title: Correlation between S-1 treatment outcome and expression of biomarkers for refractory thymic carcinoma.
abstract: BACKGROUND
  Thymic carcinoma is a rare cancer with minimal evidence of a survival benefit following chemotherapy. An oral fluoropyrimidine of S-1, however, is the recommended active cytotoxic chemotherapy agent for refractory thymic carcinoma based on a case series, whereas sunitinib or everolimus are recommended as molecular-targeted agents based on Phase II trials. We retrospectively investigated the efficacy of S-1 for refractory thymic carcinoma and performed a biomarker analysis.
  
  
  METHODS
  We assessed the clinicopathological variables of 14 consecutive patients who underwent S-1 for refractory thymic carcinoma and correlated the clinical outcomes with potential biomarkers using paraffin-embedded cancer tissues of eight patients in the cohort.
  
  
  RESULTS
  A total of 178 thymic malignancies were identified, of whom 14 patients included 12 cases of squamous cell carcinoma, one lymphoepithelioma-like carcinoma, and one undifferentiated carcinoma. Six patients exhibited a partial response (42.9 %: 95 % confidence interval [CI], 21.4-67.4) and the disease control rate was 85.7 % (60.0-96.0 %). After a median follow-up of 24.2 months, the median progression-free survival was 8.1 months (range, 2.6-12.2 months), and median overall survival was 30.0 months (range, 6.2-41.9 months). No significant correlation between biomarker expression and response was noted. However, thymidine synthase (TS)/dihydropyrimidine dehydrogenase and TS/orotate phosphoribosyltransferase were observed.
  
  
  CONCLUSIONS
  S-1 for refractory thymic carcinoma offered clinical activity and achieved an 85 % disease control rate. Although the biomarkers did not correlate with clinical outcome, the study results showed efficacy of S-1 as a cytotoxic chemotherapy for refractory thymic carcinoma, which warrants future investigation.
authors.affiliation: Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital, 3-18-22 Honkomagome, Bunkyo, Tokyo, 113-8677, Japan. y-okuma@cick.jp.|Division of Oncology, Research Center for Medical Sciences, The Jikei University School of Medicine, Minato, Tokyo, Japan. y-okuma@cick.jp.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Okuma
authors.affiliation: Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital, 3-18-22 Honkomagome, Bunkyo, Tokyo, 113-8677, Japan. yhosomi@cick.jp.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Hosomi
authors.affiliation: Department of Clinical Oncology, Japan Red Cross Medical Center, Shibuya, Tokyo, Japan. aaa17580@pop06.odn.ne.jp.
authors.forename: Shingo
authors.initials: S
authors.lastname: Miyamoto
authors.affiliation: Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital, 3-18-22 Honkomagome, Bunkyo, Tokyo, 113-8677, Japan. mshibuya@cick.jp.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Shibuya
authors.affiliation: Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital, 3-18-22 Honkomagome, Bunkyo, Tokyo, 113-8677, Japan. tokamura@cick.jp.
authors.forename: Tatsuru
authors.initials: T
authors.lastname: Okamura
authors.affiliation: Department of Pathology, Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital, Bunkyo, Tokyo, Japan. hishima@cick.jp.
authors.forename: Tsunekazu
authors.initials: T
authors.lastname: Hishima
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D015415:Biomarkers; D018450:Disease Progression; D004338:Drug Combinations; D019008:Drug Resistance, Neoplasm; D005260:Female; D005500:Follow-Up Studies; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D010094:Oxonic Acid / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012008:Recurrence; D012189:Retrospective Studies; D005641:Tegafur / Q000627:therapeutic use*; D013953:Thymus Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000964:Antimetabolites, Antineoplastic; D015415:Biomarkers; D004338:Drug Combinations; D012333:RNA, Messenger; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid