Epidermal Growth Factor Receptor Mutation Group Research Articles

The prognosis of TP53 and EGFR co-mutation in patients with advanced lung adenocarcinoma and intracranial metastasis treated with EGFR-TKIs.

TP53 mutation is a poor factor for non-small cell lung cancer (NSCLC), while the effect of TP53 on prognosis in epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma (LUAD) with brain metastasis remains elusive and needs further exploration. We retrospectively analyzed 236 patients and tested for TP53- and EGFR-mutant status in metastasis LUAD patients who had received first-line EGFR-tyrosine kinase inhibitor (TKI) treatment. Survival rates were calculated by the Kaplan-Meier method. Furthermore, univariate and multivariate Cox analyses were performed to identify the independent prognostic factors. There were 114 patients with confirmed non-brain metastasis (NBM), 74 patients with preliminary diagnosis early brain metastasis (EBM), and 48 patients with late brain metastasis (LBM). TP53 and EGFR co-mutations were found in 35/236 patients (14.8%). The median progression-free survival (PFS) and overall survival (OS) in the EGFR mutation and TP53 wild-type group were significantly longer than those in the EGFR and TP53 co-mutation group in all advanced LUAD or NBM. Concurrently, PFS and OS were found to be not significant in EBM and LBM patients. Subgroup analysis revealed longer median PFS and OS in the TP53 wild-type group compared to the TP53 mutant group in L858R patients and not significant in EGFR Exon 19 deletion patients. In LBM patients, the time to brain metastasis in the EGFR mutation and TP53 wild-type group was longer than that in the EGFR and TP53 co-mutation group, and TP53 mutant status was an independent prognostic factor for brain metastasis. The TP53 wild-type group exhibited a higher objective remission rate (ORR) and disease control rate (DCR) than the TP53 mutant group in NBM, EBM, and LBM patients, irrespective of primary lung and brain metastatic lesions. TP53/EGFR co-mutation patients receiving first-line EGFR-TKI treatment had poor prognoses in advanced LUAD, especially with L858R mutation. Moreover, TP53/EGFR co-mutation patients treated with EGFR-TKIs may more easy developed intracranial metastasis.

Apparent diffusion coefficient value of brain metastasis from lung carcinoma as potential predictor of epidermal growth factor receptor mutation

BackgroundLung carcinoma metastases to the brain occurred in 40% of all lung carcinoma cases and it occupied the top ranking of mortality of cancers. MRI plays an important role in predicting mutations of lung carcinoma.ObjectiveThis study aimed to compare apparent diffusion coefficient (ADC) values ​​from brain MRI among lung carcinoma patients with and without epidermal growth factor receptor (EGFR) mutations which result in brain metastases.MethodsData of fifty-two patients with brain metastasis from lung carcinoma during 2019 to 2022 were taken. The three regions of interest (ROI) were placed to the mutation, non-mutation, and non-lesion groups to predict ADC values.ResultsThe ADC values of the EGFR mutation group were not significantly different from either the non-EGFR mutation group or the non-lesion group. The average ADC value of the EGFR mutation group was the lowest, followed by the non-EGFR mutation group and the non-lesion group. The prediction of ADC values ​in the EGFR mutation group ranged 0,773–0,815 × 10−3 mm2/s, followed by the non-EGFR mutation group 0,82 × 10−3 mm2/s, and non-lesion group 0.841 × 10−3 mm2/s.ConclusionsThe ADC values in contrast-brain-MRI can be used as a predictor of EGFR mutations in lung carcinoma with lower prediction value than non-EGFR mutation patients. The ADC values in MRI can contribute in diagnosing and planning further management for lung carcinoma towards precision therapy era.

MRI features and whole-lesion apparent diffusion coefficient histogram analysis of brain metastasis from non-small cell lung cancer for differentiating epidermal growth factor receptor mutation status

To explore the utility of magnetic resonance imaging (MRI) characteristics and whole-lesion apparent diffusion coefficient histogram analysis of brain metastasis from non-small cell lung cancer (NSCLC) in the differentiation of epidermal growth factor receptor (EGFR) mutation status. Forty-eight patients with brain metastases from NSCLC were enrolled in this retrospective study. Patients were subtyped into EGFR mutation (23 cases) and wild-type (25 cases) groups. Whole-lesion histogram metrics were derived from the apparent diffusion coefficient (ADC) maps, and imaging features were evaluated according to conventional MRI. Student's t-test or Mann-Whitney U-test, chi-squared test, and receiver operating characteristic (ROC) curve analysis were performed to discriminate the two groups and to determine the diagnostic efficacy of ADC histogram parameters. EGFR mutation group had more multiple brain metastases, less peritumoural brain oedema (PTBO), and lower peritumoural brain oedema index (PTBO-I) than EGFR wild-type group (all p<0.05). In addition, 90th and 75th percentiles of ADC and maximum ADC in the EGFR mutation group were significantly higher than in the EGFR wild-type group (all p<0.05). Ninetieth percentile of ADC had the highest area under the curve (AUC; 0.711), and it was found to outperform 75th percentile of ADC (AUC, 0.662; p=0.039) and maximum ADC (AUC, 0.681). Whole-lesion ADC histogram analysis and MRI features of brain metastasis from NSCLC are expected to be potential biomarkers to non-invasively differentiate the EGFR mutation status.

