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Primary histiocytic sarcoma of the central nervous system: a case report with platelet derived growth factor receptor mutation and PD-L1/PD-L2 expression and literature review
Histiocytic sarcoma (HS) is an aggressive malignant neoplasm. HS in the central nervous system is exceptionally rare and associated with a poor prognosis. This report documents a case of primary HS of the central nervous system with treatment including surgery, radiotherapy, and chemotherapy. Our pa...
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Published in: | Radiation oncology (London, England) England), 2018-09, Vol.13 (1), p.167-167, Article 167 |
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creator | May, Jackson M Waddle, Mark R Miller, Daniel H Stross, William C Kaleem, Tasneem A May, Byron C Miller, Robert C Jiang, Liuyan Strong, Gerald W Trifiletti, Daniel M Chaichana, Kaisorn L Reimer, Ronald Tun, Han W Peterson, Jennifer L |
description | Histiocytic sarcoma (HS) is an aggressive malignant neoplasm. HS in the central nervous system is exceptionally rare and associated with a poor prognosis. This report documents a case of primary HS of the central nervous system with treatment including surgery, radiotherapy, and chemotherapy.
Our patient was a 47 year old female presenting with progressive ataxia, headaches, imbalance, nausea, vomiting, and diplopia. MRI showed a heterogeneously enhancing lesion approximately 2.9 × 3.0 × 2.3 cm centered upon the cerebellar vermis with mild surrounding vasogenic edema and abnormal enhancement of multiple cranial nerves. The patient underwent surgical debulking, which revealed histiocytic sarcoma with grossly purulent drainage. Staging revealed diffuse leptomeningeal involvement, primarily involving the brain and lower thoracic and lumbar spine. She underwent adjuvant radiotherapy to the brain and lower spine and was started on high dose methotrexate. However, she experienced progressive disease in the cervical and thoracic spine as well as pulmonary involvement. Genomic sequencing of her tumor showed a mutation in the platelet-derived growth factor receptor A (p.V0681) which could be targeted with Dasatinib. However, she did not tolerate Dasatinib and she succumbed to progressive disseminated disease eight months from original diagnosis. Our pathologic evaluation also revealed expression of PD-L1 and PD-L2 by tumor cells raising the potential therapeutic role for immune checkpoint inhibition.
This case provides an example of effective CNS control with resection and moderate doses of radiation therapy. A review of the literature confirms aggressive multidisciplinary treatment is the most effective treatment against this disease. In addition, genomic sequencing may play an important role in determining new therapeutic options. However, CNS histiocytic sarcoma remains an aggressive disease with a propensity for early widespread dissemination and few long term survivors. |
doi_str_mv | 10.1186/s13014-018-1115-x |
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Our patient was a 47 year old female presenting with progressive ataxia, headaches, imbalance, nausea, vomiting, and diplopia. MRI showed a heterogeneously enhancing lesion approximately 2.9 × 3.0 × 2.3 cm centered upon the cerebellar vermis with mild surrounding vasogenic edema and abnormal enhancement of multiple cranial nerves. The patient underwent surgical debulking, which revealed histiocytic sarcoma with grossly purulent drainage. Staging revealed diffuse leptomeningeal involvement, primarily involving the brain and lower thoracic and lumbar spine. She underwent adjuvant radiotherapy to the brain and lower spine and was started on high dose methotrexate. However, she experienced progressive disease in the cervical and thoracic spine as well as pulmonary involvement. Genomic sequencing of her tumor showed a mutation in the platelet-derived growth factor receptor A (p.V0681) which could be targeted with Dasatinib. However, she did not tolerate Dasatinib and she succumbed to progressive disseminated disease eight months from original diagnosis. Our pathologic evaluation also revealed expression of PD-L1 and PD-L2 by tumor cells raising the potential therapeutic role for immune checkpoint inhibition.
