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POSTOPERATIVE CTDNA IS ASSOCIATED WITH OUTCOMES AFTER CURATIVE-INTENT HEPATECTOMY: RESULTS FROM THE INTERCEPT PROGRAM
Brittany C. Fields
*, Antony Haddad, Yifan Wang, Elsa M. Arvide, Deborah E. Mrema, Kristin D. Alfaro-Munoz, Robert J. Kell, Van Karlyle Morris, Arvind Dasari, Tsuyoshi Konishi, Yun Shin Chun, Hop S. Tran Cao, Ching-Wei D. Tzeng, Scott Kopetz, Jean-Nicolas Vauthey, Timothy E. Newhook
Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
IntroductionCirculating tumor DNA (ctDNA) is a dynamic biomarker associated with minimal residual disease (MRD) status and outcomes for patients with colorectal cancer. We evaluated the impact of ctDNA detection after curative-intent hepatectomy for colorectal liver metastases (CLM) within a prospective ctDNA surveillance initiative at a comprehensive cancer center.
MethodsThe INTERCEPT Program is a prospective institutional initiative to integrate plasma ctDNA testing into post-treatment surveillance for colorectal cancer. ctDNA results were paired with clinicopathologic data from a prospectively-maintained institutional database for patients with CLM who underwent curative-intent hepatectomy +/- postoperative completion ablation from 12/2022-06/2024. ctDNA positivity (ctDNA+) was defined as any detectable value within 90 days of hepatectomy/completion ablation. MRD was defined as ctDNA+ without suspicious or confirmed metastatic disease on imaging.
ResultsNinety-day postoperative ctDNA results were available in 133 patients. Most (84%, 111/133) received preoperative chemotherapy (median 4 [IQR 4-6] cycles). A primary-first surgical approach was performed in 87% (116/133), and 13% (17/133) had combined resection of the primary and CLM. Completion ablation was performed in 4% (5/133). Postoperatively, 23% (31/133) were ctDNA+, and 77% (102/133) were ctDNA-. A somatic mutation in ?1of the following genes was identified in 92% (122/133):
BRAF, KRAS, TP53, APC, PIK3C, SMAD4. More than 1/3 (48/133) had a pathway-centric risk score of 3 (ctDNA+ 39% [12/31]; ctDNA- 35% [36/102]).
On multivariable analysis, a rectal primary tumor (OR 5.6, 95%CI 1.8-17.8, p=0.004) and greatest CLM size ?3 cm (OR 4.3, 95%CI 1.6-11.4, p=0.004) were associated with ctDNA+. Of ctDNA+ patients, 74% (23/31) had MRD for a median 60 (1-101) days until radiographic detection of disease. Most (94%, 29/31) ctDNA+ patients received adjuvant therapy regardless of MRD status, and 63% (15/24) of patients with a follow-up test became ctDNA- with treatment after a median 3.6 (3.0-5.3) months. Nearly all (90%, 28/31) ctDNA+ patients recurred, including 77% (24/31) with hepatic recurrence. The recurrence rate for ctDNA- patients was 43% (44/102), with 80% (35/44) of recurrences occurring within 1 year of hepatectomy. Compared to ctDNA- patients, ctDNA+ patients’ median recurrence-free survival (3.4 [2.3-4.6] months vs. 21.3 [13.6-29.0], p<0.001) and hepatic-specific disease-free survival (4.2 [1.1-7.2] months vs. not reached, p<0.001; respectively) were significantly lower (Figure 1).
ConclusionsPostoperative ctDNA testing for CLM is feasible and identifies patients with MRD and at risk of recurrence. Patterns of recurrence are associated with postoperative ctDNA detection and may guide postoperative therapy and surveillance strategies.
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