Tumor Response and Progression-Free Survival as Potential Surrogate Endpoints for Overall Survival in Extensive Stage Small-Cell Lung Cancer: Findings on the Basis of North Central Cancer Treatment Group Trials
The authors investigated the putative surrogate endpoints of best response, complete response (CR), confirmed response, and progression-free survival (PFS) for associations with overall survival (OS), and as possible surrogate endpoints for OS. Individual patient data from 870 untreated extensive st...
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| Veröffentlicht in: | Cancer 2011-03, Vol.117 (6), p.1262-1271 |
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| creator | FOSTER, Nathan R YINGWEI QI QIAN SHI KROOK, James E KUGLER, John W JETT, James R MOLINA, Julian R SCHILD, Steven E ADJEI, Alex A MANDREKAR, Sumithra J |
| description | The authors investigated the putative surrogate endpoints of best response, complete response (CR), confirmed response, and progression-free survival (PFS) for associations with overall survival (OS), and as possible surrogate endpoints for OS.
Individual patient data from 870 untreated extensive stage small-cell lung cancer patients participating in 6 single-arm (274 patients) and 3 randomized trials (596 patients) were pooled. Patient-level associations between putative surrogate endpoints and OS were assessed by Cox models using landmark analyses. Trial-level surrogacy of putative surrogate endpoints were assessed by the association of treatment effects on OS and individual putative surrogate endpoints. Trial-level surrogacy measures included: R(2) from weighted least squares regression model, Spearman correlation coefficient, and R(2) from bivariate survival model (Copula R(2) ).
Median OS and PFS were 9.6 (95% confidence interval [CI], 9.1-10.0) and 5.5 (95% CI, 5.2-5.9) months, respectively; best response, CR, and confirmed response rates were 44%, 22%, and 34%, respectively. Patient-level associations showed that PFS status at 4 months was a strong predictor of subsequent survival (hazard ratio [HR], 0.42; 95% CI, 0.35-0.51; concordance index 0.63; P < .01), with 6-month PFS being the strongest (HR, 0.41; 95% CI, 0.35-0.49; concordance index, 0.66, P < .01). At the trial level, PFS showed the highest level of surrogacy for OS (weighted least squares R(2) = 0.79; Copula R(2) = 0.80), explaining 79% of the variance in OS. Tumor response endpoints showed lower surrogacy levels (weighted least squares R(2) ≤0.48).
PFS was strongly associated with OS at both the patient and trial levels. PFS also shows promise as a potential surrogate for OS, but further validation is needed using data from a larger number of randomized phase 3 trials. |
| doi_str_mv | 10.1002/cncr.25526 |
| format | Article |
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Individual patient data from 870 untreated extensive stage small-cell lung cancer patients participating in 6 single-arm (274 patients) and 3 randomized trials (596 patients) were pooled. Patient-level associations between putative surrogate endpoints and OS were assessed by Cox models using landmark analyses. Trial-level surrogacy of putative surrogate endpoints were assessed by the association of treatment effects on OS and individual putative surrogate endpoints. Trial-level surrogacy measures included: R(2) from weighted least squares regression model, Spearman correlation coefficient, and R(2) from bivariate survival model (Copula R(2) ).
Median OS and PFS were 9.6 (95% confidence interval [CI], 9.1-10.0) and 5.5 (95% CI, 5.2-5.9) months, respectively; best response, CR, and confirmed response rates were 44%, 22%, and 34%, respectively. Patient-level associations showed that PFS status at 4 months was a strong predictor of subsequent survival (hazard ratio [HR], 0.42; 95% CI, 0.35-0.51; concordance index 0.63; P < .01), with 6-month PFS being the strongest (HR, 0.41; 95% CI, 0.35-0.49; concordance index, 0.66, P < .01). At the trial level, PFS showed the highest level of surrogacy for OS (weighted least squares R(2) = 0.79; Copula R(2) = 0.80), explaining 79% of the variance in OS. Tumor response endpoints showed lower surrogacy levels (weighted least squares R(2) ≤0.48).
