- 作者：Olga A. Martin ; Robin L. Anderson ; Prudence A. Russell ; R. Ashley Cox ; Alesia Ivashkevich ; Agnieszka Swierczak ; Judy P. Doherty ; Daphne H.M. Jacobs ; Jai Smith ; Shankar Siva ; Patricia E. Daly ; David L. Ball ; Roger F. Martin ; Michael P. MacManus
- 刊名：International Journal of Radiation Oncology*Biology*Physics
- 出版年：1 February, 2014
- 年：2014
- 卷：88
- 期：2
- 页码：395-403
- 全文大小：2143 K
Purpose
To determine whether radiation therapy (RT) could mobilize viable tumor cells into the circulation of non-small cell lung cancer (NSCLC) patients.Methods and Materials
We enumerated circulating tumor cells (CTCs) by fluorescence microscopy of blood samples immunostained with conventional CTC markers. We measured their DNA damage levels using 纬-H2AX, a biomarker for radiation-induced DNA double-strand breaks, either by fluorescence-activated cell sorting or by immunofluorescence microscopy.
Results
Twenty-seven RT-treated NSCLC patients had blood samples analyzed by 1 or more methods. We identified increased CTC numbers after commencement of RT in 7 of 9 patients treated with palliative RT, and in 4 of 8 patients treated with curative-intent RT. Circulating tumor cells were also identified, singly and in clumps in large numbers, during RT by cytopathologic examination (in all 5 cases studied). Elevated 纬-H2AX signal in post-RT blood samples signified the presence of CTCs derived from irradiated tumors. Blood taken after the commencement of RT contained tumor cells that proliferated extensively in聽vitro (in all 6 cases studied). Circulating tumor cells formed 纬-H2AX foci in response to ex聽vivo irradiation, providing further evidence of their viability.
Conclusions
Our findings provide a rationale for the development of strategies to reduce the concentration of viable CTCs by modulating RT fractionation or by coadministering systemic therapies.