title: Phase II trial of high-dose conformal radiation therapy with concurrent hepatic artery floxuridine for unresectable intrahepatic malignancies.
abstract: OBJECTIVE
  A phase II trial was conducted to determine if high-dose radiation with concurrent hepatic arterial floxuridine would improve survival in patients with unresectable intrahepatic malignancies.
  
  
  METHODS
  Three-dimensional conformal high-dose radiation therapy was delivered concurrently with hepatic arterial floxuridine in 128 patients. The radiation dose was based on a normal-tissue complication probability model and subjected the patient to an estimated maximum risk of radiation-induced liver disease of 10% to 15%. The study design provided more than 80% power to detect a two-fold increase in median survival compared with historical controls at a 5% significance level.
  
  
  RESULTS
  The median radiation dose delivered was 60.75 Gy (1.5-Gy fractions bid). At a median follow-up time of 16 months (26 months in patients who were alive) the median survival was 15.8 months (95% CI, 12.6 to 18.3 months), significantly longer than in the historical control. The actuarial 3-year survival was 17%. The total dose was the only significant predictor of survival. Primary hepatobiliary tumors had a significantly greater tendency to remain confined to the liver than did colorectal cancer metastases. Overall toxicity was acceptable, with 27 patients (21%) and 11 patients (9%) developing grade 3 and 4 toxicity, respectively, and one treatment-related death.
  
  
  CONCLUSIONS
  The results suggest that, compared with historical controls, high-dose focal liver irradiation with hepatic artery floxuridine prolongs survival in patients with unresectable chemotherapy-refractory metastatic colorectal cancer and primary hepatobiliary tumors. This provides a rationale for intensification of local therapy for unresectable hepatobiliary cancers and integration of this regimen with newer systemic therapy for patients with colorectal cancer.
authors.affiliation: Department of Radiation Oncology, Division of Hematology Oncology, University of Michigan, UH-B2C490, 1500 E Medical Center Dr, Ann Arbor, MI 48109-0010, USA. edgarb@med.umich.edu
authors.forename: Edgar
authors.initials: E
authors.lastname: Ben-Josef
authors.forename: Daniel
authors.initials: D
authors.lastname: Normolle
authors.forename: William D
authors.initials: WD
authors.lastname: Ensminger
authors.forename: Suzette
authors.initials: S
authors.lastname: Walker
authors.forename: Daniel
authors.initials: D
authors.lastname: Tatro
authors.forename: Randall K
authors.initials: RK
authors.lastname: Ten Haken
authors.forename: James
authors.initials: J
authors.lastname: Knol
authors.forename: Laura A
authors.initials: LA
authors.lastname: Dawson
authors.forename: Charlie
authors.initials: C
authors.lastname: Pan
authors.forename: Theodore S
authors.initials: TS
authors.lastname: Lawrence
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D001650:Bile Duct Neoplasms / Q000556:secondary / Q000628:therapy; D001653:Bile Ducts, Intrahepatic / Q000187:drug effects / Q000473:pathology* / Q000528:radiation effects; D006528:Carcinoma, Hepatocellular / Q000556:secondary / Q000628:therapy*; D018281:Cholangiocarcinoma / Q000556:secondary / Q000628:therapy; D015179:Colorectal Neoplasms / Q000473:pathology / Q000628:therapy; D003131:Combined Modality Therapy; D013505:Digestive System Surgical Procedures; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005467:Floxuridine / Q000009:adverse effects / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006499:Hepatic Artery; D006801:Humans; D007261:Infusions, Intra-Arterial; D008113:Liver Neoplasms / Q000556:secondary / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal / Q000009:adverse effects / Q000379:methods*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D005467:Floxuridine