Lurbinectedin as second- or third-line palliative therapy in malignant pleural mesothelioma: an international, multi-centre, single-arm, phase II trial (SAKK 17/16)
Systemic second- and third-line therapies for malignant pleural mesothelioma (MPM) result in a median progression-free survival (mPFS) of
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| Veröffentlicht in: | Annals of oncology 2020-04, Vol.31 (4), p.495-500 |
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| creator | Metaxas, Y. Früh, M. Eboulet, E.I. Grosso, F. Pless, M. Zucali, P.A. Ceresoli, G.L. Mark, M. Schneider, M. Maconi, A. Perrino, M. Biaggi-Rudolf, C. Froesch, P. Schmid, S. Waibel, C. Appenzeller, C. Rauch, D. von Moos, R. |
| description | Systemic second- and third-line therapies for malignant pleural mesothelioma (MPM) result in a median progression-free survival (mPFS) of |
| doi_str_mv | 10.1016/j.annonc.2019.12.009 |
| format | Article |
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Pts with progressing MPM treated with first-line platinum-pemetrexed chemotherapy with or without immunotherapy received lurbinectedin monotherapy. Treatment was given intravenously at 3.2 mg/m2 dose every 3 weeks until progression or unacceptable toxicity. Using Simon's two-stage design, the primary endpoint, progression-free survival (PFS) at 12 weeks (PFS12wks), was met if achieved by ≥21 pts (p0 ≤35% versus p1 ≥55%).
Forty-two pts from nine centres across Switzerland and Italy were recruited. Histology was epithelioid in 33 cases, sarcomatoid in 5, and biphasic in 4. Overall 10/42 (23.8%) underwent prior immunotherapy and 14/42 (33.3%) had progressed ≤6 months after first-line chemotherapy. At data cut-off PFS12wks was met by 22/42 pts (52.4%; 90% confidence interval (CI): 38.7% to 63.5%; P = 0.015) with an mPFS of 4.1 months and mOS of 11.1 months. The best response was complete and partial remission observed in one patient each and stable disease in 20 pts. The duration of disease control was 6.6 months (95% CI: 5.2–7.4). No significant difference in PFS12wks, mPFS, and mOS was recorded in epithelioid versus non-epithelioid cases and pts with prior immunotherapy versus those without. Similar mPFS but shorter mOS were observed among pts who progressed within ≤6 months after first-line chemotherapy. Lurbinectedin-related grade 3–4 toxicity was seen in 21 pts, mostly being neutropenia (23.8%) and fatigue (16.7%).
The primary efficacy endpoint was reached with acceptable toxicity. Lurbinectedin showed promising activity regardless of histology, prior immunotherapy, or outcome on prior treatment.
NCT03213301
•Lurbinectedin demonstrated clinical activity in 42 patients with progressing MPM, with acceptable toxicity.•Analysis of histology, prior immunotherapy, time to progression on first-line chemotherapy revealed benefit in all subgroups.•Lurbinectedin emerges as a new treatment option and evaluation in a larger randomised trial is warranted.</description><identifier>ISSN: 0923-7534</identifier><identifier>EISSN: 1569-8041</identifier><identifier>DOI: 10.1016/j.annonc.2019.12.009</identifier><identifier>PMID: 32085891</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Carbolines ; Heterocyclic Compounds, 4 or More Rings ; Humans ; Italy ; lurbinectedin ; mesothelioma ; Mesothelioma - drug therapy ; Mesothelioma, Malignant ; Palliative Care ; phase II trial ; Pleural Neoplasms - drug therapy ; Switzerland</subject><ispartof>Annals of oncology, 2020-04, Vol.31 (4), p.495-500</ispartof><rights>2020 European Society for Medical Oncology</rights><rights>Copyright © 2020 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c408t-3247e13a192e8c011d388fcb0a580f984c623fd8f6334fbb2348c757c45cf1e23</citedby><cites>FETCH-LOGICAL-c408t-3247e13a192e8c011d388fcb0a580f984c623fd8f6334fbb2348c757c45cf1e23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32085891$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Metaxas, Y.