PMID- 37343199 OWN - NLM STAT- MEDLINE DCOM- 20230908 LR - 20240211 IS - 1527-7755 (Electronic) IS - 0732-183X (Print) IS - 0732-183X (Linking) VI - 41 IP - 26 DP - 2023 Sep 10 TI - Severe Hepatopathy in National Wilms Tumor Studies 3-5: Prevalence, Clinical Features, and Outcomes After Reintroduction of Chemotherapy. PG - 4247-4256 LID - 10.1200/JCO.22.02555 [doi] AB - 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. FAU - Oosterom, Natanja AU - Oosterom N AUID- ORCID: 0000-0001-9871-1887 AD - Princess Maxima Center for Pediatric Oncology, Utrecht, the Netherlands. FAU - Gooskens, Saskia L M AU - Gooskens SLM AD - Princess Maxima Center for Pediatric Oncology, Utrecht, the Netherlands. FAU - Renfro, Lindsay A AU - Renfro LA AD - University of Southern California and Children's Oncology Group, Los Angeles, CA. FAU - Perlman, Elizabeth J AU - Perlman EJ AUID- ORCID: 0000-0001-6853-6221 AD - Department of Pathology and Laboratory Medicine, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL. FAU - van den Heuvel-Eibrink, Marry M AU - van den Heuvel-Eibrink MM AD - Princess Maxima Center for Pediatric Oncology, Utrecht, the Netherlands. FAU - Hamilton, Thomas E AU - Hamilton TE AD - Division of General, Thoracic and Fetal Surgery, Children's Hospital of Philadelphia, Philadelphia, PA. FAU - Green, Daniel M AU - Green DM AUID- ORCID: 0000-0002-5156-5410 AD - Department of Epidemiology and Cancer Control Oncology, St Jude Children's Research Hospital, Memphis, TN. FAU - Grundy, Paul E AU - Grundy PE AUID- ORCID: 0000-0003-2645-8266 AD - Department of Pediatric Oncology, University of Alberta Hospital, Edmonton, AB, Canada. FAU - Daw, Najat C AU - Daw NC AUID- ORCID: 0000-0002-6941-8005 AD - Division of Pediatrics, University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Geller, James I AU - Geller JI AD - Division of Oncology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH. FAU - Dome, Jeffrey S AU - Dome JS AUID- ORCID: 0000-0002-9037-369X AD - Division of Oncology, Children's National Hospital and Department of Pediatrics, George Washington University School of Medicine and Health Sciences, Washington, DC. FAU - Fernandez, Conrad V AU - Fernandez CV AUID- ORCID: 0000-0002-0746-8306 AD - Division of Pediatric Hematology and Oncology, IWK Health Centre and Dalhouise University, Halifax, NS, Canada. FAU - Mullen, Elizabeth A AU - Mullen EA AUID- ORCID: 0000-0002-6704-0002 AD - Department of Pediatric Hematology/Oncology, Dana-Farber Cancer Institute/Boston Children's Hospital, Boston, MA. LA - eng GR - R01 CA054498/CA/NCI NIH HHS/United States GR - U10 CA098543/CA/NCI NIH HHS/United States GR - U10 CA180886/CA/NCI NIH HHS/United States GR - U10 CA180899/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20230621 PL - United States TA - J Clin Oncol JT - Journal of clinical oncology : official journal of the American Society of Clinical Oncology JID - 8309333 RN - Wilms Tumor 3 SB - IM MH - Child MH - Humans MH - Infant MH - Prevalence MH - *Wilms Tumor/drug therapy/genetics/pathology MH - *Kidney Neoplasms/pathology MH - Combined Modality Therapy MH - Antineoplastic Combined Chemotherapy Protocols/therapeutic use MH - *Thrombocytopenia/drug therapy MH - *Liver Diseases PMC - PMC10852371 COIS- The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center. Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments). EDAT- 2023/06/21 19:15 MHDA- 2023/09/08 06:43 PMCR- 2024/09/10 CRDT- 2023/06/21 16:03 PHST- 2024/09/10 00:00 [pmc-release] PHST- 2023/09/08 06:43 [medline] PHST- 2023/06/21 19:15 [pubmed] PHST- 2023/06/21 16:03 [entrez] AID - JCO.22.02555 [pii] AID - 10.1200/JCO.22.02555 [doi] PST - ppublish SO - J Clin Oncol. 2023 Sep 10;41(26):4247-4256. doi: 10.1200/JCO.22.02555. Epub 2023 Jun 21.