CD4 and CD8 T-lymphocyte apoptosis can predict radiation-induced late toxicity: A prospective study in 399 patients

被引:164
作者
Ozsahin, M
Crompton, NEA
Gourgou, S
Kramar, A
Li, L
Shi, YQ
Sozzi, WJ
Zouhair, A
Mirimanoff, RO
Azria, D
机构
[1] CHU Vaudois, Dept Radiat Oncol, CH-1011 Lausanne, Switzerland
[2] Paul Scherrer Inst, CH-5232 Villigen, Switzerland
[3] Ctr Reg Lutte Contre Canc, Montpellier, France
关键词
D O I
10.1158/1078-0432.CCR-04-2634
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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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页码:7426 / 7433
页数:8
相关论文
共 38 条
[1]   COMPETING RISKS DETERMINING EVENT-FREE SURVIVAL IN EARLY BREAST-CANCER [J].
ARRIAGADA, R ;
RUTQVIST, LE ;
KRAMAR, A ;
JOHANSSON, H .
BRITISH JOURNAL OF CANCER, 1992, 66 (05) :951-957
[2]   Relationship between in vitro chromosomal radiosensitivity of peripheral blood lymphocytes and the expression of normal tissue damage following radiotherapy for breast cancer [J].
Barber, JBP ;
Burrill, W ;
Spreadborough, AR ;
Levine, E ;
Warren, C ;
Kiltie, AE ;
Roberts, SA ;
Scott, D .
RADIOTHERAPY AND ONCOLOGY, 2000, 55 (02) :179-186
[3]   LACK OF CORRELATION OF HUMAN FIBROBLAST RADIOSENSITIVITY IN-VITRO WITH EARLY SKIN REACTIONS IN PATIENTS UNDERGOING RADIOTHERAPY [J].
BEGG, AC ;
RUSSELL, NS ;
KNAKEN, H ;
LEBESQUE, JV .
INTERNATIONAL JOURNAL OF RADIATION BIOLOGY, 1993, 64 (04) :393-405
[4]  
Bentzen, 1994, Semin Radiat Oncol, V4, P68, DOI 10.1016/S1053-4296(05)80034-7
[5]   FIBROBLAST RADIOSENSITIVITY VERSUS ACUTE AND LATE NORMAL SKIN-RESPONSES IN PATIENTS TREATED FOR BREAST-CANCER [J].
BROCK, WA ;
TUCKER, SL ;
GEARA, FB ;
TURESSON, I ;
WIKE, J ;
NYMAN, J ;
PETERS, LJ .
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 1995, 32 (05) :1371-1379
[6]   Finding our sensitive patients [J].
Buchholz, TA .
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 1999, 45 (03) :547-548
[7]  
COX DR, 1972, J R STAT SOC B, V34, P187
[8]   TOXICITY CRITERIA OF THE RADIATION-THERAPY ONCOLOGY GROUP (RTOG) AND THE EUROPEAN-ORGANIZATION-FOR-RESEARCH-AND-TREATMENT-OF-CANCER (EORTC) [J].
COX, JD ;
STETZ, J ;
PAJAK, TF .
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 1995, 31 (05) :1341-1346
[9]   A versatile and rapid assay of radiosensitivity of peripheral blood leukocytes based on DNA and surface-marker assessment of cytotoxicity [J].
Crompton, NEA ;
Ozsahin, M .
RADIATION RESEARCH, 1997, 147 (01) :55-60
[10]   Sources of variation in patient response to radiation treatment [J].
Crompton, NEA ;
Shi, YQ ;
Emery, GC ;
Wisser, L ;
Blattmann, H ;
Maier, A ;
Li, L ;
Schindler, D ;
Ozsahin, H ;
Ozsahin, M .
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 2001, 49 (02) :547-554