Hyperfractionated Versus Conventional Radiotherapy Followed by Chemotherapy in Standard-Risk Medulloblastoma: Results From the Randomized Multicenter HIT-SIOP PNET 4 Trial

• Published in: JOURNAL OF CLINICAL ONCOLOGY Vol. 30; no. 26; pp. 3187 - 3193
• Main Authors: Lannering, Birgitta, Rutkowski, Stefan, Doz, Francois, Pizer, Barry, Gustafsson, Göran, Navajas, Aurora, Massimino, Maura, Reddingius, Roel, Benesch, Martin, Carrie, Christian, Taylor, Roger, Gandola, Lorenza, Björk-Eriksson, Thomas, Giralt, Jordi, Oldenburger, Foppe, Pietsch, Torsten, Figarella-Branger, Dominique, Robson, Keith, Forni, Marco, Clifford, Steven C., Warmuth-Metz, Monica, von Hoff, Katja, Faldum, Andreas, Mosseri, Véronique, Kortmann, Rolf
• Format: Journal Article Publication
• Language: English
• Published: Alexandria, VA American Society of Clinical Oncology 10.09.2012
• Subjects: Adolescent; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Cancer and Oncology; Cancer och onkologi; Cerebellar Neoplasms - radiotherapy; Chemotherapy, Adjuvant; Child; Child, Preschool; Combined Modality Therapy; Cranial Irradiation; Disease-Free Survival; Dose Fractionation, Radiation; Female; Hearing Loss - etiology; Humans; Male; Medical sciences; Medulloblastoma - radiotherapy; Neurology; Radiotherapy, Adjuvant; Recurrence; Survival Rate; Tumors; Tumors of the nervous system. Phacomatoses; Nervous system diseases; Multicenter study; Malignant tumor; Radiotherapy; Standards; Cerebral disorder; Chemotherapy; Randomization; Cancerology; Treatment; Medulloblastoma; Central nervous system disease; Risk factor; Clinical trial; Comparative study; Cancer
• ISSN: 0732-183X; 1527-7755; 1527-7755
• DOI: 10.1200/JCO.2011.39.8719

To compare event-free survival (EFS), overall survival (OS), pattern of relapse, and hearing loss in children with standard-risk medulloblastoma treated by postoperative hyperfractionated or conventionally fractionated radiotherapy followed by maintenance chemotherapy. In all, 340 children age 4 to 21 years from 122 European centers were postoperatively staged and randomly assigned to treatment with hyperfractionated radiotherapy (HFRT) or standard (conventional) fractionated radiotherapy (STRT) followed by a common chemotherapy regimen consisting of eight cycles of cisplatin, lomustine, and vincristine. After a median follow-up of 4.8 years (range, 0.1 to 8.3 years), survival rates were not significantly different between the two treatment arms: 5-year EFS was 77% ± 4% in the STRT group and 78% ± 4% in the HFRT group; corresponding 5-year OS was 87% ± 3% and 85% ± 3%, respectively. A postoperative residual tumor of more than 1.5 cm(2) was the strongest negative prognostic factor. EFS of children with all reference assessments and no large residual tumor was 82% ± 2% at 5 years. Patients with a delay of more than 7 weeks to the start of RT had a worse prognosis. Severe hearing loss was not significantly different for the two treatment arms at follow-up. In this large randomized European study, which enrolled patients with standard-risk medulloblastoma from more than 100 centers, excellent survival rates were achieved in patients without a large postoperative residual tumor and without RT treatment delays. EFS and OS for HFRT was not superior to STRT, which therefore remains standard of care in this disease.