Incidence, features and management of radionecrosis in melanoma patients treated with cerebral radiotherapy and anti‐PD‐1 antibodies
Background Brain radiotherapy is used in the management of melanoma brain metastases (MBM) and can result in radionecrosis. Anti‐PD‐1 is active in the brain and may increase the risk of radionecrosis when combined with radiotherapy. We studied the incidence, associated factors and management of radi...
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| Veröffentlicht in: | Pigment cell and melanoma research 2019-07, Vol.32 (4), p.553-563 |
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| creator | Pires da Silva, Ines Glitza, Isabella C. Haydu, Lauren E. Johnpulle, Romany Banks, Patricia D. Grass, George D. Goldinger, Simone M. A. Smith, Jessica L. Everett, Ashlyn S. Koelblinger, Peter Roberts‐Thomson, Rachel Millward, Michael Atkinson, Victoria G. Guminski, Alexander Kapoor, Rony Conry, Robert M. Carlino, Matteo S. Wang, Wei Shackleton, Mark J. Eroglu, Zeynep Lo, Serigne Hong, Angela M. Long, Georgina V. Johnson, Douglas B. Menzies, Alexander M. |
| description | Background
Brain radiotherapy is used in the management of melanoma brain metastases (MBM) and can result in radionecrosis. Anti‐PD‐1 is active in the brain and may increase the risk of radionecrosis when combined with radiotherapy. We studied the incidence, associated factors and management of radionecrosis in longer‐term survivors with MBM treated with this combination.
Methods
Patients with MBM treated with radiotherapy and anti‐PD‐1 who survived >1 year were identified to determine radionecrosis incidence (Cohort A, n = 135). Cohort A plus additional radionecrosis cases were examined for factors associated with radionecrosis and management (Cohort B, n = 148).
Results
From Cohort A, 17% developed radionecrosis, with a cumulative incidence at 2 years of 18%. Using Cohort B, multivariable analysis confirmed an association between radionecrosis and elevated lactate dehydrogenase (p = 0.0496) and prior treatment with ipilimumab (p = 0.0319). Radionecrosis was diagnosed based on MRI (100%), symptoms (69%) and pathology (56%). Treatment included corticosteroids, bevacizumab and neurosurgery.
Conclusions
Radionecrosis is a significant toxicity in longer‐term melanoma survivors with MBM treated with anti‐PD‐1 and radiotherapy. Identification of those at risk of radionecrosis who may avoid radiotherapy is required. |
| doi_str_mv | 10.1111/pcmr.12775 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8258671</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2241883375</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4485-b922c427601472452acf5fb77679091a8a6c61d11bac82b98362be01255cafe03</originalsourceid><addsrcrecordid>eNp9kc1u1DAUha2qiJbSTR8AWeoOMcV24tjZIKHhr1JRKwRSd9aNc9NxNbFTO0M1O5YseUaeBM-kjGBTL_wjf_f4XB9CTjg743m8Hmwfz7hQSu6RQ66knPFSX-_v9oofkGcp3TJWMVkXT8lBwVSlSqEPyc9zb12L3uIr2iGMq4iJgm9pDx5usEc_0tDRCK0LHm0MySXqPO1xCT70QAcYXYYSHWMux5beu3FBLUZsIiynwnGBEYb1Vhf86H7_-HX1Lk98e2pC6zA9J086WCY8fliPyLcP77_OP80uLj-ez99ezGxZajlraiFsKVTFcl-ilAJsJ7tG5X5qVnPQUNmKt5w3YLVoal1UokHGhZQWOmTFEXkz6Q6rpsfWZu_Zpxmi6yGuTQBn_r_xbmFuwnejhdSV4lng9EEghrsVptHchlX02bMRouRaF4WSmXo5UZsvSxG73QucmU1qZpOa2aaW4Rf_etqhf2PKAJ-Ae7fE9SNS5mr--csk-gfro6dk</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2241883375</pqid></control><display><type>article</type><title>Incidence, features and management of radionecrosis in melanoma patients treated with cerebral radiotherapy and