Predictive power of pretreatment prognostic factors in children with hepatoblastoma: a report from the Children's Oncology Group

Abstract

Background: PRETEXT is used to stratify risk in children with hepatoblastoma by the Liver Tumor Strategy Group (SIOPEL) of the International Society of Pediatric Oncology (SIOP). A recent analysis excluding patients that did not survive neoadjuvant chemotherapy, concluded that PRETEXT was superior to Children's Oncology Group (COG) stage for predicting survival. Puzzled by this result, we made a similar comparison of PRETEXT and COG stage. This time, however, we include all patients, and we compare predictive value at diagnosis, instead of after neoadjuvant chemotherapy.

Methods: Hepatoblastoma patients in INT-0098 were retrospectively reviewed for PRETEXT and other potential prognostic factors including pathologic subtype, and alpha-fetoprotein (AFP).

Results: Five-year overall survival by PRETEXT was 88.9%, 84.5%, 71.6%, and 30.9%, for PRETEXT I, II, III, and IV, respectively. The 5-year overall survival rates by COG stage were 100%, 97.5%, 100%, 70.2%, and 39.3% for Stage I pure fetal histology (PFH), Stage I unfavorable histology (UH = not PFH), Stage II, Stage III, and Stage IV, respectively. PRETEXT added significant additional prognostic information within the COG Stage III, but not COG Stage IV. Additional prognostic factors statistically significant for an increased risk of death were small-cell-undifferentiated (SCU) histologic subtype and AFP < 100 at diagnosis.

Conclusions: PRETEXT, COG stage, SCU histology, and AFP < 100, as assessed at diagnosis, are important determinants of survival that will allow us to better develop common international criteria for risk stratification. Common risk stratification is an essential prerequisite to establish effective cooperation across the ocean in this field of rare tumors.

Figure 1

PRETEXT = pretreatment extent of disease. May be referred to as POST-TEXT (post-treatment extent of disease) if the staging is done after neoadjuvant chemotherapy. PRETEXT I = three contiguous sections free of tumor; PRETEXT II = two contiguous sections free of tumor; PRETEXT III = one contiguous section free of tumor; PRETEXT IV = no section free of tumor. In addition any group may have: “V” Invasion vena cava or all three major hepatic veins; “P” Invasion main portal vein or portal venous bifurcation; “E” Contiguous extrahepatic growth; “M” Distant metastasis; “C” Caudate lobe involvement.

Figure 2

Survival according to COG Stage of 178 patients with retrospective assignment of PRETEXT. COG Stage I Pure Fetal n=9; Stage I Unfavorable n=45; Stage II n=7; Stage III n=79; Stage IV n=38.

Figure 3

Survival according to retrospective assignment of PRETEXT group. PRETEXT I n=19; PRETEXT II n=54; PRETEXT III n=77; PRETEXT IV n=28.

Figure 4

Overall survival of all patients in COG Stage III, each patient has been subclassified according to their PRETEXT group. PRETEXT adds additional predictive value for patients with COG Stage III tumors, p < 0.01 by log rank test. PRETEXT I n=1; PRETEXT II n=13; PRETEXT III n=44; PRETEXT IV n=21.

Figure 5

Overall survival of all patients in COG Stage IV, each patient has been subclassified according to their PRETEXT group. PRETEXT does NOT additional predictive value for patients with COG Stage IV tumors, p = 0.36 by log rank test. PRETEXT I n=2; PRETEXT II n=5; PRETEXT III n=24; PRETEXT IV n=7.

Figure 6

Overall survival according to the diagnostic risk factors “AFP at diagnosis” and “small cell undifferentiated (SCU) histology”. Both of these risk factors are independent predictors of overall survival (p < 0.0001) by log rank test. AFP > 100 and no SCU n=165; AFP >100 and presence of SCU n=6; AFP <100 and no SCU n=7.