Abstract 274P
Background
Magnetic resonance imaging (MRI)-based radiomic metrics offer a unique quantitative approach for predicting pathological complete response (pCR) to neoadjuvant therapy (NAT) in patients (pts) with locally advanced rectal cancer (LARC). We previously demonstrated that circulating tumor DNA (ctDNA), alone or as an adjunct to the neoadjuvant rectal (NAR) score may predict NAT response. Here, we assess the complementary prognostic value of radiomic parameters and ctDNA in pts with LARC.
Methods
Retrospective ctDNA analysis was performed using a clinically validated, personalized, tumor-informed 16 plex PCR-NGS ctDNA assay (SignateraTM, Natera, Inc.) on presurgical ctDNA samples post-NAT. Radiological NAR (rNAR) score was calculated based on (5 *cNpost-NAT−3[cTpre-NAT − cTpost-NAT] +12)2÷9.61. Radiomic parameters (T2W minimum [min] and Flatness [FL]) were analyzed from radiological images obtained pre-NAT. The association of ctDNA status, rNAR, and radiomic metrics with disease-free survival (DFS) was evaluated. Pts were stratified into low (NAR<8), intermediate (NAR=8-16), and high (NAR>16) risk groups; while T2Wmin and FL were stratified based on the median value (T2Wmin threshold= 30.07, FL threshold=0.541).
Results
Plasma samples (n=30) were collected from 30 pts with LARC, with a median age of 67 years (range: 38-80) and a median follow-up of 60 months (range: 10-118). Evaluating ctDNA status post-NAT alongside T2Wmin and FL, pts with high T2Wmin/FL and ctDNA-positivity experienced inferior DFS compared to ctDNA-negative pts with high T2Wmin/FL (HR: 5.93, 95% Cl: 0.97-36.21; p=0.054/HR: 12.88, 95% Cl: 1.87-88.89; p=0.010). Additionally, pts who were ctDNA-positive with an intermediate/high rNAR score had significantly worsened DFS (HR: 14.12, 95% Cl: 1.52-1881; p=0.016) compared to their ctDNA-negative counterparts. Notably, receiver operating characteristic (ROC) curves revealed that the rNAR score outperformed both T2Wmin (AUC: 0.583 [0.37-0.80]) and FL (AUC: 0.56 [0.34-0.78]) with an AUC of 0.801 [0.63-0.97].
Conclusions
Radiomic metrics together with post-NAT ctDNA status and rNAR score may be prognostic for survival outcomes in pts with LARC.
Legal entity responsible for the study
The authors.
Funding
Natera, Inc.
Disclosure
G. Laliotis: Financial Interests, Personal, Full or part-time Employment: Natera, Inc.; Financial Interests, Personal, Stocks/Shares: Natera, Inc.; Non-Financial Interests, Advisory Role: Docus, ai. S. Sharma, P. Dutta, M. Malhotra, A. Jurdi: Financial Interests, Personal, Stocks/Shares: Natera, Inc; Financial Interests, Personal, Full or part-time Employment: Natera, Inc. M.C. Liu: Financial Interests, Institutional, Research Grant: Eisai, Exact Sciences, Genentech, Genomic Health, GRAIL, Menarini Silicon Biosystems, Merck, Novartis, Seattle Genetics, Tesaro; Financial Interests, Personal, Other, Travel Support Reimbursement: AstraZeneca, Genomic Health, Ionis; Financial Interests, Institutional, Advisory Role: AstraZeneca, Celgene, Roche/Genentech, Genomic Health, GRAIL, Ionis, Merck, Pfizer, Seattle Genetics, Syndax; Financial Interests, Personal, Full or part-time Employment: Natera, Inc.; Financial Interests, Personal, Stocks/Shares: Natera, Inc. G. Martinelli: Financial Interests, Institutional, Invited Speaker: Novartis, Amgen, BMS, Pfizer, Celgene. All other authors have declared no conflicts of interest.