Histotripsy is a high-intensity focused ultrasound (HIFU)-based technology that mechanically disintegrates tissue and other material, such as blood clots and large hematomas, into subcellular debris. This is done by using sequences of short, high-amplitude focused ultrasound pulses, generating bubble activity.(3)

There are 2 main types of histotripsy, cavitation cloud histotripsy (CH) and boiling histotripsy (BH). CH uses cavitation clouds made up of microbubbles produced by transient cavitation to disintegrate the target tissue into defined liquefied lesions. BH uses shockwaves with nonlinear propagation effects to heat the target lesion, producing millimeter-sized boiling bubbles. Tissue tearing is facilitated by the shear stress created around the bubbles and enhanced by the incoming shockwaves, leading to mechanical tissue separation. The heat generated remains in one focal area, avoiding any thermal damage to surrounding tissues. While these methods differ, they both show similar treatment effects.(4)

Histotripsy has several clinical advantages compared to HIFU, such as the capacity for real-time treatment. Ultrasound imaging can be used to search for the bubbles associated with this technique and evaluate outcomes based on the loss of tissue structures in the liquefied lesion. Connective tissue structures such as blood vessels are more resistant to mechanical ablations than cells, rendering this technique tissue-selective. Histotripsy can target and eradicate tumors without destroying surrounding structures. Targeting tumors in areas surrounding critical structures such as major vessels or nerves is now possible. The mechanical versus thermal mechanism of this technique results in sharper boundaries and higher treatment precision. Lastly, the liquefied tissue from this technique is reabsorbed by the body within a couple of months, leaving only a small amount of scar tissue behind, which does not interfere with future tumor screening like thermally denatured tissue would.(5)

With the ability to liquefy soft tissue in a noninvasive and precise way, histotripsy is a promising approach for oncology treatment. The recent Food and Drug Administration (FDA) approval of the ultrasound image-guided Edison platform for histotripsy ablation of liver tumors is only the start of what is possible with this technology. Several preclinical trials have found histotripsy to be successful in ablating other tumor types, including prostate cancer, melanoma, neuroblastoma, cholangiocarcinoma, renal cell carcinoma, pancreatic adenocarcinoma, osteosarcoma, and glioma. Slowed tumor growth, increased survival, and reduced metastasis following complete or partial ablation with histotripsy have also been reported.(5)

For patients unable to undergo a surgical procedure, histotripsy also represents a noninvasive, nonionizing, and nonthermal option. While research is still underway for the use of histotripsy in various tumor types beyond the liver, this technology has great potential to improve the treatment of many diseases and improve overall prognosis.(5)

Pulsed electric fields (PEF) were first used to introduce cytotoxic agents into cancer cells.6 PEF-based therapies harness electric fields to produce therapeutically beneficial effects. The PEF technique consists of ultra-short pulsed electric fields of high amplitude for a short period of time.(6,7)

There are several types of PEF therapies, including irreversible electroporation (IRE), gene electrotransfer (GET), electrochemotherapy (ECT), calcium electroporation (Ca-EP), and tumor-treating fields (TTF).(6) PEF therapies induce transient (reversible) or permanent (irreversible) cell electropermeabilization depending on the electric field strength. Transient electropermeabilization allows for the passage of nucleotides, ions, or even chemotherapy drugs. Permanent electropermeabilization results in the destruction of cell integrity.(6) Due to the lack of thermal heat generated from these electrical signals, the tissue surrounding the tumor is preserved.(7) TTF have also been shown to stimulate autophagy, delay DNA repair, and induce antitumor immunity when targeting cancer cells in preclinical studies.(6)

These techniques offer several advantages to traditional methods of surgery or systemic treatment, including lower morbidity, increased tissue preservation, reduced costs, and shorter hospital stays.6 PEF can be used alone or in combination with genetic material, chemotherapy, or calcium, allowing more variety in the treatment strategy. In addition to these advantages, this technique has been used successfully in a wide range of indications.(6) Almost every tumor site in a human body can now be targeted safely with a PEF-based therapy, including tumors in the brain as this technique is able to temporarily disrupt the blood-brain barrier.6 For example, studies have shown that PEF is a promising treatment for glioblastoma multiforme, the most common and lethal brain cancer in adults, which often has poor outcomes when treated with other therapies.(7)

