Clinical and Translational Oncology

, Volume 21, Issue 7, pp 874–880 | Cite as

Cell-free DNA and preoperative chemoradiotherapy for rectal cancer: a systematic review

  • Anders Kindberg BoysenEmail author
  • Jakob Vasehus Schou
  • Karen-Lise Garm Spindler
Research Article



Preoperative chemoradiotherapy is the standard of care for patients with locally advanced rectal cancer, yet valid circulating biomarkers are lacking. We aimed at systematically reviewing the literature of cell-free DNA and locally advanced rectal cancer.


A systematic literature search was performed. We retrieved papers reporting a correlation between a clinical outcome and cell-free DNA for patients receiving chemoradiotherapy for locally advanced rectal cancer.


We included nine studies of a total of 615 patients. Only single-arm studies were identified, analyzing either the total level of cell-free DNA or tumor-specific DNA. Despite differences in the methodology and outcomes, eight of the nine studies showed a correlation between cell-free DNA and a clinical outcome.


Cell-free DNA might hold prognostic and predictive information for patients with locally advanced rectal cancer receiving preoperative chemoradiotherapy; although, firm conclusions are limited by the heterogeneity in this field.


Rectal cancer Cell-free DNA Chemoradiotherapy Systematic review 



No funding was used for this systematic review.

Compliance with ethical standards

Conflict of interest

All authors declare no conflicts of interest.

Statement of human/animal participants

This study did not involve human participants or animals.

Informed consent

All participants provided informed consent prior to their participation.


