BACKGROUND: Quantitative real-time (q)PCR for detection of minimal residual disease (MRD) in children with neuroblastoma (NB) can evaluate molecular bone marrow (BM) response to therapy, but the prognostic value of tumour kinetics in the BM during induction treatment remains to be established. The purpose of this study was to analyse at which time points MRD detection by sequential molecular assessment of BM was prognostic for overall survival (OS). METHODS: In this single centre study, qPCR was performed with five NB-specific markers: PHOX2B, TH, DDC, GAP43 and CHRNA3, on 106 retrospectively analysed BM samples of 53 patients >1 year with stage 4 neuroblastoma. The prognostic impact of MRD at diagnosis (n = 39), at 3 months after diagnosis (n = 38) and after completing induction chemotherapy (n = 29) was assessed using univariate and bivariate Cox regression analyses. RESULTS: There was no correlation between tumour load at diagnosis and outcome (p = 0.93). Molecular BM remission was observed in 11/38 (29%) of patients at 3 months after diagnosis and associated with favourable outcome (5-y-OS 62 ± 15.0% versus 19 ± 8%; p = 0.009). After completion of induction chemotherapy, BM of 41% (12/29) of the patients was still MRD positive, which was associated with poor outcome (5-y-OS 0% versus 52 ± 12%; p<0.001). For both time points, the prognostic value of molecular response remained significant in bivariate analysis. CONCLUSIONS: MRD detection measured by a panel of NB specific-PCR targets could identify fast responders, who clear their BM early during treatment. Fast molecular response was a prognostic factor, associated with better outcome. Our data indicate that MRD analysis during induction therapy should be included in prospective MRD studies.
BACKGROUND: Quantitative real-time (q)PCR for detection of minimal residual disease (MRD) in children with neuroblastoma (NB) can evaluate molecular bone marrow (BM) response to therapy, but the prognostic value of tumour kinetics in the BM during induction treatment remains to be established. The purpose of this study was to analyse at which time points MRD detection by sequential molecular assessment of BM was prognostic for overall survival (OS). METHODS: In this single centre study, qPCR was performed with five NB-specific markers: PHOX2B, TH, DDC, GAP43 and CHRNA3, on 106 retrospectively analysed BM samples of 53 patients >1 year with stage 4 neuroblastoma. The prognostic impact of MRD at diagnosis (n = 39), at 3 months after diagnosis (n = 38) and after completing induction chemotherapy (n = 29) was assessed using univariate and bivariate Cox regression analyses. RESULTS: There was no correlation between tumour load at diagnosis and outcome (p = 0.93). Molecular BM remission was observed in 11/38 (29%) of patients at 3 months after diagnosis and associated with favourable outcome (5-y-OS 62 ± 15.0% versus 19 ± 8%; p = 0.009). After completion of induction chemotherapy, BM of 41% (12/29) of the patients was still MRD positive, which was associated with poor outcome (5-y-OS 0% versus 52 ± 12%; p<0.001). For both time points, the prognostic value of molecular response remained significant in bivariate analysis. CONCLUSIONS: MRD detection measured by a panel of NB specific-PCR targets could identify fast responders, who clear their BM early during treatment. Fast molecular response was a prognostic factor, associated with better outcome. Our data indicate that MRD analysis during induction therapy should be included in prospective MRD studies.
Authors: Yania Yáñez; David Hervás; Elena Grau; Silvestre Oltra; Gema Pérez; Sarai Palanca; Mar Bermúdez; Catalina Márquez; Adela Cañete; Victoria Castel Journal: J Cancer Res Clin Oncol Date: 2015-10-24 Impact factor: 4.553
Authors: J Mora; O Cruz; C Lavarino; J Rios; M Vancells; A Parareda; H Salvador; M Suñol; R Carrasco; A Guillen; S Mañé; C de Torres Journal: Clin Transl Oncol Date: 2015-01-17 Impact factor: 3.405
Authors: Susan G Kreissman; Robert C Seeger; Katherine K Matthay; Wendy B London; Richard Sposto; Stephan A Grupp; Daphne A Haas-Kogan; Michael P Laquaglia; Alice L Yu; Lisa Diller; Allen Buxton; Julie R Park; Susan L Cohn; John M Maris; C Patrick Reynolds; Judith G Villablanca Journal: Lancet Oncol Date: 2013-07-25 Impact factor: 41.316
Authors: Esther M van Wezel; Lieke M J van Zogchel; Jalenka van Wijk; Ilse Timmerman; Ngoc-Kim Vo; Lily Zappeij-Kannegieter; Boris deCarolis; Thorsten Simon; Max M van Noesel; Jan J Molenaar; Tim van Groningen; Rogier Versteeg; Huib N Caron; C Ellen van der Schoot; Jan Koster; Johan van Nes; Godelieve A M Tytgat Journal: JCO Precis Oncol Date: 2019-10-03