Incidence of Thyroid-Related Adverse Events in Melanoma Patients Treated With Pembrolizumab.
Incidence of Thyroid-Related Adverse Events in Melanoma Patients Treated With Pembrolizumab.
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DOI：
10.1210/jc.2016-2300
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发表时间：
2016-11
期刊：
影响因子：
--
通讯作者：
Bravenboer B
中科院分区：
文献类型：
--
作者：
de Filette J;Jansen Y;Schreuer M;Everaert H;Velkeniers B;Neyns B;Bravenboer B
免疫检查点阻断与内分泌相关的不良事件有关。派姆单抗（一种抗程序性细胞死亡 1 (PD-1) 受体单克隆抗体）治疗期间的甲状腺功能障碍仍有待充分表征。评估派姆单抗相关甲状腺功能障碍的发生率和特征。在转诊肿瘤中心的扩大访问计划中，对开始使用派姆单抗的黑色素瘤患者进行了甲状腺功能前瞻性监测。在与炎症性甲状腺炎相符的病例中，对正电子发射断层扫描/计算机断层扫描（18FDG-PET/CT）上的 18 氟脱氧葡萄糖摄取进行了审查。 99 名晚期黑色素瘤患者（年龄，26.3-93.6 岁；63.6% 为女性）接受了至少一次派姆单抗治疗。患者特征、甲状腺功能（TSH、游离 T4）、甲状腺自身抗体和 18FDG-PET/CT。在 17 名患者中观察到 18 项甲状腺功能障碍不良事件。 12名患者出现甲状腺毒症，其中9名发展为甲状腺功能减退症。六名患者存在孤立性甲状腺功能减退症。 15 名甲状腺功能减退患者中有 10 名需要左旋甲状腺素治疗。 10 例患者中有 4 例在甲状腺功能障碍期间甲状腺自身抗体升高。在所有七名进展为甲状腺功能减退症的甲状腺毒症患者中，观察到甲状腺对 18FDG 的摄取弥漫性增加。甲状腺功能障碍在接受派姆单抗治疗的黑色素瘤患者中很常见。与炎症性甲状腺炎相关的甲状腺功能减退症和甲状腺毒症是最常见的表现。在抗 PD-1 单克隆抗体治疗期间需要进行甲状腺功能测试的连续测量。与炎症性甲状腺炎相容的甲状腺毒症与甲状腺吸收 18FDG 的弥漫性增加有关。应进一步研究甲状腺自身抗体的前瞻性作用以及组织病理学相关性。我们研究了 99 名接受派姆单抗（抗 PD-1）治疗的晚期黑色素瘤患者，发现频繁出现甲状腺功能减退症和甲状腺功能亢进症，后者与甲状腺弥漫性增加的 18FDG 摄取有关。
Immune checkpoint blockade is associated with endocrine-related adverse events. Thyroid dysfunction during pembrolizumab therapy, an anti-programmed cell death 1 (PD-1) receptor monoclonal antibody, remains to be fully characterized. To assess the incidence and characteristics of pembrolizumab-associated thyroid dysfunction. Thyroid function was monitored prospectively in melanoma patients who initiated pembrolizumab within an expanded access program at a referral oncology center. 18Fluorodeoxyglucose uptake on positron emission tomography/computed tomography (18FDG-PET/CT) was reviewed in cases compatible with inflammatory thyroiditis. Ninety-nine patients with advanced melanoma (age, 26.3–93.6 years; 63.6% females) who received at least one administration of pembrolizumab. Patient characteristics, thyroid function (TSH, free T4), thyroid autoantibodies, and 18FDG-PET/CT. Eighteen adverse events of thyroid dysfunction were observed in 17 patients. Thyrotoxicosis occurred in 12 patients, of which nine evolved to hypothyroidism. Isolated hypothyroidism was present in six patients. Levothyroxine therapy was required in 10 of 15 hypothyroid patients. Thyroid autoantibodies were elevated during thyroid dysfunction in four of 10 cases. Diffuse increased 18FDG uptake by the thyroid gland was observed in all seven thyrotoxic patients who progressed to hypothyroidism. Thyroid dysfunction is common in melanoma patients treated with pembrolizumab. Hypothyroidism and thyrotoxicosis related to inflammatory thyroiditis are the most frequent presentations. Serial measurements of thyroid function tests are indicated during anti-PD-1 monoclonal antibody therapy. Thyrotoxicosis compatible with inflammatory thyroiditis was associated with diffuse increased 18FDG uptake by the thyroid gland. The prospective role of thyroid autoantibodies should be further investigated, together with the histopathological correlates. We studied 99 advanced melanoma patients treated with pembrolizumab (anti-PD-1) and found frequent hypo- and hyperthyroidism, the latter associated with diffuse increased 18FDG uptake by the thyroid.
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DOI：
10.1038/nrc3239
发表时间：
2012-03-22
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Pardoll DM
通讯作者：
Pardoll DM
影响因子：
51.1
作者：
Ribas, Antoni;Puzanov, Igor;Dummer, Reinhard;Schadendorf, Dirk;Hamid, Omid;Robert, Caroline;Hodi, F. Stephen;Schachter, Jacob;Pavlick, Anna C.;Lewis, Karl D.;Cranmer, Lee D.;Blank, Christian U.;O'Day, Steven J.;Ascierto, Paolo A.;Salama, April K. S.;Margolin, Kim A.;Loquai, Carmen;Eigentler, Thomas K.;Gangadhar, Tara C.;Carlino, Matteo S.;Agarwala, Sanjiv S.;Moschos, Stergios J.;Sosman, Jeffrey A.;Goldinger, Simone M.;Shapira-Frommer, Ronnie;Gonzalez, Rene;Kirkwood, John M.;Wolchok, Jedd D.;Eggermont, Alexander;Li, Xiaoyun Nicole;Zhou, Wei;Zernhelt, Adriane M.;Lis, Joy;Ebbinghaus, Scot;Kang, S. Peter;Daud, Adil
通讯作者：
Daud, Adil
DOI：
10.1056/nejmoa1504030
发表时间：
2015-07-02
期刊：
The New England journal of medicine
影响因子：
--
作者：
Larkin J;Chiarion-Sileni V;Gonzalez R;Grob JJ;Cowey CL;Lao CD;Schadendorf D;Dummer R;Smylie M;Rutkowski P;Ferrucci PF;Hill A;Wagstaff J;Carlino MS;Haanen JB;Maio M;Marquez-Rodas I;McArthur GA;Ascierto PA;Long GV;Callahan MK;Postow MA;Grossmann K;Sznol M;Dreno B;Bastholt L;Yang A;Rollin LM;Horak C;Hodi FS;Wolchok JD
通讯作者：
Wolchok JD
影响因子：
158.5
作者：
Robert, Caroline;Schachter, Jacob;Ribas, Antoni
通讯作者：
Ribas, Antoni
DOI：
10.1111/j.1365-2362.1984.tb01212.x
发表时间：
1984-01-01
影响因子：
5.5
作者：
LEGER, AF;MASSIN, JP;SAVOIE, JC
通讯作者：
SAVOIE, JC