MGMT methylation may benefit overall survival in patients with moderately vascularized glioblastomas
Objectives To assess the combined role of tumor vascularity, estimated from perfusion MRI, and MGMT methylation status on overall survival (OS) in patients with glioblastoma. Methods A multicentric international dataset including 96 patients from NCT03439332 clinical study were used to study the pro...
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| Veröffentlicht in: | European radiology 2021-03, Vol.31 (3), p.1738-1747 |
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| creator | Fuster-Garcia, Elies Lorente Estellés, David Álvarez-Torres, María del Mar Juan-Albarracín, Javier Chelebian, Eduard Rovira, Alex Acosta, Cristina Auger Pineda, Jose Oleaga, Laura Mollá-Olmos, Enrique Filice, Silvano Due-Tønnessen, Paulina Meling, Torstein R. Emblem, Kyrre E. García-Gómez, Juan M. |
| description | Objectives
To assess the combined role of tumor vascularity, estimated from perfusion MRI, and
MGMT
methylation status on overall survival (OS) in patients with glioblastoma.
Methods
A multicentric international dataset including 96 patients from NCT03439332 clinical study were used to study the prognostic relationships between
MGMT
and perfusion markers. Relative cerebral blood volume (rCBV) in the most vascularized tumor regions was automatically obtained from preoperative MRIs using ONCOhabitats online analysis service. Cox survival regression models and stratification strategies were conducted to define a subpopulation that is particularly favored by
MGMT
methylation in terms of OS.
Results
rCBV distributions did not differ significantly (
p
> 0.05) in the methylated and the non-methylated subpopulations. In patients with moderately vascularized tumors (rCBV 10.73), however, there was no significant effect of
MGMT
methylation (HR = 1.72,
p
= 0.10, AUC = 0.56).
Conclusions
Our results indicate the existence of complementary prognostic information provided by
MGMT
methylation and rCBV. Perfusion markers could identify a subpopulation of patients who will benefit the most from
MGMT
methylation. Not considering this information may lead to bias in the interpretation of clinical studies.
Key Points
• MRI perfusion provides complementary prognostic information to MGMT methylation.
• MGMT methylation improves prognosis in glioblastoma patients with moderate vascular profile.
• Failure to consider these relations may lead to bias in the interpretation of clinical studies. |
| doi_str_mv | 10.1007/s00330-020-07297-4 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7880975</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2488775716</sourcerecordid><originalsourceid>FETCH-LOGICAL-c474t-7764150b8821b959e4185937b978a0c6d8459c4dafc12884e12155890ee7216b3</originalsourceid><addsrcrecordid>eNp9kUFPGzEQha2qqAlp_0APlaWeF8Zeb2xfkBAqAQnEJT1b3l0nceRdB9u7KP31mIYGuPQwmsN8782THkLfCZwRAH4eAcoSCqB5OJW8YJ_QlLCSFgQE-4ymIEtRcCnZBJ3GuAUASRj_giZZBqQkMEXt_eJ-iTuTNnunk_U97vQe16Y3K5uwH03QzuE4hNGO2mHb413GTJ8ifrJpgzvfZiQZt8ejjs3gdLB_TIvXzvra6Zh8p-NXdLLSLppvr3uGfl__Wl7dFHcPi9ury7uiYZylgvM5IxXUQlBSy0oaRkQlS15LLjQ081awSjas1auGUCGYIZRUlZBgDKdkXpczdHHw3Q11Z9omx8zx1S7YToe98tqqj5febtTaj4oLAZJX2eDnq0Hwj4OJSW39EPqcWVEmBOcVJ_NM0QPVBB9jMKvjBwLqpRl1aEblZtTfZhTLoh_vsx0l_6rIQHkAYj71axPefv_H9hl9D5rf</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2488775716</pqid></control><display><type>article</type><title>MGMT methylation may benefit overall survival in patients with moderately vascularized glioblastomas</title><source>MEDLINE</source><source>SpringerLink Journals - AutoHoldings</source><creator>Fuster-Garcia, Elies ; Lorente Estellés, David ; Álvarez-Torres, María del Mar ; Juan-Albarracín, Javier ; Chelebian, Eduard ; Rovira, Alex ; Acosta, Cristina Auger ; Pineda, Jose ; Oleaga, Laura ; Mollá-Olmos, Enrique ; Filice, Silvano ; Due-Tønnessen, Paulina ; Meling, Torstein R. ; Emblem, Kyrre E. ; García-Gómez, Juan M.</creator><creatorcontrib>Fuster-Garcia, Elies ; Lorente Estellés, David ; Álvarez-Torres, María del Mar ; Juan-Albarracín, Javier ; Chelebian, Eduard ; Rovira, Alex ; Acosta, Cristina Auger ; Pineda, Jose ; Oleaga, Laura ; Mollá-Olmos, Enrique ; Filice, Silvano ; Due-Tønnessen, Paulina ; Meling, Torstein R. ; Emblem, Kyrre E. ; García-Gómez, Juan M.</creatorcontrib><description>Objectives
To assess the combined role of tumor vascularity, estimated from perfusion MRI, and
MGMT
methylation status on overall survival (OS) in patients with glioblastoma.
