2019 ASCO Annual Meeting!
Session: Gastrointestinal (Noncolorectal) Cancer
Type: Poster Session
Time: Monday June 3, 8:00 AM to 11:00 AM
Location: Hall A
Blood-based next-generation sequencing analysis of neuroendocrine tumors.
Gastrointestinal (Noncolorectal) Cancer
2019 ASCO Annual Meeting
Poster Board Number:
Poster Session (Board #215)
J Clin Oncol 37, 2019 (suppl; abstr 4110)
Author(s): Walid Labib Shaib, Ali Roberts, Katerina Mary Zakka, Mehmet Akce, Christina Wu, Olatunji B. Alese, Bassel F. El-Rayes, Pashtoon Murtaza Kasi, Jason Scott Starr; Winship Cancer Institute, Emory University, Atlanta, GA; Guardant Health, Inc., Redwood City, CA; Winship Cancer Institute of Emory University, Atlanta, GA; Winship Cancer Institute, Atlanta, GA; Ohio State University Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, OH; Mayo Clinic, Jacksonville, FL; University of Florida Health Cancer Center, Jacksonville, FL
Background: Neuroendocrine tumors (NET) comprise around 2% of all malignant tumors of the gastrointestinal system. The genomic landscape of NET has not been well studied. The aim of this study was to confirm the feasibility of next generation sequencing (NGS) using ctDNA in NET and characterize common alterations in the genomic profile. Methods: Molecular alterations in 114 plasma samples from 114 patients with NET using clinical-grade NGS of ctDNA (Guardant360Ò) across multiple institutions were evaluated. The test detects single nucleotide variants in 54-73 genes, copy number amplifications, fusions, and indels in selected genes. Results: A total of 114 NET patients were evaluated, of which 64 (56.1%) were female. Mean age was 59.7 years with a range between 23-89 years. ctDNA NGS testing was performed on 114 plasma samples; 1 patient had testing performed twice. Genomic alterations were defined in 94 (n = 94/114, 82.5%) samples with a total of 289 alterations identified after excluding variants of uncertain significance (VUSs) and synonymous mutations. Alterations were identified in at least one sample from 83 patients; TP53 associated genes were most commonly altered (n = 83/289, 28.7%), followed by KRAS (n = 22, 7.6%), PI3CA (n = 15, 5.2%), CCNE1 (n = 15, 5.2%), BRAF (n = 13, 4.5%), MYC (n = 12, 4.1%), ERBB2 (n = 11, 3.8%), APC (n = 10, 3.5%), EGFR (n = 10, 3.5%), MET (n = 10, 3.5%), PTEN (n = 9, 3.1%), RB1 (n = 9, 3.1%), CDK6 (n = 7, 2.4%), AR (n = 5, 1.7%), ARID1A (n = 5, 1.7%), FGFR1 (n = 5, 1.7%), and PDGFRA (n = 5, 1.7%). Other genomic alterations of low frequency, but clinical relevance included: CDK4 (n = 4, 1.3%), NF1 (n = 4, 1.3%), RAF1 (n = 4, 1.3%), GNAS (n = 3, 1.0%), KIT (n = 3, 1.3%), BRCA2 (n = 2, 0.7%), CCND2 (n = 2, 0.7%), CTNNB1 (n = 2, 0.7%), JAK2 (n = 2, 0.7%), NRAS (n = 2, 0.7%), SMAD4 (n = 2, 0.7%), and TERT (n = 2, 0.7%). Alterations in AKT1, ALK, ATM, BRCA1, CCND1, CDKN2A, FGFR2, MTOR, RHOA, SMO and STK11 were all reported once (n = 1, 0.3%). Conclusions: Evaluation of ctDNA is feasible among individuals with NET. Liquid biopsies are not invasive and can provide personalized options for targeted therapies in NET patients.
2. An open label, single-arm, two-stage, multicenter, phase II study to evaluate the efficacy and safety of TLC388 as second-line treatment in subjects with poorly differentiated neuroendocrine carcinomas (TCOGT1Z14).