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Peripheral Blood Biomarkers Associated With Toxicity and Treatment Characteristics After 131 I- Metaiodobenzylguanidine Therapy in Patients With Neuroblastoma.
- Source :
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International journal of radiation oncology, biology, physics [Int J Radiat Oncol Biol Phys] 2017 Oct 01; Vol. 99 (2), pp. 468-475. Date of Electronic Publication: 2017 May 15. - Publication Year :
- 2017
-
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 <superscript>131</superscript> I-metaiodobenzylguanidine ( <superscript>131</superscript> I-MIBG) therapy in patients with neuroblastoma.<br />Methods and Materials: We conducted a prospective, single-center cohort study in children with advanced neuroblastoma treated with <superscript>131</superscript> I-MIBG as monotherapy or in combination with systemic putative radiation sensitizers. We collected serial peripheral blood samples after <superscript>131</superscript> I-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.<br />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 <superscript>131</superscript> I-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 <superscript>131</superscript> I-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).<br />Conclusions: Peripheral blood biomarkers relevant to radiation exposure are significantly modulated during the acute period after <superscript>131</superscript> I-MIBG. The degree of modulation of a subset of these markers is associated with toxicity and receipt of concomitant radiation sensitizers.<br /> (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Subjects :
- Adolescent
Adult
Child
Child, Preschool
Female
Humans
Male
Membrane Proteins blood
Neutropenia etiology
Pilot Projects
Prospective Studies
Radiation-Sensitizing Agents therapeutic use
3-Iodobenzylguanidine adverse effects
Biomarkers blood
Neuroblastoma blood
Radiopharmaceuticals adverse effects
Subjects
Details
- Language :
- English
- ISSN :
- 1879-355X
- Volume :
- 99
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- International journal of radiation oncology, biology, physics
- Publication Type :
- Academic Journal
- Accession number :
- 28871998
- Full Text :
- https://doi.org/10.1016/j.ijrobp.2017.05.008