Iressa治疗非小细胞肺癌的进展

分子靶向药物，如表皮生长因子受体酪氨酸激酶抑制剂，是近年来在血液和实体肿瘤治疗中涌现出的新治疗手段。现就表皮生长因子受体酪氨酸激酶抑制剂Iressa在非小细胞肺癌治疗中的进展作一综述。     

表皮生长因子受体酪氨酸激酶抑制剂耐药机制研究进展

含有表皮生长因子受体突变的非小细胞肺癌患者中70％～80％对表皮生长因子受体酪氨酸激酶抑制剂吉非替尼和厄洛替尼敏感,但最终仍会出现耐药导致肿瘤进展。表皮生长因子受体酪氨酸激酶抑制剂耐药分为原发耐药和继发耐药,继发耐药机制主要包括表皮生长因子受体二次突变（T790M）、HER2及HER3的代偿作用、MET扩增、胰岛素样生长因子受体结合蛋白缺失及哺乳动物雷帕霉素靶蛋白信号通路活化。     

小分子酪氨酸激酶抑制剂治疗非小细胞肺癌研究进展

介绍小分子酪氨酸激酶抑制剂(埃罗替尼和吉非替尼)的作用机制,单药治疗及和化疗药联合治疗的临床试验,探讨化疗、放疗、表皮生长因子受体表达及突变、患者的临床特点等因素与小分子酪氨酸激酶抑制剂临床疗效的关系,阐述小分子酪氨酸激酶抑制剂治疗非小细胞肺癌的进展。     

表皮生长因子受体酪氨酸激酶抑制剂治疗非小细胞肺癌脑转移的再认识

脑转移是非小细胞肺癌常见的并发症,目前的标准治疗效果欠佳.近年来,表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKI)治疗非小细胞肺癌脑转移已取得一定疗效.本综述主要从酪氨酸激酶抑制剂治疗脑转移的可能机理、疗效、人群选择及耐药后的处理等方面来阐述酪氨酸激酶抑制剂在脑转移患者中的应用.     

EGFR突变对云南省晚期肺腺癌疗效及预后影响的真实世界研究

目的 研究云南省肺腺癌患者表皮生长因子受体(epidermal growth factor receptor,EGFR)突变检测情况、表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptor-tyrosine kinase inhibitor,EGFR-TKI)应用情况及晚期肺...     

非小细胞肺癌EGFR突变的检测方法

非小细胞肺癌(non-small cell lung cancer,NSCLC)是严重危害人类健康的常见恶性肿瘤。近年来表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptortyrosine kinase inhibitor,EGFR-TKI)为NSCLC的治疗带来新的曙光,但用药前必须依据表皮生长因子受体(epidermalgrowth factor receptor,EGFR)的突变检测结果选择治疗对     

埃克替尼对非小细胞肺癌术前诱导治疗的临床疗效2例报告

表皮生长因子受体酪氨酸激酶抑制剂（EGFR—TKI）作为晚期非小细胞肺癌靶向治疗药物临床应用以来．已积累了大域的临床实验数据和临床应用经验。     

VEGF抑制剂联合酪氨酸激酶抑制剂一线治疗EGFR突变晚期非小细胞肺癌的疗效和安全性

目的:探讨血管内皮生长因子(vascular endothelial growth factor,VEGF)抑制剂联合酪氨酸激酶抑制剂(tyrosine kinase inhibitors,TKI)一线治疗表皮生长因子受体(epidermal growth factor receptor,EGFR)突变晚期非小细胞肺癌...     

表皮生长因子受体酪氨酸激酶抑制剂治疗非小细胞肺癌的耐药机制

表皮生长因子受体酪氨酸激酶抑制剂（ EGFR-TKI）在非小细胞肺癌的治疗中具有重要地位,但有研究发现患者会对EGFR-TKI产生原发性耐药或获得性耐药。目前发现获得性耐药的多种机制最终都导致表皮生长因子受体的下游信号通路被重新激活。肝X受体激动剂对表皮生长因子受体最重要的下游通路PI3K-Akt-NF-κB的多个主要环节均有不同程度的抑制作用,有望逆转EGFR-TKI的继发耐药。     

