title: Radiation dose limits and liver toxicities resulting from multiple yttrium-90 radioembolization treatments for hepatocellular carcinoma.
abstract: OBJECTIVE
  To assess the relationship between cumulative hepatic lobar radiation dose and liver toxicities in patients with hepatocellular carcinoma (HCC) treated with multiple sessions of yttrium-90 radioembolization.
  
  
  METHODS
  Forty-one patients with HCC (age range, 46-82 years) underwent radioembolization with 90Y. Patients were classified according to the Okuda scoring system. All patients received single liver lobar treatments on two or more occasions according to standard clinical 90Y embolization protocol. Cumulative radiation dose to each liver lobe was measured and patients were followed to assess liver toxicities. Statistical analysis was performed with the Student t test and Kaplan-Meier analysis.
  
  
  RESULTS
  Patients with Okuda stage I disease received more treatments than those with Okuda stage II disease (mean, 2.65 vs 2.24; P<.05). For average cumulative radiation dose, patients with Okuda stage I disease received 247 Gy (range, 88-482 Gy) and those with Okuda stage II disease received 198 Gy (range, 51-361 Gy; P<.05). A total of 13 toxicities occurred in seven patients (16%). Patients with Okuda stage I disease were given a greater cumulative dose than patients with Okuda stage II disease before worsening of liver function: 390 Gy versus 196 Gy (P<.005). For patients with Okuda stage I disease, a higher cumulative radiation dose was associated with occurrence of one or more toxicities: 222 Gy (no toxicities) versus 390 Gy (>or=1 toxicity; P<.005). No correlation between cumulative radiation dose and liver toxicities existed in patients with Okuda stage II disease. The maximum tolerated dose was between 222 and 390 Gy. Median survival times were 660 and 431 days for patients with Okuda stage I and stage II disease, respectively.
  
  
  CONCLUSIONS
  Patients with HCC can tolerate high cumulative radiation doses with 90Y therapy. Compared with patients with Okuda stage II disease, patients with Okuda stage I disease tolerate a higher cumulative radiation dose without liver toxicity, but liver toxicities increase with increasing cumulative radiation doses.
authors.affiliation: Department of Radiology, Section of Interventional Radiology, Northwestern Memorial Hospital and Robert H. Lurie Comprehensive Cancer Center, and Department of Biomedical Engineering, Northwestern University, Chicago, Illinois 60611, USA.
authors.forename: Joseph Y
authors.initials: JY
authors.lastname: Young
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Rhee
authors.forename: Bassel
authors.initials: B
authors.lastname: Atassi
authors.forename: Vanessa L
authors.initials: VL
authors.lastname: Gates
authors.forename: Laura
authors.initials: L
authors.lastname: Kulik
authors.forename: Mary F
authors.initials: MF
authors.lastname: Mulcahy
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Larson
authors.forename: Robert K
authors.initials: RK
authors.lastname: Ryu
authors.forename: Kent T
authors.initials: KT
authors.lastname: Sato
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Lewandowski
authors.forename: Reed A
authors.initials: RA
authors.lastname: Omary
authors.forename: Riad
authors.initials: R
authors.lastname: Salem
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001822:Body Burden; D006528:Carcinoma, Hepatocellular / Q000532:radiotherapy; D004307:Dose-Response Relationship, Radiation; D004621:Embolization, Therapeutic / Q000009:adverse effects; D005260:Female; D006801:Humans; D008107:Liver Diseases / Q000209:etiology*; D008113:Liver Neoplasms / Q000532:radiotherapy; D008297:Male; D008452:Maximum Allowable Concentration; D008875:Middle Aged; D011832:Radiation Injuries / Q000209:etiology*; D019275:Radiopharmaceuticals / Q000009:adverse effects / Q000627:therapeutic use; D011879:Radiotherapy Dosage; D015021:Yttrium Radioisotopes / Q000009:adverse effects* / Q000627:therapeutic use*
chemical_list: D019275:Radiopharmaceuticals; D015021:Yttrium Radioisotopes