厄洛替尼联合全脑放疗治疗非小细胞肺癌脑转移的临床疗效

目的探讨厄洛替尼联合全脑放疗治疗非小细胞肺癌(NSCLC)脑转移患者的疗效、生存分析、年龄相关性及毒副反应。方法回顾性分析2009年1月至2012年3月收治的经病理或细胞学确诊的NSCLC患者67例。32例采用厄洛替尼口服联合全脑放疗,其中厄洛替尼剂量为150 mg/d;全脑放疗的剂量为Dt(3 000~3 600)c Gy/(10~12)F。放疗完成后2个月内评价近期疗效。结果治疗组脑转移病灶控制率(DCR)为93.8%,病灶完全缓解(CR)4例、14例部分缓解(PR)、病灶稳定(SD)12例。毒副反应主要为头痛、恶心呕吐、皮疹和腹泻。结论厄洛替尼联合全脑放疗较单纯全脑放疗治疗反应率明显升高,尤其适用于EGFR突变阳性患者;毒副作用可以耐受。     

全脑照射联合局部放疗治疗小细胞肺癌脑转移疗效观察

研究显示,小细胞肺癌脑转移发生率为20％-25％,患者预后较差,姑息性手术或放疗是其主要治疗方法,三维适形放疗（3D-CRT）是常用治疗手段。2002年1月-2006年6月,我院采用全脑照射（PCI）联合3D—CRT治疗小细胞肺癌脑转移,疗效较好。现报告如下。     

全脑放疗联合靶向药物与单独全脑放疗治疗非小细胞肺癌脑转移疗效及安全性的Meta分析

目的采用Meta分析比较全脑放疗(WBRT)联合靶向药物与单用WBRT在非小细胞肺癌(NSCLC)脑转移瘤患者治疗中的疗效和安全性。方法计算机检索Pubmed、Embase、中国知网、万方数据库中有关WBRT联合靶向药物治疗NSCLC脑转移的文献,检索时间均从建库至2016年5月。通过纽卡斯尔-渥太华量表(NOS)对文献进行质量评价,采用优势比(OR)及其95%可信区间合并效应量,采用Rev Man5.2软件进行数据分析。结果最终纳入15篇研究文献,共计1 084例患者。结果显示:联合治疗组疾病控制率(OR:3.09,95%CI 2.11~4.54,P0.00001)、1年生存率(OR:2.55,95%CI 1.84~3.54,P0.00001)均高于单纯放疗组,差异具有明显统计学意义;安全性方面,联合治疗组皮疹发生率高于单纯放疗组(OR:9.10,95%CI 2.89~28.66,P=0.0002),但均属于Ⅰ~Ⅱ度不良反应,经对症处理后可缓解,其余不良反应如腹泻、恶心呕吐、乏力、骨髓抑制、呼吸困难两组比较均无统计学意义(P0.05)。结论WBRT联合靶向药物治疗NSCLC脑转移瘤明显优于单纯WBRT放疗,不良反应亦无明显增加。     

厄洛替尼联合全脑放疗治疗非小细胞肺癌脑转移的疗效及预后观察

目的观察厄洛替尼联合全脑放疗治疗非小细胞肺癌脑转移的疗效及预后。方法选取2013-05~2015-07该院收治的非小细胞肺癌脑转移患者90例,随机分为对照组和观察组,各45例。对照组采用全脑放疗治疗,共2周,总剂量为30 Gy/10 Fx。观察组在放疗的基础上联合厄洛替尼150 mg/d,共2周。对比两组临床疗效、预后情况及不良反应发生率。结果观察组完全缓解3例,部分缓解25例,稳定13例,进展4例。对照组完全缓解1例,部分缓解16例,稳定11例,进展17例。观察组临床疗效优于对照组(P0.01)。观察组平均生存时间及生存率均明显高于对照组,差异有统计学意义(P0.05)。两组患者不良反应发生率比较,差异无统计学意义(P0.05)。结论厄洛替尼联合全脑放疗治疗非小细胞肺癌脑转移临床效果显著,可有效控制肿瘤的生长,抑制肿瘤增殖,同时具有较高的安全性,对延长患者的生存时间、提高生存率具有重要的作用,值得临床应用推广。     

