肺腺癌EGFR基因19、21外显子突变与临床病理特征及预后的关系

目的分析肺腺癌表皮生长因子受体(EGFR)基因19、21外显子突变与临床病理特征及预后的关系。 方法回顾性分析2017年1月至2018年6月100例经病理证实为肺腺癌的患者临床资料与标本,采用PCR-ARMS技术检测标本EGFR基因19、21外显子突变情况,分析EGFR基因突变与临床病理特征及预后的关系。 结果100例肺腺癌标本共检测出47例EGFR突变,突变率为47.00%,其中第19号外显子突变20例(42.55%),包括6种形式的突变,以核苷酸框架缺失为主,最常见的类型为核苷酸从2234-2248位缺失15bp的delE746-A750突变,共11例,占55.00%;第21号外显子突变27例(57.45%),包括5种形式的突变,均是碱基置换突变,最常见的类型为2573位点的T被G取代的L858R,共17例,占62.96%;女性、无吸烟史、临床分期Ⅰ期患者EGFR19与EGFR21突变率高于其他患者(P<0.05);Logisitic回归分析显示性别、吸烟史、肿瘤直径、临床病理分期是影响EGFR19、EGFR21突变的因素。100例肺腺癌患者全部获得有效随访,EGFR19突变患者2年无进展生存率、总生存率分别为80.00%、85.00%,未突变患者分别为65.00%、73.75%;EGFR21突变患者2年无进展生存率、总生存率分别为81.48%、92.59%,未突变患者分别为63.01%、69.86%;女性、临床分期较早、无淋巴结转移、发生EGFR21突变患者2年生存率低于其他患者(P<0.05);Logisitic回归分析显示男性、临床分期较晚、有淋巴结转移、EGFR21未突变是肺腺癌患者不良预后的独立危险因素。 结论肺腺癌EGFR基因19、21外显子突变与性别、吸烟史、肿瘤直径、临床分期有关,同时也是预测预后的有效方法。     

晚期肺腺癌CT特征与EGFR基因突变的关系

目的探讨晚期肺腺癌的CT特征与表皮生长因子受体(EGFR)基因突变的相关性。方法回顾性分析137例晚期肺腺癌患者的CT影像学特征和临床资料,所有患者的病理组织都行EGFR基因检测,根据EGFR基因突变情况分成两组:EGFR突变组和非突变组,分别采用单因素和多因素Logistic回归分析晚期肺腺癌患者发生EGFR突变的影响因素。结果137例患者中,71例(51.82%)表皮生长因子受体突变阳性。与非突变组比较,EGFR突变组中女性患者比例较高(P<0.05)。两组在肺肿瘤大小、坏死、空洞、支气管充气征及远处转移等差异无统计学意义(P>0.05)。Logistic回归分析显示,女性、无肺气肿、原发肿瘤的分叶程度、淋巴结的大小和状态是晚期肺腺癌患者发生EGFR突变的危险因素。结论EGFR有效突变好发于女性,其CT的可靠预测因素为无肺气肿、原发肿瘤的分叶程度、淋巴结的大小和状态。在临床工作中,对晚期危重患者,当不能获取病理组织时,可以通过CT特征结合临床资料来预测晚期肺腺癌是否存在EGFR突变。     

Assessment of epidermal growth factor receptor mutation by endobronchial ultrasound-guided transbronchial needle aspiration

