TUMOR NECROSIS PREDICTS SURVIVAL FOLLOWING NEO-ADJUVANT CHEMOTHERAPY FOR HEPATOBLASTOMA


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Title: TUMOR NECROSIS PREDICTS SURVIVAL FOLLOWING NEO-ADJUVANT CHEMOTHERAPY FOR HEPATOBLASTOMA
Authors: R. Venkatramani, L. Wang, J. Malvar, R. Sposto, M. Malogolowkin, L. Mascarenhas
Theme: Solid Tumors
Primary Institution: Children's Hospital Los Angeles
Institution City: Los Angeles
Institution State: California
Year: 2011
Background: Hepatoblastoma is the most common primary hepatic malignant neoplasm in children. Majority of patients have surgically unresectable primary tumors at initial diagnosis (Stage III and IV) and require neo-adjuvant chemotherapy. These patients have a less favorable prognosis. Tumor response to chemotherapy predicts outcome in children with acute lymphoblastic leukemia, osteosarcoma and Ewing Sarcoma but has not been investigated in hepatoblastoma.

Objectives: To evaluate tumor necrosis following neo-adjuvant chemotherapy as a prognostic indicator of survival in hepatoblastoma.

Design: Children with newly diagnosed stage III and IV hepatoblastoma at Children’s Hospital Los Angeles between 1986 and 2008 were identified from the tumor registry. Those who underwent surgical resection of the primary tumor following neo-adjuvant chemotherapy were included. Demographic data, clinical features, laboratory values, tumor necrosis, disease status and vital status were collected by retrospective review of medical records.

Results: 32 patients (22 male) were included. Median age at diagnosis was 1.35 years (range 0-12.7 years). Median follow-up was 3.9 years (range 0.5-23 years). Twenty six patients (81.2%) had stage III and six patients (18.8%) had stage IV disease. Patients received a median of 4 cycles (range 2-15 cycles) of neo-adjuvant chemotherapy (cisplatin, carboplatin, doxorubicin, vincristine and fluorouracil). Gross total surgical resection was achieved in 27 patients and complete resection documented by histology in 22 patients. Three year event free survival (EFS) and overall survival (OS) were 70.3 ± 8.3% and 76.8 ± 7.6% respectively. Percent tumor necrosis, platelet count at diagnosis, serum alpha fetoprotein following 2nd and 4th chemotherapy cycles, extent of surgical resection and pathologic margins were statistically significant predictors for both EFS and OS by univariate analysis using Cox proportional hazards model. Serum alpha fetoprotein at diagnosis was significant for EFS but not OS. Multivariate analysis revealed percent tumor necrosis, platelet count at diagnosis and pathology margins as significant predictors for both EFS (all p<0.005) and OS (all p<0.02).

Conclusion: Tumor necrosis following neo-adjuvant chemotherapy predicts EFS and OS in patients with hepatoblastoma. If validated and confirmed in a larger series, tumor necrosis maybe used to modify therapy based on histological response to improve survival in children with hepatoblastoma.