Circulating Epstein–Barr virus DNA level post induction chemotherapy contributes to prognostication in advanced-stage nasopharyngeal carcinoma
To investigate the value of post-induction chemotherapy (IC) cell-free Epstein–Barr virus DNA (cfEBV DNApostIC) for prognostication in locally advanced nasopharyngeal carcinoma (LA-NPC). A total of 910 histologically proven LA-NPC undergoing radical IC + concurrent chemo-radiotherapy (CCRT) or targe...
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| Veröffentlicht in: | European journal of cancer (1990) 2021-07, Vol.151, p.63-71 |
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| creator | Chen, Fo-Ping Luo, Ying-Shan Chen, Kai Li, Jun-Yun Huo, Lan-Qing Shi, Liu Ou-Yang, Yi Cao, Xin-Ping |
| description | To investigate the value of post-induction chemotherapy (IC) cell-free Epstein–Barr virus DNA (cfEBV DNApostIC) for prognostication in locally advanced nasopharyngeal carcinoma (LA-NPC).
A total of 910 histologically proven LA-NPC undergoing radical IC + concurrent chemo-radiotherapy (CCRT) or targeted radiotherapy (CTRT) or both (CTCRT) were involved. The concentration of cfEBV DNA was measured by quantitative polymerase chain reaction pre-IC (cfEBV DNApreIC) and at IC completion. CfEBV DNApostIC was classified as undetectable (0 copy/ml) and detectable (>0 copy/ml). Recursive partitioning analysis (RPA) with respect to the overall survival (OS) was applied to construct a risk stratification system incorporating cfEBV DNApostIC and critical risk factors.
We observed that 660 (72.5%) and 250 (27.5%) patients had cfEBV DNApostIC undetectable and detectable respectively. CfEBV DNApostIC positive was associated with a significant inferior 5-year OS (76.2% versus 85.9%), metastasis-free survival (DMFS, 71.7% versus 86.4%) and disease-free survival (DFS, 57.7% versus 80.1%) than cfEBV DNApostIC negative (P |
| doi_str_mv | 10.1016/j.ejca.2021.03.052 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_journals_2549055904</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0959804921002203</els_id><sourcerecordid>2549055904</sourcerecordid><originalsourceid>FETCH-LOGICAL-c384t-479659ebccabda5af8267281ecc7355054da2c8bd87580872020e2f20869c4a93</originalsourceid><addsrcrecordid>eNp9kcFu1DAQhi1ERbeFF-CALHFOmDhxYktcytICUlUucLYcZ3bXUdYOtrNSbzwCEm_YJ8HLFo49zeWbf_75f0JeV1BWULXvxhJHo0sGrCqhLoGzZ2RViU4WIDh7TlYguSwENPKcXMQ4AkAnGnhBzutatg3v6hX5tbbBLJNO1m3p9RwTWvfw8_cHHQI92LBE-vHuik54wInOPiZq3bCYZL2jZod7n3YY9HxPjXcp2H5JGGnydA5-6zJujf7LWkf1cNDO4FDEpLdInY5-3ulw77aoJ2p0MNb5vX5JzjZ6ivjqcV6S7zfX39afi9uvn76sr24LU4smFU0nWy6xN0b3g-Z6I1jbMVGhMV3NOfBm0MyIfhAdFyC6HBIg2zAQrTSNlvUleXvSzVZ_LBiTGv0SXD6pGG8kcC6hyRQ7USb4GANu1BzsPrtWFahjCWpUxxLUsQQFtcol5KU3j9JLv8fh_8q_1DPw_gRgfvBgMahoLB7DsQFNUoO3T-n_AVl-nH8</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2549055904</pqid></control><display><type>article</type><title>Circulating Epstein–Barr virus DNA level post induction chemotherapy contributes to prognostication in advanced-stage nasopharyngeal carcinoma</title><source>ScienceDirect Journals (5 years ago - present)</source><creator>Chen, Fo-Ping ; Luo, Ying-Shan ; Chen, Kai ; Li, Jun-Yun ; Huo, Lan-Qing ; Shi, Liu ; Ou-Yang, Yi ; Cao, Xin-Ping</creator><creatorcontrib>Chen, Fo-Ping ; Luo, Ying-Shan ; Chen, Kai ; Li, Jun-Yun ; Huo, Lan-Qing ; Shi, Liu ; Ou-Yang, Yi ; Cao, Xin-Ping</creatorcontrib><description>To investigate the value of post-induction chemotherapy (IC) cell-free Epstein–Barr virus DNA (cfEBV DNApostIC) for prognostication in locally advanced nasopharyngeal carcinoma (LA-NPC).