BACKGROUND: The presence of somatic mutations in epidermal growth factor receptor (EGFR) predicts the effectiveness of EGFR tyrosine kinase inhibitors (TKIs). It would be ideal if an EGFR mutation could be detected in biopsy samples, since the majority of non-small cell lung cancer patients are inoperable at the time of presentation. We have reported the usefulness of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for the lymph node staging of lung cancer. EBUS-TBNA enables the sampling of histologic cores, which can be used for genetic analysis. METHODS: The purpose of this study was to develop and analyze the feasibility of detecting EGFR mutations in samples obtained by EBUS-TBNA. Forty-six patients with primary lung cancer in whom metastatic adenocarcinoma in the hilar and/or mediastinal lymph node was diagnosed by EBUS-TBNA were enrolled into the study. DNA was extracted from paraffin-embedded samples, and the EGFR mutation was analyzed in exons 19 and 21 using a newly developed loop-hybrid mobility shift assay. The results were confirmed by direct sequencing. RESULTS: Forty-three cases were eligible for analysis and in 11 cases, EGFR mutation (25.6%) was detected; one case was an in-frame deletion (E746-A750del) of exon 19, nine cases were point mutations (L858R) of exon 21, and one case was a double point mutation (L858R+L861V). All cases with EGFR mutations were confirmed by direct sequencing. CONCLUSIONS: EGFR mutation can easily be detected in metastatic lymph nodes sampled by EBUS-TBNA. EBUS-TBNA allows genetic evaluations of tumor cells within the lymph node and may provide us with indications for EGFR-TKI therapy in the near future.     

Gastric and colonic metastasis from NSCLC: A very unusual case report

Rationale:Lung cancer is the most common cause of cancer-related deaths worldwide. Approximately 50% of patients is metastatic at diagnosis and the most common metastatic sites are bone, lungs, brain, adrenal glands, liver, and extra thoracic lymph nodes. The occurrence of gastrointestinal metastasis from lung carcinoma is rare and seems more commonly related to small cell lung cancer compared to non-small cell lung cancer (NSCLC).Patient information and diagnosis:A 78-year-old man with completely surgically resected NSCLC and no initial evidence of distant metastases developed colon and gastric metastases 7 months after diagnosis, confirmed by serial radiological examinations and endoscopic biopsies.Interventions:The patient was subjected to total gastrectomy with D2 lymph node dissection plus partial colectomy for intraoperative detection of a transverse colon neoformation. Subsequent instrumental imaging showed bilateral lung tumor recurrence, treated with gemcitabine monotherapy for 8 months as first line chemotherapy for lung adenocarcinoma.Results:The patient presented complete response to therapy and was disease-free for 4 years.Lessons:Colonic and gastric metastasis are very infrequent in NSCLC. The resection of gastrointestinal metastasis may provide benefits in terms of both symptom control and survival in patients properly selected.     

Clinicopathologic factors and molecular markers related to lymph node metastasis in early gastric cancer

AIM: To analyze predictive factors for lymph node metastasis in early gastric cancer.METHODS: We analyzed 1104 patients with early gastric cancer(EGC) who underwent a gastrectomy with lymph-node dissection from May 2003 through July 2011. The clinicopathologic factors and molecular markers were assessed as predictors for lymph node metastasis. Molecular markers such as microsatellite instability, human mut L homolog 1, p53, epidermal growth factor receptor(EGFR) and human epidermal growth factor receptor 2(HER2) were included. The χ2 test and logistic regression analysis were used to determine clinicopathologic parameters.RESULTS: Lymph node metastasis was observed in 104(9.4%) of 1104 patients. Among 104 cases of lymph node positive patients, 24 patients(3.8%) were mucosal cancers and 80 patients(16.7%) were submucosal. According to histologic evaluation, the number of lymph node metastasis found was 4(1.7%) for well differentiated tubular adenocarcinoma, 45(11.3%) for moderately differentiated tubular adenocarcinoma, 36(14.8%) for poorly differentiated tubular adenocarcinoma, and 19(8.4%) for signet ring cell carcinoma. Of 690 EGC cases, 77 cases(11.2%) showed EGFR overexpression. HER2 overexpression was present in 110 cases(27.1%) of 406 EGC patients. With multivariate analysis, female gender(OR = 2.281, P = 0.009), presence of lymphovascular invasion(OR = 10.950, P 0.0001), diameter(≥ 20 mm, OR = 3.173, P = 0.01), and EGFR overexpression(OR = 2.185, P = 0.044) were independent risk factors for lymph node involvement.CONCLUSION: Female gender, tumor size, lymphovascular invasion and EGFR overexpression were predictive risk factors for lymph node metastasis in EGC.     

