ABSTRACT
Treatment-related morbidity drives research to identify targetable lesions in children with cancer. Neurotrophic tropomyosin receptor kinase (NTRK) alterations occur in ~1% of pediatric solid tumors. Early phase pediatric trials involving the NTRK inhibitor treatment for progressive NTRK-mutated cancers show promising results. The authors describe the adjuvant maintenance larotrectinib treatment after definitive surgical resection in 2 toddlers with NTRK fusion-positive malignancies (ETV6-NTRK3 fusion-positive undifferentiated embryonal sarcoma of the kidney and NACC2-NTRK2 fusion-positive anaplastic astrocytoma). Both are alive, in remission, developing normally and tolerating larotrectinib 15 months later, thus extending the NTRK inhibitor therapeutic spectrum by describing the adjuvant maintenance larotrectinib treatment in children with NTRK fusion-positive cancers associated with high recurrences.
Subject(s)
Astrocytoma/drug therapy , Kidney Neoplasms/drug therapy , Maintenance Chemotherapy/methods , Oncogene Proteins, Fusion/genetics , Pyrazoles/therapeutic use , Pyrimidines/therapeutic use , Astrocytoma/genetics , Astrocytoma/pathology , Chemotherapy, Adjuvant , Child, Preschool , Female , Humans , Kidney Neoplasms/genetics , Kidney Neoplasms/pathology , Male , Membrane Glycoproteins/genetics , Neoplasm Proteins/genetics , Neoplasms, Germ Cell and Embryonal/drug therapy , Neoplasms, Germ Cell and Embryonal/genetics , Neoplasms, Germ Cell and Embryonal/pathology , Prognosis , Receptor, trkB/genetics , Repressor Proteins/geneticsABSTRACT
Intratubular germ cell neoplasia (ITGCN) of the testis is a precursor to testicular germ cell tumor (TGCT), which can lead to the development of invasive cancer. In patients with a history of previously treated unilateral TGCT, treatment for ITGCN of the contralateral testis needs to be balanced with the risks of subsequent infertility. Here, we present a 17- year- old patient with ITGCN diagnosed after treatment of contralateral nonseminomatous TGCT who was successfully treated with a partial orchiectomy followed by low-dose radiation with preservation of his testosterone production.
Subject(s)
Combined Modality Therapy/methods , Neoplasms, Germ Cell and Embryonal/therapy , Neoplasms, Second Primary/therapy , Orchiectomy/methods , Radiotherapy/methods , Testicular Neoplasms/therapy , Adolescent , Humans , Male , Neoplasms, Germ Cell and Embryonal/pathology , Neoplasms, Second Primary/pathology , Testicular Neoplasms/pathologyABSTRACT
PURPOSE: Sinusoidal obstruction syndrome (SOS), also known as veno-occlusive disease, has been described following treatment of acute lymphoblastic leukemia (ALL) with the anti-metabolite 6-thioguanine (6-TG). Previous studies incorporating daily 6-TG into maintenance chemotherapy demonstrated a high incidence of SOS, typically presenting after prolonged exposures to 6-TG. 6-TG continues to be used as a single, 14-day burst during intensification; however, SOS associated with brief courses of 6-TG is poorly described. We aim to describe this rare though clinically significant phenomenon. METHODS: Children with 6-TG-related SOS were retrospectively identified from 680 de novo patients with ALL at Texas Children's Cancer Center over 8 years. Clinical characteristics and outcomes are described. RESULTS: Ten (1.5%) patients were identified with SOS. No predominant sex, ethnicity, or race was noted. SOS was diagnosed 16.5 (6-42) days from starting 6-TG. Isolated thrombocytopenia (IT) was noted in 9/10 patients and presented a median of 5 days prior to SOS. Refractoriness to platelet transfusions was noted in 8/10 patients, presenting a median of 2 days prior to SOS. Most patients were otherwise clinically stable outpatients upon presenting with IT or transfusion refractoriness. Fever was noted in 7/10 patients at diagnosis and 6/10 had documented or suspected infection within 14 days of SOS. Two patients died, while eight fully recovered. Intermediate thiopurine methyltransferase genotype was noted in 5/8 patients with data available. CONCLUSION: SOS following short courses of 6-TG in DI is clinically distinct from SOS following prolonged courses of 6-TG in maintenance, particularly in its early presentation and outcomes.
