Solid tumours showing oligoprogression to immune checkpoint inhibitors have the potential for abscopal effects
Purpose Given the uncertainty surrounding the abscopal effect (AE), it is imperative to identify promising treatment targets. In this study, we aimed to explore the incidence of AE when administering radiotherapy to patients with oligoprogressive solid tumours while they are undergoing treatment wit...
Gespeichert in:
| Veröffentlicht in: | Japanese journal of radiology 2024-04, Vol.42 (4), p.424-434 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 434 |
|---|---|
| container_issue | 4 |
| container_start_page | 424 |
| container_title | Japanese journal of radiology |
| container_volume | 42 |
| creator | Ito, Makoto Abe, Souichiro Adachi, Sou Oshima, Yukihiko Takeuchi, Arisa Ohashi, Wataru Iwata, Takashi Ogawa, Tetsuya Ota, Akiko Kubota, Yasuaki Okuda, Takahito Suzuki, Kojiro |
| description | Purpose
Given the uncertainty surrounding the abscopal effect (AE), it is imperative to identify promising treatment targets. In this study, we aimed to explore the incidence of AE when administering radiotherapy to patients with oligoprogressive solid tumours while they are undergoing treatment with immune checkpoint inhibitors (ICIs).
Materials and methods
In this multicentre prospective observational study, oligoprogressive disease was defined as a 2 months before enrolment. We enrolled patients who requested radiotherapy during the ICI rest period between 2020 and 2023. AE was considered present if ≥ 1 non-irradiated lesion decreased by ≥ 30% before the next line of systemic therapy started.
Results
Twelve patients were included in this study; the common primary lesions were in the lungs (four patients) and kidneys (three patients). AEs were observed in six (50%) patients, with a median time to onset of 4 (range 2–9) months after radiotherapy. No significant predictors of AEs were identified. Patients in the AE group had a significantly better 1-year progression-free survival (PFS) rate than those in the non-AE group (
p
= 0.008). Two patients from the AE group were untreated and progression-free at the last follow-up. Four (33%) patients experienced grade 2 toxicity, with two cases attributed to radiotherapy and the other two to ICI treatment. No grade 3 or higher toxicities were observed in any category.
Conclusion
Patients with oligoprogressive disease may be promising targets with potential for AEs. AEs can lead to improved PFS and, in rare cases, to a certain progression-free period without treatment.
Secondary Abstract
Irradiating solid tumours in patients with oligoprogressive disease during immune checkpoint inhibitor therapy may be a promising target with the potential for abscopal effects (AEs). AEs can lead to improved progression-free survival and, in rare cases, to a certain progression-free period without treatment. |
| doi_str_mv | 10.1007/s11604-023-01516-w |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10980609</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3015064029</sourcerecordid><originalsourceid>FETCH-LOGICAL-c499t-5fec60e840681382c371573976aaaa5ebf876671c50102ccdcd0e2b5078343203</originalsourceid><addsrcrecordid>eNp9Uctu1TAQtRCIlsAPsECW2LAJjOPETlYIVbykSiwoEjvL8Z0kLokdbKdX_H3d3nKhLPDGHs85Zx6HkOcMXjMA-SYyJqAuoeIlsIaJcv-AnLJWyJJB-_3h8S3ZCXkS4yWAqHldPyYnvIWOMy5PifvqZ7ujaVv8FiKNk99bN9L8Ofo1-DFgjNY7mjy1y7I5pGZC82P11iVq3WR7m3wmTvoKaZqQrj6hS1bPdPCB6j4av-YAhwFNik_Jo0HPEZ_d3QX59uH9xdmn8vzLx89n785LU3ddKpsMFoBtDaJlvK0Ml6yRvJNC59NgP7RSCMlMAwwqY3ZmB1j1DciW17wCXpC3B9116xfcmdxS0LNag110-KW8tup-xtlJjf5KMehaEHk7BXl1pxD8zw1jUouNBudZO_RbVFUHVcdrmSsW5OU_0Mu8TJfnUzwbk7d-Ay1IdUCZ4GMMOBy7YaBu_FQHP1X2U936qfaZ9OLvOY6U3wZmAD8AYk65EcOf2v-RvQZVwK5a</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3015064029</pqid></control><display><type>article</type><title>Solid tumours showing oligoprogression to immune checkpoint inhibitors have the potential for abscopal effects</title><source>MEDLINE</source><source>SpringerLink Journals</source><creator>Ito, Makoto ; Abe, Souichiro ; Adachi, Sou ; Oshima, Yukihiko ; Takeuchi, Arisa ; Ohashi, Wataru ; Iwata, Takashi ; Ogawa, Tetsuya ; Ota, Akiko ; Kubota, Yasuaki ; Okuda, Takahito ; Suzuki, Kojiro</creator><creatorcontrib>Ito, Makoto ; Abe, Souichiro ; Adachi, Sou ; Oshima, Yukihiko ; Takeuchi, Arisa ; Ohashi, Wataru ; Iwata, Takashi ; Ogawa, Tetsuya ; Ota, Akiko ; Kubota, Yasuaki ; Okuda, Takahito ; Suzuki, Kojiro</creatorcontrib><description>Purpose