Methods
A multicentric international dataset including 96 patients from NCT03439332 clinical study were used to study the prognostic relationships between
MGMT
and perfusion markers. Relative cerebral blood volume (rCBV) in the most vascularized tumor regions was automatically obtained from preoperative MRIs using ONCOhabitats online analysis service. Cox survival regression models and stratification strategies were conducted to define a subpopulation that is particularly favored by
MGMT
methylation in terms of OS.
Results
rCBV distributions did not differ significantly (
p
> 0.05) in the methylated and the non-methylated subpopulations. In patients with moderately vascularized tumors (rCBV < 10.73),
MGMT
methylation was a positive predictive factor for OS (HR = 2.73,
p
= 0.003, AUC = 0.70). In patients with highly vascularized tumors (rCBV > 10.73), however, there was no significant effect of
MGMT
methylation (HR = 1.72,
p
= 0.10, AUC = 0.56).
Conclusions
Our results indicate the existence of complementary prognostic information provided by
MGMT
methylation and rCBV. Perfusion markers could identify a subpopulation of patients who will benefit the most from
MGMT
methylation. Not considering this information may lead to bias in the interpretation of clinical studies.
Key Points
• MRI perfusion provides complementary prognostic information to MGMT methylation.
• MGMT methylation improves prognosis in glioblastoma patients with moderate vascular profile.
• Failure to consider these relations may lead to bias in the interpretation of clinical studies.</description><identifier>ISSN: 0938-7994</identifier><identifier>EISSN: 1432-1084</identifier><identifier>DOI: 10.1007/s00330-020-07297-4</identifier><identifier>PMID: 33001310</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Antineoplastic Agents, Alkylating - therapeutic use ; Bias ; Blood volume ; Brain Neoplasms - diagnostic imaging ; Brain Neoplasms - drug therapy ; Brain Neoplasms - genetics ; Cerebral blood flow ; Diagnostic Radiology ; DNA Methylation ; DNA Modification Methylases - genetics ; DNA Repair Enzymes - genetics ; Glioblastoma ; Glioblastoma - diagnostic imaging ; Glioblastoma - genetics ; Humans ; Imaging ; Internal Medicine ; Interventional Radiology ; Magnetic resonance imaging ; Markers ; Medical prognosis ; Medicine ; Medicine & Public Health ; Methylation ; Neuroradiology ; Oncology ; Perfusion ; Prognosis ; Promoter Regions, Genetic ; Radiology ; Regression analysis ; Regression models ; Subpopulations ; Survival ; Temozolomide - therapeutic use ; Tumor Suppressor Proteins - genetics ; Tumors ; Ultrasound</subject><ispartof>European radiology, 2021-03, Vol.31 (3), p.1738-1747</ispartof><rights>The Author(s) 2020</rights><rights>The Author(s) 2020. 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-c474t-7764150b8821b959e4185937b978a0c6d8459c4dafc12884e12155890ee7216b3</citedby><cites>FETCH-LOGICAL-c474t-7764150b8821b959e4185937b978a0c6d8459c4dafc12884e12155890ee7216b3</cites><orcidid>0000-0002-0716-8960</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/s00330-020-07297-4$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00330-020-07297-4$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33001310$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fuster-Garcia, Elies</creatorcontrib><creatorcontrib>Lorente Estellés, David</creatorcontrib><creatorcontrib>Álvarez-Torres, María del Mar</creatorcontrib><creatorcontrib>Juan-Albarracín, Javier</creatorcontrib><creatorcontrib>Chelebian, Eduard</creatorcontrib><creatorcontrib>Rovira, Alex</creatorcontrib><creatorcontrib>Acosta, Cristina Auger</creatorcontrib><creatorcontrib>Pineda, Jose</creatorcontrib><creatorcontrib>Oleaga, Laura</creatorcontrib><creatorcontrib>Mollá-Olmos, Enrique</creatorcontrib><creatorcontrib>Filice, Silvano</creatorcontrib><creatorcontrib>Due-Tønnessen, Paulina</creatorcontrib><creatorcontrib>Meling, Torstein R.</creatorcontrib><creatorcontrib>Emblem, Kyrre E.</creatorcontrib><creatorcontrib>García-Gómez, Juan M.</creatorcontrib><title>MGMT methylation may benefit overall survival in patients with moderately vascularized glioblastomas</title><title>European radiology</title><addtitle>Eur Radiol</addtitle><addtitle>Eur Radiol</addtitle><description>Objectives
To assess the combined role of tumor vascularity, estimated from perfusion MRI, and
MGMT
methylation status on overall survival (OS) in patients with glioblastoma.
