receptor 2 (HER-2) Status in Breast Cancer in Buddhasothorn Hospital

The Correlation between Immunohistochemistry and In Situ Hybridization for the Assessment of Human Epidermal Growth Factor Receptor 2 (HER-2) Status in Breast Cancer in Buddhasothorn Hospital

Explainable breast cancer molecular expression prediction using multi-task deep-learning based on 3D whole breast ultrasound

ObjectivesTo noninvasively estimate three breast cancer biomarkers, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) and enhance performance and interpretability via multi-task deep learning.MethodsThe study included 388 breast cancer patients who received the 3D whole breast ultrasound system (3DWBUS) examinations at Xijing Hospital between October 2020 and September 2021. Two predictive models, a single-task and a multi-task, were developed; the former predicts biomarker expression, while the latter combines tumor segmentation with biomarker prediction to enhance interpretability. Performance evaluation included individual and overall prediction metrics, and Delong’s test was used for performance comparison. The models’ attention regions were visualized using Grad-CAM + + technology.ResultsAll patients were randomly split into a training set (n = 240, 62%), a validation set (n = 60, 15%), and a test set (n = 88, 23%). In the individual evaluation of ER, PR, and HER2 expression prediction, the single-task and multi-task models achieved respective AUCs of 0.809 and 0.735 for ER, 0.688 and 0.767 for PR, and 0.626 and 0.697 for HER2, as observed in the test set. In the overall evaluation, the multi-task model demonstrated superior performance in the test set, achieving a higher macro AUC of 0.733, in contrast to 0.708 for the single-task model. The Grad-CAM + + method revealed that the multi-task model exhibited a stronger focus on diseased tissue areas, improving the interpretability of how the model worked.ConclusionBoth models demonstrated impressive performance, with the multi-task model excelling in accuracy and offering improved interpretability on noninvasive 3DWBUS images using Grad-CAM + + technology.Critical relevance statementThe multi-task deep learning model exhibits effective prediction for breast cancer biomarkers, offering direct biomarker identification and improved clinical interpretability, potentially boosting the efficiency of targeted drug screening.Key PointsTumoral biomarkers are paramount for determining breast cancer treatment.The multi-task model can improve prediction performance, and improve interpretability in clinical practice.The 3D whole breast ultrasound system-based deep learning models excelled in predicting breast cancer biomarkers.Graphical

Reduction of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant infection by blocking the epidermal growth factor receptor (EGFR) pathway.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants presents challenges in global efforts to transition from the pandemic to an endemic stage. The spike protein of the SARS-CoV-2 virus, which is pivotal for cell entry, exhibits significant mutations in its variants, potentially affecting infectivity and therapeutic efficacy. Recent findings indicate upregulation of the epidermal growth factor receptor (EGFR) pathway, a key target in cancer therapy, by the spike protein of SARS-CoV-2. This study aimed to investigate the activity of the EGFR pathway against SARS-CoV-2 variants and to assess the inhibitory effects of EGFR inhibitors using SARS-CoV variant pseudoviral particles to guide future therapeutic strategies. Omicron variant SARS-CoV pseudoviral particles exhibited heightened infectivity in human angiotensin-converting enzyme 2 (hACE2)-expressing HEK293 and A549 lung cancer cells accompanied by increased EGFR pathway activation in infected cells. Using the EGFR tyrosine kinase inhibitor, osimertinib, we observed a reduction in viral infection rates in hACE2-HEK293 and A549 cells infected with the SARS-CoV-2 variant pseudoviral particles. We conducted further experiments to confirm that the reduction in infection efficacy with osimertinib treatment was not associated to a decrease in cell viability. Furthermore, this inhibitory effect of osimertinib in cell lines was corroborated in a spheroid cell culture model derived from hACE2-A549 cells. These findings suggest the potential application of EGFR-targeted antiviral therapy against highly infectious SARS-CoV-2 variants.IMPORTANCEThe emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants is concerning as vaccines designed for one variant need not essentially protect against other novel variants. Therefore, there is an urgent need to identify therapies that can act against multiple novel variants that have heightened virulence compared with the wild type. It has been reported that the spike protein of the SARS-CoV-2 virus elicits an increased expression of the epidermal growth factor receptor (EGFR) pathway. We used this information and examined whether treatment with an EGFR inhibitor, osimertinib, which is already approved for clinical use in cancer therapy, can reduce the infection caused by SARS-CoV-2, wild type, and Omicron and Delta variants, in two cell lines and one spheroid model. The results showed that osimertinib treatment successfully reduced infection efficacy, particularly in variants, and that this effect was not related to a reduction in cell viability, making this a promising strategy for treating SARS-CoV-2 infections.

