Size selection of intrahepatic lesions for cryoablation contributes to abscopal effect and long-term survival in patients with liver metastatic melanoma receiving PD-1 blockade therapy.

OBJECTIVES: In this study, we aimed to examine parameters of cryoablation, tumor characteristics, and their correlations with distant tumor response and survival of liver metastatic melanoma patients receiving cryoablation and PD-1 blockade (cryo-PD-1) combination treatment. MATERIALS AND METHODS: A retrospective study was conducted among 45 melanoma patients who received combined PD-1 blockade therapy and cryoablation for liver metastasis from 2018 to 2022. Cox regression was utilized to determine the associations between factors and overall survival (OS). Changes in cytokines and immune cell compositions in peripheral blood samples following the combined treatment were investigated, along with their correlations with treatment response. RESULTS: The mean cycle of cryo-PD-1 combination treatment was 2.2 (range, 1-6), and the 3-month overall response rate (RECIST 1.1 criteria) was 26.7%. Of the 21 patients who failed previous PD-1 blockade therapy after diagnosis of liver metastasis, 4 (19.0%) achieved response within 3 months since combination treatment. The diameter of ablated lesion ≤ 30 mm, metastatic organs ≤ 2, and pre-treatment LDH level ≤ 300 U/L were independent prognostic factors for favorable OS. Further analysis showed patients with intrahepatic tumor size of 15-45 mm, and ablated lesion size of ≤ 30 mm had significantly higher 3-month response rate (42.9% vs 12.5%; P = 0.022) and survival time (30.5 vs 14.2 months; P = 0.045) than their counterparts. The average increase in NLR among patients with ablated tumor size of ≤ 3 cm and > 3 cm were 3.59 ± 5.01 and 7.21 ± 12.57, respectively. The average increase in serum IL-6 levels among patients with ablated tumor size of ≤ 3 cm and > 3 cm were 8.62 ± 7.95 pg/ml and 15.40 ± 11.43 pg/ml, respectively. CONCLUSION: Size selection of intrahepatic lesions for cryoablation is important in order to achieve abscopal effect and long-term survival among patients with liver metastatic melanoma receiving PD-1 blockade therapy.

Local treatment of liver metastasis in a patient with advanced malignant melanoma: A case report.

Melanoma is a fatal malignant tumor with a high rate of metastasis. Liver metastasis of melanoma is always associated with insensitivity to immunotherapy and a poor prognosis. However, the combination of cryoablation, which is believed to stimulate the antitumor immune response in the body, with immunotherapy can improve the therapeutic response to this condition. Herein, we present the case of a 79-year-old woman with BRAF (B-Raf proto-oncogene) wild-type melanoma who later developed liver metastasis. The patient received intravenous antiprogrammed cell death 1 antibody, which showed poor efficacy, and subsequent treatment with immunotherapy combined with cryoablation yielded a partial response. However, after the second cryoablation, the patient refused further treatment due to a fear of bleeding. Therefore, only immunotherapy was provided, which resulted in disease progression. This report demonstrates the need to consider immunotherapy plus cryoablation for the treatment of liver metastases in patients with BRAF wild-type melanoma.

The relationship between the efficacy of thermal ablation and inflammatory response and immune status in early hepatocellular carcinoma and the progress of postoperative adjuvant therapy.

Hepatocellular carcinoma (HCC) is a highly heterogeneous disease. Thermal ablation has the advantages of being equivalent to surgical resection, minimally invasive, low cost and significantly reducing hospital stay. Therefore, it is recommended as one of the first-line radical treatment for early HCC. However, with the deepening of research on early HCC, more and more studies have found that not all patients with early HCC can obtain similar efficacy after radical thermal ablation, which may be related to the heterogeneity of HCC. Previous studies have shown that inflammation and immunity play an extremely important role in the prognostic heterogeneity of patients with HCC. Therefore, the inflammatory response and immune status of patients may be closely related to the efficacy of early HCC after curative thermal ablation. This article elaborates the mechanism of high inflammatory response and poor immune status in the poor prognosis after radical thermal ablation of early HCC, and clarifies the population who may benefit from adjuvant therapy after radical thermal ablation in patients with early HCC, which provides a new idea for the precise adjuvant treatment after radical ablation of early HCC in the future.

Identification of prognosis-related cyclin-dependent kinases and potential response drugs in hepatocellular carcinoma.

