Monitoring Arteriovenous Malformation Response to Genotype-Targeted Therapy

Pediatrics. 2020 Sep;146(3):e20193206. doi: 10.1542/peds.2019-3206.

Abstract

Arteriovenous malformations (AVMs) have recently been reported to have a high incidence of somatic KRAS mutations suggesting potential for treatment with mitogen-activated protein kinase inhibitors. In this case report, we describe genotype-targeted treatment of a KRAS mutant metameric AVM in a patient with Cobb syndrome using the mitogen-activated protein kinase inhibitor trametinib. Therapeutic response was monitored with phase-contrast magnetic resonance angiography to quantify AVM arterial inflow as an imaging biomarker. Treatment with trametinib resulted in a substantial decrease in blood flow to the AVM, with a >75% reduction in arterial inflow after 6 months of trametinib therapy.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Amino Acid Sequence
  • Arteriovenous Malformations / diagnostic imaging
  • Arteriovenous Malformations / drug therapy*
  • Arteriovenous Malformations / genetics
  • Drug Delivery Systems / methods
  • Genotype*
  • Humans
  • Male
  • Protein Kinase Inhibitors / administration & dosage*
  • Proto-Oncogene Proteins p21(ras) / antagonists & inhibitors
  • Proto-Oncogene Proteins p21(ras) / genetics*
  • Pyridones / administration & dosage*
  • Pyrimidinones / administration & dosage*
  • Spinal Cord Diseases / diagnostic imaging
  • Spinal Cord Diseases / drug therapy*
  • Spinal Cord Diseases / genetics
  • Syndrome
  • Treatment Outcome

Substances

  • KRAS protein, human
  • Protein Kinase Inhibitors
  • Pyridones
  • Pyrimidinones
  • trametinib
  • Proto-Oncogene Proteins p21(ras)