Response to Tyrosine Kinase Inhibitors in Patients with BCR-ABL1 Positive Chronic Myeloid Leukemia; 13.5 Years’ Experience at Patan Hospital, Nepal

Background:Since the advent of Tyrosine Kinase Inhibitor (TKI), well controlled studies in developed world have shown that the life expectancy of patients with CML is comparable to normal people without the disease. But long-term follow up studies are lacking in resource poor setting. Methods:This is a retrospective follow up study looking at the molecular response and resistance to Tyrosine Kinase Inhibitors (TKI) in patients enrolled in the Max Access Program since February 2003 till March 2017. Patients with twoor more BCR-ABL1 levels by Karyotyping/ fluorescent in situ hybridization (FISH) / reverse transcriptase polymerase chain reaction (RT-PCR) were included. At baseline, complete blood count (CBC), renal function test (RFT), and liver function test (LFT) were evaluated. Bone marrow aspiration and biopsy for morphology, cytogenetic analysis by Karyotyping/FISH and/or molecular analysis by RT-PCR were also done if these tests were not performed earlier. FISH or RT-PCR was done on peripheral blood every 3–12 months as necessary if the patient could afford. Patients with warning response/failure underwent BCR-ABL1 Resistance Mutation Analysis (IRMA).Results:Three hundred and forty six (346) patients had two or more BCR-ABL1 monitoring tests done. Optimal response was seen in 49.42%. Similarly, suboptimal response and failure were seen in 16.5% and 34% respectively. Overall Survival is 89.6% (at 1.8 -165 months, mean 62 months) . If only CML related events is considered survival is 95.9%. Seventy seven (77) patients with a total of 80 BCR-ABL1 domain Imatinib Resistance Mutation Analyses (IRMA) showed 19 different types of mutations with the most common being T315I mutation (8 and 19.5%). About 22.25% of the total patients showed resistance to Glivec out of which 10.98% showed mutations. Nine patients underwent trial for treatment free response (TFR) and 5 of them relapsed between 2-8 months.Conclusions:Despite all the odds of having financial problem, accessibility problem due to distances, transportation, etc. and difficulty monitoring with routine BCR-ABL1 and IRMA, our findings show that the outcome of TKI therapy in our CML patients is comparable to well controlled studies done elsewhere. Overall survival, molecular and cytogenetic responses and mutations in our patients who developed resistance as well as TFR are also similar to other studies. The resistance rate of 22.25% is slightly higher compared to other studies in developed world. This is mainly because of poor monitoring due to unavailability of the test including IRMA in our country and affordability until 2012. It proves that TKI is very effective in CML even in a resource-poor, developing country

Research progress in the application of anti-fibroblast growth factor and its receptor signaling pathway drugs in tumor therapy / 中国肿瘤生物治疗杂志

@#[摘 要] 成纤维细胞生长因子受体（FGFR）是一种受体酪氨酸激酶（RTK），与其配体成纤维细胞生长因子（FGF）相结合，激活下游的信号转导通路，参与调控细胞的正常生理活动。当FGFR基因发生扩增、突变或者融合等异常改变时，就会导致下游细胞信号通路的异常激活，促进细胞的增殖、迁移、侵袭及上皮-间质转化，进而促进肿瘤的发展。同时，FGFR在多种肿瘤中均呈高表达，因此FGF/FGFR可作为肿瘤治疗的重要靶点。根据药物作用机制，可以将抗FGFR信号通路药物分为两大类，分别为FGFR-酪氨酸激酶抑制剂（TKI）和阻断FGF/FGFR的单克隆抗体。目前，已有多种针对FGF/FGFR的靶向药物进入临床试验阶段，在肿瘤治疗中取得较好的临床效果，有的靶向药物获批用于临床肿瘤的治疗，为肿瘤的精准治疗带来了新的曙光。

CONCORDANCE: A real?world evidence study to evaluate the concordance of detecting epidermal growth factor receptor (EGFR) mutation by circulating tumor DNA* versus tissue biopsy in patients with metastatic non?small cell lung cancer

