Treatment outcomes and prognostic factors in children with hepatoblastoma using a risk‐stratified approach

Abstract

Background Not all the significant progress made in the management of children with hepatoblastoma (HB) has translated into improved outcomes in limited‐resource settings. There are limited data on outcomes in children with HB from India. Methods All patients diagnosed with HB between July 2013 and December 2020 were risk‐stratified and treated as per International Liver Tumor Strategy Group (SIOPEL). Patients with standard‐risk HB received cisplatin monotherapy and those with high‐risk HB received alternating cycles of cisplatin and the combination of carboplatin plus doxorubicin. Data regarding demographic details, chemotherapy, surgery, liver transplantation, outcomes, prognostic factors, and toxicity were collected. Results Of 157 patients with HB, 117 (74%) were high risk, 31 (20%) were standard risk, and nine (6%) unknown. Patients with standard‐risk disease had excellent outcomes, with 3‐year event‐free survival (EFS) and overall survival (OS) of 96% and 100%, respectively. Among high‐risk HB, six underwent orthotopic liver transplantation of which four were alive at last follow‐up. The 3‐year EFS and OS of patients with high‐risk disease was 56% and 66%, respectively. Outcomes of patients with PRETEXT IV (3‐year EFS: 42%, 3‐year OS: 50%) and metastatic disease (3‐year EFS: 30%, 3‐year OS: 50%) were dismal. Patients with serum alpha‐fetoprotein (AFP) reduction greater than 90% following two courses of chemotherapy had favorable outcomes; 3‐year EFS: 80% versus 58% (p = .013) and 3‐year OS: 95% vs. 68% (p < .01). Only two (6%) of 31 patients with relapse/refractory HB were alive at a median follow‐up of 36 months, and both had received salvage chemotherapy and surgery. Conclusions While children with standard‐risk HB had excellent outcomes, those with high‐risk disease continue to do poorly. Serial monitoring of serum AFP values is a cost‐effective and reliable predictor of outcomes. Orthotopic liver transplantation remains a viable option for inoperable disease in resource‐limited settings as well.

Callow and Vernal-Hepatoblastoma

“…Epithelial/ foetal hepatoblastoma appears immune reactive to β catenin or glutamine synthetase whereas well differentiated neoplasms with minimal mitosis or tumours with mesenchymal configuration appear immune non reactive. Besides, tumour cells appear immune reactive to alpha fetoprotein(AFP), HepPar1, polyclonal carcinoembryonic antigen(pCEA), glypican 3, pancytokeratin, CK7, CK19 and integrase interactor1 (INI1) or SMARCB1 [7,8].…”

“…Subset of small cell undifferentiated hepatoblastoma appear immune non reactive to integrase interactor 1(INI1) or SMARCB1 and depict inferior prognostic outcomes [7,8]. Hepatoblastoma requires segregation from neoplasms such as rhabdoid tumour, well differentiated hepatocellular carcinoma, focal nodular hyperplasia, hepatic adenoma, malignant lymphoma or hepatic metastases from various primary carcinomas [7,8]. Hepatoblastoma can be appropriately ascertained upon assessment of clinical features, biochemical assay and radiological features.…”

“…Certain neoplasms may require evaluation with fine needle aspiration cytology (FNAC) or tissue sampling of surgical specimens. Majority (-90%) of subjects depict significantly elevated levels of serum alfa fetoprotein (AFP) [7,8].…”

“…Mixed epithelial and mesenchymal tumours represent as heterogeneous neoplasms on account of discernible components of osteoid, cartilaginous and fibrous tissue. Frequently, tumours display echogenic calcification with acoustic shadows and anechoic foci indicative of focal haemorrhage or necrosis [7,8]. Computerized tomography exhibits a well defined, hypo-attenuating tumefaction with uniform perimeter, in contrast to adjacent hepatic parenchyma.…”

“…Upon administration of contrast medium, diffuse, heterogeneous image enhancement is commonly encountered. An estimated 50% neoplasms appear lobulated or traversed by fibrous tissue septa, especially upon contrast enhanced imaging [7,8].…”