Francesca Corti1, Sara Lonardi2, Rossana Intini3, Massimiliano Salati4, Elisabetta Fenocchio5, Carmen Belli6, Beatrice Borelli7, Marta Brambilla8, Alessandra A Prete9, Virginia Quarà10, Maria Antista11, Matteo Fassan12, Federica Morano13, Andrea Spallanzani14, Margherita Ambrosini15, Giuseppe Curigliano16, Filippo de Braud17, Vittorina Zagonel18, Giovanni Fucà19, Filippo Pietrantonio20. 1. Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Giacomo Venezian 1, 20133, Milan, Italy. Electronic address: francesca.corti@istitutotumori.mi.it. 2. Department of Oncology, Istituto Oncologico Veneto, IRCCS, Via Gattamelata, 64, 35128, Padua, Italy. Electronic address: sara.lonardi@iov.veneto.it. 3. Department of Oncology, Istituto Oncologico Veneto, IRCCS, Via Gattamelata, 64, 35128, Padua, Italy. Electronic address: rossana.intini@iov.veneto.it. 4. Department of Oncology and Hematology, University Hospital of Modena, Via del Pozzo, 71, 41125, Modena, Italy; PhD Program in Clinical and Experimental Medicine, University of Modena and Reggio Emilia, Via Università, 4, 41121, Modena Italy. Electronic address: maxsalati@live.it. 5. Multidisciplinary Outpatient Oncology Clinic, Candiolo Cancer Institute, FPO-IRCCS, Strada Provinciale 142, km 3.95, 10060 Candiolo (TO), Italy. Electronic address: elisabetta.fenocchio@ircc.it. 6. Division of Early Drugs Development for Innovative Therapies, Istituto Europeo di Oncologia, IRCCS, Via Ripamonti 435, 20141, Milan, Italy. Electronic address: carmen.belli@ieo.it. 7. Unit of Medical Oncology, Azienda Ospedaliero-Universitaria Pisana, Via Roma 67, 56126, Pisa, Italy. Electronic address: b.borelli89@gmail.com. 8. Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Giacomo Venezian 1, 20133, Milan, Italy. Electronic address: marta.brambilla2@istitutotumori.mi.it. 9. Department of Oncology, Istituto Oncologico Veneto, IRCCS, Via Gattamelata, 64, 35128, Padua, Italy. Electronic address: alessandraanna.prete@iov.veneto.it. 10. Department of Oncology, University of Turin, Via Giuseppe Verdi, 8, 10124, Torino, Italy. Electronic address: virginia.quara@ircc.it. 11. Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Giacomo Venezian 1, 20133, Milan, Italy. Electronic address: maria.antista@istitutotumori.mi.it. 12. Surgical Pathology Unit, Department of Medicine (DIMED), University of Padua, Via Giustiniani 2, 35128, Padua, Italy. Electronic address: matteo.fassan@gmail.com. 13. Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Giacomo Venezian 1, 20133, Milan, Italy. Electronic address: federica.morano@istitutotumori.mi.it. 14. Department of Oncology and Hematology, University Hospital of Modena, Via del Pozzo, 71, 41125, Modena, Italy. Electronic address: andrea.spallanzani@gmail.com. 15. Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Giacomo Venezian 1, 20133, Milan, Italy. Electronic address: margherita.ambrosini@istitutotumori.mi.it. 16. Division of Early Drugs Development for Innovative Therapies, Istituto Europeo di Oncologia, IRCCS, Via Ripamonti 435, 20141, Milan, Italy; Oncology and Hemato-oncology Department, University of Milan, via Festa del Perdono 7, 20122, Milan, Italy. Electronic address: giuseppe.curigliano@ieo.it. 17. Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Giacomo Venezian 1, 20133, Milan, Italy; Oncology and Hemato-oncology Department, University of Milan, via Festa del Perdono 7, 20122, Milan, Italy. Electronic address: filippo.debraud@istitutotumori.mi.it. 18. Department of Oncology, Istituto Oncologico Veneto, IRCCS, Via Gattamelata, 64, 35128, Padua, Italy. Electronic address: vittorina.zagonel@iov.veneto.it. 19. Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Giacomo Venezian 1, 20133, Milan, Italy. Electronic address: giovanni.fuca@istitutotumori.mi.it. 20. Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Giacomo Venezian 1, 20133, Milan, Italy; Oncology and Hemato-oncology Department, University of Milan, via Festa del Perdono 7, 20122, Milan, Italy. Electronic address: filippo.pietrantonio@istitutotumori.mi.it.
