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Early BCRL treatment is associated with better outcomes, yet amid increasing evidence that lymphedema exists in a latent form, treatment is typically delayed until arm swelling is obvious. In this study, we investigated whether near-infrared fluorescence lymphatic imaging (NIRF-LI) surveillance could characterize early onset of peripheral lymphatic dysfunction as a predictor of BCRL.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>In a prospective, longitudinal cohort\/observational study (NCT02949726), subjects with locally advanced breast cancer who received axillary lymph node dissection and regional nodal radiotherapy (RT) were followed serially, between 2016 and 2021, before surgery, 4\u20138\u00a0weeks after surgery, and 6, 12, and 18\u00a0months after RT. Arm volume was measured by perometry, and lymphatic (dys) function was assessed by NIRF-LI.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>By 18\u00a0months after RT, 30 of 42 study subjects (71%) developed mild\u2013moderate BCRL (i.e.,\u2009\u2265\u20095% arm swelling relative to baseline), all manifested by \u201cdermal backflow\u201d of lymph into lymphatic capillaries or interstitial spaces. Dermal backflow had an 83% positive predictive value and 86% negative predictive value for BCRL, with a sensitivity of 97%, specificity of 50%, accuracy of 83%, positive likelihood ratio of 1.93, negative likelihood ratio of 0.07, and odds ratio of 29.00. Dermal backflow appeared on average 8.3\u00a0months, but up to 23\u00a0months, before the onset of mild BCRL.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>BCRL can be predicted by dermal backflow, which often appears months before arm swelling, enabling early treatment before the onset of edema and irreversible tissue changes.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s10549-022-06667-4","type":"journal-article","created":{"date-parts":[[2022,7,11]],"date-time":"2022-07-11T12:03:34Z","timestamp":1657541014000},"page":"33-41","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Prediction of breast cancer-related lymphedema by dermal backflow detected with near-infrared fluorescence lymphatic imaging"],"prefix":"10.1007","volume":"195","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8114-7607","authenticated-orcid":false,"given":"Melissa B.","family":"Aldrich","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.","family":"Rasmussen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah M.","family":"DeSnyder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy A.","family":"Woodward","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyaw","family":"Chan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva M.","family":"Sevick-Muraca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth A.","family":"Mittendorf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin D.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael C.","family":"Stauder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric A.","family":"Strom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George H.","family":"Perkins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen E.","family":"Hoffman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa P.","family":"Mitchell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos H.","family":"Barcenas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynn E.","family":"Isales","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona F.","family":"Shaitelman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,7,10]]},"reference":[{"key":"6667_CR1","doi-asserted-by":"publisher","first-page":"55","DOI":"10.3322\/caac.21253","volume":"65","author":"SF Shaitelman","year":"2015","unstructured":"Shaitelman SF, Cromwell KD, Rasmussen JC, Stout NL, Armer JM, Lasinski BB, Cormier JN (2015) Recent progress in the treatment and prevention of cancer-related lymphedema. 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EMS-M, JCR, and The University of Texas Health Science Center at Houston (UTHealth) have research-related financial interests in Lymphatic Science, Inc. SFS has grant funding from the Emerson Collective Foundation and research contract support from Artios Pharmaceuticals, Alpha Tau, and Exact Sciences. The remaining authors have no financial relationships or competing interests relevant to this article to disclose.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The study was conducted in line with the principles of the 1964 Declaration of Helsinki and later amendments, with offlabel use of indocyanine green under FDA Investigational New Drug (IND) application 106,345. Approval was granted by the Institutional Review Boards\/Committees for the Protection of Human Subjects at both UTHealth and MD Anderson Cancer Center. The study was conducted under the approval of the institutional review boards of both The University of Texas health Science Center at Houston and The University of Texas MD Anderson Cancer Center (under FDA combinational investigational new drug application 106,345 for off-label intradermal administration of indocyanine green (ICG) dye with NIRF-LI [NCT 02949726]).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Written informed consent was obtained from all individual participants in the study, including consent for publication of de-identified images. Signed informed consent for participation and publication of results was obtained from all study subjects.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}