Hepatoblastoma relapses after front-line therapy according to SIOPEL protocols: clinical characteristics and outcome

Hepatoblastoma (HB) is the most common primary malignant liver tumor in children. Relapses of HB are rare and make up no more than 12% of cases among patients who have achieved complete response after the first-line therapy. The aim of the study was to analyze the incidence, clinical characteristics and outcome of HB relapses in patients treated according to SIOPEL protocols. This study is supported by the Independent Ethics Committee and approved by the Academic Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology. 74 patients with HB were treated for the period 02.2012–12.2018 (82 months). Patients were stratified and treated according to SIOPEL protocols. Relapses were detected in 7/70 (10,0%) patients, who achieved complete response after front-line therapy. We analyzed demographic data, initial tumor characteristics, details of front-line therapy, characteristics of HB relapses and treatment of relapse. Median age at the time of diagnosis of HB was 13,3 (range 0,6–62,9) months. Male:female ratio – 1:0,4. The distribution by PRETEXT stages: II – 2 (28,6%), III – 1 (14,3%), IV – 4 (57,1%). 4 (57,1%) patients had distant metastases. Patients were stratified to standard-risk group – 2 (28,6%) and high-risk group – 5 (71,4%). 3 (42,8%) underwent liver transplantation (LT). Median age at the time of relapse was 33,5 (range 11,9–74,4) months. Median time from the completion of front-line therapy to relapse – 5,3 (range 3,2–19,1) months. Median AFP level at relapse – 35,0 (range 1,8–34160,4) ng/ml. Methods of relapse detection: routine follow-up – 5 (71,4%), clinical symptoms – 2 (28,6%). The latter 2 patients with initially AFP-secreting HB had normal AFP levels at relapse. Pattern of relapse: systemic – 5 (71,4%), combined – 2 (28,6%). The majority of patients received irinotecan-based chemotherapy – 5 (71,4%). Chemotherapy was combined with surgery in 6 (85,7%) cases. Median follow-up time from the moment of relapse was 22,4 (range 5,2–51,3) months. Outcomes: 5 (71,4%) alive (4/5 – with no evidence of disease, 1/5 – with active disease), 2 (28,6%) died of the disease. 3-year overall survival after relapse was 66,6 ± 19,2%. The main conclusion of the study was that combination of second-line chemotherapy with surgical resections allowed achieving long-lasting survival in some HB relapsed patients, including patients who had previously undergone LT.