The CALLY Index Is Associated with Overall Survival in Patients with De Novo Metastatic Gastric Adenocarcinoma 1 Department of Medical Oncology, Iğdır Dr. Nevruz Erez State Hospital, Iğdır 76000, Türkiye 2 Department of Medical Oncology, Faculty of Medicine, Çanakkale Onsekiz Mart University, Çanakkale 17100, Türkiye 3 Department of Medical Oncology, Faculty of Medicine, Trakya University, Edirne 22030, Türkiye Medicina 2026, 62(6), 1124; https://doi.org/10.3390/medicina62061124 (registering DOI) Submission received: 15 May 2026 / Revised: 1 June 2026 / Accepted: 8 June 2026 / Published: 9 June 2026 Background and Objectives: Systemic inflammation, nutritional impairment, and immune dysregulation are important determinants of outcomes in advanced malignancies. The C-reactive protein–albumin–lymphocyte (CALLY) index is a composite biomarker that reflects these biological domains, but its prognostic relevance in de novo metastatic gastric adenocarcinoma has not been well defined. Materials and Methods: This multicenter retrospective cohort study included 234 patients with de novo metastatic gastric adenocarcinoma treated between January 2015 and December 2025. Baseline CALLY was calculated before systemic treatment. A cohort-specific CALLY threshold of 1.21 was obtained using conventional ROC analysis, with all-cause mortality status at last follow-up as the binary outcome. Survival was evaluated using Kaplan–Meier analysis and Cox proportional hazards regression. To avoid guarantee-time bias, treatment exposure variables that became known only after treatment initiation, including the number of chemotherapy cycles delivered, were excluded from the baseline Cox models. Diagnosis period was included in the multivariable model to account for treatment-era heterogeneity. Results: Overall, 133 patients (56.8%) were classified as low-CALLY and 101 (43.2%) as high-CALLY. Median OS was significantly longer in the high-CALLY group than in the low-CALLY group (13.9 vs. 8.6 months; log-rank p 0.05) ( Table 1). Similarly, histopathological characteristics, including histological subtype, tumor differentiation, and tumor localization, as well as molecular parameters such as HER2 status and PD-L1 expression, were comparable between the groups (all p > 0.05) ( Table 1). Since the number of MSI-high patients was very limited ( n = 7, 3.4%), no subgroup comparison was performed for this parameter. Metastatic dissemination patterns were also similar between the groups. First-line systemic treatment categories were not statistically different between the low- and high-CALLY groups ( p = 0.689). 3.3. CALLY Index and Survival Analyses The median follow-up duration was 9.9 months. Kaplan–Meier survival analysis demonstrated a significant difference in overall survival (OS) between the CALLY groups (log-rank χ 2 = 15.17, p 65 (≤65) 1.09 0.82–1.46 0.548 Sex Male (Female) 0.85 0.62–1.16 0.301 ECOG performance status 2–3 (0–1) 1.41 1.01–1.97 0.044 BMI <18.5 (≥18.5) 1.21 0.72–2.02 0.479 Smoking status Smoker (Non-smoker) 0.75 0.56–1.01 0.054 Comorbidity Present (Absent) 0.90 0.67–1.20 0.460 Histology Signet ring cell carcinoma (Adenocarcinoma) 1.21 0.68–2.13 0.515 Differentiation Poor (Moderate/Well) 1.43 1.07–1.90 0.016 Tumor localization Distal (Proximal) 1.05 0.76–1.43 0.779 HER2 status Positive (Negative) 0.61 0.41–0.89 0.011 