{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T02:58:53Z","timestamp":1781060333918,"version":"3.54.1"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100007833","name":"Hamad Medical Corporation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007833","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Support Care Cancer"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Immune checkpoint inhibitors (ICIs) have transformed melanoma treatment, yet comparative real-world data characterizing ICI-associated neurologic adverse events against the well-established neurotoxicity profile of conventional chemotherapy remain limited. We sought to contextualize the neurologic risk landscape of ICIs relative to chemotherapy as a historical comparator, to inform treatment-specific supportive care and surveillance strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We performed a propensity score\u2013matched analysis using the TriNetX Global Collaborative Network, encompassing 162 healthcare organizations. Adult patients with melanoma receiving chemotherapy (dacarbazine, paclitaxel, carboplatin, or temozolomide;\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20099787) or ICI therapy (pembrolizumab, nivolumab, or ipilimumab;\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200914,627) from January 2014 through November 2025 were identified. After 1:1 nearest-neighbor matching on 52 baseline covariates, 6887 pairs were analyzed over 1\u20131095\u00a0days post-index therapy. Primary outcomes were peripheral neuropathy, encephalopathy, and laboratory-anchored myositis (ICD-10 myositis codes with creatine kinase\u2009\u2265\u2009500 U\/L). Fractures served as a negative control. A pre-specified conservative sensitivity analysis excluded bidirectional treatment switching, restricted the ICI cohort to anti-PD-1 predominant exposure, tightened outcome definitions, and extended follow-up to 5\u00a0years.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 13,774 matched patients (mean age 67.1 years; 48.5% male), peripheral neuropathy occurred in 7.2% of chemotherapy-treated versus 3.2% of ICI-treated patients (HR 2.47; 95% CI 2.10\u20132.92). Encephalopathy occurred in 1.0% versus 1.4% (HR 0.70; 95% CI 0.51\u20130.96). Laboratory-confirmed myositis occurred in 1.0% versus 2.1% (HR 0.47; 95% CI 0.35\u20130.64). No cases of Guillain\u2013Barr\u00e9 syndrome or CNS vasculitis were detected. The negative control showed no significant difference (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u2009.20). In the conservative sensitivity analysis (6640 matched pairs; 5-year follow-up), the peripheral neuropathy association was substantially strengthened (HR 5.45; 95% CI 4.16\u20137.15) and the laboratory-anchored myositis association was essentially unchanged (HR 0.46; 95% CI 0.33\u20130.64), while the encephalopathy association attenuated to null (HR 1.03; 95% CI 0.79\u20131.34).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Chemotherapy carries a substantially higher peripheral neuropathy risk, while ICI therapy confers elevated laboratory-confirmed myositis risk. These robust findings support treatment-specific neurologic surveillance and supportive care strategies in melanoma management, particularly neuropathy monitoring during chemotherapy and neuromuscular\/CK surveillance during ICI therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00520-026-10745-4","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T05:34:43Z","timestamp":1778736883000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Comparative neurologic toxicity profiles of chemotherapy versus immune checkpoint inhibitors in melanoma: a propensity score-matched analysis"],"prefix":"10.1007","volume":"34","author":[{"given":"Majd A.","family":"Abualrob","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sami","family":"Alshehab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yousef","family":"Awad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranim","family":"Toma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarneem","family":"Azzam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rand","family":"Abdellatif","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Al-Salahat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahd","family":"Hamid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,14]]},"reference":[{"issue":"1","key":"10745_CR1","first-page":"17","volume":"73","author":"RL Siegel","year":"2023","unstructured":"Siegel RL, Miller KD, Wagle NS, Jemal A (2023) Cancer statistics, 2023. 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All procedures complied with the Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule for the use of de-identified health information. TriNetX holds certification for the de-identification process in compliance with the Expert Determination method specified in Section \u00a7164.514(b)(1) of the HIPAA Privacy Rule.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"538"}}