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

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 well-differentiated 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 Ki-67: 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 non-WdNETs.