Three-times daily ultrafractionated radiation therapy, a novel and promising regimen for glioblastoma patients
Glioblastomas are considered to be one of the most radio resistant tumors. Despite new therapies, the prognosis of this disease remains dismal. Also, the mechanisms of radiation resistance in mammalian cells are more complex than once believed. Experimental studies have indicated that some human cel...
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Three-times daily ultrafractionated radiation therapy, a novel and promising regimen for glioblastoma patients |
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Beauchesne, Patrick |
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Cancer therapies glioblastoma low-dose radiation therapy Radiation therapy radiotherapy Tumors ultra fractionated regimen |
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Cancers, 2013-09, Vol.5 (4), p.1199-1211 |
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Glioblastomas are considered to be one of the most radio resistant tumors. Despite new therapies, the prognosis of this disease remains dismal. Also, the mechanisms of radiation resistance in mammalian cells are more complex than once believed. Experimental studies have indicated that some human cell lines are sensitive to low radiation doses of |
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Despite new therapies, the prognosis of this disease remains dismal. Also, the mechanisms of radiation resistance in mammalian cells are more complex than once believed. Experimental studies have indicated that some human cell lines are sensitive to low radiation doses of <1 Gy. This phenomenon has been termed low-dose hyper-radio-sensitivity (HRS), and is more apparent in radio resistant cell lines, such as glioblastoma cells. Sensitivity may result from the inability of low dose radiation to efficiently induce repair mechanisms, whereas higher doses cause enough damage to trigger repair responses for radio resistance. In vitro studies have demonstrated this phenomenon using various human malignant glioma cell lines: (1) daily repeated irradiation of cells with low doses compared to irradiation using a single biologically equivalent dose resulted in significantly higher cell killing; (2) experiments conducted on glioma xenografts demonstrated that repeated irradiation with low doses was more effective for inhibiting tumor growth than a single dose. In order to confirm and validate these promising studies on HRS, a few phase II trials were developed. For translating the experimental observations into the clinic, ultra fractionation protocols (with three daily doses) were tested in glioblastoma patients. Tolerance and toxicity were the primary endpoints, with overall survival as a secondary endpoint. These protocols were initiated before concomitant radio chemotherapy became the standard of care. For these trials, patients with an unfavorable clinical prognostic factor of newly unresectable GBM were included. When comparing the results of these trials with international literature using multivariate analysis for both progression free survival and overall survival, ultra fractionated irradiation showed superiority over radiotherapy alone. In addition, it was found to be equivalent to treatment using radiotherapy and temozolomide. Therefore, ultra fractionated protocols may prolong survival of glioblastoma patients. In this review, we describe the main experimental data regarding low-dose hypersensitivity as well as the findings of clinical trials that have investigated this new radiotherapy regimen.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers5041199</identifier><identifier>PMID: 24202441</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Cancer therapies ; glioblastoma ; low-dose radiation therapy ; Radiation therapy ; radiotherapy ; Tumors ; ultra fractionated regimen</subject><ispartof>Cancers, 2013-09, Vol.5 (4), p.1199-1211</ispartof><rights>Copyright MDPI AG 2013</rights><rights>2013 by the authors; licensee MDPI, Basel, Switzerland. 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3999-3c03911ba1f5735394a14cc4efc80ac591be78a5a94e377a0c716a98ef04ea1b3</citedby><cites>FETCH-LOGICAL-c3999-3c03911ba1f5735394a14cc4efc80ac591be78a5a94e377a0c716a98ef04ea1b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1524189298/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1524189298?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,315,734,787,791,892,2238,24369,25806,27992,27993,37084,37085,44962,54183,54185,76129</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24202441$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Beauchesne, Patrick</creatorcontrib><title>Three-times daily ultrafractionated radiation therapy, a novel and promising regimen for glioblastoma patients</title><title>Cancers</title><addtitle>Cancers (Basel)</addtitle><description>Glioblastomas are considered to be one of the most radio resistant tumors. Despite new therapies, the prognosis of this disease remains dismal. Also, the mechanisms of radiation resistance in mammalian cells are more complex than once believed. Experimental studies have indicated that some human cell lines are sensitive to low radiation doses of <1 Gy. This phenomenon has been termed low-dose hyper-radio-sensitivity (HRS), and is more apparent in radio resistant cell lines, such as glioblastoma cells. Sensitivity may result from the inability of low dose radiation to efficiently induce repair mechanisms, whereas higher doses cause enough damage to trigger repair responses for radio resistance. In vitro studies have demonstrated this phenomenon using various human malignant glioma cell lines: (1) daily repeated irradiation of cells with low doses compared to irradiation using a single biologically equivalent dose resulted in significantly higher cell killing; (2) experiments conducted on glioma xenografts demonstrated that repeated irradiation with low doses was more effective for inhibiting tumor growth than a single dose. In order to confirm and validate these promising studies on HRS, a few phase II trials were developed. For translating the experimental observations into the clinic, ultra fractionation