EGFR Mutation-Positive Unresectable Stage III Non-Squamous Lung Cancer Is Associated with a High Incidence of Brain Metastasis.

The impact of epidermal growth factor receptor (EGFR) mutation in locally advanced non-small cell lung cancer (NSCLC) remains controversial. This study was conducted to investigate the clinical outcomes and recurrence patterns after definitive chemoradiotherapy (CRT) in patients with unresectable stage III non-squamous-cell lung cancer according to EGFR mutation status. We retrospectively reviewed 604 patients with pathologically confirmed stage III NSCLC who were treated with definitive CRT and were examined for EGFR mutation at Samsung Medical Center, Korea, from January 2013 to December 2018. Among them, we identified 236 patients with stage III non-squamous-cell lung cancer who were treated with definitive CRT and were examined for EGFR mutation status. We analyzed the frequency of EGFR mutation, progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and recurrence pattern. Among 236 patients, EGFR mutation was detected in 71 patients (30.1%) and the median follow-up duration was 41.7 months. There were no significant differences in PFS (9.9 vs. 10.9 months, p=0.236), and ORR to CRT (93.0% vs. 90.3%, p=0.623) according to EGFR mutation status. However, the EGFR mutant group showed significantly higher recurrence (88.7% vs. 75.2%, p=0.022), distant metastasis (76.1% vs. 61.2%, p=0.036) rates, especially brain (38.0% vs. 12.7%, p < 0.001), and better median OS (59.2 vs. 41.3 months, p=0.037) compared with patients without EGFR mutation. Patients with EGFR mutation-positive unresectable stage III non-squamous lung cancer exhibited higher recurrence and distant metastasis rates, especially brain metastasis.

Association between squamous cell carcinoma antigen level and EGFR mutation status in Chinese lung adenocarcinoma patients.

BackgroundTo investigate the association between squamous cell carcinoma antigen (SCCAg) level and epidermal growth factor receptor (EGFR) mutation status in Chinese lung adenocarcinoma patients.MethodsWe retrospectively analyzed 293 patients with lung adenocarcinoma, divided into EGFR mutant group (n = 178) and EGFR wild‐type group (n = 115). The general data and laboratory parameters of the two groups were compared. We used univariable and multivariable logistic regression to analyze the association between SCCAg level and EGFR mutation. Generalized additive model was used for curve fitting, and a hierarchical binary logistic regression model was used for interaction analysis.ResultsSquamous cell carcinoma antigen level in the EGFR wild‐type group was significantly higher than that in the mutant group (p < 0.001). After adjusting for confounding factors, we found that elevated SCCAg was associated with a lower probability of EGFR mutation, with an OR of 0.717 (95% CI: 0.543–0.947, p = 0.019). For the tripartite SCCAg groups, the increasing trend of SCCAg was significantly associated with the decreasing probability of EGFR mutation (p for trend = 0.015), especially for Tertile 3 versus Tertile 1 (OR = 0.505; 95% CI: 0.258–0.986; p = 0.045). Curve fitting showed that there was an approximate linear negative relationship between continuous SCCAg and EGFR mutation probability (p = 0.020), which was first flattened and then decreased (p < 0.001). The association between the two was consistent among different subgroups, suggesting no interaction (all p > 0.05).ConclusionThere is a negative association between SCCAg level and EGFR mutation probability in Chinese lung adenocarcinoma patients.

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

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

Quantitative volumetric assessment of the solid portion percentage on CT images to predict ROS1/ALK rearrangements in lung adenocarcinomas.

