Prognostic factors of refractory NSCLC patients receiving anlotinib hydrochloride as the third-or further-line treatment

Objective:Anlotinib hydrochloride is a multitarget tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor,fibroblast growth factor receptor,platelet-derived growth factor receptor,c-Kit,and c-MET;therefore,it exhibits both antitumor and anti-angiogenetic activities.A phase III trial has shown that anlotinib improved progression-free survival(PFS)and overall survival(OS)in patients with advanced non-small cell lung cancer(NSCLC),who presented with progressive disease or intolerance after standard chemotherapy.This study aimed to analyze the characteristics of patients receiving anlotinib treatment to determine the dominant populations who are fit for the treatment.Methods:Data were collected from March 2015 to January 2017 from a randomized,double-blind,placebo-controlled,multicenter,phase III trial of anlotinib(ALTER0303).A total of 437 patients were enrolled and randomly allocated(2:1)to the anlotinib and placebo groups.Kaplan–Meier analysis and log-rank test were performed to compare PFS and OS.Cox proportional hazards model was adopted for multivariate prognostic analysis.Results:Multivariate analysis indicated that high post-therapeutic peripheral blood granulocyte/lymphocyte ratio and elevated alkaline phosphatase levels were independent risk factors for PFS.Meanwhile,elevated thyroid-stimulating hormone,blood glucose,and triglyceride levels;hypertension;and hand–foot syndrome were independent protective factors of PFS.High posttherapeutic peripheral blood granulocyte/lymphocyte ratio,an Eastern Cooperative Oncology Group(ECOG)score≥2,and the sum of the maximal target lesion length at baseline were independent risk factors of OS,and hypertriglyceridemia was an independent protective factor of OS.Conclusions:This study preliminarily explored the possible factors that affected PFS and OS after anlotinib treatment in patients with advanced refractory NSCLC,and the baseline characteristics of the therapeutically dominant populations were then identified.

The expression of vascular endothelial growth factor(VEGF)/endostatin(ES)and VEGF receptor 2(VEGFR2)/ES is associated with NSCLC prognosis

Objective The aim of our study was to detect the expression of angiogenesis inhibitory proteins and angiogenesis promotive proteins in the postoperative tumor tissue of non-small cell lung cancer(NSCLC)patients.We also investigated the relationship of protein expression with clinical characteristics and prognosis.Methods We examined the expression of vascular endothelial growth factor(VEGF),VEGF receptor 2(VEGFR2),and endostatin(ES)proteins in 255 specimens resected from NSCLC patients,using immune histochemistry(IHC).We then evaluated the relationships between the expression of the three proteins and clinical characteristics such as stage,histological type,differentiation,gender,tobacco use,and age.According to the value of VEGF/ES,we divided the cohort into angiogenesis-promoting group A,angiogenesis-inhibiting group A,and balance group A.The survival differences in the three groups were evaluated to determine the prognostic value of VEGF/ES.Similarly,we tested the prognostic value of VEGFR2/ES.Results VEGF-positive expression was observed in 93 patients(36.4%).VEGF expression was not correlated with the clinical characteristics.VEGFR2-positive expression was observed in 103 patients(40.4%).The expression of VEGFR2 was correlated with the clinical stage(χ^(2)=21.414,P=0.045)and histological type(χ^(2)=26.911,P=0.008).ES-positive expression was observed in 140 patients(54.9%).The expression of ES was correlated with the clinical stage(χ^(2)=26.504,P=0.009).When evaluating the prognostic values of VEGF/ES and VEGFR2/ES,the prognosis of the angiogenesis balance group was similar to that of the angiogenesis-inhibiting group.The minimum survival time was observed in the angiogenesis-promoting group.Conclusion VEGF/ES and VEGFR2/ES in resected tumors have prognostic value in postoperative NSCLC patients.The survival time of the population with predominant angiogenic factors was short.