Analysis of clinicopathological characteristics and prognostic factors in 54 metaplastic breast carcinoma patients from northwest China

Objective: Metaplastic breast carcinoma (MBC) is a special type of morphologically heterogeneous and aggressively invasive breast cancer. MBC is characterized by the transformation of tumor epithelium into squamous epithelium and/or mesenchymal components, including differentiation into spindle cells, chondrocytes, and osteocytes. Due to its rarity and invasiveness, there is a paucity of research on MBC prognosis. Furthermore, there are currently no treatment guidelines for MBC. This study analyzed the clinicopathological characteristics, immunophenotype, and prognostic features of MBC. Our aim was to better characterize MBC, thereby identifying potential prognostic factors and new treatment methods. Moreover, we also describe an MBC case treated experimentally with anti-vascular targeted therapy. Material and Methods: We retrospectively analyzed clinical pathological data on 54 female patients with MBC from Shaanxi Provincial People’s Hospital and the XiJing Hospital of Air Force Medical University. These cases were diagnosed with MBC between January 1st, 2013, and October 1st, 2018. All patients were from the northwest region of China. The gross morphological, histological, and immunohistochemical features of MBC were analyzed. Kaplan–Meier analysis was used to calculate the survival rate, and univariate analysis was performed to identify significant prognostic factors. In addition, the treatment of an MBC patient with anti-angiogenic therapy was described, and a relevant literature review was conducted. Results: MBC was diagnosed in 32 left breasts and 22 right breasts from 54 women aged 21–76 years (median age of 57 years). The maximum tumor diameter ranged from 0.6 to 14 cm (average of 4.1 cm). Of the 54 patients, 47 underwent surgical treatment, with lymph node metastasis found in 17.0% (8/47). According to the World Health Organization classification criteria for breast tumors, the study cohort consisted of 15 cases of squamous cell carcinoma, ten cases of spindle cell carcinoma, nine cases of carcinoma with associated stromal differentiation, 18 cases of mixed carcinoma, and two cases of adenocarcinoma with squamous differentiation. Based on the American Joint Committee on Cancer clinical staging criteria, the patients were classified as Stage I (10 cases, 18.5%), Stage II (26 cases, 48.1%), Stage III (11 cases, 20.4%), and Stage IV (7 cases, 13.0%). Immunohistochemical analysis revealed that 94.4% of patients had triple-negative breast cancer (TNBC), 47 cases showed mutant tumor protein 53 (TP53) expression, 29 cases showed positive epidermal growth factor receptor (EGFR) expression, 43 cases showed positive E-cadherin expression, and 37 cases showed positive Cluster of Differentiation 24 expression. The Ki-67 index ranged from 20% to 90%. Univariate analysis showed that the Ki-67 index was not significantly associated with either progression-free survival (PFS) or overall survival (OS) in MBC patients. Patients with negative axillary lymph nodes had significantly better PFS and OS than those with positive nodes (P < 0.05), and patients with clinical stage I-II disease had better PFS and OS than those with stage III-IV disease (P < 0.05). Patients treated with anthracycline-containing chemotherapy had significantly better PFS than those who did not receive chemotherapy. Univariate analysis revealed that the high expression of EGFR correlated with worse PFS (P < 0.05). The type of surgical approach employed did not affect the prognosis of MBC patients. Following the application of anti-angiogenic therapy, a rapid partial response was observed in an MBC patient with carcinoma and associated stromal differentiation. This patient subsequently underwent surgery and radiation therapy and has now achieved over 6 years of PFS. Conclusion: MBC is a heterogeneous group of tumors with high malignancy and poor prognosis. The large majority is TNBC and exhibits unique immune phenotypes. The poor PFS of MBC patients may be related to EGFR expression, which could become a potential therapeutic target in these patients. Surgery remains the primary treatment method for MBC. The present study found that sentinel lymph node biopsy was feasible in appropriate patients, and that chemotherapy regimens incorporating anthracycline-class drugs did not appear to improve OS. Anti-angiogenic therapy holds promise as a potentially effective treatment approach for MBC, and the optimization of systemic treatment strategies should be a priority in the management of these patients.

