Assessment of circulating tumor DNA in patients with locally advanced rectal cancer treated with neoadjuvant therapy
Chiara Molinari, Giorgia Marisi, George P. Laliotis, Erik Spickard, Ilario Giovanni Rapposelli, Elisabetta Petracci, Giby V. George, Punashi Dutta, Shruti Sharma, Meenakshi Malhotra, Andrea Prochowski Iamurri, Giacomo Feliciani, Minetta C. Liu, Paola Ulivi, Matteo Canale, Luca Saragoni, Graziana Gallo, Giovanni Luca Frassineti, Margherita Muratore, Antonino Romeo, Adham Jurdi, Giovanni Martinelli, Alessandro Passardi
Abstract
Post-neoadjuvant therapy (post-NAT) and post-surgical circulating tumor DNA (ctDNA) risk stratification may enhance the management of patients with locally advanced rectal cancer (LARC). In this study, we assessed the prognostic value of ctDNA-based MRD detection in LARC patients using a personalized, tumor-informed ctDNA assay. Plasma samples from LARC patients (N = 30) were analyzed retrospectively using the Signatera™ assay. The neoadjuvant rectal (NAR) score was calculated and compared to ctDNA status to predict recurrence risk and survival outcomes. ctDNA-positive patients post-NAT and post-surgery had worse Disease Free Survival (DFS) (HR: 7.82; p = 0.001, HR: 19.65; p = 0.001) when compared to ctDNA-negative patients. In the post-NAT setting, patients who responded to NAT had superior DFS compared to patients who did not clear their ctDNA or showed no radiological response (HR: 24.7, p = 0.001 and HR: 5.1, p = 0.054, respectively). When ctDNA status is used alongside the NAR score in the post-NAT setting, patients who were ctDNA-positive with an intermediate or high NAR score showed significantly worse DFS (HR: 47.5, p < 0.001) compared to ctDNA-negative patients with either a low or intermediate/high NAR score (HR: 9.8, p = 0.0301). Post-NAT ctDNA status, whether used alone or in combination with the NAR score, may predict NAT response, and improve risk stratification.