The Impact of Individual In Vivo Repair of DNA Double-Strand Breaks on Oral Mucositis in Adjuvant Radiotherapy of Head-and-Neck Cancer

Purpose To evaluate the impact of individual in vivo DNA double-strand break (DSB) repair capacity on the incidence of severe oral mucositis in patients with head-and-neck cancer undergoing adjuvant radiotherapy (RT) or radiochemotherapy (RCT). Patients and Methods Thirty-one patients with resected...

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Veröffentlicht in:International journal of radiation oncology, biology, physics biology, physics, 2011-12, Vol.81 (5), p.1465-1472
Hauptverfasser: Fleckenstein, Jochen, M.D, Kühne, Martin, Ph.D, Seegmüller, Katharina, M.D, Derschang, Sarah, M.D, Melchior, Patrick, M.D, Gräber, Stefan, M.D., Ph.D, Fricke, Andreas, Ph.D, Rübe, Claudia E., M.D., Ph.D, Rübe, Christian, M.D., Ph.D
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container_end_page 1472
container_issue 5
container_start_page 1465
container_title International journal of radiation oncology, biology, physics
container_volume 81
creator Fleckenstein, Jochen, M.D
Kühne, Martin, Ph.D
Seegmüller, Katharina, M.D
Derschang, Sarah, M.D
Melchior, Patrick, M.D
Gräber, Stefan, M.D., Ph.D
Fricke, Andreas, Ph.D
Rübe, Claudia E., M.D., Ph.D
Rübe, Christian, M.D., Ph.D
description Purpose To evaluate the impact of individual in vivo DNA double-strand break (DSB) repair capacity on the incidence of severe oral mucositis in patients with head-and-neck cancer undergoing adjuvant radiotherapy (RT) or radiochemotherapy (RCT). Patients and Methods Thirty-one patients with resected head-and-neck cancer undergoing adjuvant RT or RCT were examined. Patients underwent RT of the primary tumor site and locoregional lymph nodes with a total dose of 60–66 Gy (single dose 2 Gy, five fractions per week). Chemotherapy consisted of two cycles of cisplatin and 5-fluorouracil. To assess DSB repair, γ-H2AX foci in blood lymphocytes were quantified before and 0.5 h, 2.5 h, 5 h, and 24 h after in vivo radiation exposure (the first fraction of RT). World Health Organization scores for oral mucositis were documented weekly and correlated with DSB repair. Results Sixteen patients received RT alone; 15 patients received RCT. In patients who developed Grade ≥ 3 mucositis ( n = 18) the amount of unrepaired DSBs 24 h after radiation exposure and DSB repair half-times did not differ significantly from patients with Grade ≤2 mucositis ( n = 13). Patients with a proportion of unrepaired DSBs after 24 h higher than the mean value + one standard deviation had an increased incidence of severe oral mucositis. Conclusions Evaluation of in vivo DSB repair by determination of γ-H2AX foci loss is feasible in clinical practice and allows identification of patients with impaired DSB repair. The incidence of oral mucositis is not closely correlated with DSB repair under the evaluated conditions.
