Fibroblast growth factor receptor 1 (FGFR1) copy number is an independent prognostic factor in non-small cell lung cancer

Fibroblast growth factor receptor 1 (FGFR1) is an oncogene that can potentially be targeted by tyrosine kinase inhibitors. We aimed to investigate the prevalence and prognostic significance of alterations in FGFR1 copy number in non-small cell lung cancer (NSCLC). FGFR1 status was evaluated by chromogenic silver in situ hybridisation (ISH) in tissue microarray sections from a retrospective cohort of 304 surgically resected NSCLCs and results were correlated with the clinicopathological features and overall survival. High FGFR1 gene copy number (amplification or high-level polysomy) was significantly more frequent in squamous cell carcinomas (SCC) (24.8%) and large cell carcinomas (LCC) (25%) compared to adenocarcinomas (11.3%) (p = 0.01 and p = 0.03 respectively). Among NSCLC there was no significant correlation between FGFR1-positive status and other clinicopathological features including age, gender, smoking history, tumour size, lymph node status, stage, grade, vascular, lymphatic or perineural invasion. FGFR1-positive patients showed a tendency to longer overall survival in univariate analysis (p = 0.14). Multivariate survival analysis using Cox regression model confirmed FGFR1-positive patients had a significant reduction in the risk of death compared to FGFR1-negative patients (HR 0.6; p = 0.02). High FGFR1 gene copy number is a common finding in SCC and LCC and is an independent favourable prognostic factor.     

Erlotinib therapy in a patient with non-small-cell lung cancer and brain metastases

Brain metastases are a common occurrence and a major cause of mortality in non-small-cell lung cancer, with few systemic treatment options. Although targeting epidermal growth factor receptor-associated tyrosine kinase with erlotinib and gefitinib results in durable responses in some patients, the activity of these drugs against brain metastases has been poorly documented. In particular, few reports have so far reported the activity of erlotinib in this setting. Here we report the case of a male Italian smoker with an adeno-carcinoma of the lung whose lung cancer and brain metastases have both responded to erlotinib.     

Mutually exclusive FGFR2, HER2, and KRAS gene amplifications in gastric cancer revealed by multicolour FISH

Gastric cancer (GC) is a major cause of global cancer mortality. Previous genomic studies have reported that several RTK-RAS pathway components are amplified in GC, with individual tumours often amplifying one component and not others (“mutual exclusivity”). Here, we sought to validate these findings for three RTK/RAS components (FGFR2, HER2, KRAS) using fluorescence in situ hybridisation (FISH) on a series of gastric tumours, cell lines and patient-derived xenografts. Applying dual-colour FISH on 137 gastric tumours (89 FFPE surgical resections and 48 diagnostic biopsies), we observed FGFR2 amplification in 7.3% and HER2 amplification in 2.2% of GCs. GCs exhibiting FGFR2 amplification were associated with high tumour grade (p = 0.034). In FISH positive tumours, striking differences in copy number levels between cancer cells in the same tumour were observed, suggesting intra-tumour heterogeneity. Using a multicolour FISH assay allowing simultaneous detection of FGFR2, HER2, and KRAS amplifications, we confirmed that these components exhibited a mutually exclusive pattern of gene amplification across patients. The FISH data were also strongly correlated with Q-PCR levels and at the protein level by immunohistochemistry. Our data confirm that RTK/RAS components are mutually exclusively amplified in GC, and demonstrate the feasibility of identifying multiple aneuploidies using a single FISH assay. Application of this assay to GC samples, particularly diagnostic biopsies, may facilitate enrollment of GC patients into clinical trials evaluating RTK/RAS directed therapies. However, the presence of intra-tumour heterogeneity may require multiple biopsy samples to be obtained per patient before a definitive diagnosis can be attained.     

SIMULTANEOUS THORACO－CRANIAL OPERATION FOR THE TREATMENT OF LUNG CANCER WITH BRAIN METASTASES

ＳＩＭＵＬＴＡＮＥＯＵＳＴＨＯＲＡＣＯ－ＣＲＡＮＩＡＬＯＰＥＲＡＴＩＯＮＦＯＲＴＨＥＴＲＥＡＴＭＥＮＴＯＦＬＵＮＧＣＡＮＣＥＲＷＩＴＨＢＲＡＩＮＭＥＴＡＳＴＡＳＥＳＣｈｅｎＪｉａｎ陈建；ＬｉｕＤａｏｋｕｎ刘道坤；ＬｉｕＪｕｎｈｕａ刘俊华；ＳｈｉＺｈｏ...     

抗血管生成药物治疗肺癌脑转移的研究新进展

晚期肺癌脑转移发生率高,预后差.近年来,随着肺癌总体治疗的发展,为晚期肺癌脑转移提供了更多的治疗手段和期待.目前的临床研究提示抗血管生成药物在肺癌脑转移的治疗中占有重要地位,从大分子的单克隆抗体,到泛靶点抗血管药物,再到小分子酪氨酸激酶抑制剂(Tyrosine kinase inhibitor,TKI),均显示出一定的...     

HTP方案联合全脑放疗治疗肺癌脑转移的临床观察

目的:评价羟基喜树碱、替尼泊甙和顺铂组成的HTP方案联合全脑放疗治疗肺癌脑转移的有效性和安全性。方法:34例肺癌脑转移患者,采取化疗-放疗-化疗的治疗顺序,即先接受HTP方案化疗2周期,第2周期化疗结束后休息2周,接受全脑放疗;放疗结束后休息2周,化疗有效和稳定的患者继续接受原方案化疗2~4周期。HTP方案具体用法为:羟基喜树碱(HCPT)6~8mg/d,静脉滴注,d1~d5;替尼泊甙(VM-26)100mg/d,静脉滴注,d1~d4;顺铂(PDD)20mg/d静脉滴注d1~d5。注意血象和造血细胞因子支持。每4周重复。放射治疗采用6MV-X线全脑照射,2Gy/次,每日1次,每周5日,DT30~46Gy。每2周期化疗结束行疗效评价。结果:完成化疗-放疗-化疗的患者共30例,客观CR0例,PR14例,SD12例,PD4例,有效率(CR PR)为46.7%,疾病控制率(CR PR SD)为86.7%。而单纯颅内病灶评价为:CR4例,PR21例,SD5例,PD0例,有效率(CR PR)为83.3%。20例伴神经系统症状者,完成化疗-放疗-化疗后,19例患者症状得到缓解,15例患者一般状况得到明显改善(KPS评分提高≥20分)。肿瘤进展时间(TTP)为2~32个月,中位TTP为7个月;总生存期(OS)为5~49个月,中位生存期(MST)为10个月。骨髓抑制和脱发是主要不良反应。结论:HTP方案联合全脑放疗对肺癌脑转移具有较好的疗效,生存期得到延长,值得进一步观察研究。     

拓扑替康联合顺铂治疗肺癌脑转移28例临床观察

目的:观察拓扑替康(TPT)联合顺铂(PDD)治疗肺癌脑转移的疗效与毒性。方法:28例患者分别接受5天用药或每周用药方案化疗2~6周期。16例患者接受TPT1·2mg/m2,第1~5天;12例患者接受TPT2·5mg/m2,第1、8、15天;均联合PDD25mg/m2,第1~3天,28天为1周期。按WHO标准评价疗效及不良反应。结果:28例中无完全缓解,部分缓解(PR)11例(39·3%),稳定(SD)10例(35·7%)和进展(PD)7例(25·0%)。中位疾病进展时间为5·2个月,中位生存时间为8·7个月。结论:TPT联合PDD治疗肺癌脑转移患者效果肯定,毒副反应能够耐受,值得进一步推广使用并深入探讨。     

肺癌脑转移中国治疗指南(2021年版)

肺癌患者脑转移发生率高、预后差、自然生存时间短。近年来,随着外科手术、放射治疗和内科治疗水平的不断提高,肺癌脑转移患者的治疗选择越来越多,生存时间得以延长。为了及时反映国内外肺癌脑转移治疗的新进展,进一步提高肺癌脑转移患者的规范化治疗水平,中国医师协会肿瘤医师分会和中国医疗保健国际交流促进会肿瘤内科分会组织专家编写了《肺癌脑转移中国治疗指南(2021年版)》,以供临床医师参考。     

肺癌脑转移患者化疗配合放疗的临床研究

目的　比较化疗配合放疗与单纯放疗治疗肺癌脑转移的疗效、生存时间及不良反应。方法　将1 999年 8月～ 2 0 0 2年 2月间所治疗的 82例多发性脑转移患者随机分为单纯放疗组 (放疗组 4 4例 )和放化疗综合组 (综合组 38例 )进行治疗。放疗组 :全脑常规放疗 (30～ 4 0 )Gy/ (3～4 .5 )周。综合组 :放疗方法与单纯放疗组相同 ,在放疗前后或放疗同时进行 3～ 4周期化疗。化疗则采用EP方案或MVP方案 ,均 2 1天至 2 8天重复。结果　完成治疗且可评估共有 78例 (放疗组 4 3例 ,综合组 35例 )。放疗组和综合治疗组总有效率分别为 83.5 % (37/ 4 3例 )和 85 .7% (30 / 35例 ) ,P >0 .0 5。治疗后中位生存时间 :放疗组为 5 .1月 ,综合组为 7.3月 ;一年生存率 :放疗组 9.3% (4 / 4 3) ,综合组 2 5 .7% (9/ 35 )。两组中位生存期及一年生存率均有显著差异性 (P <0 .0 5 )。综合组的胃肠道反应及骨髓抑制高于放疗组 ,但大多数患者均能耐受。     