Background: Molecular tissue testing in non?small cell lung cancer (NSCLC) is done for the assessment of epidermal growth factor receptor (EGFR) mutation. EGFR mutation status is the basis for deciding the targeted treatment option for patients with metastatic NSCLC. The nonavailability of tissue samples and contraindications for biopsy pose a significant challenge. Hence circulating tumor DNA (ctDNA) by liquid biopsy can be a viable alternative for NSCLC patients. Methods: This study was conducted at 15 sites across India. EGFR mutation testing from plasma was done as part of the study at the central laboratory by the next?generation sequencing (NGS) method and EGFR mutation test results from tissue samples (done as part of routine practice) were recorded for all the patients. Results: Out of the total patients enrolled (N = 245) the majority (64.5% n = 158) were men. The median age of patients was 58.0 (range: 26�) years. The concordance between plasma and tissue testing was found to be 82.9% (95% confidence interval [CI]: 77.55 87.45). The sensitivity and specificity of NGS were 68.4% (95% CI: 56.92 78.37) and 90.1% [95% CI: 84.36 94.21) respectively. Plasma testing detected 1.2% (n = 3) and tissue sample testing detected 2.4% (n = 6) positive status of exon 20 T790M EGFR mutation. Out of the total number of patients enrolled 25 were tissue positive and plasma negative while 16 were plasma positive and tissue negative. Conclusions: This real?world study in Indian patients suggests that plasma testing for EGFR mutation analysis is a viable diagnostic option in newly diagnosed advanced/metastatic NSCLC patients. The noninvasive plasma procedure in patients without available/evaluable tumor sample may enable more patients to receive appropriate targeted therapies by providing clinicians with valuable insights into the patient抯 tumor mutation status. ClinicalTrials.gov Identifier: NCT03562819

Prognostic Factors in Patients with Advanced Lung Adenocarcinoma Treated with Icotinib / 肿瘤防治研究

Objective To investigate the relationship between the treatment of EGFR-TKI icotinib and the prognosis of advanced lung adenocarcinoma patients with EGFR mutation. Methods Patients with advanced lung adenocarcinoma who had EGFR19 and 21 gene mutations and were treated with EGFR-TKI icotinib were enrolled. The relationships of clinical features, EGFR gene mutation subtypes, and different sites with patients'prognosis were analyzed. Results A total of 101 patients with advanced lung adenocarcinoma were included in this study, including 58 cases (57.4%) of EGFR gene exon 19 deletion mutation (EGFR Del19) and 43 cases (42.6%) of EGFR gene exon 21 point mutation (EGFR L858R). The objective response rate was 63.4%. The mPFS and mOS were 13 months and 27 months, respectively. In addition, the mPFS and mOS of EGFR Del19 and EGFR19 mutation 746-750 were higher than those of EGFR L858R and other EGFR mutations, respectively. Meanwhile, multivariate analysis showed that the number of metastatic sites and pleural metastasis were independent influencing factors of patients'OS (P=0.027; P=0.041). The mOS of patients with the number of metastatic sites ≤3 and without pleural metastasis were 29 and 27 months, respectively. Conclusion There is no significant difference found in overall survival of advanced lung adenocarcinoma patients treated with icotinib among different EGFR mutation subtypes and sites. Herein, the overall survival time is longer in patients with less than three metastatic sites and without pleural metastasis.

Advance of synergism of immune checkpoint blockade and anti-angiogenesis in cancer treatment / 中国药理学通报

Immune checkpoint inhibitor ( ICI) activates the host' s anti-tumor immune response by blocking negative regulatory immune signals. A series of clinical trials showed that ICI could effectively induce tumor regression in a subset of advanced cancer patients. Anti-angiogenesis drugs commonly used to block tumor angiogenesis can inhibit the growth of tumors, but they cannot improve the survival of patients with limitations in application such as drug resistance. Tumor immune response is closely related to angiogenesis. In turn, tumor angiogenesis highly depends on immunosuppressive microenvironment. Recent studies have indicated that ICI resistance could be alleviated by combination therapy with anti-angiogenesis treatment, and the efficacy of combination therapy was superior to that of monotherapy. The reciprocal regulation between tumor vascular normalization and immune reprogramming forms a reinforcing loop that reconditions the tumor immune microenvironment to induce durable antitumor immunity. This review clarifies the latest understanding of ICI combined anti-angiogenesis therapy and provides ideas for subsequent research.

