Xuefeng Kan’s research while affiliated with Huazhong University of Science and Technology and other places

Preventing tumor recurrence after radiofrequency ablation (RFA) of malignant solid tumors with large size or in high-risk locations represents a great challenge. In this study, we explored the feasibility of using oncolytic peptide LTX-315 plus an anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) antibody for inhibiting residual tumors after RFA of hepatocellular carcinoma (HCC). In in vitro experiment, the CD8 ⁺ T cells from Hepa1-6 tumors, after being subjected to three different treatments (control, iRFA, iRFA + LTX-315), were extracted and were then co-cultured with Hepa1-6 cells and an anti-CTLA-4 antibody. The enzyme-linked immunospot, flow cytometry, and cell counting kit-8 assay were employed to assess the cytotoxicity of extracted CD8 ⁺ T cells on Hepa1-6 cells. In in vivo experiment, different murine orthotopic HCC models were variously treated by: (1) pseudo iRFA + phosphate-buffered saline (PBS); (2) iRFA + PBS; (3) iRFA + LTX-315; (4) iRFA + anti-CTLA-4 antibody; and (5) iRFA + LTX-315 + anti-CTLA-4 antibody. The treatment effects were compared among different groups and were pathologically confirmed. The possible mechanisms of the combination treatment (LTX-315+anti-CTLA-4 antibody) for residual tumors after iRFA of HCC were explored. LTX-315 significantly reduced the PD-1 expression and significantly increased CTLA-4 expression of CD8 ⁺ T cells in residual tumors, and additional treatment of anti-CTLA-4 antibody could significantly enhance the cytotoxicity of CD8 ⁺ T cells for Hepa1-6 cells in vitro experiments. Compared with the other treatments, the combined treatment of LTX-315 with anti-CTLA-4 antibody achieved a better tumor response and longer survival, and it could synergistically activate the cGAS-STING pathway and elicit an immunogenic cell death, leading to a strong anti-tumor immunity after iRFA of HCC. The immunosuppressive microenvironment of residual tumors was significantly improved by the combination therapy with a significantly increased ratio of M1-like tumor-associated macrophages to M2-like tumor-associated macrophages, a significantly decreased infiltration of regulatory T cells and myeloid-derived suppressor cells, and a significantly lower expression of PD-1 and CTLA-4. Overall, the results of this study demonstrated that LTX-315 plus anti-CTLA-4 antibody could synergistically improve the immunosuppressive microenvironment of residual tumors and induce a strong anti-tumor immunity after iRFA of HCC. This combination treatment strategy may offer a new alternative to reduce the tumor recurrence after RFA of malignant solid tumors with large sizes or in high-risk locations.

Background The stent type may be associated with adverse events in carotid artery stenting (CAS). This study aimed to compare the clinical outcomes (stroke/myocardial infarction (MI)/death) of CAS with open- and closed-cell stents for patients with carotid artery stenosis. Methods Between April 2012 and May 2024, the clinical data of 223 patients who underwent CAS in our center were retrospectively analyzed. In terms of the stent type used, patients were divided into a closed-cell stent group and an open-cell stent group. Clinical outcomes between the two groups were compared. Univariate and multivariate analyses were performed to identify the independent risk factors. Subgroup analyses in terms of carotid plaque types and smoking history were conducted in carotid artery stenosis patients receiving CAS with open- and closed-cell stents. Results The combined in-hospital stroke/MI/death rate was significantly lower in the closed-cell stent group than in the open-cell stent group (p=0.026). Open-cell stents, smoking, and unstable plaques were the independent risk factors associated with a higher in-hospital stroke/MI/death rate. Subgroup analyses showed that for patients with unstable plaques, the combined in-hospital stroke/MI/death rate was significantly higher in the open-cell stent group than in the closed-cell stent group (p=0.016). For patients who smoked, the combined in-hospital stroke/MI/death rate was significantly higher in the open-cell stent group than in the closed-cell stent group (p=0.038). Conclusion For carotid artery stenosis patients with unstable carotid plaques or smoking history, using closed-cell stents in CAS may help reduce the combined in-hospital stroke/MI/death rate.

