Assessment of circulating tumor DNA in patients with locally advanced rectal cancer treated with neoadjuvant therapy
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.
Authors
- Antonino Romeo (ORCID: https://orcid.org/0000-0002-7052-3267)
- Adham Jurdi (ORCID: https://orcid.org/0000-0002-2985-3053)
- Matteo Canale (ORCID: https://orcid.org/0000-0002-9768-7149)
- Minetta C. Liu (ORCID: https://orcid.org/0000-0002-8206-5232)
- Elisabetta Petracci (ORCID: https://orcid.org/0000-0001-9456-3514)
- Giorgia Marisi (ORCID: https://orcid.org/0000-0003-4012-0042)
- Punashi Dutta (ORCID: https://orcid.org/0000-0002-0166-498X)
- Meenakshi Malhotra (ORCID: https://orcid.org/0000-0002-9731-5628)
- Graziana Gallo (ORCID: https://orcid.org/0000-0003-1680-6968)
- Giby V. George (ORCID: https://orcid.org/0009-0007-9529-4564)
- Giacomo Feliciani (ORCID: https://orcid.org/0000-0002-4429-3971)
- Ilario Giovanni Rapposelli (ORCID: https://orcid.org/0000-0003-1802-5671)
- Margherita Muratore (ORCID: https://orcid.org/0000-0001-8055-8626)
- Paola Ulivi (ORCID: https://orcid.org/0000-0002-4334-9662)
- Andrea Prochowski Iamurri (ORCID: https://orcid.org/0000-0002-0836-9473)
- Erik Spickard (ORCID: https://orcid.org/0000-0002-5024-3559)
- Luca Saragoni (ORCID: https://orcid.org/0000-0002-2137-9596)
- Giovanni Martinelli (ORCID: https://orcid.org/0000-0002-1025-4210)
- George P. Laliotis (ORCID: https://orcid.org/0000-0001-6075-7687)
- Chiara Molinari (ORCID: https://orcid.org/0000-0003-1011-5656)
- Giovanni Luca Frassineti (ORCID: https://orcid.org/0000-0002-0277-5622)
- Alessandro Passardi (ORCID: https://orcid.org/0000-0002-7099-240X)
- Shruti Sharma (ORCID: https://orcid.org/0000-0003-0290-1569)
Institutions
- Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IT)
- Azienda Unità Sanitaria Locale Della Romagna (IT)
- Ospedale “M. Bufalini” di Cesena (IT)
- Natera (United States) (US)
- Istituti di Ricovero e Cura a Carattere Scientifico (IT)
Publication Details
- Journal
- Scientific Reports
- Published
- 2024-11-28
- DOI
- https://doi.org/10.1038/s41598-024-80855-8
- Citations
- 9
- Primary Topic
- Cancer Genomics and Diagnostics
- Type
- article
- Field-Weighted Citation Impact
- 2.57
Funders
- Natera
- Ministero della Salute