Tumor Necrosis After Chemotherapy May Predict Survival in Hepatoblastoma

BALTIMORE – Tumor necrosis of at least 30% following neoadjuvant chemotherapy for hepatoblastoma may predict better event-free and overall survival, based on the results of a small study.

"Histological response to neoadjuvant chemotherapy, as indicated by the percentage of tumor necrosis, is an independent prognostic factor in children with hepatoblastoma, and could potentially be used to modify postsurgical therapy to improve outcomes," lead author Dr. Rajkumar Venkatramani said at the annual meeting of the American Society of Pediatric Hematology/Oncology.

The presence of microscopic residual disease is also an adverse prognostic factor in patients undergoing gross surgical resection, reported Dr. Venkatramani, a fellow at Children’s Hospital Los Angeles.

The researchers conducted a retrospective review of medical records for all children who underwent surgical resection of the primary tumor following neoadjuvant chemotherapy at Children’s Hospital Los Angeles in 1986-2008. In all, 32 patients were included in the study. The investigators studied pathology slides or pretreatment biopsies and surgical resections after neoadjuvant chemotherapy for vascular invasion, positive margins, and tumor necrosis.

The median age at diagnosis was 1.35 years (range, 0-12.7 years), and the group was predominantly male (69%). The median serum AFP (alpha-fetoprotein) level was roughly 300,000 ng/mL. Three-fourths of the group had thrombocytosis at diagnosis, and most patients (81%) had stage III disease per COG (Children’s Oncology Group) criteria.

Most patients (23) received neoadjuvant cisplatin/fluorouracil/vinicristine chemotherapy. The median number of chemotherapy cycles was four.

Gross total resection was performed in 27 patients. Two patients had liver transplant, and three patients had partial resections.

Overall, 7 patients had less than 30% tumor necrosis in the postsurgical sample, 5 had 30%-59%, 9 had 60%-89%, and 11 had at least 90% tumor necrosis. The median tumor necrosis was 70%.

After treatment, seven tumors had evidence of vascular invasion. Most patients (22) had negative pathology margins.

The 3-year event-free survival rate for the entire group was 70%, and the 3-year overall survival rate was 77%. Patients had better event-free and overall survival if they had a greater platelet count at diagnosis, a decline in AFP after four chemotherapy cycles, greater tumor necrosis, complete surgical resection, or negative pathology margins on univariate analysis.

Patients with complete resection and negative margins had the best event-free survival rates, followed by those with complete resection with positive margins. Patients with partial resection had the worst event-free survival. The same pattern was seen for overall survival.

"Those who had greater than or equal to 30% necrosis had a better event-free survival, compared with [those with] less than 30% necrosis," said Dr. Venkatramani. The same was true for overall survival

On multivariate analysis, greater tumor necrosis, greater platelet count at diagnosis, and complete resection with negative margins were all significant predictors of better event-free survival. In the multivariate analysis for overall survival, platelet count at diagnosis dropped out.

The investigators reported that they have no relevant financial relationships.

BALTIMORE – Tumor necrosis of at least 30% following neoadjuvant chemotherapy for hepatoblastoma may predict better event-free and overall survival, based on the results of a small study.

"Histological response to neoadjuvant chemotherapy, as indicated by the percentage of tumor necrosis, is an independent prognostic factor in children with hepatoblastoma, and could potentially be used to modify postsurgical therapy to improve outcomes," lead author Dr. Rajkumar Venkatramani said at the annual meeting of the American Society of Pediatric Hematology/Oncology.

The presence of microscopic residual disease is also an adverse prognostic factor in patients undergoing gross surgical resection, reported Dr. Venkatramani, a fellow at Children’s Hospital Los Angeles.

The researchers conducted a retrospective review of medical records for all children who underwent surgical resection of the primary tumor following neoadjuvant chemotherapy at Children’s Hospital Los Angeles in 1986-2008. In all, 32 patients were included in the study. The investigators studied pathology slides or pretreatment biopsies and surgical resections after neoadjuvant chemotherapy for vascular invasion, positive margins, and tumor necrosis.

The median age at diagnosis was 1.35 years (range, 0-12.7 years), and the group was predominantly male (69%). The median serum AFP (alpha-fetoprotein) level was roughly 300,000 ng/mL. Three-fourths of the group had thrombocytosis at diagnosis, and most patients (81%) had stage III disease per COG (Children’s Oncology Group) criteria.

