domingo, 30 de julio de 2017

MOlecular Screening for CAncer Treatment Optimization (MOSCATO-01) in pediatric patients: A single institutional prospective molecular stratificati... - PubMed - NCBI

2017 Jul 21. pii: clincanres.0381.2017. doi: 10.1158/1078-0432.CCR-17-0381. [Epub ahead of print]

MOlecular Screening for CAncer Treatment Optimization (MOSCATO-01) in pediatric patients: A single institutional prospective molecular stratification trial.

Harttrampf AC1, Lacroix L2, Deloger M3, Deschamps F4, Puget S5, Auger N6, Vielh P7, Varlet P8, Balogh Z9, Abbou S9, Allorant A9, Valteau-Couanet D10, Sarnacki S11, Galmiche L12, Meurice G13, Minard-Colin V14, Grill J15, Brugières L16, Dufour C17, Gaspar N18, Michiels S19, Vassal G20, Soria JC21, Geoerger B22.

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Abstract

PURPOSE:

This single institutional feasibility study prospectively characterized genomic alterations in recurrent or refractory solid tumors of pediatric patients in order to select a targeted therapy. Experimental Design: Following treatment failure patients with signed consent and aged above 6 months, underwent tumor biopsy or surgical resection of primary or metastatic tumor site. These newly acquired samples were analyzed by comparative genomic hybridization array, next generation sequencing for 75 target genes, whole exome and RNA sequencing. Biological significance of the alterations and suggestion of most relevant targeted therapies available were discussed in a multidisciplinary tumor board. Results: From December 2012 to January 2016, 75 patients were included, 73 patients underwent 79 interventions, 56 of which were research biopsies with a low complication rate. All patients were pretreated, 37.0% had a brain tumor and 63.0% an extra-cranial solid tumor. Median tumor cell content was 70% (range 0-100%). Successful molecular analysis in 69 patients detected in 60.9% of patients an actionable alteration in various oncogenic pathways (42.4% with copy number change, 33.3% with mutation, 2.1% with fusion), and change in diagnosis in three patients. Fourteen patients received 17 targeted therapies; two had received a matched treatment prior to inclusion. Conclusions: Research biopsies are feasible in advanced pediatric malignancies that exhibit a considerable amount of potentially actionable alterations. Genetic events affecting different cancer hallmarks and limited access to targeted agents within pediatric clinical trials remain the main obstacles that are addressed in our two subsequent precision medicine studies MAPPYACTS and AcSé-ESMART.