title: Salvage Treatment with Intracerebrospinal Fluid Thiotepa in Patients with Leptomeningeal Metastasis After Failure of Methotrexate-based Treatment.
abstract: OBJECTIVE
  To evaluate the efficacy of intracerebrospinal fluid (intra-CSF) thiotepa in patients with leptomeningeal metastasis (LM) after failure of a methotrexate-based treatment.
  
  
  METHODS
  We retrospectively reviewed the medical records of patients with LM who received 10 mg of intra-CSF thiotepa twice a week.
  
  
  RESULTS
  Out of 40 patients, 25 were females (63%), and 31 (78%) had an Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2. Fourteen out of the 30 evaluable patients (47%) had a cytological response to intra-CSF thiotepa. The median overall survival (OS) after treatment with thiotepa was 19.4 weeks (95% confidence interval (CI)=15.3-23.5). Grade 3 toxicities were thrombocytopenia (N=2), bacterial meningitis (N=2), and pneumonia (N=1). According to a multivariate analysis, an ECOG PS ≥2 (hazard ratio (HR)=5.11, 95% CI=1.39-18.80, p=0.014), clinical improvement (HR=0.09, 95% CI=0.03-0.29, p<0.001), and radiation for LM after intra-CSF thiotepa (HR=0.33, 95% CI=0.11-0.97, p=0.043) were independently associated with survival.
  
  
  CONCLUSIONS
  Intra-CSF thiotepa seems to be a meaningful salvage treatment for patients with LM whose disease progresses after a methotrexate-based treatment.
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea Department of Internal Medicine, School of Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Kyoung-Min
authors.initials: KM
authors.lastname: Cho
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
authors.forename: Yu Jung
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
authors.forename: Se Hyun
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
authors.forename: Jin Won
authors.initials: JW
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
authors.forename: Jeong-Ok
authors.initials: JO
authors.lastname: Lee
authors.affiliation: Department of Neurosurgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
authors.forename: Jung Ho
authors.initials: JH
authors.lastname: Han
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
authors.forename: Keun-Wook
authors.initials: KW
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
authors.forename: Jee Hyun
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Neurosurgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
authors.forename: Chae-Yong
authors.initials: CY
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
authors.forename: Soo-Mee
authors.initials: SM
authors.lastname: Bang
authors.affiliation: Department of Radiation Oncology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
authors.forename: In-Ah
authors.initials: IA
authors.lastname: Kim
authors.affiliation: Department of Radiation Oncology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
authors.forename: Jae Sung
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea jslee0918@gmail.com.
authors.forename: Jong-Seok
authors.initials: JS
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007278:Injections, Spinal; D008297:Male; D008577:Meningeal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D008727:Methotrexate / Q000494:pharmacology*; D008875:Middle Aged; D009367:Neoplasm Staging; D009369:Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D012189:Retrospective Studies; D016879:Salvage Therapy; D015996:Survival Rate; D013852:Thiotepa / Q000627:therapeutic use*
chemical_list: D000964:Antimetabolites, Antineoplastic; D018906:Antineoplastic Agents, Alkylating; D013852:Thiotepa; D008727:Methotrexate
keywords: Leptomeningeal metastasis; intracerebrospinal fluid chemotherapy; methotrexate; thiotepa