Systemic treatments for brain metastases from breast cancer,non-small cell lung cancer,melanoma and renal cell carcinoma: An overview of the literature

The frequency of metastatic brain tumors has increased over recent years; the primary tumors most involved are breast cancer, lung cancer, melanoma and renal cell carcinoma. While radiation therapy and surgery remain the mainstay treatment in selected patients, new molecular drugs have been developed for brain metastases. Studies so far report interesting results.     

Activity of pemetrexed against brain metastases in a patient with adenocarcinoma of the lung

A 53-year-old woman was with adenocarcinoma of the lung metastatic to the brain was treated after several lines of chemotherapy with pemetrexed. After six cycles an impressive regression of the brain metastases was documented.A brief review of the literature on response of cerebral metastases to chemotherapy is added.     

Spectrum of gene mutations detected by next generation exome sequencing in brain metastases of lung adenocarcinoma

BackgroundBrain metastases (BM) are a life-threatening complication. We aimed to analyse gene mutations in lung adenocarcinoma BM.MethodsWe performed next generation sequencing (NGS) of a pre-defined set of 48 cancer-related genes in a cohort of 76 neurosurgical lung adenocarcinoma BM specimens using a cancer specific gene panel on the MiSeq platform (Illumina, San Diego, CA). NGS results were statistically correlated to patient characteristics. Data on ALK, ROS1, MET and FGFR1 gene status assessed by FISH were available from previous studies in the majority of patients.ResultsTwenty-nine (60.4%) of the 48 investigated cancer-related genes were mutated in at least one BM sample and 64 (84.2%) of the 76 BM samples carried at least one mutated gene. The number of mutated genes per sample ranged from 0 to 9 (median 2). The most commonly mutated genes were TP53, KRAS and CDKN2A, which were affected in 35/76 (46.1%), 29/76 (38.2%) and 17/76 (22.4%) samples, respectively. Other potentially druggable alterations included EGFR mutations (3/76, 3.9% of samples), PIK3CA mutation (2/76, 2.6%), BRAF mutation (1/76, 1.3%) and SMO mutation (1/76, 1.3%). Presence of KRAS mutations was associated with positive smoking history (p = 0.015, Chi square test) and presence of EGFR mutation correlated with unfavourable overall survival time from BM diagnosis (p = 0.019, log rank test).ConclusionsDeleterious gene mutations, some of them with potential therapeutic implications, are found in a high fraction of lung adenocarcinoma BM.     

Bub1在食管鳞状细胞癌组织和正常食管黏膜的表达及临床意义

目的：观察Bub1 mRNA及Bub1蛋白在食管鳞状细胞癌和正常食管黏膜组织中的表达差别,探讨Bub1在食管鳞状细胞癌发生、发展中的作用及其临床意义。方法：收集40例食管鳞状细胞癌标本及相应的食管切缘正常黏膜组织,利用免疫组化染色及原位杂交技术检测Bub1蛋白和Bub1 mRNA在食管鳞状细胞癌组织和正常食管黏膜组织中的表达。结果：与正常黏膜组织相比较,Bub1 mRNA及Bub1蛋白在食管鳞状细胞癌组织中表达水平明显降低（P〈0.005）,且Bub1 mRNA及Bub1蛋白的表达水平与食管鳞状细胞癌分化程度及有无淋巴结转移相关（P〈0.05）。结论：Bub1表达水平高低可能与食管鳞状细胞癌的发生发展及淋巴结转移具有一定关系。     

非小细胞肺癌伴脑转移患者TKI联合放疗研究进展

NSCLC患者易发生脑转移,治疗方法多样。酪氨酸激酶抑制剂(TKI)的广泛使用使得携带表皮生长因子受体(EGFR)基因突变的患者的生存得到显著延长。本文总结近年来有关TKI与NSCLC脑转移治疗的相关文献,探讨TKI与放疗联合的治疗模式。     

