O1099: Aggressive Pursuit of No Evidence of Disease Status in Hepatoblastoma Improves Survival

Background: Hepatoblastoma is the most common pediatric liver cancer. Achieving no evidence of disease (NED) status may require resection of metastatic disease. The utility of repeated interventions to achieve NED is not well-defined. We examined the association between NED status with event free (EFS) and overall survival (OS) in high-risk hepatoblastoma and described the surgical interventions required to achieve NED.

Methods: Hospital records were retrospectively queried for patients with hepatoblastoma from 2005-2021. The primary outcomes were OS and EFS. Univariate analyses were performed using two-tailed t-tests for normally distributed continuous data, Mann-Whitney tests for non-normally distributed data, and Fisher’s exact tests for categorical data. Time-to-event data were analyzed using the Kaplan-Meier method and log-rank tests. P< 0.05 denoted statistical significance.

Results: Among 50 consecutively treated patients with hepatoblastoma, 10% had PRETEXT 1 tumors, 34% PRETEXT 2, 32% PRETEXT 3, and 24% PRETEXT 4. 24/50 (48%) were high-risk due to patient age, AFP, or metastatic disease. All patients received chemotherapy. 46 patients underwent resection of the primary tumor before (n=3) or after chemotherapy (n=43). Extent of hepatectomy included 6 sectionectomies (13%), 17 hemihepatectomies (37%), 7 trisectionectomies (15%), 5 central hepatectomies (11%), and 11 total hepatectomies with transplant (24%). There was one perioperative mortality associated with liver transplantation (2%). Among 35 partial hepatectomies, there were 4 hepatic vascular exclusions (11%), 5 vascular reconstructions (14%), 5 biliary reconstructions (14%), and 8 en-bloc resections of adjacent structures (23%). Of 11 transplants, 4 required pulmonary metastasectomy before transplant (36%). 3-year overall survival was 81% for all patients, 71% for high-risk disease, and 84% for not high-risk disease.

Fifteen of 24 high-risk patients (63%) underwent 32 procedures for clearance of metastatic disease (31 pulmonary metastasectomies and 1 nonanatomic hepatectomy for local relapse). 14 patients underwent a median of 2.5 pulmonary metastasectomies (range 1-4) per patient, 7 for unilateral disease, and 7 for bilateral. A median of 4.5 (range 1-63) nodules were resected, with a median of 3 (range 0-60) nodules containing viable metastatic hepatoblastoma.

Nine patients (18%) did not achieve NED due to disease progression on therapy or treatment toxicity. All died. Failing to resect primary disease (P < 0.01) and not achieving NED (P < 0.01) were associated with mortality. 10-year OS (log-rank P< 0.01) and EFS (log-rank P< 0.01) were improved by achieving NED (Figure 1). High-risk patients with NED achieved similar 10-year OS (log-rank P=0.83) but not 10-year EFS (log-rank P< 0.05) to lower-risk patients (Figure 2). 6/19 high-risk patients who achieved NED relapsed (32%). Four were salvaged (67%).

Conclusion: NED status is necessary for survival in hepatoblastoma. Complex, bilateral, or reoperative pulmonary metastasectomy combined with complex local control strategies including liver transplantation, extreme resection, biliary or vascular reconstruction can be used to achieve NED in most patients.