The Pan-Immune-Inflammation Value is a new prognostic biomarker in metastatic colorectal cancer: results from a pooled-analysis of the Valentino and TRIBE first-line trials

Giovanni Fucà,Fotios Loupakis,Salvatore Corallo,Sara Bustreo,Matteo Claravezza,Alberto Zaniboni,Beatrice Borelli,Carlotta Antoniotti,Federica Morano,Filippo De Braud,Chiara Cremolini,Andrea Sartore‐Bianchi ,Enrico Cortesi,Roberto Murialdo,Marco Tampellini,Lorenza Rimassa,Giuseppe Tonini,Federica Marmorino,Alessandra Boccaccino,Gianluca Tomasello,Roberto Moretto,Vincenzo Adamo,Vincenzo Guarini,Sara Lonardi,Filippo Pietrantonio

doi:10.1038/s41416-020-0894-7

Abstract

BackgroundImmune-inflammatory biomarkers (IIBs) showed a prognostic relevance in patients with metastatic CRC (mCRC). We aimed at evaluating the prognostic power of a new comprehensive biomarker, the Pan-Immune-Inflammation Value (PIV), in patients with mCRC receiving first-line therapy.MethodsIn the present pooled-analysis, we included patients enrolled in the Valentino and TRIBE trials. PIV was calculated as: (neutrophil count × platelet count × monocyte count)/lymphocyte count. A cut-off was determined using the maximally selected rank statistics method. Generalised boosted regression (GBR), the Kaplan–Meier method and Cox hazards regression models were used for survival analyses.ResultsA total of 438 patients were included. Overall, 208 patients (47%) had a low-baseline PIV and 230 (53%) had a high-baseline PIV. Patients with high PIV experienced a worse PFS (HR, 1.66; 95% CI, 1.36–2.03, P < 0.001) and worse OS (HR, 2.01; 95% CI, 1.57–2.57; P < 0.001) compared to patients with low PIV. PIV outperformed the other IIBs in the GBR model and in the multivariable models.ConclusionPIV is a strong predictor of survival outcomes with better performance than other well-known IIBs in patients with mCRC treated with first-line therapy. PIV should be prospectively validated to better stratify mCRC patients undergoing first-line therapy.

Highlights

Immune-inflammatory biomarkers (IIBs) showed a prognostic relevance in patients with metastatic CRC
Neutrophil-to-lymphocyte ratio (NLR), platelets and monocytes showed a prognostic relevance in the advanced setting,[6,7,8] but the clinical usefulness of such single biomarkers is limited by their low discriminative ability
In the present pooled-analysis of patients with metastatic CRC (mCRC) receiving first-line therapy in the frame of two randomised academic trials, Valentino and TRIBE, we aimed to evaluate the prognostic power of a new biomarker, the Pan-Immune-Inflammation Value (PIV), including all the immune-inflammatory populations from peripheral blood with a proved prognostic relevance in mCRC

Summary

Introduction

Immune-inflammatory biomarkers (IIBs) showed a prognostic relevance in patients with metastatic CRC (mCRC). Even in the era of molecular selection,[1] a non-negligible fraction of patients with metastatic colorectal cancer (mCRC) receiving first-line treatment has poor outcomes.[2] the identification of new biomarkers for a better prognostic stratification and prediction of treatment outcomes is mandatory. Inflammation and immunity play a fundamental role in colorectal cancer initiation and progression,[3,4] and several blood-based, easy-toobtain, immune-inflammatory biomarkers (IIBs) have been investigated in cancer patients.[5] Among others, neutrophil-to-lymphocyte ratio (NLR), platelets and monocytes showed a prognostic relevance in the advanced setting,[6,7,8] but the clinical usefulness of such single biomarkers is limited by their low discriminative ability. The systemic immune-inflammation index (SII) based on lymphocyte, neutrophil and platelet counts, but not monocytes, was first developed for prognostic stratification in patients with hepatocellular carcinoma[9] and demonstrated a certain relevance in mCRC.[10]

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Conclusion