Given the uncertainty surrounding the abscopal effect (AE), it is imperative to identify promising treatment targets. In this study, we aimed to explore the incidence of AE when administering radiotherapy to patients with oligoprogressive solid tumours while they are undergoing treatment with immune checkpoint inhibitors (ICIs).
Materials and methods
In this multicentre prospective observational study, oligoprogressive disease was defined as a < 20% increase in lesions compared to > 2 months before enrolment. We enrolled patients who requested radiotherapy during the ICI rest period between 2020 and 2023. AE was considered present if ≥ 1 non-irradiated lesion decreased by ≥ 30% before the next line of systemic therapy started.
Results
Twelve patients were included in this study; the common primary lesions were in the lungs (four patients) and kidneys (three patients). AEs were observed in six (50%) patients, with a median time to onset of 4 (range 2–9) months after radiotherapy. No significant predictors of AEs were identified. Patients in the AE group had a significantly better 1-year progression-free survival (PFS) rate than those in the non-AE group (
p
= 0.008). Two patients from the AE group were untreated and progression-free at the last follow-up. Four (33%) patients experienced grade 2 toxicity, with two cases attributed to radiotherapy and the other two to ICI treatment. No grade 3 or higher toxicities were observed in any category.
Conclusion
Patients with oligoprogressive disease may be promising targets with potential for AEs. AEs can lead to improved PFS and, in rare cases, to a certain progression-free period without treatment.
Secondary Abstract
Irradiating solid tumours in patients with oligoprogressive disease during immune checkpoint inhibitor therapy may be a promising target with the potential for abscopal effects (AEs). AEs can lead to improved progression-free survival and, in rare cases, to a certain progression-free period without treatment.</description><identifier>ISSN: 1867-1071</identifier><identifier>EISSN: 1867-108X</identifier><identifier>DOI: 10.1007/s11604-023-01516-w</identifier><identifier>PMID: 38093137</identifier><language>eng</language><publisher>Singapore: Springer Nature Singapore</publisher><subject>Humans ; Imaging ; Immune checkpoint inhibitors ; Immune Checkpoint Inhibitors - therapeutic use ; Inhibitors ; Kidney ; Lesions ; Lung Neoplasms - drug therapy ; Lung Neoplasms - radiotherapy ; Medicine ; Medicine & Public Health ; Neoplasms - drug therapy ; Neoplasms - radiotherapy ; Nuclear Medicine ; Observational studies ; Original ; Original Article ; Progression-Free Survival ; Radiation Oncology ; Radiation therapy ; Radiology ; Radiotherapy ; Solid tumors ; Survival ; Toxicity ; Tumors</subject><ispartof>Japanese journal of radiology, 2024-04, Vol.42 (4), p.424-434</ispartof><rights>The Author(s) 2023</rights><rights>2023. The Author(s).</rights><rights>The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c499t-5fec60e840681382c371573976aaaa5ebf876671c50102ccdcd0e2b5078343203</citedby><cites>FETCH-LOGICAL-c499t-5fec60e840681382c371573976aaaa5ebf876671c50102ccdcd0e2b5078343203</cites><orcidid>0000-0001-7733-1594</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s11604-023-01516-w$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11604-023-01516-w$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38093137$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ito, Makoto</creatorcontrib><creatorcontrib>Abe, Souichiro</creatorcontrib><creatorcontrib>Adachi, Sou</creatorcontrib><creatorcontrib>Oshima, Yukihiko</creatorcontrib><creatorcontrib>Takeuchi, Arisa</creatorcontrib><creatorcontrib>Ohashi, Wataru</creatorcontrib><creatorcontrib>Iwata, Takashi</creatorcontrib><creatorcontrib>Ogawa, Tetsuya</creatorcontrib><creatorcontrib>Ota, Akiko</creatorcontrib><creatorcontrib>Kubota, Yasuaki</creatorcontrib><creatorcontrib>Okuda, Takahito</creatorcontrib><creatorcontrib>Suzuki, Kojiro</creatorcontrib><title>Solid