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Browsing by Issue Date, starting with "2021-06-11"

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  • Monitorização da mortalidade: Maio 2021
    Publication . Torres, Ana Rita; Silva, Susana Pereira; Rodrigues, Ana Paula
    Este relatório tem como objetivo principal, descrever e interpretar o padrão de mortalidade por todas as causas durante o mês de maio de 2021, entre as semanas 18/2021 e 21/2021 (03 a 30 de maio).
    2021-06-11Report Open access Show more
  • Frequency and Prognostic Impact of ALK Amplifications and Mutations in the European Neuroblastoma Study Group (SIOPEN) High-Risk Neuroblastoma Trial (HR-NBL1)
    Publication . Bellini, Angela; Pötschger, Ulrike; Bernard, Virginie; Lapouble, Eve; Baulande, Sylvain; Ambros, Peter F.; Auger, Nathalie; Beiske, Klaus; Bernkopf, Marie; Betts, David R.; Bhalshankar, Jaydutt; Bown, Nick; de Preter, Katleen; Clément, Nathalie; Combaret, Valérie; Font de Mora, Jaime; George, Sally L.; Jiménez, Irene; Jeison, Marta; Marques, Barbara; Martinsson, Tommy; Mazzocco, Katia; Morini, Martina; Mühlethaler-Mottet, Annick; Noguera, Rosa; Pierron, Gaelle; Rossing, Maria; Taschner-Mandl, Sabine; Van Roy, Nadine; Vicha, Ales; Chesler, Louis; Balwierz, Walentyna; Castel, Victoria; Elliott, Martin; Kogner, Per; Laureys, Geneviève; Luksch, Roberto; Malis, Josef; Popovic-Beck, Maja; Ash, Shifra; Delattre, Olivier; Valteau-Couanet, Dominique; Tweddle, Deborah A.; Ladenstein, Ruth; Schleiermacher, Gudrun
    Purpose: In neuroblastoma (NB), the ALK receptor tyrosine kinase can be constitutively activated through activating point mutations or genomic amplification. We studied ALK genetic alterations in high-risk (HR) patients on the HR-NBL1/SIOPEN trial to determine their frequency, correlation with clinical parameters, and prognostic impact. Materials and methods: Diagnostic tumor samples were available from 1,092 HR-NBL1/SIOPEN patients to determine ALK amplification status (n = 330), ALK mutational profile (n = 191), or both (n = 571). Results: Genomic ALK amplification (ALKa) was detected in 4.5% of cases (41 out of 901), all except one with MYCN amplification (MNA). ALKa was associated with a significantly poorer overall survival (OS) (5-year OS: ALKa [n = 41] 28% [95% CI, 15 to 42]; no-ALKa [n = 860] 51% [95% CI, 47 to 54], [P < .001]), particularly in cases with metastatic disease. ALK mutations (ALKm) were detected at a clonal level (> 20% mutated allele fraction) in 10% of cases (76 out of 762) and at a subclonal level (mutated allele fraction 0.1%-20%) in 3.9% of patients (30 out of 762), with a strong correlation between the presence of ALKm and MNA (P < .001). Among 571 cases with known ALKa and ALKm status, a statistically significant difference in OS was observed between cases with ALKa or clonal ALKm versus subclonal ALKm or no ALK alterations (5-year OS: ALKa [n = 19], 26% [95% CI, 10 to 47], clonal ALKm [n = 65] 33% [95% CI, 21 to 44], subclonal ALKm (n = 22) 48% [95% CI, 26 to 67], and no alteration [n = 465], 51% [95% CI, 46 to 55], respectively; P = .001). Importantly, in a multivariate model, involvement of more than one metastatic compartment (hazard ratio [HR], 2.87; P < .001), ALKa (HR, 2.38; P = .004), and clonal ALKm (HR, 1.77; P = .001) were independent predictors of poor outcome. Conclusion: Genetic alterations of ALK (clonal mutations and amplifications) in HR-NB are independent predictors of poorer survival. These data provide a rationale for integration of ALK inhibitors in upfront treatment of HR-NB with ALK alterations.
    2021-06-11Journal article Open access Show more