Clinical and molecular characterization of long-term survivors with extensive-stage small cell lung cancer treated with first-line atezolizumab plus carboplatin and etoposide
In the Phase I/III IMpower133 study, first-line atezolizumab plus carboplatin and etoposide (CP/ET) treatment for extensive-stage small cell lung cancer (ES-SCLC) significantly improved overall survival (OS) and progression-free survival versus placebo plus CP/ET. We explored patient and disease cha...
Gespeichert in:
| Veröffentlicht in: | Lung cancer (Amsterdam, Netherlands) Netherlands), 2023-12, Vol.186, p.107418-107418, Article 107418 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 107418 |
|---|---|
| container_issue | |
| container_start_page | 107418 |
| container_title | Lung cancer (Amsterdam, Netherlands) |
| container_volume | 186 |
| creator | Liu, Stephen V Mok, Tony S K Nabet, Barzin Y Mansfield, Aaron S De Boer, Richard Losonczy, György Sugawara, Shunichi Dziadziuszko, Rafal Krzakowski, Maciej Smolin, Alexey Hochmair, Maximilian J Garassino, Marina C Gay, Carl M Heymach, John V Byers, Lauren A Lam, Sivuonthanh Cardona, Andrés Morris, Stefanie Adler, Leah Shames, David S Reck, Martin |
| description | In the Phase I/III IMpower133 study, first-line atezolizumab plus carboplatin and etoposide (CP/ET) treatment for extensive-stage small cell lung cancer (ES-SCLC) significantly improved overall survival (OS) and progression-free survival versus placebo plus CP/ET. We explored patient and disease characteristics associated with long-term survival in IMpower133, and associations of differential gene expression and SCLC-A (ASCL1-driven), SCLC-N (NEUROD1-driven), SCLC-P (POU2F3-driven), and SCLC-inflamed (SCLC-I) transcriptional subtypes with long-term survival.
Patients with previously untreated ES-SCLC were randomized 1:1 to four 21-day cycles of CP/ET with atezolizumab or placebo. Long-term survivors (LTS) were defined as patients who lived ≥ 18 months post randomization. A generalized linear model was used to evaluate the odds of living ≥ 18 months. Differential gene expression was analyzed using RNA-sequencing data in LTS and non-LTS. OS was assessed by T-effector and B-cell gene signature expression. Distribution of SCLC transcriptional subtypes was assessed in LTS and non-LTS.
More LTS were in the atezolizumab arm (34%) than in the placebo arm (20%). The odds ratio for living ≥ 18 months in the atezolizumab arm versus the placebo arm was 2.1 (P |
| doi_str_mv | 10.1016/j.lungcan.2023.107418 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2886937864</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2886937864</sourcerecordid><originalsourceid>FETCH-LOGICAL-c356t-1cc7b4ddbedb5d40be8bd9c17e02c8ad77bd2f88a3dacfc5091a407a1d7ece113</originalsourceid><addsrcrecordid>eNo9kcFu1DAYhC1ERbeFRwD5yCWLHSdr54hWFCpV4tKeoz_2n61Xjh1sZ4F9qD4jXnbhYkujGc9YHyHvOVtzxjef9mu3-J0Gv65ZLYomG65ekRVXsq6UEPVrsiq-rmoZq6_JTUp7xrjkrHtDroXsBG-adkVets56q8FR8IZOwaFeHESqnyGCzhjtEbINnoaRuuB3VZEmmpZ4sIcQE_1p8zPFXxl9sgesUoYd0jSBc1RjOU4jaVmpMdIcETKac2a0MeWqlCMt4jE4e1wmGOjsllQCcQizK83-7y7MYQ7JGnxLrkZwCd9d7lvydPflcfutevj-9X77-aHSot3kimsth8aYAc3QmoYNqAbTaS6R1VqBkXIw9agUCAN61C3rODRMAjcSNXIubsnH87tzDD8WTLmfbDp9CDyGJfW1UptOSLVpirU9W3UMKUUc-znaCeLvnrP-hKrf9xdU_QlVf0ZVch8uFcswofmf-sdG_AHOe5lm</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2886937864</pqid></control><display><type>article</type><title>Clinical and molecular characterization of long-term survivors with