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1、甲状腺未分化癌诊疗现状及进展,陕西省人民医院放疗科 陈鑫 博士 主治医师,American Thyroid Association Guidelines for Management of Patients with Anaplastic Thyroid Cancer 2012,ATAG 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 V2,A
2、JCC 分期标准,2017 NCCN 指南推荐化疗方案,文献总结的治疗流程,Critical 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/Hem
3、atology 86 (2013) 290301,转归研究情况,Critical Reviews 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 ReviewAnaplastic Thyroid Carcinoma:Treatment in the Age of Molecular Targeted Therapy,The University of Texas MD Anderson C
4、ancer Center, Houston, TX,Journal of Oncology Practice12, 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 Practice12, no.6 (June 2016) 511-518.,Curative intent treatment is multimodal and consists of surgery (R0 or R1 resection) and external beam radiationtherapy with radiosensitizin
5、g chemotherapy,此案例也未切除对策甲状腺,Journal of Oncology Practice12, no.6 (June 2016) 511-518.,Common chemotherapy regi-mens used for radiosensitization in anaplastic thyroid carcinoma,Journal of Oncology Practice12, no.6 (June 2016) 511-518.,NOVEL THERAPIES,Molecular targeted therapy trials in anaplastic th
6、yroid 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 are ev
7、en rarer than BRAF mutations in anaplastic thyroid carcinoma (13%, 4%, and1.5%,respectively).,Journal of Oncology Practice12, no.6 (June 2016) 511-518.,BRAF-Directed Therapies,Two 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： NCT02091141 Dabrafe
8、nib 联合trametinib 也在入组： NCT02034110,Journal of Oncology Practice12, 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 Practice12, no.6 (June 2016) 511-518.,Multikinase Inhibitors,sorafenib ：1
9、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 Practice12, no.6 (June 2016) 511-518.,Miscellaneous Targeted Therapies,Crolibulin：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 Practice12, no.6 (June 2016) 511
11、-518.,Immunotherapy,PD-L1：无任何研究开展，仅有报道有表达,Journal of Oncology Practice12, no.6 (June 2016) 511-518.,Molinaro E, Romei C, Biagini A, et al. Anaplastic thyroid carcinoma: from clinicopathology to genetics and advanced therapiesJ. Nature Reviews Endocrinology, 2017.,University Hospital of Pisa.,Nature
12、Reviews Endocrinology, 2017.,Nature Reviews Endocrinology, 2017.,Nature Reviews Endocrinology, 2017.,Distribution of oncogenic alterations in anaplastic thyroid carcinoma.,Nature Reviews Endocrinology, 2017.,Imatinib：治疗后复发，II期研究， 400 mg orally twice daily， treatment responses were assessed every 8we
13、eks， 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，October2018结束 Vemurafenib： twice-daily oral dose of 960 mg，1例15岁患者效果显著 Everolimus： single-arm phaseII trial，6/40例 ATC，PFS was 10weeks (95%CI 4.816.0) and OS was 13weeks (95%CI 7.418.6) in pat
14、ients 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 lasting 16weeks in 38% of patients Sunitinib：II期研究，overall median PFS of 241days，未报道治疗反应率 Sorafenib：3 项II期研究，9例有反应但不足P
15、R；1项多种II期，20例，2例PR（10个月，27个月），5例SD,Nature 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 Immunotherapy,Nature 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,
