Treatment effect of mTOR-inhibition on tissue composition of renal angiomyolipomas in tuberous sclerosis complex (TSC)
Tuberous sclerosis complex (TSC)-associated renal angiomyolipoma (AML) have a high lifetime risk of acute bleeding. MTOR-inhibitors are a promising novel treatment for TSC-AML, however adequate response to therapy can be difficult to assess. Early changes in MRI signal may serve as a novel early ind...
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| description | Tuberous sclerosis complex (TSC)-associated renal angiomyolipoma (AML) have a high lifetime risk of acute bleeding. MTOR-inhibitors are a promising novel treatment for TSC-AML, however adequate response to therapy can be difficult to assess. Early changes in MRI signal may serve as a novel early indicator for a satisfactory response to mTOR-inhibitor therapy of AML.
Thirty-eight patients with the definite diagnosis of tuberous sclerosis receiving everolimus therapy and n = 19 patients without specific therapy were included. 1.5 Tesla MRI was performed including sequences with a selective fat suppression. Patients were investigated prior to the initiation of therapy (baseline) and after |
| doi_str_mv | 10.1371/journal.pone.0189132 |
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Thirty-eight patients with the definite diagnosis of tuberous sclerosis receiving everolimus therapy and n = 19 patients without specific therapy were included. 1.5 Tesla MRI was performed including sequences with a selective fat suppression. Patients were investigated prior to the initiation of therapy (baseline) and after <3 months (n = 21 patients), 3 to 6 months (n = 32) and 18 to 24 months (n = 28). Signal and size changes of renal AMLs were assessed at all different timepoints. Signal-to-noise-ratio (SNR), contrast-to-noise-ratio (CNR) and size of angiomyolipomas were evaluated.
Signal changes in 273 AMLs were evaluated. A significant and strong decrease of the CNR of AMLs following the initiation of therapy was measured in the fat-suppressed MR sequence at all time points, compared to the baseline: From 7.41±6.98 to 3.84±6.25 (p ≤ 0.05p = 0.002), 3.36±6.93 (p<0.0001), and 2.50±6.68 (p<0.0001) after less than 3 months, 3-6 months or 18-24 months of everolimus treatment, respectively. Also, a significant, however less pronounced, reduction of angiomyolipoma size in the different groups was measured (from baseline 2022.2±2657.7 mm2 to 1854.4±1670.9 mm2 (p = 0.009), 1875.5±3190.1 mm2 (p<0.001), and 1365.8 ± 1628.8 mm2 (p<0.0001) after less than 3 months, 3-6 months or 18-24 months of everolimus treatment, respectively). No significant changes in CNR (p>0.05) and size (p>0.05) were measured in the control group.
mTOR inhibitor therapy in TSC patients results in an early and pronounced fatty transformation of AMLs on MRI. Fatty transformation could represent a novel early indicator of response to therapy in this patient collective.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0189132</identifier><identifier>PMID: 29232371</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Age ; Angiomyolipoma ; Biology and Life Sciences ; Bleeding ; Care and treatment ; Complications and side effects ; Composition effects ; Connective tissue tumors ; Diagnosis ; Drug therapy ; Inhibitors ; Intensive care ; Kidneys ; Magnetic resonance imaging ; Medicine and Health Sciences ; Nephrology ; Noise ; Patients ; Research and Analysis Methods ; Risk factors ; Studies ; Therapy ; TOR protein ; Transformation ; Transplants & implants ; Tuberous sclerosis</subject><ispartof>PloS one, 2017-12, Vol.12 (12), p.e0189132-e0189132</ispartof><rights>COPYRIGHT 2017 Public Library of Science</rights><rights>2017 Brakemeier et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2017 Brakemeier et al 2017 Brakemeier et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-91c4ffa652621c6ccbcd7cb6374927be269dc20af0df3c55e42f5b2f9a3ec6fa3</citedby><cites>FETCH-LOGICAL-c692t-91c4ffa652621c6ccbcd7cb6374927be269dc20af0df3c55e42f5b2f9a3ec6fa3</cites><orcidid>0000-0003-3845-211X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5726644/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5726644/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29232371$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Brakemeier, Susanne</creatorcontrib><creatorcontrib>Vogt, Lars</creatorcontrib><creatorcontrib>Adams, Lisa</creatorcontrib><creatorcontrib>Zukunft, Bianca</creatorcontrib><creatorcontrib>Diederichs, Gerd</creatorcontrib><creatorcontrib>Hamm, Bernd</creatorcontrib><creatorcontrib>Budde, Klemens</creatorcontrib><creatorcontrib>Makowski, Marcus R</creatorcontrib><title>Treatment effect of mTOR-inhibition on tissue composition of renal angiomyolipomas in tuberous sclerosis complex (TSC)</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Tuberous sclerosis complex (TSC)-associated renal angiomyolipoma (AML) have a high lifetime risk of acute bleeding. MTOR-inhibitors are a promising novel treatment for TSC-AML, however adequate response to therapy can be difficult to assess. Early changes in MRI signal may serve as a novel early indicator for a satisfactory response to mTOR-inhibitor therapy of AML.
