title: Safety and efficacy of Y-90 microsphere treatment in patients with primary and metastatic liver cancer: the tumor selectivity of the treatment as a function of tumor to liver flow ratio.
abstract: BACKGROUND
  Treatment records and follow-up data on 40 patients with primary and metastatic liver malignancies who underwent a single whole-liver treatment with Y-90 resin microspheres (SIR-Spheres Sirtex Medical, Lake Forest, IL) were retrospectively reviewed. The objective of the study was to evaluate the anatomic and physiologic determinants of radiation dose distribution, and the dose response of tumor and liver toxicity in patients with liver malignancies who underwent hepatic arterial Y-90 resin microsphere treatment.
  
  
  METHODS
  Liver and tumor volume calculations were performed on pre-treatment CT scans. Fractional tumor and liver flow characteristics and lung shunt fractions were determined using hepatic arterial Tc-99m MAA imaging. Absorbed dose calculations were performed using the MIRD equations. Liver toxicity was assessed clinically and by liver function tests. Tumor response to therapy was assessed by CT and/or tumor markers.
  
  
  RESULTS
  Of the 40 patients, 5 had hepatocellular cancer (HCC), and 35 had metastatic liver tumors (15 colorectal cancer, 10 neuroendocrine tumors, 4 breast cancer, 2 lung cancer, 1 ovarian cancer, 1 endometrial cancer, and 2 unknown primary adenocarcinoma). All patients were treated in a salvage setting with a 3 to 80 week follow-up (mean: 19 weeks). Tumor volumes ranged from 15.0 to 984.2 cc (mean: 294.9 cc) and tumor to normal liver uptake ratios ranged from 2.8 to 15.4 (mean: 5.4). Average administered activity was 1.2 GBq (0.4 to 2.4 GBq). Liver absorbed doses ranged from 0.7 to 99.5 Gy (mean: 17.2 Gy). Tumor absorbed doses ranged from 40.1 to 494.8 Gy (mean: 121.5 Gy). None of the patients had clinical venoocclusive disease or therapy-induced liver failure. Seven patients (17.5 %) had transient and 7 patients (17.5 %) had persistent LFT abnormalities. There were 27 (67.5%) responders (complete response, partial response, and stable disease). Tumor response correlated with higher tumor flow ratio as measured by Tc-99m MAA imaging.
  
  
  CONCLUSIONS
  Doses up to 99.5 Gy to uninvolved liver are tolerated with no clinical venoocclusive disease or liver failure. The lowest tumor dose producing a detectable response is 40.1 Gy. The utilization of MAA-based imaging techniques to determine tumor and liver blood flow for clinical treatment planning and the calculation of administered activity may improve clinical outcomes.
authors.affiliation: Goshen Cancer Institute, Goshen, IN, USA. sgulec@goshenhealth.com
authors.forename: Seza A
authors.initials: SA
authors.lastname: Gulec
authors.forename: Geraldine
authors.initials: G
authors.lastname: Mesoloras
authors.forename: William A
authors.initials: WA
authors.lastname: Dezarn
authors.forename: Patrick
authors.initials: P
authors.lastname: McNeillie
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Kennedy
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008099:Liver / Q000378:metabolism* / Q000473:pathology*; D008113:Liver Neoplasms / Q000473:pathology / Q000628:therapy*; D008297:Male; D008863:Microspheres; D008875:Middle Aged; D009362:Neoplasm Metastasis; D051193:Toll-Like Receptors / Q000378:metabolism; D016896:Treatment Outcome; D015019:Yttrium / Q000009:adverse effects*; D015021:Yttrium Radioisotopes
chemical_list: D051193:Toll-Like Receptors; D015021:Yttrium Radioisotopes; D015019:Yttrium