Background: A protocol for the intensive treatment of non-cerebellar PNET (CNS-PNET) combining chemotherapy and radiotherapy was launched in 2000. Efforts were subsequently made to improve the prognosis and to de-escalate the treatment for selected patient groups. Procedure: Twenty-eight consecutive patients were enrolled for a high-dose drug schedule (methotrexate, etoposide, cyclophosphamide, and carboplatin±vincristine), followed by hyperfractionated accelerated CSI (HART-CSI) at total doses of 31-39Gy, depending on the patient's age, with two high-dose thiotepa courses following CSI. After the first 15 patients had been treated, craniospinal irradiation (CSI) was replaced with focal radiotherapy (RT) for selected cases (non-metastatic and not progressing during induction chemotherapy). Eight of the 28 children received the same chemotherapy but conventionally fractionated focal RT at 54Gy. Results: The 5-year progression-free survival (PFS), event-free survival (EFS), and overall survival (OS) rates were 62%, 53%, and 52%, respectively, for the whole series, and 70%, 70%, and 87% for the eight focally irradiated children. Residual disease and metastases were not prognostically significant. In children with residual disease, response to RT was significant (5-year PFS 59% vs. 20%, P=0.01), while the total dose of CSI was not. There were three treatment-related toxic events. Relapses were local in seven cases (including two of the eight focally irradiated patients), and both local and disseminated in 2. Conclusions: This intensive schedule enabled treatment stratification for the purposes of radiation, thereby sparing some children full-dose CSI. Local control is the main goal of treatment for CNS-PNET. Pediatr Blood Cancer 2013;60:2031-2035. © 2013 Wiley Periodicals, Inc.