title: Treatment variables related to liver toxicity in patients with hepatocellular carcinoma, Child-Pugh class A and B enrolled in a phase 1-2 trial of stereotactic body radiation therapy.
abstract: OBJECTIVE
  An analysis was performed on patients enrolled in a phase 1-2 trial using stereotactic body radiation therapy for hepatocellular carcinoma evaluating variables influencing liver toxicity.
  
  
  METHODS
  Thirty-eight Child-Pugh class A (CPC-A) (39 lesions) and 21 CPC-B patients (26 lesions) were followed for ≥6 months. Six months local control using modified Response Evaluation Criteria in Solid Tumors criteria, progression-free survival, overall survival, and grade III/IV treatment-related toxicity at 3 months were analyzed.
  
  
  RESULTS
  Median follow-up was 33.3 months (2.8-61.1 months) for CPC-A and 46.3 months (3.7-70.4 months) for CPC-B patients. Local control at 6 months was 92% for CPC-A and 93% for CPC-B. Kaplan-Meier estimated 2- and 3-year local control was 91% for CPC-A and 82% for CPC-B (P = .61). Median overall survival was 44.8 months and 17.0 months for CPC-A and CPC-B. Kaplan-Meier estimated 2- and 3-year overall survival was 72% and 61% for CPC-A and 33% and 26% for CPC-B (P = .03). Four (11%) CPC-A patients and 8 CPC-B patients (38%) experienced grade III/IV liver toxicity. Overall, CPC-A patients with ≥grade III liver toxicity had 4.59 (95% confidence interval, 1.19-17.66) times greater risk of death than those without toxicity (P = .0268). No such correlation was seen for CPC-B patients; however, 3 of these CPC-B patients underwent orthotopic liver transplant. CPC-B patients experiencing grade III/IV liver toxicity had significantly higher mean liver dose, higher dose to one-third normal liver, and larger volumes of liver receiving doses <2.5 to 15 Gy in 2.5-Gy increments. For CPC-A patients, there was no critical liver dose or volume constraint correlated with toxicity.
  
  
  CONCLUSIONS
  In our experience, liver stereotactic body radiation therapy is a safe therapy for patients with hepatocellular carcinoma in the context of liver cirrhosis; however, for CPC-B patients, careful attention should be paid to low-dose volumes that could potentially result in increased liver toxicity.
authors.affiliation: Mercy Radiation Oncology, Oklahoma City, Oklahoma.
authors.forename: Foster D
authors.initials: FD
authors.lastname: Lasley
authors.affiliation: Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Edward M
authors.initials: EM
authors.lastname: Mannina
authors.affiliation: Department of Biostatistics, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Cynthia S
authors.initials: CS
authors.lastname: Johnson
authors.affiliation: Department of Biostatistics, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Perkins
authors.affiliation: Department of Biostatistics, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Sandra
authors.initials: S
authors.lastname: Althouse
authors.affiliation: Department of Surgery, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Mary
authors.initials: M
authors.lastname: Maluccio
authors.affiliation: Department of Gastroenterology, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Paul
authors.initials: P
authors.lastname: Kwo
authors.affiliation: Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, Indiana. Electronic address: hcardenes@aol.com.
authors.forename: Higinia
authors.initials: H
authors.lastname: Cárdenes
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D018572:Disease-Free Survival; D019583:Dose Fractionation, Radiation; D005260:Female; D006801:Humans; D008099:Liver / Q000473:pathology*; D008113:Liver Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D016634:Radiosurgery / Q000379:methods*; D011879:Radiotherapy Dosage; D016896:Treatment Outcome; D055815:Young Adult