1、甲状腺未分化癌诊疗现状及进展American Thyroid Association Guidelines for Management of Patients with Anaplastic Thyroid Cancer2012ATAG 2012 指南ATAG 2012 指南ATAG 2012 指南ATAG 2012 指南辅助及增敏化疗方案ATAG 2012 指南进展期化疗方案ATAG 2012 指南转移情况的文献汇总2017 NCCN 指南 V2术前完整评估分期情况后MDT讨论诊疗方案2017 NCCN 指南 V2AJCC 分期标准2017 NCCN 指南推荐化疗方案文献总结的治疗流程Cr
2、itical Reviews in Oncology/Hematology 86 (2013) 290301 与NCCN指南相同放疗范围瘤床区及高危区域高剂量，淋巴结区域低剂量指南推荐IMRT放疗Critical Reviews in Oncology/Hematology 86 (2013) 290301 术后治疗方案的研究情况Critical Reviews in Oncology/Hematology 86 (2013) 290301 Critical Reviews in Oncology/Hematology 86 (2013) 290301 转归研究情况Critical Revie
3、ws in Oncology/Hematology 86 (2013) 290301 转归研究情况Critical Reviews in Oncology/Hematology 86 (2013) 290301 分化混杂ATC的研究报道结果Clinical ReviewClinical ReviewAnaplastic Thyroid Carcinoma:Treatment in the Age of Molecular Targeted TherapyThe University of Texas MD Anderson Cancer CenterMD Anderson Cancer Cen
4、ter, Houston, TX Journal of Oncology Practice 12, no. 6 (June 2016) 511-518.甲状腺未分化癌最常见的十种基因突变 Journal of Oncology Practice 12, no. 6 (June 2016) 511-518.Curative intent treatment is multimodal and consists of surgery (R0 or R1 resection) and external beam radiationtherapy with radiosensitizing chemo
5、therapy此案例也未切除对策甲状腺此案例也未切除对策甲状腺 Journal of Oncology Practice 12, no. 6 (June 2016) 511-518. Common chemotherapy regi-mens used for radiosensitization in anaplastic thyroid carcinoma Journal of Oncology Practice 12, no. 6 (June 2016) 511-518.NOVEL THERAPIESMolecular targeted therapy trials in anaplas
6、tic thyroid carcinoma have been conducted under the basket protocol design and have been largely directed at targetting BRAF mutations. Other mutation specifictrials,suchas those that target PIK3CA, HRAS, and ALK, are also available for patients with anaplastic thyroid carcinoma,but these mutations
7、are even rarer than BRAF mutations in anaplastic thyroid carcinoma (13%, 4%, and1.5%,respectively). Journal of Oncology Practice 12, no. 6 (June 2016) 511-518.BRAF-Directed TherapiesTwo basket trials have completed enroll-ment一项报道了结果： 7例患者使用单药vemurafenib；1例CR，1例PR，4例进展，1例不能评估另一项在入组中： NCT02091141Dabr
8、afenib 联合trametinib 也在入组： NCT02034110 Journal of Oncology Practice 12, no. 6 (June 2016) 511-518.mTOR Inhibitors突变率： 30% to 35% A phaseII trial using everolimusib 入组了5例：1例近CR，1例SD，3例进展该例近CR患者具有TSC2突变，并稳定了18个月 Journal of Oncology Practice 12, no. 6 (June 2016) 511-518.Multikinase Inhibitors sorafenib
9、 ：1项研究入组10例，无治疗反应；另两项 6例患者的研究，仍无治疗反应Pazopanib：single-arm, phase II study，无治疗反应Lenvatinib： phase II study，入组11例，3例PR，7例SD，1例PD； NCT02657369在开展中Lenvatinib is currently approved for treatment of differentiated thyroid cancer in the United States,but is approved for all subtypes of thyroid cancer in Jap
10、an. Journal of Oncology Practice 12, no. 6 (June 2016) 511-518.Miscellaneous Targeted TherapiesCrolibulin：A phase I and II study evaluating crolibulin and cisplatin，16例，1例PR，1例CR达1年，II期未能完成，因入组太慢Efatutazone：I期，15例患者，1例PR。NCT02152137，在研中，II期，联合紫衫类 Journal of Oncology Practice 12, no. 6 (June 2016) 51
11、1-518.ImmunotherapyPD-L1：无任何研究开展，仅有报道有表达 Journal of Oncology Practice 12, no. 6 (June 2016) 511-518. Molinaro E, Romei C, Biagini A, et al. Anaplastic thyroid carcinoma: Anaplastic thyroid carcinoma: from clinicopathology to from clinicopathology to g e n e t i c s a n d a d v a n c e d g e n e t i
12、c s a n d a d v a n c e d therapiesJ.therapiesJ. Nature Reviews Endocrinology, 2017. University Hospital of Pisa.Nature Reviews Endocrinology, 2017.Nature Reviews Endocrinology, 2017.Nature Reviews Endocrinology, 2017.Distribution of oncogenic alterations in anaplastic thyroid carcinoma. Nature Revi
13、ews Endocrinology, 2017.Imatinib：治疗后复发，II期研究， 400 mg orally twice daily， treatment responses were assessed every 8 weeks， 6-month progression-free survival (PFS) was 36% and the 6-month OS was 45% Pazopanib：II期，16例，无反应；另一项入组中，October 2018结束Vemurafenib： twice-daily oral dose of 960 mg，1例15岁患者效果显著Ever
14、olimus： single-arm phase II trial，6/40例 ATC，PFS was 10 weeks (95% CI 4.816.0) and OS was 13 weeks (95% CI 7.418.6) in patients with ATC Nature Reviews Endocrinology, 2017.Gefitinib: II期研究，250 mg of gefitinib daily，32%缩小但均不足PR，1/5例ATC稳定SD达12个月。Axitinib：II期研究，30% response rate, and with stable disease
15、 lasting 16 weeks in 38% of patients Sunitinib：II期研究，overall median PFS of 241 days，未报道治疗反应率Sorafenib：3 项II期研究，9例有反应但不足PR；1项多种II期，20例，2例PR（10个月，27个月），5例SDNature Reviews Endocrinology, 2017.Lenvatinib：日本II期，11/43例ATC，3例相比安慰剂OS获益；II其，17例，反应率24%；II其，HOPE研究，入组至2018-7；另一项II期，2018-7月入组结束；SELECT ，比照安慰剂有3.6
16、个月OS延长，反应率 64.8%Combretastatin A4 phosphate：II/III期，80/180 ATC，提高去年OS达3倍；II期，联合化疗，1年OS 23%；另一项III期开展中Nature Reviews Endocrinology, 2017.Crolibulin：I/II期入组中，联合顺铂，27例，2016年完成，未报道结果Efatutazone：I期，15例，联合紫衫，耐受性良好；II期，入组中，2017年10月结束。其它待观察药物：Cetuximab，Bortezomib，Cediranib and ImmunotherapyNature Reviews Endocrinology, 2017.总结手术全面切除最大程度影响预后术后同步防化疗可改善预后进展后化疗为主靶向治疗有获益，尚研究中免疫治疗尚未开展研究
