{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T09:10:13Z","timestamp":1748509813062,"version":"3.37.3"},"reference-count":35,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2023,2,17]],"date-time":"2023-02-17T00:00:00Z","timestamp":1676592000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["1TL1TR001443"],"award-info":[{"award-number":["1TL1TR001443"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["K08 EB026503"],"award-info":[{"award-number":["K08 EB026503"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["UL1TR001442"],"award-info":[{"award-number":["UL1TR001442"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["1KL2TR001444"],"award-info":[{"award-number":["1KL2TR001444"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["UL1TR000100"],"award-info":[{"award-number":["UL1TR000100"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["R01 CA238783-01"],"award-info":[{"award-number":["R01 CA238783-01"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000048","name":"American Cancer Society","doi-asserted-by":"publisher","award":["RSG-15-229-01-CCE"],"award-info":[{"award-number":["RSG-15-229-01-CCE"]}],"id":[{"id":"10.13039\/100000048","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Purpose<\/jats:title>\n<jats:p>Bevacizumab-related imaging abnormality (BRIA), appearing as areas of restricted diffusion on magnetic resonance imaging (MRI) and representing atypical coagulative necrosis pathologically, has been observed in patients with brain tumors receiving radiotherapy and bevacizumab. We investigated the role of cumulative radiation dose in BRIA development in a voxel-wise analysis.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>Patients (n = 18) with BRIA were identified. All had high-grade gliomas or brain metastases treated with radiotherapy and bevacizumab. Areas of BRIA were segmented semi-automatically on diffusion-weighted MRI with apparent diffusion coefficient (ADC) images. To avoid confounding by possible tumor, hypoperfusion was confirmed with perfusion imaging. ADC images and radiation dose maps were co-registered to a high-resolution T1-weighted MRI and registration accuracy was verified. Voxel-wise normal tissue complication probability analyses were performed using a logistic model analyzing the relationship between cumulative voxel equivalent total dose in 2 Gy fractions (EQD2) and BRIA development at each voxel. Confidence intervals for regression model predictions were estimated with bootstrapping.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Among 18 patients, 39 brain tumors were treated. Patients received a median of 4.5 cycles of bevacizumab and 1\u20134 radiation courses prior to BRIA appearance. Most (64%) treated tumors overlapped with areas of BRIA. The median proportion of each BRIA region of interest volume overlapping with tumor was 98%. We found a dose-dependent association between cumulative voxel EQD2 and the relative probability of BRIA (\u03b2<jats:sub>0<\/jats:sub> = -5.1, \u03b2<jats:sub>1<\/jats:sub> = 0.03 Gy<jats:sup>-1<\/jats:sup>, \u03b3 = 1.3).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>BRIA is likely a radiation dose-dependent phenomenon in patients with brain tumors receiving bevacizumab and radiotherapy. The combination of radiation effects and tumor microenvironmental factors in potentiating BRIA in this population should be further investigated.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0279812","type":"journal-article","created":{"date-parts":[[2023,2,17]],"date-time":"2023-02-17T18:35:50Z","timestamp":1676658950000},"page":"e0279812","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["The relationship between radiation dose and bevacizumab-related imaging abnormality in patients with brain tumors: A voxel-wise normal tissue complication probability (NTCP) analysis"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5195-5590","authenticated-orcid":true,"given":"Mia","family":"Salans","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jordan","family":"Houri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roshan","family":"Karunamuni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Austin","family":"Hopper","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel","family":"Delfanti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tyler M.","family":"Seibert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naeim","family":"Bahrami","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasamin","family":"Sharifzadeh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carrie","family":"McDonald","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anders","family":"Dale","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vitali","family":"Moiseenko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikdokht","family":"Farid","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8222-606X","authenticated-orcid":true,"given":"Jona A.","family":"Hattangadi-Gluth","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2023,2,17]]},"reference":[{"key":"pone.0279812.ref001","unstructured":"Burt Nabors L, Ahluwalia M, Baehring J, Brem H, Butowski N, Helen Diller Family U, et al. 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