</creatorcontrib><creatorcontrib>Früh, M.</creatorcontrib><creatorcontrib>Eboulet, E.I.</creatorcontrib><creatorcontrib>Grosso, F.</creatorcontrib><creatorcontrib>Pless, M.</creatorcontrib><creatorcontrib>Zucali, P.A.</creatorcontrib><creatorcontrib>Ceresoli, G.L.</creatorcontrib><creatorcontrib>Mark, M.</creatorcontrib><creatorcontrib>Schneider, M.</creatorcontrib><creatorcontrib>Maconi, A.</creatorcontrib><creatorcontrib>Perrino, M.</creatorcontrib><creatorcontrib>Biaggi-Rudolf, C.</creatorcontrib><creatorcontrib>Froesch, P.</creatorcontrib><creatorcontrib>Schmid, S.</creatorcontrib><creatorcontrib>Waibel, C.</creatorcontrib><creatorcontrib>Appenzeller, C.</creatorcontrib><creatorcontrib>Rauch, D.</creatorcontrib><creatorcontrib>von Moos, R.</creatorcontrib><creatorcontrib>Swiss Group for Clinical Cancer Research (SAKK)</creatorcontrib><title>Lurbinectedin as second- or third-line palliative therapy in malignant pleural mesothelioma: an international, multi-centre, single-arm, phase II trial (SAKK 17/16)</title><title>Annals of oncology</title><addtitle>Ann Oncol</addtitle><description>Systemic second- and third-line therapies for malignant pleural mesothelioma (MPM) result in a median progression-free survival (mPFS) of <2 months and median overall survival (mOS) of 6–9 months. Lurbinectedin binds to the DNA of the regulatory region while inhibiting tumour-associated macrophage transcription. In early trials, encouraging outcomes occurred in patients (pts) with MPM treated with lurbinectedin. We aimed to generate lurbinectedin efficacy and safety data among pts with progressive MPM.
Pts with progressing MPM treated with first-line platinum-pemetrexed chemotherapy with or without immunotherapy received lurbinectedin monotherapy. Treatment was given intravenously at 3.2 mg/m2 dose every 3 weeks until progression or unacceptable toxicity. Using Simon's two-stage design, the primary endpoint, progression-free survival (PFS) at 12 weeks (PFS12wks), was met if achieved by ≥21 pts (p0 ≤35% versus p1 ≥55%).
Forty-two pts from nine centres across Switzerland and Italy were recruited. Histology was epithelioid in 33 cases, sarcomatoid in 5, and biphasic in 4. Overall 10/42 (23.8%) underwent prior immunotherapy and 14/42 (33.3%) had progressed ≤6 months after first-line chemotherapy. At data cut-off PFS12wks was met by 22/42 pts (52.4%; 90% confidence interval (CI): 38.7% to 63.5%; P = 0.015) with an mPFS of 4.1 months and mOS of 11.1 months. The best response was complete and partial remission observed in one patient each and stable disease in 20 pts. The duration of disease control was 6.6 months (95% CI: 5.2–7.4). No significant difference in PFS12wks, mPFS, and mOS was recorded in epithelioid versus non-epithelioid cases and pts with prior immunotherapy versus those without. Similar mPFS but shorter mOS were observed among pts who progressed within ≤6 months after first-line chemotherapy. Lurbinectedin-related grade 3–4 toxicity was seen in 21 pts, mostly being neutropenia (23.8%) and fatigue (16.7%).
The primary efficacy endpoint was reached with acceptable toxicity. Lurbinectedin showed promising activity regardless of histology, prior immunotherapy, or outcome on prior treatment.