Expression heterogeneity research of ITGB3 and BCL-2 in lung adenocarcinoma tissue and adenocarcinoma cell line

Objective:To analyze expression heterogeneity of Integrin beta 3(ITCB3) and B-cell lymphoma2(BCL-2) in lung adenocarcinoma tissue and adenocarcinoma cell line and further provide theoretical direction for molecular biological research of lung adenocarcinoma.Methods:Tissue microarray was used to observe relation among expression,heterogeneitpy and clinical characteristics of ITGB3 and BCL-2 in lung cancer.Results:ITGB3 and BCL-2 increased significantly in A549 cells in CAFs group with β-actin as control:the expression level of BCL-2also increased in 1TGB3 transfected cells with CFP plasmid transfected A549 cells as control:immunohistochemistry staining showed that positive ratcs of 1TGB3,ITGB1 and BCL-2 in normal lung tissues were 0.the positive rates in lung adenocarcinoma were 7.049%,84.51%and 4.23%,respectively:in the results of immunohistochemistrv staining,the expression of Girdin protein in lung adenocarcinoma was homogeneous,however protein expression of 1TCB3,ITGB1 and BCL—2showed different patterns in the same location with significant heterogeneity;majority of ITGB3,TTCB1 or BCL—2 positive tissue showed heterogeneity that expression in trailing edge was higher than that of trailing edge in lung adenocarcinoma tissue,the patients with BCL-2 heterogeneity showed higher lymph node metastasis ratio and lower clinical stage(P0.05);and the expression of ITGB3 and the clinical characteristics of patients were not significant related(P0.05).Conclusions:Expression of ITGB3 and BCL-2 in lung adenocarcinoma and adenocarcinoma cell line showed heterogeneity that expression in trailing edge was higher than that of trailing edge,which may play an important role in promoting tumor lymph node metastasis and vascular invasion,and provides a new research direction for exploration of lung adenocarcinoma metastasis mechanism.     

肺腺癌中PD-L1、B7H3的表达与EGFR基因突变的关系

目的探讨程序性凋亡配体1(programmed death-ligand 1,PD-L1)、B7H3在肺腺癌中的表达与表皮生长因子受体(epidermal growth factor receptor,EGFR)基因突变状况的关系,为EGFR基因突变的肺腺癌患者提供一种新的临床治疗方法。方法收集78例手术切除的肺腺癌组织,所有标本均有EGFR基因检测结果。应用免疫组织化学PV-6 000法检测PD-L1、B7H3的表达情况。结果肺腺癌组织中有32例(41.0%)发生EGFR突变,其中女性的突变率高于男性(30.8%vs 10.3%,P0.05),不吸烟者比吸烟者有更高的突变率(28.2%vs12.8%,P0.05)。PD-L1、B7H3在EGFR突变型患者中的阳性率分别为71.9%、68.8%,均高于其在野生型患者中的发生率45.7%、43.5%(P0.05),且均与21外显子突变密切相关(P0.05),但未发现与19外显子突变相关(P0.05)。PD-L1在女性、不吸烟者及II~III期中的表达水平高于男性、吸烟者及I期患者(P0.05)。B7H3的表达与TNM分期及淋巴结转移情况相关(P0.05)。PD-L1与B7H3表达呈正相关关系(P0.05)。结论 PD-L1、B7H3高表达在EGFR突变型肺腺癌的发生发展中起重要作用,以PD-L1、B7H3为靶点的免疫治疗,可能成为这部分患者治疗的新方法。     

Dramatic response to osimertinib combined with crizotinib in EGFR T790 M mutation only in blood and Met amplification only in tumor tissue expressive non-small cell lung cancer: A case report

