{"doi":"10.1016/j.ejca.2022.02.022","title":"C-reactive protein flare predicts response to anti-PD-(L)1 immune checkpoint blockade in metastatic urothelial carcinoma","abstract":null,"journal":"European Journal of Cancer","year":2022,"id":622407,"datarank":0.5533319181170905,"base_score":3.6888794541139363,"endowment":3.6888794541139363,"self_citation_contribution":0.5533319181170905,"citation_network_contribution":0.0,"self_endowment_contribution":0.5533319181170905,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":39,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":2,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1608137,"name":"Danijel Sikic","orcid":null,"position":1,"is_corresponding":false},{"id":1608138,"name":"Jonas Saal","orcid":null,"position":2,"is_corresponding":false},{"id":1601849,"name":"Thomas Büttner","orcid":null,"position":3,"is_corresponding":false},{"id":1608139,"name":"Franziska Goldschmidt","orcid":null,"position":4,"is_corresponding":false},{"id":1608140,"name":"Jonas Jarczyk","orcid":"0000-0003-4434-7826","position":5,"is_corresponding":false},{"id":1608141,"name":"Philippe Becker","orcid":null,"position":6,"is_corresponding":false},{"id":1608142,"name":"Philip Zeuschner","orcid":null,"position":7,"is_corresponding":false},{"id":1608143,"name":"Maximilian Weinke","orcid":null,"position":8,"is_corresponding":false},{"id":1608144,"name":"Charis Kalogirou","orcid":null,"position":9,"is_corresponding":false},{"id":1608145,"name":"Johannes Breyer","orcid":null,"position":10,"is_corresponding":false},{"id":1608146,"name":"Maximilian Burger","orcid":null,"position":11,"is_corresponding":false},{"id":1608147,"name":"Philipp Nuhn","orcid":null,"position":12,"is_corresponding":false},{"id":1608148,"name":"Karl Tully","orcid":null,"position":13,"is_corresponding":false},{"id":1608149,"name":"Florian Roghmann","orcid":null,"position":14,"is_corresponding":false},{"id":633237,"name":"Christian Bolenz","orcid":"0000-0002-6171-6040","position":15,"is_corresponding":false},{"id":1608150,"name":"Friedemann Zengerling","orcid":null,"position":16,"is_corresponding":false},{"id":1608151,"name":"Ralph M. 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Recently, early C-reactive protein (CRP) kinetics and especially the novel CRP flare-response phenomenon has been associated with immunotherapy response. METHODS: We conducted a multicentre observational study comprising 154 patients with mUC treated with ICB to evaluate the predictive value of a previously described on-treatment CRP kinetics: CRP flare responders (at least doubling of baseline CRP within the first month after initiation of ICB followed by a decline below baseline within three months), CRP responders (decline in baseline CRP by ≥ 30% within three months without a prior flare) and the remaining patients as CRP non-responders. CRP kinetics groups were correlated with baseline parameters, PD-L1 status, progression-free survival (PFS) and overall survival (OS). RESULTS: Objective response was observed in 57.1% of CRP responders, 45.8% of CRP flare responders and 17.9% of CRP non-responders (P < 0.001). CRP flare response was associated with prolonged PFS and OS (P < 0.001). In multivariable Cox regression analysis, CRP flare responders showed a risk reduction of ∼70% for tumour progression and death compared to CRP non-responders. Subgroup analysis of CRP flare responders revealed that patients with a long-flare response (completed flare-response kinetics ≥6 weeks on-treatment) showed even more favourable outcomes following ICB (HR = 0.18, 95%-CI: 0.07-0.48, P < 0.001). CONCLUSION: CRP (flare)response robustly predicts immunotherapy response and outcomes in mUC independent of PD-L1 status. Thus, early on-treatment CRP kinetics is a promising low-cost and easy-to-implement biomarker to optimise therapy monitoring in patients with mUC treated with ICB.","is_dataset_classified":null,"base_score":3.6888794541139363,"endowment":3.6888794541139363,"datacite_reuse_total":2,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"35366569","pmcid":null,"openalex_id":"https://openalex.org/W4220801494","authors":[],"funders":[{"funder_name":"Rheinische Friedrich-Wilhelms-Universität Bonn","grant_id":"ID 2020-2A-12","title":null},{"funder_name":"German Society of Urologists","grant_id":"KIN1/FE-19","title":null},{"funder_name":"Else Kroner-Fresenius-Stiftung","grant_id":"2020_EKEA.129","title":null},{"funder_name":"Deutsche Forschungsgemeinschaft","grant_id":"EXC2151\\u2013390873048","title":null},{"funder_name":"Deutsche Forschungsgemeinschaft","grant_id":"EXC2151","title":null},{"funder_name":"Deutsche Forschungsgemeinschaft","grant_id":"390873048","title":null},{"funder_name":"Deutsche Forschungsgemeinschaft","grant_id":"unidentified","title":"unidentified"},{"funder_name":"Deutsche Kniegesellschaft","grant_id":"","title":null},{"funder_name":"Friedrich-Alexander-Universität Erlangen-Nürnberg","grant_id":"","title":null},{"funder_name":"Interdisziplinäres Zentrum für Klinische Forschung, Universitätsklinikum Würzburg","grant_id":"","title":null}],"total_grants":10,"fwci":6.9336,"citation_percentile":0.97901173,"influential_citations":0,"citation_trend":[{"year":2022,"count":2},{"year":2023,"count":14},{"year":2024,"count":11},{"year":2025,"count":6},{"year":2026,"count":6}],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"http://www.ejcancer.com/article/S0959804922001204/pdf","host_type":"journal"},{"url":"http://www.ejcancer.com/article/S0959804922001204/pdf","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0959804922001204?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0959804922001204?httpAccept=text/plain","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.ejca.2022.02.022","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/35366569","host_type":"repository"}],"fields_of_study":["Bladder and Urothelial Cancer Treatments","Cancer Immunotherapy and Biomarkers","Inflammatory Biomarkers in Disease Prognosis","03 medical and health sciences","0302 clinical medicine","B7-H1 Antigen","Biomarkers","C-Reactive Protein","Carcinoma, Transitional Cell","Female","Humans","Immune Checkpoint Inhibitors","Male","Urinary Bladder Neoplasms"],"mesh_terms":["Immune Checkpoint Inhibitors","Urinary Bladder Neoplasms","C-Reactive Protein","Carcinoma, Transitional Cell","Female","Humans","Male","Biomarkers","B7-H1 Antigen"],"keywords":["Medicine","C-reactive protein","Internal medicine","Oncology","Proportional hazards model","Immune system","Blockade","Metastatic Urothelial Carcinoma","Immunotherapy","Flare","Gastroenterology","Cancer","Bladder cancer","Immunology","Inflammation","Urothelial carcinoma","Receptor","Biomarker","Immune Checkpoint Blockade","Long-flare","Crp Flare","Crp Flare-response","Male","Carcinoma, Transitional Cell","Urinary Bladder Neoplasms","Humans","Female","Immune Checkpoint Inhibitors","B7-H1 Antigen","Biomarkers"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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