Thirty-eight patients with the definite diagnosis of tuberous sclerosis receiving everolimus therapy and n = 19 patients without specific therapy were included. 1.5 Tesla MRI was performed including sequences with a selective fat suppression. Patients were investigated prior to the initiation of therapy (baseline) and after <3 months (n = 21 patients), 3 to 6 months (n = 32) and 18 to 24 months (n = 28). Signal and size changes of renal AMLs were assessed at all different timepoints. Signal-to-noise-ratio (SNR), contrast-to-noise-ratio (CNR) and size of angiomyolipomas were evaluated.
Signal changes in 273 AMLs were evaluated. A significant and strong decrease of the CNR of AMLs following the initiation of therapy was measured in the fat-suppressed MR sequence at all time points, compared to the baseline: From 7.41±6.98 to 3.84±6.25 (p ≤ 0.05p = 0.002), 3.36±6.93 (p<0.0001), and 2.50±6.68 (p<0.0001) after less than 3 months, 3-6 months or 18-24 months of everolimus treatment, respectively. Also, a significant, however less pronounced, reduction of angiomyolipoma size in the different groups was measured (from baseline 2022.2±2657.7 mm2 to 1854.4±1670.9 mm2 (p = 0.009), 1875.5±3190.1 mm2 (p<0.001), and 1365.8 ± 1628.8 mm2 (p<0.0001) after less than 3 months, 3-6 months or 18-24 months of everolimus treatment, respectively). No significant changes in CNR (p>0.05) and size (p>0.05) were measured in the control group.
mTOR inhibitor therapy in TSC patients results in an early and pronounced fatty transformation of AMLs on MRI. Fatty transformation could represent a novel early indicator of response to therapy in this patient collective.</description><subject>Age</subject><subject>Angiomyolipoma</subject><subject>Biology and Life Sciences</subject><subject>Bleeding</subject><subject>Care and treatment</subject><subject>Complications and side effects</subject><subject>Composition effects</subject><subject>Connective tissue tumors</subject><subject>Diagnosis</subject><subject>Drug therapy</subject><subject>Inhibitors</subject><subject>Intensive care</subject><subject>Kidneys</subject><subject>Magnetic resonance imaging</subject><subject>Medicine and Health Sciences</subject><subject>Nephrology</subject><subject>Noise</subject><subject>Patients</subject><subject>Research and Analysis Methods</subject><subject>Risk factors</subject><subject>Studies</subject><subject>Therapy</subject><subject>TOR protein</subject><subject>Transformation</subject><subject>Transplants & implants</subject><subject>Tuberous 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effect of mTOR-inhibition on tissue composition of renal angiomyolipomas in tuberous sclerosis complex (TSC)</title><author>Brakemeier, Susanne ; Vogt, Lars ; Adams, Lisa ; Zukunft, Bianca ; Diederichs, Gerd ; Hamm, Bernd ; Budde, Klemens ; Makowski, Marcus R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-91c4ffa652621c6ccbcd7cb6374927be269dc20af0df3c55e42f5b2f9a3ec6fa3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Age</topic><topic>Angiomyolipoma</topic><topic>Biology and Life Sciences</topic><topic>Bleeding</topic><topic>Care and treatment</topic><topic>Complications and side effects</topic><topic>Composition effects</topic><topic>Connective tissue tumors</topic><topic>Diagnosis</topic><topic>Drug therapy</topic><topic>Inhibitors</topic><topic>Intensive care</topic><topic>Kidneys</topic><topic>Magnetic resonance imaging</topic><topic>Medicine and Health Sciences</topic><topic>Nephrology</topic><topic>Noise</topic><topic>Patients</topic><topic>Research and Analysis Methods</topic><topic>Risk factors</topic><topic>Studies</topic><topic>Therapy</topic><topic>TOR protein</topic><topic>Transformation</topic><topic>Transplants & implants</topic><topic>Tuberous sclerosis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Brakemeier, Susanne</creatorcontrib><creatorcontrib>Vogt, Lars</creatorcontrib><creatorcontrib>Adams, Lisa</creatorcontrib><creatorcontrib>Zukunft, Bianca</creatorcontrib><creatorcontrib>Diederichs, Gerd</creatorcontrib><creatorcontrib>Hamm, Bernd</creatorcontrib><creatorcontrib>Budde, Klemens</creatorcontrib><creatorcontrib>Makowski, Marcus R</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central 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One</addtitle><date>2017-12-12</date><risdate>2017</risdate><volume>12</volume><issue>12</issue><spage>e0189132</spage><epage>e0189132</epage><pages>e0189132-e0189132</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Tuberous sclerosis complex (TSC)-associated renal angiomyolipoma (AML) have a high lifetime risk of acute bleeding. MTOR-inhibitors are a promising novel treatment for TSC-AML, however adequate response to therapy can be difficult to assess. Early changes in MRI signal may serve as a novel early indicator for a satisfactory response to mTOR-inhibitor therapy of AML.
