Improved 6-year overall survival in AT/RT - results of the registry study Rhabdoid 2007

Cancer Med. 2016 Aug;5(8):1765-75. doi: 10.1002/cam4.741. Epub 2016 May 26.

Abstract

Atypical teratoid rhabdoid tumors (AT/RT) are characterized by mutations and subsequent inactivation of SMARCB1 (INI1, hSNF5), a predilection for very young children and an unfavorable outcome. The European Registry for rhabdoid tumors (EU-RHAB) was established to generate a common European database and to establish a standardized treatment regimen as the basis for phase I/II trials. Thus, genetic analyses, neuropathologic and radiologic diagnoses, and a consensus treatment regimen were prospectively evaluated. From 2005 to 2009, 31 patients with AT/RT from four countries were recruited into the registry study Rhabdoid 2007 and treated with systemic and intraventricular chemotherapy. Eight patients received high-dose chemotherapy, 23 radiotherapy, and 17 maintenance therapy. Reference evaluations were performed in 64% (genetic analyses, FISH, MLPA, sequencing) up to 97% (neuropathology, INI1 stain). Germ-line mutations (GLM) were detected in 6/21 patients. Prolonged overall survival was associated with age above 3 years, radiotherapy and achievement of a complete remission. 6-year overall and event-free survival rates were 46% (±0.10) and 45% (±0.09), respectively. Serious adverse events and one treatment-related death due to insufficiency of a ventriculo peritoneal shunt (VP-shunt) and consecutive herniation were noted. Acquisition of standardized data including reference diagnosis and a standard treatment schedule improved data quality along with a survival benefit. Treatment was feasible with significant but manageable toxicity. Although our analysis is biased due to heterogeneous adherence to therapy, EU-RHAB provides the best available basis for phase I/II clinical trials.

Keywords: AT/RT; EU-RHAB Registry; Rhabdoid 2007; pediatric brain tumor.

Publication types

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

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Brain Neoplasms / genetics
  • Brain Neoplasms / mortality
  • Brain Neoplasms / therapy*
  • Child
  • Child, Preschool
  • Combined Modality Therapy
  • Europe / epidemiology
  • Female
  • Germ-Line Mutation
  • Humans
  • Infant
  • Infant, Newborn
  • Kaplan-Meier Estimate
  • Male
  • Prognosis
  • Radiotherapy, Conformal / adverse effects
  • Radiotherapy, Conformal / methods
  • Registries
  • Rhabdoid Tumor / diagnosis
  • Rhabdoid Tumor / genetics
  • Rhabdoid Tumor / mortality
  • Rhabdoid Tumor / therapy*
  • Treatment Failure
  • Treatment Outcome