Radiotherapy and surgical ablation technologies for cancer treatment

What is radiotherapy?

Radiotherapy falls within the group of ablation therapies used for cancer treatment as minimally invasive alternatives to traditional surgery, where surgical intervention may not be feasible or is of high risk. The approach is based on the principle of destroying tumor tissue using targeted energy sources.

Radiotherapy can be delivered externally using high-energy particle beams, such as X-rays or protons or internally through brachytherapy, where sealed radioactive sources (seeds) are placed near the tumor using catheters or needles. When biological tissue is irradiated, atoms and molecules may be ionised, resulting in DNA damage within cells. This in turn can inhibit their ability to divide and grow or cause cell death by apoptosis.

A common external radiotherapy technique is stereotactic body radiation therapy (SBRT), which allows for high radiation doses due to its precision, achieved through a three-dimensional coordinate system and real-time imaging that accounts for patient movement.

Patient undergoing imaging for cancer treatment

Innovations optimizing radiotherapy

Radiopharmaceuticals and theranostics

Targeted radiopharmaceuticals represent an emerging class of therapies that integrate diagnostic and therapeutic functions, often referred to as theranostics. These treatments involve radioactive isotopes attached to targeting molecules that selectively bind to tumor-specific markers. Once administered systemically, these radiopharmaceuticals preferentially accumulate in tumor cells. Any unbound material is naturally expelled by the body, minimizing unnecessary exposure to healthy tissues. Depending on the radiopharmaceutical design, a single drug can emit two types of radiation:

• Primary radiation – such as beta or alpha particles, that causes direct damage to tumor DNA and leads to cell death.
• Secondary radiation – in the form of gamma rays, which may not cause tissue damage but instead can be detected using PET imaging or handheld gamma cameras to assist surgeons in locating tumors during procedures.

One notable advancement in radiopharmaceuticals is the SENSEI system. SENSEI® is a miniaturized gamma probe developed for use in minimally invasive and robot-assisted surgeries. It provides real-time guidance to surgeons by detecting gamma rays from radiopharmaceuticals tagged to cancer cells. Solutions such as these highlight the potential for radiopharmaceuticals to have accurate and practical applications in cancer treatment.

Adaptive radiotherapy

Operative planning for radiotherapy is usually based on medical images taken weeks before treatment. As time passes, tumor and body changes can render this information outdated, reducing precision and potentially affecting outcomes. Adaptive radiotherapy (ART) addresses this by allowing for treatment to be changed to respond to additional information before or even during treatment.

Systems like the RefleXion SCINTIX therapy exemplify the ART approach by combining PET imaging with radiotherapy. SCINTIX® detects tumors in real-time using radiopharmaceuticals to determine where and how much radiation is delivered second-by-second.

Modernizing traditional brachytherapy

Brachytherapy, a procedure which involves placing a radioactive material near to the treatment area, continues to be a critical adjuvant treatment for several cancers. Interstitial brachytherapy seeds have proven to be particularly effective in treating residual disease and reducing local recurrence after surgery.

Despite its efficacy and cost-effectiveness, brachytherapy has seen a decline in use. One reason for this is the challenge of adapting the process to minimally invasive surgical techniques. Traditionally, radioactive seeds are hand-sewn into tissue during open surgery, which poses exposure risks to the surgeon and is incompatible with minimally invasive approaches.

New tools are in development that are helping to modernize brachytherapy. For example, BrachyClip® is enabling radioactive seed placement via minimally invasive surgery. The innovation uses a clip attached to a seed holder tube and a suitable applicator that can be deployed manually, laparoscopically or robotically.

Surgeons performing minimally invasive surgery

Addressing challenges in radiotherapy technology development

When developing technologies that use radiotherapy approaches, there are several challenges that must be addressed – including manufacturing and laparoscopic compatibility.

Alpha-emitting radiopharmaceutical manufacturing

Alpha-emitting radiopharmaceuticals are emerging as powerful tools in cancer treatment, particularly for small tumors, due to their high-energy radiation that causes direct DNA damage.

New technologies currently in development, including ARTBIO’s ground-breaking class of alpha radioligand therapies, present potential to enhance effectiveness of cancer treatment.

