Salvage rates after progression of high-risk neuroblastoma with a soft tissue mass

Abstract

Purpose Treatment of progression in high-risk neuroblastoma remains challenging despite improved survival. We retrospectively evaluated outcomes in children with a first progression that included soft-tissue masses. Methods We reviewed records of 903 consecutive children with high-risk neuroblastoma diagnosed between 2004 and 2014, and identified 42 whose first progression included soft-tissue masses. Data on demographics, disease characteristics, treatment, and survival were collected. Primary outcome was 5-year overall survival (OS) from time of first progression. Secondary outcomes were local disease-free progression (LDFR) and progression-free survival (PFS) post-progression. We evaluated the prognostic significance of concomitant bone/bone marrow involvement, MYCN status, and multifocality of soft tissue relapse. Data are given as median(range). Results Median age at diagnosis was 3.0 (1 – 10.7) years. Median time to first relapse or progression was 1.2 (0.1 – 4.5) years after complete remission or minimal stable residual disease Twelve (29%) patients had concomitant bone or marrow involvement at progression/relapse. There were 11 (26%) patients with INSS stage 3 disease (all with MYCN amplification), and 31 (74%) with stage 4 disease (12 with MYCN amplification). Nine (21%) patients had multifocal soft tissue progression. R1 resection was achieved in 41 children (95%), 38 (95%) of whom also received salvage radiation therapy. Five-year OS post-progression was 35% (95%CI: 19–51%), 5-year LDFS was 52% (95%CI: 32–72%), and 5-year PFS post-progression was 20% (95%CI: 6–34%). Conclusion Among children with high-risk neuroblastoma who underwent aggressive treatment of a first soft-tissue recurrence, 5-year post-progression overall survival was 34%. Multifocality and MYCN amplification were the predominant prognostic correlates for worse survival.

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

“…This is the important point of our study. The five described variables appear to cover the impact of MYCN oncogene ( MYCN ) amplification, increased lactate dehydrogenase levels, and other risk factors mentioned. In the future, novel omics technologies may provide better insights into the molecular mechanism and potentially better explain clinical courses right from the first diagnosis .…”

“…Patients were stratified according to the variables palliative treatment (yes/no), MYCN amplification (yes/no), time from diagnosis to first recurrence (≤18/>18 months), and number of recurrence organs (1/>1) and then randomized with allocation ratio 2:1 into a training set (n = 310) and a validation set (n = 159). All patients treated with palliative (n = 97) or curative (n = 372) intent were included in the analysis in order to obtain the full spectrum.…”

“…The prognosis of children with recurrences of high‐risk neuroblastoma is dismal . The reported time periods from the observation of first recurrence to the subsequent progression are short (median intervals 58 days, 4.7 months, 6.4 months), and the overall survival proportions have been poor (20% after 4 years, 20% after 5 years, 7% after 10 years).…”

“…Other predictors for poor outcome were measurable tumor on computed tomography/ magnetic resonance imaging at second‐line trial enrollment, high Curie score by metaiodobenzylguanidine scintigraphy, and stem cell supported therapy . The analyzed cohorts varied and included recurrences from localized tumors, patients aged less than 18 months at diagnosis, and patients with refractory disease …”

“…[1][2][3][4][5][6][7][8][9] The reported time periods from the observation of first recurrence to the subsequent progression are short (median intervals 58 days, 1 4.7 months, 2 6.4 months 3 ), and the overall survival proportions have been poor (20% after 4 years, 1 20% after 5 years, 4 7% after 10 years 5 ). Risk factors for an inferior outcome included stage 4, 4,5 age ≥18 months at first diagnosis, 4,5 MYCN amplification, 1,2,4,6,7 loss of heterozygosity of chromosome 11q, 1 shorter time from diagnosis to first recurrence, 4,7 abdominal primary tumor, 5 bone marrow metastasis at first diagnosis, 2 recurrent disease (vs refractory disease), 3,8,10 and increased lactate dehydrogenase blood levels. 5 Other predictors for poor outcome were measurable tumor on computed tomography/ magnetic resonance imaging at second-line trial enrollment, high Curie score by metaiodobenzylguanidine scintigraphy, and stem cell supported therapy.…”