Analysis of the Reports of Adverse Dug Reaction Induced by EGFR-TKI in Shandong Province / 中国药房

OBJECTIVE：To analyze the clinical manifestations and characteristics of adverse drug reactions （ADR）induced by EGFR-TKI，and to provide reference for safe use of drugs in clinic. METHODS ：The relevant data of EGFR-TKI-induced ADR reports which were reported to Shandong ADR Monitoring Center from January 2018 to December 2020 were summarized ，and analyzed statistically in respects of age ，gender，drug variety ，ADR classification ，usage and dosage ，occurrence time ，involved organs/systems，clinical manifestations and prognosis of patients. RESULTS & CONCLUSIONS ：A total of 120 ADR reports induced by EGFR-TKI were included ，involving 120 patients. Among 120 patients，the female （60.83％）was more than the male （39.17％），and the age was mainly 50-79 years old （79.16％）. A total of 5 drugs including gefitinib ，ositinib，afatinib，ektinib and erlotinib were involved. ADR occurred in 72，11，15，6 and 16 patients using the above drugs respectively ；the main ADR was general ADR （70.83％），followed by severe ADR （22.50％），new general ADR （5.00％）and new severe ADR （1.67％）. All patients were given drugs orally ，off-label use was found in 2 patients who used ektinib ，and the rest met the medication requirements of the drug instructions. ADR occurred in 61 patients（50.83％）within 1 month after medication ，34 patients （28.33％）within 1-3 months after medication ，25 patients（20.83％）within 4-12 months after medication ，and no ADR occurred after 12 months. ADR of organs/systems involved were mainly the lesion of skin and its appendant injury，gastrointestinal system injury and hepatobiliary system injury. The main clinical manifestations were rash ，diarrhea and abnormal liver function ；in addition，some patients developed severe or new severe ADR such as interstitial pneumonia ，bone marrow suppression ，tongue swelling and cerebral infarction. Totally 102 patients recovered or improved after drug withdrawal or symptomatic treatment ，12 patients had unknown outcome ，and 6 patients did not improve. It is suggested that pharmaceutical care should be strengthened within 1 month after EGFR-TKI administration ，so as to guard against the occurrence of new and serve ADR and ensure the safety of clinical medication.

Actualización de medicamentos asociados a necrosis avascular de los maxilares: perspectiva y revisión de literatura / Update of medications associated with avascular necrosis of the jaws: a perspective and literature review

La osteonecrosis de los maxilares está definida como la exposición de hueso necrótico en la región maxilofacial al menos por ocho semanas en pacientes que están recibiendo medicamentos antirresortivos para el tratamiento del cáncer primario o metastásico hacia el hueso, osteoporosis o enfermedad de Paget, sin historia previa de radiación. Desde el año 2003, la terminología utilizada estaba en relación con los bifosfonatos, en la actualidad ha sido introducido el término osteonecrosis de los maxilares relacionada por medicamentos (OMAM). La cirugía oral (implantología o cirugía periapical) incrementa el riesgo de OMAM, así como los desbalances concomitantes de la salud oral (inflamación dental y formación de abscesos). Las estrategias conservadoras en el tratamiento varían desde el cuidado local conservador hasta la resección quirúrgica radical del hueso necrótico. En el presente artículo se expone un análisis sistemático retrospectivo de la literatura en páginas como PubMed, ScienceDirect y Springer, Cochrane Library. Con el objetivo de resaltar el aumento de la incidencia de OMAM a nivel mundial con el uso de antirresortivos y otros medicamentos asociados en su patogenia en el Hospital Regional «General Ignacio Zaragoza¼ del ISSSTE, UNAM, en la Ciudad de México (AU)

