Small Cell Undifferentiated Histology Does Not Appear to Impact Outcomes in Hepatoblastoma

A recent study found patients with hepatoblastoma who had small cell undifferentiated histology did not have worse outcomes than those who did not.

Patients with hepatoblastoma who present with small cell undifferentiated (SCU) histology were not found to have adverse outcomes compared with patients who did not, according to a phase 3 study (NCT00980460) from the Children’s Oncology Group published in the Journal of Clinical Oncology.

For those with SCU, the 5-year event-free survival (EFS) rate was 71% (95% CI, 53%-83%) vs 83% (95% CI, 76%-89%) for those with non-SCU tumors. The EFS at 5 years for patients with low-risk SCU hepatoblastoma was 86% (95% CI, 33%-98%), intermediate-risk was 81% (95% CI, 57%-92%), and high-risk was 29% (95% CI, 4%-61%) compared with EFS at 5 years for matches patients who did not have SCU, with rates including 87% (95% CI, 72%-95%), 88% (95% CI, 79%-94%), and 55% (95% CI, 32%-74%; P = .17), respectively. The 5-year overall survival (OS) was 86% (95% CI, 69%-94%) vs 90% (95% CI, 83%-94%) for those with SCU and those without.

A total of 188 patients were enrolled in the study, including those with low-, intermediate-, and high-risk disease. The median age at diagnosis was 17 months, and 111 patients were male. Overall, 177 patients were evaluable for analysis, including 49 low-risk patients, 100 intermediate-risk, and 28 high-risk. The median alpha-fetoprotein (AFP) at enrollment was 106, 483 ng/mL, and the median follow-up for patients who did not have an event was 8 years.

By central review, 35 patients had SCU, with the median percentage being 2%. Of note, 23 patients were males, and the median AFP at enrollment was 194,823 ng/mL. Of these patients, 33 patients were INI1-positive or retained at diagnosis, 2 of whom who had a focal loss of integrase interactor 1 staining, including 1 patient with stage II disease who relapsed and died 8 months later, and 1 with stage III disease who remained disease-free at 99 months from diagnosis. At initial diagnosis, 7 other patients did not have SCU detected appeared to demonstrate SCU elements that were found during second-look surgery.

Concordance of local and central review of SCU histology was poor, with agreement taking place in 26% of cases. Tumors with less than 5% SCU were observed in 25 patients, 8 had tumors ranging between 5% to 10% SCU, and 2 had tumors with more than 10% SCU.

At 97 months after relapse, 7 patients with low-risk disease were identified with SCU through central review, 1 of whom had 2% of SCU cells that recurred and remains alive and disease-free. During the initial resection, this patient experienced a bile leak and bowel perforation. The 5-year OS was 100% vs 92% (95% CI, 78%-97%) for this with low-risk SCU tumors and those without, respectively.

For those with intermediate-risk disease, 21 patients had SCU, 3 of whom experienced recurrence and died from the disease. Additionally, 1 patient with a Beckwith-Wiedemann and a second tumor is alive and in remission from both tumors. The 5-year OS for those with SCU tumors was 86% (95% CI, 62%-95%) vs 95% (95% CI, 87%-98%) for those without.

There were 7 patients with high-risk SCU, of whom 5 recurred, and 3 are alive at 61 months, 110 months, and 114 months after relapse. The 5-year OS is 71% (95% CI, 26%-92%) vs 64% (95% CI, 39%-81%).


Trobaugh-Lotrario A, Katzenstein HM, Ranganathan S, et al. Small cell undifferentiated histology does not adversely affect outcome in hepatoblastoma: a report from the children's oncology group (COG) AHEP0731 study committee. J Clin Oncol. 2022;40(5):459-467. doi:10.1200/JCO.21.00803