Histologic type predicts disparate outcomes in pediatric hepatocellular neoplasms: A Pediatric Surgical Oncology Research Collaborative study

Abstract

Background Hepatocellular carcinoma (HCC) is a rare cancer in children, with various histologic subtypes and a paucity of data to guide clinical management and predict prognosis. Methods A multi‐institutional review of children with hepatocellular neoplasms was performed, including demographic, staging, treatment, and outcomes data. Patients were categorized as having conventional HCC (cHCC) with or without underlying liver disease, fibrolamellar carcinoma (FLC), and hepatoblastoma with HCC features (HB‐HCC). Univariate and multivariate analyses identified predictors of mortality and relapse. RESULTS In total, 262 children were identified; and an institutional histologic review revealed 110 cHCCs (42%; 69 normal background liver, 34 inflammatory/cirrhotic, 7 unknown), 119 FLCs (45%), and 33 HB‐HCCs (12%). The authors observed notable differences in presentation and behavior among tumor subtypes, including increased lymph node involvement in FLC and higher stage in cHCC. Factors associated with mortality included cHCC (hazard ratio [HR], 1.63; P = .038), elevated α‐fetoprotein (HR, 3.1; P = .014), multifocality (HR, 2.4; P < .001), and PRETEXT (pretreatment extent of disease) stage IV (HR, 5.76; P < .001). Multivariate analysis identified increased mortality in cHCC versus FLC (HR, 2.2; P = .004) and in unresectable tumors (HR, 3.4; P < .001). Disease‐free status at any point predicted survival. Conclusions This multi‐institutional, detailed data set allowed a comprehensive analysis of outcomes for children with these rare hepatocellular neoplasms. The current data demonstrated that pediatric HCC subtypes are not equivalent entities because FLC and cHCC have distinct anatomic patterns and outcomes in concert with their known molecular differences. This data set will be further used to elucidate the impact of histology on specific treatment responses, with the goal of designing risk‐stratified algorithms for children with HCC. Lay Summary This is the largest reported granular data set on children with hepatocellular carcinoma. The study evaluates different subtypes of hepatocellular carcinoma and identifies key differences between subtypes. This information is pivotal in improving understanding of these rare cancers and may be used to improve clinical management and subsequent outcome in children with these rare malignancies.

Cytomorphology of paediatric hepatocellular carcinoma: A useful diagnostic adjunct

“…Although tumour with mixed morphological features of HCC and HB or hepatocellular neoplasm, not otherwise specified, has been described, none of our cases showed these features. 24,25 Large tumours can show heterogeneity at both cellular as well as molecular levels, which may occur between recurrent and primary tumours, among different synchronous tumours, and in different regions of a single tumour. 26 Owing to lesional heterogeneity, cytological or in one to two-cell-thick cords in the former as well as in hepatocellular adenoma while more than two-cell-thick cords are common in HCC.…”

Children's Oncology Group's 2023 blueprint for research: Liver tumors

“…There is no validated staging or risk‐stratification algorithm for pediatric patients with HCC; however, surgical staging and PRETEXT have been applied. A recent multi‐institutional retrospective report identified the presence of an elevated AFP level at diagnosis, multifocality (as an indicator of resectability), and PRETEXT IV as poor prognostic factors 42 . The historical approach of combining the prospective study of patients with HB and HCC on the same trial, with the same regimens, is no longer accepted in the current era, thereby resulting in the dedicated study of HCC on the current AHEP1531/PHITT trial 20,21 …”

Management of undifferentiated embryonal sarcoma of the liver: A Pediatric Surgical Oncology Research Collaborative study

“…The Pediatric Surgical Oncology Research Collaborative (PSORC, http://www.psorc.org) consists of 44 North American pediatric surgical centers that aim to improve outcomes for children with cancer through multi‐institutional collaborative investigation 16–23 . The infrastructure of PSORC provides the opportunity to study rare diseases such as UESL at a more granular level than that afforded by the evaluation of large administrative databases 9 .…”

“…9,15 The Pediatric Surgical Oncology Research Collaborative (PSORC, www.psorc.org) consists of 44 North American pediatric surgical centers that aim to improve outcomes for children with cancer through multi-institutional collaborative investigation. [16][17][18][19][20][21][22][23] The infrastructure of PSORC provides the opportunity to study rare diseases such as UESL at a more granular level than that afforded by the evaluation of large administrative databases. 9 The goal of the current study is to describe current management strategies, define factors impacting survival, and suggest potential risk stratification schema for patients with UESL using a retrospective dataset developed by PSORC institutions.…”