{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T01:37:05Z","timestamp":1776303425926,"version":"3.50.1"},"reference-count":63,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,3,10]],"date-time":"2023-03-10T00:00:00Z","timestamp":1678406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Portuguese Society of Coloproctology","award":["1\/2020"],"award-info":[{"award-number":["1\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>\u201cWatch and wait\u201d 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.<\/jats:p>","DOI":"10.3390\/ph16030427","type":"journal-article","created":{"date-parts":[[2023,3,13]],"date-time":"2023-03-13T04:04:00Z","timestamp":1678680240000},"page":"427","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Evaluation of ctDNA in the Prediction of Response to Neoadjuvant Therapy and Prognosis in Locally Advanced Rectal Cancer Patients: A Prospective Study"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6765-1233","authenticated-orcid":false,"given":"Marina","family":"Morais","sequence":"first","affiliation":[{"name":"Department of Surgery, Hospital Pedro Hispano, 4464-513 Matosinhos, Portugal"}]},{"given":"Telma","family":"Fonseca","sequence":"additional","affiliation":[{"name":"Department of Surgery, Centro Hospitalar Universit\u00e1rio de S\u00e3o Jo\u00e3o EPE, 4200-319 Porto, Portugal"}]},{"given":"Diogo","family":"Melo-Pinto","sequence":"additional","affiliation":[{"name":"Department of Surgery, Hospital Pedro Hispano, 4464-513 Matosinhos, Portugal"}]},{"given":"Isabel","family":"Prieto","sequence":"additional","affiliation":[{"name":"Department of Surgery, Hospital La Paz, 28046 Madrid, Spain"}]},{"given":"Ana Teresa","family":"Vilares","sequence":"additional","affiliation":[{"name":"Department of Radiology, Centro Hospitalar Universit\u00e1rio de S\u00e3o Jo\u00e3o EPE, 4200-319 Porto, Portugal"}]},{"given":"Ana Lu\u00edsa","family":"Duarte","sequence":"additional","affiliation":[{"name":"Department of Radiology, Centro Hospitalar Universit\u00e1rio de S\u00e3o Jo\u00e3o EPE, 4200-319 Porto, Portugal"}]},{"given":"Patr\u00edcia","family":"Leit\u00e3o","sequence":"additional","affiliation":[{"name":"Department of Radiology, Hospital Pedro Hispano, 4464-513 Matosinhos, Portugal"}]},{"given":"Lu\u00eds","family":"Cirnes","sequence":"additional","affiliation":[{"name":"Diagnostics Group, Institute of Molecular Pathology and Immunology of Porto University, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4741-8415","authenticated-orcid":false,"given":"Jos\u00e9 Carlos","family":"Machado","sequence":"additional","affiliation":[{"name":"Diagnostics Group, Institute of Molecular Pathology and Immunology of Porto University, 4200-135 Porto, Portugal"}]},{"given":"Silvestre","family":"Carneiro","sequence":"additional","affiliation":[{"name":"Department of Surgery, Centro Hospitalar Universit\u00e1rio de S\u00e3o Jo\u00e3o EPE, 4200-319 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA A Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1056\/NEJMoa010580","article-title":"Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer","volume":"345","author":"Kapiteijn","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"719","DOI":"10.6004\/jnccn.2015.0087","article-title":"Rectal Cancer, Version 1.2022","volume":"13","author":"Benson","year":"2022","journal-title":"J. Natl. Compr. Cancer Netw. JNCCN"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1002\/cncr.11075","article-title":"Response to preoperative chemoradiation increases the use of sphincter-preserving surgery in patients with locally advanced low rectal carcinoma","volume":"97","author":"Crane","year":"2003","journal-title":"Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/s13193-012-0158-y","article-title":"Is the 1-cm Rule of Distal Bowel Resection Margin in Rectal Cancer Based on Clinical Evidence? A Systematic Review","volume":"3","author":"Bujko","year":"2012","journal-title":"Indian J. Surg. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2863","DOI":"10.1245\/s10434-010-1119-8","article-title":"Long-term survival and recurrence outcomes following surgery for distal rectal cancer","volume":"17","author":"Silberfein","year":"2010","journal-title":"Ann. Surg. