Development and Validation of an Inflammatory Prognostic Index to Predict Outcomes in Advanced/Metastatic Urothelial Cancer Patients Receiving Immune Checkpoint Inhibitors

Article Article scientifique Article Development and Validation of an Inflammatory Prognostic Index to Predict Outcomes in Advanced/Metastatic Urothelial Cancer Patients Receiving Immune Checkpoint Inhibitors eng 2024-04-11 2024-04-11 author Mokbel Sara 0009-0004-7805-1606 Faculty of Medicine, UCL-University College London, London WC1H 0AP, UK. author Baciarello Giuilia Medical Oncology Department, Azienda Ospedaliera San Camillo Forlanini, 00152 Roma, Italy. author Lavaud Pernelle Medical Oncology Department, Gustave Roussy Cancer Campus, 94805 Villejuif, France. author Omlin Aurelius Medical Oncology and Haematology Department, OnkoZentrum Zürich, 8038 Zurich, Switzerland. author Calabrò Fabio 0000-0002-7863-3540 Medical Oncology 1, IRCCS National Cancer Institute Regina Elena, 00144 Rome, Italy. author Cathomas Richard 0000-0002-9677-9885 Medical Oncology 1, IRCCS National Cancer Institute Regina Elena, 00144 Rome, Italy. author Aeppli Stefanie Department of Medical Oncology and Haematology, Cantonal Hospital St.Gallen, 9000 St. Gallen, Switzerland. author Parent Pauline 0000-0001-6072-7357 Medical Oncology Departement, CHU Lille-Centre Hospitalier Régional Universitaire de Lille, 59000 Lille, France. author Giannatempo Patrizia Medical Oncology Department, Fondazione IRCCS-Istituto Nazionale dei Tumori, 20133 Milan, Italy. author Koster Kira-Lee 0000-0002-6549-8124 Department of Medical Oncology and Haematology, Cantonal Hospital St.Gallen, 9000 St. Gallen, Switzerland. author Appel Naara Medical Oncology Departement, HUG-Hopitaux Universitaires Geneve, 1205 Geneva, Switzerland. 874288 author Gonnet Philippe Medical Oncology Departement, HUG-Hopitaux Universitaires Geneve, 1205 Geneva, Switzerland. 815881 author Angius Gesuino Medical Oncology Department, Azienda Ospedaliera San Camillo Forlanini, 00152 Roma, Italy. author Tsantoulis Petros 0000-0003-3613-6682 Medical Oncology Departement, HUG-Hopitaux Universitaires Geneve, 1205 Geneva, Switzerland. 861166 Département de médecine (DEMED) author Arkenau Hendrick-Tobias SCRI, London W1G 6AD, UK. author Cattrini Carlo 0000-0003-4785-9480 Maggiore della Carità University Hospital, 28100 Novara, Italy. author Messina Carlo 0000-0002-7934-1419 Ospedale A.R.N.A.S Civico, 90127 Palermo, Italy. author Zeghondy Jean 0000-0001-8811-4085 Medical Oncology Department, Gustave Roussy Cancer Campus, 94805 Villejuif, France. author Morelli Cristina Medical Oncology Unit, Policlinico Tor Vergata, 00133 Rome, Italy. author Loriot Yohann Medical Oncology Department, Gustave Roussy Cancer Campus, 94805 Villejuif, France. author Formica Vincenzo 0000-0002-5380-3144 Medical Oncology Unit, Policlinico Tor Vergata, 00133 Rome, Italy. author Patrikidou Anna Medical Oncology Department, Gustave Roussy Cancer Campus, 94805 Villejuif, France. 1465 10.3390/cancers16081465 38672547 2072-6694 PMC11048042 https://www.mdpi.com/2072-6694/16/8/1465 Background: Immune checkpoint inhibitors (ICIs) improve overall survival (OS) in advanced/metastatic urothelial cancer (a/mUC) patients. Preliminary evidence suggests a prognostic role of inflammatory biomarkers in this setting. We aimed to develop a disease-specific prognostic inflammatory index for a/mUC patients on ICIs. Methods: Fifteen variables were retrospectively correlated with OS and progression-free survival (PFS) in a development (D, n = 264) and a validation (V, n = 132) cohort of platinum-pretreated a/mUC pts receiving ICIs at L2 or further line. A nomogram and inflammatory prognostic index (U-IPI) were developed. The index was also tested in a control cohort of patients treated with chemotherapy only (C, n = 114). Results: The strongest predictors of OS were baseline platelet/lymphocyte (PLR) and neutrophil/lymphocyte (NLR) ratios, and lactate dehydrogenase (LDH), NLR, and albumin changes at 4 weeks. These were used to build the U-IPI, which can distinctly classify patients into good or poor response groups. The nomogram scoring is significant for PFS and OS (p< 0.001 in the D, V, and combined cohorts) for the immunotherapy (IO) cohort, but not for the control cohort. Conclusions: The lack of a baseline systemic inflammatory profile and the absence of early serum inflammatory biomarker changes are associated with significantly better outcomes on ICIs in a/mUC pts. The U-IPI is an easily applicable dynamic prognostic tool for PFS and OS, allowing for the early identification of a sub-group with dismal outcomes that would not benefit from ICIs, while distinguishing another that draws an important benefit. Advanced/metastatic urothelial cancer Immune checkpoint inhibitors Inflammatory markers Dewey 616 56 Département de médecine 221 false Cancers 16 8 f85f3034-73e1-4db9-bed1-5087a200bfc4 Article (Published version) Public Article_scientifique_from_europePmc.pdf 2089081 application/pdf CC BY-4.0 6f88a4ce296519fe5857dd6bbc011205f176ebc27f5405d395ce47724c35538b openAccess Faculté de médecine / Section de médecine clinique / Département de médecine

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Development and Validation of an Inflammatory Prognostic Index to Predict Outcomes in Advanced/Metastatic Urothelial Cancer Patients Receiving Immune Checkpoint Inhibitors	Cancers			2024	112	45

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