{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T09:59:42Z","timestamp":1763978382177,"version":"3.37.3"},"reference-count":41,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2024,1,5]],"date-time":"2024-01-05T00:00:00Z","timestamp":1704412800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["#428216905"],"award-info":[{"award-number":["#428216905"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Checkpoint inhibitors have drastically improved the therapy of patients with advanced melanoma. 18F-FDG-PET\/CT parameters might act as biomarkers for response and survival and thus can identify patients that do not benefit from immunotherapy. However, little literature exists on the association of baseline 18F-FDG-PET\/CT parameters with progression free survival (PFS), best overall response (BOR), and overall survival (OS).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Materials and methods<\/jats:title>\n<jats:p>Using a whole tumor volume segmentation approach, we investigated in a retrospective registry study (n = 50) whether pre-treatment 18F-FDG-PET\/CT parameters of three subgroups (tumor burden, tumor glucose uptake and non-tumoral hematopoietic tissue metabolism), can act as biomarkers for the primary endpoints PFS and BOR as well as for the secondary endpoint OS.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Compared to the sole use of clinical parameters, baseline 18F-FDG-PET\/CT parameters did not significantly improve a Cox proportional-hazard model for PFS (C-index\/AIC: 0.70\/225.17 and 0.68\/223.54, respectively; p = 0.14). A binomial logistic regression analysis for BOR was not statistically significant (\u03c7<jats:sup>2<\/jats:sup>(15) = 16.44, p = 0.35), with a low amount of explained variance (Nagelkerke\u2019s R<jats:sup>2<\/jats:sup> = 0.38). Mean FDG uptake of the spleen contributed significantly to a Cox proportional-hazard model for OS (HR 3.55, p = 0.04).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>The present study could not confirm the capability of the pre-treatment 18F-FDG-PET\/CT parameters tumor burden, tumor glucose uptake and non-tumoral hematopoietic tissue metabolism to act as biomarkers for PFS and BOR in metastatic melanoma patients receiving first-line immunotherapy. The documented potential of 18F-FDG uptake by immune-mediating tissues such as the spleen to act as a biomarker for OS has been reproduced.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0296253","type":"journal-article","created":{"date-parts":[[2024,1,5]],"date-time":"2024-01-05T18:22:59Z","timestamp":1704478979000},"page":"e0296253","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Pre-treatment 18F-FDG-PET\/CT parameters as biomarkers for progression free survival, best overall response and overall survival in metastatic melanoma patients undergoing first-line immunotherapy"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4800-8381","authenticated-orcid":true,"given":"Felix","family":"Peisen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annika","family":"Gerken","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabel","family":"Dahm","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Konstantin","family":"Nikolaou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Eigentler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teresa","family":"Amaral","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan H.","family":"Moltz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmed E.","family":"Othman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergios","family":"Gatidis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2024,1,5]]},"reference":[{"issue":"4","key":"pone.0296253.ref001","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1056\/NEJMoa1412082","article-title":"Nivolumab in previously untreated melanoma without BRAF mutation","volume":"372","author":"C Robert","year":"2015","journal-title":"N Engl J Med"},{"issue":"14","key":"pone.0296253.ref002","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1056\/NEJMoa1709684","article-title":"Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma","volume":"377","author":"JD Wolchok","year":"2017","journal-title":"N Engl J Med"},{"issue":"17","key":"pone.0296253.ref003","doi-asserted-by":"crossref","first-page":"1889","DOI":"10.1200\/JCO.2014.56.2736","article-title":"Pooled Analysis of Long-Term Survival Data