Age and Comorbid Illness Are Associated With Late Rectal Toxicity Following Dose-Escalated Radiation Therapy for Prostate Cancer

Purpose To assess the impacts of patient age and comorbid illness on rectal toxicity following external beam radiation therapy (EBRT) for prostate cancer and to assess the Qualitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) normal tissue complication probability (NTCP) model in thi...

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Veröffentlicht in:International journal of radiation oncology, biology, physics biology, physics, 2013-04, Vol.85 (5), p.1246-1253
Hauptverfasser: Hamstra, Daniel A., MD, PhD, Stenmark, Matt H., MD, Ritter, Tim, PhD, Litzenberg, Dale, PhD, Jackson, William, BS, Johnson, Skyler, BS, Albrecht-Unger, Liesel, BS, Donaghy, Alex, BS, Phelps, Laura, BS, Blas, Kevin, MD, Halverson, Schuyler, BS, Marsh, Robin, CMD, Olson, Karin, PhD, Feng, Felix Y., MD
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container_end_page 1253
container_issue 5
container_start_page 1246
container_title International journal of radiation oncology, biology, physics
container_volume 85
creator Hamstra, Daniel A., MD, PhD
Stenmark, Matt H., MD
Ritter, Tim, PhD
Litzenberg, Dale, PhD
Jackson, William, BS
Johnson, Skyler, BS
Albrecht-Unger, Liesel, BS
Donaghy, Alex, BS
Phelps, Laura, BS
Blas, Kevin, MD
Halverson, Schuyler, BS
Marsh, Robin, CMD
Olson, Karin, PhD
Feng, Felix Y., MD
description Purpose To assess the impacts of patient age and comorbid illness on rectal toxicity following external beam radiation therapy (EBRT) for prostate cancer and to assess the Qualitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) normal tissue complication probability (NTCP) model in this context. Methods and Materials Rectal toxicity was analyzed in 718 men previously treated for prostate cancer with EBRT (≥75 Gy). Comorbid illness was scored using the Charlson Comorbidity Index (CCMI), and the NTCP was evaluated with the QUANTEC model. The influence of clinical and treatment-related parameters on rectal toxicity was assessed by Kaplan-Meier and Cox proportional hazards models. Results The cumulative incidence of rectal toxicity grade ≥2 was 9.5% and 11.6% at 3 and 5 years and 3.3% and 3.9% at 3 and 5 years for grade ≥3 toxicity, respectively. Each year of age predicted an increasing relative risk of grade ≥2 ( P
doi_str_mv 10.1016/j.ijrobp.2012.10.042
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Methods and Materials Rectal toxicity was analyzed in 718 men previously treated for prostate cancer with EBRT (≥75 Gy). Comorbid illness was scored using the Charlson Comorbidity Index (CCMI), and the NTCP was evaluated with the QUANTEC model. The influence of clinical and treatment-related parameters on rectal toxicity was assessed by Kaplan-Meier and Cox proportional hazards models. Results The cumulative incidence of rectal toxicity grade ≥2 was 9.5% and 11.6% at 3 and 5 years and 3.3% and 3.9% at 3 and 5 years for grade ≥3 toxicity, respectively. Each year of age predicted an increasing relative risk of grade ≥2 ( P <.03; hazard ratio [HR], 1.04 [95% confidence interval {CI}, 1.01-1.06]) and ≥3 rectal toxicity ( P <.0001; HR, 1.14 [95% CI,1.07-1.22]). Increasing CCMI predicted rectal toxicity where a history of either myocardial infarction (MI) ( P <.0001; HR, 5.1 [95% CI, 1.9-13.7]) or congestive heart failure (CHF) ( P <.0006; HR, 5.4 [95% CI, 0.6-47.5]) predicted grade ≥3 rectal toxicity, with lesser correlation with grade ≥2 toxicity ( P <.02 for MI, and P <.09 for CHF). An age comorbidity model to predict rectal toxicity was developed and confirmed in a validation cohort. The use of anticoagulants increased toxicity independent of age and comorbidity. NTCP was prognostic for grade ≥3 ( P =.015) but not grade ≥2 ( P =.49) toxicity. On multivariate analysis, age, MI, CHF, and an NTCP >20% all correlated with late rectal toxicity. Conclusions Patient age and a history of MI or CHF significantly impact rectal toxicity following EBRT for the treatment of prostate cancer, even after controlling for NTCP.]]