Elective Discontinuation of Larotrectinib in Pediatric Patients With TRK Fusion Sarcomas and Related Mesenchymal Tumors.

Larotrectinib is a highly selective tropomyosin receptor kinase (TRK) inhibitor with efficacy in children with TRK fusion tumors. We evaluated patient outcomes after elective discontinuation of larotrectinib in the absence of disease progression in a protocol-defined wait-and-see subset analysis of eligible patients where treatment resumption with larotrectinib was allowed if disease progressed. We also assessed the safety and efficacy of larotrectinib in all pediatric patients with sarcoma.

Paediatric strategy forum for medicinal product development in diffuse midline gliomas in children and adolescents ACCELERATE in collaboration with the European Medicines Agency with participation of the Food and Drug Administration.

Fewer than 10 % of children with diffuse midline glioma (DMG) survive 2 years from diagnosis. Radiation therapy remains the cornerstone of treatment and there are no medicinal products with regulatory approval. Although the biology of DMG is better characterized, this has not yet translated into effective treatments.

Head and Neck Paraganglioma in Pacak-Zhuang Syndrome.

Head and neck paragangliomas (HNPGLs) are typically slow-growing, hormonally inactive tumors of parasympathetic paraganglia. Inactivation of prolyl-hydroxylase domain-containing 2 protein causing indirect gain-of-function of hypoxia-inducible factor-2α (HIF-2α), encoded by EPAS1, was recently shown to cause carotid body hyperplasia. We previously described a syndrome with multiple sympathetic paragangliomas caused by direct gain-of-function variants in EPAS1 (Pacak-Zhuang syndrome, PZS) and developed a corresponding mouse model.

Melanoma Among Adult Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study.

Purpose: Melanoma as a subsequent malignant neoplasm has been described among childhood cancer survivors; however, the risk factors and long-term survival are not well understood.

Methods: We assessed incidence, risk factors, and outcomes for melanoma among participants in the Childhood Cancer Survivor Study cohort. Cumulative incidence and standardized incidence ratios (SIRs) were calculated, and multivariable Cox models were used to determine hazard ratios (HRs) and associated 95% CI for melanoma risk factors.

Paediatric strategy forum for medicinal product development of PI3-K, mTOR, AKT and GSK3β inhibitors in children and adolescents with cancer.

Phosphatidylinositol 3-kinase (PI3-K) signalling pathway is a crucial path in cancer for cell survival and thus represents an intriguing target for new paediatric anti-cancer drugs. However, the unique clinical toxicities of targeting this pathway (resulting in hyperglycaemia) difficulties combining with chemotherapy, rarity of mutations in childhood tumours and concomitant mutations have resulted in major barriers to clinical translation of these inhibitors in treating both adults and children. Mutations in PIK3CA predict response to PI3-K inhibitors in adult cancers.

Regional lymph node evaluation in pediatric conventional melanoma subtype: a single-center 10-year review.

Purpose: To assess the prognostic and therapeutic significance of sentinel lymph node biopsy (SLNB) and completion lymph node dissection (CLND) in pediatric conventional melanoma (CM), while evaluating potential predictive factors for outcomes.

Methods: We conducted a retrospective analysis of medical records spanning 2009-2020, focusing on patients aged 18 or younger with localized cutaneous conventional melanoma.

Results: Among the 33 patients, SLNB detected metastasis in 57.

Adolescent and Young Adult (AYA) Oncology, Version 2.2024, NCCN Clinical Practice Guidelines in Oncology.

This selection from the NCCN Guidelines for Adolescent and Young Adult (AYA) Oncology focuses on considerations for the comprehensive care of AYA patients with cancer. Compared with older adults with cancer, AYA patients have unique needs regarding treatment, fertility counseling, psychosocial and behavioral issues, and supportive care services. The complete version of the NCCN Guidelines for Adolescent and Young Adult (AYA) Oncology addresses additional aspects of caring for AYA patients, including risk factors, screening, diagnosis, and survivorship.

UVEAL MELANOMA PRESENTING AS HEPATIC METASTASIS IN A PATIENT WITH OCULODERMAL MELANOCYTOSIS.

Purpose: To report an atypical case of occult uveal melanoma in a patient with oculodermal melanocytosis that first presented with symptoms of hepatic metastasis.

Methods: A previously healthy 16-year-old boy with noted ocular hyperpigmentation developed abdominal pain and vomiting and was found to have a hepatic mass consistent with a metastatic lesion from an occult uveal melanoma.

Results: On examination, the patient's visual acuity was 20/20, and pupils were reactive without an afferent pupillary defect in both eyes.

Feasibility of indocyanine green-guided localization of pulmonary nodules in children with solid tumors.

Background: Clearing all pulmonary metastases is essential for curing pediatric solid tumors. However, intraoperative localization of such pulmonary nodules can be challenging. Therefore, an intraoperative tool that localizes pulmonary metastases is needed to improve diagnostic and therapeutic resections.

Progressive metastatic infantile fibrosarcoma with multiple acquired mutations.

Infantile fibrosarcoma is the most common soft-tissue sarcoma in children under the age of 1 yr and is defined molecularly by fusion proteins. This tumor is known to be locally invasive; however, although rare, metastases can occur. The fusion acts as a driver for tumor formation, which can be targeted by first- and second-generation inhibitors.

Malignant Progression of an Ancestral Bone Marrow Clone Harboring a CIC-NUTM2A Fusion in Isolated Myeloid Sarcoma.

Unlabelled: Myeloid sarcoma is a rare condition consisting of extramedullary myeloid blasts found in association with acute myeloid leukemia or, in the absence of bone marrow involvement. We identified an infant with isolated myeloid sarcoma whose bone marrow was negative for involvement by flow cytometry. Sequencing revealed the fusion oncogene CIC-NUTM2A and identified the sarcoma to be clonally evolved from the bone marrow, which carried the fusion despite the absence of pathology.

NCCN Guidelines® Insights: Gastrointestinal Stromal Tumors, Version 2.2022.

Gastrointestinal stromal tumors (GIST) are the most common type of soft tissue sarcoma that occur throughout the gastrointestinal tract. Most of these tumors are caused by oncogenic activating mutations in the KIT or PDGFRA genes. The NCCN Guidelines for GIST provide recommendations for the diagnosis, evaluation, treatment, and follow-up of patients with these tumors.

Paediatric Strategy Forum for medicinal product development in mitogen-activated protein kinase pathway inhibitors: ACCELERATE in collaboration with the European Medicines Agency with participation of the Food and Drug Administration.

As the mitogen-activated protein kinase (MAPK) signalling pathway is activated in many paediatric cancers, it is an important therapeutic target. Currently, a range of targeted MAPK pathway inhibitors are being developed in adults. However, MAPK signals through many cascades and feedback loops and perturbing the MAPK pathway may have substantial influence on other pathways as well as normal development.