TY - JOUR
T1 - Histologic type predicts disparate outcomes in pediatric hepatocellular neoplasms
T2 - A Pediatric Surgical Oncology Research Collaborative study
AU - Short, Scott S.
AU - Kastenberg, Zachary J.
AU - Wei, Guo
AU - Bondoc, Alex
AU - Dasgupta, Roshni
AU - Tiao, Greg M.
AU - Watters, Erin
AU - Heaton, Todd E.
AU - Lotakis, Dimitra
AU - La Quaglia, Michael P.
AU - Murphy, Andrew J.
AU - Davidoff, Andrew M.
AU - Mansfield, Sara A.
AU - Langham, Max R.
AU - Lautz, Timothy B.
AU - Superina, Riccardo A.
AU - Ott, Katherine C.
AU - Malek, Marcus M.
AU - Morgan, Katrina M.
AU - Kim, Eugene S.
AU - Zamora, Abigail
AU - Lascano, Danny
AU - Roach, Jonathan
AU - Murphy, Joseph T.
AU - Rothstein, David H.
AU - Vasudevan, Sanjeev A.
AU - Whitlock, Richard
AU - Lal, Dave R.
AU - Hallis, Brian
AU - Bütter, Andreana
AU - Baertschiger, Reto M.
AU - Lapidus-Krol, Eveline
AU - Putra, Juan
AU - Tracy, Elisabeth R.
AU - Aldrink, Jennifer H.
AU - Apfeld, Jordan
AU - Le, Hau D.
AU - Park, Keon Y.
AU - Rich, Barrie S.
AU - Glick, Richard D.
AU - Fialkowski, Elizabeth A.
AU - Utria, Alan F.
AU - Meyers, Rebecka L.
AU - Riehle, Kimberly J.
N1 - Funding Information:
This investigation was supported by the University of Utah Population Health Research Foundation, with funding in part from the National Center for Advancing Translational Sciences of the National Institutes of Health under award UL1TR002538.
Funding Information:
Max R. Langham reports travel support from the Children's Oncology Group outside the submitted work. Elizabeth A. Fialkowski reports a research grant from Oregon Health and Science University outside the submitted work. Kimberly J. Riehle reports a grant from the US Department of Defense and travel support from the Fibrolamellar Foundation outside the submitted work. The remaining authors made no disclosures.
Publisher Copyright:
© 2022 American Cancer Society.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - fibrolamellar
KW - hepatobiliary
KW - hepatocellular carcinoma (HCC)
KW - hepatocellular neoplasm, not otherwise specified (HCN-NOS)
KW - pediatric oncology
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U2 - 10.1002/cncr.34256
DO - 10.1002/cncr.34256
M3 - Article
C2 - 35561331
AN - SCOPUS:85129850152
SN - 0008-543X
JO - Cancer
JF - Cancer
ER -