EGFR-TKIs联合化疗在晚期非小细胞肺癌中的应用

晚期非小细胞肺癌（NSCLC）的治疗需首先明确其组织学类型与分子学特征。若存在表皮生长因子受体（EGFR）基因突变或渐变性淋巴瘤激酶（ALK）基因融合,应首选分子靶向药物治疗。但分子靶向治疗药物并未改善晚期患者的总生存,如何提高晚期NSCLC患者的总生存是目前临床医生关注的热点。表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）与含铂双药交替使用模式作为晚期NSCLC的一线治疗方案,可能将明显延长EGFR阳性突变患者总生存时间。本文就小分子酪氨酸激酶抑制剂联合化疗治疗NSCLC患者、方式及其疗效的研究进展进行综述。      

Immediate versus delayed treatment with EGFR tyrosine kinase inhibitors after first-line therapy in advanced non-small-cell lung cancer

Objective: To analyze the outcomes of patients who received TKI immediately after the first-line without progression as maintenance treatment (immediate group) vs. those received delayed treatment upon disease progression as second-line therapy (delayed group). Methods: The study included 159 no-small-cell lung cancer (NSCLC) patients who received gefitinib or erlotinib as maintenance treatment in the immediate group (85 patients) or as second-line therapy in the delayed group (74 patients). The primary end...     

低危骨髓增生异常综合征的治疗策略

低危骨髓增生异常综合征（MDS）是指国际预后积分系统修订版（IPSS．R）评分≤3．5分的MDS,支持治疗仍是主要的治疗手段。对于染色体5q缺失[del（5q）]MDS患者,如果内源性促红细胞生成素（EPO）水平〈500U／L（最好〈200U／L）,红系造血刺激剂（ESA）仍是最佳选择。对应用EPO无效或脱离输血后复发的患者,可以选择免疫抑制剂、转化生长因子抑制剂和来那度胺。del（5q）患者可以从来那度胺长期受益。血小板减少造成严重出血的情况较少,血小板生成素受体类似物可以减少出血,提高血小板数,可用于骨髓原始细胞比例〈0．05的患者。治疗失败或有进展为高危MDS和急性髓系白血病风险者,可能需要造血干细胞移植治疗。文章结合第59届美国血液学会（ASH）年会报道,介绍有关低危MDS的治疗策略。     

法乐通治疗晚期乳腺癌临床总结

目的 考察法乐通治疗晚期绝经后乳腺癌的放疗及其不良反应。方法：法乐通一线治疗每日一次６０ｍｇ口服,二线治疗每日一次１２０ｍｇ口服。结果：共６０例,有效率１８．３％,一线治疗１８例,有效率３３．３％,二线治疗４２例,有效率１１．９％,淋巴结和骨转移疗效较好,肝转移,肺转移及胸壁转移也有一定疗效。一线治疗较二线治疗,未用内分泌治疗较曾用内分泌治疗,绝经时间长（≥１０年）较经时间短（〈１０年）以及疗后无     

Methylene blue for the treatment and prophylaxis of ifosfamide-induced encephalopathy

Ifosfamide (IFOS) is used in cancer treatment. Ifosfamide-induced encephalopathy (IIE) can result in treatment delay or discontinuation as well as morbidity and mortality. Cases using methylene blue (MB) in acute and prophylactic treatments are discussed. For acute use, marked central nervous system (CNS) improvement occurred within 24h of MB administration. For prophylactic use, the severity of the symptoms decreased significantly compared with previous treatment cycles, and enabled patients to continue further IFOS therapy. MB has potential use in both the acute treatment and prophylaxis of IIE.     

Imipenem/Cilastatin Monotherapy as Salvage Treatment in Febrile Neutropenic Patients

Abstract

Imipenem/cilastatin (I/C) monotherapy was used as salvage treatment in 55 neutropenic patients (58 fever episodes) after treatment failure on first-line antibiotic therapy. Successful antibiotic treatment was defined as eradication of all signs, symptoms and microbiologic evidence of infection on I/C monotherapy alone. Twentyfive out of the 58 episodes (43%) were classified as success, 6 episodes (10%) as initial response but the regimen had to be modified (amphotericin B was added) and 27 episodes (47 %) as failures. In episodes with documented infections 9 out of 23 (39%) were classified as success. All patients survived during the first 72 hours after change to I/C therapy. One patient had to discontinue I/C due to a skin rash.