In the present study, the predictive role of the percentage of the solid portion volume (PSV) in patients with lung adenocarcinoma was investigated. The PSV was obtained through quantitative volumetric assessments based on reconstructed CT images of lung adenocarcinoma by comparing the index among tumors with c-ros oncogene 1 (ROS1) rearrangement, epidermal growth factor receptor (EGFR) mutations, echinoderm anaplastic lymphoma kinase (ALK) rearrangements or wild-type (WT) status for the three genes. Among 1,120 patients with lung adenocarcinoma, 28 patients with ROS1 rearrangement lung adenocarcinoma, 71 with ALK rearrangement and 578 with EGFR mutations were diagnosed. PSV was quantitatively measured by semi-automated nodule assessment software and compared in patients with different mutation statuses. The PSV (presented as the median with interquartile range) in the ROS1 rearrangement group [87.9 (82.7-92.3)%] was higher than that in the EGFR mutation group [70.4 (51.4-83.4%)] and the WT group [63.0 (50.9-83.2)%; P<0.001], but was similar to that in the ALK rearrangement group [84.0 (70.3-90.0)%; P=0.251]. The area under the receiver operating characteristic curve (AUC) for the PSV to predict ROS1 or ALK rearrangement combined was 0.702 (95% CI: 0.631-0.773; P<0.001); at a cut-off value of 0.805 (when the Youden index was maximal), the predictive sensitivity was 0.697 and the specificity was 0.702. Younger age and higher PSV values were independent predictors of ROS1/ALK rearrangements. The AUC for the predictive model combined with age and PSV was 0.785. In conclusion, the PSV in the lung adenocarcinomas with ROS1 rearrangement was significantly higher compared with that in the EGFR-mutated and WT lung adenocarcinoma, but was similar to that in lung adenocarcinoma with ALK rearrangement. Younger age and higher PSV values on CT in patients with lung adenocarcinomas were predictive factors for ROS1/ALK rearrangement.

Association of Carbonic Anhydrase 9 Polymorphism and the Epithelial Growth Factor Receptor Mutations in Lung Adenocarcinoma Patients.

Carbonic anhydrase 9 (CA9) plays a vital role in lung cancer progression. The current study explored the effect of CA9 gene polymorphisms and the epidermal growth factor receptor (EGFR) mutations on the clinicopathological characters of lung adenocarcinoma. In this study, three loci of CA9 single nucleotide polymorphism (SNP) (rs2071676 A > G, rs3829078 A > G, and rs1048638 C > A) were genotyped using the TaqMan allelic discrimination method in 193 EGFR wild type individuals and 281 EGFR mutation subjects. After adjusting for age, gender, and cigarette smoking status in logistic regression, all three CA9 SNPs illustrated a non-significant difference for the distribution between the EGFR wild type group and EGFR mutation group. Nevertheless, a significantly lower rate of CA9 SNP rs2071676 AG (adjusted odds ratio (AOR): 0.40, 95% confidence interval (CI): 0.16–0.95, p = 0.039) and AG + GG (AOR: 0.43, 95% CI: 0.18–0.98, p = 0.046) were found in the male population with L858R EGFR mutation compared to men with EGFR wild type. In addition, the CA9 SNP rs2071676 AG + GG genotype were significantly correlated to the lower tumor stage of lung adenocarcinoma in the whole study population (p = 0.044) and EGFR wild type individuals (p = 0.033). For the male population, the presence of CA9 SNP rs2071676 AG + GG genotype was also correlated to a lower tumor stage (p = 0.037) and fewer lymph node invasion (p = 0.003) in those with EGFR wild type. In conclusion, the existence of CA9 SNP rs2071676 is associated with the rate of EGFR L858R mutation in males. Furthermore, the CA9 SNP rs2071676 is correlated to lower tumor stage and lower risk for developing lymph node metastasis in lung adenocarcinoma, mainly in the EGFR wild type.

Clinical features of 54 cases of lung adenocarcinomas with c-ROS oncogene 1 fusion

Objective: To study the prevalence of c-ros oncogene 1 fusion in lung adenocarcinoma and to evaluate its relationship with clinical characteristics. Methods: We retrospectively analyzed epidermal growth factor receptor (EGFR) mutation, anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) fusion in 1 482 patients with adenocarcinoma from March 2014 to January 2017 in the first affiliated hospital of Zhejiang University. Furthermore, ROS1 fusion positive patients diagnosed between February 2017 and December 2017 were also included in ROS1 positive group. The data of age, sex, smoking history, TNM stage and chest computed tomography were collected by Electronic Medical Record (EMR). The clinical data were compared by the chi-squared test or Mann-Whitney test. Results: Of these 1 482 patients,54 cases were diagnosed with ROS1 rearrangement, including 19 males and 35 females, while 73 cases were diagnosed with ALK rearrangement, including 28 males and 45 females, and 679 cases diagnosed with EGFR mutation including 293 males and 386 females. And there were 676 patients without driven genes mutation. The mean age in ROS1 fusion group (54±12) was lower than EGFR mutation group (60±11, z=-3.982, P<0.001) and WT group (62±10, z=-4.944, P<0.001). Female proportion in ROS1 fusion group (64.8%, 35/54) was higher than WT group (28.4%, 192/676, χ(2)=30.94, P<0.001). Non-smoker percentages in ROS1 fusion group (72.2%, 39/54) was significantly higher than WT group (38.0%,257/676, χ(2)=24.27, P<0.001). ROS1 fusion group was similar to ALK fusion group in sex, age and smoking history, and there were no significant difference in TNM stage among these groups. On chest CT, adenocarcinomas with ROS1 fusion were found to be more peripheral in location (71.4%, 20/28) and solid in density (75%, 21/28), usually with lobulated margins (75.0%, 21/28) and spiculated in contour (57.1%,16/28). Conclusion: In our study lung adenocarcinoma with c-ROS oncogene 1 fusion was a rare subtype lung cancer and was usually detected in young, never smoking, and female patients.

