A Potential Predictive Marker for Advanced Hepatocellular Carcinoma PD-1 Inhibitors Combined with Radiation: Expression of PD-L1 on Circulating Tumor Cells

Purpose: In the treatment of advanced hepatocellular carcinoma (HCC), programmed death-1 (PD-1) immune checkpoint inhibitors has recently been shown to be highly effective when combined with radiotherapy. Furthermore, they have become the hotspot in cancer diagnosis and treatment for the detection of programmed death-ligand 1 (PD-L1) in circulating tumor cells (CTCs). However, their predictive effect is not well established. Therefore, this study examined whether PD-L1 expression in CTCs can be used as a marker to predict treatment response in patients with advanced HCC. Methods Patients treated with both PD-1 inhibitors and intensity-modulated radiation therapy (IMRT) were enrolled in the study. After radiation therapy, PD-1 inhibitor treatment was administered every 3 weeks until disease progression. Peripheral blood (2 mL) was collected from patients before and after treatment, and CTC PD-L1 was detected using the Watson Biotechnology reagent (China). Results A total of 28 patients with HCC were enrolled in this study. The disease control rate (DCR) was significantly higher in patients with PD-L1(+) CTC enrichment at baseline than in controls (92.3% and 50%, respectively). Before treatment, patients with PD-L1(+) CTCs ≥ 2 had a higher median progression-free survival (mPFS) than those with PD-L1(+) CTCs ≤ 1 (3.50 vs. 3.35 months). After treatment, CTCs with PD-L1(+) ≤ 1 were significantly associated with longer mPFS than CTCs with PD-L1(+) ≥ 2 (4.20 vs. 1.90 months, P < 0.01). Conclusions The presence of CTCs expressing PD-L1(+) might predict efficacy and prognosis in HCC patients treated with PD-1 inhibitors and radiotherapy. Retrospectively registered The study has been registered with the Chinese Clinical Trials Registry (registration number: ChiCTR2100044198).