非小细胞肺癌脑转移治疗进展

<正>肺癌是威胁人类健康的主要疾病之一,发病率死亡率较高[1]。非小细胞肺癌(non-small-cell lung cancer,NSCLC)占了肺癌的80%～85%[2]。80%左右的肺癌患者死于肿瘤的远处转移扩散[3-4]。晚期NSCL脑转移发生率高达30%～40%左右,一旦出现预后极差,未经治疗的中位总生存期(median overall survival,m OS)约1～3个月[5],1年生存率约10%～20%[6]。影响脑转移预后的因素有很多,如年龄、体力状态(performance status,PS)评分、脑转移个数、原发灶是否控制、中枢外是否转移等;因此,如何对肺癌脑转移患者进行及时有效的诊治具有重要意义。本文对NSCLC脑转移综合诊治的最新进展做一综述。     

非小细胞肺癌脑转移综合治疗进展

脑部是肺癌最常见的远处转移器官之一,是导致肺癌治疗失败的常见原因。近年来,随着肺癌发病率的上升,以及各种诊疗技术的进步,肺癌脑转移的发生呈逐年上升趋势,有文献报道其发生率为25．4％-65．0％,占脑转移癌的40％-60％。     

非小细胞肺癌脑转移的治疗进展

<正>非小细胞肺癌(NSCLC)约占肺癌的80%〔1,2〕,5年生存率仅为15.6%,约2/3患者就诊时已发生区域或远处转移〔3〕。其中,首诊NSCLC的患者约有10%伴有脑转移;初诊没有脑转移的NSCLC患者也有30%~50%最终发生脑转移〔4〕,其预后极差,未经治疗患者的中位生存期(MST)仅1~2个月。随着影像学技术的进步、治疗手段的发展及各种靶向药物的应用,生     

非小细胞肺癌脑转移放化疗联合的疗效观察

目的比较非小细胞肺癌脑转移同步放化疗及序贯放化疗的近期疗效和1年生存率。方法同步放化组:脑放疗36GY后给予顺铂为主的方案化疗。序贯放化组:脑放疗结束后序贯顺铂为主的方案化疗。结果两组的脑转移灶及胸部原发灶的有效率均无统计学差异(P0.05);1年生存率分别为83.3%及79.4%(P0.05);中位PFS分别为13.8个月及11.2个月;中位生存时间(OS)分别为19.5个月及16.5个月。骨髓抑制、恶心呕吐和头晕头痛发生率分别为90%、100%、100%及76.4%、91.2%、97.1%。结论非小细胞肺癌脑转移同步放化疗比较序贯放化疗,前者的近期疗效及1年生存率均有升高的趋势,且毒副反应可耐受。     

对于非小细胞肺癌脑转移的综述

本文主要综述非小细胞肺癌脑转移预后的影响因素及一些外科手术等治疗方法对非小细胞肺癌脑转移的作用;探讨了局部的晚期非小细胞肺癌脑转移在预防性全脑照射的临床意义。同时,我院分析了251例患者在我院进行综合学科的治疗结果,为今后非小细胞肺癌脑转移治疗提供借鉴。     

晚期非小细胞肺癌脑转移的靶向治疗

脑转移是非小细胞肺癌(NSCLC)常见的转移部位,出现脑转移的患者生活质量下降,预后不佳.目前脑转移的主要治疗方式为全脑放疗,常规化疗对脑转移治疗效果不佳.近期多个个案报道和小规模的回顾性研究发现以吉非替尼和厄洛替尼为代表的表皮生长因子受体-酪氨酸激酶抑制剂对NSCLC脑转移体现出良好治疗效果.特别是对于存在表皮生长因子受体基因突变的患者,效果更加显著.提示该类药物可能是治疗NSCLC脑转移的一个好选择.     

