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Title: Mobilization of Viable Tumor Cells Into the Circulation During Radiation Therapy

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 concentrationmore » of viable CTCs by modulating RT fractionation or by coadministering systemic therapies.« less
Authors:
 [1] ;  [2] ;  [2] ;  [3] ;  [2] ;  [4] ;  [1] ;  [5] ;  [2] ; ;  [6] ;  [1] ;  [5] ; ;  [1] ;  [1] ;  [2] ;
  1. Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne, VIC (Australia)
  2. (Australia)
  3. The Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC (Australia)
  4. Department of Anatomical Pathology, St. Vincent Hospital, Fitzroy, VIC (Australia)
  5. Molecular Radiation Biology Laboratory, Peter MacCallum Cancer Centre, East Melbourne, VIC (Australia)
  6. Metastasis Research Laboratory, Peter MacCallum Cancer Centre, East Melbourne, VIC (Australia)
Publication Date:
OSTI Identifier:
22283356
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 88; Journal Issue: 2; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; BIOLOGICAL MARKERS; BLOOD; DNA; FLUORESCENCE; LUNGS; NEOPLASMS; PATIENTS; RADIOTHERAPY; STRAND BREAKS; TUMOR CELLS