Metastatic medulloblastoma in adults: outcome of patients treated according to the HIT2000 protocol

Eur J Cancer. 2015 Nov;51(16):2434-43. doi: 10.1016/j.ejca.2015.06.124. Epub 2015 Aug 5.

Abstract

Background: Due to the rarity of metastatic medulloblastoma in adults, knowledge about the efficacy and toxicity of intensified chemotherapy and radiotherapy is limited.

Patients and methods: Adults with disseminated medulloblastoma registered in the HIT2000 trial as observational patients and treated according to one of two different treatment regimens were analysed. The sandwich strategy MET-HIT2000AB4 consists of postoperative chemotherapy, hyperfractionated craniospinal radiotherapy, and maintenance chemotherapy; while the HIT'91 maintenance strategy consists of postoperative craniospinal radiotherapy, and maintenance chemotherapy.

Results: Twenty-three patients (median age: 30.7years), diagnosed from November 2001 to July 2009, and treated in 18 institutions in Germany and Austria, were eligible. The median follow-up of surviving patients was 3.99years. The 4-year event-free survival (EFS) and overall survival (OS)±standard error (SE) were 52%±12% and 91%±6%, respectively. The survival was similar in both treatment groups (HIT'91 maintenance strategy, n=9; MET-HIT2000AB4 sandwich strategy, n=14). Patients with large cell/anaplastic medulloblastoma relapsed and died (n=2; 4-year EFS/OS: 0%) and OS differed compared to patients with classic (n=11; 4-year EFS/OS: 71%/91%) and desmoplastic medulloblastoma (n=10; 4-year EFS/OS: 48%/100%), respectively (p=0.161 for EFS and p=0.033 for OS). Treatment-induced toxicities consisted mainly of neurotoxicity (50% of patients, ⩾ °II), followed by haematotoxicity and nephrotoxicity/ototoxicity. The professional outcome appeared to be negatively affected in the majority of evaluable patients (9/10).

Conclusions: Treatment of adults with metastatic medulloblastoma according to the intensified paediatric HIT2000 protocol was feasible with acceptable toxicities. EFS rates achieved by both chemotherapeutic protocols were favourable and appear to be inferior to those obtained in older children/adolescents with metastatic disease.

Trial registration: ClinicalTrials.gov NCT00303810.

Keywords: Adults; Brain tumour; Chemotherapy; Medulloblastoma; Prognosis; Radiotherapy; Toxicity; Treatment.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Austria
  • Cerebellar Neoplasms / mortality
  • Cerebellar Neoplasms / pathology
  • Cerebellar Neoplasms / therapy*
  • Chemoradiotherapy, Adjuvant* / adverse effects
  • Chemoradiotherapy, Adjuvant* / mortality
  • Cranial Irradiation* / adverse effects
  • Cranial Irradiation* / mortality
  • Disease Progression
  • Disease-Free Survival
  • Dose Fractionation, Radiation
  • Female
  • Germany
  • Humans
  • Kaplan-Meier Estimate
  • Maintenance Chemotherapy* / adverse effects
  • Maintenance Chemotherapy* / mortality
  • Male
  • Medulloblastoma / mortality
  • Medulloblastoma / secondary
  • Medulloblastoma / therapy*
  • Neurosurgical Procedures* / adverse effects
  • Neurosurgical Procedures* / mortality
  • Prospective Studies
  • Risk Factors
  • Time Factors
  • Treatment Outcome

Associated data

  • ClinicalTrials.gov/NCT00303810