anti‐PD‐1 antibodies</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Pires da Silva, Ines ; Glitza, Isabella C. ; Haydu, Lauren E. ; Johnpulle, Romany ; Banks, Patricia D. ; Grass, George D. ; Goldinger, Simone M. A. ; Smith, Jessica L. ; Everett, Ashlyn S. ; Koelblinger, Peter ; Roberts‐Thomson, Rachel ; Millward, Michael ; Atkinson, Victoria G. ; Guminski, Alexander ; Kapoor, Rony ; Conry, Robert M. ; Carlino, Matteo S. ; Wang, Wei ; Shackleton, Mark J. ; Eroglu, Zeynep ; Lo, Serigne ; Hong, Angela M. ; Long, Georgina V. ; Johnson, Douglas B. ; Menzies, Alexander M.</creator><creatorcontrib>Pires da Silva, Ines ; Glitza, Isabella C. ; Haydu, Lauren E. ; Johnpulle, Romany ; Banks, Patricia D. ; Grass, George D. ; Goldinger, Simone M. A. ; Smith, Jessica L. ; Everett, Ashlyn S. ; Koelblinger, Peter ; Roberts‐Thomson, Rachel ; Millward, Michael ; Atkinson, Victoria G. ; Guminski, Alexander ; Kapoor, Rony ; Conry, Robert M. ; Carlino, Matteo S. ; Wang, Wei ; Shackleton, Mark J. ; Eroglu, Zeynep ; Lo, Serigne ; Hong, Angela M. ; Long, Georgina V. ; Johnson, Douglas B. ; Menzies, Alexander M.</creatorcontrib><description>Background
Brain radiotherapy is used in the management of melanoma brain metastases (MBM) and can result in radionecrosis. Anti‐PD‐1 is active in the brain and may increase the risk of radionecrosis when combined with radiotherapy. We studied the incidence, associated factors and management of radionecrosis in longer‐term survivors with MBM treated with this combination.
Methods
Patients with MBM treated with radiotherapy and anti‐PD‐1 who survived >1 year were identified to determine radionecrosis incidence (Cohort A, n = 135). Cohort A plus additional radionecrosis cases were examined for factors associated with radionecrosis and management (Cohort B, n = 148).
Results
From Cohort A, 17% developed radionecrosis, with a cumulative incidence at 2 years of 18%. Using Cohort B, multivariable analysis confirmed an association between radionecrosis and elevated lactate dehydrogenase (p = 0.0496) and prior treatment with ipilimumab (p = 0.0319). Radionecrosis was diagnosed based on MRI (100%), symptoms (69%) and pathology (56%). Treatment included corticosteroids, bevacizumab and neurosurgery.
Conclusions
Radionecrosis is a significant toxicity in longer‐term melanoma survivors with MBM treated with anti‐PD‐1 and radiotherapy. Identification of those at risk of radionecrosis who may avoid radiotherapy is required.</description><identifier>ISSN: 1755-1471</identifier><identifier>EISSN: 1755-148X</identifier><identifier>DOI: 10.1111/pcmr.12775</identifier><identifier>PMID: 30767428</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>Antibodies ; Antibodies - therapeutic use ; Bevacizumab ; Brain ; Brain - radiation effects ; Brain cancer ; brain metastases ; Cohort Studies ; Corticoids ; Corticosteroids ; Female ; Humans ; immunotherapy ; Incidence ; L-Lactate dehydrogenase ; Lactate dehydrogenase ; Lactic acid ; Magnetic Resonance Imaging ; Male ; Management ; Melanoma ; Melanoma - diagnostic imaging ; Melanoma - immunology ; Melanoma - radiotherapy ; Metastases ; Metastasis ; Middle Aged ; Monoclonal antibodies ; Multivariate Analysis ; Necrosis ; Neurosurgery ; Programmed Cell Death 1 Receptor - immunology ; Radiation Injuries - diagnostic imaging ; Radiation Injuries - epidemiology ; Radiation Injuries - etiology ; Radiation Injuries - surgery ; Radiation therapy ; radionecrosis ; radiotherapy ; Risk Factors ; Signs and symptoms ; Survival ; Survival Analysis ; Toxicity</subject><ispartof>Pigment cell and melanoma research, 2019-07, Vol.32 (4), p.553-563</ispartof><rights>2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd</rights><rights>2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.