Originally published as JCO Early Release 10.1200/JCO.2008.18.4176 on December 15 2008

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Gandola, L. Articles by Fossati-Bellani, F. Search for Related Content PubMed PubMed Citation Articles by Gandola, L. Articles by Fossati-Bellani, F. Social Bookmarking                            What's this?

Hyperfractionated Accelerated Radiotherapy in the Milan Strategy for Metastatic Medulloblastoma

Lorenza Gandola, Maura Massimino, Graziella Cefalo, Carlo Solero, Filippo Spreafico, Emilia Pecori, Daria Riva, Paola Collini, Emanuele Pignoli, Felice Giangaspero, Roberto Luksch, Serena Berretta, Geraldina Poggi, Veronica Biassoni, Andrea Ferrari, Bianca Pollo, Claudio Favre, Iacopo Sardi, Monica Terenziani, Franca Fossati-Bellani

From the Radiotherapy, Pediatrics, Pathology, and Physics Units, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Nazionale Tumori; Neurosurgery Unit, Development Neurology Unit and Neuropathology Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Neurologico Carlo Besta, Milano; Neuropathology, Università La Sapienza, Roma and Istituto Neuromed, Pozzilli; Acquired Lesions Unit, Istituto Eugenio Medea, Bosisio Parini; Pediatric Oncology Unit, Ospedale S. Chiara, Pisa; and Pediatric Oncology Unit, Ospedale Meyer, Firenze, Italy.

Corresponding author: Maura Massimino, MD, Pediatrics Unit, Fondazione IRCCS Istituto Nazionale Tumori, Via Venezian 1, 20133 Milano, Italy; e-mail: maura.massimino{at}istitutotumori.mi.it.

Purpose With a view to improving the prognosis for patients with metastatic medulloblastoma, we tested the efficacy and toxicity of a hyperfractionated accelerated radiotherapy (HART) regimen delivered after intensive sequential chemotherapy.

Patients and Methods Between 1998 and 2007, 33 consecutive patients received postoperative methotrexate (8 g/m²), etoposide (2.4 g/m²), cyclophosphamide (4 g/m²), and carboplatin (0.8 g/m²) in a 2-month schedule, then HART with a maximal dose to the neuraxis of 39 Gy (1.3 Gy/fraction, 2 fractions/d) and a posterior fossa boost up to 60 Gy (1.5 Gy/fraction,2 fractions/d). Patients with persistent disseminated disease before HART were consolidated with two myeloablative courses and circulating progenitor cell rescue.

Results Patients were classified as having M1 (n = 9), M2 (n = 6), M3 (n = 17), and M4 (n = 1) disease. Seven patients younger than 10 years old who achieved complete response after chemotherapy received a lower dose to the neuraxis (31.2 Gy). Twenty-two of the 32 assessable patients responded to chemotherapy; disease was stable in five patients and progressed in five patients. One septic death occurred before radiotherapy. Eight patients experienced relapse after a median of 12 months. Fourteen of the 33 patients underwent consolidation therapy after HART. With a median 82-month survivor follow-up, the 5-year event-free, progression-free, and overall survival rates were 70%, 72%, and 73%, respectively. No severe clinical complications of HART have emerged so far.

Conclusion HART after intensive postoperative chemotherapy, followed by myeloablative chemotherapy in selected cases, proved feasible in children with metastatic medulloblastoma. The results of our treatment compare favorably with other series treated using conventional therapies.

L.G. and M.M. contributed equally to this work.

Supported in part by the Associazione Bianca Garavaglia (Busto Arsizio, Italy) and the Associazione Italiana per la Ricerca sul Cancro.

Presented in part at the 10th International Symposium on Pediatric Neuro-Oncology, June 9-12, 2002, London, United Kingdom; and at the XXXIV Meeting of the International Society of Paediatric Oncology, September 18-21, 2002, Porto, Portugal.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?