Circulating Plasma Cell-free DNA (cfDNA) as a Predictive Biomarker for Radiotherapy: Results from a Prospective Trial in Head and Neck Cancer

循环血浆游离 DNA (cfDNA) 作为放射治疗的预测生物标志物:头颈癌前瞻性试验的结果

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作者:Michael I Koukourakis, Erasmia Xanthopoulou, Ioannis M Koukourakis, Sotirios P Fortis, Nikolaos Kesesidis, Ioannis Karakasiliotis, Constantin N Baxevanis

Aim

The plasma levels of cell-free DNA (cfDNA) in cancer patients increase due to rapid cancer cell proliferation and death. Therefore, cfDNA can be used to study specific tumor-DNA features. In addition, the non-specific cfDNA concentration may be an important biomarker of cancer prognosis. Patients and

Conclusion

High post-CRT cfDNA levels could be an early biomarker for the immediate recruitment of patients with SCHNC in consolidation chemo-immunotherapy protocols.

Methods

We prospectively examined the predictive role of cfDNA levels and the kinetics in the outcome of chemo-radiotherapy (CRT) in a cohort of 47 patients with locally advanced squamous cell head-neck cancer (SCHNC) treated with definitive chemo-radiotherapy.

Results

Increased cfDNA levels after therapy completion (after/before treatment ratio; A/B-ratio >1) were found in 26/47 patients (55.3%). Locally advanced T4-stage was significantly associated with higher cfDNA levels after CRT (3.3 ng/μl in T4-stage vs. 1.3 ng/μl in T1-3 stages, p=0.007). Patients who responded to CRT (partial/complete response) had significantly lower cfDNA levels before therapy (mean values 1.2 ng/μl vs. 2.7 ng/μl, p=0.03). A significantly worse locoregional progression-free survival in patients with an A/B-ratio >1 was documented (p=0.01; hazard ratio 3.5, 95%CI=1.2-9.7). This was also confirmed in multivariate analysis, where the A/B-ratio was an independent predictive variable of locoregional relapse (p=0.03, hazard ratio 3.9, 95%CI=1.2-13).

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