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BackgroundThe identification of new therapies for high-risk (HR) hepatoblastoma is challenging. Children's Oncology Group study AHEP0731 included a HR stratum to explore the efficacy of novel agents. Herein, the authors report the response rate to the combination of vincristine (V) and irinotecan (I) and the outcome of patients with high-risk hepatoblastoma.MethodsPatients with newly diagnosed metastatic hepatoblastoma or those with a serum α-fetoprotein (AFP) level 1 log10 ) decline in their AFP level. Responders were to receive 2 additional cycles of VI intermixed with 6 cycles of the combination of cisplatin, doxorubicin, 5-fluorouracil, and vincristine (C5VD). Nonresponders were to receive 6 cycles of C5VD alone.ResultsA total of 32 patients with a median age at diagnosis of 26 months (range, 11-159 months) were enrolled between September 2009 and February 2012. Fourteen of 30 evaluable patients were responders (RECIST and AFP in 6 patients, RECIST only in 3 patients, and AFP only in 5 patients). The median AFP decline after 2 cycles of VI for the entire group was 345,565 ng/mL (85% of the initial AFP). The 3-year event-free and overall survival rates were 49% (95% confidence interval, 30%-65%) and 62% (95% confidence interval, 42%-77%), respectively.ConclusionsThe VI combination appears to have substantial activity against HR hepatoblastoma. The ultimate impact of this regimen in improving the outcomes of children with HR hepatoblastoma remains to be determined. Cancer 2017;123:2360-2367. © 2017 American Cancer Society.

Background: Specific patients with hepatoblastoma (HB) and hepatocellular carcinoma (HCC) do not meet eligibility criteria for Children's Oncology Group (COG) trials, limiting an understanding of how comorbidities affect the outcome. We define such a population for future-focused care improvements., Methods: A questionnaire was sent to COG institutional principal investigators to obtain anonymized data regarding patients with a liver tumor diagnosis not enrolled on AHEP1531 due to ineligibility by trial criteria or other reasons (excluding parent/patient preference)., Results: Responses received for 55 patients (38 HB, 4 HCC, and 13 not reported) included 12 excluded from further analysis due to various factors, including lack of additional information. Five patients were eligible but not enrolled due to pandemic-related staffing issues (n = 1) or the best interest of the patient (physician preference, n = 1; risk for poor tolerance of chemotherapy, n = 1; not specified, n = 2). The remaining 38 patients included 1 ineligible due to a prior malignancy, 9 due to performance status, and 4 due to timing requirements. Thirty-five of 38 patients were ineligible due to organ function criteria (pulmonary/oxygen requirement, n = 25; renal, n = 10; liver, n = 4; cardiac, n = 3). Seven patients were ineligible due to two or more organ function criteria. Twenty-five of 38 patients were reported to have a preexisting condition including 4 patients with trisomy 18., Conclusions: Patients with HB, and potentially HCC, who are ineligible for COG trials are primarily patients with an oxygen requirement and/or renal insufficiency, often associated with preexisting congenital conditions. Such patients would benefit from future studies to improve outcomes., (© 2024 Wiley Periodicals LLC.)

Purpose To determine whether the pattern of lung nodules in children with metastatic hepatoblastoma (HB) correlates with outcome. Methods Thirty-two patients with metastatic HB were enrolled on Children's Oncology Group Protocol AHEP0731 and treated with vincristine and irinotecan (VI). Responders to VI received two additional cycles of VI intermixed with six cycles of cisplatin/fluorouracil/vincristine/doxorubicin (C5VD), and nonresponders received six cycles of C5VD alone. Patients were imaged after every two cycles and at the conclusion of therapy. All computed tomography scans and pathology reports were centrally reviewed, and information was collected regarding lung nodule number, size, laterality, timing of resolution, and pulmonary surgery. Results Among the 29 evaluable patients, only 31% met Response Evaluation Criteria in Solid Tumors (RECIST) for measurable metastatic disease. The presence of measurable disease by RECIST, the sum of nodule diameters greater than or equal to the cumulative cohort median size, bilateral disease, and ≥ 10 nodules were each associated with an increased risk for an event-free survival event ( P = .48, P = .08, P = .065, P = .03, respectively), with nodule number meeting statistical significance. Ten patients underwent pulmonary resection/metastasectomy at various time points, the benefit of which could not be determined because of small patient numbers. Conclusion Children with metastatic HB have a poor prognosis. Overall tumor burden may be an important prognostic factor for these patients. Lesions that fail to meet RECIST size criteria (ie, those < 10 mm) at diagnosis may contain viable tumor, whereas residual lesions at the end of therapy may constitute eradicated tumor/scar tissue. Patients may benefit from risk stratification on the basis of the burden of lung metastatic disease at diagnosis.

Complete surgical resection is essential to long-term survival in children with hepatoblastoma. We present the guidelines from the Children's Oncology Group (COG), liver tumor study group of the Societe Internationale Oncologie Pediatrique (SIOPEL), and German Pediatric Oncology Group (GPOH) for early referral of children with potentially unresectable hepatoblastoma to a specialty center with expertise in extreme resection and liver transplantation. Patients who will become candidates for liver transplantation should receive chemotherapy following the same protocols as for children undergoing a partial hepatectomy. The Pediatric Liver Unresectable Tumor Observatory (PLUTO) is an international prospective database established to collect data and make future recommendations on controversial issues regarding the use of transplant in hepatoblastoma including: 1) What is the optimal treatment of multifocal tumors. 2) What is the role of extreme resection vs. liver transplant in patients with major venous involvement. 3) What is the role of transplant in patients who present with lung metastasis. 3) Should patients with tumor relapse be offered a rescue transplant. 4) What is the role of pre- and post- transplant chemotherapy.