In conclusion, the use of a treatment algorithm with I/C monotherapy as second-line treatment was safe and effective. Other antimicrobial agents, most often vancomycin and/or amphotericin B, had to be added in half of the patients.     

Fractionated thermochemotherapy in vivo of a C3H mouse mammary carcinoma

The interaction between fractionated heat treatment and fractionated drug treatment with cyclophosphamide (CTX) was investigated in a transplantable C3H mouse mammary carcinoma inoculated into the hind leg of C3D2F1/Bom mice. A tumour core temperature of 43.5 +/- 0.1 degrees C was achieved by immersing the tumour-bearing leg into a water bath thermostatically maintained at 43.7 +/- 0.1 degrees C. CTX was administered i.p. using the maximum tolerated dose (MTD) (LD 1%) for single fraction treatment (100 mg/kg) as the maximum fraction dose. For combined treatment CTX was given 15 min prior to heating. The endpoint was the time to reach a tumour volume of 5 times the volume at first treatment. Specific growth delay was used as effect parameter. In dose-effect experiments using total treatment time at 43.5 degrees C as dose parameter, drug enhancement ratio (DER) was determined as the ratio of the slope of the dose-effect curve for MTD of CTX plus heat to the slope of the curve for heat alone. In dose-effect experiments using total CTX dose as dose parameter, thermal enhancement ratio (TER) was determined as the ratio of the slope of the dose-effect curve for CTX plus 43.5 degrees C for 30 min to the slope of the curve for CTX alone. The regimens investigated were single fraction treatment and 3 and 5 fractions with time intervals of 3 and 5 days. For single fraction treatment DER was 1.4 +/- 0.1 and TER 2.3 +/- 0.2. The drug sensitization of the effect of heat treatment tended to increase with increasing number of fractions.(ABSTRACT TRUNCATED AT 250 WORDS)     

Introduction and implementation of the basic treatment equivalent in a Varian‐based department

The increasing popularity of 3‐D planning leads to procedural alterations as both workload and resource utilization increase. Although the complexity of the techniques has increased (as well as the set‐up and treatment times), the workload statistics must still include the number of fields treated. It is commonly known that machine statistics of fields treated per day do not accurately represent workload because there are major differences between techniques. A mantle treatment technique and an opposed spine technique both have (statistically) two fields, although the set‐up requirements and treatment times are very different. A basic treatment equivalent (BTE) formula was reported in early 1999 by Delaney et al. and incorporates a large number of variables inherent in patient treatment. The formula considers different factors that affect overall treatment time, and aims to represent a more accurate treatment time indicator. The aim of introducing the BTE into the Department of Radiation Oncology at Sir Charles Gairdner Hospital was to create a more accurate scheduling system and even out workloads on all treatment units. Therefore the BTE formula was used to assess accuracy of treatment times in order to determine if the values could be relied upon as accurate time indicators. Patients undergoing a variety of treatment techniques were timed for the duration of their treatment procedure, and their treatment times compared to the time estimated using the BTE formula. A few minor alterations were made to the equation for treatment units with multi‐leaf collimation (MLC). A trial conducted at Sir Charles Gairdner Hospital found that, using the BTE formula (with a few modifications required for the MLC treatment units), of 60 patients timed for the duration of their set‐up and treatment, 85% of values were in the range of ± 3 min, and 95% were in the range of ± 5 min of the estimated times. Through the routine use of the BTE equation a more sensitive indication of treatment machine workload can be found. Advantages such as: (i) a more accurate measure of treatment workload (for comparison with other departments) and (ii) increased scheduling accuracy will succeed over the currently accepted system of fields per hour.     

Co-operative study group for childhood acute lymphoblastic leukemia (COALL): long-term follow-up of trials 82, 85, 89 and 92.