Background & Aims The effect of transarterial chemoembolization (TACE) plus radiofrequency ablation (RFA) (TACE-RFA) for hepatocellular carcinoma (HCC) in high-risk locations is not satisfactory. The aim of this study was to compare the clinical outcomes of TACE-RFA plus iodine-125 (¹²⁵I) seed implantation (TACE-RFA-¹²⁵I) therapy with those of TACE-RFA for unresectable HCC (≤5 cm) in high-risk locations. Methods From January 2010 to June 2023, the clinical data of 126 patients with unresectable HCC (≤5 cm) in high-risk locations who received TACE-RFA-¹²⁵I or TACE-RFA treatment were retrospectively analyzed. The clinical outcomes between the two groups were compared after propensity score matching (PSM) analysis. Results Forty-six pairs of patients were matched. The local progression-free survival rates at 1-, 2-, 3-, 4-, and 5-years were 100%, 82.4%, 74.8%, 63.5%, and 54% in the TACE-RFA-¹²⁵I group, which were significantly higher than 91.3%, 69.4%, 50.7%, 29.4%, and 26.7% in the TACE-RFA group, respectively (p = 0.004). The median progression-free survival in the TACE-RFA-¹²⁵I group was significantly longer than that in the TACE-RFA group (p = 0.002). The overall survival rates at 1-, 2-, 3-, 4-, and 5-years were 100%, 93.4%, 80.7%, 74.9%, and 64.7% in the TACE-RFA-¹²⁵I group, which were significantly higher than 97.8%, 78%, 68.6%, 51.1%, and 45.3% in the TACE-RFA group, respectively (p = 0.011). There was no occurrence of major complications or procedure-related deaths in the two groups. Conclusion Compared with the TACE-RFA treatment, TACE-RFA-¹²⁵I should be a more effective treatment strategy for patients with unresectable HCC (≤5 cm) in high-risk locations.

Digital subtraction angiography (DSA) devices have been commonly used in hundreds of different procedures, requiring multiple scans of the patient in a single procedure, which causes high radiation damage to doctors and patients. This study proposed a large-scale pretrained multi-frame generative model-based real-time and low-dose DSA imaging system (GenDSA). GenDSA was trained and validated by employing millions of DSA images from 35 hospitals, which demonstrated that GenDSA can achieve state-of-the-art performance and reduce the DSA radiation dose to 1/3 of clinically available protocols. Subjective ratings and statistical results from five doctors showed that the generated videos reached a comparable level to the full-sampled videos, both in terms of overall quality and lesion assessment, which fully demonstrated the potential of GenDSA for clinical applications.

Purpose To evaluate the effect of the school curriculum and on-site observation of interventional radiology (IR) operations in clinics on undergraduates’ radiation anxiety, interest, and career intention. Methods Between the academic years 2021 and 2023, all of the fourth-year undergraduates were surveyed by questionnaires, which covered their pre-curriculum, post-curriculum in-school, and post-on-site view of IR surgeries in clinic. The survey included categories of gender, fear of X-ray and IR operation, interest in IR surgery, and career-pursuing intention. Results A total of 333 (91.0%) respondents (111 students for three times) were included in analyses. The fear of X-ray and radiation exposure during IR procedures was reduced after taking school courses ( p < 0.001), and it was further decreased after on-site viewing ( p < 0.001). The association values among the three groups were 33.8% and 41.9%, respectively. The interest in IR was improved both after applying for the curriculum and after clinical exposure to IR surgery ( p < 0.001). In addition, 4 (3.6%) and 12 (10.8%) students showed a sense of achievement after taking courses and on-site viewing, respectively. The association value was 49.4%. Regarding career intention, it was both significantly increased after taking courses and on-site observation ( p < 0.001). Besides, 8 (7.2%), 17 (15.3%), and 36 (32.4%) students in the three groups considered IR as the preferred career choice, respectively. Conclusions Applying for IR curriculum could reduce undergraduates’ radiation anxiety, and activate their professional interest and career pursuing intention. Clinical exposure to IR surgeries further boosted this effect. Clinical relevance statement Educational interventions of curriculum and on-site view of IR surgery improve the undergraduates’ interest in IR and stimulate their career intention, which is crucial for the advancement of IR. Key Points Increasing interest in interventional radiology (IR) as a career is urgent, given rising demand of services . Education and on-site viewing of IR surgery reduced radiation anxiety and increased interest in IR . Early exposure to IR is effective at encouraging undergraduates to consider IR as their career .