PFS was strongly associated with OS at both the patient and trial levels. PFS also shows promise as a potential surrogate for OS, but further validation is needed using data from a larger number of randomized phase 3 trials.</description><identifier>ISSN: 0008-543X</identifier><identifier>EISSN: 1097-0142</identifier><identifier>DOI: 10.1002/cncr.25526</identifier><identifier>PMID: 20960500</identifier><identifier>CODEN: CANCAR</identifier><language>eng</language><publisher>Hoboken, NJ: Wiley-Blackwell</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Biological and medical sciences ; Biomarkers - analysis ; Biomarkers, Tumor - analysis ; Clinical Trials, Phase II as Topic - statistics & numerical data ; Clinical Trials, Phase III as Topic - statistics & numerical data ; Disease-Free Survival ; Female ; Humans ; Lung Neoplasms - diagnosis ; Lung Neoplasms - mortality ; Lung Neoplasms - therapy ; Male ; Medical sciences ; Middle Aged ; Pneumology ; Prognosis ; Randomized Controlled Trials as Topic - statistics & numerical data ; Small Cell Lung Carcinoma - diagnosis ; Small Cell Lung Carcinoma - mortality ; Small Cell Lung Carcinoma - therapy ; Survival Analysis ; Treatment Outcome ; Tumors ; Tumors of the respiratory system and mediastinum ; United States - epidemiology</subject><ispartof>Cancer, 2011-03, Vol.117 (6), p.1262-1271</ispartof><rights>2015 INIST-CNRS</rights><rights>Copyright © 2010 American Cancer Society.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c205t-cca5b848d9ab470c29d730fd76e21c7be08eadaeaf96f907632a97cac96037f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23916504$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20960500$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>FOSTER, Nathan R</creatorcontrib><creatorcontrib>YINGWEI QI</creatorcontrib><creatorcontrib>QIAN SHI</creatorcontrib><creatorcontrib>KROOK, James E</creatorcontrib><creatorcontrib>KUGLER, John W</creatorcontrib><creatorcontrib>JETT, James R</creatorcontrib><creatorcontrib>MOLINA, Julian R</creatorcontrib><creatorcontrib>SCHILD, Steven E</creatorcontrib><creatorcontrib>ADJEI, Alex A</creatorcontrib><creatorcontrib>MANDREKAR, Sumithra J</creatorcontrib><title>Tumor Response and Progression-Free Survival as Potential Surrogate Endpoints for Overall Survival in Extensive Stage Small-Cell Lung Cancer: Findings on the Basis of North Central Cancer Treatment Group Trials</title><title>Cancer</title><addtitle>Cancer</addtitle><description>The authors investigated the putative surrogate endpoints of best response, complete response (CR), confirmed response, and progression-free survival (PFS) for associations with overall survival (OS), and as possible surrogate endpoints for OS.
Individual patient data from 870 untreated extensive stage small-cell lung cancer patients participating in 6 single-arm (274 patients) and 3 randomized trials (596 patients) were pooled. Patient-level associations between putative surrogate endpoints and OS were assessed by Cox models using landmark analyses. Trial-level surrogacy of putative surrogate endpoints were assessed by the association of treatment effects on OS and individual putative surrogate endpoints. Trial-level surrogacy measures included: R(2) from weighted least squares regression model, Spearman correlation coefficient, and R(2) from bivariate survival model (Copula R(2) ).
Median OS and PFS were 9.6 (95% confidence interval [CI], 9.1-10.0) and 5.5 (95% CI, 5.2-5.9) months, respectively; best response, CR, and confirmed response rates were 44%, 22%, and 34%, respectively. Patient-level associations showed that PFS status at 4 months was a strong predictor of subsequent survival (hazard ratio [HR], 0.42; 95% CI, 0.35-0.51; concordance index 0.63; P < .01), with 6-month PFS being the strongest (HR, 0.41; 95% CI, 0.35-0.49; concordance index, 0.66, P < .01). At the trial level, PFS showed the highest level of surrogacy for OS (weighted least squares R(2) = 0.79; Copula R(2) = 0.80), explaining 79% of the variance in OS. Tumor response endpoints showed lower surrogacy levels (weighted least squares R(2) ≤0.48).
