Therapeutic strategies and clinical evolution of patients with infantile fibrosarcoma: a unique paediatric case series

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 (AU)

Prospects and Advances in Adoptive Natural Killer Cell Therapy for Unmet Therapeutic Needs in Pediatric Bone Sarcomas.

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.

Therapeutic strategies and clinical evolution of patients with infantile fibrosarcoma: a unique paediatric case series.

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.

Treatment of infantile fibrosarcoma associated to an abdominal aortic aneurysm with larotrectinib: a case report.

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.

Authorship Correction: The Association Between Pain Relief Using Video Games and an Increase in Vagal Tone in Children With Cancer: Analytic Observational Study With a Quasi-Experimental Pre/Posttest Methodology.

[This corrects the article DOI: 10.2196/16013.].

The Association Between Pain Relief Using Video Games and an Increase in Vagal Tone in Children With Cancer: Analytic Observational Study With a Quasi-Experimental Pre/Posttest Methodology.

BACKGROUND: Patients with secondary pain due to mucositis after chemotherapy require treatment with morphine. Use of electronic video games (EVGs) has been shown to be an effective method of analgesia in other clinical settings. OBJECTIVE: The main objective of this study was to assess the association between the use of EVGs and the intensity of pain caused by chemotherapy-induced mucositis in pediatric patients with cancer. The secondary objective was to assess the association between changes in pain intensity and sympathetic-parasympathetic balance in this sample of pediatric patients. METHODS: Clinical records were compared between the day prior to the use of EVGs and the day after the use of EVGs. The variables were variations in pupil size measured using the AlgiScan video pupilometer (IDMed, Marseille, France), heart rate variability measured using the Analgesia Nociception Index (ANI) monitor (Mdoloris Medical Systems, Loos, France), intensity of pain measured using the Numerical Rating Scale (score 0-10), and self-administered morphine pump parameters. RESULTS: Twenty patients (11 girls and nine boys; mean age 11.5 years, SD 4.5 years; mean weight 41.5 kg, SD 20.7 kg) who met all the inclusion criteria were recruited. EVGs were played for a mean of 2.3 (SD 1.3) hours per day, resulting in statistically significant changes. After playing EVGs, there was significantly lower daily morphine use (before vs after playing EVGs: 35.9 vs 28.6 µg/kg/day, P=.003), lower demand for additional pain relief medication (17 vs 9.6 boluses in 24 hours, P=.001), lower scores of incidental pain intensity (7.7 vs 5.4, P=.001), lower scores of resting pain (4.8 vs 3.2, P=.01), and higher basal parasympathetic tone as measured using the ANI monitor (61.8 vs 71.9, P=.009). No variation in pupil size was observed with the use of EVGs. CONCLUSIONS: The use of EVGs in pediatric patients with chemotherapy-induced mucositis has a considerable analgesic effect, which is associated physiologically with an increase in parasympathetic vagal tone despite lower consumption of morphine.

Hematopoietic stem cell transplantation for CD3δ deficiency.

BACKGROUND: CD3δ deficiency is a fatal form of severe combined immunodeficiency that can be cured by hematopoietic stem cell transplantation (HSCT). The presence of a thymus loaded with T-cell progenitors in patients with CD3δ deficiency may require special considerations in choosing the regimen of conditioning and the type of HSCT. OBJECTIVES: To study the outcome of CD3δ deficiency by using various modalities of stem cell transplantation. METHODS: We analyzed data on 13 patients with CD3δ deficiency who underwent HSCT in 7 centers. HSCT was performed by using different sources of donor stem cells as well as various conditioning regimens. RESULTS: One patient received stem cells from a matched related donor and survived after a second transplant, needing substantial conditioning in order to engraft. Only 2 of 7 other patients who received a mismatched related donor transplant survived; 2 of them had no conditioning, whereas the others received various combinations of conditioning regimens. Engraftment of T cells in the survivors appears incomplete. Three other patients who received stem cells from a matched unrelated donor survived and enjoyed full immune reconstitution. Two patients received unrelated cord blood without conditioning. One of them has had a partial but stable engraftment, whereas the other engrafted well but is only 12 months after HSCT. We also report here for the first time that patients with CD3δ deficiency can present with typical features of Omenn syndrome. CONCLUSIONS: HSCT is a successful treatment for patients with CD3δ deficiency. The small number of patients in this report prevents definitive statements on the importance of survival factors, but several are suggested: (1) HLA-matched donor transplants are associated with superior reconstitution and survival than are mismatched donor transplants; (2) substantial conditioning appears necessary; and (3) early diagnosis and absence of opportunistic infections may affect outcome.