Clinical vulnerability to chemotherapy in cholangiocarcinoma: impact of nutritional status, frailty, and systemic inflammation.

PURPOSE: To determine the contribution of frailty, nutritional status, and systemic inflammation to early toxicity and treatment modifications in patients with advanced cholangiocarcinoma (CCA) treated with gemcitabine-cisplatin plus immune checkpoint inhibitors (ICIs).

METHODS

Patients with unresectable or metastatic CCA who received first-line gemcitabine-cisplatin plus durvalumab or pembrolizumab were retrospectively analyzed. Frailty, nutritional status, and systemic inflammation were assessed using the five-item modified frailty index (mFI-5), prognostic nutritional index (PNI), and neutrophil-to-lymphocyte ratio (NLR). The primary outcome was suboptimal relative dose intensity (RDI < 75%) during the first six weeks of treatment. Secondary outcomes included grade ≥ 3 adverse events (AEs) and overall survival (OS).

RESULTS

Fifty-four patients were included. Univariable analyses indicated that lower PNI, hypoalbuminemia, older age, poorer performance status, and initial dose reduction were associated with suboptimal RDI. Lower PNI was independently associated with an increased risk of grade ≥ 3 AEs (adjusted odds ratio, 0.81; 95% confidence interval, 0.69-0.93). Patients with grade ≥ 3 AEs had significantly lower PNI and serum albumin levels; mFI-5, NLR, age, and performance status did not differ significantly between groups. In survival analyses, low PNI (< 42.9) was associated with significantly worse OS (log-rank p = 0.0036). An elevated NLR (≥ 3) was associated with OS; its prognostic impact was limited, whereas mFI-5 ≥ 2 was not. Performance status remained the strongest independent predictor of OS in multivariable models.

CONCLUSIONS

Among the evaluated vulnerability measures, PNI appeared to be an important marker associated with early treatment-related toxicity and survival in patients with advanced CCA treated with gemcitabine-cisplatin plus ICIs.