PFS was strongly associated with OS at both the patient and trial levels. PFS also shows promise as a potential surrogate for OS, but further validation is needed using data from a larger number of randomized phase 3 trials.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Biological and medical sciences</subject><subject>Biomarkers - analysis</subject><subject>Biomarkers, Tumor - analysis</subject><subject>Clinical Trials, Phase II as Topic - statistics & numerical data</subject><subject>Clinical Trials, Phase III as Topic - statistics & numerical data</subject><subject>Disease-Free Survival</subject><subject>Female</subject><subject>Humans</subject><subject>Lung Neoplasms - diagnosis</subject><subject>Lung Neoplasms - mortality</subject><subject>Lung Neoplasms - therapy</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Pneumology</subject><subject>Prognosis</subject><subject>Randomized Controlled Trials as Topic - statistics & numerical data</subject><subject>Small Cell Lung Carcinoma - diagnosis</subject><subject>Small Cell Lung Carcinoma - mortality</subject><subject>Small Cell Lung Carcinoma - therapy</subject><subject>Survival Analysis</subject><subject>Treatment Outcome</subject><subject>Tumors</subject><subject>Tumors of the respiratory system and mediastinum</subject><subject>United States - epidemiology</subject><issn>0008-543X</issn><issn>1097-0142</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkc9u1DAQxi1ERZfChQdAviAkpLS2E-cPN4h2C9KqrWAP3KJZZ7I12tip7azgNXkipnRpLx59o998tudj7I0U51IIdWGcCedKa1U-YwspmioTslDP2UIIUWe6yH-cspcx_iRZKZ2_YKdKNKXQQizYn808-sC_YZy8i8jB9fwm-F3AGK132Sog8u9zONgD7DlEfuMTumRJUJdASMiXrp-8dSnygbyuDxhgv3-aso4vf9FUtAfySrCjcyQia5Gw9ex2vAVnMHzkK-t663aRe8fTLfLPEC2JgV_5kG55S1eT9xHnm4CQRurxy-DniTS9K75iJwMVfH2sZ2yzWm7aL9n6-vJr-2mdGSV0yowBva2Lum9gW1TCqKavcjH0VYlKmmqLokboAWFoyqERVZkraCoDhlaXV0N-xt4_2E7B380YUzfaaOhH4NDPsau1bqSUuiTywwNpgo8x4NBNwY4QfndSdPcJdvcJdv8SJPjt0Xbejtg_ov8jI-DdEYBoYD8E2oWNT1zeyFKLIv8L1IGorA</recordid><startdate>20110315</startdate><enddate>20110315</enddate><creator>FOSTER, Nathan R</creator><creator>YINGWEI QI</creator><creator>QIAN SHI</creator><creator>KROOK, James E</creator><creator>KUGLER, John W</creator><creator>JETT, James R</creator><creator>MOLINA, Julian R</creator><creator>SCHILD, Steven E</creator><creator>ADJEI, Alex A</creator><creator>MANDREKAR, Sumithra J</creator><general>Wiley-Blackwell</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>7X8</scope></search><sort><creationdate>20110315</creationdate><title>Tumor Response and Progression-Free Survival as Potential Surrogate Endpoints for Overall Survival in Extensive Stage Small-Cell Lung Cancer: Findings on the Basis of North Central Cancer Treatment Group Trials</title><author>FOSTER, Nathan R ; YINGWEI QI ; QIAN SHI ; KROOK, James E ; KUGLER, John W ; JETT, James R ; MOLINA, Julian R ; SCHILD, Steven E ; ADJEI, Alex A ; MANDREKAR, Sumithra J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c205t-cca5b848d9ab470c29d730fd76e21c7be08eadaeaf96f907632a97cac96037f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Biological and medical sciences</topic><topic>Biomarkers - analysis</topic><topic>Biomarkers, Tumor - analysis</topic><topic>Clinical Trials, Phase II as Topic - statistics & numerical data</topic><topic>Clinical Trials, Phase III as Topic - statistics & numerical data</topic><topic>Disease-Free Survival</topic><topic>Female</topic><topic>Humans</topic><topic>Lung Neoplasms - diagnosis</topic><topic>Lung Neoplasms - mortality</topic><topic>Lung Neoplasms - therapy</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Pneumology</topic><topic>Prognosis</topic><topic>Randomized Controlled Trials as Topic - statistics & numerical data</topic><topic>Small Cell Lung Carcinoma - diagnosis</topic><topic>Small Cell Lung Carcinoma - mortality</topic><topic>Small Cell Lung Carcinoma - therapy</topic><topic>Survival Analysis</topic><topic>Treatment Outcome</topic><topic>Tumors</topic><topic>Tumors of the respiratory system and mediastinum</topic><topic>United States - epidemiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>FOSTER, Nathan R</creatorcontrib><creatorcontrib>YINGWEI QI</creatorcontrib><creatorcontrib>QIAN SHI</creatorcontrib><creatorcontrib>KROOK, James E</creatorcontrib><creatorcontrib>KUGLER, John