caa a22 4500 445333650 CHVBK 20180317142745.0 cr unu---uuuuu 170323e20110901xx s 000 0 eng 10.1245/s10434-011-1638-y doi (NATIONALLICENCE)springer-10.1245/s10434-011-1638-y Circulating Cell-Free DNA: A Promising Marker of Pathologic Tumor Response in Rectal Cancer Patients Receiving Preoperative Chemoradiotherapy [Elektronische Daten] [Marco Agostini, Salvatore Pucciarelli, Maria Enzo, Paola Del Bianco, Marta Briarava, Chiara Bedin, Isacco Maretto, Maria Friso, Sara Lonardi, Claudia Mescoli, Paola Toppan, Emanuele Urso, Donato Nitti] Purpose: The circulating cell-free DNA (cfDNA) in plasma has been reported to be a marker of cancer detection. The aim of this study was to investigate whether the cfDNA has a role as response biomarker in patients receiving preoperative chemoradiotherapy (CRT) for rectal cancer. Methods: Sixty-seven patients (median age 61years; male/female 42/25) who underwent CRT for rectal cancer were evaluated. After tumor regression grade (TRG) classification was made, the patients were classified as having disease that responded (TRG 1-2) and that did not respond (TRG 3-5) to therapy. Plasma samples were obtained from patients before and after CRT. The cfDNA levels were analyzed by quantitative real-time polymerase chain reaction of β-globin. On the basis of the Alu repeats, the cfDNA was considered as either total (fragments of 115bp, Alu 115) or tumoral (fragments of 247bp, Alu 247). The association between the pre- or post-CRT levels and between variations during CRT of the Alu 247, Alu 115 repeat, and Alu 247/115 ratio (cfDNA integrity index) and the pathologic tumor response was analyzed. Results: The baseline levels of cfDNA were not associated with tumor response. The post-CRT levels of the cfDNA integrity index were significantly lower in responsive compared to nonresponsive disease (P=0.0009). Both the median value of the Alu 247 repeat and the cfDNA integrity index decreased after CRT in disease that responded to therapy (P<0.005 and P<0.005, respectively) compared to disease that did not respond to therapy (P=0.83 and P=0.726, respectively). The results of the multivariable logistic regression analysis showed that only the cfDNA integrity index was significantly and independently associated with tumor response to treatment. Conclusions: The plasma levels of the longer fragments (Alu 247) of cfDNA and the cfDNA integrity index are promising markers to predict tumor response after preoperative CRT for rectal cancer. Society of Surgical Oncology, 2011 Agostini Marco Department of Oncological and Surgical Sciences, 2nd Surgical Clinic, University of Padova, Padova, Italy aut Pucciarelli Salvatore Department of Oncological and Surgical Sciences, 2nd Surgical Clinic, University of Padova, Padova, Italy aut Enzo Maria Department of Oncological and Surgical Sciences, 2nd Surgical Clinic, University of Padova, Padova, Italy aut Del Bianco Paola Clinical Trials and Biostatistics Unit, Veneto Institute of Oncology IOV - IRCCS, Padova, Italy aut Briarava Marta Department of Oncological and Surgical Sciences, 2nd Surgical Clinic, University of Padova, Padova, Italy aut Bedin Chiara Department of Oncological and Surgical Sciences, 2nd Surgical Clinic, University of Padova, Padova, Italy aut Maretto Isacco Department of Oncological and Surgical Sciences, 2nd Surgical Clinic, University of Padova, Padova, Italy aut Friso Maria Department of Radiotherapy and Nuclear Medicine, Veneto Institute of Oncology IOV - IRCCS, Padova, Italy aut Lonardi Sara Department of Medical Oncology, Unit 1st, Veneto Institute of Oncology IOV - IRCCS, Padova, Italy aut Mescoli Claudia Department of Pathology, University of Padova, Padova, Italy aut Toppan Paola Department of Oncological and Surgical Sciences, 2nd Surgical Clinic, University of Padova, Padova, Italy aut Urso Emanuele Department of Oncological and Surgical Sciences, 2nd Surgical Clinic, University of Padova, Padova, Italy aut Nitti Donato Department of Oncological and Surgical Sciences, 2nd Surgical Clinic, University of Padova, Padova, Italy aut Annals of Surgical Oncology Springer-Verlag 18/9(2011-09-01), 2461-2468 1068-9265 18:9<2461 2011 18 10434 https://doi.org/10.1245/s10434-011-1638-y text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1245/s10434-011-1638-y text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Agostini Marco Department of Oncological and Surgical Sciences, 2nd Surgical Clinic, University of Padova, Padova, Italy aut NATIONALLICENCE 700 1- Pucciarelli Salvatore Department of Oncological and Surgical Sciences, 2nd Surgical Clinic, University of Padova, Padova, Italy aut NATIONALLICENCE 700 1- Enzo Maria Department of Oncological and Surgical Sciences, 2nd Surgical Clinic, University of Padova, Padova, Italy aut NATIONALLICENCE 700 1- Del Bianco Paola Clinical Trials and Biostatistics Unit, Veneto Institute of Oncology IOV - IRCCS, Padova, Italy aut NATIONALLICENCE 700 1- Briarava Marta Department of Oncological and Surgical Sciences, 2nd Surgical Clinic, University of Padova, Padova, Italy aut NATIONALLICENCE 700 1- Bedin Chiara Department of Oncological and Surgical Sciences, 2nd Surgical Clinic, University of Padova, Padova, Italy aut NATIONALLICENCE 700 1- Maretto Isacco Department of Oncological and Surgical Sciences, 2nd Surgical Clinic, University of Padova, Padova, Italy aut NATIONALLICENCE 700 1- Friso Maria Department of Radiotherapy and Nuclear Medicine, Veneto Institute of Oncology IOV - IRCCS, Padova, Italy aut NATIONALLICENCE 700 1- Lonardi Sara Department of Medical Oncology, Unit 1st, Veneto Institute of Oncology IOV - IRCCS, Padova, Italy aut NATIONALLICENCE 700 1- Mescoli Claudia Department of Pathology, University of Padova, Padova, Italy aut NATIONALLICENCE 700 1- Toppan Paola Department of Oncological and Surgical Sciences, 2nd Surgical Clinic, University of Padova, Padova, Italy aut NATIONALLICENCE 700 1- Urso Emanuele Department of Oncological and Surgical Sciences, 2nd Surgical Clinic, University of Padova, Padova, Italy aut NATIONALLICENCE 700 1- Nitti Donato Department of Oncological and Surgical Sciences, 2nd Surgical Clinic, University of Padova, Padova, Italy aut NATIONALLICENCE 773 0- Annals of Surgical Oncology Springer-Verlag 18/9(2011-09-01), 2461-2468 1068-9265 18:9<2461 2011 18 10434 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer