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新西兰非小细胞肺癌中间变性淋巴瘤激酶(ALK)基因重排的筛查。

Screening for anaplastic lymphoma kinase (ALK) gene rearrangements in non-small-cell lung cancer in New Zealand.

机构信息

Department of Pharmacology and Clinical Pharmacology and the Auckland Cancer Society Research Centre Auckland, University of Auckland, Auckland, New Zealand.

Medical Oncology, Auckland City Hospital, Auckland, New Zealand.

出版信息

Intern Med J. 2020 Jun;50(6):716-725. doi: 10.1111/imj.14435.

Abstract

BACKGROUND

Lung cancer is a major cause of death in New Zealand. In recent years, targeted therapies have improved outcomes.

AIM

To determine the uptake of anaplastic lymphoma kinase (ALK) testing, and the prevalence, demographic profile and outcomes of ALK-positive non-small-cell lung cancer (NSCLC), in New Zealand, where no national ALK-testing guidelines or subsidised ALK tyrosine kinase inhibitor (TKI) therapies are available.

METHODS

A population-based observational study reviewed databases to identify patients presenting with non-squamous NSCLC over 6.5 years in northern New Zealand. We report the proportion tested for ALK gene rearrangements and the results. NSCLC samples tested by fluorescence in situ hybridisation were retested by next generation sequencing and ALK immunohistochemistry. A survival analysis compared ALK-positive patients treated or not treated with ALK TKI therapy.

RESULTS

From a total of 3130 patients diagnosed with non-squamous NSCLC, 407 (13%) were tested for ALK gene rearrangements, and patient selection was variable and inequitable. Among those tested, 34 (8.4%) had ALK-positive NSCLC. ALK-positive disease was more prevalent in younger versus older patients, non-smokers versus smokers and in Māori, Pacific or Asian ethnic groups than in New Zealand Europeans. Fluorescence in situ hybridisation, ALK immunohistochemistry and next generation sequencing showed broad concordance for detecting ALK-positive disease under local testing conditions. Among patients with ALK-positive metastatic NSCLC, those treated with ALK TKI survived markedly longer than those not treated with ALK TKI (median overall survival 5.12 vs 0.55 years).

CONCLUSION

Lung cancer outcomes in New Zealand may be improved by providing national guidelines and funding policy for ALK testing and access to subsidised ALK TKI therapy.

摘要

背景

肺癌是新西兰主要的死亡原因。近年来,靶向治疗改善了预后。

目的

确定间变性淋巴瘤激酶(ALK)检测的采用情况,以及在没有国家 ALK 检测指南或补贴 ALK 酪氨酸激酶抑制剂(TKI)治疗的情况下,新西兰 ALK 阳性非小细胞肺癌(NSCLC)的流行率、人口统计学特征和结局。

方法

一项基于人群的观察性研究回顾了数据库,以确定在新西兰北部 6.5 年内患有非鳞状 NSCLC 的患者。我们报告了接受 ALK 基因重排检测的比例和结果。通过荧光原位杂交检测的 NSCLC 样本通过下一代测序和 ALK 免疫组织化学进行了重新检测。生存分析比较了接受或未接受 ALK TKI 治疗的 ALK 阳性患者。

结果

在总共诊断出的 3130 名非鳞状 NSCLC 患者中,有 407 名(13%)接受了 ALK 基因重排检测,患者选择存在差异且不公平。在接受检测的患者中,有 34 名(8.4%)患有 ALK 阳性 NSCLC。与老年患者相比,ALK 阳性疾病在年轻患者中更为常见,在非吸烟者中比在吸烟者中更为常见,在毛利人、太平洋岛民或亚裔群体中比在新西兰欧洲人中更为常见。在当地检测条件下,ALK 阳性疾病的荧光原位杂交、ALK 免疫组织化学和下一代测序显示出广泛的一致性。在ALK 阳性转移性 NSCLC 患者中,接受 ALK TKI 治疗的患者的总生存期明显长于未接受 ALK TKI 治疗的患者(中位总生存期分别为 5.12 年和 0.55 年)。

结论

通过提供国家 ALK 检测指南和资金政策以及补贴 ALK TKI 治疗的途径,新西兰的肺癌预后可能会得到改善。

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