Unlike beta emitters, which spread radiation over millimetre distances, alpha particles deliver concentrated energy within micrometres, enhancing effectiveness against micro-metastatic lesions. However, manufacturing alpha radiopharmaceuticals presents significant challenges, including:

• Specialized production requirements – complex separation of alpha-emitting isotopes from co-produced isotopes, often involve gas and liquid phase purification and specialized medical devices for manufacturing, ensuring proper sealing and safe handling.
• Short half-lives – ranging from hours to days, alpha-emitting radiopharmaceuticals demand efficient supply chains to maintain potency at the point of care, posing logistical hurdles. On-site manufacturing instrumentation could be a solution, yet safety and regulatory issues remain barriers.

Expanding access to these promising therapies will require overcoming complex production and logistical challenges.

Stability and laparoscopic compatibility of brachytherapy

Brachytherapy offers localized radiotherapy, but challenges arise in ensuring the stability of implant seeds within the tumor. The seeds must be securely implanted close to the affected area as permanent fixtures. Various tissue types and geometries complicate this process. Additionally, the radiation emitted by the seeds can alter the surrounding tissue structure, potentially compromising their attachment and effectiveness over time.

Developing advanced anchoring medical devices that adapt to changes in tissue properties may provide a solution to maintain the seeds’ position effectively. These devices could include bioresorbable scaffolds, magnetic or shape-memory alloys that adjust to environmental conditions, or flexible anchors that integrate with tissue over time.

The transition to laparoscopic procedures introduces additional complexities, particularly due to the constraints of small port diameters. This complicates the design of effective medical devices for delivering the brachytherapy laparoscopically, which would need to be capable of securing multiple seeds while ensuring robust mechanical performance.

When designing such laparoscopic tools, structured analysis is an effective way to optimize the device architecture within the confines of the port diameter. This analysis should focus on ergonomic factors, material properties and mechanical performance. From this developers can understand how the device can be both compact and flexible, maintain durability under stress and adapt to the dynamic conditions of the body to help inform the device design.

Surgeons performing laparoscopic procedure

Alternative ablation therapies for cancer treatment

Beyond radiation ablation (radiotherapy), alternative ablation therapies are increasingly being employed for cancer treatment as another option from surgery. These therapies use energy sources that damage tumor tissue via heat, extreme cold or mechanical effects.

Thermal ablation techniques kill cancer cells using either heat or cold. The most common ablation methods using heat include:

• Radio-frequency ablation – using electrical currents
• Microwave ablation – using electromagnetic microwaves
• Laser ablation – using light
• High-intensity focused ultrasound ablation – using ultrasound waves.

The ablation method using extreme cold is referred to as cryoablation. Cryoablation temperatures can reach as low as -180°C, with the most common methods based on extreme cooling, generated either by:

• rapid argon gas expansion in a narrow probe or
• the phase change of liquid nitrogen from liquid to gas.

Ablation therapies are carried out using a specialized probe delivering the necessary energy to the tumor through a small incision or needle puncture. The size of the incision is usually very small—typically just a few millimetres—since the ablation probes are thin.

While ablation therapies effectively treat certain cancers such as lung cancer, accuracy during treatment can be complex. The non-specific nature of the ablation effect means that healthy cells and structures may also be affected, making precise targeting and movement control crucial to minimize collateral damage.

Tumors vary in shape, size, consistency, microenvironment and surrounding structures, with their correlation to dosing and ablation outcomes not yet well understood. Traditional dosing approaches are largely empirical, relying on established practices and clinical judgment, which can lead to inconsistent treatment outcomes. The lack of comprehensive feedback data to monitor the extent of damage during ablation makes it challenging to determine and optimize dosing effectively.

Surgeon preparing for a radio-frequency ablation procedure with small needle/electrode

Streamlining ablation therapies

While ablation therapies are effective for treating certain cancers, accurately controlling treatment delivery presents several challenges. Often, multiple probes and complex placement procedures are necessary, along with difficulties in personalizing the ablation dosing regimen. Additionally, intraoperative variability, particularly due to heat-sink effects associated with thermal-based methods, makes the process less user-friendly for clinicians. The success of these procedures frequently relies on individual clinicians’ skill and experience, highlighting the need for improved control.

Recent technological innovations are addressing these issues through various approaches such as developing non-thermal ablation modalities and integrating real-time feedback systems.

Non-thermal ablation modalities

Histotripsy, a non-invasive ultrasound technology, uses acoustic cavitation to mechanically destroy tissue without relying on heat. This process avoids the challenges associated with thermal ablation including, non-selective damage to cellular and non-cellular structures and heat sink effects which reduce ablation effectiveness near large blood vessels.

