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North American Neuroendocrine Tumor Society Symposium 2018
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Research at NANETS Cites Value of Genetic Testing in Neuroendocrine Tumors

Surabhi Dangi-Garimella, PhD
Two posters presented at the North American Neuroendocrine Tumor Society (NANETS) annual meeting, October 4-6 in Seattle, Washington, lend support to the idea of targeted treatment for neuroendocrine tumors.
Two posters presented at the North American Neuroendocrine Tumor Society annual meeting, October 4-6 in Seattle, Washington, lend support to the idea of targeted treatment for neuroendocrine tumors.

The first abstract, presented by researchers from the University of California, San Francisco (UCSF), conducted a chart review of 56 patients with grade 3 extrapulmonary neuroendocrine carcinoma (EP-NEC).1 Given the lack of sufficient knowledge on the optimal treatment options for high-grade EP-NEC, researchers are searching for biomarker-based leads to guide treatment decisions. For this study, a retrospective chart review of 56 patients with grade 3 EP-NEC whose tumors had been analyzed for actionable mutations.

The average diagnosis age among the 56 cases was 58.5 years, and this included 20 colorectal cancer, 14 pancreatic cancer, 6 other gastrointestinal cancer, and 16 other NECs. The majority of the patients (n = 30) were male.

While 7 genomic alterations were observed in over 15% of primary tumors, RB1 and TP53 were the only ones to cross the 15% threshold in every group. Actionable mutations were identified in 8 patient samples and an additional 6 tumor samples expressed gene variants with potential therapeutic implications for approved therapies (TSC1, PTEN, RET, HRAS, PTCH1, CDK4, and AKT2). Of the 25 tumor samples that were identified to have microsatellite instability (MSI), 1 sample was MSI-high.

Based on these findings, the authors concluded that commercial genomic platforms (Foundation One in this case) can prove vital in identifying potential therapeutic targets in patients with grade 3 EP-NEC.

The second poster, also by the authors of the first abstract, reported on a retrospective analysis on a different set of tumor samples, this time from 236 patients with neuroendocrine tumors who were referred to UCSF’s Cancer Genetics and Prevention Program between 2004 and 2017.2 Nearly 60% (n = 139) of those patients followed up with genetic counseling, with the probability being higher if the patient had at least 1 family member diagnosed with cancer. In the subgroup of 107 patients who underwent genetic testing, pancreatic neuroendocrine tumors were more associated with testing (odds ratio [OR], 0.15; P = .001). Prior to 2015, single-gene tests were common, after which 130-gene panels took over.

There was no significant difference between single versus multi-gene testing in differentiating between pathogenic or likely pathogenic mutations that were identified in 29% of patients (31/107). Functional tumors were statistically more likely to show a lower rate of pathogenic/likely pathogenic mutations thank non-functional tumors (OR, .17; P = .037).

The authors conclude that while their analysis underscored the value of multigene panels in detecting rare mutations in neuroendocrine tumors, the fact that only about 60% of patients followed up with genetic counseling means barriers to testing continue to exist.

References
  1. Whitman J, Shih B, Roy R, Olshen A, Joseph N, Bergsland E. Genomic profiling of extrapulmonary high-grade neuroendocrine carcinomas (EP-NEC) reveals “actionable” mutations. In: Proceedings from the North American Neuroendocrine Tumor Society annual meeting; October 4-6, 2018; Seattle, WA. Abstract B-22.
  2. Whitman J, Shih B, Blanco A, et al. Emerging value of multigene panels for germline testing in patients with neuroendocrine tumors. In: Proceedings from the North American Neuroendocrine Tumor Society annual meeting; October 4-6, 2018; Seattle, WA. Abstract B-21.


 
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