PD-L1 status Positive (Negative) 1.09 0.66–1.78 0.747 Liver metastasis Present (Absent) 1.38 1.03–1.84 0.030 Lung metastasis Present (Absent) 1.01 0.73–1.42 0.934 Lymph node metastasis Present (Absent) 1.01 0.76–1.35 0.944 Peritoneal metastasis Present (Absent) 1.35 1.02–1.80 0.039 Number of metastatic sites ≥2 (1) 1.28 0.95–1.72 0.107 Surgery Present (Absent) 0.83 0.58–1.19 0.303 Radiotherapy Present (Absent) 0.69 0.45–1.05 0.086 First-line treatment HER2-based regimen (Fluoropyrimidine-based) 0.64 0.43–0.97 0.033 Immunotherapy-based regimen (Fluoropyrimidine-based) 1.98 0.73–5.39 0.181 Abbreviations: BMI, body mass index; CALLY, C-reactive protein–albumin–lymphocyte index; CI, confidence interval; ECOG, Eastern Cooperative Oncology Group; HER2, human epidermal growth factor receptor 2; HR, hazard ratio; PD-L1, programmed death-ligand 1. Table 4. Revised multivariable Cox regression analysis for overall survival after excluding post-baseline chemotherapy-cycle variables and adjusting for diagnosis period (complete-case n = 204; death events = 164). Table 4. Revised multivariable Cox regression analysis for overall survival after excluding post-baseline chemotherapy-cycle variables and adjusting for diagnosis period (complete-case n = 204; death events = 164). Variable Category (Reference) HR 95% CI p-Value ECOG performance status 2–3 (0–1) 1.42 0.97–2.07 0.070 Smoking status Smoker (Non-smoker) 1.02 0.73–1.42 0.904 Differentiation Poor (Moderate/Well) 1.52 1.08–2.14 0.017 HER2 status Positive (Negative) 0.65 0.38–1.12 0.122 Liver metastasis Present (Absent) 1.78 1.23–2.57 0.002 Peritoneal metastasis Present (Absent) 1.67 1.17–2.40 0.005 Radiotherapy Present (Absent) 0.84 0.51–1.40 0.508 First-line treatment HER2-based regimen (Fluoropyrimidine-based) 0.96 0.54–1.73 0.897 Immunotherapy-based regimen (Fluoropyrimidine-based) 1.11 0.34–3.63 0.867 CALLY score Low (High) 1.77 1.24–2.53 0.002 Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. © 2026 by the authors. Published by MDPI on behalf of the Lithuanian University of Health Sciences. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license. Akgül, F.; Can, S.; Gökmen, İ.; Bakır Kahveci, G.; Bayrakçı, İ.; Yurdatap Koç, D.; Demirdelen, E.; Çakıcı, V.; Erdoğan, B. The CALLY Index Is Associated with Overall Survival in Patients with De Novo Metastatic Gastric Adenocarcinoma. Medicina 2026, 62, 1124. https://doi.org/10.3390/medicina62061124 Akgül F, Can S, Gökmen İ, Bakır Kahveci G, Bayrakçı İ, Yurdatap Koç D, Demirdelen E, Çakıcı V, Erdoğan B. The CALLY Index Is Associated with Overall Survival in Patients with De Novo Metastatic Gastric Adenocarcinoma. Medicina. 2026; 62(6):1124. https://doi.org/10.3390/medicina62061124 Akgül, Fahri, Süleyman Can, İvo Gökmen, Gizem Bakır Kahveci, İsmail Bayrakçı, Dicle Yurdatap Koç, Ece Demirdelen, Veli Çakıcı, and Bülent Erdoğan. 2026. "The CALLY Index Is Associated with Overall Survival in Patients with De Novo Metastatic Gastric Adenocarcinoma" Medicina 62, no. 6: 1124. https://doi.org/10.3390/medicina62061124 Akgül, F., Can, S., Gökmen, İ., Bakır Kahveci, G., Bayrakçı, İ., Yurdatap Koç, D., Demirdelen, E., Çakıcı, V., & Erdoğan, B. (2026). The CALLY Index Is Associated with Overall Survival in Patients with De Novo Metastatic Gastric Adenocarcinoma. Medicina, 62(6), 1124. https://doi.org/10.3390/medicina62061124
