If you care about precision medicine, then you care about medical devices. And, in today’s medtech climate, if you care about medical devices, then it is an exciting time to care about ablation platforms. Ablation techniques are minimally invasive, which make them the most viable option for a range of conditions, from targeting difficult-to-access cancers to managing chronic pain or hypertension through selective nerve deactivation. Yet, even with all this potential, ablation modalities are typically not first-line treatments because patient-to-patient variability reduces procedure repeatability. This is exactly where a device that can be tailored to the specific condition of the patient can lead to better procedural outcomes and ultimately benefit the patient. More importantly, this opens the door to make ablation modalities more routine for applications that are near or within sensitive organs.
For the most part, current systems designs do not incorporate our latest understanding of the biophysics; in fact, they are largely based on ablation systems that were developed decades ago. This knowledge, coupled with new sensing technologies, computational-based algorithms, and improved imaging capabilities, provides an opportunity to develop patient-specific ablation devices that could unleash the use of ablation modalities.
Challenges
Efficacy for any ablation modality is often defined as achieving the needed ablation size in the desired location, with minimal collateral damage to healthy surrounding tissue. In interventional oncology this means ablating the cancerous lesion within the needed margin. In neuromodulation applications such as renal denervation, it means precisely ablating the nerves in wall of the renal artery.
While the ablation size and location are common desired parameters, the anatomical location is an important factor since the relevant tissue properties may (and often do) significantly vary. For example, from an electromagnetic and thermal point of view, the properties of lung and liver are significantly different from each other. The surrounding anatomy is another important factor, as an ablation lesion within an organ’s parenchyma is governed by different constraints than if it is near bone anatomy or near other sensitive organs. This means that one cannot take an ablation system and just use it for another indication with only minor modifications. There also is inter-patient variability — for example, the location of the tumor within an organ varies between patients, which could mean that the same ablation algorithm could lead to different outcomes.
What is surprising is that most ablation systems are largely the same, even across indications. Of course there are some variations on the size of the probes and some differences in algorithms. But mainly, most ablation devices are based on simple impedance or temperature end points, along with a few parameters, such as power level and duration of treatment with coarse adjustment settings.
These limitations in system design have made ablations therapies operator dependent — relegating the efficacy of the therapy to the skill and experience of the clinician performing the procedure. Thus many practitioners believe in the utility of ablation, but often are hesitant about using it for treatment in sensitive regions such as the lung or pancreas. Even for applications in which ablation techniques are often used, such as liver cancer, there is a lot of uncertainty about best practices. From personal experience, I’ve spoken with many doctors who have described experiencing difficulty with basic aspects of the therapy, such as patient-to-patient variability impacting one’s ability to discern when an ablation procedure is complete.
Opportunities for future systems
Ablation biophysics
As a first step, we need to utilize our increased understanding of ablation biophysics in designing future systems. As an example, let’s look at thermal-based ablations. There is a lot that can be leveraged from the field of hyperthermia in which the concept of thermal dose, temperature-time relationship, and impact on cell viability is critical to therapy efficacy. As the figure below shows, once exposure temperatures reach above 45°C, cell survival rates significantly decrease.
Yet many clinical systems go upwards of 90°C or 100°C to try to achieve larger ablation sizes, using high temperatures to compensate for poor algorithms and energy modality selection for the indication. However, these high temperatures, that have no biophysical basis, increase the risk of damage to normal regions and increase the cost of the generator. Unfortunately, given that the preferred route for approval is based on a predicate device (e.g., 510(k)), these ‘requirements’ for high-temperatures have been incorporated into a new system design with little scrutiny.
Similarly, in non-thermal ablations such as irreversible electroporation (IRE), it is important to understand the electric field levels and pulse durations that lead to the desired ablation effect. If the specific organ biophysics is not considered, designing a cost effective system will be incredibly challenging.
Precision medicine and patient-specific ablation platforms
When it comes to patient-specific medical devices, and more specifically ablation platforms, the intriguing point is that the needed technology is mostly available. What is really needed, is an integrated design approach that is centered on the biophysics. Oddly enough, the pharma industry that has championed precision medicine much more than medical device companies, has much more significant hurdles to overcome.
A high-level overview of a patient-specific ablation platform could look like the system below. The input would be data from a 3D image (e.g., spiral CT or C-arm CT). This imaging data would then be used to develop a patient model and treatment plan via computational methods that take into consideration the local anatomy, intrinsic tissue properties, and desired lesion size. This patient-specific algorithm, along with a navigation system, would then aid the clinician in placing the probe and conducting the procedure. During the procedure, the ablation would be monitored and used for intraoperative feedback.
How ambitious is such a system? Many of the components already exist in isolation, and aspects are already part of the clinical flow. For example, CT images are routine in the diagnosis and basic treatment planning. And as C-arm technology continues to improve, high-fidelity 3D images will be even more easily accessible.
In terms of treatment planning, much work has already been conducted to rigorously quantify parameters that impact ablation methods such as RF and microwave ablation. This type of analysis could easily be integrated into software that helps doctors plan the correct treatment that is tailored to the patient.
Intraoperative feedback is an essential element in this framework — with the key being the ability to monitor over the intended 3D ablation volume (as opposed to a few discrete points). Device manufacturers currently recommend postoperative CT or ultrasound for ablation therapy assessment. However, imaging of ablation lesions is not intended for intraoperative real-time monitoring. But it is now much easier to integrate a number of small sensors in surgical tools. Another consideration is that some energy modalities such as ultrasound or microwave better lend themselves for dual-use, delivering therapy and real-time monitoring. For example, ultrasound signals can be used to measure temperature or changes in mechanical properties and microwave signals can identify ablation zone boundaries.
Next steps
So what is the path forward for making better ablation platforms? We need to start with the biology-energy interface and use that to set the overall system requirements. The key question is: what do we need to achieve to get clinical efficacy for the specific indication and how can we get more precise by having advance knowledge of the patient’s anatomy? What parameters can we sense and measure that helps improve the precision of the treatment? If we can integrate these aspects, it’s not hard to envision how we can tackle a number of medical conditions with improved patient outcomes.