Perihippocampal failure after hippocampal-avoidance whole-brain radiotherapy in cancer patients with brain metastases: Results of a retrospective analysis

Perihippocampal failure is a rare clinical scenario in brain metastatic cancer patients following hippocampal-avoidance (HA) whole-brain radiotherapy (HA-WBRT). The clinical features have not been fully identified because clinical data on intracranial failure after HA-WBRT are limited. It is thus necessary to accumulate clinical data.We retrospectively analyzed cancer patients with brain metastases who were diagnosed between January 2014 and September 2020 at a regional referral hospital. The medical records of patients who underwent HA-WBRT were reviewed. The clinical features of intracranial recurrence were described. Dosimetry parameters were compared in terms of deviation from the recommended protocol of the Radiation Therapy Oncology Report 0933.Twenty-four eligible patients with brain metastases who underwent HA-WBRT were identified; 13 (54%) were male. Seventeen patients (71%) had lung cancer, 6 (25%) had breast cancer, and 1 (4%) had liver cancer. The median overall survival was 12 months. Three patients developed intracranial failure during clinical follow-up, and 2 relapsed with intracranial failure in the perihippocampal region at 13 and 22 months, respectively. The perihippocampal failure rate was about 8%. One patient with small cell lung cancer received HA-prophylactic cranial irradiation; the minimum and maximum doses to the hippocampi were 6.8 and 10.7 Gy, respectively. Another patient with brain metastases from lung adenocarcinoma received HA-WBRT; the minimum and maximum doses to the hippocampi were 5.4 and 10.6 Gy, respectively.We reported unusual cases of intracranial failure in the perihippocampal region following HA-WBRT. Perihippocampal failure could be attributed to an under-dose of radiation partially or be resulted from aggressiveness of cancer per se. Further research on this topic is encouraged.     

厄洛替尼联合放疗在肺腺癌脑转移中的疗效观察

目的观察厄洛替尼联合脑部放疗在肺腺癌患者中的疗效、不良反应和生存率。方法回顾性分析我院2008年1月-2011年1月113例EGFR敏感突变的肺癌腺癌脑转移患者,比较单纯口服厄洛替尼药物治疗(A组)、单纯接受脑部放疗(B组)、联合厄洛替尼口服及脑部放疗(C组)三种治疗方法患者的骨髓抑制程度、胃肠道反应、皮疹程度、中位生存期、以及1年、2年、3年生存率。结果所有研究对象至治疗第3月末复查头颅MRI或全身PET/CT检查评价疗效,A组为:CR 2例、PR 14例;1年、2年、3年生存率为39.5%、23.2%、18.6%;中位生存期14.5月;B组为:CR 4例、PR 15例;1年、2年、3年生存率为47.4%、26.3%、5.3%;中位生存期11月;C组为:CR 4例、PR 14例;1年、2年、3年生存率为50%、31.3%、18.8%;中位生存期18.5月;各组主要不良反应为骨髓抑制、恶心呕吐、腹泻、皮疹,均在可控制范围。C组同A、B组比较,除中位生存期明显延长外(P0.05、P0.01),其余指标无明显变化,具有统计学意义。结论厄洛替尼联合放疗治疗EGFR敏感突变的肺腺癌脑转移患者可明显延长生存期,改善生活质量,且毒副反应轻。     

非小细胞肺癌脑转移的预后因素分析

目的探讨影响非小细胞肺癌脑转移治疗效果的预后因素。方法收集2006年3月-2009年3月在我科接受全脑放射治疗的57例非小细胞肺癌脑转移患者的临床资料,分析影响生存预后的各种因素。结果平均生存期可达到(9.7±2.8)个月。脑转移放疗后复发再次放疗组生存期(11.5月)优于复发后未放疗组(8.7月),无肺、骨转移组生存期(10.1月)优于有肺、骨转移组(8.5月),有显著统计学差异(P0.05)。多因素分析结果显示:脑转移放疗后复发再次放疗,同步放化疗和无肺、骨转移是肺癌脑转移患者的独立预后因素(P0.05)。结论影响非小细胞肺癌脑转移患者预后的主要因素是有无肺内、骨转移、是否采用同步放化疗,脑转移复发后是否再次放疗,选择同步放化疗以及对于脑转移放疗后复发的患者选择再次放疗的治疗方式,可以延长生存。     

非小细胞肺癌脑转移同步放化疗疗效分析

目的总结非小细胞肺癌脑转移患者的治疗效果。方法回顾性分析2005年1月～2007年12月我科对56例NSCLC脑转移患者采用放化疗同步治疗的近期疗效及副反应。结果非小细胞肺癌脑转移同步放化疗近期疗效较好,中位生存期12月,1年生存率50%。结论同步放化疗有较好的协同作用,延长了患者的生存时间,提高了生存质量。     

