Mobilization of Viable Tumor Cells Into the Circulation During Radiation Therapy

Journal Article · Sat Feb 01 04:00:00 EST 2014 · International Journal of Radiation Oncology, Biology and Physics

DOI:https://doi.org/10.1016/J.IJROBP.2013.10.033· OSTI ID:22283356

Martin, Olga A. ^[1]; Anderson, Robin L. ^[2]; Russell, Prudence A. ^[3]; Ashley Cox, R. ^[1]; Ivashkevich, Alesia ^[4]; Swierczak, Agnieszka; Doherty, Judy P. ^[5]; Jacobs, Daphne H.M. ^[1]; Smith, Jai ^[4]; Siva, Shankar; Daly, Patricia E. ^[1]; Ball, David L. ^[1]; others, and

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1. Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne, VIC (Australia)
2. The Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC (Australia)
3. Department of Anatomical Pathology, St. Vincent Hospital, Fitzroy, VIC (Australia)
4. Molecular Radiation Biology Laboratory, Peter MacCallum Cancer Centre, East Melbourne, VIC (Australia)
5. Metastasis Research Laboratory, Peter MacCallum Cancer Centre, East Melbourne, VIC (Australia)

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 γ-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 γ-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 γ-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.

• OSTI ID: 22283356
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Journal Name: International Journal of Radiation Oncology, Biology and Physics Journal Issue: 2 Vol. 88; ISSN IOBPD3; ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
BIOLOGICAL MARKERS
BLOOD
DNA
FLUORESCENCE
LUNGS
NEOPLASMS
PATIENTS
RADIOTHERAPY
STRAND BREAKS
TUMOR CELLS