Peripheral Blood Biomarkers Associated With Toxicity and Treatment Characteristics After 131 I- Metaiodobenzylguanidine Therapy in Patients With Neuroblastoma

Int J Radiat Oncol Biol Phys. 2017 Oct 1;99(2):468-475. doi: 10.1016/j.ijrobp.2017.05.008. Epub 2017 May 15.

Abstract

Purpose: Few tools exist to predict clinical outcomes after radiopharmaceutical therapy. Our goal was to identify associations between blood-based biomarkers of radiation effect and clinical outcomes after 131I-metaiodobenzylguanidine (131I-MIBG) therapy in patients with neuroblastoma.

Methods and materials: We conducted a prospective, single-center cohort study in children with advanced neuroblastoma treated with 131I-MIBG as monotherapy or in combination with systemic putative radiation sensitizers. We collected serial peripheral blood samples after 131I-MIBG infusions and quantified a panel of protein and messenger RNA markers. We plotted relative change from baseline to assess degree of modulation over time and then evaluated association of marker modulation with toxicity and response endpoints.

Results: The cohort included 40 patients (30 male/10 female; median age 7 years). We observed significant modulation of the majority of markers between baseline and hour 72 after 131I-MIBG. Greater fold increase of plasma FLT3 ligand was associated with subsequent grade 4 neutropenia (P=.039). Modulation of peripheral blood BCLXL and DDB2 was associated with grade 3+ nonhematologic toxicity (P=.043 and .048, respectively). No markers were associated with tumor response. Greater plasma FLT3 ligand, BCLXL, and BCL2 modulation was observed in patients receiving 131I-MIBG in combination with radiation sensitizers. Among 9 patients who received 2 courses, the degree of modulation in serum amylase was significantly lower after the second course (P=.012).

Conclusions: Peripheral blood biomarkers relevant to radiation exposure are significantly modulated during the acute period after 131I-MIBG. The degree of modulation of a subset of these markers is associated with toxicity and receipt of concomitant radiation sensitizers.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • 3-Iodobenzylguanidine / adverse effects*
  • Adolescent
  • Adult
  • Biomarkers / blood*
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Male
  • Membrane Proteins / blood
  • Neuroblastoma / blood*
  • Neutropenia / etiology
  • Pilot Projects
  • Prospective Studies
  • Radiation-Sensitizing Agents / therapeutic use
  • Radiopharmaceuticals / adverse effects*

Substances

  • Biomarkers
  • Membrane Proteins
  • Radiation-Sensitizing Agents
  • Radiopharmaceuticals
  • flt3 ligand protein
  • 3-Iodobenzylguanidine