{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T20:18:17Z","timestamp":1790367497650,"version":"4.1.0"},"reference-count":53,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T00:00:00Z","timestamp":1766361600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"MD Anderson Melanoma Moon Shots Program"},{"name":"MD Anderson NCI Cancer Center","award":["P30CA016672"],"award-info":[{"award-number":["P30CA016672"]}]},{"name":"MD Anderson NCI Cancer Center","award":["R01CA291965"],"award-info":[{"award-number":["R01CA291965"]}]},{"DOI":"10.13039\/100005190","name":"the Melanoma Research Alliance","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100005190","id-type":"DOI","asserted-by":"crossref"}]},{"name":"the Andrew Sabin Family Fellowship"},{"name":"The University of Texas MD Anderson Cancer Center SPORE in Melanoma Award","award":["P50CA221703"],"award-info":[{"award-number":["P50CA221703"]}]},{"name":"NIH\/NHLBI","award":["R01HL158796"],"award-info":[{"award-number":["R01HL158796"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Immune checkpoint blockade (ICB) therapies have significantly improved outcomes in metastatic melanoma. However, immune-related adverse events (irAEs) and persistent chronic toxicities (CTs) among this emerging survivor population likely influence different facets of quality of life. This study characterized CT, patient-reported outcomes (PROs), diet, physical activity and gut microbiome features in a cohort of long-term survivors with a history of ICB-treated metastatic melanoma. Methods: Forty-eight patients with a history of metastatic melanoma who initiated ICB treatment at least 3 years earlier and were not currently on treatment were prospectively enrolled from a melanoma survivorship clinic. Participants completed screening questionnaires for depression, anxiety, diet and physical activity. The gut microbiome was characterized via metagenomic sequencing in a subsample (n = 39). Patients\u2019 clinicopathological characteristics and experience of irAEs (during treatment) and CT (persisting &gt;6 months after completion of therapy) were extracted retrospectively from the medical record. Results: In the overall cohort, 60% were experiencing CT, while 16% and 20% reported clinically relevant levels of depression and anxiety symptoms, respectively. We observed significant differences in overall gut microbiome composition between survivors with and without CT (p = 0.02). Consumption of fruit and vegetables was inversely associated with anxiety (\u03c1 = 0.3, p = 0.038). Added sugar consumption was correlated with the severity of experienced symptoms (\u03c1 = 0.4, p = 0.003), with pronounced associations across the spectrum of symptoms, including pain, fatigue and shortness of breath (p &lt; 0.05). Conclusions: These results suggest that CT is experienced by a substantial proportion of ICB-treated metastatic melanoma survivors. Patients experiencing CT also showed distinct microbiome features. However, additional research in prospective settings is needed to confirm these hypotheses.<\/jats:p>","DOI":"10.3390\/nu18010040","type":"journal-article","created":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T11:30:18Z","timestamp":1766489418000},"page":"40","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Investigating Chronic Toxicity, Diet, Patient-Reported Outcomes and the Microbiome in Immunotherapy-Treated Metastatic Melanoma Survivors: A New Frontier"],"prefix":"10.3390","volume":"18","author":[{"given":"Margaux","family":"Robert","sequence":"first","affiliation":[{"name":"Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0117-9431","authenticated-orcid":false,"given":"Satabdi","family":"Saha","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3907-8513","authenticated-orcid":false,"given":"Nazli","family":"Dizman","sequence":"additional","affiliation":[{"name":"Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Rohlfs","sequence":"additional","affiliation":[{"name":"Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Sirmans","sequence":"additional","affiliation":[{"name":"Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Simon","sequence":"additional","affiliation":[{"name":"Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodabe N.","family":"Amaria","sequence":"additional","affiliation":[{"name":"Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4530-7765","authenticated-orcid":false,"given":"Isabella C.","family":"Glitza Oliva","sequence":"additional","affiliation":[{"name":"Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hussein A.","family":"Tawbi","sequence":"additional","affiliation":[{"name":"Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0977-0912","authenticated-orcid":false,"given":"Michael A.","family":"Davies","sequence":"additional","affiliation":[{"name":"Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4448-9755","authenticated-orcid":false,"given":"Alexandra","family":"Ikeguchi","sequence":"additional","affiliation":[{"name":"Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Basen-Engquist","sequence":"additional","affiliation":[{"name":"Department of Health Disparities Research, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1675-0514","authenticated-orcid":false,"given":"Keri","family":"Schadler","sequence":"additional","affiliation":[{"name":"Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael E.","family":"Roth","sequence":"additional","affiliation":[{"name":"Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenye","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Head & Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3968-5030","authenticated-orcid":false,"given":"Xiaotao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"},{"name":"Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3808-8576","authenticated-orcid":false,"given":"Nadim J.","family":"Ajami","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Cohen","sequence":"additional","affiliation":[{"name":"Department of Palliative, Rehabilitation, and Integrative Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer A.","family":"Wargo","sequence":"additional","affiliation":[{"name":"Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"},{"name":"Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"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":"Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L.","family":"McQuade","sequence":"additional","affiliation":[{"name":"Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6455-9482","authenticated-orcid":false,"given":"Carrie R.","family":"Daniel","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1056\/NEJMoa2407417","article-title":"Final, 10-Year Outcomes with Nivolumab plus Ipilimumab in Advanced Melanoma","volume":"392","author":"Wolchok","year":"2025","journal-title":"N. 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