extensive-stage small cell lung cancer treated with first-line atezolizumab plus carboplatin and etoposide</title><source>MEDLINE</source><source>Access via ScienceDirect (Elsevier)</source><creator>Liu, Stephen V ; Mok, Tony S K ; Nabet, Barzin Y ; Mansfield, Aaron S ; De Boer, Richard ; Losonczy, György ; Sugawara, Shunichi ; Dziadziuszko, Rafal ; Krzakowski, Maciej ; Smolin, Alexey ; Hochmair, Maximilian J ; Garassino, Marina C ; Gay, Carl M ; Heymach, John V ; Byers, Lauren A ; Lam, Sivuonthanh ; Cardona, Andrés ; Morris, Stefanie ; Adler, Leah ; Shames, David S ; Reck, Martin</creator><creatorcontrib>Liu, Stephen V ; Mok, Tony S K ; Nabet, Barzin Y ; Mansfield, Aaron S ; De Boer, Richard ; Losonczy, György ; Sugawara, Shunichi ; Dziadziuszko, Rafal ; Krzakowski, Maciej ; Smolin, Alexey ; Hochmair, Maximilian J ; Garassino, Marina C ; Gay, Carl M ; Heymach, John V ; Byers, Lauren A ; Lam, Sivuonthanh ; Cardona, Andrés ; Morris, Stefanie ; Adler, Leah ; Shames, David S ; Reck, Martin</creatorcontrib><description>In the Phase I/III IMpower133 study, first-line atezolizumab plus carboplatin and etoposide (CP/ET) treatment for extensive-stage small cell lung cancer (ES-SCLC) significantly improved overall survival (OS) and progression-free survival versus placebo plus CP/ET. We explored patient and disease characteristics associated with long-term survival in IMpower133, and associations of differential gene expression and SCLC-A (ASCL1-driven), SCLC-N (NEUROD1-driven), SCLC-P (POU2F3-driven), and SCLC-inflamed (SCLC-I) transcriptional subtypes with long-term survival.
Patients with previously untreated ES-SCLC were randomized 1:1 to four 21-day cycles of CP/ET with atezolizumab or placebo. Long-term survivors (LTS) were defined as patients who lived ≥ 18 months post randomization. A generalized linear model was used to evaluate the odds of living ≥ 18 months. Differential gene expression was analyzed using RNA-sequencing data in LTS and non-LTS. OS was assessed by T-effector and B-cell gene signature expression. Distribution of SCLC transcriptional subtypes was assessed in LTS and non-LTS.
More LTS were in the atezolizumab arm (34%) than in the placebo arm (20%). The odds ratio for living ≥ 18 months in the atezolizumab arm versus the placebo arm was 2.1 (P < 0.03). Enhanced immune-related signaling was seen in LTS in both arms. Exploratory OS analyses showed atezolizumab treatment benefit versus placebo across T-effector and B-cell gene signature expression subgroups. A higher proportion of LTS than non-LTS in both arms had the SCLC-I subtype; this difference was particularly pronounced in the atezolizumab arm.
These exploratory analyses suggest that long-term survival is more likely with atezolizumab than placebo in ES-SCLC, confirming the treatment benefit of the IMpower133 regimen.
gov Identifier: NCT02763579.</description><identifier>ISSN: 0169-5002</identifier><identifier>EISSN: 1872-8332</identifier><identifier>DOI: 10.1016/j.lungcan.2023.107418</identifier><identifier>PMID: 37931445</identifier><language>eng</language><publisher>Ireland</publisher><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Carboplatin ; Etoposide ; Humans ; Lung Neoplasms - drug therapy ; Lung Neoplasms - genetics ; Small Cell Lung Carcinoma - drug therapy ; Small Cell Lung Carcinoma - genetics ; Survivors</subject><ispartof>Lung cancer (Amsterdam, Netherlands), 2023-12, Vol.186, p.107418-107418, Article 107418</ispartof><rights>Copyright © 2023. Published by Elsevier B.V.