Anurag Mehta, Mumtaz Saifi, Ullas Batra, M Suryavanshi, Kush Gupta
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The study was conducted according to the ethical principles stated in the latest version of the Declaration of Helsinki and the applicable guidelines for good clinical practice. Clinical characteristics and treatment details were collected from patients' medical records.</p><p><strong>Results: </strong>A total of 709 stage IV NSCLC adenocarcinoma patients were included in the study. There were 457 (64.46%) men and 252 (35.54%) women, with a median age of 60 years. <i>ROS1</i>-gene rearrangement was positive in 20 (2.82%) cases, 13 using Fluorescent In-Situ Hybridization (FISH), and two and five cases, respectively, using immunohistochemistry (IHC) and next-generation sequencing (NGS), followed by confirmation with FISH. Fourteen of the 20 patients with <i>ROS1</i>-gene rearrangement received crizotinib therapy, with an objective response rate of 64.28%. At a median follow-up of 6 months, the study had not achieved the end points of median progression free survival and overall survival.</p><p><strong>Conclusion: </strong><i>ROS1</i>-gene rearrangement was present at a relatively higher frequency of 2.8% in north Indian patients with lung adenocarcinoma and was successfully targeted by crizotinib therapy. Although the only US Food and Drug Administration and Conformité Européenne approved method for testing <i>ROS1</i> rearrangement is NGS, FISH alone or IHC with D4D6 antibody as initial screen with subsequent confirmation of IHC-positive cases by FISH are cost-effective methods in institutions lacking NGS facilities.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":5.1000,"publicationDate":"2020-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d1/97/lctt-11-19.PMC7047993.pdf","citationCount":"0","resultStr":"{\"title\":\"Incidence of <i>ROS1</i>-Rearranged Non-Small-Cell Lung Carcinoma in India and Efficacy of Crizotinib in Lung Adenocarcinoma Patients.\",\"authors\":\"Anurag Mehta, Mumtaz Saifi, Ullas Batra, M Suryavanshi, Kush Gupta\",\"doi\":\"10.2147/LCTT.S244366\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The <i>ROS1</i> gene is a member of the \\\"sevenless\\\" subfamily of tyrosine-kinase insulin-receptor genes. <i>ROS1</i>-fusion rearrangement causes constitutive downstream signal transduction, with an oncogenic role in non-small-cell lung carcinoma (NSCLC). Fortunately, crizotinib, an ALK1 tyrosine-kinase inhibitor, provides long-term disease control. The objective of this molecular epidemiological study was to estimate the frequency of <i>ROS1</i> rearrangements and evaluate treatment outcomes with crizotinib therapy.</p><p><strong>Methods: </strong>Patients with stage IV NSCLC adenocarcinoma histology were considered for this study. The study was conducted according to the ethical principles stated in the latest version of the Declaration of Helsinki and the applicable guidelines for good clinical practice. Clinical characteristics and treatment details were collected from patients' medical records.</p><p><strong>Results: </strong>A total of 709 stage IV NSCLC adenocarcinoma patients were included in the study. There were 457 (64.46%) men and 252 (35.54%) women, with a median age of 60 years. <i>ROS1</i>-gene rearrangement was positive in 20 (2.82%) cases, 13 using Fluorescent In-Situ Hybridization (FISH), and two and five cases, respectively, using immunohistochemistry (IHC) and next-generation sequencing (NGS), followed by confirmation with FISH. Fourteen of the 20 patients with <i>ROS1</i>-gene rearrangement received crizotinib therapy, with an objective response rate of 64.28%. At a median follow-up of 6 months, the study had not achieved the end points of median progression free survival and overall survival.</p><p><strong>Conclusion: </strong><i>ROS1</i>-gene rearrangement was present at a relatively higher frequency of 2.8% in north Indian patients with lung adenocarcinoma and was successfully targeted by crizotinib therapy. 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引用次数: 0
摘要
背景:ROS1 基因是酪氨酸激酶胰岛素受体基因 "无七 "亚家族的成员。ROS1融合重排会导致构成性下游信号转导,在非小细胞肺癌(NSCLC)中具有致癌作用。幸运的是,ALK1 酪氨酸激酶抑制剂克唑替尼能长期控制病情。这项分子流行病学研究旨在估算ROS1重排的频率,并评估克唑替尼疗法的治疗效果:本研究考虑了组织学为 IV 期 NSCLC 腺癌的患者。研究按照最新版《赫尔辛基宣言》中规定的伦理原则和适用的良好临床实践指南进行。临床特征和治疗细节均从患者病历中收集:研究共纳入了 709 例 IV 期 NSCLC 腺癌患者。其中男性 457 例(64.46%),女性 252 例(35.54%),中位年龄为 60 岁。20例(2.82%)ROS1基因重排阳性,其中13例采用荧光原位杂交(FISH),2例和5例分别采用免疫组化(IHC)和下一代测序(NGS),然后用FISH确认。20例ROS1基因重排患者中有14例接受了克唑替尼治疗,客观反应率为64.28%。在中位随访6个月时,该研究未达到中位无进展生存期和总生存期的终点:结论:ROS1基因重排在北印度肺腺癌患者中出现的频率相对较高,为2.8%,克唑替尼疗法成功地靶向了这一基因重排。虽然美国食品药品管理局和欧洲合格评定委员会批准的唯一检测 ROS1 基因重排的方法是 NGS,但在缺乏 NGS 设备的机构中,仅用 FISH 或用 D4D6 抗体进行 IHC 初步筛查,然后用 FISH 确认 IHC 阳性病例是具有成本效益的方法。
Incidence of ROS1-Rearranged Non-Small-Cell Lung Carcinoma in India and Efficacy of Crizotinib in Lung Adenocarcinoma Patients.
Background: The ROS1 gene is a member of the "sevenless" subfamily of tyrosine-kinase insulin-receptor genes. ROS1-fusion rearrangement causes constitutive downstream signal transduction, with an oncogenic role in non-small-cell lung carcinoma (NSCLC). Fortunately, crizotinib, an ALK1 tyrosine-kinase inhibitor, provides long-term disease control. The objective of this molecular epidemiological study was to estimate the frequency of ROS1 rearrangements and evaluate treatment outcomes with crizotinib therapy.
Methods: Patients with stage IV NSCLC adenocarcinoma histology were considered for this study. The study was conducted according to the ethical principles stated in the latest version of the Declaration of Helsinki and the applicable guidelines for good clinical practice. Clinical characteristics and treatment details were collected from patients' medical records.
Results: A total of 709 stage IV NSCLC adenocarcinoma patients were included in the study. There were 457 (64.46%) men and 252 (35.54%) women, with a median age of 60 years. ROS1-gene rearrangement was positive in 20 (2.82%) cases, 13 using Fluorescent In-Situ Hybridization (FISH), and two and five cases, respectively, using immunohistochemistry (IHC) and next-generation sequencing (NGS), followed by confirmation with FISH. Fourteen of the 20 patients with ROS1-gene rearrangement received crizotinib therapy, with an objective response rate of 64.28%. At a median follow-up of 6 months, the study had not achieved the end points of median progression free survival and overall survival.
Conclusion: ROS1-gene rearrangement was present at a relatively higher frequency of 2.8% in north Indian patients with lung adenocarcinoma and was successfully targeted by crizotinib therapy. Although the only US Food and Drug Administration and Conformité Européenne approved method for testing ROS1 rearrangement is NGS, FISH alone or IHC with D4D6 antibody as initial screen with subsequent confirmation of IHC-positive cases by FISH are cost-effective methods in institutions lacking NGS facilities.