A total of 910 histologically proven LA-NPC undergoing radical IC + concurrent chemo-radiotherapy (CCRT) or targeted radiotherapy (CTRT) or both (CTCRT) were involved. The concentration of cfEBV DNA was measured by quantitative polymerase chain reaction pre-IC (cfEBV DNApreIC) and at IC completion. CfEBV DNApostIC was classified as undetectable (0 copy/ml) and detectable (>0 copy/ml). Recursive partitioning analysis (RPA) with respect to the overall survival (OS) was applied to construct a risk stratification system incorporating cfEBV DNApostIC and critical risk factors.
We observed that 660 (72.5%) and 250 (27.5%) patients had cfEBV DNApostIC undetectable and detectable respectively. CfEBV DNApostIC positive was associated with a significant inferior 5-year OS (76.2% versus 85.9%), metastasis-free survival (DMFS, 71.7% versus 86.4%) and disease-free survival (DFS, 57.7% versus 80.1%) than cfEBV DNApostIC negative (P < 0.001 for all). Additionally, cfEBV DNApostIC was independently significant for OS (hazard ratio [HR] 1.90, 95% CI 1.40–2.59), DMFS (1.99, 1.45–2.71) and DFS (2.38, 1.86–3.06) in multivariate analyses (P < 0.001 for all). RPA modelling yielded three distinct risk groups: low-risk (N0-1 and undetectable cfEBV DNApostIC or N2-3 and pre-treatment cfEBV DNA [cfEBV DNApreIC] <7000), median-risk (N0-1 and detectable cfEBV DNApostIC or N2-3 and cfEBV DNApreIC ≥7000 with undetectable cfEBV DNApostIC) and high-risk (N2-3 and cfEBV DNApreIC ≥7000 with detectable cfEBV DNApostIC), with 5-year OS of 88.1%, 79.2% and 66.9%, respectively. Our risk stratification outperformed TNM classification for predicting death (AUC, 0.631 versus 0.562; P = 0.012) and distant metastasis (0.659 versus 0.562; P = 0.004).
CfEBV DNApostIC represents an effective indicator of prognostication in LA-NPC. We developed a risk classification system that provides improved OS prediction over the current staging system by combining cfEBV DNApostIC, cfEBV DNApreIC and N-stage classification in LA-NPC.
•CfEBV DNApostIC positive was independently risk for metastasis/death in LA-NPC.•We constructed a cfEBV DNApostIC-based risk classification system in LA-NPC.•Risk stratification is superior to TNM schema in predicting death and metastasis.</description><identifier>ISSN: 0959-8049</identifier><identifier>EISSN: 1879-0852</identifier><identifier>DOI: 10.1016/j.ejca.2021.03.052</identifier><identifier>PMID: 33964573</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Chemotherapy ; Classification ; Concurrent chemotherapy ; Deoxyribonucleic acid ; DNA ; DNA viruses ; EBV DNA ; Epstein-Barr virus ; Metastases ; Metastasis ; Nasopharyngeal carcinoma ; Neoadjuvant chemotherapy ; Polymerase chain reaction ; Radiation therapy ; Risk analysis ; Risk factors ; Risk groups ; Survival ; Targeted therapy ; Throat cancer ; Treatment outcome ; Viruses</subject><ispartof>European journal of cancer (1990), 2021-07, Vol.151, p.63-71</ispartof><rights>2021 Elsevier Ltd</rights><rights>Copyright © 2021 Elsevier Ltd. All rights reserved.