Department of Radiation Oncology, Winship Cancer Institute of Emory University, Atlanta, Georgia.
Department of Biostatistics and Bioinformatics, Winship Cancer Institute of Emory University, Atlanta, Georgia.
Cancer. 2017 Oct 1;123(19):3681-3690. doi: 10.1002/cncr.30794. Epub 2017 Jun 13.
Genetic aberrations are well characterized in lung adenocarcinomas (LACs) and clinical outcomes have been influenced by targeted therapies in the advanced setting. Stereotactic body radiotherapy (SBRT) is the standard-of-care therapy for patients with nonoperable, early-stage LAC, but to the authors' knowledge, no information is available regarding the impact of genomic changes in these patients. The current study sought to determine the frequency and clinical impact of genetic aberrations in this population.
Under an Institutional Review Board-approved protocol, the records of 242 consecutive patients with early-stage lung cancers were reviewed; inclusion criteria included LAC histology with an adequate tumor sample for the successful use of next-generation sequencing and fluorescence in situ hybridization testing. Univariate analysis was performed to identify factors associated with clinical outcomes.
LAC samples from 98 of the 242 patients were reviewed (40.5%), of whom 45 patients (46.0%) had genetic testing. The following mutations were noted: KRAS in 20.0% of samples, BRAF in 2.2% of samples, SMAD family member 4 (SMAD4) in 4.4% of samples, epidermal growth factor receptor (EGFR) in 15.6% of samples, STK1 in 2.2% of samples, tumor protein 53 (TP53) in 15.6% of samples, and phosphatase and tensin homolog (PTEN) in 2.2% of samples. The following gene rearrangements were observed: anaplastic lymphoma kinase (ALK) in 8.9% of samples, RET in 2.2% of samples, and MET amplification in 17.8% of samples. The median total delivered SBRT dose was 50 grays (range, 48-60 grays) over a median of 5 fractions (range, 3-8 fractions). The KRAS mutation was associated with worse local control (odds ratio [OR], 3.64; P<.05). MET amplification was associated with worse regional (OR, 4.64; P<.05) and distant (OR, 3.73; P<.05) disease control.
To the authors' knowledge, the current series is the first to quantify genetic mutations and their association with clinical outcomes in patients with early-stage LAC treated with SBRT. KRAS mutations were associated with worse local control and MET amplification was associated with worse regional and distant disease control, findings that need to be validated in a prospective setting. Cancer 2017;123:3681-3690. © 2017 American Cancer Society.
肺腺癌（LAC）中存在明显的遗传异常，并且在晚期靶向治疗中影响了临床结果。立体定向体部放射治疗（SBRT）是不可手术的早期 LAC 患者的标准治疗方法，但据作者所知，尚无关于这些患者中基因组变化影响的信息。本研究旨在确定该人群中遗传异常的频率和临床影响。
根据机构审查委员会批准的方案，对 242 例连续早期肺癌患者的记录进行了回顾；纳入标准包括 LAC 组织学和足够的肿瘤样本，以成功使用下一代测序和荧光原位杂交检测。进行单因素分析以确定与临床结果相关的因素。
对 242 例患者中的 98 例 LAC 样本进行了回顾（40.5％），其中 45 例患者（46.0％）进行了基因检测。注意到以下突变：KRAS 在 20.0％的样本中，BRAF 在 2.2％的样本中，SMAD 家族成员 4（SMAD4）在 4.4％的样本中，表皮生长因子受体（EGFR）在 15.6％的样本中，STK1 在 2.2％的样本中，肿瘤蛋白 53（TP53）在 15.6％的样本中，磷酸酶和张力蛋白同源物（PTEN）在 2.2％的样本中。观察到以下基因重排：间变性淋巴瘤激酶（ALK）在 8.9％的样本中，RET 在 2.2％的样本中，MET 扩增在 17.8％的样本中。中位总 SBRT 剂量为 50 戈瑞（范围，48-60 戈瑞），中位 5 个分数（范围，3-8 个分数）。KRAS 突变与局部控制不良相关（优势比[OR]，3.64；P<.05）。MET 扩增与局部（OR，4.64；P<.05）和远处（OR，3.73；P<.05）疾病控制不良相关。
据作者所知，目前的系列研究首次量化了早期接受 SBRT 治疗的 LAC 患者的基因突变及其与临床结果的关联。KRAS 突变与局部控制不良相关，而 MET 扩增与局部和远处疾病控制不良相关，这些发现需要在前瞻性研究中进行验证。癌症 2017;123:3681-3690。©2017 美国癌症协会。