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1016\/S1470-2045(21)00079-6","article-title":"Neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER-PRODIGE 23): A multicentre, randomised, open-label, phase 3 trial","volume":"22","author":"Conroy","year":"2021","journal-title":"Lancet Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2627","DOI":"10.1093\/annonc\/mds056","article-title":"Induction chemotherapy with capecitabine and oxaliplatin followed by chemoradiotherapy before total mesorectal excision in patients with locally advanced rectal cancer","volume":"23","author":"Schou","year":"2012","journal-title":"Ann. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1016\/S1470-2045(10)70172-8","article-title":"Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: A pooled analysis of individual patient data","volume":"11","author":"Maas","year":"2010","journal-title":"Lancet Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1097\/01.sla.0000141194.27992.32","article-title":"Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: Long-term results","volume":"240","author":"Perez","year":"2004","journal-title":"Ann. Surg."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2390","DOI":"10.1016\/j.ejca.2014.06.020","article-title":"Health-related quality of life 14 years after preoperative short-term radiotherapy and total mesorectal excision for rectal cancer: Report of a multicenter randomised trial","volume":"50","author":"Wiltink","year":"2014","journal-title":"Eur. J. Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Osseis, M., Nehmeh, W.A., Rassy, N., Derienne, J., Noun, R., Salloum, C., Rassy, E., Boussios, S., and Azoulay, D. (2022). Surgery for T4 Colorectal Cancer in Older Patients: Determinants of Outcomes. J. Pers. Med., 12.","DOI":"10.3390\/jpm12091534"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1097\/DCR.0000000000001135","article-title":"Can Endorectal Ultrasound, MRI, and Mucosa Integrity Accurately Predict the Complete Response for Mid-Low Rectal Cancer after Preoperative Chemoradiation? A Prospective Observational Study from a Single Medical Center","volume":"61","author":"Liu","year":"2018","journal-title":"Dis. Colon Rectum"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1002\/cam4.1913","article-title":"Clinical relevance of circulating tumor DNA assessed through deep sequencing in patients with metastatic colorectal cancer","volume":"8","author":"Osumi","year":"2019","journal-title":"Cancer Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1001\/jama.2017.12131","article-title":"Cancer DNA in the Circulation: The Liquid Biopsy","volume":"318","author":"Husain","year":"2017","journal-title":"JAMA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1038\/s41571-020-0392-0","article-title":"ctDNA applications and integration in colorectal cancer: An NCI Colon and Rectal-Anal Task Forces whitepaper","volume":"17","author":"Dasari","year":"2020","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1715","DOI":"10.1093\/annonc\/mdv177","article-title":"Circulating tumor DNA as an early marker of therapeutic response in patients with metastatic colorectal cancer","volume":"26","author":"Tie","year":"2015","journal-title":"Ann. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1634\/theoncologist.2017-0621","article-title":"Clinical Utility of Analyzing Circulating Tumor DNA in Patients with Metastatic Colorectal Cancer","volume":"23","author":"Nakamura","year":"2018","journal-title":"Oncologist"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1093\/annonc\/mdx778","article-title":"Circulating cell-free DNA as predictor of treatment failure after neoadjuvant chemo-radiotherapy before surgery in patients with locally advanced rectal cancer","volume":"29","author":"Schou","year":"2018","journal-title":"Ann. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"136ra168","DOI":"10.1126\/scitranslmed.3003726","article-title":"Noninvasive identification and monitoring of cancer mutations by targeted deep sequencing of plasma DNA","volume":"4","author":"Forshew","year":"2012","journal-title":"Sci. Transl. