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Circulating Cell-Free DNA: A Promising Marker of Pathologic Tumor Response in Rectal Cancer Patients Receiving Preoperative Chemoradiotherapy

  • Colorectal Cancer
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

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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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.

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Authors and Affiliations

  1. Department of Oncological and Surgical Sciences, 2nd Surgical Clinic, University of Padova, Padova, Italy

    Marco Agostini PhD, Salvatore Pucciarelli MD, Maria Vittoria Enzo PhD, Marta Briarava PhD, Chiara Bedin PhD, Isacco Maretto MD, Paola Toppan MD, Emanuele Urso MD, PhD & Donato Nitti MD

  2. Clinical Trials and Biostatistics Unit, Veneto Institute of Oncology IOV – IRCCS, Padova, Italy

    Paola Del Bianco PhD

  3. Department of Radiotherapy and Nuclear Medicine, Veneto Institute of Oncology IOV – IRCCS, Padova, Italy

    Maria Luisa Friso MD

  4. Department of Medical Oncology, Unit 1st, Veneto Institute of Oncology IOV – IRCCS, Padova, Italy

    Sara Lonardi MD

  5. Department of Pathology, University of Padova, Padova, Italy

    Claudia Mescoli MD

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  1. Marco Agostini PhD
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  2. Salvatore Pucciarelli MD
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  3. Maria Vittoria Enzo PhD
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  12. Emanuele Urso MD, PhD
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  13. Donato Nitti MD
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Corresponding author

Correspondence to Salvatore Pucciarelli MD.

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Agostini, M., Pucciarelli, S., Enzo, M.V. et al. Circulating Cell-Free DNA: A Promising Marker of Pathologic Tumor Response in Rectal Cancer Patients Receiving Preoperative Chemoradiotherapy. Ann Surg Oncol 18, 2461–2468 (2011). https://doi.org/10.1245/s10434-011-1638-y

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  • DOI: https://doi.org/10.1245/s10434-011-1638-y

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