2019 ASCO Annual Meeting!
Type: Poster Session
Time: Saturday June 1, 8:00 AM to 11:00 AM
Location: Hall A
Identification of genomic alterations by circulating tumor DNA in leiomyosarcoma: A molecular analysis of 73 patients.
2019 ASCO Annual Meeting
Poster Board Number:
Poster Session (Board #367)
J Clin Oncol 37, 2019 (suppl; abstr 11044)
Author(s): Junaid Arshad, Ali Roberts, Jared Addison Cotta, Jonathan C. Trent; University of Miami/Sylvester Comprehensive Cancer Center, Miami, FL; Guardant Health, Inc., Redwood City, CA; University of Miami; Sylvester Comprehensive Cancer Center, Miami, FL; Sylvester Comprehensive Cancer Center, Miami, FL
Background: Leiomyosarcoma is a malignant mesenchymal tumor of cells of smooth muscle lineage arising commonly in retroperitoneum, uterus, large veins, and the limbs. In contrast to many sarcomas, the genetics of leiomyosarcomas are complex and there is very limited understanding of common driver mutations. Circulating Tumor DNA (ctDNA) offers a rapid and non-invasive method of next-generation sequencing (NGS) that could be utilized for diagnosis, therapy and detection of recurrence. Methods: ctDNA testing was performed using Guardant360, which detects single nucleotide variants, amplifications, fusions, and specific insertion/deletion mutations in 73 genes utilizing NGS. Blood samples from patients with leiomyosarcoma were analyzed, and results from December 2014-December 2018 were reviewed. Results: Of the 90 samples collected and analyzed, alterations were detected in 73 ctDNA samples. After exclusion of variants of uncertain significance (VUS), 63 ctDNA samples harbored cancer-associated genomic alterations. Of 73 patients, 59 were found to have one or more cancer-associated genomic alteration. 76% (45) were female with a median age of 63 (range, 38-87) years. All samples were designated metastatic. The following table shows common alterations and types of mutations. The other alterations included RAF1, ERBB2, MET, PTEN, TERT, APC and NOTCH1. In 24 of the 73 patients (33%) the genomic alterations detected by ctDNA are potentially targetable by an FDA-approved or clinical trial therapy. There were 4 (5%) patients who were found to have incidental germline TP53 mutations. Conclusions: NGS of ctDNA allows identification of genomic alterations in plasma from patients with leiomyosarcoma. Unfortunately, there is limited activity of targeted agents in leiomyosarcomas. These results suggest opportunities to develop therapy against TP53, cell cycle, and kinase signaling pathways. Further validation and prospective evaluation is warranted to investigate the clinical utility of ctDNA for patients with leiomyosarcoma.
|Mutation||Percent (pts)||Copy number variation count||Insertion/Deletion count||Single Nucleotide Variants count|
2. Neoadjuvant chemotherapy in high-risk soft tissue sarcomas: Final results of a randomized clinical trial from the Italian Sarcoma Group, the Spanish Sarcoma Group (GEIS), the French Sarcoma Group (FSG), and the Polish Sarcoma Group (PSG).