{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:16:40Z","timestamp":1785428200538,"version":"3.56.0"},"posted":{"date-parts":[[2026,6,29]]},"group-title":"Oncology","reference-count":40,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["1P01CA285249"],"award-info":[{"award-number":["1P01CA285249"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"name":"The MD Anderson Cancer Center Support Grant Biostatistics Resource Group"},{"name":"The Charles and Daneen Stiefel MD Anderson Oropharynx Fund and HESI\/Thrive Foundation funding"},{"DOI":"10.13039\/100000072","name":"NIH National Institute of Dental and Craniofacial Research","doi-asserted-by":"crossref","award":["R01DE025248"],"award-info":[{"award-number":["R01DE025248"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000072","name":"NIH National Institute of Dental and Craniofacial Research","doi-asserted-by":"crossref","award":["R01DE028290"],"award-info":[{"award-number":["R01DE028290"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"crossref"}]},{"award":["R01CA218148"],"award-info":[{"award-number":["R01CA218148"]}],"id":[{"id":"https:\/\/ror.org\/040gcmg81","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"U.S. National Science Foundation","doi-asserted-by":"crossref","award":["R01CA257814"],"award-info":[{"award-number":["R01CA257814"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,6,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Purpose<\/jats:title>\n                  <jats:p>Radiation-associated lower cranial neuropathy (LCNP) is a debilitating late complication among head and neck cancer (HNC) survivors, leading to progressive dysphagia, aspiration, and loss of nutritional independence. No proven therapies exist to reverse LCNP. This Phase I dose-finding trial (XXXX, XXXX) and parallel registry study prospectively evaluated the safety, feasibility, tolerability, and symptomatic response of high-dose corticosteroid therapy for radiation-associated LCNP.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods and Materials<\/jats:title>\n                  <jats:p>Eligible participants were disease-free oropharyngeal cancer survivors \u22652 years post-radiotherapy with LCNP involving CN XII \u00b1 X and no structural or malignant etiology. Phase I trial participants received oral prednisone 1 mg\/kg (Dose 1, n = 3) or 3 mg\/kg (Dose 2, n = 5) daily for 5 days followed by a 2-week taper. A parallel registry (n = 6) enrolled broader HNC survivors treated with 1 mg\/kg. Phase I dose escalation decisions were based on the balance of tolerability and symptom response. The primary endpoint was change in MDASI-HN Top 5 mean symptom score from baseline to 1\u20132 weeks post-taper; a \u2265 1.315 unit decrease indicated clinically meaningful improvement. Secondary endpoints included clinician-graded measures of bulbar function, electromyography (EMG) and patient-report outcome measures.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>All regimens were feasible and well tolerated. Insomnia (n = 4, Grade 1) was the most frequent adverse event and there were no treatment discontinuations. At 1\u20132 weeks post-taper, the median MDASI-HN Top 5 change was \u22120.2 in Dose 1 and \u22121.6 in Dose 2; three of five Dose 2 patients achieved clinically meaningful improvement versus one in Dose 1. By 6\u201310 weeks, symptom improvement persisted in a subset but diminished overall. Dose 2 met pre-specified criteria for Phase II progression. No consistent improvements were observed in objective functional or electrophysiologic measures, though exploratory trends favored higher dosing.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>High-dose corticosteroid therapy at 3 mg\/kg\/day was feasible and tolerable in long-term HNC survivors with LCNP and showed preliminary evidence of short-term symptomatic benefit. Phase II evaluation is warranted.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.06.17.26354728","type":"posted-content","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:14Z","timestamp":1782777614000},"source":"Crossref","is-referenced-by-count":0,"title":["Stop LCNP: High dose corticosteroid therapy for late radiation-associated lower cranial neuropathy: A report of the phase I dose finding trial and parallel prospective data registry"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-2668-9717","authenticated-orcid":false,"given":"Zayne A.S.","family":"Belal","sequence":"first","affiliation":[{"name":"1Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3316-0468","authenticated-orcid":false,"given":"Christine B.","family":"Peterson","sequence":"additional","affiliation":[{"name":"2Department of 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MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose A.","family":"Garcia","sequence":"additional","affiliation":[{"name":"3Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5984-0261","authenticated-orcid":false,"given":"Nicolaas C.","family":"Anderson","sequence":"additional","affiliation":[{"name":"4Department of Neurology, Baylor College of Medicine, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5264-3994","authenticated-orcid":false,"given":"Clifton D.","family":"Fuller","sequence":"additional","affiliation":[{"name":"5Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, 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