Methods
A multicentric international dataset including 96 patients from NCT03439332 clinical study were used to study the prognostic relationships between
MGMT
and perfusion markers. Relative cerebral blood volume (rCBV) in the most vascularized tumor regions was automatically obtained from preoperative MRIs using ONCOhabitats online analysis service. Cox survival regression models and stratification strategies were conducted to define a subpopulation that is particularly favored by
MGMT
methylation in terms of OS.
Results
rCBV distributions did not differ significantly (
p
> 0.05) in the methylated and the non-methylated subpopulations. In patients with moderately vascularized tumors (rCBV < 10.73),
MGMT
methylation was a positive predictive factor for OS (HR = 2.73,
p
= 0.003, AUC = 0.70). In patients with highly vascularized tumors (rCBV > 10.73), however, there was no significant effect of
MGMT
methylation (HR = 1.72,
p
= 0.10, AUC = 0.56).
Conclusions
Our results indicate the existence of complementary prognostic information provided by
MGMT
methylation and rCBV. Perfusion markers could identify a subpopulation of patients who will benefit the most from
MGMT
methylation. Not considering this information may lead to bias in the interpretation of clinical studies.
Key Points
• MRI perfusion provides complementary prognostic information to MGMT methylation.
• MGMT methylation improves prognosis in glioblastoma patients with moderate vascular profile.
• Failure to consider these relations may lead to bias in the interpretation of clinical studies.</description><subject>Antineoplastic Agents, Alkylating - therapeutic use</subject><subject>Bias</subject><subject>Blood volume</subject><subject>Brain Neoplasms - diagnostic imaging</subject><subject>Brain Neoplasms - drug therapy</subject><subject>Brain Neoplasms - genetics</subject><subject>Cerebral blood flow</subject><subject>Diagnostic Radiology</subject><subject>DNA Methylation</subject><subject>DNA Modification Methylases - genetics</subject><subject>DNA Repair Enzymes - genetics</subject><subject>Glioblastoma</subject><subject>Glioblastoma - diagnostic imaging</subject><subject>Glioblastoma - genetics</subject><subject>Humans</subject><subject>Imaging</subject><subject>Internal Medicine</subject><subject>Interventional Radiology</subject><subject>Magnetic resonance imaging</subject><subject>Markers</subject><subject>Medical prognosis</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Methylation</subject><subject>Neuroradiology</subject><subject>Oncology</subject><subject>Perfusion</subject><subject>Prognosis</subject><subject>Promoter Regions, Genetic</subject><subject>Radiology</subject><subject>Regression analysis</subject><subject>Regression models</subject><subject>Subpopulations</subject><subject>Survival</subject><subject>Temozolomide - therapeutic use</subject><subject>Tumor Suppressor Proteins - genetics</subject><subject>Tumors</subject><subject>Ultrasound</subject><issn>0938-7994</issn><issn>1432-1084</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kUFPGzEQha2qqAlp_0APlaWeF8Zeb2xfkBAqAQnEJT1b3l0nceRdB9u7KP31mIYGuPQwmsN8782THkLfCZwRAH4eAcoSCqB5OJW8YJ_QlLCSFgQE-4ymIEtRcCnZBJ3GuAUASRj_giZZBqQkMEXt_eJ-iTuTNnunk_U97vQe16Y3K5uwH03QzuE4hNGO2mHb413GTJ8ifrJpgzvfZiQZt8ejjs3gdLB_TIvXzvra6Zh8p-NXdLLSLppvr3uGfl__Wl7dFHcPi9ury7uiYZylgvM5IxXUQlBSy0oaRkQlS15LLjQ081awSjas1auGUCGYIZRUlZBgDKdkXpczdHHw3Q11Z9omx8zx1S7YToe98tqqj5febtTaj4oLAZJX2eDnq0Hwj4OJSW39EPqcWVEmBOcVJ_NM0QPVBB9jMKvjBwLqpRl1aEblZtTfZhTLoh_vsx0l_6rIQHkAYj71axPefv_H9hl9D5rf</recordid><startdate>20210301</startdate><enddate>20210301</enddate><creator>Fuster-Garcia, Elies</creator><creator>Lorente Estellés, David</creator><creator>Álvarez-Torres, María del Mar</creator><creator>Juan-Albarracín, Javier</creator><creator>Chelebian, Eduard</creator><creator>Rovira, Alex</creator><creator>Acosta, Cristina Auger</creator><creator>Pineda, Jose</creator><creator>Oleaga, Laura</creator><creator>Mollá-Olmos, Enrique</creator><creator>Filice, Silvano</creator><creator>Due-Tønnessen, Paulina</creator><creator>Meling, Torstein R.</creator><creator>Emblem, Kyrre E.</creator><creator>García-Gómez, Juan M.