></description><identifier>ISSN: 0360-3016</identifier><identifier>EISSN: 1879-355X</identifier><identifier>DOI: 10.1016/j.ijrobp.2012.10.042</identifier><identifier>PMID: 23265567</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Age Factors ; Aged ; Aged, 80 and over ; ANIMAL TISSUES ; ANTICOAGULANTS ; Anticoagulants - administration &amp; dosage ; Anticoagulants - adverse effects ; Comorbidity ; EXTERNAL BEAM RADIATION THERAPY ; HEALTH HAZARDS ; HEART FAILURE ; Heart Failure - epidemiology ; Hematology, Oncology and Palliative Medicine ; Humans ; Incidence ; Male ; Middle Aged ; Models, Statistical ; MULTIVARIATE ANALYSIS ; MYOCARDIAL INFARCTION ; Myocardial Infarction - epidemiology ; NEOPLASMS ; Organs at Risk - radiation effects ; PATIENTS ; PROSTATE ; Prostatic Neoplasms - epidemiology ; Prostatic Neoplasms - radiotherapy ; RADIATION DOSES ; Radiation Injuries - epidemiology ; Radiation Injuries - pathology ; Radiology ; RADIOLOGY AND NUCLEAR MEDICINE ; Radiotherapy Dosage ; Radiotherapy, Image-Guided ; Radiotherapy, Intensity-Modulated ; RECTUM ; Rectum - radiation effects ; Time Factors ; TOXICITY</subject><ispartof>International journal of radiation oncology, biology, physics, 2013-04, Vol.85 (5), p.1246-1253</ispartof><rights>Elsevier Inc.</rights><rights>2013 Elsevier Inc.</rights><rights>Copyright © 2013 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c445t-fbd5e2174e991802a45ba43bcea2c37c064f1b8a21c88837d9bbaf0e05fbf4393</citedby><cites>FETCH-LOGICAL-c445t-fbd5e2174e991802a45ba43bcea2c37c064f1b8a21c88837d9bbaf0e05fbf4393</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.2012.10.042$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,315,781,785,886,3551,27926,27927,45997</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23265567$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/22224411$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Hamstra, Daniel A., MD, PhD</creatorcontrib><creatorcontrib>Stenmark, Matt H., MD</creatorcontrib><creatorcontrib>Ritter, Tim, PhD</creatorcontrib><creatorcontrib>Litzenberg, Dale, PhD</creatorcontrib><creatorcontrib>Jackson, William, BS</creatorcontrib><creatorcontrib>Johnson, Skyler, BS</creatorcontrib><creatorcontrib>Albrecht-Unger, Liesel, BS</creatorcontrib><creatorcontrib>Donaghy, Alex, BS</creatorcontrib><creatorcontrib>Phelps, Laura, BS</creatorcontrib><creatorcontrib>Blas, Kevin, MD</creatorcontrib><creatorcontrib>Halverson, Schuyler, BS</creatorcontrib><creatorcontrib>Marsh, Robin, CMD</creatorcontrib><creatorcontrib>Olson, Karin, PhD</creatorcontrib><creatorcontrib>Feng, Felix Y., MD</creatorcontrib><title>Age and Comorbid Illness Are Associated With Late Rectal Toxicity Following Dose-Escalated Radiation Therapy for Prostate Cancer</title><title>International journal of radiation oncology, biology, physics</title><addtitle>Int J Radiat Oncol Biol Phys</addtitle><description><![CDATA[Purpose To assess the impacts of patient age and comorbid illness on rectal toxicity following external beam radiation therapy (EBRT) for prostate cancer and to assess the Qualitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) normal tissue complication probability (NTCP) model in this context. Methods and Materials Rectal toxicity was analyzed in 718 men previously treated for prostate cancer with EBRT (≥75 Gy). Comorbid illness was scored using the Charlson Comorbidity Index (CCMI), and the NTCP was evaluated with the QUANTEC model. The influence of clinical and