Tetsuhiko Asao1, Yutaka Fujiwara2, Kuniko Sunami3, Shinsuke Kitahara3, Yasushi Goto3, Shintaro Kanda3, Hidehito Horinouchi3, Hiroshi Nokihara3, Noboru Yamamoto3, Hitoshi Ichikawa4, Takashi Kohno5, Koji Tsuta6, Shun-ichi Watanabe7, Kazuhisa Takahashi8, Yuichiro Ohe3. 1. Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan; Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan. 2. Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan. Electronic address: yutakafu@ncc.go.jp. 3. Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan. 4. Division of Genomics, National Cancer Center Research Institute, Tokyo, Japan. 5. Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan. 6. Department of Pathology, National Cancer Center Hospital, Tokyo, Japan; Department of Clinical Sciences and Laboratory Medicine, Kansai Medical University, Moriguchi, Japan. 7. Department of Thoracic Surgery, National Cancer Center Hospital, Tokyo, Japan. 8. Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.