Significance of molecular diagnostics for therapeutic decision-making in recurrent glioma
Abstract Background Targeted therapies have substantially improved survival in cancer patients with malignancies outside the brain. Whether in-depth analysis for molecular alterations may also offer therapeutic avenues in primary brain tumors remains unclear. We herein present our institutional expe...
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creator | Blobner, Jens Dengler, Laura Blobner, Sven Eberle, Constantin Weller, Jonathan Teske, Nico Karschnia, Philipp Rühlmann, Katharina Heinrich, Kathrin Ziemann, Frank Greif, Philipp A Jeremias, Irmela Wuerstlein, Rachel Hasselmann, Korbinian Dorostkar, Mario Harter, Patrick N Quach, Stefanie Stoecklein, Veit Albert, Nathalie L Niyazi, Maximilian Tonn, Joerg-Christian Thon, Niklas Christoph Westphalen, Benedikt von Baumgarten, Louisa |
description | Abstract
Background
Targeted therapies have substantially improved survival in cancer patients with malignancies outside the brain. Whether in-depth analysis for molecular alterations may also offer therapeutic avenues in primary brain tumors remains unclear. We herein present our institutional experience for glioma patients discussed in our interdisciplinary molecular tumor board (MTB) implemented at the Comprehensive Cancer Center Munich (LMU).
Methods
We retrospectively searched the database of the MTB for all recurrent glioma patients after previous therapy. Recommendations were based on next-generation sequencing results of individual patient’s tumor tissue. Clinical and molecular information, previous therapy regimens, and outcome parameters were collected.
Results
Overall, 73 consecutive recurrent glioma patients were identified. In the median, advanced molecular testing was initiated with the third tumor recurrence. The median turnaround time between initiation of molecular profiling and MTB case discussion was 48 ± 75 days (range: 32–536 days). Targetable mutations were found for 50 recurrent glioma patients (68.5%). IDH1 mutation (27/73; 37%), epidermal growth factor receptor amplification (19/73; 26%), and NF1 mutation (8/73; 11%) were the most detected alterations and a molecular-based treatment recommendation could be made for all of them. Therapeutic recommendations were implemented in 12 cases (24%) and one-third of these heavily pretreated patients experienced clinical benefit with at least disease stabilization.
Conclusions
In-depth molecular analysis of tumor tissue may guide targeted therapy also in brain tumor patients and considerable antitumor effects might be observed in selected cases. However, future studies to corroborate our results are needed. |
doi_str_mv | 10.1093/noajnl/vdad060 |
format | Article |
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Background
Targeted therapies have substantially improved survival in cancer patients with malignancies outside the brain. Whether in-depth analysis for molecular alterations may also offer therapeutic avenues in primary brain tumors remains unclear. We herein present our institutional experience for glioma patients discussed in our interdisciplinary molecular tumor board (MTB) implemented at the Comprehensive Cancer Center Munich (LMU).
Methods
We retrospectively searched the database of the MTB for all recurrent glioma patients after previous therapy. Recommendations were based on next-generation sequencing results of individual patient’s tumor tissue. Clinical and molecular information, previous therapy regimens, and outcome parameters were collected.
Results
Overall, 73 consecutive recurrent glioma patients were identified. In the median, advanced molecular testing was initiated with the third tumor recurrence. The median turnaround time between initiation of molecular profiling and MTB case discussion was 48 ± 75 days (range: 32–536 days). Targetable mutations were found for 50 recurrent glioma patients (68.5%). IDH1 mutation (27/73; 37%), epidermal growth factor receptor amplification (19/73; 26%), and NF1 mutation (8/73; 11%) were the most detected alterations and a molecular-based treatment recommendation could be made for all of them. Therapeutic recommendations were implemented in 12 cases (24%) and one-third of these heavily pretreated patients experienced clinical benefit with at least disease stabilization.