射波刀治疗非小细胞肺癌脑转移近期疗效分析

目的观察射波刀治疗肺癌脑转移的近期疗效。方法收集2011年5月—2013年12月非小细胞肺癌脑转移行射波刀治疗的患者21例,脑转移放射剂量为低分次照射3.50~8.50 Gy/次,1~10次,中位值5次,总剂量5.50~35.00 Gy,中位值24.00 Gy,生物等效剂量15.72~48.00 Gy。结果治疗1个月后,临床症状改善率90.4%;治疗3个月后,临床有效率为71.0%,局部控制率为86.8%。患者治疗3个月后的神经功能损失评分下降、日常生活能力量表评分上升(P均0.05)。结论射波刀治疗肺癌脑转移患者能有效提高其生存率和肿瘤局部控制率,减轻不良反应,改善生活质量,是一种有效的治疗方法。     

Efficacy and safety of apatinib combined with whole-brain radiation therapy with a simultaneous integrated boost for brain metastases from non-small cell lung cancer: a multicenter retrospective study

BackgroundBrain metastases (BMs) develop in 20–65% of non-small cell lung cancer (NSCLC) patients and are associated with a poor prognosis. Apatinib, a tyrosine kinase inhibitor (TKI) that selectively inhibits the vascular endothelial growth factor receptor 2, is safe and significantly prolongs the survival of chemotherapy-refractory gastric cancer patients. This retrospective study evaluated the safety and efficacy of apatinib combined with concurrent brain radiotherapy in NSCLC patients with BMs.MethodsThis trial enrolled patients with non-recurrent BM from histologically-confirmed NSCLC without any limits regarding the BM size/quantity. Eligibility criteria were patients 18–75 years old with measurable BM from histologically-confirmed NSCLC (including both newly-diagnosed and previously treated NSCLC) and expected survival time greater than 3 months. Oral apatinib (500 or 250 mg/day) was started within 1 week prior to commencing whole brain radiotherapy with simultaneous integrated boost (WBRT-SIB) and continued until one week after radiotherapy completion. In addition to toxicities, analyzed outcomes included intracranial overall response rate (iORR), intracranial disease control rate (iDCR), intracranial progression free survival (iPFS), and overall survival (OS).ResultsFrom July 2016 to January 2020, 16 patients were enrolled in this retrospective study. After 3 months of brain radiotherapy, the iORR was 75%, the iDCR was 100%, and the brain edema index (EI) was significantly reduced compared to that before brain radiation therapy (4.2 vs. 1.9; P=0.02). The median iPFS was 16.5 months [95% confidence interval (CI): 15.1–37.4 months]. The median OS was 26 months (95% CI: 17.0–54.0 months). Most of the patients tolerated apatinib well, but 7 patients had side effects, most commonly grade 1 or 2. Only 2 patients experienced grade 3 adverse events (hypertension and oral mucositis), and no grade 4 or 5 toxicities were observed.ConclusionsApatinib combined with WBRT-SIB appears to be safe and effective in treating BMs in NSCLC patients.     

Combination of immunotherapy and radiotherapy in the treatment of brain metastases from non-small cell lung cancer

It was commonly assumed in the past that blood-brain barrier could efficiently prohibit penetration of large peptide molecules, such as monoclonal antibodies, including programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors. This belief has been recently revised by studies that demonstrate the presence of functional lymphatic vessels lining the dural sinuses. Furthermore, the activated circulating T cells have been shown to cross the blood-brain barrier. Such observations created strong rationale for attempts of immunotherapy for patients with brain metastases, used either alone or in combination with radiotherapy. The expected benefit from immunotherapy particularly refers to patients without targetable “driver” mutations who are not considered as candidates for novel targeted therapies. Current inference on efficacy and safety of combination of immunotherapy and radiotherapy in the treatment of brain metastases from non-small cell lung cancer (NSCLC) origins, in most, from the retrospective studies. The existing data suggest that use of immune checkpoint inhibitors (ICIs) with brain radiotherapy improves patients outcome, compared to brain radiotherapy alone. The available data also suggest that concurrent use of ICI and stereotactic radiation therapy (SRT) for brain metastases from NSCLC is tolerable and appears more effective than sequential combination of radiotherapy and ICI. Use of steroids appeared detrimental. Since a dependence between the risk of adverse events and type of ICI therapy as well as tumor pathology was found, further studies are required to establish optimal dosage, selection of drugs and sequence of ICI and brain radiotherapy in patients with brain metastases from NSCLC.     