There is evidence to suggest that the mechanical nature of histotripsy could allow for selective tumor damage by exploiting differences in tissue tensile strength, sparing vital structures like blood vessels. It can also stimulate immune responses, which may enhance cancer treatments. Histotripsy-generated cavitation is also detectable via standard ultrasound, making it ideal for dual-purpose systems. For instance, Histosonics’ Edison® platform offers high-precision histotripsy with real-time ultrasound imaging feedback, representing a breakthrough in non-invasive surgery.

Irreversible electroporation (IRE) is another non-thermal ablation method with similar advantages. Angiodynamics’ Nanoknife™ system uses needle electrodes to deliver high-voltage pulses that create irreversible nanopores in cell membranes, leading to cell death while preserving the extracellular matrix and crucial structures. This system minimises collateral damage to healthy tissue, enhancing patient safety.

Real-time feedback systems

Employing real-time feedback systems that characterize tissue enables monitoring of the ablation effectiveness and optimization of dosing in a more automated, dynamic way, improving the efficacy of ablation systems.

Continuous monitoring of tissue temperatures enables clinicians to minimize damage to surrounding healthy tissues while maximizing the ablation effect on tumors, by either allowing clinicians to adjust parameters “on-the-fly” or self-modulating dosing to achieve optimal outcomes.

The Exablate Prime™ system from Insightec integrates magnetic resonance (MR) thermometry with ultrasound ablation, allowing for real-time monitoring of tissue temperature during procedures. Similarly, the DiamondTemp™ radiofrequency ablation catheter by Medtronic provides real-time tissue surface temperature measurement using temperature-sensing thermocouples.

Techsomed’s BioTrace™ technology (BioTraceIO) is a software solution that provides ablation feedback for any thermal ablation method based on standard ultrasound imaging. A recent study suggests that the software also accurately predicts the ablation zone as visualized in ultrasound 24-hours post-procedure, providing information about size and shape based solely on imaging that correlates with CT information.

Ablation feedback system development

Implementing comprehensive real-time feedback systems that can be integrated with ablation medical devices is crucial for accurately monitoring tissue damage. One potential approach for thermal ablation monitoring is to focus on thermometry, which tracks thermal propagation during the procedure.

Thermometry-based feedback systems are valuable because they enable more consistent and adaptive dose delivery. By dynamically adjusting energy input based on real-time thermal information, these systems can help normalize treatment across heterogeneous tumor environments and inter-patient variability, ultimately enhancing the precision and safety of ablation procedures.

Thermometry based real-time ablation systems though present limitations as they rely on converting temperature reading into necrosis measurements though predetermined models, which may not universally apply to all cases. Different tissues exhibit varying degrees of tissue injury dependent on a variety of ablation parameters such as temperature, exposure duration, thermal cycles and heating/cooling rates. Factors such as tumor size and surrounding tissue further complicate this relationship, highlighting the need for a more accurate assessment of tissue damage beyond temperature readings alone. Thus, there is a critical demand for imaging-based lesion indexing methods that directly reflect the formation of tissue necrosis.

The ideal solution would incorporate real-time monitoring of tissue damage during procedures, referred to as necrosis feedback (NFB). Although technologies for real-time necrosis monitoring are not yet available, promising solutions are being researched, such as photoacoustic (PA) imaging.

In this technique, tissue is exposed to a laser pulse, and the absorbed light energy is converted into heat, producing an acoustic wave that is detected by an ultrasound transducer. The resulting signal reflects the optical absorption properties of the tissue’s chromophores—molecules like hemoglobin, melanin, water and lipids, which absorb light at different wavelengths. Because ablation alters the tissue’s composition and structure, it also changes these absorption properties. As a result, the detected signals differ between ablated and non-ablated tissue, providing a way to distinguish between them based on changes in optical absorption.

Clinicians monitoring imaging scans

New approaches to radiotherapy and ablation technologies are rapidly evolving to enhance precision and minimally invasive cancer treatments. Innovations in adaptive dosing, theranostics, brachytherapy and real-time feedback, could be the tools to improve patient outcomes compared to traditional cancer surgery.

The future of cancer care lies in smarter therapies that maximize tumor control while minimizing healthy tissue damage.

This blog is part of a series on “The future of oncology – medical technologies that are transforming cancer treatment”. Read the blog on innovations in surgical oncology and look out for our upcoming blog on targeted intratumoural drug delivery.