Abstract B024: Personalized tumor-informed circulating tumor (ct) DNA for advanced thyroid carcinoma

Abstract Background: Clinical adoption of personalized tumor-informed ctDNA testing is increasing with clinical validation in monitoring for recurrence for colorectal, breast, bladder, & ovarian tumors, as well as treatment response for immune-checkpoint inhibitors regardless of tumor type. However, few studies have evaluated tumor-informed ctDNA testing in patients (pts) with advanced thyroid carcinoma (TC). Methods: This retrospective cohort study identified pts with advanced TC, with any histology, treated at an academic institution with ctDNA testing (Signatera™, Natera Inc.) performed during routine clinical care at any point during the disease natural history after requiring referral to medical oncology. The goal was to investigate the feasibility of personalized, tumor-informed ctDNA testing in advanced TC, and characteristics associated with ctDNA detectability & values. Results: Between 1/1/24 & 8/20/24, ctDNA testing was obtained in 45 pts with advanced TC (median age: 63y, 58% male). Testing could not be performed in 4 (9%) pts due to inadequate tumor tissue. Initial tests were in progress for 7 (16%) pts at data cutoff. Thirty-four pts had available results for at least 1 blood draw, including 19 (56%) with radioiodine refractory (RAIR) differentiated TC (DTC), 10 (29%) with anaplastic TC (ATC), & 5 (15%) with medullary TC (MTC). ctDNA was detected in 16/34 (47%) pts with advanced TC. These included 8/19 (42%) pts with RAIR DTC (range: 0.05–346.26 mean tumor molecules, MTM/mL), including 4/4 (100%) about to initiate new systemic Rx, 1/4 (25%) on ongoing systemic Rx, & 3/11 (27.3%) on active surveillance not requiring systemic Rx. 4/10 (40%) with ATC had detectable ctDNA (range: 3.57–80.55 MTM/mL), including 4/4 (100%) about to initiate new systemic Rx, & 0/6 in those with disease control on ongoing Rx or on active surveillance after completion of Rx. 4/5 (80%) with MTC (range: 0.04–94.72 MTM/mL), including 4/4 (100%) on ongoing systemic Rx & 0/1 on active surveillance. Radiographic evidence of disease was observed in 28/34 (82%) pts, with ctDNA detection in 16/28 (57%). For all cases, there was a significant association between anatomic tumor burden represented by the no. of organ sites involved by advanced TC (median:2.5, range:0-6) & ctDNA detectability (Mann-Whitney, p=0.003). In pts with a ctDNA-positive result (n=16), there was a modest correlation between ctDNA quantitative values & no. of involved organ sites (Spearman’s rho=0.48), but was not statistically significant (p=0.06). Similarly, modest correlation with serum biomarkers was observed but not statistically significant in RAIR DTC (with serum thyroglobulin, n=8, rho=0.52, p=0.18), & MTC (with serum calcitonin, n=4, rho=0.8, p=0.2). Conclusions: Personalized ctDNA testing is feasible and often detectable in pts with advanced TC. Further research is warranted to ascertain factors associated with ctDNA test performance, and understand whether ctDNA monitoring can guide optimal timing for initiation of systemic Rx in advanced TC, as well as the dynamics of ctDNA on systemic Rx. Citation Format: Kartik Sehgal, Theodora Pappa, Michael J. Dennis, Nicole J. Scarfo, Michelle S. Mullin, Tura Coombs, Roy B. Tishler, Danielle N. Margalit, Ravindra Uppaluri, Rosh K. Sethi, Jonathan D. Schoenfeld, Justine A. Barletta, Gerard M. Doherty, Erik K. Alexander, Laura A. Goguen, Eleni M. Rettig, Robert I. Haddad, Glenn J. Hanna. Personalized tumor-informed circulating tumor (ct) DNA for advanced thyroid carcinoma [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B024.