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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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| Published in: | Clinical cancer research 2005-10, Vol.11 (20), p.7426-7433 |
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| container_title | Clinical cancer research |
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| creator | Ozsahin, Mahmut Crompton, Nigel E A Gourgou, Sophie Kramar, Andrew Li, Ling Shi, YuQuan Sozzi, Wendy Jeanneret Zouhair, Abderrahim Mirimanoff, René O Azria, David |
| description | 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. |
| doi_str_mv | 10.1158/1078-0432.CCR-04-2634 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_20796108</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>20796108</sourcerecordid><originalsourceid>FETCH-LOGICAL-c454t-9b534d2ed53db22dcbac1d2b5ff1f5969393530ae058450d82224be617dceb9d3</originalsourceid><addsrcrecordid>eNpFkM1q3DAYRUVoyG8foUWbBrJwol9bzm5w2iYwkJBO10KWPndUZmxHktv47athpmSluzhX3-Ug9ImSG0qluqWkUgURnN00zUsOBSu5OEJnVMqq4KyUH3L-z5yi8xh_E0IFJeIEndKSCa5oeYZicy-w6R1u7hVeFct5O64HOyfAi3EY0xB9xI3p8XMA523CL8Z5k_zQF4-9myw4vDQZXg1v3vo03-FFRoc4gk3-D-AfaXIz9j3mdY2fcxH6FC_RcWc2ET4e3gv089vXVfNQLJ--PzaLZWGFFKmoW8mFY-Akdy1jzrbGUsda2XW0k3VZ85pLTgwQqYQkTjHGRAslrZyFtnb8Al3t_x3D8DpBTHrro4XNxvQwTFEzUtUlJSqDcg_aPD0G6PQY_NaEWVOid7b1zqTemdTZdg56Zzv3Ph8OTO0W3HvroDcDXw6AidZsumB66-M7VzGqFKOZu95za_9r_dcH0DaTEAJEMMGu84i8Vlcin_0HtgSVBQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>20796108</pqid></control><display><type>article</type><title>CD4 and CD8 T-Lymphocyte Apoptosis Can Predict Radiation-Induced Late Toxicity: A Prospective Study in 399 Patients</title><source>Freely Accessible Science Journals - check A-Z of ejournals</source><creator>Ozsahin, Mahmut ; Crompton, Nigel E A ; Gourgou, Sophie ; Kramar, Andrew ; Li, Ling ; Shi, YuQuan ; Sozzi, Wendy Jeanneret ; Zouhair, Abderrahim ; Mirimanoff, René O ; Azria, David</creator><creatorcontrib>Ozsahin, Mahmut ; Crompton, Nigel E A ; Gourgou, Sophie ; Kramar, Andrew ; Li, Ling ; Shi, YuQuan ; Sozzi, Wendy Jeanneret ; Zouhair, Abderrahim ; Mirimanoff, René O ; Azria, David</creatorcontrib><description>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.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>DOI: 10.1158/1078-0432.CCR-04-2634</identifier><identifier>PMID: 16243816</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>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</subject><ispartof>Clinical cancer research, 2005-10, Vol.11 (20), p.7426-7433</ispartof><rights>2005 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c454t-9b534d2ed53db22dcbac1d2b5ff1f5969393530ae058450d82224be617dceb9d3</citedby><cites>FETCH-LOGICAL-c454t-9b534d2ed53db22dcbac1d2b5ff1f5969393530ae058450d82224be617dceb9d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17218821$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16243816$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ozsahin, Mahmut</creatorcontrib><creatorcontrib>Crompton, Nigel E A</creatorcontrib><creatorcontrib>Gourgou, Sophie</creatorcontrib><creatorcontrib>Kramar, Andrew</creatorcontrib><creatorcontrib>Li, Ling</creatorcontrib><creatorcontrib>Shi, YuQuan</creatorcontrib><creatorcontrib>Sozzi, Wendy Jeanneret</creatorcontrib><creatorcontrib>Zouhair, Abderrahim</creatorcontrib><creatorcontrib>Mirimanoff, René O</creatorcontrib><creatorcontrib>Azria, David</creatorcontrib><title>CD4 and CD8 T-Lymphocyte Apoptosis Can Predict Radiation-Induced Late Toxicity: A Prospective Study in 399 Patients</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>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.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Apoptosis - radiation effects</subject><subject>Biological and medical sciences</subject><subject>CD4-Positive T-Lymphocytes - pathology</subject><subject>CD4-Positive T-Lymphocytes - radiation effects</subject><subject>CD8-Positive T-Lymphocytes - pathology</subject><subject>CD8-Positive T-Lymphocytes - radiation effects</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Humans</subject><subject>Lymphocyte Apoptosis</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Neoplasms - blood</subject><subject>Neoplasms - pathology</subject><subject>Neoplasms - radiotherapy</subject><subject>Normal-Tissue Radiosensitivity</subject><subject>Predictive Assay</subject><subject>Predictive Value of Tests</subject><subject>Prospective Studies</subject><subject>Radiation Theraphy</subject><subject>Radiation therapy and radiosensitizing