Title |
STUMP un“stumped”: anti-tumor response to anaplastic lymphoma kinase (ALK) inhibitor based targeted therapy in uterine inflammatory myofibroblastic tumor with myxoid features harboring DCTN1-ALK fusion
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Published in |
Journal of Hematology & Oncology, June 2015
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DOI | 10.1186/s13045-015-0160-2 |
Pubmed ID | |
Authors |
Vivek Subbiah, Caitlin McMahon, Shreyaskumar Patel, Ralph Zinner, Elvio G Silva, Julia A. Elvin, Ishwaria M. Subbiah, Chimela Ohaji, Dhakshina Moorthy Ganeshan, Deepa Anand, Charles F. Levenback, Jenny Berry, Tim Brennan, Juliann Chmielecki, Zachary R. Chalmers, John Mayfield, Vincent A. Miller, Philip J. Stephens, Jeffrey S. Ross, Siraj M. Ali |
Abstract |
Recurrent, metastatic mesenchymal myxoid tumors of the gynecologic tract present a management challenge as there is minimal evidence to guide systemic therapy. Such tumors also present a diagnostic dilemma, as myxoid features are observed in leiomyosarcomas, inflammatory myofibroblastic tumors (IMT), and mesenchymal myxoid tumors. Comprehensive genomic profiling was performed in the course of clinical care on a case of a recurrent, metastatic myxoid uterine malignancy (initially diagnosed as smooth muscle tumor of uncertain malignant potential (STUMP)), to guide identify targeted therapeutic options. To our knowledge, this case represents the first report of clinical response to targeted therapy in a tumor harboring a DCTN1-ALK fusion protein. Hybridization capture of 315 cancer-related genes plus introns from 28 genes often rearranged or altered in cancer was applied to >50 ng of DNA extracted from this sample and sequenced to high, uniform coverage. Therapy was given in the context of a phase I clinical trial ClinicalTrials.gov Identifier: ( NCT01548144 ). Immunostains showed diffuse positivity for ALK1 expression and comprehensive genomic profiling identified an in frame DCTN1-ALK gene fusion. The diagnosis of STUMP was revised to that of an IMT with myxoid features. The patient was enrolled in a clinical trial and treated with an anaplastic lymphoma kinase (ALK) inhibitor (crizotinib/Xalkori®) and a multikinase VEGF inhibitor (pazopanib/Votrient®). The patient experienced an ongoing partial response (6+ months) by response evaluation criteria in solid tumors (RECIST) 1.1 criteria. For myxoid tumors of the gynecologic tract, comprehensive genomic profiling can identify clinical relevant genomic alterations that both direct treatment targeted therapy and help discriminate between similar diagnostic entities. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 5 | 63% |
Unknown | 3 | 38% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 3 | 38% |
Scientists | 3 | 38% |
Practitioners (doctors, other healthcare professionals) | 2 | 25% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 32 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 6 | 19% |
Other | 5 | 16% |
Student > Bachelor | 3 | 9% |
Student > Ph. D. Student | 3 | 9% |
Student > Postgraduate | 2 | 6% |
Other | 4 | 13% |
Unknown | 9 | 28% |
Readers by discipline | Count | As % |
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Medicine and Dentistry | 11 | 34% |
Biochemistry, Genetics and Molecular Biology | 3 | 9% |
Agricultural and Biological Sciences | 2 | 6% |
Sports and Recreations | 2 | 6% |
Immunology and Microbiology | 1 | 3% |
Other | 2 | 6% |
Unknown | 11 | 34% |