الملخص
Objective:To investigate the efficacy of immune checkpoint inhibitor maintenance therapy after radical radiotherapy and chemotherapy for stage Ⅲ-ⅣA esophageal squamous cell carcinoma (ESCC) in the real world.Methods:The clinical data of 65 patients with stage Ⅲ-ⅣA ESCC treated by radical radiotherapy and chemotherapy from January 1, 2018 to December 31, 2022 in Hefei Cancer Hospital, Chinese Academy of Sciences were retrospectively analyzed. According to whether to undergo immune checkpoint inhibitor maintenance therapy after radical radiotherapy and chemotherapy, the patients were divided into a control group ( n=29) and an immune maintenance therapy group ( n=36) . The objective response rate (ORR) , progression-free survival (PFS) , and overall survival (OS) between the two groups were compared. Kaplan-Meier method was used to draw the survival curve accompanied with log-rank test. Cox regression model was used to conduct both univariate and multivariate analyses. Results:The ORR was 34.5% (10/29) in the control group and 61.1% (22/36) in the immune maintenance therapy group, with a statistically significant difference ( χ2=4.56, P=0.032) . The median PFS of control group and immune maintenance therapy group were 7.2 and 17.9 months, respectively, with a statistically significant difference ( χ2=7.86, P=0.005) . The median OS was 14.1 and 27.8 months, respectively, with a statistically significant difference ( χ2=5.40, P=0.020) . Univariate analysis showed that, objective response ( HR=0.09, 95% CI: 0.03-0.28, P<0.001) and immune maintenance therapy ( HR=0.38, 95% CI: 0.17-0.88, P=0.024) were the influential factors of OS in ESCC patients treaded by radical chemoradiotherapy in stage Ⅲ-ⅣA. Multivariate analysis showed that, objective response ( HR=0.09, 95% CI: 0.03-0.29, P<0.001) and immune maintenance therapy ( HR=0.40, 95% CI: 0.17-0.92, P=0.032) were the independent influencing factors for OS in ESCC patients treaded by radical chemoracial therapy in stage Ⅲ-ⅣA. The incidence of adverse reactions was 22.22% (8/36) in the immune maintenance therapy group and 10.34% (3/29) in the control group, with no statistically significant difference ( χ2=1.61, P=0.204) . All the adverse reactions were grade 1-2, and the symptoms were relieved after symptomatic treatment. Conclusion:Maintenance therapy with immune checkpoint inhibitors after radical chemoradiotherapy of stage Ⅲ-ⅣA ESCC can significantly improve the prognosis of patients with good safety.
الملخص
Objective:To investigate the value of CD4/CD8 ratio and total B lymphocytes before radiotherapy in predicting the occurrence of radiation pneumonitis (RP) in patients with esophageal cancer and lung cancer.Methods:The clinicopathological data of 28 patients with esophageal and 16 patients with lung cancer undergoing radiotherapy from April 2018 to March 2020 in Hefei Cancer Hospital, Chinese Academy of Sciences were retrospectively analyzed, and the patients were divided into RP group ( n=16) and non-RP group ( n=28) according to whether RP occurred during and after treatment. The CD4/CD8 ratio and total B lymphocytes before radiotherapy between the two groups, and the CD4/CD8 ratio and total B lymphocytes before and after radiotherapy in the RP group were compared. Receiver operating characteristic curve was used to analyze the value of CD4/CD8 ratio and total B lymphocytes before radiotherapy in predicting RP. Results:The CD4/CD8 ratio before radiotherapy in the RP group was significantly lower than that in the non-RP group (0.993±0.179 vs. 1.708±0.170), with a statistically significant difference ( t=2.706, P=0.009); the total B lymphocytes in the RP group was significantly lower than that in non-RP group [(4.409±0.823)% vs. (8.153±1.017)%], with a statistically significant difference ( t=0.986, P=0.015). The CD4/CD8 ratio in the RP group was lower than that before radiotherapy when RP occurred (0.785±0.167 vs. 0.993±0.179), with no statistically significant difference ( t=1.376, P=0.189). The total B lymphocytes in the RP group was lower than that before radiotherapy when RP occurred [(3.487±1.018)% vs. (4.409±0.823)%], with no statistically significant difference ( t=0.804, P=0.433). The critical values of CD4/CD8 ratio and total B lymphocytes predicted RP were 0.580 and 0.357, respectively. The areas under the curve (AUC) of CD4/CD8 for predicting RP was 0.802 (95% CI: 0.653-0.932), the sensitivity was 89.29%, and the specificity was 68.75%. The AUC of total B lymphocytes for predicting RP was 0.694 (95% CI: 0.483-0.814), the sensitivity was 85.71%, and the specificity was 50.00%. The AUC of the two combined diagnostic method for RP was 0.834 (95% CI: 0.697-0.932), the sensitivity and specificity were 81.25% and 89.29%. AUC of the two combined tests was significantly higher than that of the single test, with statistically significant differences ( Z=1.115, P=0.046; Z=1.992, P=0.026). Conclusion:The CD4/CD8 ratio and total B lymphocytes in the RP group are lower than those in the non-RP group. The CD4/CD8 ratio and total B lymphocytes in the serum are of great significance in predicting the occurrence of RP in patients with malignant tumors receiving chest radiotherapy.
الملخص
<p><b>OBJECTIVE</b>To study the feasibility of preparing a therapeutic lung cancer vaccine by transfecting dendritic cells (DCs) with adeno-associated virus vector carrying carcino-embryonic antigen gene (rAAV/CEA).</p><p><b>METHODS</b>Adherent cells (monocytes) isolated from the peripheral blood of a healthy donor were infected with rAAV/CEA virus stock or pulsed with CEA peptide (control). The monocytes in both groups were induced into mature DCs with recombinant human GM-CSF, IL-4 and TNF-α. At day 7 of induction, the mature DCs were harvested and mixed with T lymphocytes. T cell proliferation stimulated by the DCs was assessed with (3)H-thymidine uptake, and the expression of IL-4, IFN-γ, CD8, CD4, CD25 and CD69 in cytotoxic T lymphocytes (CTL) was analyzed with flow cytometry. The cytotoxicity of the CTL against the target CEA-positive lung cancer A549 cells was tested by (51)Cr releasing assay.</p><p><b>RESULTS</b>The DCs transfected with rAAV/CEA strongly stimulated the proliferation of the T cell populations, and the induced CTL showed high expressions of CD8, CD69 and IFN-γ. The transfected DCs exhibited a high killing ability of CEA-positive lung cancer cells, and the killing showed a CEA antigen specificity and was limited by MHC I. These results suggested the ability of rAAV/CEA-transfected DCs in generating specific cellular immunity in vitro.</p><p><b>CONCLUSION</b>It is feasible to prepare therapeutic lung cancer vaccines by transfecting DCs with rAAV/CEA.</p>