The Correlation between EGFR Mutation Status and DNA Content of Lung Adenocarcinoma Cells in Pleural Effusion.

Objectives: Lung adenocarcinomas with or without epidermal growth factor receptor (EGFR) mutations have shown different drug effects against EGFR inhibitors. But it is not very clear if EGFR mutation status affects the biological behavior of lung adenocarcinoma, because tumor gene regulation is very complicated and can be affected by many factors. We aimed to explore if EGFR mutation status is related with tumor malignant degree by investigating the relevance of EGFR mutation status with DNA content and aneuploid peaks of lung adenocarcinoma cells in pleural fluids without using EGFR-TKIs.Materials and Methods: 591 cases of lung adenocarcinoma patients in Hebei Tumor Hospital who had undergone EGFR gene detection and DNA quantitative analysis were collected from January 2012 to August 2018.They were divided into two groups: EGFR mutant group and non-mutant group. EGFR mutations were detected by Amplification Refractory Mutation System (ARMS) and ABI 7500 Fluorescence quantitative PCR with pleural effusions. DNA content and aneuploid peaks were detected by LD DNA image cytometry (DNA-ICM). Rank-sum test of SPSS 16 was used for statistical analysis.Results: The maximum DI, the mean DI of the first 20 cells greater than 5C, the percentage of cells greater than 5C and the number of cells greater than 9C of the first 20 cells in the mutant group were all higher than those in the non-mutant group, having statistical significance (p<0.001); the peaks of aneuploid cells in the mutant group occurred more often than those in the non-mutant group, having statistical significance (p<0.001).Conclusions: Our study has shown that advanced lung adenocarcinomas with EGFR-mutations had higher DI values, more aneuploid cells and more frequent aneuploid peaks compared with those without EGFR-mutations, suggesting that advanced lung adenocarcinomas with EGFR mutations are more aggressive than those without EGFR mutations.

Radiotherapy for patients with completely resected pathologic IIIA(N2) non-small-cell lung cancer: a retrospective analysis.

IntroductionAdjuvant radiotherapy in non–small-cell lung cancer (NSCLC) remains controversial,Whether the mutation status of epidermal growth factor receptor (EGFR) will affect the recurrence and survival of patients with resected NSCLC is rarely reported. Our purpose is to study the effect of postoperative radiotherapy on patients with stage IIIA(N2) NSCLC with EGFR mutation.MethodsTotal of of 115 patients diagnosed with stage IIIA(N2) resected NSCLC were analyzed retrospectively. Their EGFR mutations were detected by real-time quantitative PCR and DNA sequencing technology together.ResultsAt a median follow-up of 34.2 months for the postoperative adjuvant radiotherapy (PORT) group and 31.0 months for the non-PORT group, PORT group significantly improved progression free survival (PFS) and overall survival (OS). The median PFS and OS in the EGFR mutant group were not significantly longer than those in the EGFR wild-type group. The number of chemotherapy cycles, postoperative radiotherapy and the number of metastatic lymph nodes were independent factors influencing long-term survival.ConclusionOur retrospective analysis showed that PORT can improve survival of patients with stage IIIA(N2) NSCLC. EGFR-mutant group with stage IIIA(N2) NSCLC has a tendency of a higher survival than the wild-type EGFR group, but there was no significant difference for both groups. The EGFR mutation status was not associated with PFS or OS of stage IIIA(N2) NSCLC.

Co-occurring genetic alterations predict distant metastasis and poor efficacy of first-line EGFR-TKIs in EGFR-mutant NSCLC.

