Influence of Surgical Excision on the Survival of Patients With Stage 4 High-Risk Neuroblastoma: A Report From the HR-NBL1/SIOPEN Study

Abstract

<jats:sec><jats:title>PURPOSE</jats:title><jats:p> To evaluate the impact of surgeon-assessed extent of primary tumor resection on local progression and survival in patients in the International Society of Pediatric Oncology Europe Neuroblastoma Group High-Risk Neuroblastoma 1 trial. </jats:p></jats:sec><jats:sec><jats:title>PATIENTS AND METHODS</jats:title><jats:p> Patients recruited between 2002 and 2015 with stage 4 disease &gt; 1 year or stage 4/4S with MYCN amplification &lt; 1 year who had completed induction without progression, achieved response criteria for high-dose therapy (HDT), and had no resection before induction were included. Data were collected on the extent of primary tumor excision, severe operative complications, and outcome. </jats:p></jats:sec><jats:sec><jats:title>RESULTS</jats:title><jats:p> A total of 1,531 patients were included (median observation time, 6.1 years). Surgeon-assessed extent of resection included complete macroscopic excision (CME) in 1,172 patients (77%) and incomplete macroscopic resection (IME) in 359 (23%). Surgical mortality was 7 (0.46%) of 1,531. Severe operative complications occurred in 142 patients (9.7%), and nephrectomy was performed in 124 (8.8%). Five-year event-free survival (EFS) ± SE (0.40 ± 0.01) and overall survival (OS; 0.45 ± 0.02) were significantly higher with CME compared with IME (5-year EFS, 0.33 ± 0.03; 5-year OS, 0.37 ± 0.03; P &lt; .001 and P = .004). The cumulative incidence of local progression (CILP) was significantly lower after CME (0.17 ± 0.01) compared with IME (0.30 ± 0.02; P &lt; .001). With immunotherapy, outcomes were still superior with CME versus IME (5-year EFS, 0.47 ± 0.02 v 0.39 ± 0.04; P = .038); CILP was 0.14 ± 0.01 after CME and 0.27 ± 0.03 after IME ( P &lt; .002). A hazard ratio of 1.3 for EFS associated with IME compared with CME was observed before and after the introduction of immunotherapy ( P = .030 and P = .038). </jats:p></jats:sec><jats:sec><jats:title>CONCLUSION</jats:title><jats:p> In patients with stage 4 high-risk neuroblastoma who have responded to induction therapy, CME of the primary tumor is associated with improved survival and local control after HDT, local radiotherapy (21 Gy), and immunotherapy. </jats:p></jats:sec>

Molecular targeting therapies for neuroblastoma: Progress and challenges

“…However, the response to IC is not sufficient in 1/3 of children with high‐risk NB 34,37 . During induction therapy, surgery is performed to resect primary tumor tissue 38,39 . The consolidation phase can provide improved event‐free survival (EFS), especially in NB patients who have undergone tandem ASCT 6 …”

Novel Treatments and Technologies Applied to the Cure of Neuroblastoma

“…Surgery represents a cornerstone within the multimodal treatment of NB. The literature supports the idea that a gross total resection is associated with better survival outcomes [54,55]. However, performing a radical NB excision is particularly demanding due to the strict adhesion of the tumour to major blood vessels and nerves and the extensive tumour fibrosis resulting from the neoadjuvant chemotherapy.…”

Surgical Approaches to Neuroblastoma: Review of the Operative Techniques

“…Direct invasion of the renal parenchyma is detected in 11 to 14% of patients and the renal vasculature is encased or narrowed in 32 to 45% of patients. Kidney-sparing surgery is widely preferred in NB surgical resection, as long as gross total resection is feasible [59]. In a recent study by Fahy et al [60] no significant differences were observed in the survival of patients undergone kidney-sparing surgery, but a better mid-term renal function was revealed in these patients compared to the patients underwent complete nephrectomy.…”