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

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...

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Bibliographic Details
Published in:Clinical cancer research 2005-10, Vol.11 (20), p.7426-7433
Main Authors: Ozsahin, Mahmut, Crompton, Nigel E A, Gourgou, Sophie, Kramar, Andrew, Li, Ling, Shi, YuQuan, Sozzi, Wendy Jeanneret, Zouhair, Abderrahim, Mirimanoff, René O, Azria, David
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Aged, 80 and over
Apoptosis - radiation effects
Biological and medical sciences
CD4-Positive T-Lymphocytes - pathology
CD4-Positive T-Lymphocytes - radiation effects
CD8-Positive T-Lymphocytes - pathology
CD8-Positive T-Lymphocytes - radiation effects
Female
Follow-Up Studies
Humans
Lymphocyte Apoptosis
Male
Medical sciences
Middle Aged
Neoplasms - blood
Neoplasms - pathology
Neoplasms - radiotherapy
Normal-Tissue Radiosensitivity
Predictive Assay
Predictive Value of Tests
Prospective Studies
Radiation Theraphy
Radiation therapy and radiosensitizing agent
Survival Analysis
Treatment Outcome
Treatment with physical agents
Treatment. General aspects
Tumors
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Summary: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.
ISSN:1078-0432
1557-3265
DOI:10.1158/1078-0432.CCR-04-2634