To determine the frequency of co-occurring genes in non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation and the predictive effect of co-mutations on the efficacy of EGFR tyrosine kinase inhibitors (EGFR-TKIs). 54 patients with advanced NSCLC were tested for 422 clinically relevant genes by next-generation sequencing (NGS) before treatment. Among them, patients with EGFR mutation received first-line treatment of EGFR-TKIs. Progression-free survival (PFS) and objective response rate (ORR) were evaluated using Kaplan-Meier methods and compared between two groups using log-rank test. Among 24 EGFR mutant and 30 EGFR wild-type patients, co-mutation rate was lower in patients with EGFR mutation (62.5% [15/24] vs 93.3% [28/30], p = 0.005). There was lower frequency for co-alterations in BRAF (0% [0/24] vs 20% [7/30], p = 0.033), NF1 (4.2% [1/24] vs 30% [9/30], p = 0.038) and RAS-RAF-MAPK pathway genes (16.6% [4/24] vs 56.7% [17/30], p = 0.003) in EGFR mutation group. 24 patients with EGFR mutation received first-line treatment of gefitinib or erlotinib, with an ORR of 83.3% and a median PFS of 12.3months (95% CI 10.00-14.60). Co-mutation was associated with shorter median PFS (10.2months [95% CI 5.20-15.20] vs 15.3months [95% CI 12.09-15.81]; HR 0.29 [95% CI 0.10-0.82]; p = 0.014) in EGFR mutation cohort. Among patients with EGFR mutation and distant metastasis, median PFS was decreased in those with co-mutations (6.3months [95% CI 3.25-9.35] vs 22.0months[95% CI 12.10-31.90]; HR 0.12 [95% CI 0.00-5.87]; p = 0.007) and frequency of PIK3CA (0% [0/12] vs 41.7% [5/12], p = 0.037) and PI3K/AKT/mTOR pathway genes (0% [0/12] vs 50% [6/12], p = 0.014) was lower. The presence of co-mutations was lower in the EGFR mutation patients and reduces the efficacy of EGFR-TKI, especially in patients with distant metastases. Lower frequency of co-mutation in PIK3CA and PI3K/AKT/mTOR pathway genes may be responsible for promoting metastasis and limiting the efficacy of EGFR-TKIs.

The effective mutation of epidermal growth factor receptor in synchronous multiple primary lung cancers: study of clinical, radiographic and pathological factors

Objective: To investigate the clinical, pathological and CT features associated with the effective mutation of epidermal growth factor receptor (EGFR) in multiple primary lung cancers (MPLCs) , and to determine the target population of EGFR mutations tests. Methods: A total of 558 nodules from 232 patients with MPLCs who underwent surgery in the Cancer Hospital of Chinese Academy of Medical Sciences from August 2017 to December 2017 were selected. Two hundreds and sixteen nodules were detected by DNA direct sequencing. Chi-square test and Mann-Whitney U test were used to compare the clinical, pathological and CT features of 216 nodules in the EGFR effective mutation group and the non-effective mutation group. Logistic regression analysis was used to explore the independent risk factors of EGFR mutation. The cut off value was determined using the receiver operating characteristic(ROC) curve. Of 232 cases 558 nodules of surgically resected MPLCs, EGFR mutation of 216 nodules was determined by direct DNA sequencing. Results: There were 58 males and 174 females with MPLCs(male︰female=1︰3). There were 117 cases of age ≥59 years old and 115 cases of age <59 years old. There were 192 non-smokers, accounting for 82.8% of all patients. There were 2-7 nodules in the patient's lungs, of which 170 patients had two nodules in the lungs, 44 patients had 3 nodules, and another patient had 7 nodules. Among them, 216 nodules were detected by EGFR gene, 136 were effective mutations, and 80 were non-effective mutations (including wild type and null mutation). EGFR effective mutation group and non-effective mutation group were statistically significant in lung adenocarcinoma patients with different gender, age, smoking history, histological type, and differentiation degree (P=0.006, 0.002, 0.002, 0.015, 0.025).Among them, the effective mutation group were 107 females, 85 cases≥ 59 years old, 117 cases with no smoking history, 68 acinar-based, 89 moderate differentiation. In the count data, 127 nodule edges were lobed, and only 9 nodule edges were smooth. Among the measurement data, the GGO CT value was approximately (-459±147) HU in the EGFR mutation group, with statistical difference (P=0.037). The GGO diameter was approximately (11±9)mm,P=0.279.Multivariate Logistic regression analysis showed that GGO diameter (OR=0.873, 95%CI: 0.780-0.997; P=0.018) and smooth margins (OR=0.183,95%CI: 0.041-0.824; P=0.027) were independent protective factors of effective mutations of EGFR. Conclusions: In MPLCs, effective EGFR mutation is more common, and associated with elder female, age≥59 years, non-smoking, GGO attenuation <-548 HU, moderately differentiated, predominant invasive papillary adenocarcinoma. Patients with MPLCs and these risk factors may be encouraged to have postoperative EGFR molecular test.

