Extended Antitumor Response of a BRAF V600E Papillary Thyroid Carcinoma to Vemurafenib.
Extended Antitumor Response of a BRAF V600E Papillary Thyroid Carcinoma to Vemurafenib.
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DOI：
10.1159/000363377
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发表时间：
2014-05
影响因子：
0.8
通讯作者：
Sharman J
中科院分区：
文献类型：
--
作者：
Ali SM;He J;Carson W;Stephens PJ;Fiorillo J;Lipson D;Palmer GA;Ross JS;Miller VA;Sharman J
对于放射性碘（RAI）治疗无效的转移性甲状腺乳头状癌（PTC）患者，全身化疗的疗效有限。这种肿瘤经常携带BRAF V600 E，这种改变可能预测对维罗非尼治疗的反应性。我们报告了一个对RAI治疗无效的转移性PTC患者，通过下一代测序进行了基因组分析。鉴定的唯一基因组改变是具有1 q三体的近二倍体基因组上的BRAF V600 E。使用vemurafenib治疗后，患者的放射学和临床表现显著改善，持续抗肿瘤反应的持续时间超过23个月。将236个癌症相关基因的3，769个外显子和19个癌症中经常重排的基因的内含子的杂交捕获应用于从含有转移性PTC的淋巴结的福尔马林固定的石蜡包埋活检中提取的>50 ng DNA，并进行测序，以达到高的均匀覆盖率×616。鉴定了BRAF V600 E改变，而在近二倍体肿瘤基因组内不存在其他体细胞基因组改变。该患者最初接受维罗非尼960 mg每日两次治疗，由于皮疹和腹泻，剂量降至480 mg每日两次，PET-CT和专用CT成像显示持续抗肿瘤反应超过23个月。转移性、RAI难治性PTC的基因组分析可以揭示靶向BRAF V600 E改变，而不会复合体细胞改变，此类患者可能从维罗非尼治疗中获得更长期的获益。前瞻性临床试验正在进行中，以证实我们的初步观察结果。
For patients with metastatic papillary thyroid carcinoma (PTC) refractory to radioactive iodine (RAI) treatment, systemic chemotherapy has limited efficacy. Such tumors frequently harbor BRAF V600E, and this alteration may predict responsiveness to vemurafenib treatment. We report a metastatic PTC patient refractory to RAI treatment that underwent genomic profiling by next-generation sequencing. The sole genomic alteration identified was BRAF V600E on a near diploid genome with trisomy 1q. With vemurafenib treatment, the patient experienced a dramatic radiographic and clinical improvement, with the duration of an ongoing antitumor response exceeding 23 months. Hybridization capture of 3,769 exons of 236 cancer-related genes and the introns of 19 genes frequently rearranged in cancer was applied to >50 ng of DNA extracted from a formalin-fixed, paraffin-embedded biopsy of a lymph node containing metastatic PTC and was sequenced to a high, uniform coverage of ×616. A BRAF V600E alteration was identified with no other somatic genomic alterations present within a near diploid tumor genome. The patient initially received vemurafenib at 960 mg twice daily that was reduced to 480 mg twice daily due to rash and diarrhea and has experienced an ongoing antitumor response exceeding 23 months by both PET-CT and dedicated CT imaging. Genomic profiling in metastatic, RAI-refractory PTC can reveal a targetable BRAF V600E alteration without compounding somatic alterations, and such patients may derive a more prolonged benefit from vemurafenib treatment. Prospective clinical trials are ongoing to confirm our preliminary observation.
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影响因子：
5.9
作者：
MAZZAFERRI, EL;JHIANG, SM
通讯作者：
JHIANG, SM
影响因子：
168.9
作者：
Xing, Mingzhao;Haugen, Bryan R.;Schlumberger, Martin
通讯作者：
Schlumberger, Martin
影响因子：
46.9
作者：
Frampton GM;Fichtenholtz A;Otto GA;Wang K;Downing SR;He J;Schnall-Levin M;White J;Sanford EM;An P;Sun J;Juhn F;Brennan K;Iwanik K;Maillet A;Buell J;White E;Zhao M;Balasubramanian S;Terzic S;Richards T;Banning V;Garcia L;Mahoney K;Zwirko Z;Donahue A;Beltran H;Mosquera JM;Rubin MA;Dogan S;Hedvat CV;Berger MF;Pusztai L;Lechner M;Boshoff C;Jarosz M;Vietz C;Parker A;Miller VA;Ross JS;Curran J;Cronin MT;Stephens PJ;Lipson D;Yelensky R
通讯作者：
Yelensky R
影响因子：
120.7
作者：
Xing, Mingzhao;Alzahrani, Ali S.;Carson, Kathryn A.;Viola, David;Elisei, Rossella;Bendlova, Bela;Yip, Linwah;Mian, Caterina;Vianello, Federica;Tuttle, R. Michael;Robenshtok, Eyal;Fagin, James A.;Puxeddu, Efisio;Fugazzola, Laura;Czarniecka, Agnieszka;Jarzab, Barbara;O'Neill, Christine J.;Sywak, Mark S.;Lam, Alfred K.;Riesco-Eizaguirre, Garcilaso;Santisteban, Pilar;Nakayama, Hirotaka;Tufano, Ralph P.;Pai, Sara I.;Zeiger, Martha A.;Westra, William H.;Clark, Douglas P.;Clifton-Bligh, Roderick;Sidransky, David;Ladenson, Paul W.;Sykorova, Vlasta
通讯作者：
Sykorova, Vlasta
影响因子：
168.9
作者：
McLeod, Donald S. A.;Sawka, Anna M.;Cooper, David S.
通讯作者：
Cooper, David S.