RESUMEN
PURPOSE: Our study aimed to explore real-world treatment scenarios for children and adolescents with neurotrophic tropomyosin receptor kinase (NTRK)-fused tumors, emphasizing access, responses, side effects, and outcomes. PATIENTS AND METHODS: Pooled clinical data from 17 pediatric cases (11 soft-tissue sarcomas, five brain tumors, and one neuroblastoma) treated with larotrectinib and radiologic images for 14 patients were centrally reviewed. Testing for gene fusions was prompted by poor response to treatment, tumor progression, or aggressiveness. RESULTS: Six different NTRK fusion subtypes were detected, and various payment sources for testing and medication were reported. Radiologic review revealed objective tumor responses (OR) in 11 of 14 patients: Complete responses: two; partial responses: nine; and stable disease: three cases. Grades 1 or 2 Common Terminology Criteria for Adverse Events adverse effects were reported in five patients. Regarding the entire cohort's clinical information, 15 of 17 patients remain alive (median observation time: 25 months): four with no evidence of disease and 11 alive with disease (10 without progression). One patient developed resistance to the NTRK inhibitor and died from disease progression while another patient died due to an unrelated cause. CONCLUSION: This real-world study confirms favorable agnostic tumor OR rates to larotrectinib in children with NTRK-fused tumors. Better coordination to facilitate access to medication remains a challenge, particularly in middle-income countries like Brazil.
Asunto(s)
Inhibidores de Proteínas Quinasas , Pirazoles , Humanos , Niño , Masculino , Femenino , Adolescente , Pirazoles/uso terapéutico , Preescolar , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirimidinas/uso terapéutico , Receptor trkA/genética , Receptor trkA/antagonistas & inhibidores , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/genética , Sarcoma/tratamiento farmacológico , Sarcoma/genética , Neuroblastoma/tratamiento farmacológico , Neuroblastoma/genética , Lactante , Receptor trkB/genética , Receptor trkC/genética , Ensayos Clínicos como AsuntoRESUMEN
OBJECTIVES: Wilm's Tumor (WT) is the most common pediatric kidney cancer. Whereas most WTs are isolated, approximately 5% are associated with syndromes such as Denys-Drash (DDS), characterized by early onset nephropathy, disorders of sex development and predisposition to WT. CASE PRESENTATION: A 46,XY patient presenting with bilateral WT and genital ambiguity without nephropathy was heterozygous for the novel c.851_854dup variant in WT1 gene sequence. This variant affects the protein generating the frameshift p.(Ser285Argfs*14) that disrupts a nuclear localization signal (NLS) region. CONCLUSIONS: This molecular finding is compatible with the severe scenario regarding the Wilm's tumor presented by the patient even though nephropathy was absent.
Asunto(s)
Síndrome de Denys-Drash , Neoplasias Renales , Tumor de Wilms , Niño , Síndrome de Denys-Drash/genética , Síndrome de Denys-Drash/patología , Genes del Tumor de Wilms , Heterocigoto , Humanos , Neoplasias Renales/genética , Proteínas WT1/genética , Tumor de Wilms/genéticaRESUMEN
A 14-year-old, male patient was referred for the treatment of mucositis, idiopathic facial asymmetry, and candidiasis. The patient had been undergoing chemotherapy for 5 years for acute lymphoblastic leukemia. He presented with a swollen face, fever, and generalized symptomatology in the mouth with burning. On physical examination, general signs of poor health, paleness, malnutrition, and jaundice were observed. The extraoral clinical examination showed edema on the right side of the face and cutaneous erythema. On intraoral clinical examination, generalized ulcers with extensive necrosis on the hard palate mucosa were observed, extending to the posterior region. Both free and attached gingivae were ulcerated and edematous with exudation and spontaneous bleeding, mainly in the superior and inferior anterior teeth region. The tongue had no papillae and was coated, due to poor oral hygiene. The patient also presented with carious white lesions and enamel hypoplasia, mouth opening limitation, and foul odor. After exfoliative cytology of the affected areas, the diagnosis was mixed infection by Candida albicans and bacteria. Recommended treatment was antibiotics and antifungal administration, periodontal prophylaxis, topical application of fluor 1.23%, and orientation on and control of proper oral hygiene and diet during the remission phase of the disease.
Asunto(s)
Candidiasis Bucal/microbiología , Gingivitis Ulcerosa Necrotizante/etiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Adolescente , Antibacterianos/uso terapéutico , Antifúngicos/uso terapéutico , Candidiasis Bucal/tratamiento farmacológico , Asimetría Facial/complicaciones , Gingivitis Ulcerosa Necrotizante/tratamiento farmacológico , Humanos , MasculinoRESUMEN
A 6-year-old girl with Glanzmann thrombasthenia presented with caries and periapical lesions in the primary mandibular second molars and moderate gingivitis of the maxillary and mandibular anterior teeth. Dental extraction was recommended, and before every surgical intervention, the patient underwent platelet-concentrate transfusion to prevent hemorrhage. Epsilon aminocaproic acid was administered 6 hours before, and 48 hours after every dental procedure to prevent bleeding. In this case, treatment was effective in the prevention of hemorrhagic complications, during the required dental procedures.