Supratentorial primitive neuroectodermal tumors (S-PNET) in children: A prospective experience with adjuvant intensive chemotherapy and hyperfractionated accelerated radiotherapy

Int J Radiat Oncol Biol Phys. 2006 Mar 15;64(4):1031-7. doi: 10.1016/j.ijrobp.2005.09.026. Epub 2005 Dec 15.

Abstract

Purpose: Supratentorial primitive neuroectodermal tumors (S-PNET) are rare and have a grim prognosis, frequently taking an aggressive course with local relapse and metastatic spread. We report the results of a mono-institutional therapeutic trial.

Methods and materials: We enrolled 15 consecutive patients to preradiation chemotherapy (CT) consisting of high-dose methotrexate, high-dose etoposide, high-dose cyclophosphamide, and high-dose carboplatin, craniospinal irradiation (CSI) with hyperfractionated accelerated radiotherapy (HART) plus focal boost, maintenance with vincristine/lomustine or consolidation with high-dose thiotepa followed by autologous stem-cell rescue.

Results: Median age was 9 years; 7 were male, 8 female. Site of disease was pineal in 3, elsewhere in 12. Six patients were had no evidence of disease after surgery (NED). Of those with evidence of disease after surgery (ED), 2 had central nervous system spread. Of the 9 ED patients, 2 had complete response (CR) and 2 partial response (PR) after CT, 4 stable disease, and 1 progressive disease. Of the 7 ED patients before radiotherapy, 1 had CR, 4 PR, and 2 minor response, thus obtaining a 44% CR + PR after CT and 71% after HART. Because of rapid progression in 2 of the first 5 patients, high-dose thiotepa was systematically adopted after HART in the subsequent 10 patients. Six of 15 patients relapsed (4 locally, 1 locally with dissemination, 1 with dissemination) a mean of 6 months after starting CT, 2 developed second tumors; 5 of 6 relapsers died at a median of 13 months. Three-year progression-free survival, event-free survival, and overall survival were 54%, 34%, and 61%, respectively.

Conclusion: Hyperfractionated accelerated RT was the main tool in obtaining responses in S-PNET; introducing the myeloablative phase improved the prognosis (3/10 vs. 3/5 relapses), though the outcome remained unsatisfactory despite the adoption of this intensive treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carboplatin / administration & dosage
  • Chemotherapy, Adjuvant
  • Chi-Square Distribution
  • Child
  • Child, Preschool
  • Cyclophosphamide / administration & dosage
  • Dose Fractionation, Radiation
  • Etoposide / administration & dosage
  • Female
  • Humans
  • Lomustine / administration & dosage
  • Male
  • Methotrexate / administration & dosage
  • Neuroectodermal Tumors, Primitive / drug therapy*
  • Neuroectodermal Tumors, Primitive / radiotherapy*
  • Prospective Studies
  • Stem Cell Transplantation / methods
  • Supratentorial Neoplasms / drug therapy*
  • Supratentorial Neoplasms / radiotherapy*
  • Survival Analysis
  • Thiotepa / administration & dosage
  • Treatment Outcome
  • Vincristine / administration & dosage

Substances

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