doi_str_mv 10.1016/j.ijrobp.2010.08.004
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Patients and Methods Thirty-one patients with resected head-and-neck cancer undergoing adjuvant RT or RCT were examined. Patients underwent RT of the primary tumor site and locoregional lymph nodes with a total dose of 60–66 Gy (single dose 2 Gy, five fractions per week). Chemotherapy consisted of two cycles of cisplatin and 5-fluorouracil. To assess DSB repair, γ-H2AX foci in blood lymphocytes were quantified before and 0.5 h, 2.5 h, 5 h, and 24 h after in vivo radiation exposure (the first fraction of RT). World Health Organization scores for oral mucositis were documented weekly and correlated with DSB repair. Results Sixteen patients received RT alone; 15 patients received RCT. In patients who developed Grade ≥ 3 mucositis ( n = 18) the amount of unrepaired DSBs 24 h after radiation exposure and DSB repair half-times did not differ significantly from patients with Grade ≤2 mucositis ( n = 13). Patients with a proportion of unrepaired DSBs after 24 h higher than the mean value + one standard deviation had an increased incidence of severe oral mucositis. Conclusions Evaluation of in vivo DSB repair by determination of γ-H2AX foci loss is feasible in clinical practice and allows identification of patients with impaired DSB repair. The incidence of oral mucositis is not closely correlated with DSB repair under the evaluated conditions.</description><identifier>ISSN: 0360-3016</identifier><identifier>EISSN: 1879-355X</identifier><identifier>DOI: 10.1016/j.ijrobp.2010.08.004</identifier><identifier>PMID: 20947264</identifier><identifier>CODEN: IOBPD3</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Biological and medical sciences ; Biomarkers - blood ; Chemoradiotherapy - adverse effects ; CHEMOTHERAPY ; Cisplatin - administration &amp; dosage ; DNA ; DNA Breaks, Double-Stranded ; DNA REPAIR ; DNA Repair - physiology ; Facial bones, jaws, teeth, parodontium: diseases, semeiology ; Female ; Fluorouracil - administration &amp; dosage ; HEAD ; Head and Neck Neoplasms - drug therapy ; Head and Neck Neoplasms - genetics ; Head and Neck Neoplasms - pathology ; Head and Neck Neoplasms - radiotherapy ; Hematology, Oncology and Palliative Medicine ; Histones - blood ; Humans ; IN VIVO ; Incidence ; IRRADIATION ; LYMPH NODES ; Lymphatic Irradiation - adverse effects ; LYMPHOCYTES ; Male ; Medical sciences ; Middle Aged ; NECK ; NEOPLASMS ; Non tumoral diseases ; Oral mucositis ; Otorhinolaryngology (head neck, general aspects and miscellaneous) ; Otorhinolaryngology. Stomatology ; PATIENTS ; Predictive test ; RADIATION DOSES ; Radiation Tolerance ; Radiology ; RADIOLOGY AND NUCLEAR MEDICINE ; RADIOSENSITIVITY ; RADIOTHERAPY ; Radiotherapy, Adjuvant - adverse effects ; Stomatitis - epidemiology ; Stomatitis - genetics ; STRAND BREAKS ; Time Factors ; Tumors ; URACILS</subject><ispartof>International journal of radiation oncology, biology, physics, 2011-12, Vol.81 (5), p.1465-1472</ispartof><rights>Elsevier Inc.</rights><rights>2011 Elsevier Inc.</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2011 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c506t-970142de6fe3077f5d3def0e31db04059041f4cb7f66609f9a4063f5eb73da03</citedby><cites>FETCH-LOGICAL-c506t-970142de6fe3077f5d3def0e31db04059041f4cb7f66609f9a4063f5eb73da03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ijrobp.2010.08.004$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=25274273$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20947264$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/22054507$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Fleckenstein, Jochen, M.D</creatorcontrib><creatorcontrib>Kühne, Martin, Ph.D</creatorcontrib><creatorcontrib>Seegmüller, Katharina, M.D</creatorcontrib><creatorcontrib>Derschang, Sarah, M.D</creatorcontrib><creatorcontrib>Melchior, Patrick, M.D</creatorcontrib><creatorcontrib>Gräber, Stefan, M.D., Ph.D</creatorcontrib><creatorcontrib>Fricke, Andreas, Ph.D</creatorcontrib><creatorcontrib>Rübe, Claudia E., M.D., Ph.D</creatorcontrib><creatorcontrib>Rübe, Christian, M.D., Ph.D</creatorcontrib><title>The Impact of Individual In Vivo Repair of DNA Double-Strand Breaks on Oral Mucositis in Adjuvant Radiotherapy of Head-and-Neck Cancer</title><title>International journal of