Conclusions
In-depth molecular analysis of tumor tissue may guide targeted therapy also in brain tumor patients and considerable antitumor effects might be observed in selected cases. However, future studies to corroborate our results are needed.</description><identifier>ISSN: 2632-2498</identifier><identifier>EISSN: 2632-2498</identifier><identifier>DOI: 10.1093/noajnl/vdad060</identifier><identifier>PMID: 37287694</identifier><language>eng</language><publisher>US: Oxford University Press</publisher><subject>Basic and Translational Investigations</subject><ispartof>Neuro-oncology advances, 2023-01, Vol.5 (1), p.vdad060-vdad060</ispartof><rights>The Author(s) 2023. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology. 2023</rights><rights>The Author(s) 2023. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c425t-5884822d733ffa91a1c17e735f2ca27fc7af6c2be3dc2d73de6f90f0a63a3c4a3</citedby><cites>FETCH-LOGICAL-c425t-5884822d733ffa91a1c17e735f2ca27fc7af6c2be3dc2d73de6f90f0a63a3c4a3</cites><orcidid>0000-0002-1254-5310 ; 0000-0001-6206-0621</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/PMC10243988/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10243988/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,861,882,1599,27905,27906,53772,53774</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37287694$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Blobner, Jens</creatorcontrib><creatorcontrib>Dengler, Laura</creatorcontrib><creatorcontrib>Blobner, Sven</creatorcontrib><creatorcontrib>Eberle, Constantin</creatorcontrib><creatorcontrib>Weller, Jonathan</creatorcontrib><creatorcontrib>Teske, Nico</creatorcontrib><creatorcontrib>Karschnia, Philipp</creatorcontrib><creatorcontrib>Rühlmann, Katharina</creatorcontrib><creatorcontrib>Heinrich, Kathrin</creatorcontrib><creatorcontrib>Ziemann, Frank</creatorcontrib><creatorcontrib>Greif, Philipp A</creatorcontrib><creatorcontrib>Jeremias, Irmela</creatorcontrib><creatorcontrib>Wuerstlein, Rachel</creatorcontrib><creatorcontrib>Hasselmann, Korbinian</creatorcontrib><creatorcontrib>Dorostkar, Mario</creatorcontrib><creatorcontrib>Harter, Patrick N</creatorcontrib><creatorcontrib>Quach, Stefanie</creatorcontrib><creatorcontrib>Stoecklein, Veit</creatorcontrib><creatorcontrib>Albert, Nathalie L</creatorcontrib><creatorcontrib>Niyazi, Maximilian</creatorcontrib><creatorcontrib>Tonn, Joerg-Christian</creatorcontrib><creatorcontrib>Thon, Niklas</creatorcontrib><creatorcontrib>Christoph Westphalen, Benedikt</creatorcontrib><creatorcontrib>von Baumgarten, Louisa</creatorcontrib><title>Significance of molecular diagnostics for therapeutic decision-making in recurrent glioma</title><title>Neuro-oncology advances</title><addtitle>Neurooncol Adv</addtitle><description>Abstract
Background
Targeted therapies have substantially improved survival in cancer patients with malignancies outside the brain. Whether in-depth analysis for molecular alterations may also offer therapeutic avenues in primary brain tumors remains unclear. We herein present our institutional experience for glioma patients discussed in our interdisciplinary molecular tumor board (MTB) implemented at the Comprehensive Cancer Center Munich (LMU).
Methods
We retrospectively searched the database of the MTB for all recurrent glioma patients after previous therapy. Recommendations were based on next-generation sequencing results of individual patient’s tumor tissue. Clinical and molecular information, previous therapy regimens, and outcome parameters were collected.
Results
Overall, 73 consecutive recurrent glioma patients were identified. In the median, advanced molecular testing was initiated with the third tumor recurrence. The median turnaround time between initiation of molecular profiling and MTB case discussion was 48 ± 75 days (range: 32–536 days). Targetable mutations were found for 50 recurrent glioma patients (68.5%). IDH1 mutation (27/73; 37%), epidermal growth factor receptor amplification (19/73; 26%), and NF1 mutation (8/73; 11%) were the most detected alterations and a molecular-based treatment recommendation could be made for all of them. Therapeutic recommendations were implemented in 12 cases (24%) and one-third of these heavily pretreated patients experienced clinical benefit with at least disease stabilization.
