ABSTRACT
Background Infantile fibrosarcoma is the most frequent soft tissue sarcoma in newborns or children under one year of age. This tumour often implies high local aggressiveness and surgical morbidity. The large majority of these patients carry the ETV6NTRK3 oncogenic fusion. Hence, the TRK inhibitor larotrectinib emerged as an efficacious and safe alternative to chemotherapy for NTRK fusion-positive and metastatic or unresectable tumours. However, real-world evidence is still required for updating soft-tissue sarcoma practice guidelines. Objective To report our experience with the use of larotrectinib in pediatric patients. Methods Our case series shows the clinical evolution of 8 patients with infantile fibrosarcoma under different treatments. All patients enrolled in this study received informed consent for any treatment. Results Three patients received larotrectinib in first line. No surgery was needed with larotrectinib, which led to the rapid and safe remission of tumours, even in unusual anatomical locations. No significant adverse effects were observed with larotrectinib. Conclusion Our case series supports that larotrectinib may be a therapeutic option for newborn and infant patients with infantile fibrosarcoma, especially in uncommon locations (AU)
Subject(s)
Humans , Infant, Newborn , Infant , Child, Preschool , Soft Tissue Neoplasms/drug therapy , Soft Tissue Neoplasms/genetics , Fibrosarcoma/drug therapy , Fibrosarcoma/genetics , Antineoplastic Agents/therapeutic use , Soft Tissue Neoplasms/pathology , Fibrosarcoma/pathology , Treatment OutcomeABSTRACT
Malignant bone tumors are aggressive tumors, with a high tendency to metastasize, that are observed most frequently in adolescents during rapid growth spurts. Pediatric patients with malignant bone sarcomas, Ewing sarcoma and osteosarcoma, who present with progressive disease have dire survival rates despite aggressive therapy. These therapies can have long-term effects on bone growth, such as decreased bone mineral density and reduced longitudinal growth. New therapeutic approaches are therefore urgently needed for targeting pediatric malignant bone tumors. Harnessing the power of the immune system against cancer has improved the survival rates dramatically in certain cancer types. Natural killer (NK) cells are a heterogeneous group of innate effector cells that possess numerous antitumor effects, such as cytolysis and cytokine production. Pediatric sarcoma cells have been shown to be especially susceptible to NK-cell-mediated killing. NK-cell adoptive therapy confers numerous advantages over T-cell adoptive therapy, including a good safety profile and a lack of major histocompatibility complex restriction. NK-cell immunotherapy has the potential to be a new therapy for pediatric malignant bone tumors. In this manuscript, we review the general characteristics of osteosarcoma and Ewing sarcoma, discuss the long-term effects of sarcoma treatment on bones, and the barriers to effective immunotherapy in bone sarcomas. We then present the laboratory and clinical studies on NK-cell immunotherapy for pediatric malignant bone tumors. We discuss the various donor sources and NK-cell types, the engineering of NK cells and combinatorial treatment approaches that are being studied to overcome the current challenges in adoptive NK-cell therapy, while suggesting approaches for future studies on NK-cell immunotherapy in pediatric bone tumors.
Subject(s)
Bone Neoplasms , Neoplasms , Osteosarcoma , Sarcoma, Ewing , Sarcoma , Adolescent , Humans , Child , Sarcoma, Ewing/therapy , Osteosarcoma/therapy , Neoplasms/therapy , Immunotherapy, Adoptive , Bone Neoplasms/therapy , Killer Cells, Natural , Immunotherapy , Cell- and Tissue-Based TherapyABSTRACT
BACKGROUND: Infantile fibrosarcoma is the most frequent soft tissue sarcoma in newborns or children under one year of age. This tumour often implies high local aggressiveness and surgical morbidity. The large majority of these patients carry the ETV6-NTRK3 oncogenic fusion. Hence, the TRK inhibitor larotrectinib emerged as an efficacious and safe alternative to chemotherapy for NTRK fusion-positive and metastatic or unresectable tumours. However, real-world evidence is still required for updating soft-tissue sarcoma practice guidelines. OBJECTIVE: To report our experience with the use of larotrectinib in pediatric patients. METHODS: Our case series shows the clinical evolution of 8 patients with infantile fibrosarcoma under different treatments. All patients enrolled in this study received informed consent for any treatment. RESULTS: Three patients received larotrectinib in first line. No surgery was needed with larotrectinib, which led to the rapid and safe remission of tumours, even in unusual anatomical locations. No significant adverse effects were observed with larotrectinib. CONCLUSION: Our case series supports that larotrectinib may be a therapeutic option for newborn and infant patients with infantile fibrosarcoma, especially in uncommon locations.
Subject(s)
Fibrosarcoma , Sarcoma , Soft Tissue Neoplasms , Infant , Humans , Child , Infant, Newborn , Fibrosarcoma/drug therapy , Fibrosarcoma/genetics , Fibrosarcoma/pathology , Sarcoma/drug therapy , Soft Tissue Neoplasms/drug therapy , Soft Tissue Neoplasms/genetics , Soft Tissue Neoplasms/pathology , Protein Kinase Inhibitors/therapeutic useABSTRACT
Infantile fibrosarcoma (IFS) is a rare pediatric tumor which often presents the ETV6-NTRK3 gene fusion. NTRK3 encodes the neurotrophin-3 growth factor receptor tyrosine kinase, a druggable therapeutic target. Selective tropomyosin receptor kinase (TRK) inhibitors, such as larotrectinib, have shown efficacy and safety in the treatment of IFS. We report a case of an abdominal IFS diagnosed in a newborn associated with an aortic aneurysm that was successfully treated with larotrectinib without relevant adverse effects.
Subject(s)
Abdominal Neoplasms/drug therapy , Aortic Aneurysm, Abdominal/complications , Fibrosarcoma/drug therapy , Protein Kinase Inhibitors/therapeutic use , Pyrazoles/therapeutic use , Pyrimidines/therapeutic use , Abdominal Neoplasms/complications , Abdominal Neoplasms/diagnosis , Female , Fibrosarcoma/complications , Fibrosarcoma/diagnosis , Humans , Infant , Infant, NewbornSubject(s)
Child of Impaired Parents , Chromosomes, Human, Pair 16/genetics , Granulomatous Disease, Chronic/diagnosis , Immunologic Deficiency Syndromes/diagnosis , Mutation/genetics , NADPH Oxidases/genetics , Female , Genetic Counseling , Granulomatous Disease, Chronic/genetics , Humans , Immunologic Deficiency Syndromes/genetics , Infant , Male , Mothers , Polymorphism, Single Nucleotide , Prognosis , Uniparental DisomyABSTRACT
Uveal melanoma is extremely rare in children. Its clinical and histopathological features have been reported to be similar to those observed in adults. The tumor usually presents as a sessile or dome-shaped mass with secondary nonrhegmatogenous retinal detachment. We report a 19-month-old boy with a choroidal melanoma presenting as hemorrhagic retinal detachment and buphthalmos. The eye was enucleated, but the child subsequently died from systemic metastases.
Subject(s)
Choroid Neoplasms/diagnosis , Melanoma/diagnosis , Fatal Outcome , Humans , Hydrophthalmos/etiology , Infant , Male , Retinal Detachment/etiologyABSTRACT
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