</rights><rights>Copyright © 2019 John Wiley & Sons A/S</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4485-b922c427601472452acf5fb77679091a8a6c61d11bac82b98362be01255cafe03</citedby><cites>FETCH-LOGICAL-c4485-b922c427601472452acf5fb77679091a8a6c61d11bac82b98362be01255cafe03</cites><orcidid>0000-0002-6390-773X ; 0000-0001-5092-5544 ; 0000-0003-3540-8906 ; 0000-0002-4530-7765</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fpcmr.12775$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fpcmr.12775$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30767428$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pires da Silva, Ines</creatorcontrib><creatorcontrib>Glitza, Isabella C.</creatorcontrib><creatorcontrib>Haydu, Lauren E.</creatorcontrib><creatorcontrib>Johnpulle, Romany</creatorcontrib><creatorcontrib>Banks, Patricia D.</creatorcontrib><creatorcontrib>Grass, George D.</creatorcontrib><creatorcontrib>Goldinger, Simone M. A.</creatorcontrib><creatorcontrib>Smith, Jessica L.</creatorcontrib><creatorcontrib>Everett, Ashlyn S.</creatorcontrib><creatorcontrib>Koelblinger, Peter</creatorcontrib><creatorcontrib>Roberts‐Thomson, Rachel</creatorcontrib><creatorcontrib>Millward, Michael</creatorcontrib><creatorcontrib>Atkinson, Victoria G.</creatorcontrib><creatorcontrib>Guminski, Alexander</creatorcontrib><creatorcontrib>Kapoor, Rony</creatorcontrib><creatorcontrib>Conry, Robert M.</creatorcontrib><creatorcontrib>Carlino, Matteo S.</creatorcontrib><creatorcontrib>Wang, Wei</creatorcontrib><creatorcontrib>Shackleton, Mark J.</creatorcontrib><creatorcontrib>Eroglu, Zeynep</creatorcontrib><creatorcontrib>Lo, Serigne</creatorcontrib><creatorcontrib>Hong, Angela M.</creatorcontrib><creatorcontrib>Long, Georgina V.</creatorcontrib><creatorcontrib>Johnson, Douglas B.</creatorcontrib><creatorcontrib>Menzies, Alexander M.</creatorcontrib><title>Incidence, features and management of radionecrosis in melanoma patients treated with cerebral radiotherapy and anti‐PD‐1 antibodies</title><title>Pigment cell and melanoma research</title><addtitle>Pigment Cell Melanoma Res</addtitle><description>Background
Brain radiotherapy is used in the management of melanoma brain metastases (MBM) and can result in radionecrosis. Anti‐PD‐1 is active in the brain and may increase the risk of radionecrosis when combined with radiotherapy. We studied the incidence, associated factors and management of radionecrosis in longer‐term survivors with MBM treated with this combination.
Methods
Patients with MBM treated with radiotherapy and anti‐PD‐1 who survived >1 year were identified to determine radionecrosis incidence (Cohort A, n = 135). Cohort A plus additional radionecrosis cases were examined for factors associated with radionecrosis and management (Cohort B, n = 148).
Results
From Cohort A, 17% developed radionecrosis, with a cumulative incidence at 2 years of 18%. Using Cohort B, multivariable analysis confirmed an association between radionecrosis and elevated lactate dehydrogenase (p = 0.0496) and prior treatment with ipilimumab (p = 0.0319). Radionecrosis was diagnosed based on MRI (100%), symptoms (69%) and pathology (56%). Treatment included corticosteroids, bevacizumab and neurosurgery.
