Asao Tetsuhiko, Fujiwara Yutaka, Sunami Kuniko, Kitahara Shinsuke, Goto Yasushi, Kanda Shintaro, Horinouchi Hidehito, Nokihara Hiroshi, Yamamoto Noboru, Ichikawa Hitoshi, Kohno Takashi, Tsuta Koji, Watanabe Shun-ichi, Takahashi Kazuhisa, Ohe Yuichiro
Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan; Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
Lung Cancer. 2016 Mar;93:77-81. doi: 10.1016/j.lungcan.2016.01.004. Epub 2016 Jan 11.
Thymic carcinoma is a rare neoplasm of the thymus, and information regarding its genetic profile and optimal medical treatment is limited. We sought to characterize the genetic profile of thymic carcinoma and to evaluate the efficacy of various medical treatments, including treatment with tyrosine kinase inhibitors (TKIs), cytotoxic agents, and immune checkpoint inhibitors.
We retrospectively reviewed medical records of 64 consecutive patients with thymic carcinoma at the National Cancer Center Hospital between April 1973 and March 2014. We analyzed treatment course of patients who underwent medical treatment involving investigational drugs. For patients with available tissue samples, targeted sequencing of 50 cancer-related genes using next-generation sequencing was performed.
Thirty-six patients had received chemotherapy. Median progression-free survival in patients receiving first-line chemotherapy was 7.07 months (95% confidence interval, 5.67-8.93). Median survival time was 32.6 months (95% confidence interval, 23.2-43.4). As second- or later-line chemotherapy, a total of 13 patients were treated with 24 investigational drugs, including 8 multi-targeted TKIs, 5 cytotoxic agents, and 2 immune checkpoint inhibitors. Six (24%) of the patients treated with investigational drugs maintained disease control for at least 6 months. Tissue samples of 52 patients (81.3%) were available for targeted sequencing, consisting of 52 formalin-fixed, paraffin-embedded (FFPE) and 16 fresh frozen tissue samples. The genetic alterations of TP53, KRAS, FBXW7, and NRAS were detected in 7 patients (13.5%), and no KIT mutations were noted.
Multi-targeted TKIs exhibited potential clinical efficacy for previously-treated thymic carcinoma. The frequency of genetic alterations in this study was low, with no apparent relationship with the efficacy of chemotherapy.
胸腺癌是一种罕见的胸腺肿瘤，关于其基因特征和最佳医学治疗的信息有限。我们试图描述胸腺癌的基因特征，并评估各种医学治疗方法的疗效，包括酪氨酸激酶抑制剂（TKIs）、细胞毒性药物和免疫检查点抑制剂的治疗效果。
我们回顾性分析了1973年4月至2014年3月期间国立癌症中心医院连续64例胸腺癌患者的病历。我们分析了接受含研究性药物治疗的患者的治疗过程。对于有可用组织样本的患者，使用下一代测序对50个癌症相关基因进行靶向测序。
36例患者接受了化疗。接受一线化疗的患者的无进展生存期中位数为7.07个月（95%置信区间，5.67 - 8.93）。总生存期中位数为32.6个月（95%置信区间，23.2 - 43.4）。作为二线或后续化疗，共有13例患者接受了24种研究性药物治疗，包括8种多靶点TKIs、5种细胞毒性药物和2种免疫检查点抑制剂。接受研究性药物治疗的患者中有6例（24%）维持疾病控制至少6个月。52例患者（81.3%）的组织样本可用于靶向测序，包括52份福尔马林固定石蜡包埋（FFPE）样本和16份新鲜冷冻组织样本。7例患者（13.5%）检测到TP53、KRAS、FBXW7和NRAS的基因改变，未发现KIT突变。
多靶点TKIs对既往治疗过的胸腺癌显示出潜在的临床疗效。本研究中基因改变的频率较低，与化疗疗效无明显关系。