</rights><rights>Copyright Elsevier Science Ltd. Jul 2021</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c384t-479659ebccabda5af8267281ecc7355054da2c8bd87580872020e2f20869c4a93</citedby><cites>FETCH-LOGICAL-c384t-479659ebccabda5af8267281ecc7355054da2c8bd87580872020e2f20869c4a93</cites><orcidid>0000-0001-9981-2583 ; 0000-0002-4998-8502</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ejca.2021.03.052$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33964573$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Fo-Ping</creatorcontrib><creatorcontrib>Luo, Ying-Shan</creatorcontrib><creatorcontrib>Chen, Kai</creatorcontrib><creatorcontrib>Li, Jun-Yun</creatorcontrib><creatorcontrib>Huo, Lan-Qing</creatorcontrib><creatorcontrib>Shi, Liu</creatorcontrib><creatorcontrib>Ou-Yang, Yi</creatorcontrib><creatorcontrib>Cao, Xin-Ping</creatorcontrib><title>Circulating Epstein–Barr virus DNA level post induction chemotherapy contributes to prognostication in advanced-stage nasopharyngeal carcinoma</title><title>European journal of cancer (1990)</title><addtitle>Eur J Cancer</addtitle><description>To investigate the value of post-induction chemotherapy (IC) cell-free Epstein–Barr virus DNA (cfEBV DNApostIC) for prognostication in locally advanced nasopharyngeal carcinoma (LA-NPC).
A total of 910 histologically proven LA-NPC undergoing radical IC + concurrent chemo-radiotherapy (CCRT) or targeted radiotherapy (CTRT) or both (CTCRT) were involved. The concentration of cfEBV DNA was measured by quantitative polymerase chain reaction pre-IC (cfEBV DNApreIC) and at IC completion. CfEBV DNApostIC was classified as undetectable (0 copy/ml) and detectable (>0 copy/ml). Recursive partitioning analysis (RPA) with respect to the overall survival (OS) was applied to construct a risk stratification system incorporating cfEBV DNApostIC and critical risk factors.
We observed that 660 (72.5%) and 250 (27.5%) patients had cfEBV DNApostIC undetectable and detectable respectively. CfEBV DNApostIC positive was associated with a significant inferior 5-year OS (76.2% versus 85.9%), metastasis-free survival (DMFS, 71.7% versus 86.4%) and disease-free survival (DFS, 57.7% versus 80.1%) than cfEBV DNApostIC negative (P < 0.001 for all). Additionally, cfEBV DNApostIC was independently significant for OS (hazard ratio [HR] 1.90, 95% CI 1.40–2.59), DMFS (1.99, 1.45–2.71) and DFS (2.38, 1.86–3.06) in multivariate analyses (P < 0.001 for all). RPA modelling yielded three distinct risk groups: low-risk (N0-1 and undetectable cfEBV DNApostIC or N2-3 and pre-treatment cfEBV DNA [cfEBV DNApreIC] <7000), median-risk (N0-1 and detectable cfEBV DNApostIC or N2-3 and cfEBV DNApreIC ≥7000 with undetectable cfEBV DNApostIC) and high-risk (N2-3 and cfEBV DNApreIC ≥7000 with detectable cfEBV DNApostIC), with 5-year OS of 88.1%, 79.2% and 66.9%, respectively. Our risk stratification outperformed TNM classification for predicting death (AUC, 0.631 versus 0.562; P = 0.012) and distant metastasis (0.659 versus 0.562; P = 0.004).
CfEBV DNApostIC represents an effective indicator of prognostication in LA-NPC. We developed a risk classification system that provides improved OS prediction over the current staging system by combining cfEBV DNApostIC, cfEBV DNApreIC and N-stage classification in LA-NPC.
