title: Tumor necrosis predicts survival following neo-adjuvant chemotherapy for hepatoblastoma.
abstract: BACKGROUND
  Tumor response to chemotherapy has been shown to predict outcome in children with acute lymphoblastic leukemia, osteosarcoma, and Ewing Sarcoma. We evaluated whether tumor necrosis following neo-adjuvant chemotherapy is prognostic for survival in hepatoblastoma (HB).
  
  
  METHODS
  Primary tumors from children with newly diagnosed stage III and IV HB who underwent surgical resection following neo-adjuvant chemotherapy were evaluated histologically for the extent of tumor necrosis (total diameter of necrotic and fibrotic tissue divided by total diameter of tumor). Clinical features, laboratory values, pathological features, treatment delivered, and vital status were recorded. Univariate and multivariate Cox regression analyses were performed to evaluate prognostic factors.
  
  
  RESULTS
  Thirty-two patients were evaluable. After a median of four cycles of neo-adjuvant chemotherapy gross total surgical resection was achieved in 29 patients and complete resection documented by histology in 22 patients. Three-year event free survival (EFS) and overall survival (OS) of the evaluable patients were 70.3 ± 8.3% and 76.8 ± 7.6%, respectively. Extent of tumor necrosis, platelet count at diagnosis, decline in serum alpha fetoprotein, and surgical margin status (positive vs. negative) were statistically significant predictors for both EFS and OS by univariate analysis. Multivariate analyses revealed that extent of tumor necrosis and surgical margin status predicted improved EFS (P < 0.001) and OS (P < 0.0001).
  
  
  CONCLUSIONS
  Extent of tumor necrosis following neo-adjuvant chemotherapy is an independent prognostic factor in patients with newly diagnosed HB. Histological response may potentially be used in strategies to modify post-surgical therapy to improve survival in HB.
authors.affiliation: Division of Hematology/Oncology, Children's Hospital Los Angeles, Los Angeles, California 90027, USA. rvenkatramani@chla.usc.edu
authors.forename: Rajkumar
authors.initials: R
authors.lastname: Venkatramani
authors.forename: Larry
authors.initials: L
authors.lastname: Wang
authors.forename: Jemily
authors.initials: J
authors.lastname: Malvar
authors.forename: Dennis
authors.initials: D
authors.lastname: Dias
authors.forename: Richard
authors.initials: R
authors.lastname: Sposto
authors.forename: Marcio H
authors.initials: MH
authors.lastname: Malogolowkin
authors.forename: Leo
authors.initials: L
authors.lastname: Mascarenhas
mesh_terms: D017024:Chemotherapy, Adjuvant; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D018197:Hepatoblastoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D008297:Male; D009336:Necrosis; D020360:Neoadjuvant Therapy; D011379:Prognosis; D000509:alpha-Fetoproteins / Q000627:therapeutic use
chemical_list: D000509:alpha-Fetoproteins