PEF-based therapy is a highly effective treatment strategy for patients who cannot undergo radical surgery, showing outcomes such as increased local control, improved quality of life, and even survival in addition to the clinical benefits observed. Overall, PEF represents a clinically effective treatment option that is minimally invasive, selective in targeting tumor cells, and stimulates the immune response. With the potential to treat multiple tumor types and be combined with other treatments, PEF-based therapies show great promise within the field of oncology.(6)

Transarterial radioembolization, also known as selective internal radiation therapy (SIRT), involves the selective, minimally-invasive delivery of microspheres loaded with a radioactive compound, Yttrium-90. Yttrium-90 is a pure β emitter that has a short half-life and limited tissue penetration.(8) When delivering these microspheres to liver tumors, radioembolization can move directly through the arterial supply, resulting in concentrated internal radiation therapy.(9)

There are 2 main types of microspheres used in this process: the glass TheraSphere® and the resin Sir-Spheres®. While these 2 types of microspheres differ in size, activity for each individual bead, and number of microspheres injected, both methods have been shown to be equally effective.(8)

While this technology has been used to successfully treat hepatic neoplasia, innovative improvements over time have been limited.(10) Resin microspheres provide flexibility in the quantity and activity administered by using a dose-draw from a parent vial. However, this flexibility comes with the price of an additional burden placed on operators. Glass microspheres lack flexibility with the customization of quantity and activity delivered. In addition, neither existing glass nor resin microspheres are directly visible on x-ray imaging. Thus, post-treatment detection via single photon emission computed tomography or positron emission tomography of radiation emission is required to assess microsphere distribution, confirm tumor targeting, and evaluate liver/tumor absorbed dose estimates.(10)

Recently, an investigational radiopaque Yttrium-90 glass microsphere (Eye90®) was given a breakthrough device designation from the FDA. These radiopaque microspheres allow for direct visualization of accumulated microsphere distribution through computed tomography (CT) imaging by including imageable elements in the microspheres. This allows for accurate tumor targeting and the potential to adjust treatment through microcatheter repositioning in real time using Hybrid Angio/CT and potentially Cone Beam CT. The administration system of Eye90 has a continuous or start/stop methodology and allows for the ability to modulate delivery speed and amount of radioactivity.10 Beyond the real-time feedback, Eye90’s radiopacity retention within tumors could act as a biomarker, informing follow-up treatment decisions.(10)

Radioembolization has already been established as a minimally invasive, precise, safe, and effective treatment of liver tumors. With the introduction of radiopaque Yttrium-90 glass microspheres, treatment can be better customized to each individual patient’s needs. With real-time imaging capabilities, tumor targeting is more accurate, and treatment can be immediately adjusted. Research is still underway on a larger scale to further evaluate the effectiveness of this technique.(10)

For many patients with various types of cancer, liver metastases represent the sole or predominant site of disease progression. Many of these metastases are unresectable and represent a significant therapeutic challenge. If primary metastases are confined to the liver, targeted therapy has the potential to target chemotherapy to the tumor-bearing tissue without inducing systemic toxicity. This technique has evolved over time, moving away from a highly invasive open surgical procedure to a minimally invasive procedure.(11)

Isolated hepatic perfusion (IHP) was first applied over 60 years ago to treat liver metastases.(12) This is a highly invasive procedure involving temporary surgical isolation of the hepatic circulation and delivery of high-dose cytotoxic chemotherapy through the hepatic artery.(13) Vena cava circulation is bypassed through a veno-venous shunt from the femoral vein to the external jugular vein. Using laparotomy, the liver is isolated from systemic circulation and a catheter is positioned in the proper hepatic artery. Another catheter is positioned in the infra-hepatic caval vein. Each catheter is connected to a heart-lung machine while the liver is perfused with high-dose chemotherapy.(12)