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c356t-1cc7b4ddbedb5d40be8bd9c17e02c8ad77bd2f88a3dacfc5091a407a1d7ece113</citedby><cites>FETCH-LOGICAL-c356t-1cc7b4ddbedb5d40be8bd9c17e02c8ad77bd2f88a3dacfc5091a407a1d7ece113</cites><orcidid>0000-0002-4852-3914</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37931445$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liu, Stephen V</creatorcontrib><creatorcontrib>Mok, Tony S K</creatorcontrib><creatorcontrib>Nabet, Barzin Y</creatorcontrib><creatorcontrib>Mansfield, Aaron S</creatorcontrib><creatorcontrib>De Boer, Richard</creatorcontrib><creatorcontrib>Losonczy, György</creatorcontrib><creatorcontrib>Sugawara, Shunichi</creatorcontrib><creatorcontrib>Dziadziuszko, Rafal</creatorcontrib><creatorcontrib>Krzakowski, Maciej</creatorcontrib><creatorcontrib>Smolin, Alexey</creatorcontrib><creatorcontrib>Hochmair, Maximilian J</creatorcontrib><creatorcontrib>Garassino, Marina C</creatorcontrib><creatorcontrib>Gay, Carl M</creatorcontrib><creatorcontrib>Heymach, John V</creatorcontrib><creatorcontrib>Byers, Lauren A</creatorcontrib><creatorcontrib>Lam, Sivuonthanh</creatorcontrib><creatorcontrib>Cardona, Andrés</creatorcontrib><creatorcontrib>Morris, Stefanie</creatorcontrib><creatorcontrib>Adler, Leah</creatorcontrib><creatorcontrib>Shames, David S</creatorcontrib><creatorcontrib>Reck, Martin</creatorcontrib><title>Clinical and molecular characterization of long-term survivors with extensive-stage small cell lung cancer treated with first-line atezolizumab plus carboplatin and etoposide</title><title>Lung cancer (Amsterdam, Netherlands)</title><addtitle>Lung Cancer</addtitle><description>In the Phase I/III IMpower133 study, first-line atezolizumab plus carboplatin and etoposide (CP/ET) treatment for extensive-stage small cell lung cancer (ES-SCLC) significantly improved overall survival (OS) and progression-free survival versus placebo plus CP/ET. We explored patient and disease characteristics associated with long-term survival in IMpower133, and associations of differential gene expression and SCLC-A (ASCL1-driven), SCLC-N (NEUROD1-driven), SCLC-P (POU2F3-driven), and SCLC-inflamed (SCLC-I) transcriptional subtypes with long-term survival.
Patients with previously untreated ES-SCLC were randomized 1:1 to four 21-day cycles of CP/ET with atezolizumab or placebo. Long-term survivors (LTS) were defined as patients who lived ≥ 18 months post randomization. A generalized linear model was used to evaluate the odds of living ≥ 18 months. Differential gene expression was analyzed using RNA-sequencing data in LTS and non-LTS. OS was assessed by T-effector and B-cell gene signature expression. Distribution of SCLC transcriptional subtypes was assessed in LTS and non-LTS.
More LTS were in the atezolizumab arm (34%) than in the placebo arm (20%). The odds ratio for living ≥ 18 months in the atezolizumab arm versus the placebo arm was 2.1 (P < 0.03). Enhanced immune-related signaling was seen in LTS in both arms. Exploratory OS analyses showed atezolizumab treatment benefit versus placebo across T-effector and B-cell gene signature expression subgroups. A higher proportion of LTS than non-LTS in both arms had the SCLC-I subtype; this difference was particularly pronounced in the atezolizumab arm.
These exploratory analyses suggest that long-term survival is more likely with atezolizumab than placebo in ES-SCLC, confirming the treatment benefit of the IMpower133 regimen.