From Phase II and Phase III Trials of Ipilimumab in Unresectable or Metastatic Melanoma","volume":"33","author":"D Schadendorf","year":"2015","journal-title":"J Clin Oncol"},{"key":"pone.0296253.ref004","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.ejca.2017.05.031","article-title":"Health-related quality of life results from the phase III CheckMate 067 study","volume":"82","author":"D Schadendorf","year":"2017","journal-title":"Eur J Cancer"},{"issue":"3","key":"pone.0296253.ref005","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1038\/bjc.2015.467","article-title":"Serum lactate dehydrogenase as an early marker for outcome in patients treated with anti-PD-1 therapy in metastatic melanoma","volume":"114","author":"S Diem","year":"2016","journal-title":"Br J Cancer"},{"issue":"18","key":"pone.0296253.ref006","doi-asserted-by":"crossref","first-page":"2785","DOI":"10.1016\/j.ejca.2015.09.007","article-title":"Prognostic score for patients with advanced melanoma treated with ipilimumab","volume":"51","author":"S Diem","year":"2015","journal-title":"Eur J Cancer"},{"issue":"6","key":"pone.0296253.ref007","doi-asserted-by":"crossref","first-page":"3183","DOI":"10.1007\/s00330-018-5933-x","article-title":"Metastatic melanoma: pretreatment contrast-enhanced CT texture parameters as predictive biomarkers of survival in patients treated with pembrolizumab","volume":"29","author":"C Durot","year":"2019","journal-title":"Eur Radiol"},{"issue":"6","key":"pone.0296253.ref008","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1093\/annonc\/mdz108","article-title":"Predicting response to cancer immunotherapy using noninvasive radiomic biomarkers","volume":"30","author":"S Trebeschi","year":"2019","journal-title":"Ann Oncol"},{"issue":"16","key":"pone.0296253.ref009","doi-asserted-by":"crossref","first-page":"4414","DOI":"10.1158\/1078-0432.CCR-20-0020","article-title":"Radiomics, Tumor Volume, and Blood Biomarkers for Early Prediction of Pseudoprogression in Patients with Metastatic Melanoma Treated with Immune Checkpoint Inhibition","volume":"26","author":"L Basler","year":"2020","journal-title":"Clin Cancer Res"},{"issue":"5","key":"pone.0296253.ref010","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1002\/cam4.2709","article-title":"Novel cancer therapies for advanced cutaneous melanoma: The added value of radiomics in the decision making process-A systematic review","volume":"9","author":"A Guerrisi","year":"2020","journal-title":"Cancer Med"},{"key":"pone.0296253.ref011","doi-asserted-by":"crossref","first-page":"704607","DOI":"10.3389\/fonc.2021.704607","article-title":"Exploring CT Texture Parameters as Predictive and Response Imaging Biomarkers of Survival in Patients With Metastatic Melanoma Treated With PD-1 Inhibitor Nivolumab: A Pilot Study Using a Delta-Radiomics Approach","volume":"11","author":"A Guerrisi","year":"2021","journal-title":"Front Oncol"},{"key":"pone.0296253.ref012","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.3389\/fonc.2020.01524","article-title":"Pilot Study of CT-Based Radiomics Model for Early Evaluation of Response to Immunotherapy in Patients With Metastatic Melanoma","volume":"10","author":"ZL Wang","year":"2020","journal-title":"Front Oncol"},{"issue":"12","key":"pone.0296253.ref013","doi-asserted-by":"crossref","DOI":"10.3390\/cancers14122992","article-title":"Combination of Whole-Body Baseline CT Radiomics and Clinical Parameters to Predict Response and Survival in a Stage-IV Melanoma Cohort Undergoing Immunotherapy","volume":"14","author":"F Peisen","year":"2022","journal-title":"Cancers (Basel)"},{"issue":"10151","key":"pone.0296253.ref014","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/S0140-6736(18)31559-9","article-title":"Melanoma","volume":"392","author":"D Schadendorf","year":"2018","journal-title":"Lancet"},{"issue":"2","key":"pone.0296253.ref015","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1007\/s00259-020-04967-9","article-title":"The value of (18)F-FDG PET\/CT for predicting or monitoring immunotherapy response in patients with metastatic melanoma: a systematic review and meta-analysis","volume":"48","author":"N Ayati","year":"2021","journal-title":"Eur J Nucl Med Mol Imaging"},{"issue":"Suppl 1","key":"pone.0296253.ref016","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/s00259-017-3691-7","article-title":"The Advantages and Challenges of Using