{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T17:37:03Z","timestamp":1793381823248,"version":"4.5.0"},"reference-count":18,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,11,19]],"date-time":"2021-11-19T00:00:00Z","timestamp":1637280000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Laryngoscope"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives\/Hypothesis<\/jats:title>\n                    <jats:p>To describe outcomes of advanced head and neck cutaneous squamous cell carcinoma (cSCC) with clinical perineural invasion (cPNI) treated with immune checkpoint inhibitor (ICI) therapy, and to describe post\u2010treatment radiographic findings in the context of clinical response to treatment using a new grading system.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study Design<\/jats:title>\n                    <jats:p>Retrospective chart review.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Retrospective chart review was performed for 11 patients treated with ICI for head and neck cSCC with cPNI of large named nerves. The primary outcome was response to treatment as defined by radiographic and clinical evidence. Clinical responses were defined as improvement in symptoms of neuropathic pain, hypoesthesia, nerve weakness, or decrease in visible tumor. Imaging studies were graded based on a new classification system for perineural invasion and reviewed by two neuroradiologists since RECISTv1.1 is inadequate to adjudicate response in these patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Nine (82%) patients had radiographic perineural disease control on ICI. Eight patients had improved radiographic perineural disease and one had stable disease. Of these, complete resolution of radiographic evidence of perineural disease was seen in only one patient. Seven (64%) patients had clinical responses, with either improved or stable radiographic disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>ICI therapy is a viable treatment option for head and neck cSCC with cPNI. Radiographic and clinical evidence of response correlate well, with improvement in neuropathic pain being the most sensitive clinical marker of response. Even with favorable findings on repeat imaging and stable clinical course, complete resolution of perineural thickening and enhancement is rare. A grading system for classifying changes in perineural disease over time is proposed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Level of Evidence<\/jats:title>\n                    <jats:p>\n                      4\n                      <jats:italic>Laryngoscope<\/jats:italic>\n                      , 132:1213\u20131218, 2022\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/lary.29953","type":"journal-article","created":{"date-parts":[[2021,11,19]],"date-time":"2021-11-19T11:29:08Z","timestamp":1637321348000},"page":"1213-1218","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Clinical Perineural Invasion and Immunotherapy for Head and Neck Cutaneous Squamous Cell Carcinoma"],"prefix":"10.1002","volume":"132","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3881-1020","authenticated-orcid":false,"given":"Michael P.","family":"Wu","sequence":"first","affiliation":[{"name":"Harvard Medical School  Boston Massachusetts U.S.A."},{"name":"Department of Otolaryngology Massachusetts Eye and Ear  Boston Massachusetts U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine L.","family":"Reinshagen","sequence":"additional","affiliation":[{"name":"Harvard Medical School  Boston Massachusetts U.S.A."},{"name":"Department of Radiology Massachusetts Eye and Ear  Boston Massachusetts U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary B.","family":"Cunnane","sequence":"additional","affiliation":[{"name":"Harvard Medical School  Boston Massachusetts U.S.A."},{"name":"Department of Radiology Massachusetts Eye and Ear  Boston Massachusetts U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia Z.","family":"Shalhout","sequence":"additional","affiliation":[{"name":"Harvard Medical School  Boston Massachusetts U.S.A."},{"name":"Division of Hematology\/Oncology, Department of Medicine Massachusetts General Hospital  Boston Massachusetts U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard L.","family":"Kaufman","sequence":"additional","affiliation":[{"name":"Harvard Medical School  Boston Massachusetts U.S.A."},{"name":"Department of Surgery Massachusetts General Hospital  Boston Massachusetts U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Miller","sequence":"additional","affiliation":[{"name":"Harvard Medical School  Boston Massachusetts U.S.A."},{"name":"Division of Hematology\/Oncology, Department of Medicine Massachusetts General Hospital  Boston Massachusetts U.S.A."},{"name":"Department of Dermatology Massachusetts General Hospital  Boston Massachusetts U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin S.","family":"Emerick","sequence":"additional","affiliation":[{"name":"Harvard Medical School  Boston Massachusetts U.S.A."},{"name":"Department of Otolaryngology Massachusetts Eye and Ear  Boston Massachusetts U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,11,19]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.23982"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0360-3016(00)01407-3"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjoto.2011.11.004"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0036-1579777"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.24607"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2016.06.011"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/COC.0b013e3182468019"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1805131"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-09-1624"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.61.6870"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(17)30074-8"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamadermatol.2013.2456"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2012.48.5326"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2021.01.048"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.24453"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1177\/0194599811434897"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0036-1571840"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(19)30728-4"}],"container-title":["The 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