Investigation of therapeutic modalities of G719X, an uncommon mutation in the EGFR gene in non-small cell lung cancer

Objective G719 X is the most frequently seen uncommon mutation of the epidermal growth factor receptor(EGFR) gene, which is a point mutation at exon 18 with three common subtypes, G719 A/G719 C/G719 S. This study explored the clinicopathological characteristics of the G719 X mutation and investigated the efficacy of EGFR-tyrosine kinase inhibitor(TKI) treatment and chemotherapy in patients with the G719 X mutation; the survival rate after these different treatment modalities were then analyzed in order to provide evidence for clinical treatment.Methods Clinical data of 41 patients with the G719 X mutation admitted in the Beijing Chest Hospital, Capital Medical University from September 2014 to July 2018, were collected and the EGFR mutations were detected by amplification refractory mutation system-polymerase chain reaction(ARMS-PCR). The clinicopathological characteristics of the G719 X mutation were analyzed, and the relationship among the G719 X mutation, the efficacy of different treatment modalities, and the progression-free survival(PFS) was analyzed. Results Of the 41 cases, 24(58.5%) were G719 X single mutations and 17(41.5%) were compound mutations, including G719 X/S768 I, G719 X/L861 Q, G719 X/19 del, and G719 X/c-Met compound mutation. The objective response rate(ORR) of first-line EGFR-TKI therapy was 50%(6/12), the disease control rate(DCR) was 83.3%(10/12), and the median PFS(mPFS) was 9 months. After resistance to EGFR-TKI in the previous treatment, the ORR(71.4%, 5/7) and DCR(100%, 7/7) were still high following EGFR-TKIs, by an mPFS of 8 months. The ORR of chemotherapy was 33.3%(2/6), the DCR was 100%(6/6), and the mPFS was 6 months. Conclusion G719 X is an uncommon mutation of the EGFR gene and is sensitive to many EGFR-TKIs. It can be treated with the second-or third-generation EGFR-TKIs after resistance to the first-generation EGFR-TKIs. G719 X mutation also showed favorable effect to chemotherapy.

Bronchoscopic biopsy for diagnosis of lung cancer in the absence of visible endobronchial abnormalities

Objective Bronchoscopy has been extensively used in the diagnosis of respiratory diseases, and particularly, malignant diseases. However, endoscopists do not normally perform bronchoscopic biopsy in case lesions are undetected via bronchoscopy. The aim of this study was to evaluate whether performing bronchoscopic biopsy could be established in the diagnosis of lung cancer in case of endobronchial abnormalities undetectable to the naked eye. Methods We retrospectively analyzed 109 cases between January 2008 and December 2012. The inclusion criteria were confirmed lung cancer diagnosis, transbronchial biopsy performed in the absence of visible endobronchial manifestations, brushing, and bronchoalveolar lavage(BAL) according to the images obtained from high-resolution computed tomography(HRCT). Data regarding age, sex, pathology, tumor stage; the method of diagnosis; location of primary lesion(central, peripheral, or intermediate); tumor size, mediastinal lymph node metastasis, and the serum carcinoembryonic antigen(CEA) value were collected. The Pearson chi-square test or Fisher's exact and Mc Nemar tests were used in the univariate analysis.Results Among the 109 patients, the diagnosis of 37(33.9%) patients was confirmed through bronchoscopy. Brushing and BAL had higher positive detection rates than biopsy(P = 0.004). There were no differences in the positive detection rates between the sex, pathology, lesion location, tumor size, lymph node metastasis, and the serum CEA value(P > 0.05 for all groups).Conclusion Despite the normal appearance of the endobronchial manifestations, lesions undetectable by bronchoscopy could be indicated. Therefore, we suggest performing bronchoscopic biopsy and that brushing and BAL might increase the positive detection rate of bronchoscopic examination.