NCT03213301
•Lurbinectedin demonstrated clinical activity in 42 patients with progressing MPM, with acceptable toxicity.•Analysis of histology, prior immunotherapy, time to progression on first-line chemotherapy revealed benefit in all subgroups.•Lurbinectedin emerges as a new treatment option and evaluation in a larger randomised trial is warranted.</description><subject>Carbolines</subject><subject>Heterocyclic Compounds, 4 or More Rings</subject><subject>Humans</subject><subject>Italy</subject><subject>lurbinectedin</subject><subject>mesothelioma</subject><subject>Mesothelioma - drug therapy</subject><subject>Mesothelioma, Malignant</subject><subject>Palliative Care</subject><subject>phase II trial</subject><subject>Pleural Neoplasms - drug therapy</subject><subject>Switzerland</subject><issn>0923-7534</issn><issn>1569-8041</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kV1rFDEUhoModlv9ByK5rLAzzcd8JF4IpVRduuCFeh0ymTNtlkwyJplC_48_1CxbvfTqQM7znsPJg9A7SmpKaHd1qLX3wZuaESprympC5Au0oW0nK0Ea-hJtiGS86lvenKHzlA6EkE4y-RqdcUZEKyTdoN_7NQ7Wg8kwWo91wglM8GOFQ8T5wcaxcqWNF-2c1dk-QnmFqJcnXPBZO3vvtc94cbBG7fAMKRTA2TDrj1j7QmWIviSD126L59VlWxnwOcIWJ-vvHVQ6zlu8POgEeLfDOdoy6PL79d0dpv0V7T68Qa8m7RK8fa4X6Ofn2x83X6v9ty-7m-t9ZRoicsVZ0wPlmkoGwhBKRy7EZAaiW0EmKRrTMT6NYuo4b6ZhYLwRpm9707RmosD4Bbo8zV1i-LVCymq2yYBz2kNYk2K8O35cS_uCNifUxJBShEkt0c46PilK1NGPOqiTH3X0oyhTxU-JvX_esA4zjP9Cf4UU4NMJgHLno4WokrHgTbETiyQ1Bvv_DX8ASyOj8w</recordid><startdate>202004</startdate><enddate>202004</enddate><creator>Metaxas, Y.</creator><creator>Früh, M.</creator><creator>Eboulet, E.I.</creator><creator>Grosso, F.</creator><creator>Pless, M.</creator><creator>Zucali, P.A.</creator><creator>Ceresoli, G.L.</creator><creator>Mark, M.</creator><creator>Schneider, M.</creator><creator>Maconi, A.</creator><creator>Perrino, M.</creator><creator>Biaggi-Rudolf, C.</creator><creator>Froesch, P.</creator><creator>Schmid, S.</creator><creator>Waibel, C.</creator><creator>Appenzeller, C.</creator><creator>Rauch, D.</creator><creator>von Moos, R.</creator><general>Elsevier Ltd</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>7X8</scope></search><sort><creationdate>202004</creationdate><title>Lurbinectedin as second- or third-line palliative therapy in malignant pleural mesothelioma: an international, multi-centre, single-arm, phase II trial (SAKK 17/16)</title><author>Metaxas, Y. ; Früh, M. ; Eboulet, E.I. ; Grosso, F. ; Pless, M. ; Zucali, P.A. ; Ceresoli, G.L. ; Mark, M. ; Schneider, M. ; Maconi, A. ; Perrino, M. ; Biaggi-Rudolf, C. ; Froesch, P. ; Schmid, S. ; Waibel, C. ; Appenzeller, C. ; Rauch, D. ; von Moos, R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c408t-3247e13a192e8c011d388fcb0a580f984c623fd8f6334fbb2348c757c45cf1e23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Carbolines</topic><topic>Heterocyclic Compounds, 4 or More Rings</topic><topic>Humans</topic><topic>Italy</topic><topic>lurbinectedin</topic><topic>mesothelioma</topic><topic>Mesothelioma - drug therapy</topic><topic>Mesothelioma, Malignant</topic><topic>Palliative Care</topic><topic>phase II trial</topic><topic>Pleural Neoplasms - drug therapy</topic><topic>Switzerland</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Metaxas, Y.</creatorcontrib><creatorcontrib>Früh, M.</creatorcontrib><creatorcontrib>Eboulet, E.I.</creatorcontrib><creatorcontrib>Grosso, F.</creatorcontrib><creatorcontrib>Pless, M.</creatorcontrib><creatorcontrib>Zucali, P.A.</creatorcontrib><creatorcontrib>Ceresoli, G.L.</creatorcontrib><creatorcontrib>Mark, M.</creatorcontrib><creatorcontrib>Schneider, M.</creatorcontrib><creatorcontrib>Maconi, A.</creatorcontrib><creatorcontrib>Perrino, M.</creatorcontrib><creatorcontrib>Biaggi-Rudolf, C.</creatorcontrib><creatorcontrib>Froesch, P.</creatorcontrib><creatorcontrib>Schmid, S.</creatorcontrib><creatorcontrib>Waibel, C.</creatorcontrib><creatorcontrib>Appenzeller, C.</creatorcontrib><creatorcontrib>Rauch, D.</creatorcontrib><creatorcontrib>von Moos, R.</creatorcontrib><creatorcontrib>Swiss Group for Clinical Cancer Research (SAKK)</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>Annals of oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Metaxas, Y.</au><au>Früh, M.