Prognostic role of C-reactive protein-albumin-lymphocyte (CALLY) index in gastrointestinal malignancies: a systematic review and meta-analysis.

Abstract

Gastrointestinal (GI) malignancies are a major cause of cancer-related morbidity and mortality. While prognostic tools such as TNM staging and serum biomarkers are widely used, they have limitations. The C-reactive protein-albumin-lymphocyte (CALLY) index, an integrated marker of inflammation, nutrition, and immunity, has emerged as a potential prognostic tool. However, its prognostic value across GI malignancies remains unclear. This systematic review aims to assess the prognostic significance of the CALLY index in GI malignancies, with a primary focus on survival outcomes and a secondary assessment of its association with postoperative complications. Relevant literature was screened through December 2024 to identify studies assessing the prognostic significance of the CALLY index in GI malignancies. Outcomes included overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), recurrence-free survival (RFS), recurrence rates, and postoperative complications. Eligible studies underwent qualitative synthesis, while meta-analysis was conducted for gastric cancer only. Relative risks (RRs) were pooled using a fixed- or random-effects model based on heterogeneity (I² > 50%). Subgroup analyses were performed based on CALLY cutoff values and TNM stage. Publication bias was assessed using funnel plots and Egger's test. A total of 21 studies (8,600 patients) met inclusion criteria. Across all GI malignancies, higher CALLY values, regardless of cutoff variations (range: 0.369-6.96), were consistently associated with improved OS, CSS, DFS, and RFS, while lower values correlated with increased recurrence rates and higher postoperative complication rates. In gastric cancer, a higher CALLY index was associated with improved 5-year OS (RR = 0.81, p < 0.00001) and lower major postoperative complications (RR = 1.48, p = 0.02). Subgroup analysis suggested that a CALLY cutoff < 3 and TNM stage IV inclusion contributed to heterogeneity. No significant publication bias was detected. The CALLY index appears to be a promising independent prognostic biomarker in GI malignancies, with higher values associated with improved survival and fewer postoperative complications. In gastric cancer specifically, meta-analysis confirms its predictive value for 5-year overall survival and major postoperative outcomes. Larger prospective studies are warranted to establish standardized cutoff points and to optimize its clinical utility across diverse patient populations.