gov Identifier: NCT02763579.</description><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Carboplatin</subject><subject>Etoposide</subject><subject>Humans</subject><subject>Lung Neoplasms - drug therapy</subject><subject>Lung Neoplasms - genetics</subject><subject>Small Cell Lung Carcinoma - drug therapy</subject><subject>Small Cell Lung Carcinoma - genetics</subject><subject>Survivors</subject><issn>0169-5002</issn><issn>1872-8332</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kcFu1DAYhC1ERbeFRwD5yCWLHSdr54hWFCpV4tKeoz_2n61Xjh1sZ4F9qD4jXnbhYkujGc9YHyHvOVtzxjef9mu3-J0Gv65ZLYomG65ekRVXsq6UEPVrsiq-rmoZq6_JTUp7xrjkrHtDroXsBG-adkVets56q8FR8IZOwaFeHESqnyGCzhjtEbINnoaRuuB3VZEmmpZ4sIcQE_1p8zPFXxl9sgesUoYd0jSBc1RjOU4jaVmpMdIcETKac2a0MeWqlCMt4jE4e1wmGOjsllQCcQizK83-7y7MYQ7JGnxLrkZwCd9d7lvydPflcfutevj-9X77-aHSot3kimsth8aYAc3QmoYNqAbTaS6R1VqBkXIw9agUCAN61C3rODRMAjcSNXIubsnH87tzDD8WTLmfbDp9CDyGJfW1UptOSLVpirU9W3UMKUUc-znaCeLvnrP-hKrf9xdU_QlVf0ZVch8uFcswofmf-sdG_AHOe5lm</recordid><startdate>202312</startdate><enddate>202312</enddate><creator>Liu, Stephen V</creator><creator>Mok, Tony S K</creator><creator>Nabet, Barzin Y</creator><creator>Mansfield, Aaron S</creator><creator>De Boer, Richard</creator><creator>Losonczy, György</creator><creator>Sugawara, Shunichi</creator><creator>Dziadziuszko, Rafal</creator><creator>Krzakowski, Maciej</creator><creator>Smolin, Alexey</creator><creator>Hochmair, Maximilian J</creator><creator>Garassino, Marina C</creator><creator>Gay, Carl M</creator><creator>Heymach, John V</creator><creator>Byers, Lauren A</creator><creator>Lam, Sivuonthanh</creator><creator>Cardona, Andrés</creator><creator>Morris, Stefanie</creator><creator>Adler, Leah</creator><creator>Shames, David S</creator><creator>Reck, Martin</creator><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><orcidid>https://orcid.org/0000-0002-4852-3914</orcidid></search><sort><creationdate>202312</creationdate><title>Clinical and molecular characterization of long-term survivors with extensive-stage small cell lung cancer treated with first-line atezolizumab plus carboplatin and etoposide</title><author>Liu, Stephen V ; Mok, Tony S K ; Nabet, Barzin Y ; Mansfield, Aaron S ; De Boer, Richard ; Losonczy, György ; Sugawara, Shunichi ; Dziadziuszko, Rafal ; Krzakowski, Maciej ; Smolin, Alexey ; Hochmair, Maximilian J ; Garassino, Marina C ; Gay, Carl M ; Heymach, John V ; Byers, Lauren A ; Lam, Sivuonthanh ; Cardona, Andrés ; Morris, Stefanie ; Adler, Leah ; Shames, David S ; Reck, Martin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-1cc7b4ddbedb5d40be8bd9c17e02c8ad77bd2f88a3dacfc5091a407a1d7ece113</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Carboplatin</topic><topic>Etoposide</topic><topic>Humans</topic><topic>Lung Neoplasms - drug therapy</topic><topic>Lung Neoplasms - genetics</topic><topic>Small Cell Lung Carcinoma - drug therapy</topic><topic>Small Cell Lung Carcinoma - genetics</topic><topic>Survivors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liu, Stephen V</creatorcontrib><creatorcontrib>Mok, Tony S K</creatorcontrib><creatorcontrib>Nabet, Barzin Y</creatorcontrib><creatorcontrib>Mansfield, Aaron S</creatorcontrib><creatorcontrib>De Boer, Richard</creatorcontrib><creatorcontrib>Losonczy, György</creatorcontrib><creatorcontrib>Sugawara, Shunichi</creatorcontrib><creatorcontrib>Dziadziuszko, Rafal</creatorcontrib><creatorcontrib>Krzakowski, Maciej</creatorcontrib><creatorcontrib>Smolin, Alexey</creatorcontrib><creatorcontrib>Hochmair, Maximilian J</creatorcontrib><creatorcontrib>Garassino, Marina C</creatorcontrib><creatorcontrib>Gay, Carl M</creatorcontrib><creatorcontrib>Heymach, John V</creatorcontrib><creatorcontrib>Byers, Lauren A</creatorcontrib><creatorcontrib>Lam, Sivuonthanh</creatorcontrib><creatorcontrib>Cardona, Andrés</creatorcontrib><creatorcontrib>Morris, Stefanie</creatorcontrib><creatorcontrib>Adler, Leah</creatorcontrib><creatorcontrib>Shames, David S</creatorcontrib><creatorcontrib>Reck, Martin</creatorcontrib><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>Lung cancer (Amsterdam, Netherlands)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liu, Stephen V</au><au>Mok, Tony S K</au><au>Nabet, Barzin Y</au><au>Mansfield, Aaron S</au><au>De Boer, Richard</au><au>Losonczy, György</au><au>Sugawara, Shunichi</au><au>Dziadziuszko, Rafal</au><au>Krzakowski, Maciej</au><au>Smolin, Alexey</au><au>Hochmair, Maximilian