Predictive value of the pretreatment extent of disease system in hepatoblastoma: results from the International Society of Pediatric Oncology Liver Tumor Study Group SIOPEL-1 study.

PURPOSE: Preoperative staging (pretreatment extent of disease [PRETEXT]) was developed for the first prospective liver tumor study by the International Society of Pediatric Oncology (SIOPEL-1 study; preoperative chemotherapy and delayed surgery). Study aims were to analyze the accuracy and interobserver agreement of PRETEXT and to compare the predictive impact of three currently used staging systems. PATIENTS AND METHODS: Hepatoblastoma (HB) patients younger than 16 years who underwent surgical resection (128 of 154 patients) were analyzed. The centrally reviewed preoperative staging was compared with postoperative pathology (accuracy) in 91 patients (81%), and the local center staging was compared with the central review (interobserver agreement) in 97 patients (86%), using the agreement beyond change method (weighted kappa). The predictive values of the three staging systems were compared in 110 patients (97%) using survival curves and Cox proportional hazard ratio estimates. RESULTS: Preoperative PRETEXT staging compared with pathology was correct in 51%, overstaged in 37%, and understaged in 12% of patients (weighted kappa = 0.44; 95% CI, 0.26 to 0.62). The weighted kappa value of the interobserver agreement was 0.76 (95% CI, 0.64 to 0.88). The Children's Cancer Study Group/Pediatric Oncology Group-based staging system showed no predictive value for survival (P = .516), but the tumor-node-metastasis-based system and PRETEXT system showed good predictive values (P = .0021 and P = .0006, respectively). PRETEXT seemed to be superior in the statistical fit. CONCLUSION: PRETEXT has moderate accuracy with a tendency to overstage patients, shows good interobserver agreement (reproducibility), shows superior predictive value for survival, offers the opportunity to monitor the effect of preoperative therapy, and can also be applied in patients who have not had operations. For comparability reasons, we recommend that all HB patients included in trials also be staged according to PRETEXT.

Surgical view of the treatment of patients with hepatoblastoma: results from the first prospective trial of the International Society of Pediatric Oncology Liver Tumor Study Group.

BACKGROUND: Surgical resection is the cornerstone of treatment for patients with hepatoblastoma (HB). The Society of Pediatric Oncology Liver Tumor Study Group launched its first prospective trial (SIOPEL-1) with the intention to treat all patients with preoperative chemotherapy and delayed surgical resection. The objective of this article was to assess the assumed surgical advantages of primary chemotherapy. METHODS: Between 1990 and 1994, 154 patients age < 16 years with HB were registered on SIOPEL-1. The pretreatment extent of disease was assessed, and, after undergoing biopsy, patients were treated with cisplatin 80 mg/m(2) intravenously over 24 hours and doxorubicin 60 mg/m(2) intravenously over 48 hours by continuous infusion (PLADO). Generally, tumors were resected after four of a total of six courses of PLADO. RESULTS: One hundred twenty eight patients underwent surgical resection (13 patients underwent primary surgery, and 115 patients underwent delayed surgery after PLADO). A pretreatment surgical biopsy was performed in 96 of 128 patients (75%). Biopsy complications occurred in 7 of 96 patients (7%). Twenty-two patients showed pulmonary metastases at the time of diagnosis, and 7 patients underwent thoracotomy. Operative morbidity and mortality were 18% and 5%, respectively. Complete macroscopic surgical resection was achieved in 106 patients (92%), including 6 patients who underwent orthotopic liver transplantation. The actuarial 5-year event free survival (EFS) rate for all 154 patients in the study was 66%, and the overall survival (OS) rate was 75%. For the 115 patients who were included in the surgical analysis that followed the exact protocol, the EFS and OS rates were 75% and 85%, respectively. CONCLUSIONS: Biopsy is a safe procedure and should be performed routinely. Preoperative chemotherapy seems to make tumor resection easier. Reresection of a positive resection margin does not necessarily have to be performed, because postoperative chemotherapy showed good results. Resection of lung metastases can be curative if there is local control of the primary tumor; however, results showed that the patient's prognosis was worse. Surgical morbidity or mortality rates were not necessarily higher in large multicenter studies. More importantly, countries of lesser economic status also can contribute effectively to these trials.