This case provides an example of effective CNS control with resection and moderate doses of radiation therapy. A review of the literature confirms aggressive multidisciplinary treatment is the most effective treatment against this disease. In addition, genomic sequencing may play an important role in determining new therapeutic options. However, CNS histiocytic sarcoma remains an aggressive disease with a propensity for early widespread dissemination and few long term survivors.</description><identifier>ISSN: 1748-717X</identifier><identifier>EISSN: 1748-717X</identifier><identifier>DOI: 10.1186/s13014-018-1115-x</identifier><identifier>PMID: 30185195</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Ataxia ; B7-H1 Antigen - metabolism ; Blood platelets ; Brain ; Brain cancer ; Brain Neoplasms - genetics ; Brain Neoplasms - metabolism ; Brain Neoplasms - pathology ; Brain Neoplasms - therapy ; Care and treatment ; Case Report ; Case reports ; Case studies ; Central nervous system ; Cerebellum ; Chemotherapy ; CNS ; Cranial nerves ; Diagnosis ; Edema ; Fatal Outcome ; Female ; Growth factors ; Headache ; Histiocytic sarcoma ; Histiocytic Sarcoma - genetics ; Histiocytic Sarcoma - metabolism ; Histiocytic Sarcoma - pathology ; Histiocytic Sarcoma - therapy ; Humans ; Immune checkpoint inhibitors ; Literature reviews ; Lymphoma ; Magnetic resonance imaging ; Medical prognosis ; Medical treatment ; Meninges ; Methotrexate ; Middle Aged ; Mutation ; Mutation - genetics ; Nausea ; Neoplasia ; Nerves ; Nervous system ; Nervous system cancer ; Neuropathology ; Patient outcomes ; Patients ; PD-L1 protein ; Platelet-derived growth factor ; Programmed Cell Death 1 Ligand 2 Protein - metabolism ; Radiation ; Radiation therapy ; Receptor, Platelet-Derived Growth Factor alpha - genetics ; Review ; Sarcoma ; Spinal Neoplasms - diagnostic imaging ; Spinal Neoplasms - secondary ; Spine ; Spine (lumbar) ; Spine (thoracic) ; Surgery ; Terminal Care ; Tumor cells ; Tumors ; Vomiting</subject><ispartof>Radiation oncology (London, England), 2018-09, Vol.13 (1), p.167-167, Article 167</ispartof><rights>COPYRIGHT 2018 BioMed Central Ltd.</rights><rights>Copyright © 2018. This work is licensed 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><rights>The Author(s). 2018</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c560t-584cfb290fe336ae048fa18ff45243a38e468d04a2feadd7832140c21eeaf67b3</citedby><cites>FETCH-LOGICAL-c560t-584cfb290fe336ae048fa18ff45243a38e468d04a2feadd7832140c21eeaf67b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6126020/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2108704362?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30185195$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>May, Jackson M</creatorcontrib><creatorcontrib>Waddle, Mark R</creatorcontrib><creatorcontrib>Miller, Daniel H</creatorcontrib><creatorcontrib>Stross, William C</creatorcontrib><creatorcontrib>Kaleem, Tasneem A</creatorcontrib><creatorcontrib>May, Byron C</creatorcontrib><creatorcontrib>Miller, Robert C</creatorcontrib><creatorcontrib>Jiang, Liuyan</creatorcontrib><creatorcontrib>Strong, Gerald W</creatorcontrib><creatorcontrib>Trifiletti, Daniel M</creatorcontrib><creatorcontrib>Chaichana, Kaisorn L</creatorcontrib><creatorcontrib>Reimer, Ronald</creatorcontrib><creatorcontrib>Tun, Han W</creatorcontrib><creatorcontrib>Peterson, Jennifer L</creatorcontrib><title>Primary histiocytic sarcoma of the central nervous system: a case report with platelet derived growth factor receptor mutation and PD-L1/PD-L2 expression and literature review</title><title>Radiation oncology (London, England)</title><addtitle>Radiat Oncol</addtitle><description>Histiocytic sarcoma (HS) is an aggressive malignant neoplasm. HS in the central nervous system is exceptionally rare and associated with a poor prognosis. This report documents a case of primary HS of the central nervous system with treatment including surgery, radiotherapy, and chemotherapy.
Our patient was a 47 year old female presenting with progressive ataxia, headaches, imbalance, nausea, vomiting, and diplopia. MRI showed a heterogeneously enhancing lesion approximately 2.9 × 3.0 × 2.3 cm centered upon the cerebellar vermis with mild surrounding vasogenic edema and abnormal enhancement of multiple cranial nerves. The patient underwent surgical debulking, which revealed histiocytic sarcoma with grossly purulent drainage. Staging revealed diffuse leptomeningeal involvement, primarily involving the brain and lower thoracic and lumbar spine. She underwent adjuvant radiotherapy to the brain and lower spine and was started on high dose methotrexate. However, she experienced progressive disease in the cervical and thoracic spine as well as pulmonary involvement. Genomic sequencing of her tumor showed a mutation in the platelet-derived growth factor receptor A (p.V0681) which could be targeted with Dasatinib. However, she did not tolerate Dasatinib and she succumbed to progressive disseminated disease eight months from original diagnosis. Our pathologic evaluation also revealed expression of PD-L1 and PD-L2 by tumor cells raising the potential therapeutic role for immune checkpoint inhibition.