Rationale:Besides the T790 M mutation, it may coexist with bypass pathway activation in real clinical cases for patients with EGFR mutations who resisted to the first- and second-generation tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC). There are limited clinical trial data describing the efficacy of osimertinib combined with MET inhibition in EGFR T790M-mutant NSCLC patients with Met amplification.Patient concerns:A non-smoking 53-year-old male patient with lung adenocarcinoma underwent gefitinib, afatinib, and osimertinib combined with crizotinib treatment and developed different EGFR resistance mutations.Diagnoses:The patient was diagnosed with lung adenocarcinoma (stage cT4N2M0, IIIB). After resistance to the therapy targeting EGFR exon 21 L858R point mutation, T790 M mutation was detected in liquid biopsy and Met amplification was detected via tissue biopsy by next-generation sequencing (NGS).Interventions:The patient received systemic treatments, including chemotherapy, gefitinib, afatinib, and osimertinib combined with crizotinib.Outcomes:The patient died of multisystem organ failure and had an overall survival of 24 months.Lessons:Although osimertinib combined with crizotinib therapy showed dramatic tumor shrinkage in both the primary tumor and bone metastasis to an EGFR T790M-mutant NSCLC patient with MET amplification, the progression-free survival (PFS) was only two months.     

Clinicopathological features and prognostic factors associated with gastroenteropancreatic mixed neuroendocrine non-neuroendocrine neoplasms in Chinese patients

BACKGROUND The incidence of mixed neuroendocrine-non-neuroendocrine neoplasms(MiNEN)is low.To improve our understanding of this rare tumor type and optimally guide clinical treatment,associated risk factors,clinical manifestations,and prognosis must be explored.AIM To identify risk factors that influence the prognosis of patients with gastroenteropancreatic MiNEN(GEP-MiNEN).METHODS We retrospectively analyzed the clinical data of 46 patients who were diagnosed with GEP-MiNEN at the First Affiliated Hospital of Bengbu Medical College(Anhui,China)between January 2013 and December 2017.Risk factors influencing the prognosis of the patients were assessed using Kaplan-Meier curves and cox regression models.We compared the results with 55 randomly selected patients with gastroenteropancreatic GEP neuroendocrine tumors,47 with neuroendocrine carcinomas(NEC),and 58 with poorly differentiated adenocarcinoma.RESULTS Among the 46 patients with GEP-MiNEN,thirty-five had gastric tumors,nine had intestinal tumors(four in the small intestine and five in the colon and rectum),and two had pancreatic tumors.The median age of the patients was 66(41-84)years,and the male-to-female ratio was 2.83.Thirty-three(71.7%)patients had clinical stage III and IV cancers.Distant metastasis occurred in 14 patients,of which 13 had metastasis to the liver.The follow-up period was 11-72 mo,and the median overall survival was 30 mo.Ki-67 index≥50%,high proportion of NEC,lymph node involvement,distant metastasis,and higher clinical stage were independent risk factors affecting the prognosis of patients with GEP-MiNEN.The median overall survival was shorter for patients with NEC than for those with MiNEN(14 mo vs 30 mo,P=0.001),but did not significantly differ from those with poorly differentiated adenocarcinoma and MiNEN(30 mo vs 18 mo,P=0.453).CONCLUSION A poor prognosis is associated with rare,aggressive GEP-MiNEN.Ki-67 index,tumor composition,lymph node involvement,distant metastasis,and clinical stage are important factors for patient prognosis.     

Afatinib in Treatment-Naive Patients With EGFR-Mutated Lung Adenocarcinoma With Brain Metastasis: A Case Series

