Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Observational Study
. 2023 Sep 28;59(10):1742.
doi: 10.3390/medicina59101742.

Evaluation of Changes in Circulating Cell-Free DNA as an Early Predictor of Response to Chemoradiation in Rectal Cancer-A Pilot Study

Wee Liam Ong  1 , Sorinel Lunca  1   2 , Stefan Morarasu  1   2 , Ana-Maria Musina  1   2 , Alina Puscasu  1   2 , Stefan Iacob  1   2 , Irina Iftincai  3 , Andreea Marinca  3 , Iuliu Ivanov  4 , Cristian Ena Roata  1   2 , Natalia Velenciuc  1   2 , Gabriel Dimofte  1   2
Affiliations
Observational Study

Evaluation of Changes in Circulating Cell-Free DNA as an Early Predictor of Response to Chemoradiation in Rectal Cancer-A Pilot Study

Wee Liam Ong et al. Medicina (Kaunas). .

Abstract

Background and Objectives: The objective of this study was to investigate quantitative changes in cell-free DNA (cfDNA) found in the bloodstream of patients with locally advanced rectal cancer who received neoadjuvant long-course chemoradiation, assuming a change in DNA fragments release during therapeutic stress. Materials and Methods: This was a prospective observational study that involved 49 patients who had three distinct pathologies requiring neoadjuvant chemoradiation: 18 patients with breast cancer, 18 patients with cervical cancer, and 13 patients with rectal cancer. Both breast cancer and cervical cancer patients were used as a control groups. Breast cancer patients were used as a control group as irradiation targeted healthy tissue after the tumor resection (R0), while cervical cancer patients were used as a control group to evaluate the effect of chemoradiation regarding cfDNA in a different setting (squamous cell carcinomas) and a different tumor burden. Rectal cancer patients were the study group, and were prospectively evaluated for a correlation between fragmentation of cfDNA and late response to chemoradiation. Blood samples were collected before the initiation of treatment and after the fifth radiation dose delivery. cfDNA was quantified in peripheral blood and compared with the patients' clinicopathological characteristics and tumor volume. Conclusion: Thirteen patients with locally advanced rectal cancer (T3/T4/N+/M0) were included in the study, and all of them had their samples analyzed. Eight were male (61.54%) and five were female (38.46%), with an average age of 70.85 years. Most of the patients had cT3 (53.85%) or cT4 (46.15%) tumors, and 92.31% had positive lymph nodes (N2-3). Of the thirteen patients, only six underwent surgery, and one of them achieved a pathological complete response (pCR). The mean size of the tumor was 122.60 mm3 [35.33-662.60 mm3]. No significant correlation was found between cfDNA, tumor volume, and tumor regression grade. cfDNA does not seem to predict response to neoadjuvant chemoradiotherapy and it is not correlated to tumor volume or tumor regression grade.

Keywords: DNA; neoadjuvant therapy; prognosis; radiotherapy; rectal cancer.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Diagram depicting management and response in the thirteen rectal cancer patients.
Figure 2
Figure 2
Example of result for cfDNA before and after 5th session of radiotherapy.
Figure 3
Figure 3
Box and Whisker plot of cfDNA ratio between samples.
Figure 4
Figure 4
cfDNA ratio regression graph in all three groups of patients: (a) breast cancer group, (b) cervical cancer group, (c) rectal cancer group, (d) rectal cancer subgroup (underwent surgical treatment).
See this image and copyright information in PMC

References

    1. Yan Y.Y., Guo Q.R., Wang F.H., Adhikari R., Zhu Z.Y., Zhang H.Y., Zhou W.M., Yu H., Li J.Q., Zhang J.Y. Cell-Free DNA: Hope and Potential Application in Cancer. Front. Cell Dev. Biol. 2021;9:639233. - PMC - PubMed
    1. Kasi A., Abbasi S., Handa S., Al-Rajabi R., Saeed A., Baranda J., Sun W. Total Neoadjuvant Therapy vs Standard Therapy in Locally Advanced Rectal Cancer. JAMA Netw. Open. 2020;3:e2030097. - PMC - PubMed
    1. Hartley A., Ho K.F., McConkey C., Geh J.I. Pathological complete response following pre-operative chemoradiotherapy in rectal cancer: Analysis of phase II/III trials. Br. J. Radiol. 2005;78:934–938. doi: 10.1259/bjr/86650067. - DOI - PubMed
    1. Ceelen W., Fierens K., Van Nieuwenhove Y., Pattyn P. Preoperative chemoradiation versus radiation alone for stage II and III resectable rectal cancer: A systematic review and meta-analysis. Int. J. Cancer. 2009;124:2966–2972. doi: 10.1002/ijc.24247. - DOI - PubMed
    1. Johnson G.G., Park J., Helewa R.M., Goldenberg B.A., Nashed M., Hyun E. Total neoadjuvant therapy for rectal cancer: A guide for surgeons. Can. J. Surg. 2023;66:E196–E201. doi: 10.1503/cjs.005822. - DOI - PMC - PubMed

Publication types

Substances