TY - JOUR
T1 - Mobilization of viable tumor cells into the circulation during radiation therapy
AU - Martin, Olga
AU - Anderson, Robin L
AU - Russell, Prudence A
AU - Cox, R Ashley
AU - Ivashkevich, Alesia
AU - Swierczak, Agnieszka
AU - Doherty, Judy
AU - Jacobs, Daphne H M
AU - Smith, Jai
AU - Siva, Shankar
AU - Daly, Patricia E
AU - Ball, David Lee
AU - Martin, Roger F
AU - MacManus, Michael Patrick
PY - 2014
Y1 - 2014
N2 - 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 gamma-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 gamma-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 vitro (in all 6 cases studied). Circulating tumor cells formed gamma-H2AX foci in response to ex 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.
AB - 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 gamma-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 gamma-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 vitro (in all 6 cases studied). Circulating tumor cells formed gamma-H2AX foci in response to ex 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.
UR - http://www.sciencedirect.com/science/article/pii/S036030161303280X
U2 - 10.1016/j.ijrobp.2013.10.033
DO - 10.1016/j.ijrobp.2013.10.033
M3 - Article
VL - 88
SP - 395
EP - 403
JO - International Journal of Radiation Oncology, Biology, Physics
JF - International Journal of Radiation Oncology, Biology, Physics
SN - 0360-3016
IS - 2
ER -