Percutaneous hepatic perfusion (PHP) is a minimally invasive technique that was developed to reduce the morbidity and mortality associated with IHP. One catheter is percutaneously placed in the proper hepatic artery to allow the infusion of chemotherapy. Another double-balloon catheter is placed in the inferior caval vein, preventing potential leakage to the systemic circulation. Between these balloons, the catheter aspirates blood coming from hepatic veins, running it through an extra-corporeal filtration system before it returns to the patient via a third catheter placed in the jugular vein. In addition to PHP providing better outcomes, the length of the procedure is reduced compared to IHP. PHP can also be repeated if needed.(12)

PHP is especially important in the treatment of metastatic uveal melanoma. With a prognosis of just 1 year and survival rates of less than 25%, there are no effective systemic treatments for this disease.(13) Studies have shown that while IHP and PHP show similar survival data for patients with liver metastases from uveal melanoma, PHP can allow patients to potentially have a lower risk of complications and mortality following the procedure.(12)

Despite advances in immunotherapy and targeted therapies, pancreatic cancer remains extremely difficult to treat. Patients with pancreatic cancer have a 5-year survival rate of 11%. For those with localized early-stage disease, surgery remains the most viable option. Chemotherapy is used in more advanced and/or metastatic cases. The majority of patients present with an advanced stage of pancreatic cancer and often have liver metastases as well.(14)

Pancreatic tumors are difficult to target and treat due to their intra-abdominal location and surrounding vital structures. Delivering treatment to pancreatic tumors via the arterial blood supply has been suggested as a potential approach. Intra-arterial (IA) delivery represents a minimally invasive, image-guided delivery of chemotherapy directly to a tumor. IA-delivered chemotherapy has several advantages over traditional intravenous (IV)-delivered chemotherapy, including bypassing systemic toxicity, first-pass metabolism, and non-target delivery. This technique was not possible until recent advances in microcatheter technology and imaging equipment, which now allow access to the complicated arterial blood supply of the pancreas. Now, IA-delivered chemotherapy is a possibility for the treatment of pancreatic cancer.(15)  

A similar technique has been studied in animal models, particularly for pancreatic ductal adenocarcinoma (PDAC). While IA-delivered chemotherapy can be an option for pancreatic cancer, it is sometimes unable to penetrate the thick barrier of a PDAC tumor. In addition, PDAC tumors are supplied by smaller arteries that have limited perfusion capacity. Pancreatic retrograde venous infusion has been proposed as an alternative treatment for this disease, potentially improving the delivery of therapy while reducing off-target toxicity. A microvalvular catheter pressurizes the venous drainage, allowing for this retrograde infusion to occur directly into the tumor vasculature. The technique described is known as Pressure-Enabled Drug Delivery (PEDD),(16) and the combination of delivering chemotherapy in a transvenous route with PDAC, combined with PEDD, has the potential to resolve some of the unmet needs remaining with the IA approach. This is a promising technique within pancreatic cancer, possibly improving selectivity, isolation, and perfusion of target tumors within the pancreas. While this is a new technique for pancreatic cancer, this methodology has been used in other organ systems with limited arterial access.(16)

Treatment of pancreatic cancer, with and without metastases, remains an unmet need within the field. The goal of therapy is to increase overall survival and improve disease-related symptoms and quality of life.(17) Further research is needed to improve survival of this challenging disease.

Minimally invasive procedures such as percutaneous biopsy and ablation have replaced the need for surgery for many eligible patients. However, the success of these procedures requires accurate needle placement, which can be a challenge for less experienced operators. Tumor visualization, location, and proximity to other structures can all impact one’s ability to target a particular tumor. To compensate for these issues, operators often need to make frequent needle adjustments and extend the procedure time, increasing the risk of complications and exposure to radiation for both patients and physicians.(18) Despite these challenges, percutaneous procedures are widely used for their clinical effectiveness and safety.

