{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:49:15Z","timestamp":1790124555926,"version":"4.0.1"},"reference-count":39,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,10,22]],"date-time":"2023-10-22T00:00:00Z","timestamp":1697932800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Head &amp; Neck"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Polymorphous low\u2010grade adenocarcinoma (PLGA) is an extremely rare finding in the nasopharynx. There are no guidelines for the treatment of PLGA in this localization. Radiotherapy may be administered to treat this malignancy; however, in radiosensitive individuals, it is associated with a risk of severe radiotherapy\u2010induced toxicity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We present a case of a 73\u2010year\u2010old woman with locally advanced polymorphous low\u2010grade adenocarcinoma of the nasopharynx who developed a severe adverse acute reaction to radiotherapy leading to treatment discontinuation. Despite intensive treatment, the patient died 40\u2009days after RT initiation. Whole genome sequencing was performed using DNA from peripheral blood mononuclear cells in the search for variants that could explain such extreme toxicity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified a combination of pathogenic variants that may have contributed to the patient's reaction to radiation therapy, including predisposing variants in <jats:italic>XRCC1<\/jats:italic>, <jats:italic>XRCC3<\/jats:italic>, and <jats:italic>LIG4<\/jats:italic>. We also identified candidate variants, not previously described in this context, which could be associated with radiation toxicity based on plausible mechanisms. We discuss previous reports of this rare tumor from the literature and known contributors to radiation\u2010induced toxicity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Genetic causes should be considered in cases of extreme radiosensitivity, especially when is not explained by clinical factors.<\/jats:p><\/jats:sec>","DOI":"10.1002\/hed.27555","type":"journal-article","created":{"date-parts":[[2023,10,23]],"date-time":"2023-10-23T05:29:56Z","timestamp":1698038996000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Extreme acute radiation\u2010induced toxicity in a patient with polymorphous low\u2010grade adenocarcinoma of the nasopharynx and rare variants in <scp>DNA<\/scp> repair genes"],"prefix":"10.1002","volume":"46","author":[{"given":"Zuzanna","family":"Nowicka","sequence":"first","affiliation":[{"name":"Department of Biostatistics and Translational Medicine Medical University of \u0141\u00f3d\u017a  \u0141\u00f3d\u017a Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2033-1140","authenticated-orcid":false,"given":"Kasper","family":"Kuna","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Translational Medicine Medical University of \u0141\u00f3d\u017a  \u0141\u00f3d\u017a Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konrad","family":"Stawiski","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Translational Medicine Medical University of \u0141\u00f3d\u017a  \u0141\u00f3d\u017a Poland"},{"name":"Department of Radiotherapy Medical University of \u0141\u00f3d\u017a  \u0141\u00f3d\u017a Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"So\u0142ek","sequence":"additional","affiliation":[{"name":"Department of Pathology, Chair of Oncology Medical University of \u0141\u00f3d\u017a  \u0141\u00f3d\u017a Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"\u015awiderek","sequence":"additional","affiliation":[{"name":"Department of Radiotherapy Medical University of \u0141\u00f3d\u017a  \u0141\u00f3d\u017a Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Papis\u2010Ubych","sequence":"additional","affiliation":[{"name":"Department of Radiotherapy Medical University of \u0141\u00f3d\u017a  \u0141\u00f3d\u017a Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacek","family":"Fijuth","sequence":"additional","affiliation":[{"name":"Department of Radiotherapy Medical University of \u0141\u00f3d\u017a  \u0141\u00f3d\u017a Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wojciech","family":"Fendler","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Translational Medicine Medical University of 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