Conclusions
In-depth molecular analysis of tumor tissue may guide targeted therapy also in brain tumor patients and considerable antitumor effects might be observed in selected cases. However, future studies to corroborate our results are needed.</description><subject>Basic and Translational Investigations</subject><issn>2632-2498</issn><issn>2632-2498</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>TOX</sourceid><recordid>eNqFkb1PwzAQxS0EolXpyog8wpDWsZ2vCaGKL6kSAzAwWVfHTl0Su9hJJf57UrVUZWK6093v3j3pIXQZk0lMCja1Dla2nm5KKElKTtCQpoxGlBf56VE_QOMQVoQQmvCEE3qOBiyjeZYWfIg-Xk1ljTYSrFTYady4WsmuBo9LA5V1oTUyYO08bpfKw1p1_QCXSppgnI0a-DS2wsZi3595r2yLq9q4Bi7QmYY6qPG-jtD7w_3b7Cmavzw-z-7mkeQ0aaMkz3lOaZkxpjUUMcQyzlTGEk0l0EzLDHQq6UKxUm6pUqW6IJpAyoBJDmyEbne6627RqFL2DjzUYu1NA_5bODDi78aapajcRsSEclbkea9wvVfw7qtToRWNCVLVNVjluiBoTllREB5v0ckOld6F4JU-_ImJ2GYidpmIfSb9wdWxuwP-m0AP3OwA163_E_sBO12bpA</recordid><startdate>20230101</startdate><enddate>20230101</enddate><creator>Blobner, Jens</creator><creator>Dengler, Laura</creator><creator>Blobner, Sven</creator><creator>Eberle, Constantin</creator><creator>Weller, Jonathan</creator><creator>Teske, Nico</creator><creator>Karschnia, Philipp</creator><creator>Rühlmann, Katharina</creator><creator>Heinrich, Kathrin</creator><creator>Ziemann, Frank</creator><creator>Greif, Philipp A</creator><creator>Jeremias, Irmela</creator><creator>Wuerstlein, Rachel</creator><creator>Hasselmann, Korbinian</creator><creator>Dorostkar, Mario</creator><creator>Harter, Patrick N</creator><creator>Quach, Stefanie</creator><creator>Stoecklein, Veit</creator><creator>Albert, Nathalie L</creator><creator>Niyazi, Maximilian</creator><creator>Tonn, Joerg-Christian</creator><creator>Thon, Niklas</creator><creator>Christoph Westphalen, Benedikt</creator><creator>von Baumgarten, Louisa</creator><general>Oxford University Press</general><scope>TOX</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-1254-5310</orcidid><orcidid>https://orcid.org/0000-0001-6206-0621</orcidid></search><sort><creationdate>20230101</creationdate><title>Significance of molecular diagnostics for therapeutic decision-making in recurrent glioma</title><author>Blobner, Jens ; Dengler, Laura ; Blobner, Sven ; Eberle, Constantin ; Weller, Jonathan ; Teske, Nico ; Karschnia, Philipp ; Rühlmann, Katharina ; Heinrich, Kathrin ; Ziemann, Frank ; Greif, Philipp A ; Jeremias, Irmela ; Wuerstlein, Rachel ; Hasselmann, Korbinian ; Dorostkar, Mario ; Harter, Patrick N ; Quach, Stefanie ; Stoecklein, Veit ; Albert, Nathalie L ; Niyazi, Maximilian ; Tonn, Joerg-Christian ; Thon, Niklas ; Christoph Westphalen, Benedikt ; von Baumgarten, Louisa</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c425t-5884822d733ffa91a1c17e735f2ca27fc7af6c2be3dc2d73de6f90f0a63a3c4a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Basic and Translational Investigations</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Blobner, Jens</creatorcontrib><creatorcontrib>Dengler, Laura</creatorcontrib><creatorcontrib>Blobner, Sven</creatorcontrib><creatorcontrib>Eberle, Constantin</creatorcontrib><creatorcontrib>Weller, Jonathan</creatorcontrib><creatorcontrib>Teske, Nico</creatorcontrib><creatorcontrib>Karschnia, Philipp</creatorcontrib><creatorcontrib>Rühlmann, Katharina</creatorcontrib><creatorcontrib>Heinrich, Kathrin</creatorcontrib><creatorcontrib>Ziemann, Frank</creatorcontrib><creatorcontrib>Greif, Philipp A</creatorcontrib><creatorcontrib>Jeremias, Irmela</creatorcontrib><creatorcontrib>Wuerstlein, Rachel</creatorcontrib><creatorcontrib>Hasselmann, Korbinian</creatorcontrib><creatorcontrib>Dorostkar, Mario</creatorcontrib><creatorcontrib>Harter, Patrick N</creatorcontrib><creatorcontrib>Quach, Stefanie</creatorcontrib><creatorcontrib>Stoecklein, Veit</creatorcontrib><creatorcontrib>Albert, Nathalie