This case provides an example of effective CNS control with resection and moderate doses of radiation therapy. A review of the literature confirms aggressive multidisciplinary treatment is the most effective treatment against this disease. In addition, genomic sequencing may play an important role in determining new therapeutic options. However, CNS histiocytic sarcoma remains an aggressive disease with a propensity for early widespread dissemination and few long term survivors.</description><subject>Ataxia</subject><subject>B7-H1 Antigen - metabolism</subject><subject>Blood platelets</subject><subject>Brain</subject><subject>Brain cancer</subject><subject>Brain Neoplasms - genetics</subject><subject>Brain Neoplasms - metabolism</subject><subject>Brain Neoplasms - pathology</subject><subject>Brain Neoplasms - therapy</subject><subject>Care and treatment</subject><subject>Case Report</subject><subject>Case reports</subject><subject>Case studies</subject><subject>Central nervous system</subject><subject>Cerebellum</subject><subject>Chemotherapy</subject><subject>CNS</subject><subject>Cranial nerves</subject><subject>Diagnosis</subject><subject>Edema</subject><subject>Fatal Outcome</subject><subject>Female</subject><subject>Growth factors</subject><subject>Headache</subject><subject>Histiocytic sarcoma</subject><subject>Histiocytic Sarcoma - genetics</subject><subject>Histiocytic Sarcoma - metabolism</subject><subject>Histiocytic Sarcoma - pathology</subject><subject>Histiocytic Sarcoma - therapy</subject><subject>Humans</subject><subject>Immune checkpoint inhibitors</subject><subject>Literature reviews</subject><subject>Lymphoma</subject><subject>Magnetic resonance imaging</subject><subject>Medical prognosis</subject><subject>Medical treatment</subject><subject>Meninges</subject><subject>Methotrexate</subject><subject>Middle Aged</subject><subject>Mutation</subject><subject>Mutation - genetics</subject><subject>Nausea</subject><subject>Neoplasia</subject><subject>Nerves</subject><subject>Nervous system</subject><subject>Nervous system cancer</subject><subject>Neuropathology</subject><subject>Patient outcomes</subject><subject>Patients</subject><subject>PD-L1 protein</subject><subject>Platelet-derived growth factor</subject><subject>Programmed Cell Death 1 Ligand 2 Protein - metabolism</subject><subject>Radiation</subject><subject>Radiation therapy</subject><subject>Receptor, Platelet-Derived Growth Factor alpha - genetics</subject><subject>Review</subject><subject>Sarcoma</subject><subject>Spinal Neoplasms - diagnostic imaging</subject><subject>Spinal Neoplasms - secondary</subject><subject>Spine</subject><subject>Spine (lumbar)</subject><subject>Spine (thoracic)</subject><subject>Surgery</subject><subject>Terminal Care</subject><subject>Tumor cells</subject><subject>Tumors</subject><subject>Vomiting</subject><issn>1748-717X</issn><issn>1748-717X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNptUl1vFCEUnRiNrdUf4Ish8aUv08LAMKwPJk39arKJfdDEN8LAZZfNzLACs7v9Vf5FGXdbu8aQwM3lnHPD4RTFa4IvCBH8MhKKCSsxESUhpC53T4pT0jBRNqT58fRRfVK8iHGFMaspnj0vTjJN1GRWnxa_boPrVbhDSxeT8_ouOY2iCtr3CnmL0hKQhiEF1aEBwsaPEcW7mKB_hxTSKgIKsPYhoa1LS7TuVIIOEjIQ3AYMWgS_zX2rdPIhQzWsp6Ifk8rjBqQGg24_lHNyOe0Vgt06QIz3V51LEFQawzRm42D7snhmVRfh1eE8K75_-vjt-ks5__r55vpqXuqa41TWgmnbVjNsgVKuADNhFRHWsrpiVFEBjAuDmaosKGMaQSvCsK4IgLK8aelZcbPXNV6t5HpvkvTKyT8NHxZShexVB9I2lohWCMGtYcboFlphec0bbLme8Unr_V5rPbY9mIOdR6LHN4NbyoXfSE4qjiucBc4PAsH_HCEm2buooevUAPlDZEUwppRVDcvQt_9AV34MQ7ZqQokGM8qrv6iFyg9wg_V5rp5E5VVdNw2ltOYZdfEfVF4Geqf9ANbl_hGB7Ak6-BgD2Ic3EiynxMp9YmWOn5wSK3eZ8-axOQ-M-4jS3zHq6k0</recordid><startdate>20180905</startdate><enddate>20180905</enddate><creator>May, Jackson M</creator><creator>Waddle, Mark R</creator><creator>Miller, Daniel H</creator><creator>Stross, William C</creator><creator>Kaleem, Tasneem A</creator><creator>May, Byron C</creator><creator>Miller, Robert C</creator><creator>Jiang, Liuyan</creator><creator>Strong, Gerald W</creator><creator>Trifiletti, Daniel M</creator><creator>Chaichana, Kaisorn L</creator><creator>Reimer, Ronald</creator><creator>Tun, Han W</creator><creator>Peterson, Jennifer L</creator><general>BioMed Central Ltd</general><general>BioMed Central</general><general>BMC</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>3V.