Background: Patients with metastatic NB typically have a poor prognosis; however case series have suggested that those with 4N disease may have improved outcomes. Methods: Retrospective analysis of data from INRG database for patients diagnosed 1990–2002. 4N patients (INSS stage 4 disease confined to distant lymph nodes) were compared to the balance of stage 4 patients (‘non-4N’), excluding those with missing metastatic site data. 5-yr estimates of overall (OS) and event-free survival (EFS) were calculated ± standard error (Kaplan-Meier method). Patient characteristics were compared by Mann-Whitney or Fisher’s exact/Chi-square tests. Results: 2,250 INSS stage 4 patients with complete data were identified, of whom 146 (6%) had 4N disease. For 4N patients, EFS and OS (5-yr: 77% ± 4%, 85% ± 3%), were significantly better than EFS and OS (5-yr: 35% ± 1%, 42% ± 1%) for non-4N stage 4 patients (p<0.0001). 4N patients were more likely to be younger (median age at diagnosis 1.2 yr vs 2.5 yr for non-4N; p<0.0001) and have tumors with favourable International Neuroblastoma Pathologic Classification (INPC) (63% vs 26%, p<0.0001), differentiating grade (21% vs 8%, p=0.006), lower MKI (p=0.0011) and non-MYCN amplified tumors (89% vs 69%, p<0.0001). Within subgroups defined by age at diagnosis and MYCN status, 4N pattern of disease remained significantly associated with improved outcomes. For patients aged 547 days at diagnosis and MYCN non-amplified, 5-yr EFS for 4N patients (n=42) was 63% ± 8% vs 27% ± 2% for non-4N (n=785); OS 74% ± 7% vs 38% ± 2% (both p<0.0001). Within this subgroup, favourable INPC and differentiating grade remained more frequent in the 4N vs non-4N patients (45% vs 10%, p<0.0001; 45% vs 8%, p=0.0017, respectively). Conclusions: 4N represents a subgroup of metastatic patients with better outcome than other INSS stage 4 patients. These findings indicate that the biology and response to treatment of 4N tumors differs from other stage 4 tumors, and different therapies should be considered for this cohort. Future exploration of biological factors determining pattern of metastatic spread and response to therapy is warranted.

Metastatic neuroblastoma confined to distant lymph nodes (stage 4N) to predict outcome in patients with stage 4 disease: A study from the International Neuroblastoma (NB) Risk Group (INRG) Database. J Clin Oncol 31,15 Suppl. Annual Meeting of the American Society of Clinical Oncology (Chicago, 31 May- 4 June 2013).

DI CATALDO, Andrea;
2013

Abstract

Background: Patients with metastatic NB typically have a poor prognosis; however case series have suggested that those with 4N disease may have improved outcomes. Methods: Retrospective analysis of data from INRG database for patients diagnosed 1990–2002. 4N patients (INSS stage 4 disease confined to distant lymph nodes) were compared to the balance of stage 4 patients (‘non-4N’), excluding those with missing metastatic site data. 5-yr estimates of overall (OS) and event-free survival (EFS) were calculated ± standard error (Kaplan-Meier method). Patient characteristics were compared by Mann-Whitney or Fisher’s exact/Chi-square tests. Results: 2,250 INSS stage 4 patients with complete data were identified, of whom 146 (6%) had 4N disease. For 4N patients, EFS and OS (5-yr: 77% ± 4%, 85% ± 3%), were significantly better than EFS and OS (5-yr: 35% ± 1%, 42% ± 1%) for non-4N stage 4 patients (p<0.0001). 4N patients were more likely to be younger (median age at diagnosis 1.2 yr vs 2.5 yr for non-4N; p<0.0001) and have tumors with favourable International Neuroblastoma Pathologic Classification (INPC) (63% vs 26%, p<0.0001), differentiating grade (21% vs 8%, p=0.006), lower MKI (p=0.0011) and non-MYCN amplified tumors (89% vs 69%, p<0.0001). Within subgroups defined by age at diagnosis and MYCN status, 4N pattern of disease remained significantly associated with improved outcomes. For patients aged 547 days at diagnosis and MYCN non-amplified, 5-yr EFS for 4N patients (n=42) was 63% ± 8% vs 27% ± 2% for non-4N (n=785); OS 74% ± 7% vs 38% ± 2% (both p<0.0001). Within this subgroup, favourable INPC and differentiating grade remained more frequent in the 4N vs non-4N patients (45% vs 10%, p<0.0001; 45% vs 8%, p=0.0017, respectively). Conclusions: 4N represents a subgroup of metastatic patients with better outcome than other INSS stage 4 patients. These findings indicate that the biology and response to treatment of 4N tumors differs from other stage 4 tumors, and different therapies should be considered for this cohort. Future exploration of biological factors determining pattern of metastatic spread and response to therapy is warranted.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/20.500.11769/107191
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