Epidermal growth factor receptor mutations: association with favorable local tumor control following Gamma Knife radiosurgery in patients with non-small cell lung cancer and brain metastases.

The presence of epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) has been associated with elevated radiosensitivity in vitro. However, results from clinical studies on radiosensitivity in cases of NSCLC with EGFR mutations are inconclusive. This paper presents a retrospective analysis of patients with NSCLC who underwent regular follow-up imaging after radiotherapy for brain metastases (BMs). The authors also investigated the influence of EGFR mutations on the efficacy of Gamma Knife radiosurgery (GKRS). This study included 264 patients (1069 BMs) who underwent GKRS treatment and for whom EGFR mutation status, demographics, performance status, and tumor characteristics were available. Radiological images were obtained at 3 months after GKRS and at 3-month intervals thereafter. Kaplan-Meier plots and Cox regression analysis were used to correlate EGFR mutation status and other clinical features with tumor control and overall survival. The tumor control rates and overall 12-month survival rates were 87.8% and 65.5%, respectively. Tumor control rates in the EGFR mutant group versus the EGFR wild-type group were 90.5% versus 79.4% at 12 months and 75.0% versus 24.5% at 24 months. During the 2-year follow-up period after SRS, the intracranial response rate in the EGFR mutant group was approximately 3-fold higher than that in the wild-type group (p < 0.001). Cox regression multivariate analysis identified EGFR mutation status, extracranial metastasis, primary tumor control, and prescribed margin dose as predictors of tumor control (p = 0.004, p < 0.001, p = 0.004, and p = 0.026, respectively). Treatment with a combination of GKRS and tyrosine kinase inhibitors (TKIs) was the most important predictor of overall survival (p < 0.001). The current study demonstrated that, among patients with NSCLC-BMs, EGFR mutations were independent prognostic factors of tumor control. It was also determined that a combination of GKRS and TKI had the most pronounced effect on prolonging survival after SRS. In select patient groups, treatment with SRS in conjunction with EGFR-TKIs provided effective tumor control for NSCLC-BMs.

Prediction of EGFR mutations by conventional CT-features in advanced pulmonary adenocarcinoma

ObjectiveThis study assessed the ability of conventional computed tomography (CT) features (including primary tumors, metastatic lesions, lymph nodes, and emphysema) to predict epidermal growth factor receptor (EGFR) mutations in advanced pulmonary adenocarcinoma. MethodsPatients who were diagnosed with advanced pulmonary adenocarcinoma between January 2017 and August 2017 and had undergone a chest CT and EGFR mutation testing were enrolled in this retrospective study. Qualitative and quantitative CT-features and clinical characteristics evaluated in this study included: primary tumor location, size, and morphology (including degree of lobulation, density, calcification, cavitation, vacuole sign, and air bronchogram), size and distribution of lung and pleural metastatic nodules, size and status of hilar and mediastinal lymph nodes, emphysema, organs with distant metastasis, and patient age, sex, and smoking history. ResultsOf 201 patients, 107 (53.23%) were EGFR-mutation positive. The multivariate logistic regression indicated that EGFR mutations were significantly associated with smaller lymph nodes, a lower percentage of deep lobulation of the primary tumor and partial fusion of lymph nodes, and absence of emphysema. The area under the curve of logistic regression model for predicting EGFR mutations was 0.898. ConclusionsConventional CT-features, including emphysema, degree of primary tumor lobulation, and lymph node size and status, help to predict the presence or absence of EGFR mutations in advanced pulmonary adenocarcinoma. Additionally, these same CT-features demonstrated that the CT manifestations of the EGFR mutant group were of relatively lower malignancy and less invasive as compared to the wild-type EGFR group.

Epidermal growth factor receptor mutation accelerates radiographic progression in lung adenocarcinoma presented as a solitary ground-glass opacity.

