Cell-free DNA as predictor of pathological complete response in locally advanced rectal cancer
Christina Truelsen,
Denmark
OC-0268
Abstract
Cell-free DNA as predictor of pathological complete response in locally advanced rectal cancer
Authors: Christina Truelsen1, Camilla Kronborg2, Brita Singer Sørensen2, Louise Callesen3, Karen-Lise Spindler3,4
1Aarhus University Hospital, Department of Clinical Experimental Oncology, AArhus, Denmark; 2Aarhus University Hospital, Danish Centre for Particle Therapy, Aarhus, Denmark; 3Aarhus University Hospital, Department of Clinical Experimental Oncology, Aarhus, Denmark; 4Aarhus University Hospital, Department of Oncology, Aarhus, Denmark
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Purpose or Objective
Neoadjuvant radiotherapy followed by total
mesorectal excision is the standard treatment strategy for locally advanced
rectal cancer (LARC). For patients achieving clinical complete response (cCR)
after neoadjuvant radiotherapy the watch and wait strategy (W&W) is
proposed as an organ-sparing approach surpassing surgical morbidity. There are, however, concerns related to
persisting, viable cancers cells despite cCR- as cCR is only in
partial concordance with pathological complete response (pCR), which substantiates
the need for complimentary information for patient stratification for a
non-operative management. The aim of this study was to investigate circulating cell-free deoxyribonucleic-acid (cfDNA) as a biomarker for prediction of pCR.
Material and Methods
A prospective biomarker study was conducted at
Aarhus University Hospital, Denmark from 2017 to 2020 including patients with
LARC treated with neoadjuvant radiotherapy. Plasma obtained at baseline, mid-
and end of therapy was quantified for cfDNA by a direct fluorescent assay
(DFA). Surgical specimens were reviewed by pathologist to categorize response to
chemoradiotherapy.
Results
Samples were collected from 76 patients at baseline
(n=70), mid therapy (n=50), and end of therapy (n=54). Significantly higher
cfDNA levels were observed in this cohort of LARC patients compared with cfDNA
of healthy subjects (p < 0.01). By ROC analysis (AUC: 0.87 (95 % CI,
0.81-0.92)) an optimal cut-off of 0.71 ng/µL was found for distinction between healthy
subjects and LARC patients. 13 patients (17.1 %) obtained pCR with a median
cfDNA of 0.57 ng/µL (95 % CI, 0.38-0.7) at end of therapy. Patients with cfDNA
at end of therapy under the cut-off had a significantly higher chance of pCR (p
= 0.02). cfDNA levels decreased significantly during treatment (p < 0.01), when
decrease in cfDNA was greater than the 75th percentile a significantly higher
chance of pCR was observed (p < 0.01).
Conclusion
In this study, we demonstrated that low cfDNA at end
of neo-adjuvant treatment and ´cfDNA responders´ with a decrease in cfDNA above
the 75th percentile during radiotherapy were associated with pCR.
Quantification of cfDNA by a rapid and cost-effective DFA analysis could
potentially facilitate an individualized treatment as a complimentary tool to imaging
for identification of candidates for a W&W strategy.