treatment-related parameters on rectal toxicity was assessed by Kaplan-Meier and Cox proportional hazards models. Results The cumulative incidence of rectal toxicity grade ≥2 was 9.5% and 11.6% at 3 and 5 years and 3.3% and 3.9% at 3 and 5 years for grade ≥3 toxicity, respectively. Each year of age predicted an increasing relative risk of grade ≥2 ( P <.03; hazard ratio [HR], 1.04 [95% confidence interval {CI}, 1.01-1.06]) and ≥3 rectal toxicity ( P <.0001; HR, 1.14 [95% CI,1.07-1.22]). Increasing CCMI predicted rectal toxicity where a history of either myocardial infarction (MI) ( P <.0001; HR, 5.1 [95% CI, 1.9-13.7]) or congestive heart failure (CHF) ( P <.0006; HR, 5.4 [95% CI, 0.6-47.5]) predicted grade ≥3 rectal toxicity, with lesser correlation with grade ≥2 toxicity ( P <.02 for MI, and P <.09 for CHF). An age comorbidity model to predict rectal toxicity was developed and confirmed in a validation cohort. The use of anticoagulants increased toxicity independent of age and comorbidity. NTCP was prognostic for grade ≥3 ( P =.015) but not grade ≥2 ( P =.49) toxicity. On multivariate analysis, age, MI, CHF, and an NTCP >20% all correlated with late rectal toxicity. Conclusions Patient age and a history of MI or CHF significantly impact rectal toxicity following EBRT for the treatment of prostate cancer, even after controlling for NTCP.]]></description><subject>Age Factors</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>ANIMAL TISSUES</subject><subject>ANTICOAGULANTS</subject><subject>Anticoagulants - administration &amp; dosage</subject><subject>Anticoagulants - adverse effects</subject><subject>Comorbidity</subject><subject>EXTERNAL BEAM RADIATION THERAPY</subject><subject>HEALTH HAZARDS</subject><subject>HEART FAILURE</subject><subject>Heart Failure - epidemiology</subject><subject>Hematology, Oncology and Palliative Medicine</subject><subject>Humans</subject><subject>Incidence</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Models, Statistical</subject><subject>MULTIVARIATE ANALYSIS</subject><subject>MYOCARDIAL INFARCTION</subject><subject>Myocardial Infarction - epidemiology</subject><subject>NEOPLASMS</subject><subject>Organs at Risk - radiation effects</subject><subject>PATIENTS</subject><subject>PROSTATE</subject><subject>Prostatic Neoplasms - epidemiology</subject><subject>Prostatic Neoplasms - radiotherapy</subject><subject>RADIATION DOSES</subject><subject>Radiation Injuries - epidemiology</subject><subject>Radiation Injuries - pathology</subject><subject>Radiology</subject><subject>RADIOLOGY AND NUCLEAR MEDICINE</subject><subject>Radiotherapy Dosage</subject><subject>Radiotherapy, Image-Guided</subject><subject>Radiotherapy, Intensity-Modulated</subject><subject>RECTUM</subject><subject>Rectum - radiation effects</subject><subject>Time Factors</subject><subject>TOXICITY</subject><issn>0360-3016</issn><issn>1879-355X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUtvEzEUhS0EoqHwDxCyxHqCX_PaIEWhpZUigdogurP8uNN4mNiRPQWy60_Hw7Qs2NQbW1fn3HvuZ4TeUrKkhFYf-qXrY9CHJSOU5dKSCPYMLWhTtwUvy5vnaEF4RQqexSfoVUo9IYTSWrxEJ4yzqiyreoHuV7eAlbd4HfYhamfx5TB4SAmvIuBVSsE4NYLF3924w5v8xFdgRjXgbfjtjBuP-DwMQ_jl_C3-FBIUZ8mo4a_lStnsdcHj7Q6iOhxxFyL-GkMapz5r5Q3E1-hFp4YEbx7uU_Tt_Gy7vig2Xz5frlebwghRjkWnbQksp4e2pQ1hSpRaCa4NKGZ4bUglOqobxahpmobXttVadQRI2elO8Jafovdz3zzdyZSTg9mZ4H3eRrJ8hKA0q8SsMjllitDJQ3R7FY-SEjlhl72cscsJ-1TN2LPt3Ww73Ok92H-mR85Z8HEWQF7xp4M4JYC8v3VxCmCDe2rC_w3M4LzLqH_AEVIf7qLP-CSViUkir6evn36eMsJrwW74Hz9Wq28</recordid><startdate>20130401</startdate><enddate>20130401</enddate><creator>Hamstra, Daniel A., MD, PhD</creator><creator>Stenmark, Matt