FDG PET\/CT for Response Assessment in Melanoma in the Era of Targeted Agents and Immunotherapy","volume":"44","author":"ANM Wong","year":"2017","journal-title":"Eur J Nucl Med Mol Imaging"},{"issue":"11","key":"pone.0296253.ref017","doi-asserted-by":"crossref","first-page":"2298","DOI":"10.1007\/s00259-019-04411-7","article-title":"Prognostic and theranostic 18F-FDG PET biomarkers for anti-PD1 immunotherapy in metastatic melanoma: association with outcome and transcriptomics","volume":"46","author":"RD Seban","year":"2019","journal-title":"Eur J Nucl Med Mol Imaging"},{"issue":"12","key":"pone.0296253.ref018","doi-asserted-by":"crossref","first-page":"2787","DOI":"10.1007\/s00259-020-04792-0","article-title":"Prognostic value of volumetric PET parameters at early response evaluation in melanoma patients treated with immunotherapy","volume":"47","author":"R Nakamoto","year":"2020","journal-title":"Eur J Nucl Med Mol Imaging"},{"issue":"9","key":"pone.0296253.ref019","article-title":"Development of a Hybrid-Imaging-Based Prognostic Index for Metastasized-Melanoma Patients in Whole-Body 18F-FDG PET\/CT and PET\/MRI Data","volume":"12","author":"T Kustner","year":"2022","journal-title":"Diagnostics (Basel)"},{"issue":"1","key":"pone.0296253.ref020","doi-asserted-by":"crossref","first-page":"18795","DOI":"10.1038\/s41598-021-98310-3","article-title":"FDG PET biomarkers for prediction of survival in metastatic melanoma prior to anti-PD1 immunotherapy","volume":"11","author":"A Flaus","year":"2021","journal-title":"Sci Rep"},{"issue":"10","key":"pone.0296253.ref021","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.2967\/jnumed.120.254482","article-title":"Prognostic Value of Bone Marrow Metabolism on Pretreatment 18F-FDG PET\/CT in Patients with Metastatic Melanoma Treated with Anti-PD-1 Therapy","volume":"62","author":"R Nakamoto","year":"2021","journal-title":"Journal of Nuclear Medicine"},{"issue":"2","key":"pone.0296253.ref022","doi-asserted-by":"crossref","first-page":"925","DOI":"10.7150\/thno.35989","article-title":"Cancer immunotherapy is accompanied by distinct metabolic patterns in primary and secondary lymphoid organs observed by non-invasive in vivo(18)F-FDG-PET","volume":"10","author":"J Schwenck","year":"2020","journal-title":"Theranostics"},{"issue":"1","key":"pone.0296253.ref023","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1186\/s13550-021-00832-4","article-title":"Assessment of early metabolic progression in melanoma patients under immunotherapy: an (18)F-FDG PET\/CT study","volume":"11","author":"C Sachpekidis","year":"2021","journal-title":"EJNMMI Res"},{"issue":"11","key":"pone.0296253.ref024","first-page":"1898","article-title":"Clinical significance of serum S100 in metastatic malignant melanoma","volume":"31a","author":"HB Guo","year":"1995","journal-title":"Eur J Cancer"},{"issue":"16","key":"pone.0296253.ref025","doi-asserted-by":"crossref","first-page":"4014","DOI":"10.1002\/cncr.26724","article-title":"NRAS mutation status is an independent prognostic factor in metastatic melanoma","volume":"118","author":"JA Jakob","year":"2012","journal-title":"Cancer"},{"issue":"7","key":"pone.0296253.ref026","doi-asserted-by":"crossref","first-page":"562","DOI":"10.3349\/ymj.2020.61.7.562","article-title":"KIT and Melanoma: Biological Insights and Clinical Implications","volume":"61","author":"DDM Pham","year":"2020","journal-title":"Yonsei Med J"},{"issue":"2","key":"pone.0296253.ref027","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.ejca.2008.10.026","article-title":"New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1)","volume":"45","author":"EA Eisenhauer","year":"2009","journal-title":"Eur J Cancer"},{"issue":"3","key":"pone.0296253.ref028","doi-asserted-by":"crossref","first-page":"e143","DOI":"10.1016\/S1470-2045(17)30074-8","article-title":"iRECIST: guidelines for response criteria for use in trials testing immunotherapeutics","volume":"18","author":"L Seymour","year":"2017","journal-title":"Lancet Oncol"},{"issue":"2","key":"pone.0296253.ref029","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1148\/radiol.2016142043","article-title":"Practical PERCIST: A Simplified Guide to PET Response Criteria in Solid Tumors 1.0","volume":"280","author":"JH O","year":"2016","journal-title":"Radiology"},{"issue":"3","key":"pone.0296253.ref030","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1093\/biomet\/78.3.691","article-title":"A