L</creatorcontrib><creatorcontrib>Niyazi, Maximilian</creatorcontrib><creatorcontrib>Tonn, Joerg-Christian</creatorcontrib><creatorcontrib>Thon, Niklas</creatorcontrib><creatorcontrib>Christoph Westphalen, Benedikt</creatorcontrib><creatorcontrib>von Baumgarten, Louisa</creatorcontrib><collection>Oxford Journals Open Access Collection</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Neuro-oncology advances</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Blobner, Jens</au><au>Dengler, Laura</au><au>Blobner, Sven</au><au>Eberle, Constantin</au><au>Weller, Jonathan</au><au>Teske, Nico</au><au>Karschnia, Philipp</au><au>Rühlmann, Katharina</au><au>Heinrich, Kathrin</au><au>Ziemann, Frank</au><au>Greif, Philipp A</au><au>Jeremias, Irmela</au><au>Wuerstlein, Rachel</au><au>Hasselmann, Korbinian</au><au>Dorostkar, Mario</au><au>Harter, Patrick N</au><au>Quach, Stefanie</au><au>Stoecklein, Veit</au><au>Albert, Nathalie L</au><au>Niyazi, Maximilian</au><au>Tonn, Joerg-Christian</au><au>Thon, Niklas</au><au>Christoph Westphalen, Benedikt</au><au>von Baumgarten, Louisa</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Significance of molecular diagnostics for therapeutic decision-making in recurrent glioma</atitle><jtitle>Neuro-oncology advances</jtitle><addtitle>Neurooncol Adv</addtitle><date>2023-01-01</date><risdate>2023</risdate><volume>5</volume><issue>1</issue><spage>vdad060</spage><epage>vdad060</epage><pages>vdad060-vdad060</pages><issn>2632-2498</issn><eissn>2632-2498</eissn><abstract>Abstract
Background
Targeted therapies have substantially improved survival in cancer patients with malignancies outside the brain. Whether in-depth analysis for molecular alterations may also offer therapeutic avenues in primary brain tumors remains unclear. We herein present our institutional experience for glioma patients discussed in our interdisciplinary molecular tumor board (MTB) implemented at the Comprehensive Cancer Center Munich (LMU).
Methods
We retrospectively searched the database of the MTB for all recurrent glioma patients after previous therapy. Recommendations were based on next-generation sequencing results of individual patient’s tumor tissue. Clinical and molecular information, previous therapy regimens, and outcome parameters were collected.
Results
Overall, 73 consecutive recurrent glioma patients were identified. In the median, advanced molecular testing was initiated with the third tumor recurrence. The median turnaround time between initiation of molecular profiling and MTB case discussion was 48 ± 75 days (range: 32–536 days). Targetable mutations were found for 50 recurrent glioma patients (68.5%). IDH1 mutation (27/73; 37%), epidermal growth factor receptor amplification (19/73; 26%), and NF1 mutation (8/73; 11%) were the most detected alterations and a molecular-based treatment recommendation could be made for all of them. Therapeutic recommendations were implemented in 12 cases (24%) and one-third of these heavily pretreated patients experienced clinical benefit with at least disease stabilization.
Conclusions
In-depth molecular analysis of tumor tissue may guide targeted therapy also in brain tumor patients and considerable antitumor effects might be observed in selected cases. However, future studies to corroborate our results are needed.</abstract><cop>US</cop><pub>Oxford University Press</pub><pmid>37287694</pmid><doi>10.1093/noajnl/vdad060</doi><orcidid>https://orcid.org/0000-0002-1254-5310</orcidid><orcidid>https://orcid.org/0000-0001-6206-0621</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Basic and Translational Investigations |
title | Significance of molecular diagnostics for therapeutic decision-making in recurrent glioma |
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