Thirty-eight patients with the definite diagnosis of tuberous sclerosis receiving everolimus therapy and n = 19 patients without specific therapy were included. 1.5 Tesla MRI was performed including sequences with a selective fat suppression. Patients were investigated prior to the initiation of therapy (baseline) and after <3 months (n = 21 patients), 3 to 6 months (n = 32) and 18 to 24 months (n = 28). Signal and size changes of renal AMLs were assessed at all different timepoints. Signal-to-noise-ratio (SNR), contrast-to-noise-ratio (CNR) and size of angiomyolipomas were evaluated.
Signal changes in 273 AMLs were evaluated. A significant and strong decrease of the CNR of AMLs following the initiation of therapy was measured in the fat-suppressed MR sequence at all time points, compared to the baseline: From 7.41±6.98 to 3.84±6.25 (p ≤ 0.05p = 0.002), 3.36±6.93 (p<0.0001), and 2.50±6.68 (p<0.0001) after less than 3 months, 3-6 months or 18-24 months of everolimus treatment, respectively. Also, a significant, however less pronounced, reduction of angiomyolipoma size in the different groups was measured (from baseline 2022.2±2657.7 mm2 to 1854.4±1670.9 mm2 (p = 0.009), 1875.5±3190.1 mm2 (p<0.001), and 1365.8 ± 1628.8 mm2 (p<0.0001) after less than 3 months, 3-6 months or 18-24 months of everolimus treatment, respectively). No significant changes in CNR (p>0.05) and size (p>0.05) were measured in the control group.
mTOR inhibitor therapy in TSC patients results in an early and pronounced fatty transformation of AMLs on MRI. Fatty transformation could represent a novel early indicator of response to therapy in this patient collective.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>29232371</pmid><doi>10.1371/journal.pone.0189132</doi><tpages>e0189132</tpages><orcidid>https://orcid.org/0000-0003-3845-211X</orcidid><oa>free_for_read</oa></addata></record> |
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| source | Public Library of Science (PLoS) Journals Open Access; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Age Angiomyolipoma Biology and Life Sciences Bleeding Care and treatment Complications and side effects Composition effects Connective tissue tumors Diagnosis Drug therapy Inhibitors Intensive care Kidneys Magnetic resonance imaging Medicine and Health Sciences Nephrology Noise Patients Research and Analysis Methods Risk factors Studies Therapy TOR protein Transformation Transplants & implants Tuberous sclerosis |
| title | Treatment effect of mTOR-inhibition on tissue composition of renal angiomyolipomas in tuberous sclerosis complex (TSC) |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-08T02%3A49%3A15IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Treatment%20effect%20of%20mTOR-inhibition%20on%20tissue%20composition%20of%20renal%20angiomyolipomas%20in%20tuberous%20sclerosis%20complex%20(TSC)&rft.jtitle=PloS%20one&rft.au=Brakemeier,%20Susanne&rft.date=2017-12-12&rft.volume=12&rft.issue=12&rft.spage=e0189132&rft.epage=e0189132&rft.pages=e0189132-e0189132&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0189132&rft_dat=%3Cgale_plos_%3EA518545480%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1976005143&rft_id=info:pmid/29232371&rft_galeid=A518545480&rft_doaj_id=oai_doaj_org_article_ce6394abf969410481efa1d710b4abbe&rfr_iscdi=true |