{"doi":"10.3390/nu18010040","title":"Investigating Chronic Toxicity, Diet, Patient-Reported Outcomes and the Microbiome in Immunotherapy-Treated Metastatic Melanoma Survivors: A New Frontier","abstract":"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’ clinicopathological characteristics and experience of irAEs (during treatment) and CT (persisting >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 (ρ = 0.3, p = 0.038). Added sugar consumption was correlated with the severity of experienced symptoms (ρ = 0.4, p = 0.003), with pronounced associations across the spectrum of symptoms, including pain, fatigue and shortness of breath (p < 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.","journal":"Nutrients","year":2025,"id":549684,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9487,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":996324,"name":"Satabdi Saha","orcid":"0000-0002-0117-9431","position":1,"is_corresponding":false},{"id":1444801,"name":"Nazli Dizman","orcid":null,"position":2,"is_corresponding":false},{"id":1023316,"name":"Michelle Rohlfs","orcid":null,"position":3,"is_corresponding":false},{"id":90487,"name":"Elizabeth Sirmans","orcid":null,"position":4,"is_corresponding":false},{"id":90452,"name":"J. M. Gardner","orcid":"0000-0001-5484-6691","position":5,"is_corresponding":false},{"id":682716,"name":"R. Amaria","orcid":null,"position":6,"is_corresponding":false},{"id":90458,"name":"I. C. Glitza","orcid":"0000-0002-4530-7765","position":7,"is_corresponding":false},{"id":1444802,"name":"H. Tawbi","orcid":null,"position":8,"is_corresponding":false},{"id":72141,"name":"Michael A. Davies","orcid":"0000-0002-0977-0912","position":9,"is_corresponding":false},{"id":803887,"name":"Alexandra P. Ikeguchi","orcid":"0000-0002-4448-9755","position":10,"is_corresponding":false},{"id":1444803,"name":"Basen-Engquist Karen","orcid":null,"position":11,"is_corresponding":false},{"id":278745,"name":"Keri Schadler","orcid":"0000-0002-1675-0514","position":12,"is_corresponding":false},{"id":501723,"name":"Michael Roth","orcid":"0000-0002-6411-8353","position":13,"is_corresponding":false},{"id":1399090,"name":"Wenye Song","orcid":"0000-0001-9630-3417","position":14,"is_corresponding":false},{"id":634371,"name":"Xiaotao Zhang","orcid":"0000-0002-3968-5030","position":15,"is_corresponding":false},{"id":90467,"name":"Nadim J. Ajami","orcid":"0000-0002-3808-8576","position":16,"is_corresponding":false},{"id":307383,"name":"Lorenzo Cohen","orcid":"0000-0003-4372-9208","position":17,"is_corresponding":false},{"id":72152,"name":"Jennifer A. Wargo","orcid":"0000-0003-3438-7576","position":18,"is_corresponding":false},{"id":295093,"name":"Christine B. Peterson","orcid":"0000-0003-3316-0468","position":19,"is_corresponding":false},{"id":254694,"name":"Jennifer L. McQuade","orcid":"0000-0002-2393-2172","position":20,"is_corresponding":false},{"id":90493,"name":"Carrie R. Daniel","orcid":"0000-0002-6455-9482","position":21,"is_corresponding":false},{"id":1444800,"name":"Margaux Robert","orcid":null,"position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:54:12.321988Z","pmid":"41515159","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}