Association of BRAF V600E mutations with vasoactive intestinal peptide syndrome in MYCN-amplified neuroblastoma

Pediatr Blood Cancer. 2021 Oct;68(10):e29265. doi: 10.1002/pbc.29265. Epub 2021 Jul 31.

Abstract

Very rarely, vasoactive intestinal peptide-related diarrhea (VIP-D) is observed in patients with high-risk neuroblastoma (HR-NB) where the associated fluid and electrolyte abnormalities can pose a major clinical challenge for administering the required aggressive multimodality treatment. Two patients with HR-NB developed VIP-D during induction and were found to have a somatic BRAF V600E mutation. Serum VIP levels and diarrhea promptly resolved in both patients after initiating treatment with BRAF and MEK inhibitors. This illustrates an association of VIP-D with BRAF V600E mutations and demonstrates a therapeutic strategy in the specific context of VIP-D and BRAF V600E mutations in HR-NB patients. The addition of BRAF and MEK inhibitors allows continued conventional tumor-directed treatment by decreasing the severity of symptoms caused by this life-threatening complication.

Trial registration: ClinicalTrials.gov NCT02684058 NCT02124772 NCT03919071.

Keywords: BRAF V600E mutation; MYCN-amplified neuroblastoma; paraneoplastic syndrome; vasoactive intestinal peptide.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Diarrhea*
  • Humans
  • Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors
  • Mutation
  • N-Myc Proto-Oncogene Protein*
  • Neuroblastoma* / drug therapy
  • Neuroblastoma* / genetics
  • Neuroblastoma* / metabolism
  • Protein Kinase Inhibitors / therapeutic use
  • Proto-Oncogene Proteins B-raf* / antagonists & inhibitors
  • Vasoactive Intestinal Peptide* / genetics
  • Vasoactive Intestinal Peptide* / metabolism

Substances

  • MYCN protein, human
  • N-Myc Proto-Oncogene Protein
  • Protein Kinase Inhibitors
  • Vasoactive Intestinal Peptide
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • Mitogen-Activated Protein Kinase Kinases

Associated data

  • ClinicalTrials.gov/NCT02684058
  • ClinicalTrials.gov/NCT02124772
  • ClinicalTrials.gov/NCT03919071