Background Systemic administration of immunotherapy via intravenous injection is frequently associated with off-target toxicity throughout the body. In contrast, intratumoral injection has emerged as a promising strategy to mitigate systemic adverse effects. However, data regarding the safety of CT-guided intratumoral immunotherapy remain limited. Methods This pooled prospective cohort study included patients from several single-arm clinical trials. Eligible participants had histologically confirmed advanced solid tumors that were refractory or intolerant to standard therapies. Each participant had at least one measurable tumor lesion accessible for puncture under imaging guidance. All patients received CT-guided intratumoral injection of various ICIs (PD-1, PD-L1, and CTLA-4 inhibitors) either alone or in combination, or of CAR-T cells. The primary endpoint was safety of the treatment. Results A total of 169 patients were included in the study cohort, with a median follow-up duration of 8.4 months (range, 1.0–38.0 months). Grade 3–4 adverse events occurred in 15 patients (8.88%), comprising 10 (5.92%) grade 3 and 5 (2.96%) grade 4 events; no treatment-related deaths were observed. Efficacy outcomes included 4 patients (2.37%) with complete response (CR), 15 (8.88%) with partial response (PR), 142 (84.02%) with stable disease (SD), and 8 (4.73%) with progressive disease (PD). The objective response rate (ORR) was 11.24%, and the disease control rate (DCR) was 95.27%. The median progression-free survival (PFS) was 3.6 months (95% CI, 3.1–4.1 months), and the median overall survival (OS) was 8.8 months (95% CI, 8.2–9.3 months). Conclusion This study indicates the safety and preliminary therapeutic potential of intratumoral injection. Intratumoral injection may be a promising strategy for mitigating systemic toxicity; however, further research is necessary to validate its therapeutic efficacy. Clinical trial registrationhttps://clinicaltrials.gov, identifier NCT03198052, NCT03769129, NCT03755739, NCT03952065, and NCT05341492.
Yong Ou, Jian Zhang, H. Tan et al.· Frontiers in Immunology· 0 citations
Objective: Genetic factors contribute to physical activity (PA) and sedentary behavior (SB), two complex behavioral traits. They may be associated with musculoskeletal and inflammatory diseases. However, the relationships of domain-specific PA and SB traits with osteoporosis (OS), psoriatic arthritis (PsA), and rheumatoid arthritis (RA) remain unclear. A two-sample Mendelian randomization (MR) analysis assessed potential bidirectional associations between these behavioral traits and the three diseases. Methods: GWAS summary statistics were used to examine five domain-specific PA traits, three SB traits, and OS, RA, and PsA. Primary causal estimates were obtained using the inverse-variance weighted (IVW) method. Complementary analyses used MR-Egger regression, the weighted median method, and the weighted mode method. Sensitivity analyses were performed using Cochran’s Q test, the MR-Egger intercept test, MR-PRESSO, and leave-one-out analysis. Multiple testing was addressed using false discovery rate (FDR) correction. Results: In the forward MR analyses, genetically predicted liability to Light DIY was associated with lower odds of PsA after FDR correction (OR = 0.006, 95% CI = 0.0002–0.236, FDR-adjusted p = 0.018). Genetically predicted longer television viewing was linked to increased odds of PsA (OR = 2.205, 95% CI = 1.089–4.463, FDR-adjusted p = 0.028) and RA (OR = 1.006, 95% CI = 1.002–1.010, FDR-adjusted p = 0.004). Walking for pleasure showed a nominal inverse association with PsA, and computer use showed a nominal inverse association with RA. Neither association remained significant after FDR correction. No evidence of associations with the broad self-reported OS diagnosis was observed. Reverse MR analyses showed lower odds of Walking for pleasure (OR = 0.662, 95% CI = 0.484–0.906, FDR-adjusted p = 0.013) and Other exercises (OR = 0.651, 95% CI = 0.490–0.864, FDR-adjusted p = 0.006) for genetic liability to RA. RA liability was also associated with longer television viewing time (β = 0.708, 95% CI = 0.251–1.165, FDR-adjusted p = 0.006). No reverse associations were observed for PsA. Conclusions: This bidirectional MR study identified several potential genetically predicted associations of domain-specific PA and SB traits with PsA and RA. The findings for television viewing and RA may suggest a potential bidirectional association. However, the results should be considered hypothesis-generating. These findings require independent replication and further validation before causal or clinical conclusions can be drawn.
Tianyu Sun, Fei-Yao Zhang, Chang Liu et al.· Genes· 0 citations
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