Conclusions
Radionecrosis is a significant toxicity in longer‐term melanoma survivors with MBM treated with anti‐PD‐1 and radiotherapy. Identification of those at risk of radionecrosis who may avoid radiotherapy is required.</description><subject>Antibodies</subject><subject>Antibodies - therapeutic use</subject><subject>Bevacizumab</subject><subject>Brain</subject><subject>Brain - radiation effects</subject><subject>Brain cancer</subject><subject>brain metastases</subject><subject>Cohort Studies</subject><subject>Corticoids</subject><subject>Corticosteroids</subject><subject>Female</subject><subject>Humans</subject><subject>immunotherapy</subject><subject>Incidence</subject><subject>L-Lactate dehydrogenase</subject><subject>Lactate dehydrogenase</subject><subject>Lactic acid</subject><subject>Magnetic Resonance Imaging</subject><subject>Male</subject><subject>Management</subject><subject>Melanoma</subject><subject>Melanoma - diagnostic imaging</subject><subject>Melanoma - immunology</subject><subject>Melanoma - radiotherapy</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Middle Aged</subject><subject>Monoclonal antibodies</subject><subject>Multivariate Analysis</subject><subject>Necrosis</subject><subject>Neurosurgery</subject><subject>Programmed Cell Death 1 Receptor - immunology</subject><subject>Radiation Injuries - diagnostic imaging</subject><subject>Radiation Injuries - epidemiology</subject><subject>Radiation Injuries - etiology</subject><subject>Radiation Injuries - surgery</subject><subject>Radiation therapy</subject><subject>radionecrosis</subject><subject>radiotherapy</subject><subject>Risk Factors</subject><subject>Signs and symptoms</subject><subject>Survival</subject><subject>Survival Analysis</subject><subject>Toxicity</subject><issn>1755-1471</issn><issn>1755-148X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc1u1DAUha2qiJbSTR8AWeoOMcV24tjZIKHhr1JRKwRSd9aNc9NxNbFTO0M1O5YseUaeBM-kjGBTL_wjf_f4XB9CTjg743m8Hmwfz7hQSu6RQ66knPFSX-_v9oofkGcp3TJWMVkXT8lBwVSlSqEPyc9zb12L3uIr2iGMq4iJgm9pDx5usEc_0tDRCK0LHm0MySXqPO1xCT70QAcYXYYSHWMux5beu3FBLUZsIiynwnGBEYb1Vhf86H7_-HX1Lk98e2pC6zA9J086WCY8fliPyLcP77_OP80uLj-ez99ezGxZajlraiFsKVTFcl-ilAJsJ7tG5X5qVnPQUNmKt5w3YLVoal1UokHGhZQWOmTFEXkz6Q6rpsfWZu_Zpxmi6yGuTQBn_r_xbmFuwnejhdSV4lng9EEghrsVptHchlX02bMRouRaF4WSmXo5UZsvSxG73QucmU1qZpOa2aaW4Rf_etqhf2PKAJ-Ae7fE9SNS5mr--csk-gfro6dk</recordid><startdate>201907</startdate><enddate>201907</enddate><creator>Pires da Silva, Ines</creator><creator>Glitza, Isabella C.</creator><creator>Haydu, Lauren E.</creator><creator>Johnpulle, Romany</creator><creator>Banks, Patricia D.</creator><creator>Grass, George D.</creator><creator>Goldinger, Simone M. A.</creator><creator>Smith, Jessica L.</creator><creator>Everett, Ashlyn S.</creator><creator>Koelblinger, Peter</creator><creator>Roberts‐Thomson, Rachel</creator><creator>Millward, Michael</creator><creator>Atkinson, Victoria G.</creator><creator>Guminski, Alexander</creator><creator>Kapoor, Rony</creator><creator>Conry, Robert M.</creator><creator>Carlino, Matteo S.</creator><creator>Wang, Wei</creator><creator>Shackleton, Mark J.</creator><creator>Eroglu, Zeynep</creator><creator>Lo, Serigne</creator><creator>Hong, Angela M.</creator><creator>Long, Georgina V.</creator><creator>Johnson, Douglas B.</creator><creator>Menzies, Alexander M.