</scope><scope>7QO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20180905</creationdate><title>Primary histiocytic sarcoma of the central nervous system: a case report with platelet derived growth factor receptor mutation and PD-L1/PD-L2 expression and literature review</title><author>May, Jackson M ; Waddle, Mark R ; Miller, Daniel H ; Stross, William C ; Kaleem, Tasneem A ; May, Byron C ; Miller, Robert C ; Jiang, Liuyan ; Strong, Gerald W ; Trifiletti, Daniel M ; Chaichana, Kaisorn L ; Reimer, Ronald ; Tun, Han W ; Peterson, Jennifer L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c560t-584cfb290fe336ae048fa18ff45243a38e468d04a2feadd7832140c21eeaf67b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Ataxia</topic><topic>B7-H1 Antigen - metabolism</topic><topic>Blood platelets</topic><topic>Brain</topic><topic>Brain cancer</topic><topic>Brain Neoplasms - genetics</topic><topic>Brain Neoplasms - metabolism</topic><topic>Brain Neoplasms - pathology</topic><topic>Brain Neoplasms - therapy</topic><topic>Care and treatment</topic><topic>Case Report</topic><topic>Case reports</topic><topic>Case studies</topic><topic>Central nervous system</topic><topic>Cerebellum</topic><topic>Chemotherapy</topic><topic>CNS</topic><topic>Cranial nerves</topic><topic>Diagnosis</topic><topic>Edema</topic><topic>Fatal Outcome</topic><topic>Female</topic><topic>Growth factors</topic><topic>Headache</topic><topic>Histiocytic sarcoma</topic><topic>Histiocytic Sarcoma - genetics</topic><topic>Histiocytic Sarcoma - metabolism</topic><topic>Histiocytic Sarcoma - pathology</topic><topic>Histiocytic Sarcoma - therapy</topic><topic>Humans</topic><topic>Immune checkpoint inhibitors</topic><topic>Literature reviews</topic><topic>Lymphoma</topic><topic>Magnetic resonance imaging</topic><topic>Medical prognosis</topic><topic>Medical treatment</topic><topic>Meninges</topic><topic>Methotrexate</topic><topic>Middle Aged</topic><topic>Mutation</topic><topic>Mutation - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Radiation oncology (London, England)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>May, Jackson M</au><au>Waddle, Mark R</au><au>Miller, Daniel H</au><au>Stross, William C</au><au>Kaleem, Tasneem A</au><au>May, Byron C</au><au>Miller, Robert C</au><au>Jiang, Liuyan</au><au>Strong, Gerald W</au><au>Trifiletti, Daniel M</au><au>Chaichana, Kaisorn L</au><au>Reimer, Ronald</au><au>Tun, Han W</au><au>Peterson, Jennifer L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Primary histiocytic sarcoma of the central nervous system: a case report with platelet derived growth factor receptor mutation and PD-L1/PD-L2 expression and literature review</atitle><jtitle>Radiation oncology (London, England)</jtitle><addtitle>Radiat Oncol</addtitle><date>2018-09-05</date><risdate>2018</risdate><volume>13</volume><issue>1</issue><spage>167</spage><epage>167</epage><pages>167-167</pages><artnum>167</artnum><issn>1748-717X</issn><eissn>1748-717X</eissn><abstract>Histiocytic sarcoma (HS) is an aggressive malignant neoplasm. HS in the central nervous system is exceptionally rare and associated with a poor prognosis. This report documents a case of primary HS of the central nervous system with treatment including surgery, radiotherapy, and chemotherapy.