radiation oncology, biology, physics</title><addtitle>Int J Radiat Oncol Biol Phys</addtitle><description>Purpose To evaluate the impact of individual in vivo DNA double-strand break (DSB) repair capacity on the incidence of severe oral mucositis in patients with head-and-neck cancer undergoing adjuvant radiotherapy (RT) or radiochemotherapy (RCT). Patients and Methods Thirty-one patients with resected head-and-neck cancer undergoing adjuvant RT or RCT were examined. Patients underwent RT of the primary tumor site and locoregional lymph nodes with a total dose of 60–66 Gy (single dose 2 Gy, five fractions per week). Chemotherapy consisted of two cycles of cisplatin and 5-fluorouracil. To assess DSB repair, γ-H2AX foci in blood lymphocytes were quantified before and 0.5 h, 2.5 h, 5 h, and 24 h after in vivo radiation exposure (the first fraction of RT). World Health Organization scores for oral mucositis were documented weekly and correlated with DSB repair. Results Sixteen patients received RT alone; 15 patients received RCT. In patients who developed Grade ≥ 3 mucositis ( n = 18) the amount of unrepaired DSBs 24 h after radiation exposure and DSB repair half-times did not differ significantly from patients with Grade ≤2 mucositis ( n = 13). Patients with a proportion of unrepaired DSBs after 24 h higher than the mean value + one standard deviation had an increased incidence of severe oral mucositis. Conclusions Evaluation of in vivo DSB repair by determination of γ-H2AX foci loss is feasible in clinical practice and allows identification of patients with impaired DSB repair. The incidence of oral mucositis is not closely correlated with DSB repair under the evaluated conditions.</description><subject>Adult</subject><subject>Aged</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Biomarkers - blood</subject><subject>Chemoradiotherapy - adverse effects</subject><subject>CHEMOTHERAPY</subject><subject>Cisplatin - administration &amp; dosage</subject><subject>DNA</subject><subject>DNA Breaks, Double-Stranded</subject><subject>DNA REPAIR</subject><subject>DNA Repair - physiology</subject><subject>Facial bones, jaws, teeth, parodontium: diseases, semeiology</subject><subject>Female</subject><subject>Fluorouracil - administration &amp; dosage</subject><subject>HEAD</subject><subject>Head and Neck Neoplasms - drug therapy</subject><subject>Head and Neck Neoplasms - genetics</subject><subject>Head and Neck Neoplasms - pathology</subject><subject>Head and Neck Neoplasms - radiotherapy</subject><subject>Hematology, Oncology and Palliative Medicine</subject><subject>Histones - blood</subject><subject>Humans</subject><subject>IN VIVO</subject><subject>Incidence</subject><subject>IRRADIATION</subject><subject>LYMPH NODES</subject><subject>Lymphatic Irradiation - adverse effects</subject><subject>LYMPHOCYTES</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>NECK</subject><subject>NEOPLASMS</subject><subject>Non tumoral diseases</subject><subject>Oral mucositis</subject><subject>Otorhinolaryngology (head neck, general aspects and miscellaneous)</subject><subject>Otorhinolaryngology. 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Stomatology</topic><topic>PATIENTS</topic><topic>Predictive test</topic><topic>RADIATION DOSES</topic><topic>Radiation Tolerance</topic><topic>Radiology</topic><topic>RADIOLOGY AND NUCLEAR MEDICINE</topic><topic>RADIOSENSITIVITY</topic><topic>RADIOTHERAPY</topic><topic>Radiotherapy, Adjuvant - adverse effects</topic><topic>Stomatitis - epidemiology</topic><topic>Stomatitis - genetics</topic><topic>STRAND BREAKS</topic><topic>Time Factors</topic><topic>Tumors</topic><topic>URACILS</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fleckenstein, Jochen, M.D</creatorcontrib><creatorcontrib>Kühne, Martin, Ph.D</creatorcontrib><creatorcontrib>Seegmüller, Katharina, M.D</creatorcontrib><creatorcontrib>Derschang, Sarah, M.D</creatorcontrib><creatorcontrib>Melchior, Patrick, M.D</creatorcontrib><creatorcontrib>Gräber, Stefan, M.D., Ph.D</creatorcontrib><creatorcontrib>Fricke, Andreas, Ph.D</creatorcontrib><creatorcontrib>Rübe, Claudia E., M.D., Ph.D</creatorcontrib><creatorcontrib>Rübe, Christian, M.D., Ph.D</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>MEDLINE - Academic</collection><collection>Nucleic Acids Abstracts</collection><collection>OSTI.GOV</collection><jtitle>International