Robotic systems have been developed over the past few years in an effort to overcome some of the potential challenges associated with these procedures. The goal of robotic systems in interventional oncology is to provide an accurate, reproducible, and time-efficient approach to these procedures while minimizing the amount of exposure to radiation. Thus far, studies have shown that robotic systems have the potential to achieve all of the above, in addition to decreasing the learning curve associated with the protocols of these procedures.(18)

Epione (by Quantum Surgical), for example, is a commercially available, floor-mounted robotic system compatible with commonly used imaging systems. Physician operators can use the robot to complete their preferred ablation technique. Epione is equipped with 2- and 3-dimensional software, allowing for better visualization of the target area. The robot is registered to the patient and synchronized with a respiratory monitor, and the robotic arm follows the path to the entry site. The physician operator is then able to manually advance the probe.(18)

Robotic interventions have been studied in multiple phases of development. Some of the procedures studied beyond biopsy and ablation include drainage, vertebroplasty, drilling of osteochondral lesions, percutaneous pelvic fracture fixation, nerve and facet blocks, and neurolysis.(19) Robotic interventions ensure minimally invasive, accurate, and reproducible targeting of tumors. Less pressure is placed on the operating physician, as the robotic system can guide the needle accurately to its destination.(18) This intervention is especially interesting as it can be operated remotely, depending on the system and the role of the operator.(19) Several robotic systems are available for clinical and commercial use, rendering this intervention less experimental and more mainstream within the field of interventional oncology.(18)

There are several types of embolization agents, including mechanical, particles or gelatin, and liquid or gel-based. The clinical context, vessel size, durability, and preference of the operator all determine which agent to use.(20)

Originally, liquid embolics were used for the embolization of intracranial arteriovenous malformations. Since liquid embolics can penetrate more deeply into tissues, this class of embolics has been used increasingly more often.(2) For reference, catheters and coils often cannot penetrate as deeply into the vascular bed as liquid embolic agents can.(20) Liquid embolics solidify during administration, form a cast that molds vessels, and block blood flow to the targeted tissue. This process induces ischemia in the targeted tissue. The degree of penetration can be controlled with the viscosity or properties of the embolic used. Unlike other classes of embolic agents, these agents are also able to function independently from a patient’s own coagulation process and can be used in patients with clotting disorders.(2)  

Two well-known liquid embolics include Lipiodol and Hydrogel. Lipiodol is a well-established liquid embolic used in transarterial embolization or in combination with chemotherapy in transcatheter arterial chemoembolization (TACE). It has the ability to act as an emulsifier for drugs, penetrate deeply within the tumor microvasculature, and serve as a contrast agent for fluoroscopy.(2) It is also radiopaque, allowing the distribution of the drug to be assessed radiologically.(20) Research is underway to expand its clinical use.(2)

Hydrogel (Instylla HES) is unique in that it consists of two low-viscosity precursors (polymer and initiator) that solidify when combined in the blood, forming a soft hydrogel cast in the downstream vasculature.(2) In the first-in-human, pilot study of HES for a variety of hypervascular tumors, technical success was achieved in 100% of patients. Administration of the agent was determined to be convenient, and any toxicities observed were mild.(21)

More traditional liquid embolics can be challenging to use due to potential side effects, and they often require experienced operators to avoid catheter blockage/trapping. Traditional liquid embolics can also induce vascular injury and inflammation. However, novel liquid embolic agents are currently at various stages of development, including hydrogel-based agents. These agents are more tolerable as they form a gel-like cast which results in little vascular irritation or toxicity. Liquid embolic agents have the potential to be used for peripheral and neurovascular embolization as well as more specialized embolization such as TACE.(20)

With the increasing importance of immunotherapy over the past several years, there has been an effort to determine how to deliver these agents directly to the target tumor, to increase the response rate among patients and avoid off-target toxicities. The direct inoculation of these immune-stimulating agents into the target tumor is known as intratumoral immunotherapy.(22)