Abstract
BACKGROUND: Immune checkpoint inhibitors (ICIs) yielded unprecedented efficacy in patients with microsatellite instability (MSI)-high metastatic colorectal cancer (mCRC). Since the Pan-Immune-Inflammation Value (PIV) is a blood-based biomarker with prognostic usefulness in mCRC, it might predict clinical outcomes and primary resistance to ICIs. METHODS: We retrospectively analysed the association of PIV and its early modulation at 3/4 weeks after treatment initiation with the outcomes of MSI-high mCRC patients receiving anti-programmed death-(ligand)1 (PD-[L]1) +/- anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) agents. PIV was calculated as follows: (neutrophil count × platelet count × monocyte count)/lymphocyte count. PIV cut-offs were determined using the maximally selected rank statistics. RESULTS: A total of 163 patients were included. In the multivariable models for overall survival (OS) and progression-free survival (PFS), both high (>492) baseline PIV (OS: adjusted [a] HR, 3.00; 95% CI, 1.49-6.04, p = 0.002; PFS: aHR, 1.91; 95% CI, 1.06-3.44, p = 0.031) and early PIV increase ≥+30% (OS: aHR, 3.21; 95% CI, 1.65-6.23, p < 0.001; PFS: aHR, 2.25; 95% CI, 1.30-3.89, p = 0.003) confirmed an independent prognostic impact. After stratifying patients according to baseline PIV and ICI regimen, OS and PFS were significantly worse in subjects with high PIV receiving anti-PD-1/PD-L1 monotherapy. Early PIV increase was an independent predictor of clinical benefit (aOR, 0.23; 95% CI, 0.08-0.66; p = 0.007), whereas a trend was observed for baseline PIV (aOR, 0.33; 95% CI, 0.10-1.07; p = 0.065). CONCLUSION: PIV is a strong predictor of outcomes in MSI-high mCRC patients receiving ICIs. Prospective validation of these results is required to establish its role as a stratification factor for personalised combination strategies.
BACKGROUND: Immune checkpoint inhibitors (ICIs) yielded unprecedented efficacy in patients with microsatellite instability (MSI)-high metastatic colorectal cancer (mCRC). Since the Pan-Immune-Inflammation Value (PIV) is a blood-based biomarker with prognostic usefulness in mCRC, it might predict clinical outcomes and primary resistance to ICIs. METHODS: We retrospectively analysed the association of PIV and its early modulation at 3/4 weeks after treatment initiation with the outcomes of MSI-high mCRC patients receiving anti-programmed death-(ligand)1 (PD-[L]1) +/- anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) agents. PIV was calculated as follows: (neutrophil count × platelet count × monocyte count)/lymphocyte count. PIV cut-offs were determined using the maximally selected rank statistics. RESULTS: A total of 163 patients were included. In the multivariable models for overall survival (OS) and progression-free survival (PFS), both high (>492) baseline PIV (OS: adjusted [a] HR, 3.00; 95% CI, 1.49-6.04, p = 0.002; PFS: aHR, 1.91; 95% CI, 1.06-3.44, p = 0.031) and early PIV increase ≥+30% (OS: aHR, 3.21; 95% CI, 1.65-6.23, p < 0.001; PFS: aHR, 2.25; 95% CI, 1.30-3.89, p = 0.003) confirmed an independent prognostic impact. After stratifying patients according to baseline PIV and ICI regimen, OS and PFS were significantly worse in subjects with high PIV receiving anti-PD-1/PD-L1 monotherapy. Early PIV increase was an independent predictor of clinical benefit (aOR, 0.23; 95% CI, 0.08-0.66; p = 0.007), whereas a trend was observed for baseline PIV (aOR, 0.33; 95% CI, 0.10-1.07; p = 0.065). CONCLUSION: PIV is a strong predictor of outcomes in MSI-high mCRC patients receiving ICIs. Prospective validation of these results is required to establish its role as a stratification factor for personalised combination strategies.
Authors: Michele Guida; Nicola Bartolomeo; Davide Quaresmini; Pietro Quaglino; Gabriele Madonna; Jacopo Pigozzo; Anna Maria Di Giacomo; Alessandro Marco Minisini; Marco Tucci; Francesco Spagnolo; Marcella Occelli; Laura Ridolfi; Paola Queirolo; Ivana De Risi; Monica Valente; Angela Monica Sciacovelli; Vanna Chiarion Sileni; Paolo Antonio Ascierto; Lucia Stigliano; Sabino Strippoli Journal: J Transl Med Date: 2022-04-05 Impact factor: 5.531
Authors: Martín Pérez-Martelo; Alejandro González-García; Yolanda Vidal-Ínsua; Cristina Blanco-Freire; Elena María Brozos-Vázquez; Ihab Abdulkader-Nallib; Javier Álvarez-Fernández; Héctor Lázare-Iglesias; Carolina García-Martínez; Yoel Z Betancor; María Sánchez-Ares; Jose M C Tubío; Francisca Vázquez-Rivera; Sonia Candamio-Folgar; Rafael López-López; Juan Ruiz-Bañobre Journal: Sci Rep Date: 2022-04-27 Impact factor: 4.996