Evidence-based clinical practice guidelines for pediatric hepatoblastoma: a systematic review and expert...

Hepatoblastoma (HB) is the most common primary liver malignancy in children, predominantly affecting those younger than 3 years of age. Although the overall survival rate has improved significantly over the past few decades, standardized clinical practice guidelines for HB in Korea have been lacking. This clinical practice guideline was developed to provide evidence-based recommendations for the diagnosis and treatment of HB in children. A multidisciplinary working group comprising pediatric hematologists/oncologists, radiologists, surgeons, pathologists, and methodologists systematically reviewed the literature published up to May 2023. For pretreatment imaging, both abdominal computed tomography and magnetic resonance imaging are useful for PRE-Treatment EXTent of disease (PRETEXT) staging, with each modality offering distinct advantages. PRETEXT staging at diagnosis is recommended as it provides valuable prognostic information. For standard-risk HB (PRETEXT I-III without metastasis and alpha-fetoprotein ≥100 ng/mL), cisplatinbased chemotherapy without doxorubicin is recommended over cisplatin-doxorubicin combination therapy, as it demonstrates equivalent survival outcomes with fewer adverse effects. In carefully selected patients who are eligible for complete resection at diagnosis, upfront surgery without neoadjuvant chemotherapy should be considered to spare unnecessary chemotherapy and its toxicities. For patients with residual pulmonary metastases after chemotherapy, pulmonary metastasectomy should be considered. Sodium thiosulfate administration following cisplatin should be considered to reduce ototoxicity, although the supporting evidence is derived predominantly from standard-risk patients and its availability in Korea remains limited. Regarding histological subtypes, well-differentiated fetal HB is associated with favorable outcomes and may be treated with surgery alone, whereas the small cell undifferentiated pattern is no longer classified as a HB subtype and requires immunohistochemical and molecular testing to distinguish it from malignant rhabdoid tumor and other small round cell tumors. This guideline represents the first evidence-based clinical practice guideline for pediatric HB in Korea. It aims to standardize the diagnostic and therapeutic approaches, ultimately improving outcomes for Korean children with HB. Given the rarity of this tumor, international collaboration and prospective data collection remain essential for future guideline updates.