Osteonecrosis of the jaws is defined as the exposure of necrotic bone in the maxillofacial region for at least 8 weeks in patients receiving antiresorptive medications for the treatment of primary or metastatic cancer towards the bone, osteoporosis, or Paget's disease, without previous history of radiation. Since 2003, the terminology used was related to bisphosphonates, the term medication-related osteonecrosis of the jaws has now been introduced. Oral surgery (implantology or periapical surgery) increases the risk of avascular necrosis, as well as concomitant imbalances in oral health (dental inflammation and abscess formation). Conservative strategies in treatment vary from conservative local care to radical surgical resection of the necrotic bone. In this article, a systematic retrospective analysis of the literature is presented on pages such as PubMed, Science Direct and Springer, Cochrane Library. And in which the objective is to highlight the increase in the incidence of medication related osteonecrosis of the jaws worldwide with the use of antiresorptive, and other associated medications in its pathogenesis at the Hospital Regional «General Ignacio Zaragoza¼ ISSSTE, UNAM in Mexico City (AU)

Acquired Drug Resistance Mechanism of Osimertinib in the Targeted Therapy of Non-small Cell Lung Cancer / 中国肺癌杂志

While treating cancer, epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) still faces inevitable drug resistance. Investigations into the mechanisms which foster resistance to EGFR-TKI has led to the discovery of novel biomarkers and drug targets, and in turn has enabled the development of third-generation TKIs and proposals for rational therapeutic combinations. The threonine-to-methionine substitution mutation at position 790 (T790M) is clinically validated to engender refractoriness to first- and second-generation TKI, and is a standard-of-care predictive biomarker used in therapeutic stratification. For patients who are T790M-negative, cytotoxic chemotherapy or protracted EGFR-TKI treatment are acceptable treatment standards after disease progression, although combinations of targeted therapies and checkpoint blockade immunotherapy may offer promising alternatives in the future. Among T790M-positive patients, the third-generation EGFR-TKI, osimertinib, has shown superiority over both platinum-doublet chemotherapy and first-generation EGFR-TKI in randomized clinical trials. This article appraises the key literature on the contemporary management of non-small cell lung cancer patients with acquired resistance to EGFR-TKIs, and envisions future directions in translational and clinical research.

Efficacy and safety of bevacizumab combined with first-generation egfr-tki in the first-line treatment of egfr-mutated advanced non-small cell lung cancer: A meta-analysis / 肿瘤

Objective: To evaluate the efficacy and safety of Bevacizumab (BEV) combined with first-generation EGFR-TKI versus first-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) alone in the first-line treatment of EGFR-mutated positive (EGFRm) advanced non-small cell lung cancer(NSCLC). Methods: PubMed, Cochrane Library, Embase, Weipu chinese journal, China Biology Medicine database, China National Knowledge Infrastructure and Wanfang relevant databases were searched to collect randomized controlled trials (RCTs) of BEV combined with first-generation EGFR-TKI (experimental group) versus first-generation EGFR-TKI alone (control group) in the first-line treatment of EGFRm advanced NSCLC from database foundation to July, 2019. The data in the included RCTs were extracted, and the qualities were assessed in accordance with Cochrane Collaboration, and a Meta-analysis was conducted with RevMan 5.3 software, Risk ratio (RR), hazard ratio (HR) and 95% confidence interval (CI) were calculated. Results: A total of 7 RCTs were enrolled, including 834 patients. The results of meta-analysis showed that experimental group was better than control group in objective response rate (ORR) (RR = 1.27, 95% CI: 1.15-1.41, P < 0.000 01), disease control rate (DCR) (RR = 1.10, 95% CI: 1.02-1.20, P = 0.02) and progression-free survival (PFS) (HR = 0.57, 95% CI: 0.44-0.75, P < 0.000 1) in terms of efficacy. In terms of safety, the incidences of hypertension (RR = 4.11, 95% CI: 2.95-5.93, P < 0.000 01], proteinuria (RR = 5.16, 95% CI: 3.40-7.83, P < 0.000 01), hemorrhage (RR = 3.34, 95% CI: 2.37-4.72, P<0.000 01) were higher in experimental group. There was no significant difference between the two groups in the incidences of rash (RR = 1.00, 95% CI: 0.92-1.08, P = 0.91), diarrhea (RR=1.05, 95% CI: 0.91-1.21, P = 0.52), hypohepatia (RR = 0.91, 95% CI: 0.72-1.14, P = 0.42). Conclusion: BEV combined with first-generation EGFR-TKI significantly improve ORR, DCR and PFS in the first-line treatment of EGFRm advanced NSCLC, but also increase the risks of hypertension, proteinuria and hemorrhage.