tumours showing oligoprogression to immune checkpoint inhibitors have the potential for abscopal effects</title><title>Japanese journal of radiology</title><addtitle>Jpn J Radiol</addtitle><addtitle>Jpn J Radiol</addtitle><description>Purpose
Given the uncertainty surrounding the abscopal effect (AE), it is imperative to identify promising treatment targets. In this study, we aimed to explore the incidence of AE when administering radiotherapy to patients with oligoprogressive solid tumours while they are undergoing treatment with immune checkpoint inhibitors (ICIs).
Materials and methods
In this multicentre prospective observational study, oligoprogressive disease was defined as a < 20% increase in lesions compared to > 2 months before enrolment. We enrolled patients who requested radiotherapy during the ICI rest period between 2020 and 2023. AE was considered present if ≥ 1 non-irradiated lesion decreased by ≥ 30% before the next line of systemic therapy started.
Results
Twelve patients were included in this study; the common primary lesions were in the lungs (four patients) and kidneys (three patients). AEs were observed in six (50%) patients, with a median time to onset of 4 (range 2–9) months after radiotherapy. No significant predictors of AEs were identified. Patients in the AE group had a significantly better 1-year progression-free survival (PFS) rate than those in the non-AE group (
p
= 0.008). Two patients from the AE group were untreated and progression-free at the last follow-up. Four (33%) patients experienced grade 2 toxicity, with two cases attributed to radiotherapy and the other two to ICI treatment. No grade 3 or higher toxicities were observed in any category.
Conclusion
Patients with oligoprogressive disease may be promising targets with potential for AEs. AEs can lead to improved PFS and, in rare cases, to a certain progression-free period without treatment.
Secondary Abstract
Irradiating solid tumours in patients with oligoprogressive disease during immune checkpoint inhibitor therapy may be a promising target with the potential for abscopal effects (AEs). AEs can lead to improved progression-free survival and, in rare cases, to a certain progression-free period without treatment.</description><subject>Humans</subject><subject>Imaging</subject><subject>Immune checkpoint inhibitors</subject><subject>Immune Checkpoint Inhibitors - therapeutic use</subject><subject>Inhibitors</subject><subject>Kidney</subject><subject>Lesions</subject><subject>Lung Neoplasms - drug therapy</subject><subject>Lung Neoplasms - radiotherapy</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Neoplasms - drug therapy</subject><subject>Neoplasms - radiotherapy</subject><subject>Nuclear Medicine</subject><subject>Observational studies</subject><subject>Original</subject><subject>Original Article</subject><subject>Progression-Free Survival</subject><subject>Radiation Oncology</subject><subject>Radiation therapy</subject><subject>Radiology</subject><subject>Radiotherapy</subject><subject>Solid