Treatment of children with central nervous system primitive neuroectodermal tumors/pinealoblastomas in the prospective multicentric trial HIT 2000 using hyperfractionated radiation therapy followed by maintenance chemotherapy

Int J Radiat Oncol Biol Phys. 2014 Jul 15;89(4):863-71. doi: 10.1016/j.ijrobp.2014.04.017.

Abstract

Purpose: The prognosis for children with central nervous system primitive neuroectodermal tumor (CNS-PNET) or pinealoblastoma is still unsatisfactory. Here we report the results of patients between 4 and 21 years of age with nonmetastatic CNS-PNET or pinealoblastoma diagnosed from January 2001 to December 2005 and treated in the prospective GPOH-trial P-HIT 2000-AB4.

Methods and materials: After surgery, children received hyperfractionated radiation therapy (36 Gy to the craniospinal axis, 68 Gy to the tumor region, and 72 Gy to any residual tumor, fractionated at 2 × 1 Gy per day 5 days per week) accompanied by weekly intravenous administration of vincristine and followed by 8 cycles of maintenance chemotherapy (lomustine, cisplatin, and vincristine).

Results: Twenty-six patients (15 with CNS-PNET; 11 with pinealoblastoma) were included. Median age at diagnosis was 11.5 years old (range, 4.0-20.7 years). Gross total tumor resection was achieved in 6 and partial resection in 16 patients (indistinct, 4 patients). Median follow-up of the 15 surviving patients was 7.0 years (range, 5.2-10.0 years). The combined response rate to postoperative therapy was 17 of 20 (85%). Eleven of 26 patients (42%; 7 of 15 with CNS-PNET; 4 of 11 with pinealoblastoma) showed tumor progression or relapse at a median time of 1.3 years (range, 0.5-1.9 years). Five-year progression-free and overall survival rates (± standard error [SE]) were each 58% (± 10%) for the entire cohort: CNS-PNET was 53% (± 13); pinealoblastoma was 64% (± 15%; P=.524 and P=.627, respectively).

Conclusions: Postoperative hyperfractionated radiation therapy with local dose escalation followed by maintenance chemotherapy was feasible without major acute toxicity. Survival rates are comparable to those of a few other recent studies but superior to those of most other series, including the previous trial, HIT 1991.

Trial registration: ClinicalTrials.gov NCT00303810.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antineoplastic Agents / therapeutic use
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / mortality
  • Brain Neoplasms / radiotherapy*
  • Brain Neoplasms / surgery
  • Child
  • Child, Preschool
  • Clinical Protocols
  • Disease-Free Survival
  • Dose Fractionation, Radiation
  • Female
  • Humans
  • Maintenance Chemotherapy / methods*
  • Male
  • Memory, Short-Term
  • Mental Processes
  • Neoplasm Recurrence, Local
  • Neoplasm, Residual
  • Neuroectodermal Tumors, Primitive / drug therapy*
  • Neuroectodermal Tumors, Primitive / mortality
  • Neuroectodermal Tumors, Primitive / radiotherapy*
  • Neuroectodermal Tumors, Primitive / surgery
  • Neuropsychological Tests
  • Pineal Gland*
  • Pinealoma / drug therapy*
  • Pinealoma / mortality
  • Pinealoma / radiotherapy*
  • Pinealoma / surgery
  • Prospective Studies
  • Regression Analysis
  • Survival Rate
  • Young Adult

Substances

  • Antineoplastic Agents

Associated data

  • ClinicalTrials.gov/NCT00303810