The German Co-operative Study Group COALL for treatment of acute lymphoblastic leukemia (ALL) in childhood started the first trial in 1980. This report gives an overview of the long-term results of the four consecutive studies COALL-82, COALL-85, COALL-89 and COALL-92. Besides improvement in long-term survival major objectives were reduction of treatment-related toxicity by transferring asparaginase (ASP) from induction therapy to intensive phase and omitting CNS irradiation by stepwise increase of the initial white blood count (WBC) up to 50 x 10(9)/l (exception T-ALL) as criterion for irradiation. In study COALL-85 in high risk patients slow vs rapid rotational treatment was randomized. In study COALL-92 initial response to daunorubicin (DNR) as a 1-h vs 24-h infusion and its prognostic value was investigated. Furthermore, 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) were randomized in maintenance treatment. In total, 1191 eligible patients were enrolled. Induction treatment without ASP has been shown to be as effective and less hazardous than the former four-drug induction. CNS control could be obtained in most without cranial irradiation (CNS relapse-free survival >95%). The leukemic cell kill with a 24-h DNR infusion was equivalent to that of a 1-h infusion. DNR response was of less prognostic significance than prednisone response. The rapid rotation regimen failed to improve outcome as well as 6-TG in maintenance treatment. However, intensification of systemic treatment resulted in an increase in overall event-free survival (EFS) to approximately 80% which is comparable to other groups.     

Role of BIM Deletion Polymorphism and BIM Expression as Predictive Biomarkers to Maximize the Benefit of EGFR-TKI Treatment in EGFR-Positive NSCLC

Objective: BIM is a modulator of apoptosis that is triggered by EGFR-TKIs. This study evaluated the role of BIM deletion and its expression as predictor of EGFR-TKI treatment outcome. Methods: The medical record of 185 EGFR-positive advanced non-small cell lung cancer (NSCLC) patients with/ without EGFR-TKI treatment between 9/2012 and 12/2014 were retrospectively reviewed. BIM deletion polymorphism and expression were tested by RT-PCR and immunohistochemistry, respectively. Survival outcomes in EGFR-TKI-treated patients were analyzed according to treatment sequence and EGFR mutation. The correlation between BIM deletion polymorphism, expression, response rate (as a function of EGFR-TKI treatment) and schedule was also explored. Result: EGFR-TKIs were administered to 139 (75.1%) of the 185 patients: as the first-line in 52 (37.4%) patients and as later-line treatment in 87 (62.6%) patients. Median overall survival (mOS) was significantly longer in EGFR-TKIs treated patients (28.9 vs. 7.4 months, P<0.001). Among L858R-mutated patients, median progression-free survival (mPFS) was significantly longer in first-line EGFR TKI treatment than a later-line (12.6 vs. 6.3 months, P=0.03). BIM deletion polymorphism and expression was detected in 20.2% and 52.7%, respectively. Patients without BIM deletion polymorphism had a significantly longer mOS when treated with a first-line than with a later-line EGFR-TKI (28.9 vs. 20.7 months, P= 0.04). Patients without BIM expression had a significantly longer mPFS (9.6 vs. 7.3 months, P=0.01) better mOS and response rate (RR). Conclusion: BIM deletion polymorphism and expression may predict an EGFR-TKI response in patients with EGFR-positive during therapy.     

头颈部肿瘤大分割放疗的研究进展及在新冠疫情中的临床价值

放疗是头颈部肿瘤综合治疗的重要部分,也是根治性手段之一。2019年新型冠状病毒肺炎疫情暴发持续至今,对肿瘤患者的治疗造成很大影响。由于常规分割放疗(2 Gy/次)往往需要6周以上连续照射,给疫情防控带来巨大挑战。大分割放疗增加单次剂量,从而减少照射次数,缩短治疗时间,可能较常规分割更适用于疫情期间的治疗。早期研究对大分割方案在头颈部肿瘤姑息治疗中的应用已有诸多探索,其安全性和有效性已得到部分确认。近期,以根治性为目的的大分割放疗及联合化疗、免疫治疗的综合治疗方案也有初步的尝试。根据疫情防控需要,国外多个专家共识也对头颈部肿瘤大分割方案进行了推荐。本文就上述进展做一综述,并讨论疫情期间实施大分割放疗的临床价值。