•CfEBV DNApostIC positive was independently risk for metastasis/death in LA-NPC.•We constructed a cfEBV DNApostIC-based risk classification system in LA-NPC.•Risk stratification is superior to TNM schema in predicting death and metastasis.</description><subject>Chemotherapy</subject><subject>Classification</subject><subject>Concurrent chemotherapy</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA viruses</subject><subject>EBV DNA</subject><subject>Epstein-Barr virus</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Nasopharyngeal carcinoma</subject><subject>Neoadjuvant chemotherapy</subject><subject>Polymerase chain reaction</subject><subject>Radiation therapy</subject><subject>Risk analysis</subject><subject>Risk factors</subject><subject>Risk groups</subject><subject>Survival</subject><subject>Targeted therapy</subject><subject>Throat cancer</subject><subject>Treatment outcome</subject><subject>Viruses</subject><issn>0959-8049</issn><issn>1879-0852</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNp9kcFu1DAQhi1ERbeFF-CALHFOmDhxYktcytICUlUucLYcZ3bXUdYOtrNSbzwCEm_YJ8HLFo49zeWbf_75f0JeV1BWULXvxhJHo0sGrCqhLoGzZ2RViU4WIDh7TlYguSwENPKcXMQ4AkAnGnhBzutatg3v6hX5tbbBLJNO1m3p9RwTWvfw8_cHHQI92LBE-vHuik54wInOPiZq3bCYZL2jZod7n3YY9HxPjXcp2H5JGGnydA5-6zJujf7LWkf1cNDO4FDEpLdInY5-3ulw77aoJ2p0MNb5vX5JzjZ6ivjqcV6S7zfX39afi9uvn76sr24LU4smFU0nWy6xN0b3g-Z6I1jbMVGhMV3NOfBm0MyIfhAdFyC6HBIg2zAQrTSNlvUleXvSzVZ_LBiTGv0SXD6pGG8kcC6hyRQ7USb4GANu1BzsPrtWFahjCWpUxxLUsQQFtcol5KU3j9JLv8fh_8q_1DPw_gRgfvBgMahoLB7DsQFNUoO3T-n_AVl-nH8</recordid><startdate>20210701</startdate><enddate>20210701</enddate><creator>Chen, Fo-Ping</creator><creator>Luo, Ying-Shan</creator><creator>Chen, Kai</creator><creator>Li, Jun-Yun</creator><creator>Huo, Lan-Qing</creator><creator>Shi, Liu</creator><creator>Ou-Yang, Yi</creator><creator>Cao, Xin-Ping</creator><general>Elsevier Ltd</general><general>Elsevier Science Ltd</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TO</scope><scope>7U7</scope><scope>C1K</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><orcidid>https://orcid.org/0000-0001-9981-2583</orcidid><orcidid>https://orcid.org/0000-0002-4998-8502</orcidid></search><sort><creationdate>20210701</creationdate><title>Circulating Epstein–Barr virus DNA level post induction chemotherapy contributes to prognostication in advanced-stage nasopharyngeal carcinoma</title><author>Chen, Fo-Ping ; Luo, Ying-Shan ; Chen, Kai ; Li, Jun-Yun ; Huo, Lan-Qing ; Shi, Liu ; Ou-Yang, Yi ; Cao, Xin-Ping</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c384t-479659ebccabda5af8267281ecc7355054da2c8bd87580872020e2f20869c4a93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Chemotherapy</topic><topic>Classification</topic><topic>Concurrent chemotherapy</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA viruses</topic><topic>EBV DNA</topic><topic>Epstein-Barr virus</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Nasopharyngeal carcinoma</topic><topic>Neoadjuvant chemotherapy</topic><topic>Polymerase chain reaction</topic><topic>Radiation therapy</topic><topic>Risk analysis</topic><topic>Risk factors</topic><topic>Risk groups</topic><topic>Survival</topic><topic>Targeted therapy</topic><topic>Throat cancer</topic><topic>Treatment outcome</topic><topic>Viruses</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Fo-Ping</creatorcontrib><creatorcontrib>Luo, Ying-Shan</creatorcontrib><creatorcontrib>Chen, Kai</creatorcontrib><creatorcontrib>Li, Jun-Yun</creatorcontrib><creatorcontrib>Huo, Lan-Qing</creatorcontrib><creatorcontrib>Shi, Liu</creatorcontrib><creatorcontrib>Ou-Yang, Yi</creatorcontrib><creatorcontrib>Cao, Xin-Ping</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><jtitle>European journal of cancer (1990)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Fo-Ping</au><au>Luo, Ying-Shan</au><au>Chen, Kai</au><au>Li, Jun-Yun</au><au>Huo, Lan-Qing</au><au>Shi, Liu</au><au>Ou-Yang, Yi</au><au>Cao, Xin-Ping</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Circulating Epstein–Barr virus DNA level post induction chemotherapy contributes to prognostication in advanced-stage nasopharyngeal carcinoma</atitle><jtitle>European journal of cancer (1990)</jtitle><addtitle>Eur J Cancer</addtitle><date>2021-07-01</date><risdate>2021</risdate><volume>151</volume><spage>63</spage><epage>71</epage><pages>63-71</pages><issn>0959-8049</issn><eissn>1879-0852</eissn><abstract>To investigate the value of post-induction chemotherapy (IC) cell-free Epstein–Barr virus DNA (cfEBV DNApostIC) for prognostication in locally advanced nasopharyngeal carcinoma (LA-NPC).
