Patients were identified in the Calgary prospective thyroid cancer database (N= 482). Patients were \'pre-screened\' with clinically available MassARRAY® BRAF test, Colon Panel, Melanoma Panel, or ThyroSPEC™. Mutation-negative tumors were \'screened\' for NTRK fusions and RET fusions/mutations with the Oncomine™ Comprehensive Assay v3 (OCAv3).
A total of 86 patients were included in 1 of 2 separate analyses. Analysis A included 42 patients with radioactive iodine (RAI)-resistant distant metastases. After pre-screening, 20 BRAF and RAS mutation-negative patients underwent OCAv3 screening, resulting in the detection of 4 patients with NTRKfusions and 4 patients with RET fusions (8/20, 40% of analyzed patients). Analysis B included 44 patients, 42 with American Thyroid Association (ATA) high and intermediate risk of recurrence and 2 with medullary thyroid carcinoma. During pre-screening, 1 patient with an NTRK fusion, 1 patient with a RET fusion, and 30 patients with BRAF mutations were identified. The remaining 9 patients received OCAv3 screening, resulting in detection of 1 patient with an NTRKfusion and 1 with a RET fusion (4/11, 36% of analyzed patients).
Our findings indicate a higher rate of NTRK fusions and RETfusions in patients with thyroid cancer with RAI-resistant distant metastases and ATA high or intermediate risk of recurrence. This highlights the importance of early screening to enable intervention with a NTRK or RET inhibitor.
在卡尔加里前瞻性甲状腺癌数据库中确定了患者(N=482)。使用临床可用的MassARRAY®BRAF测试对患者进行预筛选,结肠面板,黑色素瘤小组,或ThyroSPEC™。用Oncomine™综合测定v3(OCAv3)筛选突变阴性肿瘤的NTRK融合和RET融合/突变。
共有86名患者被纳入2个独立分析中的1个。分析A包括42例放射性碘(RAI)耐药的远处转移患者。预筛查后,20例BRAF和RAS突变阴性患者接受了OCAv3筛查,结果检测到4例NTRKfusions患者和4例RET融合患者(8/20,占分析患者的40%)。分析B包括44例患者,42与美国甲状腺协会(ATA)高和中间复发风险和2与甲状腺髓样癌。在筛查前,1例NTRK融合患者,1例RET融合患者,并鉴定出30例BRAF突变患者.其余9例患者接受OCAv3筛查,结果检测到1例NTRK融合患者和1例RET融合患者(4/11,占分析患者的36%)。
我们的研究结果表明,在有RAI耐药远处转移和ATA高或中等复发风险的甲状腺癌患者中,NTRK融合和RETfusion的发生率更高。这凸显了早期筛查对NTRK或RET抑制剂干预的重要性。