IV. Pediatric Liver Tumor Projects
a. International Scientific Collaborations
The Pediatric Oncology and Hematology Research Platform is currently conducting a medical research project on pediatric liver cancer (hepatoblastoma and hepatocarcinoma), a very rare cancer that accounts for only 1% of all childhood cancers. To carry out this project, Prof. Ansari has partnered with other researchers from Europe, Japan, and the United States. The pediatric liver tumor group, integrated within the HUG, is responsible for all children with liver cancer at the national level. The international clinical study on the treatment of liver tumors in children, titled PHITT (Paediatric Hepatic International Tumour Trial), as well as the SIOPEL group study—for which Prof. Ansari is also the lead international investigator—have contributed to this centralization. This project has received support from the European Union via the Horizon 2020 program, as well as support from the Swiss Cancer League.
b. RELIEVE
This project involves developing an international registry for children who relapse from liver cancer (RELIVE). Even though cure rates are high (80 to 90%) thanks to therapeutic progress, a relapse or tumor progression carries an extremely poor prognosis. The more relapses occur, the more long-term survival chances decrease. The goal is to identify the most promising therapeutic combinations. The RELIVE project is the first of its scale to collect clinical, therapeutic, and biological data internationally for children with refractory or recurrent liver tumors (hepatoblastoma, hepatocellular carcinoma, or HCN NOS). It aims to describe the treatments applied—chemotherapy, surgery, and local interventions—and their short- and long-term results, in order to identify the most effective strategies. This study, based on the largest cohort of patients with relapsed or refractory hepatoblastoma, shows that certain factors (type and timing of relapse, age, previous treatments such as cisplatin/doxorubicin) significantly influence overall survival, regardless of the response to other treatments. It highlights an urgent need to develop new therapies, particularly for patients with early progression or relapse. This data collection will therefore help guide the drafting of future international protocols and the development of new pediatric therapies. Thanks to this project, hospitals in 15 countries (Switzerland, Spain, France, Belgium, the Netherlands, Poland, Germany, the United Kingdom, Ireland, the United States, Canada, Japan, Australia, New Zealand, and Hong Kong) are already participating. They are analyzing patient medical records from the last 30 years. The analysis of the RELIVE registry is expected to help harmonize and improve treatments for these high-risk patients. Results are expected by 2026.
Learn more https://relive-international.net/
c. SWISSLIVER, the Swiss national registry for pediatric patients with malignant liver tumors
Liver tumors are the third most common group of intra-abdominal tumors in children, after neuroblastoma and renal tumors. Pediatric malignant liver tumors are rare and mainly include hepatoblastoma (HB), hepatocellular carcinoma (HCC), hepatocellular neoplasm not otherwise specified (HCN NOS), and undifferentiated embryonal sarcoma of the liver (UESL). The prospective national Swissliver registry aims to systematically collect clinical, biological, histological, genetic, pharmacokinetic, and radiological data, as well as biological samples (blood, urine) and tumor and non-tumor samples from biopsies or surgeries, for patients under 18 years of age diagnosed with a malignant liver tumor in Switzerland. The samples are stored in the Geneva-based BaHOP biobank.
The Swiss national registry for pediatric malignant liver tumors tracks incidence, subtypes, and sociodemographic factors, and collects biological samples to better understand these cancers. This project involves the nine centers of the Swiss Pediatric Oncology Group (SPOG)—Aarau, Bern, Basel, Bellinzona, Geneva, Lausanne, Lucerne, St. Gallen, and Zurich. Furthermore, a national tumor board has been established to discuss each case and harmonize therapeutic decisions according to international standards, notably by leveraging data from the PHITT study. Its objectives include: describing epidemiology and clinical outcomes, evaluating and evolving therapeutic practices, enriching the biobank to identify prognostic and toxicity biomarkers, and supporting the national coordination of specialized pediatric care. The protocol was approved by the General Assembly of the Swiss Pediatric Oncology Group (SPOG) in November 2025 and is currently undergoing regulatory and administrative procedures. The HUG now acts as the sponsor and coordinator for pediatric liver tumors.
d. IT system for radiological review of the PHITT (Paediatric Hepatic International Tumour Trial), an international trial on pediatric liver tumors
The Paediatric Hepatic International Tumour Trial (PHITT) is the largest clinical trial ever conducted in pediatric liver cancers, including hepatoblastoma (HB), hepatocellular carcinoma (HCC), and hepatocellular neoplasms not otherwise specified (HCN-NOS). Conducted in collaboration between Europe, the United States, and Japan, the trial opened in Europe in 2017. It aims to optimize treatments by adapting their intensity to the risk level in order to improve survival while reducing toxicity. Patient stratification relies heavily on imaging (PRETEXT staging), but limited concordance between local and central radiological assessments highlights the need for an internationally harmonized central review.
This project proposes a retrospective centralized radiological review of 1,825 imaging exams from European patients using a dedicated cloud platform (QP-Insights). Expert radiologists from the international SIOPEL network will analyze the images at key time points to compare local and central assessments, validate the international CHIC stratification system, and meet the radiological objectives of PHITT. The platform will allow for the creation of a unique pediatric imaging repository, fostering international exploratory projects that integrate artificial intelligence, particularly for automated image analysis and the improvement of pediatric liver cancer management.
Artificial intelligence (AI) will be used in exploratory projects based on a unique pediatric imaging repository created from PHITT data. After the compilation and centralized radiological review of the exams by experts, the validated datasets will be used to evaluate the performance of AI tools for automated image analysis. AI will be tested for the automatic detection of pulmonary nodules to assess its ability to identify metastatic lesions, improve detection sensitivity, and reduce inter-observer variability. These approaches may also support quantitative image analysis and complement human expertise, without replacing the centralized radiological review.
The integration of AI is part of a later phase of the project, once the data is structured and harmonized, and aims to strengthen radiological analysis, generate new research hypotheses, and prepare for the future integration of decision-support tools in international clinical trials. Funding for this platform will enable the full completion of the centralized radiological review, which is essential for analyzing PHITT results, refining risk stratification, optimizing treatments, and supporting future research projects on pediatric liver cancers, including the integration of AI tools.
e. EXPLORER study
Despite significant progress, the prognosis for children with metastatic hepatoblastoma remains unfavorable, and PLADO neoadjuvant chemotherapy allows for complete remission in approximately 79% of patients, with complete resection in 74% of cases. The SIOPEL Explorer Phase Ib-II study is evaluating the addition of panobinostat, a histone deacetylase inhibitor, to the PLADO regimen to target the epigenetic alterations of hepatoblastoma. The study measures the pharmacokinetic and pharmacodynamic profile of panobinostat and cisplatin, as well as their combined effect on antitumor efficacy and toxicity. This scientific protocol is currently being written. Pharmacogenetic analyses and tests on patient-derived models aim to identify predictive markers of response and toxicity to personalize treatments. This work will help define safe and effective doses, optimize treatments, and potentially improve survival while reducing adverse effects in this high-risk pediatric population.
