A Prospective Multicenter Clinical Study of SCCG Protocol and ctDNA 5hmc in Predicting the Chemotherapy Sensitivity and Monitoring the Recurrence and Metastasis of Hepatoblastoma in Children and Adolescents

Summary

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.

Conditions

• Hepatoblastoma

Interventions

DRUG

Very low-risk group

Very low-risk group: No chemotherapy after pure fetal type surgery, followed up and observed. Chemotherapy with other types of single-agent DDP regimens for 4 courses.

DRUG

Low-risk group

Low-risk group: 2 to 4 courses of DDP monotherapy chemotherapy, elective surgery, 2 courses of DDP monotherapy chemotherapy after surgery, totaling 4 to 6 courses.

DRUG

Intermediate-risk group

Intermediate risk group: randomized treatment: group A SIOPEL - 3 HR solutions can be 2 \~ 4 course of chemotherapy, continue to A total of 6 course of chemotherapy after surgery. Group B C5VD solution after 2 \~ 4 course of chemotherapy, elective surgical procedures continue to a total of 6 course of chemotherapy after surgery.

DRUG

High-risk group

High-risk group：Chemotherapy with the C-CD+ICE+ sorafenib regimen for 3 to 5 courses was followed by elective surgery, with a total of 6 to 7 courses

OTHER

5hmc dynamic monitoring

Peripheral blood was regularly drawn from patients in the very low-risk group, low-risk group, intermediate-risk group and high-risk group for 5hmc dynamic monitoring to evaluate its value in clinical efficacy and recurrence detection

Sponsors & Collaborators

• Sun Yat-sen University

  lead OTHER

Principal Investigators

• Junting Huang · SunYat Sen University Cancer Center

• Huang · SunYat Sen University Cancer Center

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Max Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-06-23

Primary Completion

2027-12-30

Completion

2028-12-31

Countries

• China

Study Locations