Simple Summary: Clinical 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.

Rothmund-Thomson syndrome (RTS) is characterized by a rash that begins in the first few months of life and eventually develops into poikiloderma. Associated symptoms are alterations in the teeth, sparse hair, thin eyebrows, lack of eyelashes, low stature, bone abnormalities, hematological illnesses, gastrointestinal disease, malnutrition, cataracts, and predisposition to cancer, principally to bone tumors and skin cancer. Diagnostic certitude is provided by a genetic study involving detection of pathogenic variants of the RECQL4 gene. We hereby present a familiar case of RTS in two siblings from a Portuguese family, both diagnosed with osteosarcoma. Genomic analysis (203 genes) of both tumors as well as germline analysis of the RECQL4 gene, thus confirming the syndrome in the family, have been performed. The relevance of clinical recognition of the hallmarks of the disease and thus early diagnosis with early intervention is highlighted.

Objective: To assess the effect of metformin on weight, BMI, body fat, and insulin sensitivity in obese children and adolescents. Methodology: The study was prospective, and included 21 patients with obesity (8 male, 13 female) with a mean age of 12.31 (3.87) years. Inclusion criteria were a fat mass percentage (FM%) of over 25% in males and over 30% in females, a BMI of greater than the 95th percentile, and a lack of response to nutritional and lifestyle changes over three months. Informed consent was obtained from children, parents and the treatment was approved by the hospital's Ethics Committee, and the Spanish health ministry. All subjects received treatment with metformin for six months and each month was instructed to follow nutritional and lifestyle changes. The oral glucose tolerance test (OGTT) was done for 95% of the patients. Results: A decrease in weight-SDS (p< 0.001), BMI-SDS (p< 0.001), FM% (p = 0.002), waist/hip ratio (p = 0.141), HOMA (p = 0.198 and plasma glucose level at 120 min. (p = 0.008) was observed after six months of metformin therapy in association with nutritional and lifestyle changes. At the onset of the study, plasma glucose level at 120 min. was above 140 mg/dL in 38% (n = 8) of patients, and the HOMA index was above 3.8 in 42% (n = 9). Altogether, 11 patients had insulin resistance. Mean dose of metformin was built up to a maximum of 1275 mg/day. Twenty-four percent of the subjects complained of dyspepsia or diarrhea or both. Conclusion: In this study, metformin, combined with diet and lifestyle changes, contributed to an improvement in BMI and to a loss of weight and body fat in children with obesity, whether or not that obesity was associated with insulin resistance.