A total of 910 histologically proven LA-NPC undergoing radical IC + concurrent chemo-radiotherapy (CCRT) or targeted radiotherapy (CTRT) or both (CTCRT) were involved. The concentration of cfEBV DNA was measured by quantitative polymerase chain reaction pre-IC (cfEBV DNApreIC) and at IC completion. CfEBV DNApostIC was classified as undetectable (0 copy/ml) and detectable (>0 copy/ml). Recursive partitioning analysis (RPA) with respect to the overall survival (OS) was applied to construct a risk stratification system incorporating cfEBV DNApostIC and critical risk factors.
We observed that 660 (72.5%) and 250 (27.5%) patients had cfEBV DNApostIC undetectable and detectable respectively. CfEBV DNApostIC positive was associated with a significant inferior 5-year OS (76.2% versus 85.9%), metastasis-free survival (DMFS, 71.7% versus 86.4%) and disease-free survival (DFS, 57.7% versus 80.1%) than cfEBV DNApostIC negative (P < 0.001 for all). Additionally, cfEBV DNApostIC was independently significant for OS (hazard ratio [HR] 1.90, 95% CI 1.40–2.59), DMFS (1.99, 1.45–2.71) and DFS (2.38, 1.86–3.06) in multivariate analyses (P < 0.001 for all). RPA modelling yielded three distinct risk groups: low-risk (N0-1 and undetectable cfEBV DNApostIC or N2-3 and pre-treatment cfEBV DNA [cfEBV DNApreIC] <7000), median-risk (N0-1 and detectable cfEBV DNApostIC or N2-3 and cfEBV DNApreIC ≥7000 with undetectable cfEBV DNApostIC) and high-risk (N2-3 and cfEBV DNApreIC ≥7000 with detectable cfEBV DNApostIC), with 5-year OS of 88.1%, 79.2% and 66.9%, respectively. Our risk stratification outperformed TNM classification for predicting death (AUC, 0.631 versus 0.562; P = 0.012) and distant metastasis (0.659 versus 0.562; P = 0.004).
CfEBV DNApostIC represents an effective indicator of prognostication in LA-NPC. We developed a risk classification system that provides improved OS prediction over the current staging system by combining cfEBV DNApostIC, cfEBV DNApreIC and N-stage classification in LA-NPC.
•CfEBV DNApostIC positive was independently risk for metastasis/death in LA-NPC.•We constructed a cfEBV DNApostIC-based risk classification system in LA-NPC.•Risk stratification is superior to TNM schema in predicting death and metastasis.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>33964573</pmid><doi>10.1016/j.ejca.2021.03.052</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0001-9981-2583</orcidid><orcidid>https://orcid.org/0000-0002-4998-8502</orcidid></addata></record> |
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| subjects | Chemotherapy Classification Concurrent chemotherapy Deoxyribonucleic acid DNA DNA viruses EBV DNA Epstein-Barr virus Metastases Metastasis Nasopharyngeal carcinoma Neoadjuvant chemotherapy Polymerase chain reaction Radiation therapy Risk analysis Risk factors Risk groups Survival Targeted therapy Throat cancer Treatment outcome Viruses |
| title | Circulating Epstein–Barr virus DNA level post induction chemotherapy contributes to prognostication in advanced-stage nasopharyngeal carcinoma |
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