J</au><au>Garassino, Marina C</au><au>Gay, Carl M</au><au>Heymach, John V</au><au>Byers, Lauren A</au><au>Lam, Sivuonthanh</au><au>Cardona, Andrés</au><au>Morris, Stefanie</au><au>Adler, Leah</au><au>Shames, David S</au><au>Reck, Martin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Clinical and molecular characterization of long-term survivors with extensive-stage small cell lung cancer treated with first-line atezolizumab plus carboplatin and etoposide</atitle><jtitle>Lung cancer (Amsterdam, Netherlands)</jtitle><addtitle>Lung Cancer</addtitle><date>2023-12</date><risdate>2023</risdate><volume>186</volume><spage>107418</spage><epage>107418</epage><pages>107418-107418</pages><artnum>107418</artnum><issn>0169-5002</issn><eissn>1872-8332</eissn><abstract>In the Phase I/III IMpower133 study, first-line atezolizumab plus carboplatin and etoposide (CP/ET) treatment for extensive-stage small cell lung cancer (ES-SCLC) significantly improved overall survival (OS) and progression-free survival versus placebo plus CP/ET. We explored patient and disease characteristics associated with long-term survival in IMpower133, and associations of differential gene expression and SCLC-A (ASCL1-driven), SCLC-N (NEUROD1-driven), SCLC-P (POU2F3-driven), and SCLC-inflamed (SCLC-I) transcriptional subtypes with long-term survival.
Patients with previously untreated ES-SCLC were randomized 1:1 to four 21-day cycles of CP/ET with atezolizumab or placebo. Long-term survivors (LTS) were defined as patients who lived ≥ 18 months post randomization. A generalized linear model was used to evaluate the odds of living ≥ 18 months. Differential gene expression was analyzed using RNA-sequencing data in LTS and non-LTS. OS was assessed by T-effector and B-cell gene signature expression. Distribution of SCLC transcriptional subtypes was assessed in LTS and non-LTS.
More LTS were in the atezolizumab arm (34%) than in the placebo arm (20%). The odds ratio for living ≥ 18 months in the atezolizumab arm versus the placebo arm was 2.1 (P < 0.03). Enhanced immune-related signaling was seen in LTS in both arms. Exploratory OS analyses showed atezolizumab treatment benefit versus placebo across T-effector and B-cell gene signature expression subgroups. A higher proportion of LTS than non-LTS in both arms had the SCLC-I subtype; this difference was particularly pronounced in the atezolizumab arm.
These exploratory analyses suggest that long-term survival is more likely with atezolizumab than placebo in ES-SCLC, confirming the treatment benefit of the IMpower133 regimen.
gov Identifier: NCT02763579.</abstract><cop>Ireland</cop><pmid>37931445</pmid><doi>10.1016/j.lungcan.2023.107418</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-4852-3914</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0169-5002 |
| ispartof | Lung cancer (Amsterdam, Netherlands), 2023-12, Vol.186, p.107418-107418, Article 107418 |
| issn | 0169-5002 1872-8332 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2886937864 |
| source | MEDLINE; Access via ScienceDirect (Elsevier) |
| subjects | Antineoplastic Combined Chemotherapy Protocols - therapeutic use Carboplatin Etoposide Humans Lung Neoplasms - drug therapy Lung Neoplasms - genetics Small Cell Lung Carcinoma - drug therapy Small Cell Lung Carcinoma - genetics Survivors |
| title | Clinical and molecular characterization of long-term survivors with extensive-stage small cell lung cancer treated with first-line atezolizumab plus carboplatin and etoposide |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T14%3A01%3A10IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Clinical%20and%20molecular%20characterization%20of%20long-term%20survivors%20with%20extensive-stage%20small%20cell%20lung%20cancer%20treated%20with%20first-line%20atezolizumab%20plus%20carboplatin%20and%20etoposide&rft.jtitle=Lung%20cancer%20(Amsterdam,%20Netherlands)&rft.au=Liu,%20Stephen%20V&rft.date=2023-12&rft.volume=186&rft.spage=107418&rft.epage=107418&rft.pages=107418-107418&rft.artnum=107418&rft.issn=0169-5002&rft.eissn=1872-8332&rft_id=info:doi/10.1016/j.lungcan.2023.107418&rft_dat=%3Cproquest_cross%3E2886937864%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2886937864&rft_id=info:pmid/37931445&rfr_iscdi=true |