Predictors of differential response to induction therapy in high-risk neuroblastoma: A report from the Children's Oncology Group (COG)

Abstract

Background-Induction chemotherapy plays an important role in the management of patients with high-risk neuroblastoma. Predictors of response to induction therapy are largely lacking. We sought to describe clinical and biological features associated with induction response. Methods-Patients from four consecutive COG high-risk trials were included. Response was evaluated by the 1993 International Neuroblastoma Response Criteria. The primary endpoint was end-induction partial response (PR) or better. Univariate analyses were performed to compare response as a function of clinical or biologic predictors. A multivariate logistic regression model using significant predictors from univariate analyses was constructed to model PR or better. Results-The analytic cohort included 1,242 patients. End-induction response ≥PR was significantly associated with higher event-free and overall survival. Baseline factors associated

Upfront consolidation treatment with 131I‐mIbG followed by myeloablative chemotherapy and hematopoietic stem cell transplantation in high‐risk neuroblastoma

“…I m p r o v e d e n d -i n d u c t i o n r e s p o n s e i n h i g h -r i s k neuroblastoma has been reported to be associated with superior EFS and OS. 39 In the present pilot study, compared with the patients who were in PR/MR at the time of 131 I-mIBG therapy, those patients who were in CR/VGPR at the time of 131 I-mIBG therapy showed a better clinical outcome (5-year EFS: 53% ± 17% versus 11% ± 10%; 5-year OS: 67% ± 16% versus 12% ± 11%). In addition to the survival benefit associated with improved end-induction response, following highdose chemotherapy, surgical resection, auto-HSCT and radiation therapy, anti-GD2 immunotherapy was shown in several studies to have superior survival when compared with standard therapy with isotretinoin alone in high-risk neuroblastoma patients.…”

Trends in conditional survival and predictors of late death in neuroblastoma

“…Moreover, recent improvements in the treatment of patients with high‐risk disease are positioned in the later phases of therapy (consolidation and postconsolidation phases that begin approximately 5 and 8 months from initial diagnosis). In contrast, few advances have addressed the ∼10% of patients who progress during the initial 5 months of induction therapy 9 . Conditional survival techniques that calculate survival conditional upon having survived a designated number of years post‐diagnosis may provide insight into the differential impact of interventions made earlier versus later in a treatment course.…”

Association between end‐induction response according to the revised International Neuroblastoma Response Criteria (INRC) and outcome in high‐risk neuroblastoma patients

“…More recently, Pinto et al. found post induction response of PR or better in HR neuroblastoma patients, as determined by the 1993 INRC, was associated with improved OS and EFS 12 …”

“…Treatment response, defined by MIBG Curie scores or the 1993 INRC, is known to be significantly associated with outcome for children with HR neuroblastoma 11‐15 . We hypothesized that the revised 2017 INRC would enable a more refined assessment of response and be more highly prognostic of outcome in HR neuroblastoma patients compared with the 1993 INRC criteria.…”