Naito Yoichi, Takahashi Hideaki, Shitara Kohei, Okamoto Wataru, Bando Hideaki, Kuwata Takeshi, Kuboki Yasutoshi, Matsumoto Shingo, Miki Izumi, Yamanaka Takeharu, Watanabe Atsushi, Kojima Motohiro
National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577, Japan.
Yokohama City University, Kanagawa, Japan.
Jpn J Clin Oncol. 2018 Jun 1;48(6):559-564. doi: 10.1093/jjco/hyy052.
To confirm the feasibility and explore the clinical applicability of amplicon sequencing by next generation sequencing (NGS) of biopsy samples from patients with advanced solid tumors, we conducted a prospective study.
Patients with unresectable, advanced, or recurrent solid tumors were included. Key eligibility criteria were as follows: 20 years or older, any planned systemic therapy, adequate lesion for biopsy, and written informed consent. Samples were fixed in 10% buffered formalin and embedded in paraffin. Cancer-derived DNA was extracted, and amplicon sequencing was performed using Ion AmpliseqTM Cancer Hotspot Panel version 1.0 or version 2.0 by central vendor. We evaluated the success rate of sequencing, and the proportion of the patients with actionable mutations. We organized an expert panel to share the results of targeted sequence, make annotations and reports, and discuss concomitant ethical/legal/social issues.
A total of 232 patients were included, and 208 were successfully analyzed (success rate of 89.7%). The biopsy procedures were safe, with only one case of Grade 3 vasovagal reaction. The proportion of actionable/druggable mutations was 38.9% (81/208), which was not significantly different between the cancer panel version 1.0 and version 2.0 (P = 0.476). Expert panel could discuss the findings and make sufficient reports.
We confirmed the feasibility of NGS-based amplicon sequencing using biopsy samples, making the basis for nationwide genome screening for cancer patients using biopsy samples. Our results suggest that focused panel may be sufficient to detect major mutations.
为了证实对晚期实体瘤患者活检样本进行二代测序（NGS）的扩增子测序的可行性，并探索其临床适用性，我们开展了一项前瞻性研究。
纳入不可切除、晚期或复发性实体瘤患者。关键纳入标准如下：年龄20岁及以上、任何计划进行的全身治疗、有足够的活检病变组织且签署书面知情同意书。样本用10%中性福尔马林固定并石蜡包埋。提取肿瘤来源的DNA，并由中心供应商使用Ion AmpliseqTM癌症热点Panel 1.0版或2.0版进行扩增子测序。我们评估了测序成功率以及具有可操作突变的患者比例。我们组建了一个专家小组来分享靶向测序结果、进行注释和报告，并讨论相关的伦理/法律/社会问题。
共纳入232例患者，其中208例成功分析（成功率89.7%）。活检操作安全，仅1例出现3级血管迷走神经反应。可操作/可用药突变的比例为38.9%（81/208），癌症Panel 1.0版和2.0版之间无显著差异（P = 0.476）。专家小组能够讨论研究结果并做出充分报告。
我们证实了使用活检样本进行基于NGS的扩增子测序的可行性，为使用活检样本对癌症患者进行全国范围的基因组筛查奠定了基础。我们的结果表明，针对性的Panel可能足以检测主要突变。