不同EGFR突变肺腺癌脑转移患者WBRT分析

目的 探讨肺腺癌脑转移患者不同EGFR突变状态WBRT疗效差别。方法 回顾分析2010—2015年在本院诊治的89例肺腺癌脑转移患者,所有患者均行EGFR检测。脑转移一线6 MV X线外照射:WBRT30 Gy分10次或40 Gy分20次(≤3个脑转移灶IMRT同步加量40~45 Gy分10次或50~60 Gy分20次)。比较EGFR突变和野生型患者的有效率、IPFS、OS。Kaplan-Meier法计算IPFS、OS并Logrank检验和单因素分析,Cox模型多因素分析。结果 89例患者总有效率为62%,中位IPFS为7.0个月(95%CI为6.060~7.940),中位OS为12.0个月(95%CI为9.539~14.465)。单因素和多因素分析结果显示脑转移患者有效率与KPS评分、EGFR突变状态相关(P=0.009、0.035),KPS评分、EGFR突变状态是IPFS的影响因素(P=0.048、0.000),KPS评分、原发灶控制是OS的影响因素(P=0.000、0.031)。结论 肺腺癌脑转移患者WBRT后,EGFR突变较野生型有效率高,IPFS时间长,OS无差别。     

Bub1在食管鳞状细胞癌组织和正常食管黏膜的表达及临床意义

目的:观察Bub1 mRNA及Bub1蛋白在食管鳞状细胞癌和正常食管黏膜组织中的表达差别,探讨Bub1在食管鳞状细胞癌发生、发展中的作用及其临床意义。方法:收集40例食管鳞状细胞癌标本及相应的食管切缘正常黏膜组织,利用免疫组化染色及原位杂交技术检测Bub1蛋白和Bub1 mRNA在食管鳞状细胞癌组织和正常食管黏膜组织中的表达。结果:与正常黏膜组织相比较,Bub1 mRNA及Bub1蛋白在食管鳞状细胞癌组织中表达水平明显降低(P<0.005),且Bub1 mRNA及Bub1蛋白的表达水平与食管鳞状细胞癌分化程度及有无淋巴结转移相关(P<0.05)。结论:Bub1表达水平高低可能与食管鳞状细胞癌的发生发展及淋巴结转移具有一定关系。     

乳腺癌脑转移的信号通路和分子机制的研究进展

乳腺癌是女性发病率较高的癌症之一,经常发生转移的部位是肺、骨、肝脏和中枢神经系统,其中中枢神经系统转移的发生率大约为15%.目前已知乳腺癌发生脑转移的信号通路可能有Wnt和Notch通路、EGFR和PTEN通路,与乳腺癌脑转移相关的受体可能有VEGF和STAT3、微管蛋白和TOP2A、BNC1、GALNT9、CCDC8、HER2、HER3、MMP、FBPS、肌氨酸等.本文对可能导致乳腺癌脑转移的信号通路和分子机制进行综述,希望为乳腺癌脑转移的靶向治疗提供新的思路.     

Long-term survival following concurrent chemoradiotherapy in patients with non-small-cell lung cancer with concomitant brain metastases only

We report two patients with non-small-cell lung cancer (NSCLC) with concomitant metastases to the brain only who received chemotherapy with concurrent radiotherapy for the thoracic disease and brain disease, resulting in long-term survival. One patient was a 56-year-old woman who was diagnosed as having adenocarcinoma and showed T2N1 thoracic disease; the other patient was a 57-year-old man diagnosed with squamous cell carcinoma who had T1N3 thoracic disease. Both patients demonstrated multiple metastases to the brain only. Chemotherapy, consisting of cisplatin (40mg/m²) and docetaxel (40mg/m²), was administered on days 1 and 8, with the drugs being given separately, and the chemotherapy was repeated every 4 weeks for up to three cycles. Whole-brain irradiation (2Gy/day; total, 36Gy) and thoracic irradiation (2Gy/day; total, 60Gy) were started on days 1 and 29, respectively. Toxicities encountered were manageable by conventional therapy. The concurrent chemoradiation therapy resulted in complete regression of the brain disease in both patients. Brain disease relapsed in the female patient, but it is being controlled by the administration of gefitinib. She has survived for 53 months since the start of treatment, without new metastatic lesions or relapse of the thoracic lesions. The male patient has survived for 37 months without new metastatic lesions or relapses. Concurrent chemoradiotherapy in which radiotherapy is applied to both the brain and thoracic lesions may be effective for patients with NSCLC with metastases to the brain only.