We aimed to investigate the impact of epidermal growth factor receptor (EGFR) mutation in the progression of lung adenocarcinoma presented as a solitary ground-glass opacity (GGO) by retrospectively evaluating the correlation between EGFR mutation status and the radiographic features. One hundred fifty-six cases of lung adenocarcinoma presented as a solitary GGO were enrolled between 2013 and 2015. Chest CT scans were performed 3 times (1st ≥3 months, 2nd ≤1 week preoperatively and 3rd ≥3 months postoperatively) in each patient. The diameter and volume of every lesion was measured by semiautomated algorithm. EGFR mutation hotspots from exons 18, 19 and 21 were detected by real-time PCR. In the 156 patients who were enrolled in our study, tumors in 75 patients (48.1%) were pathologically diagnosed with EGFR-mutant, with 1, 29 and 45 cases harboring tumors with mutation in exon 18, 19 and 21, respectively. EGFR mutation occurred more frequently in women (P=0.005) and non-smokers (P=0.019). Comparison between the 1st and 2nd preoperative CT scans showed that 28 (37.3%) of 75 patients with EGFR mutations had an over 50% increment of tumor size and 38 (52.0%) displayed a growth of solid component. On the other hand, we found only 9 (11.1%) and 14 (17.3%) in 81 lesions without EGFR mutation had a distinct volume growth and component solidification, respectively, which is significantly less than that in EGFR mutation lesions (P<0.001). Further, in the postoperative CT scan, recurrent GGOs or nodes were identified in 6 (8%) EGFR-mutant patients and 6 (7.4%) in wild-type patients (P=0.89), which indicates no overt statistically difference. At last, we found that EGFR amplification is more frequent as GGO volume percentage decreases and diameter increases. We found GGOs with EGFR mutation grew faster in volume and solidified more quickly in component than wild-type GGOs. Moreover, in the follow-up after surgery, patients in the EGFR mutation group and EGFR wild-type group showed no significant difference in the imaging evolvement.

Identification of epidermal growth factor receptor mutations in pulmonary adenocarcinoma using dual-energy spectral computed tomography.

To explore the role of dual-energy spectral computed tomography (DESCT) quantitative characteristics for the identification of epidermal growth factor receptor (EGFR) mutation status in a cohort of East Asian patients with pulmonary adenocarcinoma. Patients with lung adenocarcinoma who underwent both DESCT chest examination and EGFR test were retrospectively selected from our institution's database. The DESCT visual morphological features and quantitative parameters, including the CT number at 70keV, normalized iodine concentration (NIC), normalized water concentration, and slopes of the spectral attenuation curves (slope λ HU [Hounsfield unit]), were evaluated or calculated. The patients were divided into two groups: the EGFR mutation group and EGFR wild-type group. Statistical analyses were performed to identify the DESCT quantitative parameters for diagnosis of EGFR mutation status. EGFR mutations were detected in 66 (55.0%) of the 120 enrolled patients. The univariate analysis revealed that sex, smoking history, CT texture, NIC, and slope λ HU were significantly associated with EGFR mutation status (p = 0.037, 0.001, 0.047, 0.010, and 0.018, respectively). The multivariate logistic analysis revealed that smoking history (odds ratio [OR] = 3.23, p = 0.005) and NIC (OR = 58.026, p = 0.049) were the two significant predictive factors associated with EGFR mutations. Based on this analysis, the smoking history and NIC were combined to determine the predictive value for EGFR mutations with the area under the curve of 0.702. NIC may be a potential quantitative DESCT parameter for predicting EGFR mutations in patients with pulmonary adenocarcinoma. • DESCT can provide multiple quantitative image parameters compared to conventional CT. • Identification of the radio-genomic relation between DESCT and EGFR status can help to define molecular subcategories of lung adenocarcinoma, which is valuable for personalized clinical targeted therapy. • NIC may be a potential DESCT quantitative parameter for predicting EGFR mutations in pulmonary adenocarcinoma.

P3.16-11 Pattern of Recurrence of Completely Resected Lung Adenocarcinoma Varies According to EGFR Mutation Status

The prognostic significance of epidermal growth factor receptor (EGFR) mutations in resectable lung adenocarcinoma is not well defined. We evaluated the influence of EGFR mutation status on postoperative recurrence timing with the use of event dynamics. A total of 644 patients with lung adenocarcinoma who underwent complete resection and examined for EGFR mutation status between 2008 and 2015 were studied. Disease-free survival (DFS) were calculated using the Kaplan-Meier method and compared between EGFR mutation-positive patients (n=322) and EGFR wild-type patients (n=322). Event dynamics, based on the hazard rate, were evaluated and only first events (distant metastases or local recurrence) were considered. There was no statistical significance in recurrence rate (9.9% versus 14.6%; p=0.09) between EGFR mutation-positive patients and EGFR wild-type patients. In patients with pathological stage I, DFS was significantly better in the EGFR mutant group than the wild-type group (p=0.009), whereas the EGFR mutant group had an inferior DFS compared with the wild-type group among patients with pathological stage II or higher (p=0.110). The resulting hazard rate curves indicated that the recurrence risk pattern was definitely correlated with EGFR mutation status, with an early highest peak during the first year for EGFR wild-type patients and a late maximum peak in the fifth year for EGFR mutation-positive patients. The prognostic value of EGFR mutations appears to be different according to pathological stage in completely resected adenocarcinoma. The hazard and the peak times of recurrence differ considerably between EGFR-mutant and wild-type patients.

