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J Hematol Oncol. 2015 Jun 11;8:66. doi: 10.1186/s13045-015-0160-2.

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.

Author information

1
Division of Cancer Medicine, Department of Investigational Cancer Therapeutic (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, FC8.3038, Box 0455, Houston, TX, 77030, USA. vsubbiah@mdanderson.org.
2
Foundation Medicine, Inc, Cambridge, MA, 02141, USA. cmcmahon@foundationmedicine.com.
3
Division of Cancer Medicine, Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA. spatel@mdanderson.org.
4
Division of Cancer Medicine, Department of Investigational Cancer Therapeutic (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, FC8.3038, Box 0455, Houston, TX, 77030, USA. rzinner@mdanderson.org.
5
Division of Diagnostic Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA. esilva@mdanderson.org.
6
Foundation Medicine, Inc, Cambridge, MA, 02141, USA. jelvin@foundationmedicine.com.
7
Division of Cancer Medicine, Department of Investigational Cancer Therapeutic (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, FC8.3038, Box 0455, Houston, TX, 77030, USA. ISubbiah@mdanderson.org.
8
Division of Cancer Medicine, Department of Investigational Cancer Therapeutic (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, FC8.3038, Box 0455, Houston, TX, 77030, USA. COhaji@mdanderson.org.
9
Division of Diagnostic Imaging and Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA. DGaneshan@mdanderson.org.
10
Division of Diagnostic Imaging and Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA. Adeepa003@gmail.com.
11
Division of Surgery, Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. clevenba@mdanderson.org.
12
Division of Cancer Medicine, Department of Investigational Cancer Therapeutic (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, FC8.3038, Box 0455, Houston, TX, 77030, USA. JRBerry@mdanderson.org.
13
Foundation Medicine, Inc, Cambridge, MA, 02141, USA. tibrennan@foundationmedicine.com.
14
Foundation Medicine, Inc, Cambridge, MA, 02141, USA. jchmielecki@foundationmedicine.com.
15
Foundation Medicine, Inc, Cambridge, MA, 02141, USA. zchalmers@foundationmedicine.com.
16
Foundation Medicine, Inc, Cambridge, MA, 02141, USA. jmayfield@foundationmedicine.com.
17
Foundation Medicine, Inc, Cambridge, MA, 02141, USA. vmiller@foundationmedicine.com.
18
Foundation Medicine, Inc, Cambridge, MA, 02141, USA. pstephens@foundationmedicine.com.
19
Foundation Medicine, Inc, Cambridge, MA, 02141, USA. rossj@mail.amc.edu.
20
Foundation Medicine, Inc, Cambridge, MA, 02141, USA. sali@foundationmedicine.com.

Abstract

BACKGROUND:

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.

METHODS:

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 ).

RESULTS:

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.

CONCLUSIONS:

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.

PMID:
26062823
PMCID:
PMC4467062
DOI:
10.1186/s13045-015-0160-2
[Indexed for MEDLINE]
Free PMC Article

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