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.
Original language | English (US) |
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Pages (from-to) | 348-353 |
Number of pages | 6 |
Journal | Oncology (Switzerland) |
Volume | 91 |
Issue number | 6 |
DOIs | |
State | Published - Nov 1 2016 |
Keywords
- CREB1
- Case report
- Clear-cell sarcoma
- Comprehensive genomic profiling
- Crizotinib
- EWSR1
- Gastrointestinal neuroectodermal tumor
- Genomic profiling
- Pazopanib
ASJC Scopus subject areas
- Oncology
- Cancer Research