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Abstract：
Neurotrophic tyrosine receptor kinase gene fusions (NTRK) are oncogenic drivers present at a low frequency in most tumour types (<5%), and at a higher frequency (>80%) in a small number of rare tumours (e.g., infantile fibrosarcoma [IFS]) and considered mutually exclusive with other common oncogenic drivers. Health Canada recently approved two tyrosine receptor kinase (TRK) inhibitors, larotrectinib (for adults and children) and entrectinib (for adults), for the treatment of solid tumours harbouring NTRK gene fusions. In Phase I/II trials, these TRK inhibitors have demonstrated promising overall response rates and tolerability in patients with TRK fusion cancer who have exhausted other treatment options. In these studies, children appear to have similar responses and tolerability to adults. In this report, we provide a Canadian consensus on when and how to test for NTRK gene fusions and when to consider treatment with a TRK inhibitor for pediatric patients with solid tumours. We focus on three pediatric tumour types: non-rhabdomyosarcoma soft tissue sarcoma/unspecified spindle cell tumours including IFS, differentiated thyroid carcinoma, and glioma. We also propose a tumour-agnostic consensus based on the probability of the tumour harbouring an NTRK gene fusion. For children with locally advanced or metastatic TRK fusion cancer who have either failed upfront therapy or lack satisfactory treatment options, TRK inhibitor therapy should be considered.
摘要：
神经营养酪氨酸受体激酶基因融合（NTRK）是大多数肿瘤类型（<5％）的低频率存在的致癌驱动因素，在少数罕见肿瘤中以更高的频率(>80%)(例如，婴儿纤维肉瘤[IFS]），并被认为与其他常见致癌因素互斥。加拿大卫生部最近批准了两种酪氨酸受体激酶（TRK）抑制剂，larotrectinib（成人和儿童）和entrectinib（成人），用于治疗携带NTRK基因融合的实体瘤。在I/II期试验中，这些TRK抑制剂在已经用尽其他治疗选择的TRK融合癌患者中显示出有希望的总体缓解率和耐受性.在这些研究中,儿童似乎与成人有相似的反应和耐受性。在这份报告中,我们就何时以及如何检测NTRK基因融合以及何时考虑使用TRK抑制剂治疗患有实体瘤的儿科患者提供了加拿大共识.我们专注于三种儿科肿瘤类型：非横纹肌肉瘤软组织肉瘤/未指定的梭形细胞肿瘤，包括IFS，分化型甲状腺癌,还有神经胶质瘤.我们还基于携带NTRK基因融合的肿瘤的概率提出了与肿瘤无关的共识。对于患有局部晚期或转移性TRK融合癌的儿童，如果前期治疗失败或缺乏令人满意的治疗选择，应考虑使用TRK抑制剂治疗。
