Abstract
Simple SummaryClinical management of sarcomas is complex because they are rare and heterogeneous tumors. Management requires a coordinated multidisciplinary approach, especially in children. Genomic characterization of this complex group of tumors contributes to the identification of prognostic biomarkers and to the continued expansion of therapeutic options. In this article, we present the positive experience of two Spanish hospitals in the use of genomic analysis in the overall clinical management of sarcomas in children and young adults. We describe on a case-by-case basis how genomic analysis has contributed to both diagnosis and treatment.Genomic techniques enable diagnosis and management of children and young adults with sarcomas by identifying high-risk patients and those who may benefit from targeted therapy or participation in clinical trials. Objective: to analyze the performance of an NGS gene panel for the clinical management of pediatric sarcoma patients. We studied 53 pediatric and young adult patients diagnosed with sarcoma, from two Spanish centers. Genomic data were obtained using the Oncomine Childhood Cancer Research Assay, and categorized according to their diagnostic, predictive, or prognostic value. In 44 (83%) of the 53 patients, at least one genetic alteration was identified. In 80% of these patients, the diagnosis was obtained (n = 11) or changed (n = 9), and thus genomic data affected therapy. The most frequent initial misdiagnosis was Ewing’s sarcoma, instead of myxoid liposarcoma (FUS-DDDIT3), rhabdoid soft tissue tumor (SMARCB1), or angiomatoid fibrous histiocytoma (EWSR1-CREB1). In our series, two patients had a genetic alteration with an FDA-approved targeted therapy, and 30% had at least one potentially actionable alteration. NGS-based genomic studies are useful and feasible in diagnosis and clinical management of pediatric sarcomas. Genomic characterization of these rare and heterogeneous tumors also helps in the search for prognostic biomarkers and therapeutic opportunities.
Highlights
Cancer is one of the main causes of morbidity and mortality in children and adolescents worldwide
All sarcomas included in the study were histopathologically evaluated on hematoxylin slides, and FISH and IHC techniques, used as primary detection approaches for possible fusion events, were carried out during routine diagnostic procedures with validated reagents according to standard laboratory guidelines
Three of our patients benefited from targeted therapies based on genomic findings, and a further four patients could have received targeted therapy if the drug had been available at the time of diagnosis
Summary
Cancer is one of the main causes of morbidity and mortality in children and adolescents worldwide. The survival of children and adolescents with sarcomas, patients with metastatic disease, has barely improved in recent decades, despite intensification of treatments such as chemotherapy, surgery, and/or radiotherapy. Present specific pathognomonic genetic alterations, such as gene fusions. Detection of these alterations is not possible with the typical techniques and equipment of a pathology laboratory, and requires precise diagnostic techniques at the molecular level [4]. Implementation of new molecular diagnostic techniques makes it possible to obtain a correct diagnosis that enables prior identification of high-risk patients and improved management in certain complex cases, and can be regarded as a further step toward more-personalized medicine in pediatric sarcomas. The new techniques need to be fast and work with just a small sample of material obtainable by conventional methods
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