Evaluation of ctDNA in the Prediction of Response to Neoadjuvant Therapy and Prognosis in Locally Advanced Rectal Cancer Patients: A Prospective Study

Author:

Morais Marina1ORCID,Fonseca Telma2,Melo-Pinto Diogo1,Prieto Isabel3,Vilares Ana Teresa4,Duarte Ana Luísa4,Leitão Patrícia5,Cirnes Luís6,Machado José Carlos6ORCID,Carneiro Silvestre2

Affiliation:

1. Department of Surgery, Hospital Pedro Hispano, 4464-513 Matosinhos, Portugal

2. Department of Surgery, Centro Hospitalar Universitário de São João EPE, 4200-319 Porto, Portugal

3. Department of Surgery, Hospital La Paz, 28046 Madrid, Spain

4. Department of Radiology, Centro Hospitalar Universitário de São João EPE, 4200-319 Porto, Portugal

5. Department of Radiology, Hospital Pedro Hispano, 4464-513 Matosinhos, Portugal

6. Diagnostics Group, Institute of Molecular Pathology and Immunology of Porto University, 4200-135 Porto, Portugal

Abstract

“Watch and wait” is becoming a common treatment option for patients with locally advanced rectal cancer (LARC) submitted to neoadjuvant treatment. However, currently, no clinical modality has an acceptable accuracy for predicting pathological complete response (pCR). The aim of this study was to assess the clinical utility of circulating tumor DNA (ctDNA) in predicting the response and prognosis in these patients. We prospectively enrolled a cohort of three Iberian centers between January 2020 and December 2021 and performed an analysis on the association of ctDNA with the main response outcomes and disease-free survival (DFS). The rate of pCR in the total sample was 15.3%. A total of 24 plasma samples from 18 patients were analyzed by next-generation sequencing. At baseline, mutations were detected in 38.9%, with the most common being TP53 and KRAS. Combination of either positive magnetic resonance imaging (MRI) extramural venous invasion (mrEMVI) and ctDNA increased the risk of poor response (p = 0.021). Also, patients with two mutations vs. those with fewer than two mutations had a worse DFS (p = 0.005). Although these results should be read carefully due to sample size, this study suggests that baseline ctDNA combined with mrEMVI could potentially help to predict the response and baseline ctDNA number of mutations might allow the discrimination of groups with different DFS. Further studies are needed to clarify the role of ctDNA as an independent tool in the selection and management of LARC patients.

Funder

Portuguese Society of Coloproctology

Publisher

MDPI AG

Subject

Drug Discovery,Pharmaceutical Science,Molecular Medicine

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