Severe Hepatopathy in National Wilms Tumor Studies 3-5: Prevalence, Clinical Features, and Outcomes After Reintroduction of Chemotherapy

Natanja Oosterom, Princess Maxima Center for Pediatric Oncology, Utrecht, the Netherlands.
Saskia L. Gooskens, Princess Maxima Center for Pediatric Oncology, Utrecht, the Netherlands.
Lindsay A. Renfro, University of Southern California and Children's Oncology Group, Los Angeles, CA.
Elizabeth J. Perlman, Department of Pathology and Laboratory Medicine, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL.
Marry M. van den Heuvel-Eibrink, Princess Maxima Center for Pediatric Oncology, Utrecht, the Netherlands.
Thomas E. Hamilton, Division of General, Thoracic and Fetal Surgery, Children's Hospital of Philadelphia, Philadelphia, PA.
Daniel M. Green, Department of Epidemiology and Cancer Control Oncology, St Jude Children's Research Hospital, Memphis, TN.
Paul E. Grundy, Department of Pediatric Oncology, University of Alberta Hospital, Edmonton, AB, Canada.
Najat C. Daw, Division of Pediatrics, University of Texas MD Anderson Cancer Center, Houston, TX.
James I. Geller, Division of Oncology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH.
Jeffrey S. Dome, Division of Oncology, Children's National Hospital and Department of Pediatrics, George Washington University School of Medicine and Health Sciences, Washington, DC.
Conrad V. Fernandez, Division of Pediatric Hematology and Oncology, IWK Health Centre and Dalhouise University, Halifax, NS, Canada.
Elizabeth A. Mullen, Department of Pediatric Hematology/Oncology, Dana-Farber Cancer Institute/Boston Children's Hospital, Boston, MA.

Document Type

Journal Article

Publication Date

6-21-2023

Journal

Journal of clinical oncology : official journal of the American Society of Clinical Oncology

DOI

10.1200/JCO.22.02555

Abstract

PURPOSE: The safety of reintroducing chemotherapy in the pediatric renal tumor setting after severe hepatopathy (SH), including sinusoidal obstruction syndrome (SOS), is uncertain. We describe the incidence, severity, outcomes, and impact on subsequent treatment for patients with SH from National Wilms Tumor Study (NWTS) protocols 3-5. PATIENTS AND METHODS: Archived charts for patients enrolled on NWTS 3-5 who met study inclusion criteria for SH by using established hepatopathy grading scales and clinical criteria were reviewed for demographics, tumor characteristics, radio- and chemotherapy details, SH-related dose modifications, and oncologic outcomes. Genomic analysis for candidate polymorphisms associated with SH was performed in 14 patients. RESULTS: Seventy-one of 8,862 patients (0.8%) met study inclusion criteria. The median time from therapy initiation to SH was 51 days (range, 2-293 days). Sixty percent received radiotherapy, and 56% had right-sided tumors. Grade 1-4 thrombocytopenia was noted in 70% at initial occurrence of SH (median 22,000/microliter). Among 69 of 71 children with SH occurring before the end of therapy (EOT) and post-SH treatment information available, chemotherapy was delayed posthepatopathy for 65% (69% of these at a reduced dose), continued without delay for 20% (57% of these at reduced dose), and stopped completely for 15% (4 of 10 of whom died of SH). Overall, 42% of patients with dose reductions achieved full dose by EOT. The five-year post-SH event-free survival for patients who continued therapy was 89% (95% CI, 81 to 98), with no significant differences by whether delay or dose reduction occurred. We identified no SH-associated pharmacogenomic polymorphism. CONCLUSION: The incidence of SH on NWTS 3-5 was low; many had associated severe thrombocytopenia. Careful reintroduction of chemotherapy appeared to be feasible for the majority of patients who developed severe chemotherapy- and/or radiotherapy-induced liver toxicity.

Department

Pediatrics

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