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"6159","DOI":"10.1093\/nar\/gkq421","article-title":"Origin and quantification of circulating DNA in mice with human colorectal cancer xenografts","volume":"38","author":"Thierry","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4786","DOI":"10.1158\/1078-0432.CCR-14-1190","article-title":"Circulating Tumor Cells and Circulating Tumor DNA: Challenges and Opportunities on the Path to Clinical Utility","volume":"21","author":"Ignatiadis","year":"2015","journal-title":"Clin. Cancer Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"38360","DOI":"10.18632\/oncotarget.5256","article-title":"The use of personalized biomarkers and liquid biopsies to monitor treatment response and disease recurrence in locally advanced rectal cancer after neoadjuvant chemoradiation","volume":"6","author":"Carpinetti","year":"2015","journal-title":"Oncotarget"},{"key":"ref_24","first-page":"4365","article-title":"Monitoring colorectal cancer following surgery using plasma circulating tumor DNA","volume":"15","author":"Sun","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.gde.2013.11.011","article-title":"The evolution of the unstable cancer genome","volume":"24","author":"Burrell","year":"2014","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.ejso.2021.08.034","article-title":"ctDNA on liquid biopsy for predicting response and prognosis in locally advanced rectal cancer: A systematic review","volume":"48","author":"Morais","year":"2022","journal-title":"Eur. J. Surg. Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"286","DOI":"10.3389\/fonc.2015.00286","article-title":"Predictors of Complete Response and Disease Recurrence Following Chemoradiation for Rectal Cancer","volume":"5","author":"Bitterman","year":"2015","journal-title":"Front. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1245\/s10434-012-2669-8","article-title":"Elevated CEA levels and low distance of the tumor from the anal verge are predictors of incomplete response to chemoradiation in patients with rectal cancer","volume":"20","author":"Restivo","year":"2013","journal-title":"Ann. Surg. Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1007\/s00384-013-1821-7","article-title":"Clinical tumour size and nodal status predict pathologic complete response following neoadjuvant chemoradiotherapy for rectal cancer","volume":"29","author":"Garland","year":"2014","journal-title":"Int. J. Color. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1692","DOI":"10.1007\/DCR.0b013e3181f42b89","article-title":"Complete clinical response after neoadjuvant chemoradiation therapy for distal rectal cancer: Characterization of clinical and endoscopic findings for standardization","volume":"53","author":"Perez","year":"2010","journal-title":"Dis. Colon Rectum"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1007\/s10350-007-9080-8","article-title":"Complete clinical response after preoperative chemoradiation in rectal cancer: Is a \u201cwait and see\u201d policy justified?","volume":"51","author":"Wallace","year":"2008","journal-title":"Dis Colon Rectum"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2537","DOI":"10.1016\/S0140-6736(18)31078-X","article-title":"Long-term outcomes of clinical complete responders after neoadjuvant treatment for rectal cancer in the International Watch & Wait Database (IWWD): An international multicentre registry study","volume":"391","author":"Hilling","year":"2018","journal-title":"Lancet"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Wang, Y., Yang, L., Bao, H., Fan, X., Xia, F., Wan, J., Shen, L., Guan, Y., Bao, H., and Wu, X. (2021). Utility of ctDNA in predicting response to neoadjuvant chemoradiotherapy and prognosis assessment in locally advanced rectal cancer: A prospective cohort study. PLoS Med., 18.","DOI":"10.1371\/journal.pmed.1003741"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e185896","DOI":"10.1001\/jamaoncol.2018.5896","article-title":"Assessment of a Watch-and-Wait Strategy for Rectal Cancer in Patients with a Complete Response after Neoadjuvant Therapy","volume":"5","author":"Smith","year":"2019","journal-title":"JAMA Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1136\/gutjnl-2014-308859","article-title":"Analysis of circulating tumour DNA to monitor disease burden following colorectal cancer surgery","volume":"65","author":"Reinert","year":"2016","journal-title":"Gut"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1136\/gutjnl-2017-315852","article-title":"Serial circulating