H., MD</creator><creator>Ritter, Tim, PhD</creator><creator>Litzenberg, Dale, PhD</creator><creator>Jackson, William, BS</creator><creator>Johnson, Skyler, BS</creator><creator>Albrecht-Unger, Liesel, BS</creator><creator>Donaghy, Alex, BS</creator><creator>Phelps, Laura, BS</creator><creator>Blas, Kevin, MD</creator><creator>Halverson, Schuyler, BS</creator><creator>Marsh, Robin, CMD</creator><creator>Olson, Karin, PhD</creator><creator>Feng, Felix Y., MD</creator><general>Elsevier Inc</general><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>OTOTI</scope></search><sort><creationdate>20130401</creationdate><title>Age and Comorbid Illness Are Associated With Late Rectal Toxicity Following Dose-Escalated Radiation Therapy for Prostate Cancer</title><author>Hamstra, Daniel A., MD, PhD ; Stenmark, Matt H., MD ; Ritter, Tim, PhD ; Litzenberg, Dale, PhD ; Jackson, William, BS ; Johnson, Skyler, BS ; Albrecht-Unger, Liesel, BS ; Donaghy, Alex, BS ; Phelps, Laura, BS ; Blas, Kevin, MD ; Halverson, Schuyler, BS ; Marsh, Robin, CMD ; Olson, Karin, PhD ; Feng, Felix Y., MD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c445t-fbd5e2174e991802a45ba43bcea2c37c064f1b8a21c88837d9bbaf0e05fbf4393</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Age Factors</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>ANIMAL TISSUES</topic><topic>ANTICOAGULANTS</topic><topic>Anticoagulants - administration &amp; dosage</topic><topic>Anticoagulants - adverse effects</topic><topic>Comorbidity</topic><topic>EXTERNAL BEAM RADIATION THERAPY</topic><topic>HEALTH HAZARDS</topic><topic>HEART FAILURE</topic><topic>Heart Failure - epidemiology</topic><topic>Hematology, Oncology and Palliative Medicine</topic><topic>Humans</topic><topic>Incidence</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Models, Statistical</topic><topic>MULTIVARIATE ANALYSIS</topic><topic>MYOCARDIAL INFARCTION</topic><topic>Myocardial Infarction - epidemiology</topic><topic>NEOPLASMS</topic><topic>Organs at Risk - radiation effects</topic><topic>PATIENTS</topic><topic>PROSTATE</topic><topic>Prostatic Neoplasms - epidemiology</topic><topic>Prostatic Neoplasms - radiotherapy</topic><topic>RADIATION DOSES</topic><topic>Radiation Injuries - epidemiology</topic><topic>Radiation Injuries - pathology</topic><topic>Radiology</topic><topic>RADIOLOGY AND NUCLEAR MEDICINE</topic><topic>Radiotherapy Dosage</topic><topic>Radiotherapy, Image-Guided</topic><topic>Radiotherapy, Intensity-Modulated</topic><topic>RECTUM</topic><topic>Rectum - radiation effects</topic><topic>Time Factors</topic><topic>TOXICITY</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hamstra, Daniel A., MD, PhD</creatorcontrib><creatorcontrib>Stenmark, Matt H., MD</creatorcontrib><creatorcontrib>Ritter, Tim, PhD</creatorcontrib><creatorcontrib>Litzenberg, Dale, PhD</creatorcontrib><creatorcontrib>Jackson, William, BS</creatorcontrib><creatorcontrib>Johnson, Skyler, BS</creatorcontrib><creatorcontrib>Albrecht-Unger, Liesel, BS</creatorcontrib><creatorcontrib>Donaghy, Alex, BS</creatorcontrib><creatorcontrib>Phelps, Laura, BS</creatorcontrib><creatorcontrib>Blas, Kevin, MD</creatorcontrib><creatorcontrib>Halverson, Schuyler, BS</creatorcontrib><creatorcontrib>Marsh, Robin, CMD</creatorcontrib><creatorcontrib>Olson, Karin, PhD</creatorcontrib><creatorcontrib>Feng, Felix Y., MD</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</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>Hamstra, Daniel A., MD, PhD</au><au>Stenmark, Matt H., MD</au><au>Ritter, Tim, PhD</au><au>Litzenberg, Dale, PhD</au><au>Jackson, William, BS</au><au>Johnson, Skyler, BS</au><au>Albrecht-Unger, Liesel, BS</au><au>Donaghy, Alex, BS</au><au>Phelps, Laura, BS</au><au>Blas, Kevin, MD</au><au>Halverson, Schuyler, BS</au><au>Marsh, Robin, CMD</au><au>Olson, Karin, PhD</au><au>Feng, Felix Y., MD</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Age and Comorbid Illness Are Associated With Late Rectal Toxicity Following