ABCB1 and BMI1 mRNA expression in patients with chronic myeloid leukemia: impact on imatinib efficacy

BACKGROUND: ATP-binding cassette transporters are important in the mechanism of multidrug resistance. ABCB1 displays a high affinity for imatinib. BMI1 is a polycomb group protein thought to be overexpressed in leukemic cells. METHODS: This study was conducted to investigate the prognostic value of ABCB1 and BMI1 expressions in chronic myeloid leukemia (CML). Expression levels were measured in 81 patients newly diagnosed with CML and 20 healthy controls by real time reverse transcription- PCR. RESULTS: The ABCB1 expression levels did not differ between patients with CML and controls. Low ABCB1 mRNA levels were observed in patients who achieved an optimal response compared to suboptimal and resistant cases (P=0.005). Non-responders showed the highest ABCB1 levels. ABCB1 expression did not affect the progression-free survival (PFS) of patients. BMI1 expression was higher in patients than that in controls (P=0.001). Patients in advanced phases expressed higher levels of BMI1 than those in the chronic phase (P=0.004). High BMI1 expression was associated with a shorter PFS. CONCLUSION: ABCB1 mRNA expression may serve as a predictor of the optimal response to imatinib treatment in patients with CML. BMI1 expression was higher in the accelerated and blastic crisis phases of CML and associated with a shorter PFS.

Prognostic Analysis of EGFR-TKIs Combined with Gamma Knife in EGFR-mutant Lung Adenocarcinoma with Brain Metastasis / 中国肺癌杂志

BACKGROUND@#Advanced epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma had a high overall incidence of brain metastasis during the full course, and local brain radiotherapy combined with systemic targeted therapy may be a better strategy. This study aimed to identify the prognostic factors of EGFR-mutant brain-metastatic lung adenocarcinoma patients who received EGFR-tyrosine kinase inhibitors (EGFR-TKIs) in combination with gamma knife radiosurgery.@*METHODS@#Retrospective analysis of EGFR-mutant lung adenocarcinoma patients with brain metastases which developed at initial diagnosis or during EGFR-TKIs treatment period were performed. Intracranial progression free survival (PFS) was statistically analyzed between different subgroups to find out the prognostic factors including gender, age, smoking history, extracranial metastasis, EGFR mutation type, size and number of intracranial lesions, carcino-embryonic antigen (CEA) level, lung-molGPA score and so on.@*RESULTS@#A total of 74 EGFR-mutant brain-metastatic lung adenocarcinoma patients were enrolled in this study, with median intracranial PFS of 14.7 months. One-year intracranial-progression-free rate was 58.5%, and two-year rate was 22.2%. Univariate survival analysis showed that patients with lower CEA level at initial diagnosis (3)(15 months vs 12.6 months, P=0.041) were prone to have a superior intracranial PFS. Multivariate analysis showed that CEA≥10 ng/mL and intracranial lesion≥2 cm were the independent risk factors of intracranial PFS.@*CONCLUSIONS@#EGFR-TKIs in combination with gamma knife radiosurgery was an efficient treatment option to control the cranial tumor lesion. CEA≥10 μg/L at initial diagnosis and intracranial lesion≥2 cm were the risk factors of EGFR-mutant brain-metastatic lung adenocarcinoma patients receiving EGFR-TKIs in combination with gamma knife radiosurgery.

Molecular Mechanism and Progression of Primary Resistance to EGFR-TKI - Analysis of 2 Cases / 中国肺癌杂志

Tyrosine kinase inhibitor (TKI) have been proved to be effective in the treatment of advanced non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) sensitive mutation, which is superior to chemotherapy. However, there are still some patients with sensitive mutations have primary drug resistance. It may be related to the coexistence of susceptible and resistant mutations of EGFR gene, downstream mutations of EGFR pathway, MET amplification and BIM deletion polymorphism. We present 2 cases of primary drug resistance and analyze the reasons.
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EGFR-TKI ADR Management Chinese Expert Consensus / 中国肺癌杂志