</creator><general>Wiley Subscription Services, Inc</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>7QO</scope><scope>7TO</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-6390-773X</orcidid><orcidid>https://orcid.org/0000-0001-5092-5544</orcidid><orcidid>https://orcid.org/0000-0003-3540-8906</orcidid><orcidid>https://orcid.org/0000-0002-4530-7765</orcidid></search><sort><creationdate>201907</creationdate><title>Incidence, features and management of radionecrosis in melanoma patients treated with cerebral radiotherapy and anti‐PD‐1 antibodies</title><author>Pires da Silva, Ines ; Glitza, Isabella C. ; Haydu, Lauren E. ; Johnpulle, Romany ; Banks, Patricia D. ; Grass, George D. ; Goldinger, Simone M. A. ; Smith, Jessica L. ; Everett, Ashlyn S. ; Koelblinger, Peter ; Roberts‐Thomson, Rachel ; Millward, Michael ; Atkinson, Victoria G. ; Guminski, Alexander ; Kapoor, Rony ; Conry, Robert M. ; Carlino, Matteo S. ; Wang, Wei ; Shackleton, Mark J. ; Eroglu, Zeynep ; Lo, Serigne ; Hong, Angela M. ; Long, Georgina V. ; Johnson, Douglas B. ; Menzies, Alexander M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4485-b922c427601472452acf5fb77679091a8a6c61d11bac82b98362be01255cafe03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Antibodies</topic><topic>Antibodies - therapeutic use</topic><topic>Bevacizumab</topic><topic>Brain</topic><topic>Brain - radiation effects</topic><topic>Brain cancer</topic><topic>brain metastases</topic><topic>Cohort Studies</topic><topic>Corticoids</topic><topic>Corticosteroids</topic><topic>Female</topic><topic>Humans</topic><topic>immunotherapy</topic><topic>Incidence</topic><topic>L-Lactate dehydrogenase</topic><topic>Lactate dehydrogenase</topic><topic>Lactic acid</topic><topic>Magnetic Resonance Imaging</topic><topic>Male</topic><topic>Management</topic><topic>Melanoma</topic><topic>Melanoma - diagnostic imaging</topic><topic>Melanoma - immunology</topic><topic>Melanoma - radiotherapy</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Middle Aged</topic><topic>Monoclonal antibodies</topic><topic>Multivariate Analysis</topic><topic>Necrosis</topic><topic>Neurosurgery</topic><topic>Programmed Cell Death 1 Receptor - immunology</topic><topic>Radiation Injuries - diagnostic imaging</topic><topic>Radiation Injuries - epidemiology</topic><topic>Radiation Injuries - etiology</topic><topic>Radiation Injuries - surgery</topic><topic>Radiation therapy</topic><topic>radionecrosis</topic><topic>radiotherapy</topic><topic>Risk Factors</topic><topic>Signs and symptoms</topic><topic>Survival</topic><topic>Survival Analysis</topic><topic>Toxicity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pires da Silva, Ines</creatorcontrib><creatorcontrib>Glitza, Isabella C.</creatorcontrib><creatorcontrib>Haydu, Lauren E.</creatorcontrib><creatorcontrib>Johnpulle, Romany</creatorcontrib><creatorcontrib>Banks, Patricia D.</creatorcontrib><creatorcontrib>Grass, George D.</creatorcontrib><creatorcontrib>Goldinger, Simone M. A.</creatorcontrib><creatorcontrib>Smith, Jessica L.</creatorcontrib><creatorcontrib>Everett, Ashlyn S.</creatorcontrib><creatorcontrib>Koelblinger, Peter</creatorcontrib><creatorcontrib>Roberts‐Thomson, Rachel</creatorcontrib><creatorcontrib>Millward, Michael</creatorcontrib><creatorcontrib>Atkinson, Victoria G.</creatorcontrib><creatorcontrib>Guminski, Alexander</creatorcontrib><creatorcontrib>Kapoor, Rony</creatorcontrib><creatorcontrib>Conry, Robert M.</creatorcontrib><creatorcontrib>Carlino, Matteo S.</creatorcontrib><creatorcontrib>Wang, Wei</creatorcontrib><creatorcontrib>Shackleton, Mark J.</creatorcontrib><creatorcontrib>Eroglu, Zeynep</creatorcontrib><creatorcontrib>Lo, Serigne</creatorcontrib><creatorcontrib>Hong, Angela M.</creatorcontrib><creatorcontrib>Long, Georgina V.</creatorcontrib><creatorcontrib>Johnson, Douglas B.</creatorcontrib><creatorcontrib>Menzies, Alexander M.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Pigment cell and melanoma research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pires da Silva, Ines</au><au>Glitza, Isabella C.</au><au>Haydu, Lauren E.</au><au>Johnpulle, Romany</au><au>Banks, Patricia D.</au><au>Grass, George D.</au><au>Goldinger, Simone M. A.</au><au>Smith, Jessica L.</au><au>Everett, Ashlyn S.