Hepatoblastoma is the most common malignant liver tumor in infants and preschool children, comprising 65% of pediatric liver malignancies in those under 15, with its incidence on the rise in recent years [1]. Standard therapy combines surgical resection and chemotherapy: early-stage patients boast a survival rate over 90%, yet high-risk cases only reach around 40%, highlighting unmet treatment needs.

Notably, there is no universal definition for high-risk hepatoblastoma. The U.S. COG (AHEP0731) categorizes it as stage 4 disease, AFP <100ng/ml at diagnosis (any stage), or small cell undifferentiated histology; conversely, SIOP includes factors like major vascular invasion (inferior vena cava/portal vein), intra-abdominal extrahepatic spread, distant metastasis, AFP <100ng/ml, or tumor rupture, regardless of PRETEXT stage. To improve outcomes, international teams have tested intensified chemotherapy: Europe's SIOPEL reported that escalated cisplatin-doxorubicin regimens lifted high-risk patients' 3-year overall survival to over 80% [2], though with heightened toxicity. Similarly, Germany's IPA (ifosfamide-cisplatin-doxorubicin) and Japan's ITEC (ifosfamide-doxorubicin-carboplatin-VP-16) regimens delivered significant survival benefits but also amplified side effects [3,4].

Against this backdrop, the Guangdong Anti-Cancer Association's Pediatric Oncology Committee, led by Sun Yat-sen University Cancer Center and involving 15 hospitals, is launching a multicenter prospective trial to identify optimal chemotherapy regimens for Chinese hepatoblastoma children.

Parallelly, liquid biopsy has become an oncology research priority, offering four core advantages over tissue biopsy: non-invasiveness (peripheral blood sampling avoids tumor seeding), real-time genetic/progression monitoring (eliminating repeated invasive procedures), comprehensive molecular profiling (overcoming intratumoral heterogeneity), and high accuracy (capturing primary tumor-derived data). Given hepatoblastoma's propensity for early distant metastasis and 30-40% advanced-stage survival (with limited late-stage chemo efficacy), the Nano-5hmC-Seal cfDNA epigenetic profiling method holds promise as a novel biomarker for early diagnosis, treatment prediction, recurrence monitoring, and prognosis assessment in this disease.

Sun Yat-sen University Cancer Center, the Guangdong Anti-Cancer Association's Pediatric Oncology Committee (15 participating hospitals) is launching a multicenter prospective trial to optimize chemotherapy for Chinese patients.

Liquid biopsy, with advantages of non-invasiveness, real-time monitoring, comprehensive profiling, and high accuracy, is an oncology priority. Given hepatoblastoma's early metastasis and poor advanced-stage outcomes (30-40% survival), Nano-5hmC-Seal cfDNA epigenetic profiling is a promising biomarker for diagnosis, treatment prediction, recurrence monitoring, and prognosis.

Inclusion Criteria:

• Patients with primary hepatoblastoma confirmed by pathology.

  • The age of the subjects was less than 18 years old. ③ Obtain the informed consent from the guardians and sign the informed consent form

Exclusion Criteria:

• Recurrent hepatoblastoma or other malignant tumor.

  • Age> 18 years old. ③ Patients with other tumors and received chemotherapy and abdominal radiotherapy.

    • Heart, brain and kidney failure patients.