ErbB receptor tyrosine kinase inhibitors (EGFR-TKI), gefitinib, erlotinib, icotinib and aftinib, which are approved as a frontline treatment for patients with non-small cell lung cancer (NSCLC) who have tumors harboring EGFR mutations in China. And osimertinib was approved in second line setting for patients with EGFRT 790M-positive NSCLC. Rash, paronychia, diarrhea, stomatitis, liver dysfunction and (interstitial lung disease, ILD) are frequently observed in patients treated with EGFR-TKI. Chinese Society of Lung Cancer, Chinese Anti-Cancer Association, organized Chinese experts to develop the Chinese expert consensus on EGFR-TKI adverse event (AE) management based on domestic diagnosis and treatment of ADR and also incorporating international updated theory and recommendations.
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Progress in targeted therapy and immunotherapy of epidermal growth factor receptor mutation-positive non-small cell lung cancer with brain metastases / 中国肿瘤生物治疗杂志

@#表皮生长因子受体(EGFR)突变型非小细胞肺癌（NSCLC）容易出现脑转移，EGFR酪氨酸激酶抑制剂(TKI)(EGFRTKI)则为此类患者的治疗带来极大获益。但第一、二代靶向药物脑穿透力弱和最终获得性耐药，导致颅内疾病进展，是脑转移治 疗的主要挑战。近年来，随着第三代EGFR-TKI、免疫检查点抑制剂（ICB）的深入研发，EGFR突变型NSCLC脑转移的治疗发生 了极大变化。本文将回顾脑转移的靶向治疗及免疫治疗方面取得的进展，并对目前存在的问题及未来发展方向进行探讨。

Current Status for Anaplastic Lymphoma Kinase in Non-small Cell Lung Cancer / 中国肺癌杂志

The incidence of ALK gene rearrangement in non-small cell lung cancer (NSCLC) was about 3% to 5%. ALK gene inhibitors have made great breakthrough in recent years, significantly extending the survival period of patients with ALK(+) advanced NSCLC. But the majority of patients will be acquired drug resistance after treatment. This article has been explained separately from the ALK genetic background, the detection method, the treatment of the three generations of ALK inhibitors and the strategy after drug resistance. It is desire to have reference value and reference meaning for clinical work.
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Analysis of Epidermal Growth Factor Receptor Gene Mutation in 274 Cases of Non-Small Cell Lung Cancer / 中国药房

OBJECTIVE:To study the gene mutation status of epidermal growth factor receptor(EGFR)in non-small cell lung cancer(NSCLC)patients and its relationship with clinical indexes,and to provide reference for individualized administration of EGFR-TKI in NSCLC patients. METHODS:Totally of 274 NSCLC patients from the northern of Jiangsu area were selected from our hospital during Jan. 2015-Dec. 2017. Mutation status of EGFR gene in lung tissue was determined by amplification refractory mutation system (ARMS)-TaqMan PCR assay. The relationship of EGFR gene mutation with clinical indexes as gender,age, smoking status, staging, tumor differentiation and pathological type were analyzed retrospectively. Compared with related literatures,the regional differences of EGFR gene mutation were analyzed. RESULTS:Among 274 NSCLC patients,112 patients suffered from EGFR gene mutation with total mutation rate of 40.88%. There were 50,57,3,2 cases of exon 19,exon 21,exon 20 and exon 19+21 mutation,and the types of EGFR gene mutation were delE746-A750,L858R and insH773-V774H,etc. The mutation rates of EGFR gene exon 19,exon 21 in non-smoking,early,well-differentiated and adenocarcinoma patients were 52.50%,47.24%,46.36% and 45.00%,which were significantly higher than smoking (28.57%),advanced (27.03%), poor-differentiated(31.71%)and squamous cell carcinoma(27.66%)patients,with statistical significance(P＜0.05). There was no statistical significance in mutation rates of EGFR gene exon 19 and exon 21 between male and female,≥65 year-old and ＜65 year-old patients (P＞0.05). EGFR mutation rate of NSCLC subjects from the northern of Jiangsu area was significantly higher than Shanghai area(P＜0.05);there was no statistical significance compared with Yunnan area(P＞0.05)but mutation types were different. CONCLUSIONS:There is the highest EGFR gene mutation rate in its exon 21,lesser in exon 19,rare in exon 20 and exon 19+21 among NSCLC patients from the Northern of Jiangsu area. There are obvious regional differences. The mutation rate of EGFR gene mutation exon 19 and exon 21 are associated with smoking status,staging,tumor differentiation and pathological type of NSCLC patients. The non-smoking, early stage, well-differentiated and adenocarcinoma patients are more likely to benefit from EGFR-TKI targeted therapy.