Intratumor injections allow the therapeutic effects of immunomodulatory therapies to be maximized while reducing systemic effects. In this technique, the target tumor acts as its own vaccine, enhancing the pre-existing antitumor immune response. Intratumoral immunotherapies can be administered by direct or image-guided injections. The quality of delivery is often dependent on the physician operator.(23) Dosages can depend on the size of the tumor, the overall burden of the tumor, or the patient’s weight.(22)

There is a plethora of intratumoral therapies currently undergoing research. Intratumoral gene therapy has been explored, with intratumoral electroporation of the interleukin (IL)-12 gene being shown to be safe and effective within the metastatic disease setting, even showing antitumor effects. Intratumoral administration of antibodies to various tumor types is being investigated. Combination therapies are also being explored, mostly investigating the combination of intratumoral immunotherapy with other treatment modalities in patients with advanced disease.(22)

Intratumor injections are increasingly being studied within the neoadjuvant space.(22) After all, the efficacy of localized immunotherapy is expected to be higher in patients with early-stage cancer.(23) Recent trials evaluating intratumoral immunotherapy for neoadjuvant treatment have utilized ex situ dendritic cell vaccines, sometimes in combination with radiotherapy. Cell-based vaccines such as this are labor- and resource-intensive, and while results thus far have been positive, in situ administration may offer advantages.(22)

Intratumoral and tumor tissue-targeted immunotherapies have the potential to improve outcomes and reduce the toxicity profile associated with immunotherapy, especially when used as neoadjuvant therapy in patients with locally advanced, resectable tumors.(23)

Starting out with foundational work in the fields of ophthalmology, radiology, and dermatology, AI has since expanded into oncology. One of the earlier applications of AI involved supporting physician-led risk prediction and diagnosis, including AI-based pathology. Now, AI has applications ranging from drug discovery, development, and dosing within the field of oncology.(24)

One of the most common applications of AI within oncology is the analysis of digital images. Images can be subject to interpretation, and certain features within an image may be undetectable to the naked eye.(25) AI-based algorithms, particularly deep learning algorithms, can analyze imaging data and aid in disease classification, detection, segmentation, characterization, and monitoring. For interventional oncologists, these applications can aid in patient selection, pre-procedural planning, and predicting response to treatments.(26) Future development of cancer can also be predicted from normal scans using deep learning models.(27)

AI can assist in the interpretation of data collected through electronic health records (EHR) and other systems, which may further enhance patient selection for procedures. EHR data is processed by AI-based natural language processing algorithms, enabling researchers to identify trends and patterns within the data.(27)

Large language models (LLM) are increasingly being used with the development of ChatGPT. These LLMs can converse with patients, researching and responding to their medical questions, which serves to augment patient-facing care and enhance the patient experience in interventional oncology and all medical fields.(25, 26)

Virtual reality creates the perception of being immersed in a virtual space, usually via a head-mounted display. Virtual reality can play an important role in education and training, allowing remote users to observe procedures and ask questions in real time. Augmented reality differs from virtual reality in that it overlays virtual objects in a real-world environment using a specialized lens or display. Virtual images of anatomy can be superimposed over real-life patients to aid in navigation. For instance, augmented reality can be especially helpful during percutaneous interventions, helping physicians achieve more accurate needle placement.(1)

While AI provides an endless number of opportunities within the oncology field, there are several considerations to be addressed. Ethical and legal considerations have arisen related to the issue of patient privacy with data collection, as well as the protection of sensitive patient data from theft. The validation of AI methods is essential in confirming the accuracy and generalizability of results. Implementation of AI methods into the current workflow may require additional thought and planning.(24)

All these advancements move providers closer to the goal of optimal patient care. In a field like interventional oncology, it is ever important to keep aware of the progression of new technologies and emerging techniques. By learning about advances in precision oncology, immunotherapy, advanced imagining, artificial intelligence, robotics, and more, interventional oncologists can ensure they are offering their patients the best and most up-to-date treatment and care.