# 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

## TL;DR

A blood test called the Systemic Immune-Inflammation Index (SII) can predict how well patients with advanced liver bile duct cancer will respond to a combination of chemotherapy and immunotherapy.

## Contribution

The study shows that a low baseline SII is independently linked to better treatment outcomes in intrahepatic cholangiocarcinoma patients receiving first-line GC plus PD-L1 inhibitor.

## Key findings

- Patients with a lower SII had higher tumor response rates and longer survival times.
- SII remained an independent predictor of progression-free and overall survival in multivariable analysis.
- The SII cut-off value of 495.75 effectively distinguished between high- and low-risk patients.

## Abstract

Bile duct cancer that starts inside the liver is difficult to treat, and people can respond very differently to the same medicines. Doctors need simple and inexpensive ways to identify patients who may do better or worse before treatment begins. In this study, we reviewed the medical records of 193 patients who received first-line treatment with two standard chemotherapy drugs (gemcitabine and cisplatin) together with durvalumab, a medicine that helps the immune system attack cancer. We used routine blood tests taken before treatment to create an index that reflects the balance between inflammation and immune strength. Patients with a lower index were more likely to have their tumors shrink on scans, and they lived longer without the cancer getting worse, as well as longer overall, compared with patients who had a higher index. This blood-based measure is easy to obtain in everyday practice and could help doctors counsel patients, plan follow-up, and identify those who may need closer monitoring or additional treatment strategies. Because this was a single-hospital study looking back at on existing records, the findings require confirmation in other groups of patients.

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 (×109/L) × neutrophil count (×109/L)/lymphocyte count (×109/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 (p < 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 p < 0.001; median PFS: 8.5 vs. 6.0 months, p = 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.