journal of radiation oncology, biology, physics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fleckenstein, Jochen, M.D</au><au>Kühne, Martin, Ph.D</au><au>Seegmüller, Katharina, M.D</au><au>Derschang, Sarah, M.D</au><au>Melchior, Patrick, M.D</au><au>Gräber, Stefan, M.D., Ph.D</au><au>Fricke, Andreas, Ph.D</au><au>Rübe, Claudia E., M.D., Ph.D</au><au>Rübe, Christian, M.D., Ph.D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Impact of Individual In Vivo Repair of DNA Double-Strand Breaks on Oral Mucositis in Adjuvant Radiotherapy of Head-and-Neck Cancer</atitle><jtitle>International journal of radiation oncology, biology, physics</jtitle><addtitle>Int J Radiat Oncol Biol Phys</addtitle><date>2011-12-01</date><risdate>2011</risdate><volume>81</volume><issue>5</issue><spage>1465</spage><epage>1472</epage><pages>1465-1472</pages><issn>0360-3016</issn><eissn>1879-355X</eissn><coden>IOBPD3</coden><abstract>Purpose To evaluate the impact of individual in vivo DNA double-strand break (DSB) repair capacity on the incidence of severe oral mucositis in patients with head-and-neck cancer undergoing adjuvant radiotherapy (RT) or radiochemotherapy (RCT). Patients and Methods Thirty-one patients with resected head-and-neck cancer undergoing adjuvant RT or RCT were examined. Patients underwent RT of the primary tumor site and locoregional lymph nodes with a total dose of 60–66 Gy (single dose 2 Gy, five fractions per week). Chemotherapy consisted of two cycles of cisplatin and 5-fluorouracil. To assess DSB repair, γ-H2AX foci in blood lymphocytes were quantified before and 0.5 h, 2.5 h, 5 h, and 24 h after in vivo radiation exposure (the first fraction of RT). World Health Organization scores for oral mucositis were documented weekly and correlated with DSB repair. Results Sixteen patients received RT alone; 15 patients received RCT. In patients who developed Grade ≥ 3 mucositis ( n = 18) the amount of unrepaired DSBs 24 h after radiation exposure and DSB repair half-times did not differ significantly from patients with Grade ≤2 mucositis ( n = 13). Patients with a proportion of unrepaired DSBs after 24 h higher than the mean value + one standard deviation had an increased incidence of severe oral mucositis. Conclusions Evaluation of in vivo DSB repair by determination of γ-H2AX foci loss is feasible in clinical practice and allows identification of patients with impaired DSB repair. The incidence of oral mucositis is not closely correlated with DSB repair under the evaluated conditions.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>20947264</pmid><doi>10.1016/j.ijrobp.2010.08.004</doi><tpages>8</tpages></addata></record>
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identifier ISSN: 0360-3016
ispartof International journal of radiation oncology, biology, physics, 2011-12, Vol.81 (5), p.1465-1472
issn 0360-3016
1879-355X
language eng
recordid cdi_osti_scitechconnect_22054507
source MEDLINE; Elsevier ScienceDirect Journals Complete
subjects Adult
Aged
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Biological and medical sciences
Biomarkers - blood
Chemoradiotherapy - adverse effects
CHEMOTHERAPY
Cisplatin - administration & dosage
DNA
DNA Breaks, Double-Stranded
DNA REPAIR
DNA Repair - physiology
Facial bones, jaws, teeth, parodontium: diseases, semeiology
Female
Fluorouracil - administration & dosage
HEAD
Head and Neck Neoplasms - drug therapy
Head and Neck Neoplasms - genetics
Head and Neck Neoplasms - pathology
Head and Neck Neoplasms - radiotherapy
Hematology, Oncology and Palliative Medicine
Histones - blood
Humans
IN VIVO
Incidence
IRRADIATION
LYMPH NODES
Lymphatic Irradiation - adverse effects
LYMPHOCYTES
Male
Medical sciences
Middle Aged
NECK
NEOPLASMS
Non tumoral diseases
Oral mucositis
Otorhinolaryngology (head neck, general aspects and miscellaneous)
Otorhinolaryngology. Stomatology
PATIENTS
Predictive test
RADIATION DOSES
Radiation Tolerance
Radiology
RADIOLOGY AND NUCLEAR MEDICINE
RADIOSENSITIVITY
RADIOTHERAPY
Radiotherapy, Adjuvant - adverse effects
Stomatitis - epidemiology
Stomatitis - genetics
STRAND BREAKS
Time Factors
Tumors
URACILS
title The Impact of Individual In Vivo Repair of DNA Double-Strand Breaks on Oral Mucositis in Adjuvant Radiotherapy of Head-and-Neck Cancer
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