Computed tomography characteristics of lung adenocarcinomas with epidermal growth factor receptor mutation: A propensity score matching study

ObjectivesWe investigated the relationship between computed tomography (CT) characteristics and epidermal growth factor receptor (EGFR) mutations in a large Asian cohort who received surgical resection of invasive lung adenocarcinoma. Materials and MethodsWe retrospectively included 864 patients (524 with EGFR mutation and 340 with EGFR wild-type) who received surgical resections for invasive lung adenocarcinomas. After applying propensity score matching, 312 patients with mutated EGFR were matched with 312 patients with wild-type EGFR. CT characteristics, predominant histologic subtype, and CT measurement parameters (volume and estimated diameter of the total tumor and inner solid portion and ground-glass opacity [GGO] proportion) were compared within matched pairs. ResultsTumors in the EGFR mutation group showed higher proportions of pure ground-glass nodules (4.1% vs 1.3%), GGO-predominant (23.7% vs 14.7%), and solid-predominant part-solid nodules (37.2% vs 31.7%) CT characteristics, whereas EGFR wild-type tumors predominantly presented as pure solid nodules (34.6% vs 52.2%, P < 0.0001). EGFR mutation tumors more frequently had a lepidic-predominant subtype than did EGFR wild-type tumors (20.2% and 11.9%; P < 0.0001), and showed a smaller whole tumor size and solid portion (P < 0.0001) with a higher GGO proportion (P < 0.0001). Tumors with exon 21 missense mutations showed the highest GGO proportion and the smallest inner solid portion size, followed by tumors harboring an exon 19 deletion, compared with EGFR wild-type tumors (posthoc P < 0.01). ConclusionAdenocarcinomas with EGFR mutations had a higher GGO proportion than those with wild-type EGFR after matching of clinical variables. Lesions with an exon 21 mutation had a higher GGO proportion than lesions with other mutations.

Detection of epidermal growth factor receptor mutation in the peripheral blood of patients with esophageal carcinoma to guide epidermal growth factor receptor-tyrosine kinase inhibitor treatment.

This study aimed to explore the epidermal growth factor receptor (EGFR) mutation in the peripheral blood of patients with esophageal carcinoma and analyze the relationship between EGFR-tyrosine kinase inhibitor (EGFR-TKI) therapeutic effect and EGFR mutation in peripheral blood. A retrospective analysis was performed on 66 patients with esophageal carcinoma treated with EGFR-TKI (Gefitinib) from February 2014 to March 2017 in our hospital. Real-time polymerase chain reaction was applied to detect the mutation of the EGFR gene in peripheral blood specimens before patients were treated with EGFR-TKI. The relationship between EGFR mutation in the peripheral blood and clinical features of patients were analyzed. The correlation between EGFR mutation in peripheral blood and EGFR-TKI treatment response was also demonstrated. Among the 66 patients, 18 cases were determined as EGFR mutation in peripheral blood. The mutation rate was 27.3%. Among these patients, it observed 1 case of exon 18 2155G>A mutation, 3 cases of exon 19 2235-2249Del mutation, 5 cases of 2236-2250Del mutation, 1 case of 2254-2277Del mutation, 1 case of L747-A750Del mutation, 3 cases of exon 21 2576T>G mutation, 3 cases of 2497T>G mutation, and 1 case of 2504A>T mutation. EGFR mutation in the peripheral blood of patients with esophageal carcinoma was unrelated to the gender, age, and the location of the tumor (P < 0.05). By contrast, EGFR mutation was related to the pathological types of the patients (P < 0.05). The mutation rate of the EGFR of squamous cell carcinoma patients was significantly higher than that of adenocarcinoma patients (P < 0.05). Among EGFR wild-type patients, 8 cases were stable disease (SD), and 40 cases were progressive disease (PD), after EGFR-TIK treatment. No complete response (CR) and partial response (PR) patients were reported. The overall response rate (ORR) was 0.0%. Among the EGFR mutation group, 5 were SD cases, 5 were PD cases, and 8 were PR cases. No CR case was reported. The ORR was 44.4%. The ORR of the EGFR group was significantly higher than that of the wild-type group (P < 0.05). The detection of EGFR mutation in peripheral blood can be applied as an effective index for EGFR-TKI (Gefitinib) treatment in patients with esophageal carcinoma.