title: The treatment of colorectal liver metastases with conformal radiation therapy and regional chemotherapy.
abstract: OBJECTIVE
  Whole-liver radiation, with or without chemotherapy, has been of modest benefit in the treatment of unresectable hepatic metastases from colorectal cancer. A Phase I/II study combining escalating doses of conformally planned radiation therapy (RT) with intraarterial hepatic (IAH) fluorodeoxyuridine (FdUrd) was performed.
  
  
  METHODS
  Twenty-two patients with unresectable hepatic metastases from colorectal cancer, 14 of whom had progressed after previous chemotherapy (2 with prior IAH FdUrd), were treated with concurrent IAH FdUrd (0.2 mg/kg/day) and conformal hepatic radiation therapy (1.5-1.65 Gy/fraction twice a day). The total dose of radiation given to the tumor (48-72.6 Gy) depended on the fraction of normal liver excluded from the high-dose volume. All patients were assessed for response, toxicity, hepatobiliary relapse, and survival. Median potential follow-up was 42 months.
  
  
  RESULTS
  Eleven of 22 patients demonstrated an objective response, with the remainder showing stable disease. Actuarial freedom from hepatic progression was 25% at 1 years. The most common acute toxicity was mild to moderate nausea and transient liver function test abnormalities. There were three patients with gastrointestinal bleeding (none requiring surgical intervention) after the completion of treatment. Overall median survival was 20 months. The presence of extrahepatic disease was associated with decreased survival (p < 0.01).
  
  
  CONCLUSIONS
  Combined conformal radiation therapy and IAH FdUrd can produce an objective response in 50% of patients with hepatic metastases from colorectal cancer. However, response was not durable, and hepatic progression was frequent. Improvements in hepatic tumor control for patients with metastatic colorectal cancer may require higher doses of conformal radiation and/or improved radiosensitization. In an effort to increase radiosensitization, we have recently initiated a clinical trial combining IAH bromode-oxyuridine, a thymidine analog radiosensitizer, with conformal high dose radiation therapy.
authors.affiliation: Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Robertson
authors.forename: T S
authors.initials: TS
authors.lastname: Lawrence
authors.forename: S
authors.initials: S
authors.lastname: Walker
authors.forename: M L
authors.initials: ML
authors.lastname: Kessler
authors.forename: J C
authors.initials: JC
authors.lastname: Andrews
authors.forename: W D
authors.initials: WD
authors.lastname: Ensminger
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms; D003131:Combined Modality Therapy; D005260:Female; D005467:Floxuridine / Q000008:administration & dosage*; D006801:Humans; D007261:Infusions, Intra-Arterial; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy* / Q000556:secondary; D008297:Male; D008875:Middle Aged; D011879:Radiotherapy Dosage
chemical_list: D005467:Floxuridine