Extended Antitumor Responseof a BRAF V600E Papillary Thyroid Carcinoma to Vemurafenib
Context: 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 vemura-fenib treatment. Objective: We repo...
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doaj-068b19060d6f45fe85af7a3c1eb323532020-11-24T23:22:56ZengKarger PublishersCase Reports in Oncology1662-65752014-05-017234334810.1159/000363377363377Extended Antitumor Responseof a BRAF V600E Papillary Thyroid Carcinoma to VemurafenibSiraj M. AliJe HeWade CarsonPhil J. StephensJoseph FiorilloDoron LipsonGary A. PalmerJeffrey S. RossVincent A. MillerJeffrey SharmanContext: 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 vemura-fenib treatment. Objective: 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. Design: 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. Results: 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. Conclusions: 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.http://www.karger.com/Article/FullText/363377BRAF V600EVemurafenibPapillary thyroid carcinoma |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Siraj M. Ali Je He Wade Carson Phil J. Stephens Joseph Fiorillo Doron Lipson Gary A. Palmer Jeffrey S. Ross Vincent A. Miller Jeffrey Sharman |
spellingShingle |
Siraj M. Ali Je He Wade Carson Phil J. Stephens Joseph Fiorillo Doron Lipson Gary A. Palmer Jeffrey S. Ross Vincent A. Miller Jeffrey Sharman Extended Antitumor Responseof a BRAF V600E Papillary Thyroid Carcinoma to Vemurafenib Case Reports in Oncology BRAF V600E Vemurafenib Papillary thyroid carcinoma |
author_facet |
Siraj M. Ali Je He Wade Carson Phil J. Stephens Joseph Fiorillo Doron Lipson Gary A. Palmer Jeffrey S. Ross Vincent A. Miller Jeffrey Sharman |
author_sort |
Siraj M. Ali |
title |
Extended Antitumor Responseof a BRAF V600E Papillary Thyroid Carcinoma to Vemurafenib |
title_short |
Extended Antitumor Responseof a BRAF V600E Papillary Thyroid Carcinoma to Vemurafenib |
title_full |
Extended Antitumor Responseof a BRAF V600E Papillary Thyroid Carcinoma to Vemurafenib |
title_fullStr |
Extended Antitumor Responseof a BRAF V600E Papillary Thyroid Carcinoma to Vemurafenib |
title_full_unstemmed |
Extended Antitumor Responseof a BRAF V600E Papillary Thyroid Carcinoma to Vemurafenib |
title_sort |
extended antitumor responseof a braf v600e papillary thyroid carcinoma to vemurafenib |
publisher |
Karger Publishers |
series |
Case Reports in Oncology |
issn |
1662-6575 |
publishDate |
2014-05-01 |
description |
Context: 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 vemura-fenib treatment. Objective: 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. Design: 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. Results: 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. Conclusions: 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. |
topic |
BRAF V600E Vemurafenib Papillary thyroid carcinoma |
url |
http://www.karger.com/Article/FullText/363377 |
work_keys_str_mv |
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