tumour DNA analysis during multimodality treatment of locally advanced rectal cancer: A prospective biomarker study","volume":"68","author":"Tie","year":"2019","journal-title":"Gut"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1038\/s41416-020-0941-4","article-title":"Serial circulating tumour DNA analysis for locally advanced rectal cancer treated with preoperative therapy: Prediction of pathological response and postoperative recurrence","volume":"123","author":"Murahashi","year":"2020","journal-title":"Br. J. Cancer"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1002\/jso.26244","article-title":"Impact of KRAS status on tumor response and survival after neoadjuvant treatment of locally advanced rectal cancer","volume":"123","author":"Zhou","year":"2021","journal-title":"J. Surg. Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2890","DOI":"10.1158\/1078-0432.CCR-20-4769","article-title":"Clinical Impact of Presurgery Circulating Tumor DNA after Total Neoadjuvant Treatment in Locally Advanced Rectal Cancer: A Biomarker Study from the GEMCAD 1402 Trial","volume":"27","author":"Vidal","year":"2021","journal-title":"Clin. Cancer Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.3389\/fonc.2020.01028","article-title":"Monitoring of Early Changes of Circulating Tumor DNA in the Plasma of Rectal Cancer Patients Receiving Neoadjuvant Concomitant Chemoradiotherapy: Evaluation for Prognosis and Prediction of Therapeutic Response","volume":"10","author":"Pazdirek","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e174","DOI":"10.1002\/ctm2.174","article-title":"Noninvasive prediction of response to cancer therapy using promoter profiling of circulating cell-free DNA","volume":"10","author":"Guo","year":"2020","journal-title":"Clin. Transl. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.ab.2012.06.018","article-title":"Mutation-based detection and monitoring of cell-free tumor DNA in peripheral blood of cancer patients","volume":"433","author":"Benesova","year":"2013","journal-title":"Anal. Biochem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1200\/PO.20.00220","article-title":"Circulating Tumor DNA Predicts Pathologic and Clinical Outcomes Following Neoadjuvant Chemoradiation and Surgery for Patients with Locally Advanced Rectal Cancer","volume":"5","author":"McDuff","year":"2021","journal-title":"JCO Precis. Oncol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"15618","DOI":"10.1038\/ncomms15618","article-title":"DNA exonuclease Trex1 regulates radiotherapy-induced tumour immunogenicity","volume":"8","author":"Alard","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"900945","DOI":"10.3389\/fonc.2022.900945","article-title":"A Pilot, Prospective, Observational Study to Investigate the Value of NGS in Liquid Biopsies to Predict Tumor Response after Neoadjuvant Chemo-Radiotherapy in Patients with Locally Advanced Rectal Cancer: The LiBReCa Study","volume":"12","author":"Roesel","year":"2022","journal-title":"Front. Oncol."},{"key":"ref_46","first-page":"1665","article-title":"Adenoviral-mediated wild-type p53 gene expression sensitizes colorectal cancer cells to ionizing radiation","volume":"2","author":"Spitz","year":"1996","journal-title":"Clin. Cancer Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"9641","DOI":"10.18632\/oncotarget.2438","article-title":"Chemoradiation provides a physiological selective pressure that increases the expansion of aberrant TP53 tumor variants in residual rectal cancerous regions","volume":"5","author":"Sakai","year":"2014","journal-title":"Oncotarget"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Chen, M.B., Wu, X.Y., Yu, R., Li, C., Wang, L.Q., Shen, W., and Lu, P.H. (2012). P53 status as a predictive biomarker for patients receiving neoadjuvant radiation-based treatment: A meta-analysis in rectal cancer. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0045388"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Boussios, S., Ozturk, M.A., Moschetta, M., Karathanasi, A., Zakynthinakis-Kyriakou, N., Katsanos, K.H., Christodoulou, D.K., and Pavlidis, N. (2019). The Developing Story of Predictive Biomarkers in Colorectal Cancer. J. Pers. Med., 9.","DOI":"10.3390\/jpm9010012"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Beganton, B., Coyaud, E., Laurent, E.M.N., Mange, A., Jacquemetton, J., Le Romancer, M., Raught, B., and Solassol, J. (2020). Proximal Protein Interaction Landscape of RAS Paralogs. Cancers, 12.","DOI":"10.3390\/cancers12113326"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"O\u2019Connell, E., Reynolds, I.S., McNamara, D.A., Burke, J.P., and Prehn, J.H.M. (2021). Resistance to Cell Death in Mucinous Colorectal Cancer\u2014A Review. Cancers, 13.","DOI":"10.3390\/cancers13061389"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2548","DOI":"10.1245\/s10434-016-5205-4","article-title":"KRAS and Combined KRAS\/TP53 Mutations in Locally Advanced Rectal Cancer are Independently Associated with Decreased Response to Neoadjuvant Therapy","volume":"23","author":"Chow","year":"2016","journal-title":"Ann. Surg. Oncol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1097\/SLA.0b013e31822b8cfa","article-title":"Identification of a biomarker profile associated with resistance to neoadjuvant chemoradiation therapy in rectal cancer","volume":"254","author":"Chen","year":"2011","journal-title":"Ann. Surg."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1186\/1748-717X-6-114","article-title":"Phospho-ERK and AKT status, but not KRAS mutation status, are associated with outcomes in rectal cancer treated with chemoradiotherapy","volume":"6","author":"Davies","year":"2011","journal-title":"Radiat. Oncol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"277","DOI":"10.2217\/pme-2021-0128","article-title":"Microsatellite instability testing in colorectal patients with Lynch syndrome: Lessons learned from a case report and how to avoid such pitfalls","volume":"19","author":"Adeleke","year":"2022","journal-title":"Pers. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1158\/1078-0432.CCR-19-1996","article-title":"MRI Tumor Regression Grade and Circulating Tumor DNA as Complementary Tools to Assess Response and Guide Therapy Adaptation in Rectal Cancer","volume":"26","author":"Khakoo","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.ijrobp.2007.12.019","article-title":"Prognostic value of pathologic complete response after neoadjuvant therapy in locally advanced rectal cancer: Long-term analysis of 566 ypCR patients","volume":"72","author":"Capirci","year":"2008","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1245\/s10434-014-3982-1","article-title":"Survival paradox between stage IIB\/C (T4N0) and stage IIIA (T1-2N1) colon cancer","volume":"22","author":"Kim","year":"2015","journal-title":"Ann. Surg. Oncol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1016\/j.ygeno.2020.10.029","article-title":"Tumor mutation burden in blood predicts benefit from neoadjuvant chemo\/radiotherapy in locally advanced rectal cancer","volume":"113","author":"Ji","year":"2021","journal-title":"Genomics"},{"key":"ref_60","unstructured":"Amin, M.B., Edge, S.B., and Greene, F.L. (2017). AJCC Cancer Staging Manual, Springer International Publishing AG."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"W486","DOI":"10.2214\/AJR.11.8210","article-title":"MRI after treatment of locally advanced rectal cancer: How to report tumor response--the MERCURY experience","volume":"199","author":"Patel","year":"2012","journal-title":"AJR Am. J. Roentgenol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1111\/j.1365-2559.2005.02176.x","article-title":"Pathological response following long-course neoadjuvant chemoradiotherapy for locally advanced rectal cancer","volume":"47","author":"Ryan","year":"2005","journal-title":"Histopathology"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.csbj.2018.01.003","article-title":"A review of somatic single nucleotide variant calling algorithms for next-generation sequencing data","volume":"16","author":"Xu","year":"2018","journal-title":"Comput. Struct. Biotechnol. J."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/16\/3\/427\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:52:31Z","timestamp":1760122351000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/16\/3\/427"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,10]]},"references-count":63,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["ph16030427"],"URL":"https:\/\/doi.org\/10.3390\/ph16030427","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,10]]}}}