Background Although numerous studies have reported the prognostic value of the lung immune prognostic index (LIPI) in non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs), the prognostic value of the LIPI in a pancancer setting remains unclear. Methods A comprehensive search was conducted until July 2023 across the PubMed, Embase, Web of Science, and Cochrane Library databases to identify relevant studies evaluating the prognostic value of the LIPI in cancer patients treated with ICIs. The outcomes were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). We described and compared the pooled outcomes by stratifying the patients based on different groupings of LIPI (good vs. intermediate [0 vs. 1], good vs. poor [0 vs. 2], and good vs. intermediate / poor [0 vs. 1 + 2]). Results A total of 9959 patients in 35 studies were included. A higher score of LIPI was associated with impaired OS. The pooled HRs were 1.69 (95% CI: 1.55–1.85, p < 0.001; 0 vs. 1), 3.03 (95% CI: 2.53–3.63, p < 0.001; 0 vs. 2), and 2.38 (95% CI: 1.97–2.88, p < 0.001; 0 vs. 1 + 2). A higher LIPI score was associated with shorter PFS. The pooled HRs were 1.41 (95% CI: 1.31–1.52, p < 0.001; 0 vs. 1), 2.23 (95% CI: 1.87–2.66, p < 0.001; 0 vs. 2), and 1.65 (95% CI: 1.46–1.86, p < 0.001; 0 vs. 1 + 2). Similarly, a higher LIPI score was associated with a lower ORR. The pooled ORs were 0.63 (95% CI: 0.54–0.75, p < 0.001; 0 vs. 1) and 0.38 (95% CI: 0.29–0.50, p < 0.001; 0 vs. 2). A higher LIPI score was associated with a lower DCR. The pooled ORs were 0.47 (95% CI: 0.35–0.61, p < 0.001; 0 vs. 1) and 0.19 (95% CI: 0.12–0.30, p < 0.001; 0 vs. 2). Conclusion In patients with NSCLC or other solid tumours, the lung immune prognostic index could robustly stratify the clinical outcomes into three groups among the patients who receive ICIs. LIPI is a low-cost, simple, accessible, and accurate prognostic tool in a pancancer setting and it may contribute to the evaluation of risk stratification in patients treated with ICIs.

Background & aims: The effect of transarterial chemoembolization (TACE) plus radiofrequency ablation (RFA) (TACE-RFA) for hepatocellular carcinoma (HCC) in high-risk locations is not satisfactory. The aim of this study was to compare the clinical outcomes of TACE-RFA plus iodine-125 (¹²⁵I) seed implantation (TACE-RFA-¹²⁵I) therapy with those of TACE-RFA for unresectable HCC (≤5 cm) in high-risk locations. Methods: From January 2010 to June 2023, the clinical data of 126 patients with unresectable HCC (≤5 cm) in high-risk locations who received TACE-RFA-¹²⁵I or TACE-RFA treatment were retrospectively analyzed. The clinical outcomes between the two groups were compared after propensity score matching (PSM) analysis. Results: Forty-six pairs of patients were matched. The local progression-free survival rates at 1-, 2-, 3-, 4-, and 5-years were 100%, 82.4%, 74.8%, 63.5%, and 54% in the TACE-RFA-¹²⁵I group, which were significantly higher than 91.3%, 69.4%, 50.7%, 29.4%, and 26.7% in the TACE-RFA group, respectively (p = 0.004). The median progression-free survival in the TACE-RFA-¹²⁵I group was significantly longer than that in the TACE-RFA group (p = 0.002). The overall survival rates at 1-, 2-, 3-, 4-, and 5-years were 100%, 93.4%, 80.7%, 74.9%, and 64.7% in the TACE-RFA-¹²⁵I group, which were significantly higher than 97.8%, 78%, 68.6%, 51.1%, and 45.3% in the TACE-RFA group, respectively (p = 0.011). There was no occurrence of major complications or procedure-related deaths in the two groups. Conclusions: Compared with the TACE-RFA treatment, TACE-RFA-¹²⁵I should be a more effective treatment strategy for patients with unresectable HCC (≤5 cm) in high-risk locations.

Radiofrequency ablation (RFA) is an effective alternative to surgery for managing some malignant solid tumors. However, for medium-to-large tumors (>3 cm), tumors adjacent to large blood vessels, and certain irregular tumors, sublethal radiofrequency hyperthermia (RFH) often produces a margin of ablated tumor owing to the “heat-sink" effect. This effect typically leaves behind viable residual tumors at the margin. Several studies have reported that a sublethal RFH can significantly enhance the efficacy of chemotherapy, radiotherapy, immunotherapy, and gene therapy for malignant solid tumors. The possible mechanisms by which RFH enhances these therapies include heat-induced tissue fracturing, increased permeability of the cytoplasmic membrane, exaggerated cellular metabolism, blockade of the repair pathways of radiation-damaged tumor cells, and activation of the heat shock protein pathways. Therefore, RFA in combination with chemotherapy, radiotherapy, immunotherapy, or gene therapy may help reduce the rates of residual and recurrent tumors after RFA of malignant solid tumors.