Tyrosine kinase inhibitors (TKIs) of epidermal growth factor receptor (EGFR) were previously the standard first-line treatments for lung cancers with activating EGFR mutations. The first-generation reversible EGFR TKIs, gefitinib and erlotinib, demonstrated substantial efficacy in the treatment of brain metastases from EGFR-mutated lung adenocarcinoma. However, the efficacy of afatinib, the second-generation irreversible EGFR TKI, as the first-line treatment in lung adenocarcinoma patients with brain metastasis has yet to be evaluated.Here, we report cases of 3 patients who received afatinib alone as the first-line treatment in combination with whole-brain radiotherapy or following surgical resection of brain metastases. All 3 patients had EGFR L858R mutation. The first patient had lung adenocarcinoma with brain metastasis and no neurologic symptoms. After consultation, she received afatinib as a first-line treatment. Chest computed tomography and brain magnetic resonance imaging (MRI) showed partial response. The second patient had lung adenocarcinoma accompanied with a metastatic brain lesion associated with seizures. This patient received whole-brain radiotherapy and afatinib treatment following brain MRI and subsequently showed significant regression of the brain metastasis. The third patient had strabismus of the right eye, and brain MRI showed a single tumor at the cerebellar pontine angle. This patient underwent surgical resection of the tumor followed by afatinib treatment. He refused adjuvant radiotherapy after surgery for brain metastasis. The brain MRI showed no recurrent brain metastasis, and the patient had relatively less neurologic deficiency.This series of 3 cases indicate that afatinib may be an appropriate first-line treatment alternative in patients having lung adenocarcinoma with EGFR mutations. Further retrospective analyses and prospective clinical trials are required to substantiate the efficacy of afatinib in the treatment of brain metastases of lung adenocarcinoma.     

A nomogram for predicting brain metastases of EGFR-mutated lung adenocarcinoma patients and estimating the efficacy of therapeutic strategies

BackgroundTo establish a nomogram for predicting the outcome of EGFR-mutated lung adenocarcinoma patients with brain metastases (BMs) and to estimate the efficacy of different therapeutic strategies.MethodsThe data of 129 cases with BM from the period between January 1st 2011 and December 31st 2014 were collected, and all of the cases were pathologically confirmed to be lung adenocarcinoma, stages I–IV and with 19 and/or 21 exon mutations of EGFR. Cox regression analysis and log-rank test were used for data analysis. The nomogram was used to establish the progression models.ResultsIn the univariate analysis, the stage, ECOG score, interval between the diagnosis of lung cancer and BM, the number of brain metastatic lesions, and the diameter of the maximal brain metastatic lesion correlated well with overall survival (OS). In multivariate Cox proportional hazard analysis, the ECOG score, interval between the diagnosis of lung cancer and BM, and the number of brain metastatic lesions correlated well with the OS. Patients were divided into the poor prognostic group and the good prognostic group based on the nomogram prognostic model score. Subgroup analysis showed that in the poor prognostic group, the OS of patients who received radiotherapy was better than that of the patients who did not receive radiotherapy as the first-line treatment (30 vs. 19 months, P<0.05). The OS was 30 months in the TKI subgroup and 21 months in the no TKI subgroup, but no statistical difference was found (P>0.05). Patients in the good prognostic group who received radiotherapy had a better 3-y OS rate than the patients who received no radiotherapy as the first-line treatment (91.2% vs. 58.1%, P<0.05). The 3-y OS rate was 87.6% in the TKI subgroup and 67.8% in the no TKI group (P<0.05).ConclusionsWe established an effective nomogram model to predict the progression of EGFR-mutated lung adenocarcinoma patients with BM and the therapeutic effect of the individual treatments. Radiotherapy was beneficial for the patients of both the poor and good prognostic groups, but TKI may be better suited for treating the patients with good prognosis.     

High Incidence of EGFR Mutations in Pneumonic-Type Non-Small Cell Lung Cancer

To retrospectively identify computed tomography (CT) features that correlate with epidermal growth factor receptor (EGFR) mutation in surgically resected pneumonic-type lung cancer (P-LC).A total of 953 consecutive patients with surgically resected lung cancer in the First Affiliated Hospital of Guangzhou Medical University from August 2011 to August 2013 were studied. The CT manifestations were reevaluated independently by 2 radiologists. The presence of pneumonic-type consolidation with pathological confirmed non-small lung cancer (NSCLC) was defined as P-LC. EGFR mutation was determined by direct DNA sequencing or amplification refractory mutation system-PCR. EGFR mutation rates as well as clinical and pathological manifestations between P-LC and control lung cancer patients were compared.P-LC was diagnosed in 85 patients. Among these patients, 82 were adenocarcinoma (including 78 cases of invasive adenocarcinoma and 4 cases of microinvasive adenocarcinoma), 2 were squamous carcinoma and 1 was other type. P-LC occurred more frequently in female (58.8% vs 37.1%, P < 0.01), nonsmoking (76.5% vs 56.5%, P = 0.001) and adenocarcinoma (58.8% vs 37.1%, P < 0.01) patients. Moreover, EGFR mutations were found in 39 of 52 P-LC patients (75%) and 263 of 542 non-P-LC NSCLC patients (48.5%). However, no difference was found on the mutation sites of EGFR. Histological type, sex, and radiological manifestations (P-LC vs non-P-LC) but not smoking or sequencing method can be served as the independent predictor of EGFR mutations.P-LC patients showed a significant higher incidence of EGFR mutations, which was independent of sex, histological type, and smoking history. The patients with imaging manifestation of pneumonic-type consolidation are highly suggested to perform EGFR mutation analysis to guide the sequential treatment.     

