Evaluation of ctDNA in the Prediction of Response to Neoadjuvant Therapy and Prognosis in Locally Advanced Rectal Cancer Patients: A Prospective Study
“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 ass...
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| Format: | Article |
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MDPI AG
2023-03-01
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| Online Access: | https://www.mdpi.com/1424-8247/16/3/427 |
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| author | Marina Morais Telma Fonseca Diogo Melo-Pinto Isabel Prieto Ana Teresa Vilares Ana Luísa Duarte Patrícia Leitão Luís Cirnes José Carlos Machado Silvestre Carneiro |
| author_facet | Marina Morais Telma Fonseca Diogo Melo-Pinto Isabel Prieto Ana Teresa Vilares Ana Luísa Duarte Patrícia Leitão Luís Cirnes José Carlos Machado Silvestre Carneiro |
| author_sort | Marina Morais |
| collection | DOAJ |
| description | “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 <i>TP53</i> and <i>KRAS</i>. Combination of either positive magnetic resonance imaging (MRI) extramural venous invasion (mrEMVI) and ctDNA increased the risk of poor response (<i>p</i> = 0.021). Also, patients with two mutations vs. those with fewer than two mutations had a worse DFS (<i>p</i> = 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. |
| first_indexed | 2024-03-11T06:03:44Z |
| format | Article |
| id | doaj.art-f26f94be3dd14f86b2317d710db876e6 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-11T06:03:44Z |
| publishDate | 2023-03-01 |
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| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-f26f94be3dd14f86b2317d710db876e62023-11-17T13:12:40ZengMDPI AGPharmaceuticals1424-82472023-03-0116342710.3390/ph16030427Evaluation of ctDNA in the Prediction of Response to Neoadjuvant Therapy and Prognosis in Locally Advanced Rectal Cancer Patients: A Prospective StudyMarina Morais0Telma Fonseca1Diogo Melo-Pinto2Isabel Prieto3Ana Teresa Vilares4Ana Luísa Duarte5Patrícia Leitão6Luís Cirnes7José Carlos Machado8Silvestre Carneiro9Department of Surgery, Hospital Pedro Hispano, 4464-513 Matosinhos, PortugalDepartment of Surgery, Centro Hospitalar Universitário de São João EPE, 4200-319 Porto, PortugalDepartment of Surgery, Hospital Pedro Hispano, 4464-513 Matosinhos, PortugalDepartment of Surgery, Hospital La Paz, 28046 Madrid, SpainDepartment of Radiology, Centro Hospitalar Universitário de São João EPE, 4200-319 Porto, PortugalDepartment of Radiology, Centro Hospitalar Universitário de São João EPE, 4200-319 Porto, PortugalDepartment of Radiology, Hospital Pedro Hispano, 4464-513 Matosinhos, PortugalDiagnostics Group, Institute of Molecular Pathology and Immunology of Porto University, 4200-135 Porto, PortugalDiagnostics Group, Institute of Molecular Pathology and Immunology of Porto University, 4200-135 Porto, PortugalDepartment of Surgery, Centro Hospitalar Universitário de São João EPE, 4200-319 Porto, Portugal“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 <i>TP53</i> and <i>KRAS</i>. Combination of either positive magnetic resonance imaging (MRI) extramural venous invasion (mrEMVI) and ctDNA increased the risk of poor response (<i>p</i> = 0.021). Also, patients with two mutations vs. those with fewer than two mutations had a worse DFS (<i>p</i> = 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.https://www.mdpi.com/1424-8247/16/3/427ctDNAnext-generation sequencinglocally advanced rectal cancerneoadjuvant chemoradiationprediction of responsedisease-free survival |
| spellingShingle | Marina Morais Telma Fonseca Diogo Melo-Pinto Isabel Prieto Ana Teresa Vilares Ana Luísa Duarte Patrícia Leitão Luís Cirnes José Carlos Machado Silvestre Carneiro Evaluation of ctDNA in the Prediction of Response to Neoadjuvant Therapy and Prognosis in Locally Advanced Rectal Cancer Patients: A Prospective Study Pharmaceuticals ctDNA next-generation sequencing locally advanced rectal cancer neoadjuvant chemoradiation prediction of response disease-free survival |
| title | Evaluation of ctDNA in the Prediction of Response to Neoadjuvant Therapy and Prognosis in Locally Advanced Rectal Cancer Patients: A Prospective Study |
| title_full | Evaluation of ctDNA in the Prediction of Response to Neoadjuvant Therapy and Prognosis in Locally Advanced Rectal Cancer Patients: A Prospective Study |
| title_fullStr | Evaluation of ctDNA in the Prediction of Response to Neoadjuvant Therapy and Prognosis in Locally Advanced Rectal Cancer Patients: A Prospective Study |
| title_full_unstemmed | Evaluation of ctDNA in the Prediction of Response to Neoadjuvant Therapy and Prognosis in Locally Advanced Rectal Cancer Patients: A Prospective Study |
| title_short | Evaluation of ctDNA in the Prediction of Response to Neoadjuvant Therapy and Prognosis in Locally Advanced Rectal Cancer Patients: A Prospective Study |
| title_sort | evaluation of ctdna in the prediction of response to neoadjuvant therapy and prognosis in locally advanced rectal cancer patients a prospective study |
| topic | ctDNA next-generation sequencing locally advanced rectal cancer neoadjuvant chemoradiation prediction of response disease-free survival |
| url | https://www.mdpi.com/1424-8247/16/3/427 |
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