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

Kevin Campbell, Erin E. Karski, Aleksandra Olow, David A. Edmondson, Ayano C. Kohlgruber, Matthew A Coleman, Daphne A. Haas-Kogan, Katherine K. Matthay, Steven G. DuBois

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)468-475
Number of pages8
JournalInternational Journal of Radiation Oncology Biology Physics
Volume99
Issue number2
DOIs
StatePublished - Oct 1 2017

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biomarkers
Radiation-Sensitizing Agents
Neuroblastoma
toxicity
blood
therapy
Biomarkers
markers
modulation
Ligands
Radiopharmaceuticals
Radiation Effects
Therapeutics
Amylases
Neutropenia
grade
radiation
Cohort Studies
ribonucleic acids
ligands

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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Peripheral Blood Biomarkers Associated With Toxicity and Treatment Characteristics After 131I- Metaiodobenzylguanidine Therapy in Patients With Neuroblastoma. / Campbell, Kevin; Karski, Erin E.; Olow, Aleksandra; Edmondson, David A.; Kohlgruber, Ayano C.; Coleman, Matthew A; Haas-Kogan, Daphne A.; Matthay, Katherine K.; DuBois, Steven G.

In: International Journal of Radiation Oncology Biology Physics, Vol. 99, No. 2, 01.10.2017, p. 468-475.

Research output: Contribution to journalArticle

Campbell, Kevin ; Karski, Erin E. ; Olow, Aleksandra ; Edmondson, David A. ; Kohlgruber, Ayano C. ; Coleman, Matthew A ; Haas-Kogan, Daphne A. ; Matthay, Katherine K. ; DuBois, Steven G. / Peripheral Blood Biomarkers Associated With Toxicity and Treatment Characteristics After 131I- Metaiodobenzylguanidine Therapy in Patients With Neuroblastoma. In: International Journal of Radiation Oncology Biology Physics. 2017 ; Vol. 99, No. 2. pp. 468-475.
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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.",
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T1 - Peripheral Blood Biomarkers Associated With Toxicity and Treatment Characteristics After 131I- Metaiodobenzylguanidine Therapy in Patients With Neuroblastoma

AU - Campbell, Kevin

AU - Karski, Erin E.

AU - Olow, Aleksandra

AU - Edmondson, David A.

AU - Kohlgruber, Ayano C.

AU - Coleman, Matthew A

AU - Haas-Kogan, Daphne A.

AU - Matthay, Katherine K.

AU - DuBois, Steven G.

PY - 2017/10/1

Y1 - 2017/10/1

N2 - 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.

AB - 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.

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