Chemo plus surgery may improve survival in high-risk neuroblastoma in Southeast Asia

Treatment outcomes for patients with high-risk neuroblastoma in Southeast Asia are poor all in all, but intensified medical and surgical procedures appear effective at improving survival rates, according to a study in Singapore.

“Effective chemotherapeutic regimens combined with total or near-complete surgical excision will help Southeast Asian centres to catch up with the survival rates from Europe and North America,” said the researchers, noting that most children with high-risk neuroblastoma in Europe and North America survive the disease.

The researchers conducted a retrospective review of children treated for high-risk neuroblastoma in a single institution in Singapore from 2007 to 2019. They then assessed survival data on certain clinical and laboratory factors.

Treatment regimen included the following: intensive chemotherapy; surgery aimed at gross total resection of residual disease after chemotherapy; consolidation with high-dose therapy, followed by autologous stem cell rescue; and radiotherapy to the primary and metastatic sites, followed by maintenance treatment with cis-retinoic acid or antidisialogangliside monoclonal antibody therapy.

Survival advantage

Fifty-seven children (mean age 3.9 years, 32 boys) received treatment for high-risk neuroblastoma. Median follow-up time for the surviving patients was 5.5 years. Thirty-one of them survived, with 27 surviving in first remission. Overall and event-free survival rates were 52.5 percent and 47.4 percent, respectively. [Singapore Med J 2023;64:319-325]

Log-rank testing showed that only the group of 17 patients who received treatment at the institution benefitted from a survival advantage. Their overall survival rate at 5 years was 81.6 percent compared with 41.1 percent (p=0.011) in those who received initial chemotherapy elsewhere. Moreover, event-free survival rate was 69.7 percent vs 36.1 percent, respectively (p=0.032).

Published treatment results were acquired from four Southeast Asian countries (ie, Malaysia, Thailand, Vietnam, and Singapore), with 5-year overall survival rates ranging from 13.5 percent to 28.2 percent. [Singapore Med J 2012;53:19-25; Malays J Pathol 1986;8:49-56; Asian Pacific J Cancer Prev 2011;12:2215-2220; Asian Pacific J Cancer Prev 2016;17:3515-3519; Pediatr Dimensions 2019;4]

Surgical management

The last two decades saw neuroblastomatologists still in dispute regarding the need for aggressive surgical management for optimal overall treatment outcome in these patients. [J Clin Oncol 2013;31:752-758; BMC Cancer 2015;15:79]

“With a tumour that frequently infiltrates and intertwines with the major abdominal vasculature, the disease is often considered inoperable or only partially resectable (25 percent to 75 percent tumour resection) in less-experienced centres,” the researchers said.

In earlier studies, near-complete resection (>90 percent) or more resulted in better survival rates. Hence, combined intensive chemotherapy and aggressive surgery could lead to long-term survival in patients with high-risk neuroblastoma.

Complications

“Treatment-related complications remain a concern,” according to the researchers. Five of the 26 deaths (19.2 percent) recorded in the current study were due to nonrelapse-related causes, in which four were treatment-related deaths.

“The frequent occurrence of hepatic sinusoidal obstruction syndrome or veno-occlusive disease in our patients suggests that busulfan exposure may be a common underlying factor for these adverse events,” they said. “Therapeutic drug monitoring or use of alternative conditioning regimens may improve our patients’ survival in the future.” [Pediatr Blood Cancer 2019;66:e27518]