Most patients (23) received neoadjuvant cisplatin/fluorouracil/vinicristine chemotherapy. The median number of chemotherapy cycles was four.

Gross total resection was performed in 27 patients. Two patients had liver transplant, and three patients had partial resections.

Overall, 7 patients had less than 30% tumor necrosis in the postsurgical sample, 5 had 30%-59%, 9 had 60%-89%, and 11 had at least 90% tumor necrosis. The median tumor necrosis was 70%.

After treatment, seven tumors had evidence of vascular invasion. Most patients (22) had negative pathology margins.

The 3-year event-free survival rate for the entire group was 70%, and the 3-year overall survival rate was 77%. Patients had better event-free and overall survival if they had a greater platelet count at diagnosis, a decline in AFP after four chemotherapy cycles, greater tumor necrosis, complete surgical resection, or negative pathology margins on univariate analysis.

Patients with complete resection and negative margins had the best event-free survival rates, followed by those with complete resection with positive margins. Patients with partial resection had the worst event-free survival. The same pattern was seen for overall survival.

"Those who had greater than or equal to 30% necrosis had a better event-free survival, compared with [those with] less than 30% necrosis," said Dr. Venkatramani. The same was true for overall survival

On multivariate analysis, greater tumor necrosis, greater platelet count at diagnosis, and complete resection with negative margins were all significant predictors of better event-free survival. In the multivariate analysis for overall survival, platelet count at diagnosis dropped out.

The investigators reported that they have no relevant financial relationships.

BALTIMORE – Tumor necrosis of at least 30% following neoadjuvant chemotherapy for hepatoblastoma may predict better event-free and overall survival, based on the results of a small study.

"Histological response to neoadjuvant chemotherapy, as indicated by the percentage of tumor necrosis, is an independent prognostic factor in children with hepatoblastoma, and could potentially be used to modify postsurgical therapy to improve outcomes," lead author Dr. Rajkumar Venkatramani said at the annual meeting of the American Society of Pediatric Hematology/Oncology.

The presence of microscopic residual disease is also an adverse prognostic factor in patients undergoing gross surgical resection, reported Dr. Venkatramani, a fellow at Children’s Hospital Los Angeles.

The researchers conducted a retrospective review of medical records for all children who underwent surgical resection of the primary tumor following neoadjuvant chemotherapy at Children’s Hospital Los Angeles in 1986-2008. In all, 32 patients were included in the study. The investigators studied pathology slides or pretreatment biopsies and surgical resections after neoadjuvant chemotherapy for vascular invasion, positive margins, and tumor necrosis.

The median age at diagnosis was 1.35 years (range, 0-12.7 years), and the group was predominantly male (69%). The median serum AFP (alpha-fetoprotein) level was roughly 300,000 ng/mL. Three-fourths of the group had thrombocytosis at diagnosis, and most patients (81%) had stage III disease per COG (Children’s Oncology Group) criteria.

Most patients (23) received neoadjuvant cisplatin/fluorouracil/vinicristine chemotherapy. The median number of chemotherapy cycles was four.

Gross total resection was performed in 27 patients. Two patients had liver transplant, and three patients had partial resections.

Overall, 7 patients had less than 30% tumor necrosis in the postsurgical sample, 5 had 30%-59%, 9 had 60%-89%, and 11 had at least 90% tumor necrosis. The median tumor necrosis was 70%.

After treatment, seven tumors had evidence of vascular invasion. Most patients (22) had negative pathology margins.

The 3-year event-free survival rate for the entire group was 70%, and the 3-year overall survival rate was 77%. Patients had better event-free and overall survival if they had a greater platelet count at diagnosis, a decline in AFP after four chemotherapy cycles, greater tumor necrosis, complete surgical resection, or negative pathology margins on univariate analysis.

Patients with complete resection and negative margins had the best event-free survival rates, followed by those with complete resection with positive margins. Patients with partial resection had the worst event-free survival. The same pattern was seen for overall survival.

"Those who had greater than or equal to 30% necrosis had a better event-free survival, compared with [those with] less than 30% necrosis," said Dr. Venkatramani. The same was true for overall survival

On multivariate analysis, greater tumor necrosis, greater platelet count at diagnosis, and complete resection with negative margins were all significant predictors of better event-free survival. In the multivariate analysis for overall survival, platelet count at diagnosis dropped out.

The investigators reported that they have no relevant financial relationships.