Olga A Martin1, Robin L Anderson2, Prudence A Russell3, R Ashley Cox4, Alesia Ivashkevich5, Agnieszka Swierczak6, Judy P Doherty6, Daphne H M Jacobs4, Jai Smith7, Shankar Siva4, Patricia E Daly4, David L Ball8, Roger F Martin9, Michael P MacManus10. 1. Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia; Molecular Radiation Biology Laboratory, Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia; The Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia. 2. The Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia; Metastasis Research Laboratory, Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia. 3. Department of Anatomical Pathology, St. Vincent Hospital, Fitzroy, VIC, Australia. 4. Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia. 5. Molecular Radiation Biology Laboratory, Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia; Laboratory of DNA Repair and Genomics, Centre for Innate Immunity and Infectious Disease, Monash Institute for Medical Research, Monash University, Clayton, VIC, Australia. 6. Metastasis Research Laboratory, Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia. 7. Molecular Radiation Biology Laboratory, Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia. 8. Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia; The Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia. 9. Molecular Radiation Biology Laboratory, Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia; The Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia. 10. Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia; The Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia. Electronic address: Michael.macmanus@petermac.org.
Abstract
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.
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 NSCLCpatients 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.
Authors: Nathan A Koonce; Mazen A Juratli; Chengzhong Cai; Mustafa Sarimollaoglu; Yulian A Menyaev; Judith Dent; Charles M Quick; Ruud P M Dings; Dmitry Nedosekin; Vladimir Zharov; Robert J Griffin Journal: Biochem Biophys Res Commun Date: 2017-08-16 Impact factor: 3.575
Authors: Michael MacManus; Sarah Everitt; Tanja Schimek-Jasch; X Allen Li; Ursula Nestle; Feng-Ming Spring Kong Journal: Transl Lung Cancer Res Date: 2017-12
Authors: Ja Hye Myung; Michael J Eblan; Joseph M Caster; Sin-Jung Park; Michael J Poellmann; Kyle Wang; Kevin A Tam; Seth M Miller; Colette Shen; Ronald C Chen; Tian Zhang; Joel E Tepper; Bhishamjit S Chera; Andrew Z Wang; Seungpyo Hong Journal: Clin Cancer Res Date: 2018-03-15 Impact factor: 12.531