W</creatorcontrib><creatorcontrib>JETT, James R</creatorcontrib><creatorcontrib>MOLINA, Julian R</creatorcontrib><creatorcontrib>SCHILD, Steven E</creatorcontrib><creatorcontrib>ADJEI, Alex A</creatorcontrib><creatorcontrib>MANDREKAR, Sumithra J</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><jtitle>Cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>FOSTER, Nathan R</au><au>YINGWEI QI</au><au>QIAN SHI</au><au>KROOK, James E</au><au>KUGLER, John W</au><au>JETT, James R</au><au>MOLINA, Julian R</au><au>SCHILD, Steven E</au><au>ADJEI, Alex A</au><au>MANDREKAR, Sumithra J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Tumor Response and Progression-Free Survival as Potential Surrogate Endpoints for Overall Survival in Extensive Stage Small-Cell Lung Cancer: Findings on the Basis of North Central Cancer Treatment Group Trials</atitle><jtitle>Cancer</jtitle><addtitle>Cancer</addtitle><date>2011-03-15</date><risdate>2011</risdate><volume>117</volume><issue>6</issue><spage>1262</spage><epage>1271</epage><pages>1262-1271</pages><issn>0008-543X</issn><eissn>1097-0142</eissn><coden>CANCAR</coden><abstract>The authors investigated the putative surrogate endpoints of best response, complete response (CR), confirmed response, and progression-free survival (PFS) for associations with overall survival (OS), and as possible surrogate endpoints for OS.
Individual patient data from 870 untreated extensive stage small-cell lung cancer patients participating in 6 single-arm (274 patients) and 3 randomized trials (596 patients) were pooled. Patient-level associations between putative surrogate endpoints and OS were assessed by Cox models using landmark analyses. Trial-level surrogacy of putative surrogate endpoints were assessed by the association of treatment effects on OS and individual putative surrogate endpoints. Trial-level surrogacy measures included: R(2) from weighted least squares regression model, Spearman correlation coefficient, and R(2) from bivariate survival model (Copula R(2) ).
Median OS and PFS were 9.6 (95% confidence interval [CI], 9.1-10.0) and 5.5 (95% CI, 5.2-5.9) months, respectively; best response, CR, and confirmed response rates were 44%, 22%, and 34%, respectively. Patient-level associations showed that PFS status at 4 months was a strong predictor of subsequent survival (hazard ratio [HR], 0.42; 95% CI, 0.35-0.51; concordance index 0.63; P < .01), with 6-month PFS being the strongest (HR, 0.41; 95% CI, 0.35-0.49; concordance index, 0.66, P < .01). At the trial level, PFS showed the highest level of surrogacy for OS (weighted least squares R(2) = 0.79; Copula R(2) = 0.80), explaining 79% of the variance in OS. Tumor response endpoints showed lower surrogacy levels (weighted least squares R(2) ≤0.48).
PFS was strongly associated with OS at both the patient and trial levels. PFS also shows promise as a potential surrogate for OS, but further validation is needed using data from a larger number of randomized phase 3 trials.</abstract><cop>Hoboken, NJ</cop><pub>Wiley-Blackwell</pub><pmid>20960500</pmid><doi>10.1002/cncr.25526</doi><tpages>10</tpages></addata></record> |
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| source | Wiley-Blackwell Journals; MEDLINE; Wiley Online Library Free Content; Alma/SFX Local Collection; EZB Electronic Journals Library |
| subjects | Adult Aged Aged, 80 and over Biological and medical sciences Biomarkers - analysis Biomarkers, Tumor - analysis Clinical Trials, Phase II as Topic - statistics & numerical data Clinical Trials, Phase III as Topic - statistics & numerical data Disease-Free Survival Female Humans Lung Neoplasms - diagnosis Lung Neoplasms - mortality Lung Neoplasms - therapy Male Medical sciences Middle Aged Pneumology Prognosis Randomized Controlled Trials as Topic - statistics & numerical data Small Cell Lung Carcinoma - diagnosis Small Cell Lung Carcinoma - mortality Small Cell Lung Carcinoma - therapy Survival Analysis Treatment Outcome Tumors Tumors of the respiratory system and mediastinum United States - epidemiology |
| title | Tumor Response and Progression-Free Survival as Potential Surrogate Endpoints for Overall Survival in Extensive Stage Small-Cell Lung Cancer: Findings on the Basis of North Central Cancer Treatment Group Trials |
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