Department of Pathology, Brigham & Women's Hospital, Boston, Massachusetts 02115-6110, USA.
J Thorac Oncol. 2013 Jul;8(7):823-59. doi: 10.1097/JTO.0b013e318290868f.
To establish evidence-based recommendations for the molecular analysis of lung cancers that are that are required to guide EGFR- and ALK-directed therapies, addressing which patients and samples should be tested, and when and how testing should be performed.
Three cochairs without conflicts of interest were selected, one from each of the 3 sponsoring professional societies: College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology. Writing and advisory panels were constituted from additional experts from these societies.
Three unbiased literature searches of electronic databases were performed to capture articles published published from January 2004 through February 2012, yielding 1533 articles whose abstracts were screened to identify 521 pertinent articles that were then reviewed in detail for their relevance to the recommendations. Evidence was formally graded for each recommendation.
Initial recommendations were formulated by the cochairs and panel members at a public meeting. Each guideline section was assigned to at least 2 panelists. Drafts were circulated to the writing panel (version 1), advisory panel (version 2), and the public (version 3) before submission (version 4).
The 37 guideline items address 14 subjects, including 15 recommendations (evidence grade A/B). The major recommendations are to use testing for EGFR mutations and ALK fusions to guide patient selection for therapy with an epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) inhibitor, respectively, in all patients with advanced-stage adenocarcinoma, regardless of sex, race, smoking history, or other clinical risk factors, and to prioritize EGFR and ALK testing over other molecular predictive tests. As scientific discoveries and clinical practice outpace the completion of randomized clinical trials, evidence-based guidelines developed by expert practitioners are vital for communicating emerging clinical standards. Already, new treatments targeting genetic alterations in other, less common driver oncogenes are being evaluated in lung cancer, and testing for these may be addressed in future versions of these guidelines.
制定针对需要指导 EGFR 和 ALK 靶向治疗的肺癌的分子分析的循证建议，解决应测试哪些患者和样本，以及何时以及如何进行测试。
从三个赞助专业协会（美国病理学家学院、国际肺癌研究协会和分子病理学会）中各选出一位无利益冲突的三位联合主席。还从这些协会的其他专家中组成了写作和咨询小组。
进行了三次针对电子数据库的无偏见文献搜索，以捕获 2004 年 1 月至 2012 年 2 月期间发表的文章，共获得 1533 篇文章，对其摘要进行筛选以确定 521 篇相关文章，然后详细审查这些文章与建议的相关性。为每个建议正式分级证据。
联合主席和小组成员在公开会议上制定初步建议。每个指南部分至少分配给 2 名小组成员。草案在提交前分发给写作小组（第 1 版）、咨询小组（第 2 版）和公众（第 3 版）（第 4 版）。
这 37 条指南项目涉及 14 个主题，包括 15 条建议（证据等级 A/B）。主要建议是在所有晚期腺癌患者中，无论性别、种族、吸烟史或其他临床危险因素如何，分别使用 EGFR 突变和 ALK 融合测试来指导表皮生长因子受体（EGFR）或间变性淋巴瘤激酶（ALK）抑制剂的治疗选择，并将 EGFR 和 ALK 测试优先于其他分子预测测试。随着科学发现和临床实践的发展超过随机临床试验的完成，由专家从业者制定的循证指南对于传达新兴的临床标准至关重要。针对其他较少见驱动致癌基因的遗传改变的新治疗方法正在肺癌中进行评估，这些测试可能会在这些指南的未来版本中得到解决。
