In an analysis of National Wilms Tumor Study (NWTS) protocols reported in the Journal of Clinical Oncology, Oosterom et al identified the incidence of treatment-related severe hepatopathy in patients with Wilms tumor and described outcomes in these patients.
Study Details
The study involved data from 8,862 patients enrolled in NWTS protocols 3–5 (May 1979 to May 2002) who received chemotherapy with or without radiotherapy. Severe hepatopathy was defined using established hepatopathy grading scales and clinical criteria.
Key Findings
Overall, 71 (0.8%) patients met criteria for severe hepatopathy. Patients received a variety of treatment regimens, but severe hepatopathy was observed most frequently (80.3%) after chemotherapy with actinomycin and vincristine. A total of 60.6% of patients received radiotherapy, and 56.3% had right-sided tumors. Median time from therapy initiation to severe hepatopathy was 51 days (range = 2–293 days). Among patients receiving radiotherapy, onset of hepatopathy occurred after initiation of radiotherapy in 85%; median time from radiotherapy initiation to onset of hepatopathy was 52 days (range = 1–287 days).
Grade 1 to 4 thrombocytopenia was observed in 67.6% of patients at initial occurrence of severe hepatopathy (median = 22,000/µL); of those with thrombocytopenia, 84.1% had grade 3 or 4 thrombocytopenia.
Among 69 children with severe hepatopathy occurring before the end of therapy and posthepatopathy treatment information available, chemotherapy was delayed for 65% (69% of these at reduced dose), continued without delay for 20% (57% of these at reduced dose), and stopped completely for 15% (n = 10, with 4 dying from hepatopathy). A total of 42% of patients with dose reductions achieved full dose by end of therapy.
Among the 59 patients who resumed chemotherapy with or without delay or dose reduction after severe hepatopathy, 5-year posthepatopathy event-free survival was 89% (95% confidence interval [CI] = 81%–98%). Event-free survival did not differ according to whether chemotherapy was delayed (P = .89) or reduced in dose (P = .62).
Genomic analysis for candidate polymorphisms associated with severe hepatopathy was performed in 14 patients, with no associated pharmacogenomic polymorphisms being identified.
The investigators concluded, “The incidence of severe hepatopathy 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.”
Elizabeth A. Mullen, MD, of Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The research was supported by grants from the National Institutes of Health, National Cancer Institute, and others. For full disclosures of the study authors, visit ascopubs.org.