protocols (with three daily doses) were tested in glioblastoma patients. Tolerance and toxicity were the primary endpoints, with overall survival as a secondary endpoint. These protocols were initiated before concomitant radio chemotherapy became the standard of care. For these trials, patients with an unfavorable clinical prognostic factor of newly unresectable GBM were included. When comparing the results of these trials with international literature using multivariate analysis for both progression free survival and overall survival, ultra fractionated irradiation showed superiority over radiotherapy alone. In addition, it was found to be equivalent to treatment using radiotherapy and temozolomide. Therefore, ultra fractionated protocols may prolong survival of glioblastoma patients. In this review, we describe the main experimental data regarding low-dose hypersensitivity as well as the findings of clinical trials that have investigated this new radiotherapy regimen.</description><subject>Cancer therapies</subject><subject>glioblastoma</subject><subject>low-dose radiation therapy</subject><subject>Radiation therapy</subject><subject>radiotherapy</subject><subject>Tumors</subject><subject>ultra fractionated regimen</subject><issn>2072-6694</issn><issn>2072-6694</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNpdkkFv1DAQhS0EotXSK0dkiQsHUuzYieMLEqqgVKrEpZytiTPJeuXYi51U2n-Py7ZVF1_G9rz5NDN6hLzn7FIIzb5YCBZTbpjkXOtX5Lxmqq7aVsvXL-5n5CLnHStHCK5a9Zac1bJmtZT8nIS7bUKsFjdjpgM4f6CrXxKMCeziYoAFB5pgcPDwossWE-wPnynQEO_RUwgD3ac4u-zCRBNOBRToGBOdvIu9h7zEGei-lGNY8jvyZgSf8eIxbsjvH9_vrn5Wt7-ub66-3VZWaK0rYZnQnPfAx0aJRmgJXForcbQdA9to3qPqoAEtUSgFzCregu5wZBKB92JDbo7cIcLO7JObIR1MBGf-fcQ0GUiLsx6N1JzhiGxoB5RcjR3vB4YorWw1Y3IsrK9H1n7tZxxsmSOBP4GeZoLbmineG9GpRpfuN-TTIyDFPyvmxZR1WfQeAsY1Gy6lVq3ULSvSj_9Jd3FNoazK8KaWvNO17orq8qiyKeaccHxuhjPz4Axz6oxS8OHlCM_yJx-Iv8-_t64</recordid><startdate>20130925</startdate><enddate>20130925</enddate><creator>Beauchesne, Patrick</creator><general>MDPI AG</general><general>MDPI</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7TO</scope><scope>7XB</scope><scope>8FE</scope><scope>8FH</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20130925</creationdate><title>Three-times daily ultrafractionated radiation therapy, a novel and promising regimen for glioblastoma patients</title><author>Beauchesne, Patrick</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3999-3c03911ba1f5735394a14cc4efc80ac591be78a5a94e377a0c716a98ef04ea1b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Cancer therapies</topic><topic>glioblastoma</topic><topic>low-dose radiation therapy</topic><topic>Radiation therapy</topic><topic>radiotherapy</topic><topic>Tumors</topic><topic>ultra fractionated regimen</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Beauchesne, Patrick</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection (Proquest) (PQ_SDU_P3)</collection><collection>ProQuest Biological Science Collection</collection><collection>ProQuest Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Publicly Available Content Database (ProQuest Open Access資料庫)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>Open Access: DOAJ - Directory of Open Access Journals</collection><jtitle>Cancers</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Beauchesne, Patrick</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Three-times daily ultrafractionated radiation therapy, a novel and promising regimen for glioblastoma patients</atitle><jtitle>Cancers</jtitle><addtitle>Cancers (Basel)</addtitle><date>2013-09-25</date><risdate>2013</risdate><volume>5</volume><issue>4</issue><spage>1199</spage><epage>1211</epage><pages>1199-1211</pages><issn>2072-6694</issn><eissn>2072-6694</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><abstract>Glioblastomas are considered to be one of the most radio resistant tumors. Despite new therapies, the prognosis of this disease remains dismal. Also, the mechanisms of radiation resistance in mammalian cells are more complex than once believed. Experimental studies have indicated that some human cell lines are sensitive to low radiation doses of <1 Gy. This phenomenon has been termed low-dose hyper-radio-sensitivity (HRS), and is more apparent in radio resistant cell lines, such as glioblastoma cells. Sensitivity may result from the inability of low dose radiation to efficiently induce repair mechanisms, whereas higher doses cause enough damage to trigger repair responses for radio resistance. In vitro studies have demonstrated this phenomenon using various human malignant glioma cell lines: (1) daily repeated irradiation of cells with low doses compared to irradiation using a single biologically equivalent dose resulted in significantly higher cell killing; (2) experiments conducted on glioma xenografts demonstrated that repeated irradiation with low doses was more effective for inhibiting tumor growth than a single dose. In order to confirm and validate these promising studies on HRS, a few phase II trials were developed. For translating the experimental observations into the clinic, ultra fractionation protocols (with three daily doses) were tested in glioblastoma patients. Tolerance and toxicity were the primary endpoints, with overall survival as a secondary endpoint. These protocols were initiated before concomitant radio chemotherapy became the standard of care. For these trials, patients with an unfavorable clinical prognostic factor of newly unresectable GBM were included. When comparing the results of these trials with international literature using multivariate analysis for both progression free survival and overall survival, ultra fractionated irradiation showed superiority over radiotherapy alone. In addition, it was found to be equivalent to treatment using radiotherapy and temozolomide. Therefore, ultra fractionated protocols may prolong survival of glioblastoma patients. In this review, we describe the main experimental data regarding low-dose hypersensitivity as well as the findings of clinical trials that have investigated this new radiotherapy regimen.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>24202441</pmid><doi>10.3390/cancers5041199</doi><oa>free_for_read</oa></addata></record> |