title: Relapse in medulloblastoma: what can be done after abandoning high-dose chemotherapy? A mono-institutional experience.
abstract: OBJECTIVE
  We retrospectively report strategies used for medulloblastoma patients progressing after craniospinal irradiation where we aimed for: symptom control, a satisfactory quality of life, accrual in phase 1-2 trials, when available, and the first two conditions could no longer be satisfied by already experienced second-line strategies.
  
  
  METHODS
  Surgery was used in cases of doubtful relapse or when only one site was affected. Radiotherapy was given whenever possible, especially to relieve symptoms. The main chemotherapy regimens were oral temozolomide/etoposide, intravenous (iv.) cisplatin/etoposide, iv. gemcitabine/oxaliplatin, an oral sonic hedgehog pathway inhibitor and oral melphalan.
  
  
  RESULTS
  Between 1998 and 2011, we treated 18 patients relapsed after median 20 months. Nine had relapsed locally, four had dissemination, three single metastases, and two had one synchronous local and metastatic recurrence. Responses to chemotherapy were seen in 32% of cases. The median hospital stay for treatments/complications was 19 days. The 1- and 3-year progression-free survival (PFS) rates were 28 ± 10% and 0%, respectively, for OS, they were 44 ± 12% and 22 ± 10% but no patient was cured. The median PFS after a first relapse was 7 months (range 1-29); the median OS was 7 months (range 4-44). No patients died due to treatment toxicity. Late recurrence (more than 1-2 years after diagnosis) and involvement of single sites were favorable prognostic factors.
  
  
  CONCLUSIONS
  Without succeeding in patients cure, we ensured them further treatment with short hospital stay thus affording low personal and social costs. The chances of cure may emerge from tailored therapies according to genetic stratification.
authors.affiliation: Pediatric Oncology Unit, Fond. IRCCS Istituto Nazionale dei Tumori, Milano, Via Venezian, 1-20133, Milan, Italy. maura.massimino@istitutotumori.mi.it.
authors.forename: Maura
authors.initials: M
authors.lastname: Massimino
authors.affiliation: Pediatric Oncology Unit, Fond. IRCCS Istituto Nazionale dei Tumori, Milano, Via Venezian, 1-20133, Milan, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Casanova
authors.affiliation: Pediatric Oncology Unit, Fond. IRCCS Istituto Nazionale dei Tumori, Milano, Via Venezian, 1-20133, Milan, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Polastri
authors.affiliation: Pediatric Oncology Unit, Fond. IRCCS Istituto Nazionale dei Tumori, Milano, Via Venezian, 1-20133, Milan, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Biassoni
authors.affiliation: Genetics Unit, Ospedale S.Anna, Como, Italy.
authors.forename: Piergiorgio
authors.initials: P
authors.lastname: Modena
authors.affiliation: Radiotherapy Unit, Fond. IRCCS Istituto Nazionale dei Tumori, Milano, Milan, Italy.
authors.forename: Emilia
authors.initials: E
authors.lastname: Pecori
authors.affiliation: Pediatric Oncology Unit, Fond. IRCCS Istituto Nazionale dei Tumori, Milano, Via Venezian, 1-20133, Milan, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Schiavello
authors.affiliation: Pediatric Oncology Unit, Fond. IRCCS Istituto Nazionale dei Tumori, Milano, Via Venezian, 1-20133, Milan, Italy.
authors.forename: Marco Vajna
authors.initials: MV
authors.lastname: De Pava
authors.affiliation: Pediatric Oncology Unit, Fond. IRCCS Istituto Nazionale dei Tumori, Milano, Via Venezian, 1-20133, Milan, Italy.
authors.forename: Alice
authors.initials: A
authors.lastname: Indini
authors.affiliation: Neurosurgery Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milano, Milan, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Rampini
authors.affiliation: Department of Pathology, San Paolo Hospital and Department of Health Sciences, University of Milano, Milan, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Bauer
authors.affiliation: Pediatric Oncology Unit, Fond. IRCCS Istituto Nazionale dei Tumori, Milano, Via Venezian, 1-20133, Milan, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Catania
authors.affiliation: Pediatric Oncology Unit, Fond. IRCCS Istituto Nazionale dei Tumori, Milano, Via Venezian, 1-20133, Milan, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Podda
authors.affiliation: Radiotherapy Unit, Fond. IRCCS Istituto Nazionale dei Tumori, Milano, Milan, Italy.
authors.forename: Lorenza
authors.initials: L
authors.lastname: Gandola
mesh_terms: D061605:Administration, Intravenous; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000628:therapy; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D002528:Cerebellar Neoplasms / Q000628:therapy*; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000008:administration & dosage; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D016371:Cranial Irradiation / Q000379:methods*; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018450:Disease Progression; D018572:Disease-Free Survival; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008527:Medulloblastoma / Q000628:therapy*; D008558:Melphalan / Q000008:administration & dosage; D009364:Neoplasm Recurrence, Local / Q000628:therapy*; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D018579:Patient Selection; D011788:Quality of Life; D011878:Radiotherapy / Q000379:methods; D012189:Retrospective Studies; D016879:Salvage Therapy; D000077204:Temozolomide; D055815:Young Adult; D000093542:Gemcitabine
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D005047:Etoposide; D000077146:Irinotecan; D003606:Dacarbazine; D002945:Cisplatin; D008558:Melphalan; D002166:Camptothecin; D000077204:Temozolomide; D000093542:Gemcitabine
keywords: Childhood brain tumors; Dissemination; Hospital stay; Medulloblastoma; Treatment toxicity