TY - JOUR
T1 - Circulating cell-free DNA
T2 - A promising marker of pathologic tumor response in rectal cancer patients receiving preoperative chemoradiotherapy
AU - Agostini, Marco
AU - Pucciarelli, Salvatore
AU - Enzo, Maria Vittoria
AU - Del Bianco, Paola
AU - Briarava, Marta
AU - Bedin, Chiara
AU - Maretto, Isacco
AU - Friso, Maria Luisa
AU - Lonardi, Sara
AU - Mescoli, Claudia
AU - Toppan, Paola
AU - Urso, Emanuele
AU - Nitti, Donato
N1 - Funding Information:
ACKNOWLEDGMENT This study was supported in part by grants from the Banca AntonVeneta, CARIPARO, and the AIRC Foundation. Biological samples were provided by 2nd Surgical Clinic, Tumor Tissue Biobank. The article was reviewed and edited for English-language usage by American Journal Experts.
Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.
PY - 2011/9
Y1 - 2011/9
N2 - 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 61 years; 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 115 bp, Alu 115) or tumoral (fragments of 247 bp, 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.
AB - 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 61 years; 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 115 bp, Alu 115) or tumoral (fragments of 247 bp, 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.
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U2 - 10.1245/s10434-011-1638-y
DO - 10.1245/s10434-011-1638-y
M3 - Article
C2 - 21416156
AN - SCOPUS:80052741601
SN - 1068-9265
VL - 18
SP - 2461
EP - 2468
JO - Annals of Surgical Oncology
JF - Annals of Surgical Oncology
IS - 9
ER -