171例肺癌脑转移的治疗与预后

目的回顾性分析171例肺癌脑转移的治疗,探讨其疗效及预后因素。方法收集2001年3月至2008年10月我科171例肺癌脑转移患者的资料。所有病例均采用了放射治疗,全脑放疗DT30~40Gy/10~20f,肿瘤数目≤2个者局部加量至DT56~60Gy/25~30f。其中103例接受放化联合治疗。生存率计算采用Kaplan-Meier法,生存差异比较采用Log-rank检验,多因素分析采用Cox比例风险模型。结果全组患者中位生存期8.6个月。1年和2年生存率分别为28.7%、9.4%。多因素分析表明:颅外有无转移性病灶、脑转移灶数目和是否合并化疗是患者的独立预后因素。结论肺癌发生脑转移后应用放射治疗可减轻患者临床症状,延长生命。颅外有无转移性病灶、脑转移灶数目和是否合并化疗可作为患者的预后因素。     

48例非小细胞肺癌再程放疗临床探究

目的探究非小细胞肺癌再程放疗的临床效果。方法收集我院非小细胞肺癌复发48例,再次放疗距初次放疗时间为19.1±8.6周。分为观察组与对照组,观察组患者进行辅助化疗1～6周期后给予再程放疗,对照组只进行辅助化疗,观察患者的存活率。结果观察组的患者治疗三个月后复查胸部CT,CR2例;PR17例;SD为3例;PD为2例,有效率为70.8%,远高于对照组。48例中1年生存率63%,中位生存时间为10.5个月。接受再程放疗的患者均有较高的存活率。结论再程放疗能较安全地应用于非小细胞肺癌,疗效较好,不良反应较轻,值得进一步推广应用。     

Successful treatment of 2 patients with brain metastases from non-small cell lung cancer with epidermal growth factor receptor mutation receiving dacomitinib: A case report

Rationale:Approximately 20% of patients with non-small cell lung cancer (NSCLC) are diagnosed with brain metastasis, which is related to poor survival outcomes. The ability of tyrosine kinase inhibitor drugs to penetrate the blood–brain barrier makes them a potential option for intracranial metastases. Dacomitinib, an irreversible second-generation pan-HER tyrosine kinase inhibitor, has become a standard therapy for patients with epidermal growth factor receptor mutations. However, its efficacy in patients with brain metastases (BMs) is not yet established. Here, we present 2 patients with epidermal growth factor receptor-mutant NSCLC with brain metastasis. After initiation of dacomitinib as first-line treatment, a significant clinical response was achieved, and a long-lasting complete remission was achieved in 1 patient up to this date.Patient concern:Case 1 was a 47-year-old man who was admittedtothe hospital because of recurrent cough and expectoration for >1 year. Chest computed tomography scans revealed a high-density shadow in the left upper lobe. Cranial magnetic resonance imaging indicated an abnormal nodular enhancement in the right cerebellar hemisphere. Case 2 was a 55-year-old man with a chief complaint of intermittent cough and expectoration for >1 month. Chest computed tomography revealed a high-density mass in the left superior lobe. Magnetic resonance imaging of the central nervous system revealed 2 abnormal nodular enhancements in the left frontal lobe.Diagnosis:Both patients were diagnosed with lung adenocarcinoma by bronchoscopy and lymph node biopsy.Interventions:Both patients received dacomitinib 30 mg once daily as first-line therapy for 8 and 11 months, respectively until disease progression.Outcome:After treatment with dacomitinib, both patients achieved complete response in BMs. Progression-free survival was 11 and 8 months, respectively.Lessons:Dacomitinib strongly controlled BMs in patients with advanced NSCLC, and the adverse reactions were tolerable. Dacomitinib may be considered a new treatment option for these patients. Further prospective studies are recommended to confirm this conclusion.