Radiotherapy increases plasma levels of tumoral cell-free DNA in non-small cell lung cancer patients

Abstract

We investigated the plasma levels of tumor-specific cell-free DNA (cfDNA) in 17 stage I–II (early) and IV (advanced) non-small cell lung cancer (NSCLC) patients who underwent radiotherapy. Digital polymerase chain reaction (PCR) and targeted sequencing showed that total and tumor-specific cfDNA levels increased in response to radiotherapy in both early- and advanced-stage NSCLC patients. We detected high copy numbers of epidermal growth factor receptor mutations (L858R and T790M) in the cfDNA samples from stage IV NSCLC patients who underwent stereotactic body radiation therapy to treat brain metastasis related to tyrosine kinase inhibitor (TKI) treatment failure. In conclusion, our study demonstrates that radiotherapy increases tumoral cfDNA levels in the plasma and shows potential to serve as an indicator for diagnosing drug-resistant tumor-related gene mutations in early-stage NSCLC patients or those undergoing molecular targeted therapy.

Radiation Induced Upregulation of DNA Sensing Pathways is Cell-Type Dependent and Can Mediate the Off-Target Effects

“…However, the effect was rare and was not potent enough to induce the upregulation of the DNA sensors mRNAs. Nevertheless, this basic in vitro study may extend to the in vivo setting, so this mechanism may become significant in the case of solid tumors, which contain large numbers of distinct cell types and also larger concentrations of cfDNA have been described in studies in patients receiving conventional radiotherapy or SBRT [ 34 , 35 ]. However, cfDNA is probably not the only source of DNA, which was detected to enter into the bystander cells in our study.…”

Cell-free DNA in newly diagnosed patients with glioblastoma – a clinical prospective feasibility study

“…As expected, the mean cfDNA concentration decreased one month after surgery due to surgical removal of the tumor burden [21]. The stable levels or increase in cfDNA during RT can be caused by tumor and normal tissue necrosis as was also shown in a recent study with non-small-cell lung cancer (NSCLC) patients [27]. Approximately one month after RT and with no other interventions, the mean level decreased again which could be due to decrease of RT-induced edema and inflammation.…”

Early circulating tumour DNA kinetics measured by ultra-deep next-generation sequencing during radical radiotherapy for non-small cell lung cancer: a feasibility study

“…There is only one known published report of cfDNA monitoring during radiotherapy for lung cancer [20]. In this study of 17 patients, cfDNA was assessed after each quarter of the radiotherapy treatment course with digital PCR, and NGS where possible (2 cases of thoracic radiotherapy; 2 cases of cranial stereotactic radiosurgery).…”

“…Although approximately 45% stage I-III NSCLC cases receive radical radiotherapy as multi-or single modality treatment [19], there is only one published series on the impact of radiotherapy on cfDNA in NSCLC [20]. Furthermore, the paucity of data on ctDNA dynamics during radiotherapy across other tumour sites means there are few transferable lessons about any possible interplay in NSCLC [20][21][22][23][24][25][26] As the anti-tumour activity of radiotherapy is achieved through DNA damage-mediated cell death, it is expected that an interaction will be observed. Additional evidence for transient ctDNA increases on commencing treatment may support the evaluation of radiotherapy as a preparatory procedure for liquid biopsy.…”