Our patient was a 47 year old female presenting with progressive ataxia, headaches, imbalance, nausea, vomiting, and diplopia. MRI showed a heterogeneously enhancing lesion approximately 2.9 × 3.0 × 2.3 cm centered upon the cerebellar vermis with mild surrounding vasogenic edema and abnormal enhancement of multiple cranial nerves. The patient underwent surgical debulking, which revealed histiocytic sarcoma with grossly purulent drainage. Staging revealed diffuse leptomeningeal involvement, primarily involving the brain and lower thoracic and lumbar spine. She underwent adjuvant radiotherapy to the brain and lower spine and was started on high dose methotrexate. However, she experienced progressive disease in the cervical and thoracic spine as well as pulmonary involvement. Genomic sequencing of her tumor showed a mutation in the platelet-derived growth factor receptor A (p.V0681) which could be targeted with Dasatinib. However, she did not tolerate Dasatinib and she succumbed to progressive disseminated disease eight months from original diagnosis. Our pathologic evaluation also revealed expression of PD-L1 and PD-L2 by tumor cells raising the potential therapeutic role for immune checkpoint inhibition.
This case provides an example of effective CNS control with resection and moderate doses of radiation therapy. A review of the literature confirms aggressive multidisciplinary treatment is the most effective treatment against this disease. In addition, genomic sequencing may play an important role in determining new therapeutic options. However, CNS histiocytic sarcoma remains an aggressive disease with a propensity for early widespread dissemination and few long term survivors.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>30185195</pmid><doi>10.1186/s13014-018-1115-x</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Ataxia B7-H1 Antigen - metabolism Blood platelets Brain Brain cancer Brain Neoplasms - genetics Brain Neoplasms - metabolism Brain Neoplasms - pathology Brain Neoplasms - therapy Care and treatment Case Report Case reports Case studies Central nervous system Cerebellum Chemotherapy CNS Cranial nerves Diagnosis Edema Fatal Outcome Female Growth factors Headache Histiocytic sarcoma Histiocytic Sarcoma - genetics Histiocytic Sarcoma - metabolism Histiocytic Sarcoma - pathology Histiocytic Sarcoma - therapy Humans Immune checkpoint inhibitors Literature reviews Lymphoma Magnetic resonance imaging Medical prognosis Medical treatment Meninges Methotrexate Middle Aged Mutation Mutation - genetics Nausea Neoplasia Nerves Nervous system Nervous system cancer Neuropathology Patient outcomes Patients PD-L1 protein Platelet-derived growth factor Programmed Cell Death 1 Ligand 2 Protein - metabolism Radiation Radiation therapy Receptor, Platelet-Derived Growth Factor alpha - genetics Review Sarcoma Spinal Neoplasms - diagnostic imaging Spinal Neoplasms - secondary Spine Spine (lumbar) Spine (thoracic) Surgery Terminal Care Tumor cells Tumors Vomiting |
title | Primary histiocytic sarcoma of the central nervous system: a case report with platelet derived growth factor receptor mutation and PD-L1/PD-L2 expression and literature review |
url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T21%3A41%3A19IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_doaj_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Primary%20histiocytic%20sarcoma%20of%20the%20central%20nervous%20system:%20a%20case%20report%20with%20platelet%20derived%20growth%20factor%20receptor%20mutation%20and%20PD-L1/PD-L2%20expression%20and%20literature%20review&rft.jtitle=Radiation%20oncology%20(London,%20England)&rft.au=May,%20Jackson%20M&rft.date=2018-09-05&rft.volume=13&rft.issue=1&rft.spage=167&rft.epage=167&rft.pages=167-167&rft.artnum=167&rft.issn=1748-717X&rft.eissn=1748-717X&rft_id=info:doi/10.1186/s13014-018-1115-x&rft_dat=%3Cgale_doaj_%3EA557733356%3C/gale_doaj_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c560t-584cfb290fe336ae048fa18ff45243a38e468d04a2feadd7832140c21eeaf67b3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2108704362&rft_id=info:pmid/30185195&rft_galeid=A557733356&rfr_iscdi=true |