[Preliminary efficacy and safety analysis of modified SIOPEL-4 protocol for newly diagnosed pediatric hepatoblastoma with lung metastases].

Objective

To assess the preliminary efficacy and safety of modified Société Internationale d'Oncologie Pédiatrique Epithelial Liver Tumor Study Group (SIOPEL)-4 protocol for pediatric hepatoblastoma (HB) with lung metastases.

Methods

This prospective cohort study enrolled 27 newly diagnosed pediatric HB with lung metastases who received the modified SIOPEL-4 protocol at Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, and Shanghai Children's Hospital between January 2020 to December 2023. Clinical characteristics, lung response rates to induction chemotherapy, treatment outcomes, prognostic factors and sever chemotherapy toxicities at different stages were analyzed. Survival analysis was performed by Kaplan-Meier method. Univariate prognostic analysis was conducted by Log-Rank test.

Results

Of the 27 patients, there were 17 males and 10 females, with the age of 21 (15, 33) months. During the follow-up of 31 (12, 45) months for 17 continuous complete remission patients, 4 cases disease progression (2 cases death) and 6 cases relapse were observed. The 2-year event free survival (EFS) and overall survival (OS) rate was (58±11)% and (89±7)%, respectively. All the 27 patients had response to block 1-3 induction chemotherapy (cisplatin+doxorubicin), with 14 cases (52%) achieving complete response and 13 cases (48%) achieving partial response of lung metastatic lesions, the 2-year EFS rate was (81±12)% and (34±14)%, respectively (χ2=6.76, P=0.009), the 2-year OS rate was 100% and (79±13)%, respectively (χ2=2.12, P=0.145). Patients with caudate lobe tumors or ≥10 pulmonary metastatic nodules had significantly lower EFS rates (χ2=5.36, 7.84,P=0.021, 0.005, respectively). The incidence of grade 3/4 neutropenia after block 1-3 induction chemotherapy, CD (carboplatin+doxorubicin), and VI (vincristine+irinotecan) consolidation chemotherapy was 90% (73/81), 75% (58/77), and 31% (11/35), respectively. The incidence of grade 3/4 thrombocytopenia was 77% (62/81), 69% (53/77), and 14% (5/35), respectively. The incidence of grade 3/4 infections was 64% (52/81), 25% (19/77), and 20% (7/35), respectively. The differences between the groups were statistically significant (χ2=43.51, 42.69, 33.00, all P<0.001). Two patients (10%) of the 20 evaluable patients for ototoxicity occurred grade 3 and higher hearing impairment, with 1 patient requiring a hearing aid.

Conclusions

The modified SIOPEL-4 regimen shows good preliminary efficacy and safety in treating pediatric HB with lung metastases. The prognosis for patients with residual lesions in the lungs after induction chemotherapy needs to be improved. Attention should be given to the ototoxicity induced by high-dose cisplatin chemotherapy.