tumors</subject><subject>Survival</subject><subject>Toxicity</subject><subject>Tumors</subject><issn>1867-1071</issn><issn>1867-108X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><recordid>eNp9Uctu1TAQtRCIlsAPsECW2LAJjOPETlYIVbykSiwoEjvL8Z0kLokdbKdX_H3d3nKhLPDGHs85Zx6HkOcMXjMA-SYyJqAuoeIlsIaJcv-AnLJWyJJB-_3h8S3ZCXkS4yWAqHldPyYnvIWOMy5PifvqZ7ujaVv8FiKNk99bN9L8Ofo1-DFgjNY7mjy1y7I5pGZC82P11iVq3WR7m3wmTvoKaZqQrj6hS1bPdPCB6j4av-YAhwFNik_Jo0HPEZ_d3QX59uH9xdmn8vzLx89n785LU3ddKpsMFoBtDaJlvK0Ml6yRvJNC59NgP7RSCMlMAwwqY3ZmB1j1DciW17wCXpC3B9116xfcmdxS0LNag110-KW8tup-xtlJjf5KMehaEHk7BXl1pxD8zw1jUouNBudZO_RbVFUHVcdrmSsW5OU_0Mu8TJfnUzwbk7d-Ay1IdUCZ4GMMOBy7YaBu_FQHP1X2U936qfaZ9OLvOY6U3wZmAD8AYk65EcOf2v-RvQZVwK5a</recordid><startdate>20240401</startdate><enddate>20240401</enddate><creator>Ito, Makoto</creator><creator>Abe, Souichiro</creator><creator>Adachi, Sou</creator><creator>Oshima, Yukihiko</creator><creator>Takeuchi, Arisa</creator><creator>Ohashi, Wataru</creator><creator>Iwata, Takashi</creator><creator>Ogawa, Tetsuya</creator><creator>Ota, Akiko</creator><creator>Kubota, Yasuaki</creator><creator>Okuda, Takahito</creator><creator>Suzuki, Kojiro</creator><general>Springer Nature Singapore</general><general>Springer Nature B.V</general><scope>C6C</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>7QO</scope><scope>7TK</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>P64</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-7733-1594</orcidid></search><sort><creationdate>20240401</creationdate><title>Solid tumours showing oligoprogression to immune checkpoint inhibitors have the potential for abscopal effects</title><author>Ito, Makoto ; Abe, Souichiro ; Adachi, Sou ; Oshima, Yukihiko ; Takeuchi, Arisa ; Ohashi, Wataru ; Iwata, Takashi ; Ogawa, Tetsuya ; Ota, Akiko ; Kubota, Yasuaki ; Okuda, Takahito ; Suzuki, Kojiro</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c499t-5fec60e840681382c371573976aaaa5ebf876671c50102ccdcd0e2b5078343203</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Humans</topic><topic>Imaging</topic><topic>Immune checkpoint inhibitors</topic><topic>Immune Checkpoint Inhibitors - therapeutic use</topic><topic>Inhibitors</topic><topic>Kidney</topic><topic>Lesions</topic><topic>Lung Neoplasms - drug therapy</topic><topic>Lung Neoplasms - radiotherapy</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Neoplasms - drug therapy</topic><topic>Neoplasms - radiotherapy</topic><topic>Nuclear Medicine</topic><topic>Observational studies</topic><topic>Original</topic><topic>Original Article</topic><topic>Progression-Free Survival</topic><topic>Radiation Oncology</topic><topic>Radiation therapy</topic><topic>Radiology</topic><topic>Radiotherapy</topic><topic>Solid tumors</topic><topic>Survival</topic><topic>Toxicity</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ito, Makoto</creatorcontrib><creatorcontrib>Abe, Souichiro</creatorcontrib><creatorcontrib>Adachi, Sou</creatorcontrib><creatorcontrib>Oshima, Yukihiko</creatorcontrib><creatorcontrib>Takeuchi, Arisa</creatorcontrib><creatorcontrib>Ohashi, Wataru</creatorcontrib><creatorcontrib>Iwata, Takashi</creatorcontrib><creatorcontrib>Ogawa, Tetsuya</creatorcontrib><creatorcontrib>Ota, Akiko</creatorcontrib><creatorcontrib>Kubota, Yasuaki</creatorcontrib><creatorcontrib>Okuda, Takahito</creatorcontrib><creatorcontrib>Suzuki, Kojiro</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Japanese journal of radiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ito, Makoto</au><au>Abe, Souichiro</au><au>Adachi, Sou</au><au>Oshima, Yukihiko</au><au>Takeuchi, Arisa</au><au>Ohashi, Wataru</au><au>Iwata, Takashi</au><au>Ogawa, Tetsuya</au><au>Ota, Akiko</au><au>Kubota, Yasuaki</au><au>Okuda, Takahito</au><au>Suzuki, Kojiro</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Solid tumours showing oligoprogression to immune checkpoint inhibitors have the potential for abscopal effects</atitle><jtitle>Japanese journal of radiology</jtitle><stitle>Jpn J Radiol</stitle><addtitle>Jpn J Radiol</addtitle><date>2024-04-01</date><risdate>2024</risdate><volume>42</volume><issue>4</issue><spage>424</spage><epage>434</epage><pages>424-434</pages><issn>1867-1071</issn><eissn>1867-108X</eissn><abstract>Purpose
Given the uncertainty surrounding the abscopal effect (AE), it is imperative to identify promising treatment targets. In this study, we aimed to explore the incidence of AE when administering radiotherapy to patients with oligoprogressive solid tumours while they are undergoing treatment with immune checkpoint inhibitors (ICIs).
