Treatment options for hepatoblastoma that is resectable at diagnosis

Patients with well-differentiated fetal histology (4% of hepatoblastomas) have a 3- to 5-year OS rate of 100% with minimal or no adjuvant chemotherapy.[50-52,96]

Patients with non–well-differentiated fetal histology, non–small cell undifferentiated hepatoblastomas have a 3- to 4-year OS rate of 90% to 100% with adjuvant chemotherapy.[50,51,54,56,97]

If any small cell undifferentiated elements are present, the 3-year survival rate is 40% to 70%.[50,53]

Resection followed by two to four cycles of chemotherapy.[58]

In the COG AHEP0731 (NCT00980460) trial, 49 of 51 patients with stage I or stage II hepatoblastoma (without pure fetal histology) received two cycles of adjuvant chemotherapy consisting of cisplatin, fluorouracil, and vincristine.[93][Level of evidence C1]

In the COG AHEP0731 (NCT00980460) trial, 49 of 51 patients with stage I or stage II hepatoblastoma (without pure fetal histology) received two cycles of adjuvant chemotherapy consisting of cisplatin, fluorouracil, and vincristine.[93][Level of evidence C1]

The 5-year EFS rate was 88%, and the 5-year OS rate was 91%.

In the COG AHEP0731 (NCT00980460) trial, 49 of 51 patients with stage I or stage II hepatoblastoma (without pure fetal histology) received two cycles of adjuvant chemotherapy consisting of cisplatin, fluorouracil, and vincristine.[93][Level of evidence C1]

This outcome is comparable to the outcomes for children treated with four cycles after initial resection, and to the outcomes for children treated with two cycles of neoadjuvant chemotherapy before resection followed by two cycles of chemotherapy after resection.

There is no reliable data for local recurrence risk in patients with a positive microscopic margin status who underwent resection at diagnosis.[68] SIOPEL studies suggest that in patients who received preoperative chemotherapy, positive microscopic margin did not increase risk of local recurrence.[56,57,73]; [95][Level of evidence C1]

There is no reliable data for local recurrence risk in patients with a positive microscopic margin status who underwent resection at diagnosis.[68] SIOPEL studies suggest that in patients who received preoperative chemotherapy, positive microscopic margin did not increase risk of local recurrence.[56,57,73]; [95][Level of evidence C1]

In a European study conducted between 1990 and 1994, 11 patients had tumor found at the surgical margins after hepatic resection and two patients died, neither of whom had a local recurrence. None of the 11 patients underwent a second resection, and only one patient received radiation therapy postoperatively. All of the patients were treated with four courses of cisplatin and doxorubicin before surgery and received two courses of postoperative chemotherapy.[73]

There is no reliable data for local recurrence risk in patients with a positive microscopic margin status who underwent resection at diagnosis.[68] SIOPEL studies suggest that in patients who received preoperative chemotherapy, positive microscopic margin did not increase risk of local recurrence.[56,57,73]; [95][Level of evidence C1]

In another European study of high-risk hepatoblastoma, 11 patients had microscopic residual tumor remaining after initial surgery and received two to four postoperative cycles of chemotherapy with no additional surgery. Of these 11 patients, 9 survived.[57]

There is no reliable data for local recurrence risk in patients with a positive microscopic margin status who underwent resection at diagnosis.[68] SIOPEL studies suggest that in patients who received preoperative chemotherapy, positive microscopic margin did not increase risk of local recurrence.[56,57,73]; [95][Level of evidence C1]

In the SIOPEL-2 study, 13 of 13 patients with microscopic positive resection margins survived.[56]

There is no reliable data for local recurrence risk in patients with a positive microscopic margin status who underwent resection at diagnosis.[68] SIOPEL studies suggest that in patients who received preoperative chemotherapy, positive microscopic margin did not increase risk of local recurrence.[56,57,73]; [95][Level of evidence C1]

An unplanned retrospective study of the SIOPEL-2 and SIOPEL-3 trials found that after four courses of cisplatin for standard-risk patients and seven courses of cisplatin alternating with doxorubicin/carboplatin for high-risk patients, resection was performed where imaging suggested it would be safe. Of the 431 children treated in these trials, 58 patients had positive microscopic tumor margins, and 371 patients were in complete remission. There were no statistically significant differences in the rates of local recurrence, EFS, or OS between the two groups.[95][Level of evidence C1]

A randomized clinical trial demonstrated comparable efficacy with postoperative cisplatin/vincristine/fluorouracil and cisplatin/doxorubicin in the treatment of patients with hepatoblastoma.[51]

A randomized clinical trial demonstrated comparable efficacy with postoperative cisplatin/vincristine/fluorouracil and cisplatin/doxorubicin in the treatment of patients with hepatoblastoma.[51]

Although survival outcomes were nominally higher for the children who received cisplatin/doxorubicin, this difference was not statistically significant.

A randomized clinical trial demonstrated comparable efficacy with postoperative cisplatin/vincristine/fluorouracil and cisplatin/doxorubicin in the treatment of patients with hepatoblastoma.[51]

The combination of cisplatin/vincristine/fluorouracil was significantly less toxic than were the doses of cisplatin/doxorubicin.

Complete surgical resection followed by watchful waiting or chemotherapy.[52]

In a COG prospective clinical trial (INT0098), nine children with stage I (completely resected) well-differentiated fetal histology and fewer than two mitoses per high-power field were treated with four cycles of adjuvant doxorubicin.[51]

In a COG prospective clinical trial (INT0098), nine children with stage I (completely resected) well-differentiated fetal histology and fewer than two mitoses per high-power field were treated with four cycles of adjuvant doxorubicin.[51]

At a median follow-up of 5.1 years, the EFS and OS rates were 100% for all nine children.

In the COG P9645 (NCT00003994) study, 16 patients with stage I (completely resected) tumors had well-differentiated fetal histology and received no adjuvant chemotherapy. In a retrospective PRETEXT classification of 21 of these 25 patients with adequate data, PRETEXT I, II, and III tumors were found in 7, 10, and 4 patients, respectively.[52]

In the COG P9645 (NCT00003994) study, 16 patients with stage I (completely resected) tumors had well-differentiated fetal histology and received no adjuvant chemotherapy. In a retrospective PRETEXT classification of 21 of these 25 patients with adequate data, PRETEXT I, II, and III tumors were found in 7, 10, and 4 patients, respectively.[52]

The EFS and OS rates were 100% for patients with stage I well-differentiated fetal histology, including one patient who had a second surgery to address a positive tumor margin.