Inflammatory indices as prognostic markers in metastatic colorectal cancer patients treated with chemotherapy plus Bevacizumab

Alessandro Passardi; Irene Azzali; Alessandro Bittoni; Giorgia Marisi; Francesca Rebuzzi; Chiara Molinari; Giulia Bartolini; Laura Matteucci; Francesco Giulio Sullo; Silvia Angela Debonis; Chiara Gallio; Manlio Monti; Martina Valgiusti; Margherita Muratore; Ilario Giovanni Rapposelli; Paola Ulivi; Giovanni Luca Frassineti

doi:10.1177/17588359231212184

Inflammatory indices as prognostic markers in metastatic colorectal cancer patients treated with chemotherapy plus Bevacizumab

Ther Adv Med Oncol. 2023 Dec 11:15:17588359231212184. doi: 10.1177/17588359231212184. eCollection 2023.

Authors

Alessandro Passardi¹, Irene Azzali², Alessandro Bittoni³, Giorgia Marisi⁴, Francesca Rebuzzi⁴, Chiara Molinari⁴, Giulia Bartolini¹, Laura Matteucci¹, Francesco Giulio Sullo¹, Silvia Angela Debonis¹, Chiara Gallio¹, Manlio Monti¹, Martina Valgiusti¹, Margherita Muratore¹, Ilario Giovanni Rapposelli¹, Paola Ulivi⁴, Giovanni Luca Frassineti¹

Affiliations

¹ Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) 'Dino Amadori', Meldola, Italy.
² Unit of Biostatistics and Clinical Trials, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) 'Dino Amadori', Meldola, Italy.
³ Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) 'Dino Amadori', Via P. Maroncelli 40, Meldola 47014, Italy.
⁴ Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) 'Dino Amadori', Meldola, Italy.

Abstract

Background: Validated predictors of sensitivity or resistance to Bevacizumab (Bev) are not available, and Inflammatory Indexes (IIs) has been reported to be useful prognostic factors in various malignant solid tumours, including metastatic colorectal cancer (mCRC).

Objectives: To explore the prognostic value of IIs in mCRC patients treated with first-line chemotherapy plus Bev.

Design: One hundred and eighty-two patients diagnosed with mCRC and treated with first line chemotherapy plus Bev were considered for this prospective non-pharmacological study. Neutrophil, lymphocyte, platelet, aspartate transaminase (AST) and lactate dehydrogenase (LDH) tests were carried out at baseline and before each treatment cycle, according to clinical practice.

Methods: Pre-treatment Systemic Immune-inflammation Index (SII), Colon Inflammatory Index (CII) and Aspartate aminotransferase-Lymphocyte Ratio Index (ALRI) were evaluated to assess a correlation with progression-free survival (PFS) and overall survival (OS).

Results: In the overall population, PFS and OS were lower in patients with high SII (HR 1.64, p = 0.006 and HR 1.75, p = 0.004, respectively) and high ALRI (HR 2.13, p = 0.001 and HR 1.76, p = 0.02, respectively), but no difference was detected according to CII value. The multivariate analysis confirmed both SII and ALRI as independent prognostic factors for PFS (HR 1.64 and 2.82, respectively) and OS (HR 1.65 and 2.12, respectively).

Conclusion: Our results demonstrate and confirm that IIs, and in particular SII and ALRI, are easy to measure prognostic markers for patient candidates to first line chemotherapy plus Bev for mCRC.

Keywords: ALRI; CII; SII; bevacizumab; inflammatory indexes; metastatic colorectal cancer; prognosis.

Plain language summary

Inflammatory Indexes can predict the efficacy of bevacizumab in metastatic colorectal cancer Bevacizumab (Bev) is a humanized monoclonal antibody with antiangiogenic activity, used in combination with chemotherapy as a standard first line treatment for many metastatic colorectal cancer patients. Validated predictors of sensitivity or resistance to Bevacizumab are not available, although several studies have investigated this issue in recent years. In this study, we investigated whether some selected baseline inflammatory indexes levels, namely Systemic Immune-inflammation Index (SII) and Aspartate aminotransferase-Lymphocyte Ratio Index (ALRI) could predict the survival in patients with metastatic colorectal cancer treated with Bevacizumab plus chemotherapy. We enrolled 182 patients diagnosed with mCRC and treated with first line chemotherapy plus Bev. For each patient we tested blood neutrophils, lymphocytes, platelets, aspartate transaminase (AST) and lactate dehydrogenase (LDH) before each treatment cycle, according to clinical practice. We calculated the SII value as platelet count × neutrophil count/lymphocyte count, and ALRI as AST/lymphocyte count. We found that patients with high SII and high ALRI values had lower survival as compared to those with low values. These parameters represent reproducible, inexpensive and easy to measure biomarkers to be used in both clinical practice and clinical trials, for patient selection.