Cytoplasmic expression of G protein-coupled estrogen receptor 1 correlates with poor postoperative prognosis in non-small cell lung cancer

BackgroundA hormonal role in the development of non-small cell lung cancer (NSCLC) has been well documented, and the classic estrogen receptors (ERs)—ERα and ERβ have been extensively investigated over the past decade. The expression of ERβ was found to be high and display biological activity in NSCLC, but anti-estrogen therapy targeting this receptor has shown limited efficacy for the disease. The third estrogen receptor, G protein-coupled estrogen receptor 1 (GPER1/GPR30), was recently found to be highly expressed in NSCLC. Herein, we aimed to investigate the expression profile of GPER1 and correlate it with clinicopathological factors as well as postoperative prognosis in NSCLC.MethodsWe examined GPER1 and ERβ expression using immunohistochemistry among 183 NSCLC cases, including 132 lung adenocarcinoma (LUAD) with identified epidermal growth factor receptor (EGFR) mutation status and 51 squamous cell carcinoma (SCC) patients. We then conducted correlation analysis between the expression of GPER1 and clinicopathological factors and patients’ postoperative prognosis.ResultsPositive expression of GPER1 was categorized into 2 main classes: nuclei-GPER1 (nGPER1) and concurrent nuclei-and cytoplasm-GPER1 (n/cGPER1), according to its subcellular localization. The LUAD with wild-type EGFR (wt-EGFR) had a higher frequency of n/cGPER1 (50%) but a lower frequency of nGPER1 (31%) when compared with those with mutated EGFR (n/cGPER1: 31%, nGPER1: 41%, respectively). The expression of GPER1, regardless of subcellular localization, was positively correlated with tumor stage and lymph node metastasis. The median recurrence-free survival (mRFS) and overall survival (OS) were significantly worse in participants with n/cGPER1 expression than in those with nGPER1 or without GPER1 expression.ConclusionsThis study revealed that GPER1 is aberrantly highly expressed and presents a unique GPER1 expression profile in NSCLC. The n/cGPER1 expression was significantly associated with EGFR mutation status, tumor stage, lymph node metastasis, and poor postoperative prognosis in NSCLC.     

Prognostic assessment of different lymph node staging methods for pancreatic cancer with R0 resection: pN staging,lymph node ratio,log odds of positive lymph nodes

Background and aimsSurvival after surgical resection of pancreatic adenocarcinoma is poor. Several prognostic factors such as the status of the resection margin, lymph node status, or tumour grading have been identified. The aims of the present study were to evaluate and compare the prognostic assessment of different lymph nodes staging methods: standard lymph node (pN) staging, metastatic lymph node ratio (LNR), and log odds of positive lymph nodes (LODDS) in pancreatic cancer after pancreatic resection.Materials and methodsData were retrospectively collected from 143 patients who had undergone R0 pancreatic resection for pancreatic ductal adenocarcinoma. Survival curves (Kaplan–Meier and Cox proportional hazard models), accuracy, and homogeneity of the 3 methods (LNR, LODDS, and pN) were compared to evaluate the prognostic effects.ResultsMultivariate analysis demonstrated that LODDS and LNR were an independent prognostic factors, but not pN classification. The scatter plots of the relationship between LODDS and the LNR suggested that the LODDS stage had power to divide patients with the same ratio of node metastasis into different groups. For patients in each of the pN or LNR classifications, significant differences in survival could be observed among patients in different LODDS stages.ConclusionLODDS and LNR are more powerful predictors of survival than the lymph node status in patients undergoing pancreatic resection for ductal adenocarcinoma. LODDS allows better prognostic stratification comparing LNR in node negative patients.     