  1. 1.
    Giovannucci E, Wu K. Cancers of the colon and rectum. In: Schottenfeld D, Fraumeni J, editors. Cancer. Epidemiology and prevention. 3rd ed. Oxford: Oxford University Press; 2006.Google Scholar
  2. 2.
    Glynne-Jones R, Wyrwicz L, Tiret E, et al. Rectal cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017;28:iv22–40.CrossRefGoogle Scholar
  3. 3.
    Kapiteijn E, Marijnen C, Nagtegaal I, et al. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med. 2001;345:638–46.CrossRefGoogle Scholar
  4. 4.
    Ngan S, Burmeister B, Fisher R, et al. Randomized trial of short course radiotherapy versus long course chemoradiation comparing rates of local recurrence in patients with T4 rectal cancer: Trans Tasman Radiation Oncology Group Trial 01.04. J Clin Oncol. 2012;30:3827–33.CrossRefGoogle Scholar
  5. 5.
    Leichman C, McDonough S, Smalley S, et al. Cetuximab combined with induction oxaliplatin and capecitabine, followed by neoadjuvant chemoradiation for locally advanced rectal cancer: SWOG 0713. Clin Colorectal Cancer. 2017;17:e121–5.CrossRefGoogle Scholar
  6. 6.
    Appelt A, Pløen J, Harling H, et al. High dose chemoradiotherapy and watchful waiting for distal rectal cancer: a prospective observational study. Lancet Oncol. 2015;16:919–27.CrossRefGoogle Scholar
  7. 7.
    Brown G, et al. Morphologic predictors of lymph node status in rectal cancer with use of high-spatial-resolution MR imaging with histopathological comparison. Radiology. 2003;227(2):371–7.CrossRefGoogle Scholar
  8. 8.
    Dayde D, Tanaka I, Tai M, et al. Predictive and Prognostic molecular biomarkers for response to neoadjuvant chemoradiation in rectal cancer. Int J Mol Sci. 2017;18:573.CrossRefGoogle Scholar
  9. 9.
    Mandel P, Metasis P. Les acides nucleiques du plasma sanguis chez l’homme. CR Seances Soc Biol Fil. 1948;142:241–3.Google Scholar
  10. 10.
    Leon SA, Shapiro B, Sklaroff DM, et al. Free DNA in the serum of patients and the effect of therapy. Cancer Res. 1977;37:646–50.Google Scholar
  11. 11.
    Spindler KL, Boysen AK, Pallisgaard N, et al. Cell free DNA in metastatic colorectal cancer—a systematic review and meta analysis. Oncologist. 2017;22(9):1049–55.CrossRefGoogle Scholar
  12. 12.
    Moher D, Liberati A, Tetzlaff J, Altman DG, Prisma Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;151(4):264–9.Google Scholar
  13. 13.
    Whitting PF, Rutjes A, Westwood M, et al. QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med. 2011;155:529–36.CrossRefGoogle Scholar
  14. 14.
    Zitt M, Muller H, Rochel M, et al. Circulating cell free DNA in plasma of locally advanced rectal cancer patients undergoing preoperative chemoradiation: a potential diagnostic tool for therapy monitoring. Dis Markers. 2008;25(3):159–65.CrossRefGoogle Scholar
  15. 15.
    Agostine M, Pucciarelli S, Vittoria M, et al. Circulating cell free DNA: a promising marker of pathologic tumor response in rectal cancer patients receiving preoperative chemoradiation. Ann Surg Oncol. 2011;18:2461–8.CrossRefGoogle Scholar
  16. 16.
    Sun W, Sun Y, Zhu M, et al. The role of plasma cell free DNA detection in predicting preoperative chemoradiotherapy response in rectal cancer patients. Oncol Rep. 2014;31:1466–72.CrossRefGoogle Scholar
  17. 17.
    Carpinetti P, Donnard E, Bettoni F, et al. The use of personalized biomarkers and liquid biopsies to monitor treatment response and disease recurrence in locally advanced rectal cancer after neoadjuvant chemoradiation. Oncotarget. 2015;6(35):38360–71.CrossRefGoogle Scholar
  18. 18.
    Boysen AK, Wettergren Y, Sørensen BS, et al. Cell-free DNA levels and correlation to stage and outcome following treatment of locally advanced rectal cancer. Tumor Biol. 2017;39(11):1–6.CrossRefGoogle Scholar
  19. 19.
    Schou JV, Larsen FO, Sørensen BS, et al. Circulating cell-free DNA as predictor of treatment failure after neoadjuvant chemo-radiotherapy before surgery in patients with locally advanced rectal cancer. Ann Oncol. 2018;0:1–6.Google Scholar
  20. 20.
    Sclafani F, Chau I, Cunningham D, et al. KRAS and BRAF mutations in circulating tumour DNA from locally advanced rectal cancer. Sci Rep. 2018;8:1445.CrossRefGoogle Scholar
  21. 21.
    Tie J, Cohen J, Wang Y, et al. Serial circulating tumour DNA analysis during multimodality treatment of locally advanced rectal cancer: a prospective biomarker study. Gut. 2018;0:1–9.Google Scholar
  22. 22.
    Li M, Xiao W, Zhao G, et al. Predictive value of circulating tumor DNA in locally advanced rectal cancer patients receiving neoadjuvant radiochemotherapy. J Clin Oncol. 2017;35:n15_supplement.Google Scholar
  23. 23.
    Ryan JE, Warrier SK, Lynch AC, et al. Assessing pathological complete response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer: a systematic review. Colorectal Dis. 2015;17:849–61.CrossRefGoogle Scholar
  24. 24.
    Glynne-Jones R, Wyrwicz L, Tiret E, et al. Rectal cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017;28((Supplement 4)):iv22–40.CrossRefGoogle Scholar
  25. 25.
    Negri FV, Campanini N, Camisa R, et al. Biological predictive factors in rectal cancer treated with preoperative radiotherapy or radiochemotherapy. Br J Cancer. 2008;98:143–7.CrossRefGoogle Scholar
  26. 26.
    Sturm I, Rau B, Schlag PM, et al. Genetic dissection of apoptosis and cell cycle control in response of colorectal cancer treated with preoperative radiochemotherapy. BMC Cancer. 2006;6:124.CrossRefGoogle Scholar
  27. 27.
    Spindler KL, Nielsen JN, Lindebjerg J, et al. Prediction of response to chemoradiation in rectal cancer by a gene polymorphism in the epidermal growth factor receptor promoter region. Int J Radiat Oncol Biol Phys. 2006;66:500–4.CrossRefGoogle Scholar
  28. 28.
    Hur H, Kim NK, Min B, et al. Can a biomarker-based scoring system predict pathologic complete response after preoperative chemoradiothreapy for rectal cancer? Dis Colon Rectum. 2014;57:5.CrossRefGoogle Scholar
  29. 29.
    Probst C, Beccera A, Acuina C, et al. Watch and wait?—elevated pretreatment CEA Is associated with decreased pathological complete response in rectal cancer. J Gastrointest Surg. 2016;20:43–52.CrossRefGoogle Scholar
  30. 30.
    Spindler KL. Methodological, biological and clinical aspects of circulating free DNA in metastatic colorectal cancer. Acta Oncol. 2017;56(1):7–16.CrossRefGoogle Scholar
  31. 31.
    Misale S, Yaeger R, Hobor S, et al. Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer. Nature. 2012;486:532–6.CrossRefGoogle Scholar

Copyright information

© Federación de Sociedades Españolas de Oncología (FESEO) 2018

Authors and Affiliations

  • Anders Kindberg Boysen
    • 1
    • 2
    Email author
  • Jakob Vasehus Schou
    • 3
  • Karen-Lise Garm Spindler
    • 1
    • 2
  1. 1.Department of Experimental Clinical OncologyAarhus University HospitalAarhusDenmark
  2. 2.Department of OncologyAarhus University HospitalAarhusDenmark
  3. 3.Department of Oncology, Herlev and Gentofte HospitalCopenhagen University HospitalHellerupDenmark

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