小细胞肺癌肿瘤组织及血清CD44表达及临床预后意义

背景与目的小细胞肺癌(small cell lung cancer,SCLC)是一种以增殖迅速、易早期远处转移和获得性治疗耐药为特征的高侵袭性恶性肿瘤,临床预后极差。研究发现干细胞标志物CD44与肿瘤复发转移及治疗抵抗有关,而有关CD44在SCLC患者中的表达及其临床预后意义研究不多。本研究拟通过检测SCLC患者肿瘤组织和血清中CD44的表达水平,初步探索其与患者临床特征的关系并评估其判断预后的临床价值。方法将本院47例初治SCLC患者肿瘤组织和血清标本配对,分别应用免疫组化法(immunohistochemistry,IHC)和酶联免疫吸附试验方法(enzyme-linked immunosorbent assay,ELISA)对CD44进行检测,分析其与患者临床特征及预后的关系。结果SCLC患者肿瘤组织和血清中均可检测到干细胞标志物CD44的表达,体能状态(performance status,PS)2分的患者肿瘤组织CD44阳性率明显高于PS 0分-1分的患者(85.71%vs 30%,P=0.017),根据化疗疗效对患者进行分组,疾病进展组肿瘤组织CD44免疫组化得分及血清CD44浓度均明显高于疾病控制组且差异均达到统计学意义(P=0.006,P=0.034),单因素分析肿瘤组织CD44阳性患者无进展生存期(progression-free survival,PFS)较CD44阴性患者PFS明显缩短(5.23个月vs 9.03个月,P=0.036)。结论初治SCLC患者肿瘤组织中CD44的表达水平与PFS相关,CD44在SCLC中的临床意义值得进一步深入研究。

408例70岁以上老年肺癌患者的预后因素分析(英文)

Objective: The incidence and mortality of lung cancer in people over 70 years were increased in the past 10 years. We defined age 70 years as boundary line of the elderly patients in lung cancer and analyzed and identified the factors affecting prognosis. Methods: A retrospective study had enrolled 408 cases of lung cancer aged over 70 years old and SPSS13.0 software was used in univariate analysis and COX regression analysis to analyze factors affecting prognosis, such as gender, age, complications, symptoms, pathological type, clinical stage, effusion, surgery, radiotherapy, chemotherapy and so on. Results: In univariate analysis, symptoms, stage, effusion, surgery, chemotherapy and chemotherapy cycles showed affecting prognosis significantly. In COX regression analysis, it showed that clinical stage (P = 0.000), surgery (P = 0.013), chemotherapy cycles (P = 0.001) were independent prognostic factors. Conclusion: Elderly lung cancer patients could be benefit from surgery and adjuvant chemotherapy while early stage. At late stage, their survival time may be prolonged when receive chemotherapy at least 4 cycles. Single-agent chemotherapy would be a good choice for elderly lung cancer. Effusion, particularly, pericardial effusion significantly influenced the prognosis, so that it should be effectively controlled.

Icotinib, an EGFR-TKI, for the treatment of brain metastases in non-small cell lung cancer:a retrospective study

Objective Treatment of brain metastases from non-small cell lung cancer(NSCLC) is a challenge because of the poor prognosis. Icotinib is a new type of oral epidermal growth factor receptor(EGFR) tyrosine kinase inhibitor(TKI) used in the treatment of advanced NSCLC. The aim of this study was to evaluate the efficacy of icotinib in NSCLC patients with brain metastasis.Methods This study reviewed records of 51 NSCLC patients with brain metastases who took icotinib 125 mg, 3 times a day. Response rate, progression free survival, and overall survival were analyzed. SPSS software version 17.0 was used for univariate analysis, and Cox regression analysis to analyze factors affecting survival. Results Thirty-six cases had partial response, 6 cases had stable disease, and 10 cases had progressive disease. In 31 cases, EGFR gene mutation test were performed. EGFR was mutated in 26 cases and was with wild-type in 5 cases. In patients with EGFR mutations, 23 patients responded to icotinib [the disease control rate(DCR) was 88.5%], significantly higher than in patients with wild-type EGFR(1 patient, DCR 20%)(P = 0.005). The overall median progression-free survival(PFS) was 7.6 months. PFS was longer in the patients with EGFR mutations than in those with wild type EGFR(7.8 months vs 1.2 months, P = 0.03). The overall median overall survival(OS) time was 10.7 months. OS was longer in patients with EGFR mutations than in those with wild type EGFR(15.1 months vs 6.7 months, P = 0.003). The main side effects of the treatment were skin rash and diarrhea; no stage 3 or 4 toxic effects occurred. Univariate analysis demonstrated that OS was related to sex, Eastern Cooperative Oncology Group performance status(ECOG PS), smoking history, and EGFR mutation. Multivariate analysis showed that OS was independently related to sex, ECOG PS, and EGFR mutations.Conclusion Icotinib has a favorable effect on NSCLC patients with brain metastases harboring EGFR mutations. Icotinib can be a new choice of treatment for brain metastases in patients with NSCLC harboring EGFR mutations.