Association between EGFR mutation status and efficacy of first-line EGFR-TKI in patients with ;advanced non-small cell lung cancer / 国际肿瘤学杂志

Objective To evaluated the effect of first-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI)on advanced non-small cell lung cancer (NSCLC)patients with different EGFR mutation status (exon 1 9 deletion and exon 21 mutation).Methods Seventy-two advanced NSCLC patients with EGFR mutation confirmed by histopathology were enrolled.All of the patients received first-line EGFR-TKI.The relationships between EGFR mutation status and objective response rate (ORR),disease control rate (DCR),progression free survival (PFS ) and overall survival (OS ) were analyzed.Results Of the 72 patients,37 patients expressed exon 1 9 deletion,35 patients expressed exon 21 mutation,and all of them could be evaluated.The ORR and DCR of patients with exon 1 9 deletion were higher than those of patients with exon 21 mutation (75.7%vs.51 .4%,χ2 =4.583,P=0.032;89.2%vs.68.6%,χ2 =4.636,P=0.031 ).The modified median PFS of patients with exon 1 9 deletion was significantly higher than that of patients with exon 21 mutation (1 3.2 month vs.1 0.8 month,χ2 =4.700,P=0.030).The median OS of patients with exon 1 9 deletion was significantly higher than that of patients with exon 21 mutation (30.2 month vs.25.6 month,χ2 =4.686,P=0.030).The side effects were similar between the two groups.The most common adverse reaction was rash,and the incidence had no significant difference between the two groups (48.7% vs.48.6%,χ2 =0.000,P=0.995 ).Conclusion EGFR mutation status is a predictor for PFS,OS and ORR of first-line EGFR-TKI in patients with advanced NSCLC.NSCLC patients with EGFR exon 1 9 deletion are associated with longer survival time and better response rate compared with those with exon 21 mutation.

Pulmonary toxicity related to EGFR-TKI monotherapy or its combination with radia-tion as treatment for non-small cell lung cancer / 中国肿瘤临床

Monotherapy of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) serves as the first-line treatment for non-small cell lung cancer (NSCLC) patients with EGFR mutation. Pre-clinical studies confirmed that TKIs can increase radiation sensitiv-ity. Clinical studies confirmed that EGFR-TKI combined with radiotherapy may improve survival of patients and can be used as alterna-tive to chemoradiotherapy. Pulmonary toxicity induced by EGFR-TKIs monotherapy features low incidence rate but high mortality rate, and the incidence rate raries when TKIs is combined with radiotherapy. In this review, we summarise related literature on pulmonary toxicity in EGFR-TKI monotherapy or its combination with radiotherapy for advanced NSCLC. This study can serve as reference for safe-ty of this combined therapy.

Current status of anti-angiogenesis therapy for non-small cell lung cancer / 实用肿瘤学杂志

Angiogenesis is the physiological process of generating new blood vessels from existing net-works.In the tumor microenvironment,the dynamic balance of a growing tumor facilitates the transition to persis-tent angiogenesis.Antiangiogenic drugs have been used in a variety of solid tumors,including lung cancers,by re-sisting tumor angiogenesis and inhibiting tumor growth,since human recognized its ability.In this paper,recent re-search status of tumor angiogenesis and non-small cell lung cancer anti-angiogenesis are reviewed in details.

Current status of anti-angiogenesis therapy for non-small cell lung cancer / 实用肿瘤学杂志

Angiogenesis is the physiological process of generating new blood vessels from existing net-works.In the tumor microenvironment,the dynamic balance of a growing tumor facilitates the transition to persis-tent angiogenesis.Antiangiogenic drugs have been used in a variety of solid tumors,including lung cancers,by re-sisting tumor angiogenesis and inhibiting tumor growth,since human recognized its ability.In this paper,recent re-search status of tumor angiogenesis and non-small cell lung cancer anti-angiogenesis are reviewed in details.