title: Medical treatment involving investigational drugs and genetic profile of thymic carcinoma.
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.
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan; Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Tetsuhiko
authors.initials: T
authors.lastname: Asao
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan. Electronic address: yutakafu@ncc.go.jp.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Fujiwara
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Kuniko
authors.initials: K
authors.lastname: Sunami
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Kitahara
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Goto
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Kanda
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Hidehito
authors.initials: H
authors.lastname: Horinouchi
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nokihara
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Noboru
authors.initials: N
authors.lastname: Yamamoto
authors.affiliation: Division of Genomics, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ichikawa
authors.affiliation: Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kohno
authors.affiliation: Department of Pathology, National Cancer Center Hospital, Tokyo, Japan; Department of Clinical Sciences and Laboratory Medicine, Kansai Medical University, Moriguchi, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Tsuta
authors.affiliation: Department of Thoracic Surgery, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Shun-ichi
authors.initials: S
authors.lastname: Watanabe
authors.affiliation: Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Ohe
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers; D003131:Combined Modality Therapy; D004252:DNA Mutational Analysis; D015507:Drugs, Investigational / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D012189:Retrospective Studies; D013953:Thymus Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D015507:Drugs, Investigational
keywords: Chemotherapy; Genetic profile; Investigational drugs; Next-generation sequencing; Thymic carcinoma