Abstract:
:Malignant gastrointestinal neuroectodermal tumor (GNET) is an aggressive rare tumor, primarily occurring in young adults with frequent local-regional metastases and recurrence after local control. The tumor is characterized by the presence of EWSR1-ATF1 or EWSR1-CREB1 and immunohistochemical positivity for S-100 protein without melanocytic marker positivity. Due to poor responses to standard sarcoma regimens, GNET has a poor prognosis, and development of effective systemic therapy is desperately needed to treat these patients. Herein, we present a patient with a small bowel GNET who experienced recurrent hepatic and skeletal metastases after a primary resection. Comprehensive genomic profiling (CGP) in the course of clinical care with DNA and RNA sequencing demonstrated the presence of an exon 7 to exon 6 EWSR1-CREB1 fusion in the context of a diploid genome with no other genomic alterations. In a clinical trial, the patient received a combination of 250 mg crizotinib with 600 mg pazopanib quaque die and achieved partial response and durable clinical benefit for over 2.8 years, and with minimal toxicity from therapy. Using a CGP database of over 50,000 samples, we identified 11 additional cases that harbor EWSR1-CREB1 and report clinicopathologic characteristics, as these patients may also benefit from such a regimen.
journal_name
Oncologyjournal_title
Oncologyauthors
Subbiah V,Holmes O,Gowen K,Spritz D,Amini B,Wang WL,Schrock AB,Meric-Bernstam F,Zinner R,Piha-Paul S,Zarzour M,Elvin JA,Erlich RL,Stockman DL,Vergilio JA,Suh JH,Stephens PJ,Miller V,Ross JS,Ali SMdoi
10.1159/000449204subject
Has Abstractpub_date
2016-01-01 00:00:00pages
348-353issue
6eissn
0030-2414issn
1423-0232pii
000449204journal_volume
91pub_type
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