Materials and methods
In this multicentre prospective observational study, oligoprogressive disease was defined as a < 20% increase in lesions compared to > 2 months before enrolment. We enrolled patients who requested radiotherapy during the ICI rest period between 2020 and 2023. AE was considered present if ≥ 1 non-irradiated lesion decreased by ≥ 30% before the next line of systemic therapy started.
Results
Twelve patients were included in this study; the common primary lesions were in the lungs (four patients) and kidneys (three patients). AEs were observed in six (50%) patients, with a median time to onset of 4 (range 2–9) months after radiotherapy. No significant predictors of AEs were identified. Patients in the AE group had a significantly better 1-year progression-free survival (PFS) rate than those in the non-AE group (
p
= 0.008). Two patients from the AE group were untreated and progression-free at the last follow-up. Four (33%) patients experienced grade 2 toxicity, with two cases attributed to radiotherapy and the other two to ICI treatment. No grade 3 or higher toxicities were observed in any category.
Conclusion
Patients with oligoprogressive disease may be promising targets with potential for AEs. AEs can lead to improved PFS and, in rare cases, to a certain progression-free period without treatment.
Secondary Abstract
Irradiating solid tumours in patients with oligoprogressive disease during immune checkpoint inhibitor therapy may be a promising target with the potential for abscopal effects (AEs). AEs can lead to improved progression-free survival and, in rare cases, to a certain progression-free period without treatment.</abstract><cop>Singapore</cop><pub>Springer Nature Singapore</pub><pmid>38093137</pmid><doi>10.1007/s11604-023-01516-w</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0001-7733-1594</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1867-1071 |
| ispartof | Japanese journal of radiology, 2024-04, Vol.42 (4), p.424-434 |
| issn | 1867-1071 1867-108X |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10980609 |
| source | MEDLINE; SpringerLink Journals |
| subjects | Humans Imaging Immune checkpoint inhibitors Immune Checkpoint Inhibitors - therapeutic use Inhibitors Kidney Lesions Lung Neoplasms - drug therapy Lung Neoplasms - radiotherapy Medicine Medicine & Public Health Neoplasms - drug therapy Neoplasms - radiotherapy Nuclear Medicine Observational studies Original Original Article Progression-Free Survival Radiation Oncology Radiation therapy Radiology Radiotherapy Solid tumors Survival Toxicity Tumors |
| title | Solid tumours showing oligoprogression to immune checkpoint inhibitors have the potential for abscopal effects |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-10T06%3A53%3A33IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Solid%20tumours%20showing%20oligoprogression%20to%20immune%20checkpoint%20inhibitors%20have%20the%20potential%20for%20abscopal%20effects&rft.jtitle=Japanese%20journal%20of%20radiology&rft.au=Ito,%20Makoto&rft.date=2024-04-01&rft.volume=42&rft.issue=4&rft.spage=424&rft.epage=434&rft.pages=424-434&rft.issn=1867-1071&rft.eissn=1867-108X&rft_id=info:doi/10.1007/s11604-023-01516-w&rft_dat=%3Cproquest_pubme%3E3015064029%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=3015064029&rft_id=info:pmid/38093137&rfr_iscdi=true |