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Journal Article
Review
Too many targets, not enough patients: rethinking neuroblastoma clinical trials.
Nature Reviews. Cancer 2018 June
Neuroblastoma is a rare solid tumour of infancy and early childhood with a disproportionate contribution to paediatric cancer mortality and morbidity. Combination chemotherapy, radiation therapy and immunotherapy remains the standard approach to treat high-risk disease, with few recurrent, actionable genetic aberrations identified at diagnosis. However, recent studies indicate that actionable aberrations are far more common in relapsed neuroblastoma, possibly as a result of clonal expansion. In addition, although the major validated disease driver, MYCN, is not currently directly targetable, multiple promising approaches to target MYCN indirectly are in development. We propose that clinical trial design needs to be rethought in order to meet the challenge of providing rigorous, evidence-based assessment of these new approaches within a fairly small patient population and that experimental therapies need to be assessed at diagnosis in very-high-risk patients rather than in relapsed and refractory patients.
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