title: Insights into the Dose-Response Relationship of Radioembolization with Resin 90Y-Microspheres: A Prospective Cohort Study in Patients with Colorectal Cancer Liver Metastases.
abstract: Randomized controlled trials are investigating the benefit of hepatic radioembolization added to systemic therapy in the first- and second-line treatment of patients with colorectal liver metastases (CRLM). Remarkably, administered activity may still be suboptimal, because a dose-response relationship has not been defined. The purpose of this study was to characterize the relationship between tumor-absorbed dose and response after (90)Y radioembolization treatment for CRLM.
  
  
  METHODS
  Thirty patients with unresectable chemorefractory CRLM were treated with resin (90)Y-microspheres in a prospective phase II clinical trial. Tumor-absorbed dose was quantified on (90)Y PET. Metabolic tumor activity, defined as tumor lesion glycolysis (TLG*) on (18)F-FDG PET, was measured at baseline and 1 mo after treatment. The relationship between tumor-absorbed dose and posttreatment metabolic activity was assessed per metastasis with a linear mixed-effects regression model.
  
  
  RESULTS
  Treated metastases (n = 133) were identified. The mean tumor-absorbed dose was 51 ± 28 Gy (range, 7-174 Gy). A 50% reduction in TLG* was achieved in 46% of metastases and in 11 of 30 (37%) patients for the sum of metastases. The latter was associated with a prolonged median overall survival (11.6 vs. 6.6 mo, P = 0.02). A strong and statistically significant dose-response relationship was found (P < 0.001). The dose effect depended on baseline TLG* (P < 0.01). The effective tumor-absorbed dose was conservatively estimated at a minimum of 40-60 Gy.
  
  
  CONCLUSIONS
  A strong dose-response relationship exists for the treatment of CRLM with resin microsphere (90)Y radioembolization. Treatment efficacy is, however, still limited, because the currently used pretreatment activity calculation methods curb potentially achievable tumor-absorbed dose values. A more personalized approach to radioembolization is required before concluding on its clinical potential.
authors.affiliation: Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht, The Netherlands a.f.vandenhoven@umcutrecht.nl.
authors.forename: Andor F
authors.initials: AF
authors.lastname: van den Hoven
authors.affiliation: Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Charlotte E N M
authors.initials: CE
authors.lastname: Rosenbaum
authors.affiliation: Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht, The Netherlands Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Sjoerd G
authors.initials: SG
authors.lastname: Elias
authors.affiliation: Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Hugo W A M
authors.initials: HW
authors.lastname: de Jong
authors.affiliation: Department of Medical Oncology, University Medical Center Utrecht, Utrecht, The Netherlands; and.
authors.forename: Miriam
authors.initials: M
authors.lastname: Koopman
authors.affiliation: Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Helena M
authors.initials: HM
authors.lastname: Verkooijen
authors.affiliation: Division of Nuclear Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Abass
authors.initials: A
authors.lastname: Alavi
authors.affiliation: Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Maurice A A J
authors.initials: MA
authors.lastname: van den Bosch
authors.affiliation: Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Marnix G E H
authors.initials: MG
authors.lastname: Lam
mesh_terms: D000368:Aged; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D004307:Dose-Response Relationship, Radiation; D004621:Embolization, Therapeutic / Q000379:methods*; D005260:Female; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000532:radiotherapy* / Q000556:secondary*; D008297:Male; D008863:Microspheres; D008875:Middle Aged; D011446:Prospective Studies; D011874:Radiometry; D019275:Radiopharmaceuticals / Q000627:therapeutic use*; D016019:Survival Analysis; D015899:Tomography, Emission-Computed, Single-Photon; D015021:Yttrium Radioisotopes / Q000627:therapeutic use*
chemical_list: D019275:Radiopharmaceuticals; D015021:Yttrium Radioisotopes
keywords: 90Y PET; CRLM; dose-response relationship; metabolic tumor response; radioembolization