note on a general definition of the coefficient of determination","volume":"78","author":"NJD NAGELKERKE","year":"1991","journal-title":"Biometrika"},{"issue":"1","key":"pone.0296253.ref031","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40425-019-0513-4","article-title":"Are tumor size changes predictive of survival for checkpoint blockade based immunotherapy in metastatic melanoma?","volume":"7","author":"M Wang","year":"2019","journal-title":"Journal for immunotherapy of cancer"},{"issue":"22","key":"pone.0296253.ref032","doi-asserted-by":"crossref","first-page":"5487","DOI":"10.1158\/1078-0432.CCR-16-0127","article-title":"Baseline Biomarkers for Outcome of Melanoma Patients Treated with Pembrolizumab","volume":"22","author":"B Weide","year":"2016","journal-title":"Clin Cancer Res"},{"issue":"2","key":"pone.0296253.ref033","doi-asserted-by":"crossref","DOI":"10.3390\/cancers13020168","article-title":"A Comprehensive Analysis of Baseline Clinical Characteristics and Biomarkers Associated with Outcome in Advanced Melanoma Patients Treated with Pembrolizumab","volume":"13","author":"G Awada","year":"2021","journal-title":"Cancers (Basel)"},{"issue":"4","key":"pone.0296253.ref034","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1007\/s00259-018-4211-0","article-title":"Prognostic value of baseline metabolic tumor volume measured on (18)F-fluorodeoxyglucose positron emission tomography\/computed tomography in melanoma patients treated with ipilimumab therapy","volume":"46","author":"K Ito","year":"2019","journal-title":"Eur J Nucl Med Mol Imaging"},{"issue":"1","key":"pone.0296253.ref035","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/s40644-020-00313-2","article-title":"(18)F-FDG PET\/CT based spleen to liver ratio associates with clinical outcome to ipilimumab in patients with metastatic melanoma","volume":"20","author":"A Wong","year":"2020","journal-title":"Cancer Imaging"},{"issue":"7069","key":"pone.0296253.ref036","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1038\/nature04186","article-title":"VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche","volume":"438","author":"RN Kaplan","year":"2005","journal-title":"Nature"},{"issue":"4","key":"pone.0296253.ref037","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/S1535-6108(02)00153-8","article-title":"MMP9 induction by vascular endothelial growth factor receptor-1 is involved in lung-specific metastasis","volume":"2","author":"S Hiratsuka","year":"2002","journal-title":"Cancer Cell"},{"issue":"11","key":"pone.0296253.ref038","doi-asserted-by":"crossref","first-page":"e493","DOI":"10.1016\/S1470-2045(14)70263-3","article-title":"Cancer-related inflammation and treatment effectiveness","volume":"15","author":"CI Diakos","year":"2014","journal-title":"Lancet Oncol"},{"issue":"2","key":"pone.0296253.ref039","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1200\/JCO.21.02229","article-title":"Long-Term Outcomes With Nivolumab Plus Ipilimumab or Nivolumab Alone Versus Ipilimumab in Patients With Advanced Melanoma","volume":"40","author":"JD Wolchok","year":"2022","journal-title":"J Clin Oncol"},{"issue":"19","key":"pone.0296253.ref040","doi-asserted-by":"crossref","first-page":"1824","DOI":"10.1056\/NEJMoa1709030","article-title":"Adjuvant Nivolumab versus Ipilimumab in Resected Stage III or IV Melanoma","volume":"377","author":"J Weber","year":"2017","journal-title":"N Engl J Med"},{"issue":"21","key":"pone.0296253.ref041","doi-asserted-by":"crossref","first-page":"2006","DOI":"10.1056\/NEJMoa1414428","article-title":"Nivolumab and ipilimumab versus ipilimumab in untreated melanoma","volume":"372","author":"MA Postow","year":"2015","journal-title":"N Engl J Med"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0296253","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,5]],"date-time":"2024-01-05T18:23:40Z","timestamp":1704479020000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0296253"}},"subtitle":[],"editor":[{"given":"Francesco","family":"Dondi","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2024,1,5]]},"references-count":41,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,1,5]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0296253","relation":{},"ISSN":["1932-6203"],"issn-type":[{"type":"electronic","value":"1932-6203"}],"subject":[],"published":{"date-parts":[[2024,1,5]]}}}