甲状腺间变性癌的靶向治疗

P. Nikiforovich, A. Polyakov, I. Sleptsov, N. S. Boyko, Yu.  A. Gronskaya, N. Timofeeva, R. Chernikov
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引用次数: 1

摘要

介绍。间变性甲状腺癌(ATC)是一种非常罕见的甲状腺恶性肿瘤,占所有甲状腺癌的1 - 2%。在这种病理中,标准全身治疗的有效率低于15%,长期效果仍不令人满意。此外,没有确切的数据表明细胞毒性化疗可以改善atc患者的生存或生活质量。通过评价BRAFV600E突变病例靶向治疗的有效性,提高ATC患者的治疗效果。材料和方法。这项多中心前瞻性研究包括29例ATC IVB-C, T4a-bN1a-bM0-1患者。患者分为两组。第1组(对照组)包括15例可切除/不可切除、转移性/非转移性ATC(无BRAFV600E突变)、IVB-C期接受标准治疗(手术干预、放疗和化疗)的患者。第2组包括14例不可切除或转移性ATC患者,IVB-C期,接受联合治疗(手术干预,放疗和化疗),在新辅助和辅助方案中纳入BRAF抑制剂达非尼和曲美替尼。该研究表明,BRAF突变抑制剂靶向治疗BRAFV600E突变的局部晚期不可手术转移性ATC的有效性。组1总有效率(完全有效率+部分有效率)为0%,组2总有效率为64%。因此,达非尼+曲美替尼治疗方案是ATC和BRAFV600E突变患者联合靶向治疗的一种很有前景的方法。结论。对于BRAFV600突变的ATC患者来说,Dabrafenib + trametinib是一种很有前景的联合靶向治疗选择,具有高的总缓解率,延长的缓解持续时间,并在毒性控制的情况下增加生存率。
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Targeted therapy of anaplastic thyroid cancer
Introduction. Anaplastic thyroid cancer (ATC) is a very rare malignant tumor of the thyroid comprising 1–2 % of all thyroid cancers. In this pathology, response rate for standard systemic therapy is less than 15 %, and long-term results remain unsatisfactory. Additionally, there are no data conclusively showing that cytotoxic chemotherapy improves survival or quality of life in patients with ATC.Aim. To improve the results of treatment of patients with ATC through evaluation of the effectiveness of targeted therapy in cases of BRAFV600E mutation.Materials and methods. The multicenter prospective study included 29 patients with ATC IVB–C, T4a–bN1a–bM0–1. The patients were divided into 2 groups. The Group 1 (control) included 15 patients with resectable / nonresectable, metastatic / nonmetastatic ATC (without BRAFV600E mutation), stages IVB–C who received standard types of treatment (surgical intervention, radiation, and chemotherapy). The Group 2 consisted of 14 patients with nonresectable or metastatic ATC, stages IVB–C, who received combination therapy (surgical intervention, radiation, and chemotherapy) with inclusion of inhibitors of BRAF dabrafenib and trametinib in neoadjuvant and adjuvant regimens.Results. The study showed the effectiveness of targeted therapy with inhibitors of BRAF mutations in treatment of locally advanced non-operable metastatic ATC with BRAFV600E mutation. Overall response (complete response + partial response) in the Group 1 was 0 %, in the Group 2 it was 64 %. Therefore, treatment scheme dabrafenib + trametinib is a prmising approach to combination targeted therapy in patients with ATC and BRAFV600E mutation. Conclusion. Dabrafenib + trametinib is a promising combination targeted therapy option for patients with ATC with a BRAFV600 mutation demonstrates a high overall response rate, a prolonged duration of response, and an increase in survival rates with controlled toxicity.
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