Context and Aims: Which cyclin-dependent kinases (CDKs) involved in the progress of hepatocellular carcinoma (HCC) need to be further clarified. To identify prognostic-relevant biomarkers in HCC through a systematic investigation of the prognostic value of CDKs. Methods and Material: We explored the relationship between CDKs expression and the prognosis of patients with HCC using multiple online databases. In addition, their biological functions and correlation with the immune system and drug response were investigated. Results: Among the 20 CDKs (CDK1 ~20) altered in HCC, the significantly high expression of CDK1 and CDK4 in patients with HCC was significantly associated with worse prognosis. Interestingly, CDK1 had significant co-occurrence with CDK4 and CDK1-related and CDK4-related signaling pathways are closely related to hepatitis virus-related HCC. We identified multiple transcription factors of CDK1 and CDK4; of those, only four (E2F1, PTTG1, RELA, and SP1) were significantly associated with the prognosis of HCC patients. Genetic alterations in CDKs were significantly correlated with disease-free and progression-free survival, which may be associated with aberrant expression of progesterone receptor. Moreover, we found a significantly positive correlation between CDK1 and CDK4 expression and tumor-infiltrating activated CD4+ T cell and exhausted T cell-related signature. Finally, we identified drugs with good potential prognostic value predicted by CDK1 and CDK4 levels. Conclusions: CDK1 and CDK4 may be potential prognostic biomarkers for HCC. Moreover, targeting four transcription factors (E2F1, PTTG1, RELA, and SP1) combined with immunotherapy may be a new therapeutic strategy for treating HCC patients with high CDK1 and CDK4 expression, especially hepatitis-related HCC.

Cryoablation reshapes the immune microenvironment in the distal tumor and enhances the anti-tumor immunity.

As one of the local treatments, cryoablation plays an increasingly important role in the comprehensive treatment of malignant tumors with its advantages of less trauma, high reproducibility, and minimally invasive. Activation of anti-tumor immunity, another characteristic of cryoablation, has attracted more and more attention with the extensive application of immunotherapy. Unfortunately, the mechanism by which cryoablation enhances anti-tumor immunity is still unclear. In this study, we applied a multi-omics approach to investigate the effects of local cryoablation in the distal tumor microenvironment. The results revealed that large amounts of tumor antigens were released post-cryoablation, leading to a sterile inflammatory response in distant tumors. During this period, activated lysosome-related pathways result in over-expression of SNAP23 (Synaptosome associated protein 23) and STXBP2 (Syntaxin binding protein 2), activation of immune effector cells, suppression of the release of immunosuppressive factors, and finally enhancement of anti-tumor immunity, which shows a broad prospect in combined immunotherapy.

Feasibility and efficacy of superconducting open-configuration magnetic resonance-guided microwave ablation of malignant liver tumors with real-time imaging sequences.

Objective: To evaluate the safety and effectiveness of open superconducting magnetic resonance (MR)-guided microwave ablation of liver tumors and explore feasibility of real-time imaging sequence-guided needle insertion technique. Materials and Methods: Medical records of December 2019-May 2021 of microwave ablations of liver tumors under MR guidance in XX University Cancer Center were reviewed. Real-time imaging-guided puncture technique refers to real-time insertion and adjusting the position of a microwave applicator under a fast imaging sequence. The safety and efficacy of the procedure among the enrolled patients were assessed. Results: Twenty-six patients underwent 27 procedures, with 30 lesions ablated (long diameter: 1.51 ± 0.81 cm, short diameter: 1.30 ± 0.61 cm). There were 20 cases of primary liver cancer and 10 of liver metastases. All lesions were identified by MR imaging (MRI), and all procedures were successfully performed using the finger positioning method for puncture sites. Five patients underwent real-time guided needle insertion techniques. Further, the microwave applicators reached the target position at once, and the entire insertion process was completed within 3 min. The completion rate of the real-time guided needle insertion technology was 100%, and 25 (92.6%) patients had minor complications. No severe complications were observed, and the technical success rate of 30 MRI-guided lesions was 100%. Finally, the complete ablation rate of the MRI-guided ablation after the first procedure was 93.1%. Conclusion: Open MR-guided microwave ablation is safe and effective in treating liver tumors. Furthermore, real-time imaging sequence-guided puncture technique under MRI is feasible and efficient.

Knockdown of LINC00467 contributed to Axitinib sensitivity in hepatocellular carcinoma through miR-509-3p/PDGFRA axis.

Hepatocellular carcinoma (HCC) is a common histological class of primary liver cancer with dismal prognosis. Long noncoding RNAs (lncRNAs) are increasingly documented as participators in cancers. Present study aimed to explore the role of long intergenic nonprotein-coding RNA 467 (LINC00467) in HCC. LINC00467 was upregulated in HCC samples in TCGA database, and was confirmed to be elevated in HCC cell lines. Functionally, LINC00467 depletion impeded proliferation and invasion, induced apoptosis, and promoted cellular sensitivity to Axitinib in HCC. Mechanistically, LINC00467 performed as a sponge of microRNA (miR)-509-3p and upregulated the expression of platelet-derived growth factor receptor alpha (PDGFRA) in HCC cells. In conclusion, our study illustrated that LINC00467 promoted proliferation and invasion, impedes apoptosis, and contributed to Axitinib resistance of hepatocellular carcinoma through miR-509-3p/PDGFRA, indicating LINC00467 as a promising biological target for HCC treatment.