A new risk score for patients after first recurrence of stage 4 neuroblastoma aged ≥18 months at first diagnosis

Abstract

Background The prognosis of patients with recurrences from stage 4 neuroblastoma is not uniformly dismal. The evaluation of new therapies therefore needs to consider the individual risks of the treated patients. This study aims to define clinically useful risk criteria. Patients and Methods Inclusion criteria were: first recurrence of neuroblastoma stage 4 aged ≥18 months and enrollment in first line trials between 1997 and 2016. Patients were randomized into a training set (N = 310) and an independent validation set (N = 159). The primary endpoint was secondary event‐free survival. The individual treatment elements the patients received during initial and recurrent disease were analyzed as binary and time‐dependent variables. A five‐step multiple time‐dependent Cox regression analysis was performed on the training set to identify prognostic variables adjusted for the individual frontline treatment. The selected variables resulted in a prognostic index (PI) and were used to build a risk score system. The score was validated with the validation set. Results Of the 469 patients, 372 were treated with curative intent and 97 with palliative intent. The PI included the variables number of recurrence organs (hazard ratio [HR] = 2.27), time to recurrence (HR = 2.03), liver metastasis at diagnosis (HR = 1.77), first recurrence at site of the primary tumor (HR = 1.55), and age (HR = 1.29). Three risk groups were built and confirmed in the validation set. The scoring system was likewise useful for the curatively or palliatively treated subgroups. Conclusion A new risk score system for patients with first recurrence of stage 4 neuroblastoma aged ≥18 months at diagnosis is proposed.

Survival Impact of Anti-GD2 Antibody Response in a Phase II Ganglioside Vaccine Trial Among Patients With High-Risk Neuroblastoma With Prior Disease Progression

“…For children with high-risk metastatic and/or relapsed neuroblastoma, survival remains poor and long-term morbidities are common. [1][2][3] Immunotherapy holds promise not just for the treatment of chemorefractory disease but also in improving long-term survival without additive toxicities. With the integration of anti-disialoganglioside (GD)2 monoclonal antibody (mAb) into the standard of care, 50%-60% of children with high-risk neuroblastoma (HR-NB) are long-term survivors.…”

Gene Expression Signature of Acquired Chemoresistance in Neuroblastoma Cells

“…To our knowledge, no study has investigated the predictive potential of the expression levels of genes obtained from NB cell lines resistant to a specific chemotherapeutic agent. In the past, we and others have proposed gene-based classifiers but specifically generated to stratify high-risk or ultra-high-risk tumors [ 38 , 39 , 40 , 41 ]. Another study found a pivotal role of cytoskeleton and transport in vincristine resistance by in-silico reconstruction of protein networks and by using the concept of synthetic lethality and protein hubs [ 42 ].…”

Phase I Trial of Oral Yeast-Derived β-Glucan to Enhance Anti-GD2 Immunotherapy of Resistant High-Risk Neuroblastoma

“…MTD of BG was not reached, and the study was completed at the planned dose of 200 mg/kg/day. While the post-3F8/BG treatment was variable and patient selection bias was inevitable in single-center trials, 27 patients survived past 2 years, and 16 patients survived past 5 years—61% and 36%, respectively, an improvement over the dismal outcome reported in recent summaries [ 7 , 8 , 9 ].…”

“…The chimeric anti-GD2 monoclonal antibodies (mAb) dinutuximab [ 2 , 3 ] and dinutuximab-beta [ 4 ], as well as the humanized anti-GD2 mAb naxitamab (previously named hu3F8) [ 5 , 6 ], have been approved by USA and European regulatory agencies for therapeutic treatment of high-risk NB (HR-NB). The prognosis for relapsed or refractory HR-NB, i.e., those with MYCN amplification or those diagnosed with stage 4 disease after 18 months of age, was dismal prior to the advent of immunotherapy [ 7 , 8 , 9 ].…”