PURPOSE: The purpose of this study was to set up a prognostic model for the identification of survival predictors specific for melanoma patients treated with ipilimumab. EXPERIMENTAL DESIGN: The following prospectively collected data were utilised: patient and primary tumour characteristics, relapse-free-interval, site and number of metastases, previous therapies and level of serum biomarkers (lactic dehydrogenase (LDH), C-reactive protein, β2-microglobulin, vascular endothelial growth factor (VEGF), IL2, IL6, S-100, alkaline phosphatase (ALP), transaminases, leucocyte count, lymphocytes subpopulations). A multivariate prognostic model was developed using the Cox regression model fitted to the data of 113 consecutive metastatic patients treated with ipilimumab (3 mg/kg, q3w) at Veneto Institute of Oncology (IOV). External validation was obtained using the data of 69 and 34 patients treated at European Oncology Institute (IEO) and University of Torino (UT), respectively. RESULTS: Median survival was 8.3, 4.9 and 7.1 months from first ipilimumab administration at IOV, IEO and UT, respectively. Both higher baseline levels of LDH (Hazard Ratio [HR] v=1.36, 95% Confidence Interval [CI] 1.16-1.58, P<.001) and neutrophils (HR=1.76, 95% CI 1.41-2.10, P<.001) were associated with worse prognosis. Model performance was satisfactory both upon internal validation (Dxy=0.42) and external validation (Dxy=0.40). Serum LDH and neutrophil count discriminated patients who lived more (low neutrophils and low LDH) or less (high LDH or neutrophils) than 24 months. CONCLUSION: Serum LDH and neutrophil count were significant independent prognostic factors. This externally validated prognostic nomogram, could help clinicians to identify the patients who would benefit most from ipilimumab and consequently to improve resource allocation. These easily available biomarkers deserve further validation.

Personalised medicine: Development and external validation of a prognostic model for metastatic melanoma patients treated with ipilimumab

FAVA, PAOLO;MOCELLIN, SILVIA;QUAGLINO, Pietro;ASTRUA, Chiara;
2015-01-01

Abstract

PURPOSE: The purpose of this study was to set up a prognostic model for the identification of survival predictors specific for melanoma patients treated with ipilimumab. EXPERIMENTAL DESIGN: The following prospectively collected data were utilised: patient and primary tumour characteristics, relapse-free-interval, site and number of metastases, previous therapies and level of serum biomarkers (lactic dehydrogenase (LDH), C-reactive protein, β2-microglobulin, vascular endothelial growth factor (VEGF), IL2, IL6, S-100, alkaline phosphatase (ALP), transaminases, leucocyte count, lymphocytes subpopulations). A multivariate prognostic model was developed using the Cox regression model fitted to the data of 113 consecutive metastatic patients treated with ipilimumab (3 mg/kg, q3w) at Veneto Institute of Oncology (IOV). External validation was obtained using the data of 69 and 34 patients treated at European Oncology Institute (IEO) and University of Torino (UT), respectively. RESULTS: Median survival was 8.3, 4.9 and 7.1 months from first ipilimumab administration at IOV, IEO and UT, respectively. Both higher baseline levels of LDH (Hazard Ratio [HR] v=1.36, 95% Confidence Interval [CI] 1.16-1.58, P<.001) and neutrophils (HR=1.76, 95% CI 1.41-2.10, P<.001) were associated with worse prognosis. Model performance was satisfactory both upon internal validation (Dxy=0.42) and external validation (Dxy=0.40). Serum LDH and neutrophil count discriminated patients who lived more (low neutrophils and low LDH) or less (high LDH or neutrophils) than 24 months. CONCLUSION: Serum LDH and neutrophil count were significant independent prognostic factors. This externally validated prognostic nomogram, could help clinicians to identify the patients who would benefit most from ipilimumab and consequently to improve resource allocation. These easily available biomarkers deserve further validation.
2015
51
14
2086
2094
http://www.journals.elsevier.com/european-journal-of-cancer/
Immunotherapy; Ipilimumab; Metastatic melanoma; Nomogram; Prognostic model; Cancer Research; Oncology; Medicine (all)
Valpione, S; Martinoli, C.; Fava, P.; Mocellin, S.; Campana, L.G.; Quaglino, P.; Ferrucci, P.F.; Pigozzo, J.; Astrua, C.; Testori, A.; Chiarion-Sileni...espandi
File in questo prodotto:
File Dimensione Formato  
Valpione Quaglino EJC 2015 personalised medicine.pdf

Accesso riservato

Descrizione: Articolo principale
Tipo di file: PDF EDITORIALE
Dimensione 815.42 kB
Formato Adobe PDF
815.42 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
1569260_4aperto.pdf

Accesso aperto

Tipo di file: POSTPRINT (VERSIONE FINALE DELL’AUTORE)
Dimensione 690.27 kB
Formato Adobe PDF
690.27 kB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1569260
Citazioni
  • ???jsp.display-item.citation.pmc??? 24
  • Scopus 40
  • ???jsp.display-item.citation.isi??? 38
social impact