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CD4 and CD8 T-Lymphocyte Apoptosis Can Predict Radiation-Induced Late Toxicity: A Prospective Study in 399 Patients

Authors' Affiliations: ¹ Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; ² Paul Scherrer Institute, Villigen, Switzerland; and ³ Centre Régional de Lutte Contre le Cancer, Val d'Aurelle-Paul Lamarque, Montpellier, France

Requests for reprints: Mahmut Ozsahin, Department of Radiation Oncology, Centre Hospitalier Universitaire Vaudois, Bugnon 46, CH-1011 Lausanne, Switzerland. Phone: 41-21-314-4603; Fax: 41-21-314-4601; E-mail: eozsahin{at}hospvd.ch.

Purpose: Predicting late effects in patients treated with radiation therapy by assessing in vitro radiation-induced CD4 and CD8 T-lymphocyte apoptosis can be useful in individualizing treatment.

Experimental Design: In a prospective study, 399 curatively irradiated patients were tested using a rapid assay where fresh blood samples were in vitro irradiated with 8 Gy X-rays. Lymphocytes were collected and prepared for flow cytometric analysis. Apoptosis was assessed by associated condensation of DNA. The incidences of late toxicities were compared for CD4 and CD8 T-lymphocyte apoptoses using receiver-operating characteristic curves and cumulative incidence.

Results: No association was found between early toxicity and T-lymphocyte apoptosis. Grade 2 and 3 late toxicities were observed in 31% and 7% of patients, respectively. More radiation-induced T-lymphocyte apoptosis was significantly associated with less grade 2 and 3 late toxicity (Gray's test, P < 0.0001). CD8 (area under the curve = 0.83) was more sensitive and specific than CD4. No grade 3 late toxicity was observed for patients with CD4 and CD8 values greater than 15% and 24%, respectively. The 2-year cumulative incidence for grade 2 or 3 late toxicity was 70%, 32%, and 12% for patients with absolute change in CD8 T-lymphocyte apoptosis of 16, 16 to 24, and >24, respectively.

Conclusions: Radiation-induced T-lymphocyte apoptosis can significantly predict differences in late toxicity between individuals. It could be used as a rapid screen for hypersensitive patients to radiotherapy. In future dose escalation studies, patients could be selected using the apoptosis assay.

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				D. Azria, M. Ozsahin, A. Kramar, S. Peters, D. P. Atencio, N. E.A. Crompton, F. Mornex, A. Pelegrin, J.-B. Dubois, R.-O. Mirimanoff, et al. Single Nucleotide Polymorphisms, Apoptosis, and the Development of Severe Late Adverse Effects After Radiotherapy Clin. Cancer Res., October 1, 2008; 14(19): 6284 - 6288. [Abstract] [Full Text] [PDF]