</au><au>Koelblinger, Peter</au><au>Roberts‐Thomson, Rachel</au><au>Millward, Michael</au><au>Atkinson, Victoria G.</au><au>Guminski, Alexander</au><au>Kapoor, Rony</au><au>Conry, Robert M.</au><au>Carlino, Matteo S.</au><au>Wang, Wei</au><au>Shackleton, Mark J.</au><au>Eroglu, Zeynep</au><au>Lo, Serigne</au><au>Hong, Angela M.</au><au>Long, Georgina V.</au><au>Johnson, Douglas B.</au><au>Menzies, Alexander M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Incidence, features and management of radionecrosis in melanoma patients treated with cerebral radiotherapy and anti‐PD‐1 antibodies</atitle><jtitle>Pigment cell and melanoma research</jtitle><addtitle>Pigment Cell Melanoma Res</addtitle><date>2019-07</date><risdate>2019</risdate><volume>32</volume><issue>4</issue><spage>553</spage><epage>563</epage><pages>553-563</pages><issn>1755-1471</issn><eissn>1755-148X</eissn><abstract>Background
Brain radiotherapy is used in the management of melanoma brain metastases (MBM) and can result in radionecrosis. Anti‐PD‐1 is active in the brain and may increase the risk of radionecrosis when combined with radiotherapy. We studied the incidence, associated factors and management of radionecrosis in longer‐term survivors with MBM treated with this combination.
Methods
Patients with MBM treated with radiotherapy and anti‐PD‐1 who survived >1 year were identified to determine radionecrosis incidence (Cohort A, n = 135). Cohort A plus additional radionecrosis cases were examined for factors associated with radionecrosis and management (Cohort B, n = 148).
Results
From Cohort A, 17% developed radionecrosis, with a cumulative incidence at 2 years of 18%. Using Cohort B, multivariable analysis confirmed an association between radionecrosis and elevated lactate dehydrogenase (p = 0.0496) and prior treatment with ipilimumab (p = 0.0319). Radionecrosis was diagnosed based on MRI (100%), symptoms (69%) and pathology (56%). Treatment included corticosteroids, bevacizumab and neurosurgery.
Conclusions
Radionecrosis is a significant toxicity in longer‐term melanoma survivors with MBM treated with anti‐PD‐1 and radiotherapy. Identification of those at risk of radionecrosis who may avoid radiotherapy is required.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>30767428</pmid><doi>10.1111/pcmr.12775</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-6390-773X</orcidid><orcidid>https://orcid.org/0000-0001-5092-5544</orcidid><orcidid>https://orcid.org/0000-0003-3540-8906</orcidid><orcidid>https://orcid.org/0000-0002-4530-7765</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
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| ispartof | Pigment cell and melanoma research, 2019-07, Vol.32 (4), p.553-563 |
| issn | 1755-1471 1755-148X |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8258671 |
| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Antibodies Antibodies - therapeutic use Bevacizumab Brain Brain - radiation effects Brain cancer brain metastases Cohort Studies Corticoids Corticosteroids Female Humans immunotherapy Incidence L-Lactate dehydrogenase Lactate dehydrogenase Lactic acid Magnetic Resonance Imaging Male Management Melanoma Melanoma - diagnostic imaging Melanoma - immunology Melanoma - radiotherapy Metastases Metastasis Middle Aged Monoclonal antibodies Multivariate Analysis Necrosis Neurosurgery Programmed Cell Death 1 Receptor - immunology Radiation Injuries - diagnostic imaging Radiation Injuries - epidemiology Radiation Injuries - etiology Radiation Injuries - surgery Radiation therapy radionecrosis radiotherapy Risk Factors Signs and symptoms Survival Survival Analysis Toxicity |
| title | Incidence, features and management of radionecrosis in melanoma patients treated with cerebral radiotherapy and anti‐PD‐1 antibodies |
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