agent</subject><subject>Survival Analysis</subject><subject>Treatment Outcome</subject><subject>Treatment with physical agents</subject><subject>Treatment. General aspects</subject><subject>Tumors</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><recordid>eNpFkM1q3DAYRUVoyG8foUWbBrJwol9bzm5w2iYwkJBO10KWPndUZmxHktv47athpmSluzhX3-Ug9ImSG0qluqWkUgURnN00zUsOBSu5OEJnVMqq4KyUH3L-z5yi8xh_E0IFJeIEndKSCa5oeYZicy-w6R1u7hVeFct5O64HOyfAi3EY0xB9xI3p8XMA523CL8Z5k_zQF4-9myw4vDQZXg1v3vo03-FFRoc4gk3-D-AfaXIz9j3mdY2fcxH6FC_RcWc2ET4e3gv089vXVfNQLJ--PzaLZWGFFKmoW8mFY-Akdy1jzrbGUsda2XW0k3VZ85pLTgwQqYQkTjHGRAslrZyFtnb8Al3t_x3D8DpBTHrro4XNxvQwTFEzUtUlJSqDcg_aPD0G6PQY_NaEWVOid7b1zqTemdTZdg56Zzv3Ph8OTO0W3HvroDcDXw6AidZsumB66-M7VzGqFKOZu95za_9r_dcH0DaTEAJEMMGu84i8Vlcin_0HtgSVBQ</recordid><startdate>20051015</startdate><enddate>20051015</enddate><creator>Ozsahin, Mahmut</creator><creator>Crompton, Nigel E A</creator><creator>Gourgou, Sophie</creator><creator>Kramar, Andrew</creator><creator>Li, Ling</creator><creator>Shi, YuQuan</creator><creator>Sozzi, Wendy Jeanneret</creator><creator>Zouhair, Abderrahim</creator><creator>Mirimanoff, René O</creator><creator>Azria, David</creator><general>American Association for Cancer Research</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7U7</scope><scope>C1K</scope><scope>H94</scope></search><sort><creationdate>20051015</creationdate><title>CD4 and CD8 T-Lymphocyte Apoptosis Can Predict Radiation-Induced Late Toxicity: A Prospective Study in 399 Patients</title><author>Ozsahin, Mahmut ; Crompton, Nigel E A ; Gourgou, Sophie ; Kramar, Andrew ; Li, Ling ; Shi, YuQuan ; Sozzi, Wendy Jeanneret ; Zouhair, Abderrahim ; Mirimanoff, René O ; Azria, David</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c454t-9b534d2ed53db22dcbac1d2b5ff1f5969393530ae058450d82224be617dceb9d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Apoptosis - radiation effects</topic><topic>Biological and medical sciences</topic><topic>CD4-Positive T-Lymphocytes - pathology</topic><topic>CD4-Positive T-Lymphocytes - radiation effects</topic><topic>CD8-Positive T-Lymphocytes - pathology</topic><topic>CD8-Positive T-Lymphocytes - radiation effects</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Humans</topic><topic>Lymphocyte Apoptosis</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Neoplasms - blood</topic><topic>Neoplasms - pathology</topic><topic>Neoplasms - radiotherapy</topic><topic>Normal-Tissue Radiosensitivity</topic><topic>Predictive Assay</topic><topic>Predictive Value of Tests</topic><topic>Prospective Studies</topic><topic>Radiation Theraphy</topic><topic>Radiation therapy and radiosensitizing agent</topic><topic>Survival Analysis</topic><topic>Treatment Outcome</topic><topic>Treatment with physical agents</topic><topic>Treatment. General aspects</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ozsahin, Mahmut</creatorcontrib><creatorcontrib>Crompton, Nigel E A</creatorcontrib><creatorcontrib>Gourgou, Sophie</creatorcontrib><creatorcontrib>Kramar, Andrew</creatorcontrib><creatorcontrib>Li, Ling</creatorcontrib><creatorcontrib>Shi, YuQuan</creatorcontrib><creatorcontrib>Sozzi, Wendy Jeanneret</creatorcontrib><creatorcontrib>Zouhair, Abderrahim</creatorcontrib><creatorcontrib>Mirimanoff, René O</creatorcontrib><creatorcontrib>Azria, David</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ozsahin, Mahmut</au><au>Crompton, Nigel E A</au><au>Gourgou, Sophie</au><au>Kramar, Andrew</au><au>Li, Ling</au><au>Shi, YuQuan</au><au>Sozzi, Wendy Jeanneret</au><au>Zouhair, Abderrahim</au><au>Mirimanoff, René O</au><au>Azria, David</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>CD4 and CD8 T-Lymphocyte Apoptosis Can Predict Radiation-Induced Late Toxicity: A Prospective Study in 399 Patients</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2005-10-15</date><risdate>2005</risdate><volume>11</volume><issue>20</issue><spage>7426</spage><epage>7433</epage><pages>7426-7433</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>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.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>16243816</pmid><doi>10.1158/1078-0432.CCR-04-2634</doi><tpages>8</tpages></addata></record> |
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| source | Freely Accessible Science Journals - check A-Z of ejournals |
| 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 |
| title | CD4 and CD8 T-Lymphocyte Apoptosis Can Predict Radiation-Induced Late Toxicity: A Prospective Study in 399 Patients |
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