Dose-Escalated Radiation Therapy for Prostate Cancer</atitle><jtitle>International journal of radiation oncology, biology, physics</jtitle><addtitle>Int J Radiat Oncol Biol Phys</addtitle><date>2013-04-01</date><risdate>2013</risdate><volume>85</volume><issue>5</issue><spage>1246</spage><epage>1253</epage><pages>1246-1253</pages><issn>0360-3016</issn><eissn>1879-355X</eissn><abstract><![CDATA[Purpose To assess the impacts of patient age and comorbid illness on rectal toxicity following external beam radiation therapy (EBRT) for prostate cancer and to assess the Qualitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) normal tissue complication probability (NTCP) model in this context. Methods and Materials Rectal toxicity was analyzed in 718 men previously treated for prostate cancer with EBRT (≥75 Gy). Comorbid illness was scored using the Charlson Comorbidity Index (CCMI), and the NTCP was evaluated with the QUANTEC model. The influence of clinical and treatment-related parameters on rectal toxicity was assessed by Kaplan-Meier and Cox proportional hazards models. Results The cumulative incidence of rectal toxicity grade ≥2 was 9.5% and 11.6% at 3 and 5 years and 3.3% and 3.9% at 3 and 5 years for grade ≥3 toxicity, respectively. Each year of age predicted an increasing relative risk of grade ≥2 ( P <.03; hazard ratio [HR], 1.04 [95% confidence interval {CI}, 1.01-1.06]) and ≥3 rectal toxicity ( P <.0001; HR, 1.14 [95% CI,1.07-1.22]). Increasing CCMI predicted rectal toxicity where a history of either myocardial infarction (MI) ( P <.0001; HR, 5.1 [95% CI, 1.9-13.7]) or congestive heart failure (CHF) ( P <.0006; HR, 5.4 [95% CI, 0.6-47.5]) predicted grade ≥3 rectal toxicity, with lesser correlation with grade ≥2 toxicity ( P <.02 for MI, and P <.09 for CHF). An age comorbidity model to predict rectal toxicity was developed and confirmed in a validation cohort. The use of anticoagulants increased toxicity independent of age and comorbidity. NTCP was prognostic for grade ≥3 ( P =.015) but not grade ≥2 ( P =.49) toxicity. On multivariate analysis, age, MI, CHF, and an NTCP >20% all correlated with late rectal toxicity. Conclusions Patient age and a history of MI or CHF significantly impact rectal toxicity following EBRT for the treatment of prostate cancer, even after controlling for NTCP.]]></abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>23265567</pmid><doi>10.1016/j.ijrobp.2012.10.042</doi><tpages>8</tpages></addata></record>
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identifier ISSN: 0360-3016
ispartof International journal of radiation oncology, biology, physics, 2013-04, Vol.85 (5), p.1246-1253
issn 0360-3016
1879-355X
language eng
recordid cdi_osti_scitechconnect_22224411
source MEDLINE; Access via ScienceDirect (Elsevier)
subjects Age Factors
Aged
Aged, 80 and over
ANIMAL TISSUES
ANTICOAGULANTS
Anticoagulants - administration & dosage
Anticoagulants - adverse effects
Comorbidity
EXTERNAL BEAM RADIATION THERAPY
HEALTH HAZARDS
HEART FAILURE
Heart Failure - epidemiology
Hematology, Oncology and Palliative Medicine
Humans
Incidence
Male
Middle Aged
Models, Statistical
MULTIVARIATE ANALYSIS
MYOCARDIAL INFARCTION
Myocardial Infarction - epidemiology
NEOPLASMS
Organs at Risk - radiation effects
PATIENTS
PROSTATE
Prostatic Neoplasms - epidemiology
Prostatic Neoplasms - radiotherapy
RADIATION DOSES
Radiation Injuries - epidemiology
Radiation Injuries - pathology
Radiology
RADIOLOGY AND NUCLEAR MEDICINE
Radiotherapy Dosage
Radiotherapy, Image-Guided
Radiotherapy, Intensity-Modulated
RECTUM
Rectum - radiation effects
Time Factors
TOXICITY
title Age and Comorbid Illness Are Associated With Late Rectal Toxicity Following Dose-Escalated Radiation Therapy for Prostate Cancer
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