Evolving of therapeutic strategies for CNS-PNET

Pediatr Blood Cancer. 2013 Dec;60(12):2031-5. doi: 10.1002/pbc.24540. Epub 2013 Jul 13.

Abstract

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 31-39 Gy, 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 54 Gy.

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.

Keywords: CNS-PNET; childhood brain tumors; dissemination; local relapse; treatment stratification; treatment toxicity.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Brain Neoplasms / mortality*
  • Brain Neoplasms / therapy*
  • Carboplatin / administration & dosage
  • Carboplatin / adverse effects
  • Child
  • Child, Preschool
  • Combined Modality Therapy
  • Cranial Irradiation
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects
  • Disease-Free Survival
  • Etoposide / administration & dosage
  • Etoposide / adverse effects
  • Female
  • Humans
  • Infant
  • Kaplan-Meier Estimate
  • Male
  • Methotrexate / administration & dosage
  • Methotrexate / adverse effects
  • Neuroectodermal Tumors, Primitive / mortality*
  • Neuroectodermal Tumors, Primitive / therapy*
  • Thiotepa / administration & dosage
  • Thiotepa / adverse effects
  • Vincristine / administration & dosage
  • Vincristine / adverse effects

Substances

  • Vincristine
  • Etoposide
  • Cyclophosphamide
  • Thiotepa
  • Carboplatin
  • Methotrexate