Kevin Campbell1, Erin E Karski2, Aleksandra Olow3, David A Edmondson4, Ayano C Kohlgruber4, Matthew Coleman4, Daphne A Haas-Kogan5, Katherine K Matthay2, Steven G DuBois6. 1. Dana-Farber/Boston Children's Cancer and Blood Disorders Center and Harvard Medical School, Boston, Massachusetts. 2. Department of Pediatrics, University of California, San Francisco (UCSF) Benioff Children's Hospital and UCSF School of Medicine, San Francisco, California. 3. Department of Radiation Oncology, University of California, San Francisco (UCSF) Benioff Children's Hospital and UCSF School of Medicine, San Francisco, California. 4. Department of Radiation Oncology, University of California, Davis School of Medicine and Lawrence Livermore National Laboratory, Sacramento, California. 5. Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center and Harvard Medical School, Boston, Massachusetts. 6. Dana-Farber/Boston Children's Cancer and Blood Disorders Center and Harvard Medical School, Boston, Massachusetts. Electronic address: steven_dubois@dfci.harvard.edu.
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.
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.
Authors: Angela C Evans; Tim Setzkorn; David A Edmondson; Haley Segelke; Paul F Wilson; Katherine K Matthay; M Meaghan Granger; Araz Marachelian; Daphne A Haas-Kogan; Steven G DuBois; Matthew A Coleman Journal: Radiat Res Date: 2022-02-01 Impact factor: 2.841
Authors: Steven G DuBois; M Meaghan Granger; Susan Groshen; Denice Tsao-Wei; Lingyun Ji; Anasheh Shamirian; Scarlett Czarnecki; Fariba Goodarzian; Rachel Berkovich; Hiroyuki Shimada; Judith G Villablanca; Kieuhoa T Vo; Navin Pinto; Yael P Mosse; John M Maris; Suzanne Shusterman; Susan L Cohn; Kelly C Goldsmith; Brian Weiss; Gregory A Yanik; Clare J Twist; Meredith S Irwin; Daphne A Haas-Kogan; Julie R Park; Araz Marachelian; Katherine K Matthay Journal: J Clin Oncol Date: 2021-07-16 Impact factor: 44.544