title: Reduced-dose craniospinal radiotherapy followed by tandem high-dose chemotherapy and autologous stem cell transplantation in patients with high-risk medulloblastoma.
abstract: BACKGROUND
  We assessed the feasibility and effectiveness of reduced-dose craniospinal (CS) radiotherapy (RT) followed by tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/autoSCT) in reducing late adverse effects without jeopardizing survival among children with high-risk medulloblastoma (MB).
  
  
  METHODS
  From October 2005 through September 2010, twenty consecutive children aged >3 years with high-risk MB (presence of metastasis and/or postoperative residual tumor >1.5 cm(2)) were assigned to receive 2 cycles of pre-RT chemotherapy, CSRT (23.4 or 30.6 Gy) combined with local RT to the primary site (total 54.0 Gy), and 4 cycles of post-RT chemotherapy followed by tandem HDCT/autoSCT. Carboplatin-thiotepa-etoposide and cyclophosphamide-melphalan regimens were used for the first and second HDCT, respectively.
  
  
  RESULTS
  Of 20 patients with high-risk MB, 17 had metastatic disease and 3 had a postoperative residual tumor >1.5 cm(2) without metastasis. The tumor relapsed/progressed in 4 patients, and 2 patients died of toxicities during the second HDCT/autoSCT. Therefore, 14 patients remained event-free at a median follow-up of 46 months (range, 23-82) from diagnosis. The probability of 5-year event-free survival was 70.0% ± 10.3% for all patients and 70.6% ± 11.1% for patients with metastases. Late adverse effects evaluated at a median of 36 months (range, 12-68) after tandem HDCT/autoSCT were acceptable.
  
  
  CONCLUSIONS
  In children with high-risk MB, CSRT dose might be reduced when accompanied by tandem HDCT/autoSCT without jeopardizing survival. However, longer follow-up is needed to evaluate whether the benefits of reduced-dose CSRT outweigh the long-term risks of tandem HDCT/autoSCT.
authors.affiliation: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Ki Woong
authors.initials: KW
authors.lastname: Sung
authors.forename: Do Hoon
authors.initials: DH
authors.lastname: Lim
authors.forename: Meong Hi
authors.initials: MH
authors.lastname: Son
authors.forename: Soo Hyun
authors.initials: SH
authors.lastname: Lee
authors.forename: Keon Hee
authors.initials: KH
authors.lastname: Yoo
authors.forename: Hong Hoe
authors.initials: HH
authors.lastname: Koo
authors.forename: Ji Hye
authors.initials: JH
authors.lastname: Kim
authors.forename: Yeon-Lim
authors.initials: YL
authors.lastname: Suh
authors.forename: Yoo Sook
authors.initials: YS
authors.lastname: Joung
authors.forename: Hyung Jin
authors.initials: HJ
authors.lastname: Shin
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002528:Cerebellar Neoplasms / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D003520:Cyclophosphamide / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D060828:Induction Chemotherapy; D008297:Male; D008527:Medulloblastoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008558:Melphalan / Q000008:administration & dosage; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D011879:Radiotherapy Dosage; D012307:Risk Factors; D016879:Salvage Therapy; D033581:Stem Cell Transplantation; D015996:Survival Rate; D013852:Thiotepa / Q000008:administration & dosage; D014182:Transplantation, Autologous; D055815:Young Adult
chemical_list: D005047:Etoposide; D003520:Cyclophosphamide; D013852:Thiotepa; D016190:Carboplatin; D008558:Melphalan