</au><au>Eboulet, E.I.</au><au>Grosso, F.</au><au>Pless, M.</au><au>Zucali, P.A.</au><au>Ceresoli, G.L.</au><au>Mark, M.</au><au>Schneider, M.</au><au>Maconi, A.</au><au>Perrino, M.</au><au>Biaggi-Rudolf, C.</au><au>Froesch, P.</au><au>Schmid, S.</au><au>Waibel, C.</au><au>Appenzeller, C.</au><au>Rauch, D.</au><au>von Moos, R.</au><aucorp>Swiss Group for Clinical Cancer Research (SAKK)</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Lurbinectedin as second- or third-line palliative therapy in malignant pleural mesothelioma: an international, multi-centre, single-arm, phase II trial (SAKK 17/16)</atitle><jtitle>Annals of oncology</jtitle><addtitle>Ann Oncol</addtitle><date>2020-04</date><risdate>2020</risdate><volume>31</volume><issue>4</issue><spage>495</spage><epage>500</epage><pages>495-500</pages><issn>0923-7534</issn><eissn>1569-8041</eissn><abstract>Systemic second- and third-line therapies for malignant pleural mesothelioma (MPM) result in a median progression-free survival (mPFS) of <2 months and median overall survival (mOS) of 6–9 months. Lurbinectedin binds to the DNA of the regulatory region while inhibiting tumour-associated macrophage transcription. In early trials, encouraging outcomes occurred in patients (pts) with MPM treated with lurbinectedin. We aimed to generate lurbinectedin efficacy and safety data among pts with progressive MPM.
Pts with progressing MPM treated with first-line platinum-pemetrexed chemotherapy with or without immunotherapy received lurbinectedin monotherapy. Treatment was given intravenously at 3.2 mg/m2 dose every 3 weeks until progression or unacceptable toxicity. Using Simon's two-stage design, the primary endpoint, progression-free survival (PFS) at 12 weeks (PFS12wks), was met if achieved by ≥21 pts (p0 ≤35% versus p1 ≥55%).
Forty-two pts from nine centres across Switzerland and Italy were recruited. Histology was epithelioid in 33 cases, sarcomatoid in 5, and biphasic in 4. Overall 10/42 (23.8%) underwent prior immunotherapy and 14/42 (33.3%) had progressed ≤6 months after first-line chemotherapy. At data cut-off PFS12wks was met by 22/42 pts (52.4%; 90% confidence interval (CI): 38.7% to 63.5%; P = 0.015) with an mPFS of 4.1 months and mOS of 11.1 months. The best response was complete and partial remission observed in one patient each and stable disease in 20 pts. The duration of disease control was 6.6 months (95% CI: 5.2–7.4). No significant difference in PFS12wks, mPFS, and mOS was recorded in epithelioid versus non-epithelioid cases and pts with prior immunotherapy versus those without. Similar mPFS but shorter mOS were observed among pts who progressed within ≤6 months after first-line chemotherapy. Lurbinectedin-related grade 3–4 toxicity was seen in 21 pts, mostly being neutropenia (23.8%) and fatigue (16.7%).
The primary efficacy endpoint was reached with acceptable toxicity. Lurbinectedin showed promising activity regardless of histology, prior immunotherapy, or outcome on prior treatment.
NCT03213301
•Lurbinectedin demonstrated clinical activity in 42 patients with progressing MPM, with acceptable toxicity.•Analysis of histology, prior immunotherapy, time to progression on first-line chemotherapy revealed benefit in all subgroups.•Lurbinectedin emerges as a new treatment option and evaluation in a larger randomised trial is warranted.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>32085891</pmid><doi>10.1016/j.annonc.2019.12.009</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0923-7534 |
| ispartof | Annals of oncology, 2020-04, Vol.31 (4), p.495-500 |
| issn | 0923-7534 1569-8041 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2362085517 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Carbolines Heterocyclic Compounds, 4 or More Rings Humans Italy lurbinectedin mesothelioma Mesothelioma - drug therapy Mesothelioma, Malignant Palliative Care phase II trial Pleural Neoplasms - drug therapy Switzerland |
| title | Lurbinectedin as second- or third-line palliative therapy in malignant pleural mesothelioma: an international, multi-centre, single-arm, phase II trial (SAKK 17/16) |
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