WISP1 and Macrophage Migration Inhibitory Factor in Respiratory Inflammation: Novel Insights and Therapeutic Potentials for Asthma and COPD.

Recent advancements highlight the intricate interplay between the extracellular matrix (ECM) and immune responses, notably in respiratory diseases such as asthma and Chronic Obstructive Pulmonary Disease (COPD). The ECM, a dynamic structural framework within tissues, orches-trates a plethora of cellular processes, including immune cell behavior and tissue repair mecha-nisms. WNT1-inducible-signaling pathway protein 1 (WISP1), a key ECM regulator, controls immune cell behavior, cytokine production, and tissue repair by modulating integrins, PI3K, Akt, β-catenin, and mTOR signaling pathways. WISP1 also induces macrophage migration inhibitory factor (MIF) expression via Src kinases and epidermal growth factor receptor (EGFR) activation. MIF, through its wide range of activities, enhances inflammation and tissue restructuring. Rec-ognized for its versatile roles in regulating the immune system, MIF interacts with multiple immune components, such as the NLRP3 inflammasome, thereby sustaining inflammatory pro-cesses. The WISP1-MIF axis potentially unveils complex molecular mechanisms governing im-mune responses and inflammation. Understanding the intricate roles of WISP1 and MIF in the pathogenesis of chronic respiratory diseases such as asthma and COPD could lead to the identi-fication of novel targets for therapeutic intervention to alleviate disease severity and enhance patient outcomes.

Detection of Circulating Tumor Cells and EGFR Mutation in Pulmonary Vein and Arterial Blood of Lung Cancer Patients Using a Newly Developed Immunocytology-Based Platform.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors are powerful molecular targeted therapeutic agents for lung cancer. We recently developed an original immunocytology and glass slide-based circulating tumor cell (CTC) detection platform for both CTC enumeration and EGFR mutation analysis with DNA extracted from CTCs. Using this platform, we conducted a pilot clinical study for CTC enumeration in peripheral blood (PB), pulmonary arterial blood (PA), and pulmonary venous blood (PV) from 33 patients with lung cancer (Stage I-III) who underwent surgery, followed by digital PCR-based EGFR mutation analysis of CTCs in PV from 12 patients. The results showed that CTC levels were significantly higher in PV and PA than in PB (p < 0.05, p < 0.01. respectively), with a notably greater number of small and large CTC clusters (p < 0.01). Genetic analysis of EGFR mutations of CTCs from PV (n = 12) revealed six mutations, including three Exon19del and three L856R, in CTCs and eight EGFR mutations, including five Exon19del and three L856R, in lung tumor tissue. CTC mutation status matched that of tissue samples in nine patients, was unmatched in two patients, and controversial in one patient, indicating a sensitivity of 0.75 (6/8) and specificity of 1.0 (4/4) with some false-negative results for the mutation analysis of CTCs. This immunocytology-based CTC detection platform is a convenient method for detecting both CTC number and EGFR mutation status under microscopy, suggesting its potential as a liquid biopsy tool in the hospital for patients with lung cancer in some clinical settings.

EGFR-TKI combined with radiotherapy in 105 patients of lung adenocarcinoma with brain metastasis: a retrospective study of prognostic factors analysis.

