1. Basic characteristics of the patients with HCC
The study comprised 28 patients with HCC. All patients enrolled were men, their ages ranged from 28 to 72 years, had BCLC stage B or C, and Child-Pugh was either A or B. Triweekly PD-1 inhibitor treatments were administered to the patients after radiotherapy until disease progression occurred. The total dose of radiotherapy was 48Gy, with 3Gy per fraction. The predominant PD-1 inhibitors used were tirelizumab (18 cases), sindilizumab (3 cases), and karelizumab (7 cases). The use of the ROC curve to estimate the expected number of PD-L1(+) CTCs led to the determination of the critical value to be 2 PD-L1(+) CTCs in our previous work (Su et al. 2022).
BCLC, Barcelona clinic liver cancer; AFP, alpha-fetoprotein; CTCs, circulating tumor cells; PD-L1, programmed death-ligand 1
2. Dynamic Changes In Pd-l1(+) Ctcs Before And After Treatment
As shown in Table 1, each of the 28 patients included in the study had CTCs in their peripheral blood. The total number of CTCs in the patients before the treatment varied from 2 to 10, and PD-L1(+) CTCs were detected in 26/28 patients before the treatment. Figure 1 shows the percentage of PD-L1(+) CTCs per patient at baseline. The total number of CTCs decreased in all 28 patients and the number of PD-L1(+) CTCs decreased in 19 patients after receiving PD-1 inhibitor along with radiotherapy.
3. Correlation Between Therapeutic Effect And Pd-l1(+) Ctc Expression
After treatment with PD-1 inhibitor combined with IMRT, 24 of the 28 patients with HCC had DC (SD13 + PR11) and 4 patients had PD. Patients with and without PD-L1(+) CTCs at baseline exhibited disease control rates of 92.3% and 50%, respectively, as shown in Fig. 2. The cotreatment of PD-1 inhibitor and radiotherapy was found to benefit patients with HCC in whom PD-L1(+) CTCs were detected at baseline. In the pre- and post-treatment comparisons, an overall reduction of CTCs was observed in 100% (24/24) of the DC patients and 50% (2/4) of the PD patients, as shown in Fig. 3A. PD-L1(+) CTCs were reduced in 75% (18/24) of the DC patients and 25%(1/4) of the PD patients in the analysis of PD-L1 expression, as shown in Fig. 3B.
4. Pre- and post-treatment correlation between PD-L1(+) CTCs and alpha-fetal protein (AFP) values in patients with HCC
When the AFP values recorded before and after the treatment were recorded, as shown in Fig. 4, patients with ≥ 2 PD-L1(+) CTCs before the treatment were found to show a significantly higher declining trend after the treatment than those with ≤ 1 PD-L1(+) CTCs. AFP values can, to a certain extent, determine the disease status of patients with HCC, and the dynamic variations in AFP reflect the better treatment outcomes of the patients if they had more PD-L1(+) CTCs before the treatment.
5. Pd-l1(+) Ctcs Indicate A Favorable Prognosis For Patients With Hcc Before And After Treatment
The patients’ PFS was monitored, which revealed that it was inversely correlated with the number of PD-L1(+) CTCs at baseline and after the treatment. At baseline, ≥ 2 PD-L1(+) CTCs were associated with an mPFS of 3.50 months, which was longer than that of ≤ 1 PD-L1(+) CTCs (3.35 months), as shown in Fig. 5A. After treatment, the mPFS of patients with ≤ 1 PD-L1(+) CTCs was 4.20 months, whereas that of patients with ≥ 2 PD-L1(+) CTCs was only 1.90 months; hence, the former was significantly better than the latter, as shown in Fig. 5B. The results demonstrated that both elevated PD-L1(+) CTCs before treatment and low PD-L1(+) CTCs after treatment can serve as prognostic indicators in patients with HCC.