Molecular profiling of well-differentiated neuroendocrine tumors: Role of ctDNA

Angela Lamarca, Melissa Frizziero, Jorge Barriuso, Zainul Kapacee, Was Mansoor, Mairead Mcnamara, Richard Hubner, Juan Valle

Research output: Contribution to conferenceAbstractpeer-review

Abstract

Introduction: Tumor molecular profiling has proven relevant for the clinical
management of cancer. Circulating tumor DNA (ctDNA) may be a useful
surrogate of tumor tissue when this is insufficient for analysis. Aim(s): Aims:
Rate of test failure, detection rate of pathological alterations (PAs) and impact
on management. Materials and methods: Patients (pts) with welldifferentiated neuroendocrine tumors (WdNETs) underwent ctDNA-based
molecular profiling (FoundationLiquid®); non-WdNETs (paraganglioma, goblet
cell or poorly differentiated neuroendocrine carcinoma) were used for
comparison. Results: Fifteen pts with WdNET (18 ctDNA samples) included: 8
female (53.33%), median age 63.2 years (range 23.5-86.8). Primary: small
bowel (8;53.3%); pancreas (5;33.3%); gastric (1;6.7%) and unknown primary
(1;6.7%); grade (G)1 (n=5;33.3%); G2 (9;60.0%) and G3 (1;6.7%); median Ki67: 5% (range 1-30). Thirty pts with non-WdNETs pts (34 ctDNA samples)
were included. Five WdNETs samples (27.78%) failed analysis (vs 17.65% in
non-WdNETs; p 0.395). Of 13 WdNET samples with successful ctDNA, PAs
were detected in 6 (46.15%) (vs 82.14% in non-WdNETs; p 0.018). In
WdNETs, PA rate was independent of anti-cancer systemic therapy
(2/7;28.57% vs 4/6;66.67%; p 0.286) at time of ctDNA: 4, 1 and 1 samples had
1, 2 and 3 PAs, respectively; these were: CDKN2A mutation (m) (1 sample),
CHEK2m (1), TP53m (2), FGFR2amplif (1), IDH2m (1), CTNNB1m (1), NF1m
(1), PALB2m (1); nontargetable (0%) or impacted management (0%). There
was a trend towards lower maximum mutant allele frequency (mMAF) in
WdNETs (mean 0.33) vs non-WdNETs (mean 26.99); p 0.0584. Conclusion:
Although feasible, ctDNA molecular profiling was of limited clinical utility for
advanced WdNETs. Identification of PAs and mMAF seem higher in nonWdNETs.
Original languageEnglish
Publication statusPublished - 2021
Event18th Annual ENETs conference -
Duration: 25 Feb 202127 Feb 2021

Conference

Conference18th Annual ENETs conference
Period25/02/2127/02/21

Keywords

  • ctDNA
  • Well-differentiated
  • neuroendocrine

Research Beacons, Institutes and Platforms

  • Manchester Cancer Research Centre

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