This study aimed to retrospectively analyze the response and prognosis factors for patients of lung adenocarcinoma with brain metastasis and epidermal growth factor receptor (EGFR) mutation, who were treated by EGFR-tyrosine kinase inhibitor (TKI) combined with brain radiotherapy (RT). From Jan 2021 to Jan 2024, the clinicopathological data of lung adenocarcinoma patients were collected from the First Affiliated Hospital of Hebei North University. SPSS version 26.0 statistical software was used for statistical analysis. P &lt; 0.05 was determined to be statistically significant. 105 patients were included. The 1, 2, 3-year overall survival (OS) rate was 82.9%, 61.2%, and 33.7%, respectively. 1, 2 ,3-year progression-free survival 1 (PFS1) rate was 62.7%, 36.6%, 22.1%. 1,2,3-year PFS2 rate was 80.8%, 54.6%, and 31.4%. The median OS, PFS1 and PFS2 was 29.8, 18.0 and 28.1 months, respectively. The COX multivariate analysis showed that gene mutation status and brain radiation dose were independent prognostic factors for OS; Gene mutation status, brain radiation dose, and response evaluation to initial treatment (response evaluation) are independent prognostic factors for PFS1; Clinical stage, gene mutation status, brain radiation dose, and response evaluation are independent prognostic factors for PFS2. TKI combined with brain radiotherapy is effective on lung adenocarcinoma patients with EGFR mutation and brain metastasis. Patients with 19 Del or 21 L858R mutation and brain radiation doses ≥ 40 Gy have longer OS, PFS1, and PFS2, and complete remission (CR) + partial remission (PR) is associated with longer PFS1 and PFS2, Patients in stage IVA have longer PFS2.

The Factors Associated With Mutant Epidermal Growth Factor Receptor Positivity in Patients With Lung Cancer: A Study From a Tertiary Care Center in Pakistan

The Factors Associated With Mutant Epidermal Growth Factor Receptor Positivity in Patients With Lung Cancer: A Study From a Tertiary Care Center in Pakistan

Ultrasound-based radiomics nomogram for predicting HER2-low expression breast cancer.

Accurate preoperative identification of Human epidermal growth factor receptor 2 (HER2) low expression breast cancer (BC) is critical for clinical decision-making. Our aim was to use machine learning methods to develop and validate an ultrasound-based radiomics nomogram for predicting HER2-low expression in BC. In this retrospective study, 222 patients (108 HER2-0 expression and 114 HER2-low expression) with BC were included. The enrolled patients were randomly divided into a training cohort and a test cohort with a ratio of 8:2. The tumor region of interest was manually delineated from ultrasound image, and radiomics features were subsequently extracted. The features underwent dimension reduction using the least absolute shrinkage and selection operator (LASSO) algorithm, and rad-score were calculated. Five machine learning algorithms were applied for training, and the algorithm demonstrating the best performance was selected to construct a radiomics (USR) model. Clinical risk factors were integrated with rad-score to construct the prediction model, and a nomogram was plotted. The performance of the nomogram was assessed using receiver operating characteristic curve and decision curve analysis. A total of 480 radiomics features were extracted, out of which 11 were screened out. The majority of the extracted features were wavelet features. Subsequently, the USR model was established, and rad-scores were computed. The nomogram, incorporating rad-score, tumor shape, border, and microcalcification, achieved the best performance in both the training cohort (AUC 0.89; 95%CI 0.836-0.936) and the test cohort (AUC 0.84; 95%CI 0.722-0.958), outperforming both the USR model and clinical model. The calibration curves showed satisfactory consistency, and DCA confirmed the clinical utility of the nomogram. The nomogram model based on ultrasound radiomics exhibited high prediction value for HER2-low BC.

Cutaneous Toxicities With Amivantamab for Non-Small Cell Lung Cancer: A Practical Guide and Best Practices.

