Nomogram to predict the outcomes of patients with microsatellite instability-high metastatic colorectal cancer receiving immune checkpoint inhibitors
| Autor: | Giuseppe Curigliano, Michael J. Overman, Massimiliano Salati, Chiara Cremolini, Aakash Tushar Shah, Gabriele Infante, Sara Lonardi, Rossana Intini, Priya Jayachandran, Giovanni Fucà, Floriana Nappo, Rosalba Miceli, Marwan Fakih, Francesca Corti, Lisa Salvatore, Federica Morano, Javier Ros, Filippo Pietrantonio, Margherita Ambrosini, Elisabetta Fenocchio, Silvia Damian, Maria Elena Elez |
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| Přispěvatelé: | Institut Català de la Salut, [Pietrantonio F, Corti F] Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. [Lonardi S] Medical Oncology 3, Istituto Oncologico Veneto IOV-IRCSS, Padua, Italy. [Infante G] Unit of Clinical Epidemiology and Trial Organization, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. [Elez ME, Ros J] Servei d’Oncologia Mèdica, Vall d'Hebron Hospital Universitari, Barcelona, Spain. Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Fakih M] Department of Medical Oncology, City of Hope Comprehensive Cancer Center, Duarte, California, USA, Vall d'Hebron Barcelona Hospital Campus |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Oncology
Male Cancer Research Nomografia (Matemàtica) diagnóstico::pronóstico::nomogramas [TÉCNICAS Y EQUIPOS ANALÍTICOS DIAGNÓSTICOS Y TERAPÉUTICOS] Colorectal cancer Immune checkpoint inhibitors medicine.medical_treatment Other subheadings::Other subheadings::/drug therapy [Other subheadings] Còlon - Càncer - Tractament Immunology and Allergy Neoplasm Metastasis fenómenos genéticos::variación genética::mutación::inestabilidad genómica::fenómenos genéticos::inestabilidad de microsatélites [FENÓMENOS Y PROCESOS] Immune Checkpoint Inhibitors RC254-282 Prior treatment Clinical/Translational Cancer Immunotherapy Neoplasms. Tumors. Oncology. Including cancer and carcinogens Middle Aged Prognosis neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias gastrointestinales::neoplasias intestinales::neoplasias colorrectales [ENFERMEDADES] Disease control Treatment Outcome Genetic Phenomena::Genetic Variation::Mutation::Genomic Instability::Genetic Phenomena::Microsatellite Instability [PHENOMENA AND PROCESSES] Molecular Medicine Female Microsatellite Instability gastrointestinal neoplasms immunotherapy Colorectal Neoplasms Diagnosis::Prognosis::Nomograms [ANALYTICAL DIAGNOSTIC AND THERAPEUTIC TECHNIQUES AND EQUIPMENT] medicine.medical_specialty Immunology Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores] Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms [DISEASES] Internal medicine Recte - Càncer - Tractament medicine Humans In patient Aged Pharmacology business.industry Microsatellite instability Immunotherapy Nomogram medicine.disease Nomograms business |
| Zdroj: | Scientia Journal for Immunotherapy of Cancer Journal for ImmunoTherapy of Cancer, Vol 9, Iss 8 (2021) |
| Popis: | Neoplasias gastrointestinales; Inmunoterapia Neoplàsies gastrointestinals; Immunoteràpia Gastrointestinal neoplasms; Immunotherapy Background The efficacy of immune checkpoint inhibitors (ICIs) in patients with microsatellite instability (MSI)-high metastatic colorectal cancer (mCRC) is unprecedented. A relevant proportion of subjects achieving durable disease control may be considered potentially ‘cured’, as opposed to patients experiencing primary ICI refractoriness or short-term clinical benefit. We developed and externally validated a nomogram to estimate the progression-free survival (PFS) and the time-independent event-free probability (EFP) in patients with MSI-high mCRC receiving ICIs. Methods The PFS and EFP were estimated using a cure model fitted on a developing set of 163 patients and validated on a set of 146 patients with MSI-high mCRC receiving anti-programmed death (ligand)1 (PD-(L)1) ± anticytotoxic T-lymphocyte antigen 4 (CTLA-4) agents. A total of 23 putative prognostic factors were chosen and then selected using a random survival forest (RSF). The model performance in estimating PFS probability was evaluated by assessing calibration (internally—developing set and externally—validating set) and quantifying the discriminative ability (Harrell C index). Results RFS selected five variables: ICI type (anti-PD-(L)1 monotherapy vs anti-CTLA-4 combo), ECOG PS (0 vs >0), neutrophil-to-lymphocyte ratio (≤3 vs >3), platelet count, and prior treatment lines. As both in the developing and validation series most PFS events occurred within 12 months, this was chosen as cut-point for PFS prediction. The combination of the selected variables allowed estimation of the 12-month PFS (focused on patients with low chance of being cured) and the EFP (focused on patients likely to be event-free at a certain point of their follow-up). ICI type was significantly associated with disease control, as patients receiving the anti-CTLA-4-combination experienced the best outcomes. The calibration of PFS predictions was good both in the developing and validating sets. The median value of the EFP (46%) allowed segregation of two prognostic groups in both the developing (PFS HR=3.73, 95% CI 2.25 to 6.18; p |
| Databáze: | OpenAIRE |
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