</creator><general>Springer Berlin Heidelberg</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>3V.</scope><scope>7QO</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-0716-8960</orcidid></search><sort><creationdate>20210301</creationdate><title>MGMT methylation may benefit overall survival in patients with moderately vascularized glioblastomas</title><author>Fuster-Garcia, Elies ; Lorente Estellés, David ; Álvarez-Torres, María del Mar ; Juan-Albarracín, Javier ; Chelebian, Eduard ; Rovira, Alex ; Acosta, Cristina Auger ; Pineda, Jose ; Oleaga, Laura ; Mollá-Olmos, Enrique ; Filice, Silvano ; Due-Tønnessen, Paulina ; Meling, Torstein R. ; Emblem, Kyrre E. ; García-Gómez, Juan M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-7764150b8821b959e4185937b978a0c6d8459c4dafc12884e12155890ee7216b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Antineoplastic Agents, Alkylating - therapeutic use</topic><topic>Bias</topic><topic>Blood volume</topic><topic>Brain Neoplasms - diagnostic imaging</topic><topic>Brain Neoplasms - drug therapy</topic><topic>Brain Neoplasms - genetics</topic><topic>Cerebral blood flow</topic><topic>Diagnostic Radiology</topic><topic>DNA Methylation</topic><topic>DNA Modification Methylases - genetics</topic><topic>DNA Repair Enzymes - genetics</topic><topic>Glioblastoma</topic><topic>Glioblastoma - diagnostic imaging</topic><topic>Glioblastoma - genetics</topic><topic>Humans</topic><topic>Imaging</topic><topic>Internal Medicine</topic><topic>Interventional Radiology</topic><topic>Magnetic resonance imaging</topic><topic>Markers</topic><topic>Medical prognosis</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Methylation</topic><topic>Neuroradiology</topic><topic>Oncology</topic><topic>Perfusion</topic><topic>Prognosis</topic><topic>Promoter Regions, Genetic</topic><topic>Radiology</topic><topic>Regression analysis</topic><topic>Regression models</topic><topic>Subpopulations</topic><topic>Survival</topic><topic>Temozolomide - therapeutic use</topic><topic>Tumor Suppressor Proteins - genetics</topic><topic>Tumors</topic><topic>Ultrasound</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fuster-Garcia, Elies</creatorcontrib><creatorcontrib>Lorente Estellés, David</creatorcontrib><creatorcontrib>Álvarez-Torres, María del Mar</creatorcontrib><creatorcontrib>Juan-Albarracín, Javier</creatorcontrib><creatorcontrib>Chelebian, Eduard</creatorcontrib><creatorcontrib>Rovira, Alex</creatorcontrib><creatorcontrib>Acosta, Cristina Auger</creatorcontrib><creatorcontrib>Pineda, Jose</creatorcontrib><creatorcontrib>Oleaga, Laura</creatorcontrib><creatorcontrib>Mollá-Olmos, Enrique</creatorcontrib><creatorcontrib>Filice, Silvano</creatorcontrib><creatorcontrib>Due-Tønnessen, Paulina</creatorcontrib><creatorcontrib>Meling, Torstein R.</creatorcontrib><creatorcontrib>Emblem, Kyrre E.</creatorcontrib><creatorcontrib>García-Gómez, Juan M.</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>ProQuest Central (Corporate)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>European radiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fuster-Garcia, Elies</au><au>Lorente Estellés, David</au><au>Álvarez-Torres, María del Mar</au><au>Juan-Albarracín, Javier</au><au>Chelebian, Eduard</au><au>Rovira, Alex</au><au>Acosta, Cristina Auger</au><au>Pineda, Jose</au><au>Oleaga, Laura</au><au>Mollá-Olmos, Enrique</au><au>Filice, Silvano</au><au>Due-Tønnessen, Paulina</au><au>Meling, Torstein R.</au><au>Emblem, Kyrre E.</au><au>García-Gómez, Juan M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>MGMT methylation may benefit overall survival in patients with moderately vascularized glioblastomas</atitle><jtitle>European radiology</jtitle><stitle>Eur Radiol</stitle><addtitle>Eur Radiol</addtitle><date>2021-03-01</date><risdate>2021</risdate><volume>31</volume><issue>3</issue><spage>1738</spage><epage>1747</epage><pages>1738-1747</pages><issn>0938-7994</issn><eissn>1432-1084</eissn><abstract>Objectives
To assess the combined role of tumor vascularity, estimated from perfusion MRI, and
MGMT
methylation status on overall survival (OS) in patients with glioblastoma.