Amivantamab is an epidermal growth factor receptor (EGFR) and MET bispecific antibody approved for certain patients with advanced non-small cell lung cancer with EGFR variant. Cutaneous toxicities are known on-target effects of EGFR inhibition. This article describes the occurrence and management of cutaneous toxicities in patients whose disease progressed on platinum chemotherapy treated with amivantamab. Post hoc analysis evaluated incidence, severity, and time to first onset of rash and paronychia. Five nurses and advanced practice providers were interviewed. Of 380 patients, 296 (78%) experienced treatment-related rash and/or paronychia. Paronychia (43%), rash (36%), and dermatitis acneiform (35%) were most frequent, with scalp rash reported by 17%. Treatment modifications because of rash and paronychia were infrequent. Nurses and advanced practice providers collaborate with physicians to manage cutaneous toxicities by administering comedications, modifying amivantamab dose, and educating patients.

Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Cancer: Current Use and Future Prospects.

Tyrosine kinase inhibitors (TKIs) have emerged as a leading targeted cancer therapy, reducing the side effects often seen with non-targeted treatments, especially the damage to healthy cells. To tackle resistance, typically caused by epidermal growth factor receptor (EGFR) mutations, four generations of TKIs have been developed. Each generation has shown improved effectiveness and fewer side effects, resulting in better patient outcomes. For example, patients on gefitinib, a first-generation TKI, experienced a progression-free survival (PFS) of 10 months compared to 5 months with conventional chemotherapy. Second-generation TKI afatinib outperformed erlotinib and extended PFS to 11.1 months compared to 6.9 months with cisplatin. Third-generation TKIs further increased survival to 38.6 months, compared to 31.8 months with first-generation TKIs. This progress demonstrates the ability of newer TKIs to overcome resistance, particularly the T790M mutation, while reducing adverse effects. Ongoing research focuses on overcoming resistance from newer mutations like C797S to further improve patient survival. These developments highlight the significant progress in TKI therapy and the continued effort to refine cancer treatment. Recent research in South Korea shows that third-generation TKIs are ineffective against non-small cell lung cancer (NSCLC) with the C797S mutation. Several trials have started showing promising in vitro and in vivo results, but more trials are needed before clinical approval. This review underscores notable advancements in the field of EGFR TKIs, offering a comprehensive analysis of their mechanisms of action and the progression of various TKI generations in response to resistance.

Racial Differences in Breast Cancer Survival Between Black and White Women According to Tumor Subtype: A Systematic Review and Meta-Analysis.

Despite effective early-detection approaches and innovative treatments, Black women in the United States have higher breast cancer mortality rates compared with White women. The purpose of this systematic review and meta-analysis is to determine the extent of disparities in breast cancer survival between Black and White women according to tumor subtype. A comprehensive database search was performed for full-text, English-language articles published from January 1, 2000, to December 31, 2022. Included studies compared survival between Black and White female patients with breast cancer within subtypes defined by hormone receptor and human epidermal growth factor receptor 2 (HER2)/neu (HER2; now known as ERBB2) status. Random-effects models were used to combine study-specific results and generate pooled relative risks (RRs) and 95% CIs for breast cancer-specific or overall survival (OS). A protocol for this review was registered in PROSPERO (CRD42021268212). Eighteen studies including 228,885 (34,262 Black; 182,466 White) patients with breast cancer were identified. Compared with White women, Black women had a higher risk of breast cancer death for all tumor subtypes. The summary risk of breast cancer death was 50% higher among hormone receptor-positive HER2-negative [HER2-] tumors (RR, 1.50 [95% CI, 1.30 to 1.72]), 34% higher for hormone receptor+/HER2+ (RR, 1.34 [95% CI, 1.10 to 1.64]), 20% higher for hormone receptor-negative (-)/HER2+ (RR, 1.29 [95% CI, 1.00 to 1.43]), and 17% higher among individuals with hormone receptor-/HER2- tumors (hazard ratio, 1.17; 95% CI, 1.10 to 1.25). Black women also had poorer OS than White women for all subtypes. These results suggest there are both subtype-specific and subtype-independent mechanisms that contribute to disparities in breast cancer survival between Black and White women, which require multilevel interventions to address and achieve health equity.