Prognostic Value of Baseline Systemic Immune-Inflammation Index in Advanced Intrahepatic Cholangiocarcinoma Treated with First-Line Gemcitabine-Cisplatin Plus PD-L1 Inhibitor: A Single-Center Retrospective Study.

[BACKGROUND] Gemcitabine-cisplatin (GC) combined with a programmed death-ligand 1 (PD-L1) inhibitor has become an important first-line regimen for advanced intrahepatic cholangiocarcinoma (ICC). However, overall efficacy remains modest, and inter-patient heterogeneity in outcomes is substantial, highlighting the need for simple biomarkers for pretreatment risk stratification. The systemic immune-inflammation index (SII), derived from peripheral neutrophil, lymphocyte, and platelet counts, has been associated with prognosis in various malignancies, but its clinical relevance in advanced ICC treated with first-line GC plus PD-L1 inhibitor remains unclear.

[AIMS] To evaluate the association of baseline SII with objective response and survival outcomes in patients with advanced ICC receiving first-line GC plus PD-L1 inhibitor.

[METHODS] We retrospectively analyzed 193 consecutive patients with advanced ICC who received first-line GC plus a PD-L1 inhibitor at our center. Baseline clinicopathologic characteristics and laboratory parameters were collected, and SII was calculated as platelet count (×10/L) × neutrophil count (×10/L)/lymphocyte count (×10/L). Receiver operating characteristic (ROC) analysis was performed to assess the discriminative ability of baseline SII for objective response and to determine an internally derived cut-off value. Patients were categorized into low- and high-SII groups accordingly. Logistic regression was used to identify factors associated with objective response rate (ORR). Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method and compared using the log-rank test. Multivariable Cox proportional hazards models were constructed to evaluate the independent prognostic significance of SII for PFS and OS.

[RESULTS] Among the 193 patients included, 55 achieved complete or partial response and 138 had stable or progressive disease, yielding an ORR of 28.5%. Baseline SII showed good discrimination for objective response (AUC = 0.91), and the optimal cut-off value was 495.75. Patients in the low-SII group had a significantly higher ORR than those in the high-SII group ( < 0.001). Kaplan-Meier analysis demonstrated that both PFS and OS were longer in the low-SII group than in the high-SII group (median OS: 13.0 vs. 8.0 months, log-rank < 0.001; median PFS: 8.5 vs. 6.0 months, = 0.025). In multivariable Cox models adjusting for differentiation, CA19-9, tumor multiplicity, and distant metastasis, SII grouping remained independently associated with PFS and OS, and distant metastasis was consistently associated with increased risks of progression and death.

[CONCLUSIONS] Baseline SII is a readily available prognostic biomarker associated with objective response and survival in patients with advanced ICC treated with first-line GC plus PD-L1 inhibitor. Given the retrospective single-center design, the absence of a non-immunotherapy comparator cohort, and internal cut-off derivation, these findings should be interpreted as hypothesis-generating and warrant external validation.