Lorenzo Fornaro1, Francesco Leone2, Angélique Vienot3, Andrea Casadei-Gardini4, Caterina Vivaldi5, Astrid Lièvre6, Pasquale Lombardi2, Emmanuele De Luca7, Dewi Vernerey8, Elisa Sperti9, Gianna Musettini5, Maria Antonietta Satolli10, Julien Edeline11, Rosella Spadi12, Cindy Neuzillet13, Alfredo Falcone14, Giulia Pasquini5, Mario Clerico15, Alessandro Passardi16, Paola Buscaglia17, Aurélia Meurisse8, Massimo Aglietta2, Clémence Brac18, Enrico Vasile5, Francesco Montagnani15. 1. Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy. Electronic address: lorenzo.fornaro@gmail.com. 2. Department of Medical Oncology, University of Turin, Turin, Italy; Medical Oncology, Candiolo Cancer Institute, FPO, IRCCS, Candiolo, Italy. 3. Department of Medical Oncology, Besancon University Hospital, Besançon, France. 4. Department of Oncology, University Hospital of Modena and Reggio Emilia, Modena, Italy. 5. Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy. 6. Department of Gastroenterology, Rennes University Hospital, Rennes 1 University, COSS (Chemistry Oncogenesis Stress Signaling), UMR_S 1242, Rennes, France. 7. Department of Medical Oncology, University of Turin, Turin, Italy; S.C.D.U. Oncologia, A.O. Ordine Mauriziano, Ospedale Umberto I, Turin, Italy. 8. Methodological and Quality of Life in Oncology Unit, EA 3181, Besançon University Hospital, Besançon, France. 9. S.C.D.U. Oncologia, A.O. Ordine Mauriziano, Ospedale Umberto I, Turin, Italy. 10. Department of Medical Oncology, University of Turin, Turin, Italy; Medical Oncology 1 Division, Città della Salute e della Scienza, Turin, Italy. 11. Oncology Department, Cancer Institute Eugène Marquis, Rennes 1 University, INSERM, INRA, Rennes 1 University, Nutrition Metabolism and Cancer (NuMeCan), Rennes, France. 12. Medical Oncology 1 Division, Città della Salute e della Scienza, Turin, Italy. 13. Department of Medical Oncology, Curie Institute, Saint Cloud, France. 14. Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy; Department of Translational Research and New Technologies in Medicine, University of Pisa, Pisa, Italy. 15. S.C. Oncologia, Department of Oncology, ASL BI, Biella, Italy. 16. Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. 17. Oncology, ASL VCO Verbano Cusio Ossola, Verbania, Italy. 18. Oncology Department, Cancer Institute Eugène Marquis, Rennes, France.
Abstract
BACKGROUND: FOLFIRINOX (leucovorin, 5-fluorouracil, irinotecan, and oxaliplatin) is an option for fit patients with metastatic (MPC) and locally advanced unresectable (LAPC) pancreatic cancer. However, no criteria reliably identify patients with better outcomes. PATIENTS AND METHODS: We investigated putative prognostic factors among 137 MPC/LAPC patients treated with triplet chemotherapy. Association with 6-month survival status (primary endpoint) was assessed by multivariate logistic regression models. A nomogram predicting the risk of death at 6 months was built by assigning a numeric score to each identified variable, weighted on its level of association with survival. External validation was performed in an independent data set of 206 patients. The study was registered at ClinicalTrials.gov (NCT03590275). RESULTS: Four variables (performance status, liver metastases, baseline carbohydrate antigen 19-9 level, and neutrophil-to-lymphocyte ratio) were found to be associated with 6-month survival by multivariate analysis or had sufficient clinical plausibility to be included in the nomogram. Accuracy was confirmed in the validation cohort (C index = 0.762; 95% confidence interval, 0.713-0.825). After grouping all cases, 4 subsets with different outcomes were identified by 0, 1, 2, or > 2 poor prognostic features (P < .0001). CONCLUSION: The nomogram we constructed accurately predicts the risk of death in the first 6 months after initiation of FOLFIRINOX in MPC/LAPC patients. This tool could be useful to guide communication about prognosis, and to inform the design and interpretation of clinical trials.
BACKGROUND:FOLFIRINOX (leucovorin, 5-fluorouracil, irinotecan, and oxaliplatin) is an option for fit patients with metastatic (MPC) and locally advanced unresectable (LAPC) pancreatic cancer. However, no criteria reliably identify patients with better outcomes. PATIENTS AND METHODS: We investigated putative prognostic factors among 137 MPC/LAPCpatients treated with triplet chemotherapy. Association with 6-month survival status (primary endpoint) was assessed by multivariate logistic regression models. A nomogram predicting the risk of death at 6 months was built by assigning a numeric score to each identified variable, weighted on its level of association with survival. External validation was performed in an independent data set of 206 patients. The study was registered at ClinicalTrials.gov (NCT03590275). RESULTS: Four variables (performance status, liver metastases, baseline carbohydrate antigen 19-9 level, and neutrophil-to-lymphocyte ratio) were found to be associated with 6-month survival by multivariate analysis or had sufficient clinical plausibility to be included in the nomogram. Accuracy was confirmed in the validation cohort (C index = 0.762; 95% confidence interval, 0.713-0.825). After grouping all cases, 4 subsets with different outcomes were identified by 0, 1, 2, or > 2 poor prognostic features (P < .0001). CONCLUSION: The nomogram we constructed accurately predicts the risk of death in the first 6 months after initiation of FOLFIRINOX in MPC/LAPCpatients. This tool could be useful to guide communication about prognosis, and to inform the design and interpretation of clinical trials.
Authors: Antonin Vary; Loïc Lebellec; Frédéric Di Fiore; Nicolas Penel; Claire Cheymol; Emilia Rad; Farid El Hajbi; Astrid Lièvre; Julien Edeline; André Michel Bimbai; Marie-Cécile Le Deley; Anthony Turpin Journal: Ther Adv Med Oncol Date: 2021-07-16 Impact factor: 8.168