The Impact of Histotripsy Technique in Tumor Ablation - a Systematic Review

According to a study conducted in the U.S., cancer affects more than 700,000 individuals worldwide each year, with 35,660 new cases diagnosed in the U.S. in 2015 alone. However, there are only a few standard treatment choices, which include radiation, chemotherapy, and surgery. This systematic review report on the impact of histotripsy in tumor ablation. In this paper, the effectiveness, safety and advantages of histotripsy compared to other methods are explored. A search was done on ScienceDirect, PubMed, Google Scholar, and Scopus databases for articles published from the date of inception of the databases to 21st March 2023. Reference lists of identified studies were also screened. Non-duplicate articles were identified, and 12 articles were included for thematic analysis. During the analysis, different effects of histotripsy were categorized. This categorization led to the realization of the effectiveness, immunological effects, safety and advantages of histotripsy compared to the therapeutic options. Histotripsy is effective and safe treatment for various types of cancer, including cholangiocarcinoma, pancreatic cancer, breast cancer, colorectal cancer, osteosarcoma, and hepatocellular carcinoma (HCC)

Focused ultrasound : tumour ablation and its potential to enhance immunological therapy to cancer

Various kinds of image-guided techniques have been successfully applied in the last years for the treatment of tumours, as alternative to surgical resection. High intensity focused ultrasound (HIFU) is a novel, totally non-invasive, image-guided technique that allows for achieving tissue destruction with the application of focused ultrasound at high intensity. This technique has been successfully applied for the treatment of a large variety of diseases, including oncological and non-oncological diseases. One of the most fascinating aspects of image-guided ablations, and particularly of HIFU, is the reported possibility of determining a sort of stimulation of the immune system, with an unexpected \u201csystemic\u201d response to treatments designed to be \u201clocal\u201d. In the present article the mechanisms of action of HIFU are described, and the main clinical applications of this technique are reported, with a particular focus on the immune-stimulation process that might originate from tumour ablations

Mechanical HIFU and immune checkpoint inhibition: toward clinical implementation

Objective: Immune checkpoint inhibition (ICI) has significantly advanced the field of immuno-oncology, yet not all patients benefit from this therapy. Combining ICI with other therapeutic modalities, including tumor ablation, is currently being explored as a method to enhance ICI efficacy. Mechanical High-Intensity Focused Ultrasound (M-HIFU) represents a promising tumor ablative therapy, inducing cavitation within the tumor, resulting in tumor cell destruction and the release of danger signals and tumor antigens, two key factors contributing to anti-tumor immune responses. Methods/Results: Preclinical studies on the impact of M-HIFU on the anti-tumor immune response are guiding the translational application of this technique in the clinical setting. This review provides a comprehensive overview of the current understanding of the effects of M-HIFU on the immune system. We report on the effect of M-HIFU on soluble immune modulators and immune cells in different preclinical models, and potential contributions to the anti-tumor immune response. We discuss clinical studies applying M-HIFU and studies that have combined ICI with other ablative therapies to draw parallels to clinical implementation of M-HIFU. Further, we will highlight essential questions that should be addressed in future clinical trials exploring the combination of M-HIFU and ICI in the clinical setting. Conclusion: Overall, this review offers guidance for the clinical implementation of combining M-HIFU with ICI and highlights key questions that remain to be addressed in first clinical studies

Overview of Therapeutic Ultrasound Applications and Safety Considerations: 2024 Update

A 2012 review of therapeutic ultrasound was published to educate researchers and physicians on potential applications and concerns for unintended bioeffects (doi: 10.7863/jum.2012.31.4.623). This review serves as an update to the parent article, highlighting advances in therapeutic ultrasound over the past 12 years. In addition to general mechanisms for bioeffects produced by therapeutic ultrasound, current applications, and the pre-clinical and clinical stages are outlined. An overview is provided for image guidance methods to monitor and assess treatment progress. Finally, other topics relevant for the translation of therapeutic ultrasound are discussed, including computational modeling, tissue-mimicking phantoms, and quality assurance protocols

Ultrasound-assisted immunotherapy for malignant tumour

Malignant tumour represents a significant global public health concern. The advent of immunotherapy has brought about a revolutionary shift in the landscape of tumour treatment, offering a ray of hope to patients across the globe. Immunotherapy strategies have demonstrated considerable promise in clinical trials. However, the immunosuppressive environment within the tumour microenvironment has constituted a significant obstacle to the advancement of immunotherapies. It is therefore imperative to develop more efficacious and personalised approaches. The utilisation of non-invasive ultrasound-assisted immunotherapy represents a promising strategy. Ultrasound has the capacity to induce an immune response and stimulate other drugs to achieve a specific response, thereby reducing the toxic side effects of treatment and enhancing the outcome of immunotherapy. This paper presents a systematic introduction to the various mechanisms related to ultrasound and reviews the recent advancements of ultrasound-assisted tumour immunotherapy, including ultrasonic ablation, combined application with contrast agents, and sonodynamic therapy

Transcriptomic Profiling of the Immune Response in Orthotopic Pancreatic Tumours Exposed to Combined Boiling Histotripsy and Oncolytic Reovirus Treatment

Background: Boiling histotripsy (BH) uses high-amplitude, short-pulse focused ultrasound to disrupt tissue mechanically. Oncolytic virotherapy using reovirus has shown modest clinical benefit in pancreatic cancer patients. Here, reovirus and BH were used to treat pancreatic tumours, and their effects on the immune transcriptome of these tumours were characterised. Methods: Orthotopic syngeneic murine pancreatic KPC tumours grown in immune-competent subjects, were allocated to control, reovirus, BH and combined BH and reovirus treatment groups. Acoustic cavitation was monitored using a passive broadband cavitation sensor. Treatment effects were assessed histologically with hematoxylin and eosin staining. Single-cell multi-omics combining whole-transcriptome analysis with the expression of surface-expressed immune proteins was used to assess the effects of treatments on tumoural leukocytes. Results: Acoustic cavitation was detected in all subjects exposed to BH, causing cellular disruption in tumours 6 h after treatment. Distinct cell clusters were identified in the pancreatic tumours 24 h post-treatment. These included neutrophils and cytotoxic T cells overexpressing genes associated with an N2-like and an exhaustion phenotype, respectively. Reovirus decreased macrophages, and BH decreased regulatory T cells compared to controls. The combined treatments increased neutrophils and the ratio of various immune cells to Treg. All treatments overexpressed genes associated with an innate immune response, while ultrasound treatments downregulated genes associated with the transporter associated with antigen processing (TAP) complex. Conclusions: Our results show that the combined BH and reovirus treatments maximise the overexpression of genes associated with the innate immune response compared to that seen with each individual treatment, and illustrate the anti-immune phenotype of key immune cells in the pancreatic tumour microenvironment