Methods
A multicentric international dataset including 96 patients from NCT03439332 clinical study were used to study the prognostic relationships between
MGMT
and perfusion markers. Relative cerebral blood volume (rCBV) in the most vascularized tumor regions was automatically obtained from preoperative MRIs using ONCOhabitats online analysis service. Cox survival regression models and stratification strategies were conducted to define a subpopulation that is particularly favored by
MGMT
methylation in terms of OS.
Results
rCBV distributions did not differ significantly (
p
> 0.05) in the methylated and the non-methylated subpopulations. In patients with moderately vascularized tumors (rCBV < 10.73),
MGMT
methylation was a positive predictive factor for OS (HR = 2.73,
p
= 0.003, AUC = 0.70). In patients with highly vascularized tumors (rCBV > 10.73), however, there was no significant effect of
MGMT
methylation (HR = 1.72,
p
= 0.10, AUC = 0.56).
Conclusions
Our results indicate the existence of complementary prognostic information provided by
MGMT
methylation and rCBV. Perfusion markers could identify a subpopulation of patients who will benefit the most from
MGMT
methylation. Not considering this information may lead to bias in the interpretation of clinical studies.
Key Points
• MRI perfusion provides complementary prognostic information to MGMT methylation.
• MGMT methylation improves prognosis in glioblastoma patients with moderate vascular profile.
• Failure to consider these relations may lead to bias in the interpretation of clinical studies.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>33001310</pmid><doi>10.1007/s00330-020-07297-4</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-0716-8960</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0938-7994 |
| ispartof | European radiology, 2021-03, Vol.31 (3), p.1738-1747 |
| issn | 0938-7994 1432-1084 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7880975 |
| source | MEDLINE; SpringerLink Journals - AutoHoldings |
| subjects | Antineoplastic Agents, Alkylating - therapeutic use Bias Blood volume Brain Neoplasms - diagnostic imaging Brain Neoplasms - drug therapy Brain Neoplasms - genetics Cerebral blood flow Diagnostic Radiology DNA Methylation DNA Modification Methylases - genetics DNA Repair Enzymes - genetics Glioblastoma Glioblastoma - diagnostic imaging Glioblastoma - genetics Humans Imaging Internal Medicine Interventional Radiology Magnetic resonance imaging Markers Medical prognosis Medicine Medicine & Public Health Methylation Neuroradiology Oncology Perfusion Prognosis Promoter Regions, Genetic Radiology Regression analysis Regression models Subpopulations Survival Temozolomide - therapeutic use Tumor Suppressor Proteins - genetics Tumors Ultrasound |
| title | MGMT methylation may benefit overall survival in patients with moderately vascularized glioblastomas |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-26T23%3A15%3A31IST&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=MGMT%20methylation%20may%20benefit%20overall%20survival%20in%20patients%20with%20moderately%20vascularized%20glioblastomas&rft.jtitle=European%20radiology&rft.au=Fuster-Garcia,%20Elies&rft.date=2021-03-01&rft.volume=31&rft.issue=3&rft.spage=1738&rft.epage=1747&rft.pages=1738-1747&rft.issn=0938-7994&rft.eissn=1432-1084&rft_id=info:doi/10.1007/s00330-020-07297-4&rft_dat=%3Cproquest_pubme%3E2488775716%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=2488775716&rft_id=info:pmid/33001310&rfr_iscdi=true |