Quantification of circulating cell‐free DNA in the plasma of cancer patients during radiation therapy

Abstract

Cell-free plasma DNA is elevated in cancer patients and decreases in response to effective treatments. Consequently, these nucleic acids have potential as new tumor markers. In our current study, we investigated whether the plasma DNA concentrations in patients with cancer are altered during the course of radiation therapy. To first determine the origin of cell-free plasma DNA, plasma samples from mice bearing transplanted human tumors were analyzed for human-specific and mouse-specific cell-free DNA. Human-specific DNA was detectable only in plasma from tumor-bearing mice. However, mouse-specific plasma DNA was significantly higher in tumorbearing mice than in normal mice, suggesting that cell-free plasma DNA originated from both tumor and normal cells. We measured the total cell-free plasma DNA levels by quantitative polymerase chain reaction in 15 cancer patients undergoing radiation therapy and compared these values with healthy control subjects. The cancer patients showed higher pretreatment plasma DNA concentrations than the healthy controls. Eleven of these patients showed a transient increase of up to eightfold in their cell-free plasma DNA concentrations during the first or second week of radiation therapy, followed by decreasing concentrations toward the end of treatment. In two other cancer patients, the cell-free plasma DNA concentrations only decreased over the course of the treatment. The total cell-free plasma DNA levels in cancer patients thus show dynamic changes associated with the progression of radiation therapy. Additional prospective studies will be required to elucidate the potential clinical utility and biological implications of dynamic changes in cell-free plasma DNA during radiation therapy. (Cancer Sci 2009; 100: 303-309) T he response of malignant tumors to radiation therapy varies, even if they show similar histopathological origins and clinical staging. An accurate assessment of the radiation sensitivity of individual tumors during the early phase of radiation therapy could provide valuable guidance for selecting the most appropriate treatment plan for individual patients, such as patientspecific modifications of the dose and field of radiation therapy, or additional or alternative therapeutic modalities earlier in the course of treatment. This in turn might contribute to better patient outcomes. However, conventional methods, including imaging diagnoses using computed tomography and magnetic resonance imaging or histopathological examination of biopsy samples, are limited in their ability to evaluate the radiation sensitivity of individual tumors during or immediately following radiation therapy. Hence, alternative assessment methods are required.Previous studies have shown that cell-free DNA is present in the bloodstream of cancer patients at higher concentrations than in healthy controls.(1-4) Although the cell origins and the mechanisms underlying cell-free DNA generation in cancer patients are not yet fully understood, it has been suggested that tumor cells might actively secr...

The role of plasma cell-free DNA detection in predicting preoperative chemoradiotherapy response in rectal cancer patients

“…In the present study, we also demonstrated that plasma cell-free DNA levels were higher in patients with rectal cancer than in healthy individuals, which was consistent with results of previous reports (31). A previous study demonstrated that the concentration of plasma cell-free DNA showed dynamic changes during radiotherapy (15). In addition, the plasma cell-free DNA level decreased after treatment but increased in patients with recurrent cancer (32).…”

“…A high concentration of tumor-associated cell-free DNA and high mutant KRAS levels are related to poor prognosis, outcome and recurrence risk in patients with colorectal cancer (14). In addition, a previous study demonstrated that plasma cell-free DNA concentration showed dynamic changes during radiotherapy (15). Another study revealed that baseline DNA integrity and variations induced by treatment were closely related to pathologic tumor response (16).…”

Quantification of Plasma Cell-Free DNA1in Predicting Therapeutic Efficacy of Sorafenib on Metastatic Clear Cell Renal Cell Carcinoma

“…Cheng's group demonstrates that the total plasma cfDNA levels in cancer patients show dynamic changes associated with the progression of radiation therapy [12].Öfner's group demonstrates that circulating DNA in plasma of rectal cancer patients undergoing preoperative chemoradiation might serve as a surrogate marker to discriminate between responders and nonresponders [24]. Kumar's group demonstrates that monitoring of plasma DNA levels during the course of chemotherapy could identify patients who are likely to exhibit an insufficient therapeutic response and disease progression at an early stage [25].…”

“…It is noteworthy that the levels of circulating cfDNA associate with the progression of radiotherapy or cytotoxic therapy in some cancer patients [12,13]. Thus, we hypothesize that circulating cfDNA might be a novel biomarker for response to sorafenib therapy on metastatic clear cell renal cell carcinoma (cRCC).…”

Share of extracellular mitochondrial DNA with a mutations increases in the plasma of patients lung cancer after radiotherapy

“…Во многих исследованиях количественные и качественные изменения циркулирующей внеклеточной ДНК (вк-ДНК) плазмы (сыворотки) крови рассматриваются как дополнительные маркеры для неинвазивного диагностирования и прогнозирования различных опухолевых патологий [1][2][3][4]. Эти же изменения циркулирующей вк-ДНК могут быть использованы также для оценки эффективности терапии онкологических заболеваний у пациентов [5][6][7]. Однако, использование внеклеточной митохондриальной ДНК (вк-мтДНК) в качестве маркера имеет существенные преимущества относительно ядерной ДНК (яДНК) [8,9].…”