Lung cancer, thyroid cancer or both: An unusual case presentation

Cancer metastasis to the thyroid is rare. Primary sites that have been reported to metastasize to the thyroid gland include breast and kidney. There are very few case reports describing metastasis of a lung primary cancer to the thyroid gland. We describe a case of a never-smoker patient with metastatic adenocarcinoma of the lung and a malignant thyroid mass presenting simultaneously. The thyroid biopsy could not distinguish whether it was a metastasis or incidentally found thyroid primary carcinoma. Based on EGFR mutational status it was determined that he has a primary lung cancer and thyroid metastasis. He was started on erlotinib and has had a marked response in both the lung and the thyroid masses. The presence of mutations within the EGFR gene can help distinguish lung adenocarcinoma from other carcinomas like thyroid cancer. This is the first published case of primary lung adenocarcinoma with metastasis to thyroid and with EGFR mutation.     

Clinicopathologic features and prognostic value of epidermal growth factor receptor mutation in patients with pT1a and pT1b invasive lung adenocarcinoma after surgical resection

BackgroundPrevious studies have evaluated the prognostic value of epidermal growth factor receptor (EGFR) mutation in different subgroups of lung adenocarcinoma, but there remains controversial on this issue. We conduct this study aimed to reveal the prognostic value of EGFR mutation in patients with pT1a and pT1b invasive lung adenocarcinoma.MethodsFrom August 2009 to February 2015, 338 patients with pT1a and pT1b invasive lung adenocarcinoma who underwent EGFR mutation analysis were enrolled into this study. According to clinicopathologic and radiologic characteristics, survival analysis was conducted in different subgroups using Kaplan-Meier methods and Cox regression models.ResultsEGFR mutation was detected in 216 (63.9%) patients. In the entire cohort, EGFR mutation was significantly frequent in female (P=0.011), never smoking (P=0.014) patients, patients with part-solid nodules (P=0.005) and patients with lepidic pattern-predominant adenocarcinoma (LPA)/acinar pattern-predominant adenocarcinoma (APA)/papillary pattern-predominant adenocarcinoma (PPA) (P=0.005). No difference in recurrence-free survival (RFS) was seen between patients harboring EGFR mutation and patients without EGFR mutation in the entire cohort (P=0.664) and the subgroup cohorts. Patients with EGFR mutation had a longer overall survival (OS) compared with patients without EGFR mutation in the entire cohort (P=0.005) and the subgroups of N0 stage cohort (P=0.013), N1–2 stage cohort (P=0.033), APA/PPA/invasive mucinous adenocarcinoma (IMA) cohort (P=0.011) and pT1b cohort (P=0.002). Tyrosine kinase inhibitors (TKIs) could significantly prolong the OS in patients with EGFR mutation after recurrence (P=0.04).ConclusionsEGFR mutation was not a risk factor for recurrence of patients with pT1a and pT1b invasive lung adenocarcinoma.     

The Difference of Clinical Characteristics Between Patients With Exon 19 Deletion and Those With L858R Mutation in Nonsmall Cell Lung Cancer

