PDF(Pubmed)
Abstract：
The aim of the study was to identify patients with NTRK fusion-positive or RET fusion/mutation-positive thyroid cancers, who could benefit from neurotrophic tyrosine kinase receptor (NTRK) or receptor tyrosine kinase (RET) inhibitors.
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.
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.
摘要：
该研究的目的是确定NTRK融合阳性或RET融合/突变阳性的甲状腺癌患者，谁可以受益于神经营养性酪氨酸激酶受体（NTRK）或受体酪氨酸激酶（RET）抑制剂。
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。
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。
