In an analysis from the International Society of Pediatric Oncology Europe Neuroblastoma Group (SIOPEN) High-Risk Neuroblastoma 1 (HR-NBL1/SIOPEN) trial reported in the Journal of Clinical Oncology, Holmes et al found that surgeon-assessed complete macroscopic excision was associated with improved event-free and overall survival vs incomplete macroscopic excision in patients with stage IV high-risk neuroblastoma.
Study Details
The study included 1,531 patients enrolled from 128 SIOPEN institutions between 2002 and 2015. Patients either had stage IV disease for more than 1 year or stage IV/IVS disease with MYCN amplification for less than 1 year. Patients had completed induction without progression, achieved response criteria for high-dose therapy, and had no resection before induction. After high-dose therapy with hematopoietic stem cell rescue, patients were to receive radiotherapy (21 Gy in 14 fractions). After June 2009, patients were to receive immunotherapy following radiotherapy (n = 788). Most patients (1,018) were age > 1 to 5.
“In patients with stage IV high-risk neuroblastoma who have responded to induction therapy, complete macroscopic excision of the primary tumor is associated with improved survival and local control after high-dose therapy, local radiotherapy (21 Gy), and immunotherapy.”— Holmes et al
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Key Findings
Median observation time was 6.1 years. Complete macroscopic excision was achieved in 1,172 patients (77%) and incomplete macroscopic excision was performed in 359 (23%).
Surgical mortality occurred in three patients (0.3%) with complete macroscopic excision and in four (1.1%) with incomplete macroscopic excision (P = .056). Severe surgical complications (excluding nephrectomy) occurred in 7.9% vs 15.8% (P < .001). Nephrectomy was performed in 7.9% vs 11.9% (P = .028).
The probability of event-free survival with complete macroscopic excision vs incomplete macroscopic excision was 40% vs 33% at 5 years (P < .001). The probability of overall survival with complete macroscopic excision vs incomplete macroscopic excision was 45% vs 37% at 5 years (P = .004). On multivariate analysis, hazard ratios for incomplete macroscopic excision vs complete macroscopic excision were 1.3 (P = .005) for event-free survival and 1.3 (P < .0001) for overall survival. Neither severe operative complications nor nephrectomy had a significant adverse effect on event-free or overall survival.
The cumulative incidence of local progression was 17% vs 30% (P < .001). On multivariate analysis, the hazard ratio for incomplete macroscopic excision vs complete macroscopic excision was 2.0 (95% confidence interval = 1.5–2.5).
Among patients treated after the introduction of immunotherapy into the treatment protocol, 5-year event-free survival was 47% vs 39% (adjusted hazard ratio [HR] = 1.3, P = .038), 5-year overall survival was 54% vs 45% (adjusted HR = 1.3, P = .049), and cumulative incidence of local progression was 14% vs 27% (HR = 1.8, P = .002).
The investigators concluded, “In patients with stage IV high-risk neuroblastoma who have responded to induction therapy, complete macroscopic excision of the primary tumor is associated with improved survival and local control after high-dose therapy, local radiotherapy (21 Gy), and immunotherapy.”
Ruth Lydia Ladenstein, MD, PhD, of the Children’s Cancer Research Institute, Vienna, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by a European Commission 5th Framework grant. For full disclosures of the study authors, visit ascopubs.org.
