Assessment of the CALLY Index, a Novel Immunonutrivite Marker, in Perioperatively Treated Gastric Cancer Patients - Gazi Medical Journal

Growth differentiation factor-15 (GDF-15), a member of the TGF-β superfamily, is overexpressed in various cancers and facilitates immune evasion by inhibiting T-cell activation. GDFATHER-TRIAL’s phase 2a results demonstrated promising outcomes when combining the GDF-15 neutralizing antibody visugromab (CTL002) with nivolumab, enhancing the response to immunotherapy. This study evaluated the prognostic significance of GDF-15 expression in non-small cell lung cancer (NSCLC) tumor tissues in terms of immunotherapy response. This retrospective study included 50 patients with metastatic NSCLC treated with nivolumab at Gazi University Hospital between January 2021 and July 2023. GDF-15 expression was evaluated using immunochemistry staining and categorized based on the intensity of cytoplasmic or membranous staining. Samples were divided into a low expression group (scores 0 and 1) and a high expression group (scores 2 and 3). The primary outcomes were progression-free survival (PFS) and overall survival (OS), which were analyzed using Kaplan‒Meier and Cox proportional hazards models. Objective response rates were assessed in secondary outcomes. Of the 50 patients, 43 were men (86%), with a median age of 63.9 years. Half of the patients exhibited low GDF-15 expression. High GDF-15 expression correlated with shorter PFS and OS. The median PFS was 7.8 months for the low-expression group versus 4.4 months for the high-expression group (HR, 0.41; 95% CI, 0.20–0.83; p = 0.013). The median OS was 18.1 months for the low-expression group compared to 11.8 months for the high-expression group (HR, 0.36; 95% CI, 0.16–0.78; p = 0.007). The objective response rate was significantly greater in the low GDF-15 group (52%) than in the high GDF-15 group (24%) (p = 0.040). Elevated GDF-15 expression in NSCLC tumor tissues is associated with poorer response to nivolumab, suggesting that GDF-15 is a potential prognostic biomarker for immunotherapy efficacy. These findings warrant further validation through prospective studies to optimize treatment strategies for NSCLC patients.

Objective: The Prognostic Nutritional Index (PNI), reflects the nutritional and immunological status of the patient and has been associated with outcomes in various cancers. In this study, the prognostic significance of PNI in metastatic hormone‐sensitive prostate cancer (mHSPC) and its potential role in guiding treatment decisions between abiraterone acetate and enzalutamide is investigated.Methods: Retrospective analysis was performed on 167 mHSPC patients treated between 2019 and 2024. PNI was calculated using the formula: 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (/mm³). Patients were stratified into high and low PNI groups according to a cutoff value of 49.98, determined via receiver operating characteristic (ROC) analysis. Survival outcomes, including overall survival (OS), radiographic progression‐free survival (rPFS), and PSA progression‐free survival (PSA‐PFS), were assessed. Treatment responses to abiraterone acetate and enzalutamide were compared within PNI strata.Results: Patients with PNI > 49.98 had significantly longer median OS than those with PNI ≤ 49.98 (36.6 months vs. 30.0 months, p < 0.01). Multivariate analysis identified high PNI, ECOG performance status 0–1, and absence of visceral metastasis as independent predictors of improved OS. Among patients with low PNI, those treated with enzalutamide had superior OS compared to those receiving abiraterone acetate (p = 0.004), while no significant OS difference was noted between treatments in the high PNI group (p = 0.55).Conclusion: PNI serves as a significant prognostic biomarker in mHSPC, correlating with overall survival and potentially influencing treatment efficacy between abiraterone acetate and enzalutamide. Integrating PNI into clinical practice may aid in tailoring individualized treatment options.

Background: Immunotherapy has transformed cancer treatment; however, predicting treatment response remains challenging. Serum biomarkers can help identify patients who are most likely to benefit from immunotherapy. Objective: This study evaluates the relationship between serum growth differentiation factor 15 (GDF-15) and interleukin-6 (IL-6) levels and treatment outcomes in cancer patients undergoing second-line immunotherapy. Methods: We conducted a prospective observational study involving 85 patients with non-small-cell lung cancer (NSCLC), renal cell carcinoma (RCC), or malignant melanoma treated with nivolumab. The baseline serum levels of GDF-15 and IL-6 were measured by using ELISA kits. The primary endpoints were progression-free survival (PFS) and overall survival (OS), with cachexia as a secondary outcome. Results: Elevated GDF-15 levels were significantly associated with shorter PFS (HR: 0.55, 95% CI: 0.32–0.96, p = 0.032) and OS (HR: 0.47, 95% CI: 0.25–0.90, p = 0.020). Higher IL-6 levels correlated with shorter PFS, though statistical significance was not achieved. Additionally, high GDF-15 levels were linked to increased cachexia incidence (p = 0.037). Conclusion: Our findings indicate that GDF-15 could serve as a prognostic biomarker for immunotherapy response and may also be a target for cachexia management. Further studies should explore its potential to guide clinical decision making in oncology.