Recent studies have demonstrated that exon 19 deletion (19 Del) and exon 21 L858R mutation (L858R) are 2 different types of sensitive epidermal growth factor receptor (EGFR) mutations in nonsmall cell lung cancer (NSCLC). However, whether there are some differences between those 2 groups in baseline clinical characteristics is still unclear.We enrolled consecutive 1271 NSCLC patients detected with either 19 Del or L858R and collected their baseline clinical characteristics including age, sex, comorbidity, smoking and drinking status, body mass index (BMI), TNM stage, histologic type, differentiation, tumor maximum diameter (TMD), and CEA level. χ² test and multivariate logistic regression analysis were used to compare the difference.We found a higher percentage of 19 Del in younger patients group (< = 50 yr) than L858R (P < 0.001) through χ² test. Besides, patients with 19 Del have higher risk of lymph node metastasis (P < 0.001). However, there were no significant differences in other items of clinical characteristics between 19 Del and L858R. Multivariate analysis showed similar significant results. Subgroup analysis in different age groups (10 yr as an interval) and N stages (stratified by N0, N1, N2, and N3) also indicated above-mentioned trends.NSCLC patients with 19 Del are more likely to be young and have lymphatic metastasis than those with L858R. Age and N stage might be considered in predicting EGFR mutation type in NSCLC.     

Erlotinib as a salvage treatment after gefitinib failure for advanced non-small-cell lung cancer patients with brain metastasis: A successful case report and review

Rationale:The guidelines recommended gefitinib as a first-line targeted treatment for stage IV non-small-cell lung cancer (NSCLC) patients with EGFR mutations. However, resistance to gefitinib ensues invariably and there is little evidence as for the effectiveness of subsequent salvage treatment for patients without T790m mutation. The case is to evaluate the efficacy of erlotinib, another EGFR-TKI, after failed first-line use of gefitinib.Patient concerns:We described a 55-year-old man with good performance status (PS).Diagnoses:He was histopathologically diagnosed stage IV lung adenocarcinoma with EGFR mutations in November 2018.Interventions:He was administrated with gefitinib daily (250 mg) for activating epidermal growth factor receptor (EGFR) mutations (exon 19 deletions,19del), and combined with platinum-based dual-drug chemotherapy. During the target treatments, the optimal efficacy evaluation was partial remission (PR) with a 12-month progression-free survival (PFS) time. Later, the intracranial progression of the patient rendered the treatment change to erlotinib.Outcomes:It is surprising that the tumor lesion in brain as well as lung relieved obviously. His progression-free survival (PFS)was nearly 11 months, and the overall survival (OS)was>36 months up to now. The adverse events were tolerable.Lessions:This case manifests that re-biopsy of advanced or recurrent NSCLC is beneficial to make a better therapeutic regimen, and erlotinib can be used as a salvage treatment after gefitinib failure.     

Prognostic value of surgical intervention in advanced lung adenocarcinoma: a population-based study

BackgroundSurgical intervention is generally not considered as a treatment option in patients with advanced non-small cell lung cancer (NSCLC). Accumulating data suggest that surgery may have beneficial effects for these advanced patients. However, no evidence supports the significance of primary tumor resection (PTR) and metastatic tumor resection (MTR) in patients with stage IV lung adenocarcinoma (LUAD).MethodsA total of 32,497 patients diagnosed with primary stage IV LUAD were selected through the Surveillance, Epidemiology, and End Results (SEER) database. Possible confounders were eliminated by propensity score matching (PSM). The overall survival (OS) and lung cancer-specific survival (LCSS) were estimated as the primary endpoints. Furthermore, the independent prognostic factors of patients with the surgical intervention were retrospectively analyzed.ResultsPatients underwent surgical intervention had better OS and LCSS than those who did not (P=0.001 for OS; P<0.001 for LCSS). Meanwhile, patients who underwent surgery combined with lymph node dissection had better survival outcomes (P<0.001 for OS and LCSS) in the K-M analysis. For different metastatic sites, PTR was beneficial to the survival of patients with isolated lung metastases (LUM) and multiple organ metastases (MOM) (LUM: P=0.041; MOM: P=0.003). As for metastatic surgery, no patients were found to benefit from resection of metastatic tumor [bone metastasis (BOM): P=0.696; brain metastasis (BRM): P=0.951; LUM: P=0.402; MOM: P=0.365].ConclusionsSurgical intervention strategies can prolong survival to some extent, depending on different sites of metastasis and highly selected patients.