Interview with Dr. Sharma

Good morning, Dr. Sharma! Thank you very much for joining us today. Based on the resent FDA approval under a Humanitarian Device Exemption for the treatment of osteoid osteoma, I’d like to talk with you about your experience, the disease, your trial results, and how MR Guided High Intensity Therapeutic Ultrasound can make a difference for patients.

Good morning Hartmut thanks for giving me the opportunity to speak with you today and I’m happy to discuss all of those things.

Absolutely, great! Let’s get started then.

So, first question, can you briefly introduce yourself and provide a little bit of background on MR Guided High Intensity Focused Ultrasound, MR HIFU?

Sure, my name is Karun Sharma, I’m the Director of Interventional Radiology here at Children’s National Hospital in Washington DC. I’m also the associate director for clinical translation for our Sheikh Zayed Institute for pediatric surgical innovation.

MR HIFU as you know basically combines an MRI scanner to identify a target or target tumors in our case, and an extra corporeal ultrasound transducer. The extra corporeal transducer generates ultrasound waves that can be focused on targets that are selected based on the MRI imaging. The energy of the sound waves is focused and focused to a point and generates enough heat to thoroughly ablate the target.

Because the ultrasound transducer is external to the body, the treatment is completely non-invasive and also because the guidance is provided by MRI rather than X Ray or CT it’s also radiation-free.

I was first introduced to this technology in 2008 when I was working at NIH in Brad Woods Lab, and at that time, we were looking at uterine fibroid embolization and ablation and looking at doing a trial comparing the radiology findings and the pathology of uterine fibroids. But we started the beginning, even back then thinking about pediatric applications, especially in the pediatric oncology space. And when I moved to Children’s National, we were fortunate to have this on a lead system here and I’ve been working with that to treat patients on a clinical trial since about 2014.

Thank you. Let’s talk now a little bit about the disease. What is Osteoid Osteoma, it’s symptoms, and how does it impact children and young adults living with it?

Sure, so osteoid osteoma is a benign but painful bone tumor, and as you suggested it occurs mostly in children and young adults. It’s a relatively rare condition, but it does account for about 10% of all benign bone tumors. Here at Children’s, we typically see about six to ten patients per year. And the hallmark of this benign tumor is that it causes localized pain, pain that is not associated with trauma in children and typically this pain is worst at night and interferes with their sleep. And because it interferes with their sleep, it also interferes with their daily activities, including school and schoolwork and physical activity and participation in sports.

In the past it was treated generally with something called radiofrequency ablation.

And even going back further before so about the 1990s it was actually treated with surgical resection where we would take out the focus or the nidus of the osteoid osteoma.

That was a little bit more invasive and involved some collateral damage to the overlying tissues, such as muscle, connective tissue and bone.

And then, in the 1990s, there was a technique introduced called radiofrequency ablation.

With radiofrequency ablation we typically place a patient on the CT scanner to visualize the osteoid osteoma and then use a bone drill to place a needle – a special needle called a radio frequency probe into the osteoid osteoma nidus and essentially burn it from the inside.

Okay, thank you. And in that context, so how can MR HIFU improve therapy outcomes and minimize complications and why is MR guidance so beneficial?

Well, that’s a good question too. You know, our guiding principle in Sheikh Zayed and in our surgical institute, is to is to really minimize and make treatments and surgeries less invasive.

Another guiding principle in radiation and pediatric radiology is really to minimize radiation exposure to children. So, we’re bringing together in MR HIFU these two sort of guiding principles, to really minimize radiation exposure to the patient and also to perform a treatment that is non-invasive and really minimizes the risk of collateral tissue damage.

In 2014 or so we began our MR HIFU program thinking about clinical applications in pediatrics and osteoid osteoma was at the time a very relevant application, one that we could begin to translate into the pediatric population. And, although we had been doing radio frequency ablation for several years at the time, we wanted to move towards something that was more non-invasive so we’re moving from minimally-invasive radiofrequency ablation to completely non-invasive MR HIFU.

Great! Now a little bit about your findings from your pilot trials, so can you describe the results and findings from your osteoid osteoma trial?

Sure sure, so in our osteoid osteoma trial, the pilot trial that we perform, we treated nine patients and we found that MR HIFU was safe in all nine patients, without any serious adverse events and we followed these patients up initially close, closely for 12 months and we found that there was complete pain relief, without any further medication use in eight of nine patients.

Although one patient did have a recurrence after one year, the same patient had previously failed radiofrequency ablation and surgery as well, so that patient may have been a bit of an outlier.

And one other patient had partial relief early on and that was because the osteoid osteoma was within the bone at a deeper area so intermedullary osteoid osteoma.

We also contacted these patients for at about five years after treatment and found that all of the patients who had complete response at one year also continued to have complete response at five years. And they no longer we’re taking any medications and they were back to their usual activities, including sports and schoolwork and some in their jobs now.

Excellent. So, can you provide maybe an example on how MR HIFU has changed the lives of patients and their families?

Sure, I think I think there are several children that we followed up with who are even now, five years later, not so young anymore. But I think complete pain relief without interference in their sleep and without interference in their schooling and sports activities and so on, participating in physical education classes and getting back to swimming, for example, and in a couple of patients and other sports where things that the osteoid osteoma patients, at least, I feel we’re happiest about that’s what they commented to us.

For the younger patients that were in our trial, their parents and the patients were extremely happy that they no longer had to take pain medication and that they were able to sleep throughout the night, without waking up.

These are the sort of things that I think – and you know, this treatment for osteoid osteoma, although it is not a malignant tumor, has a lot of beneficial effect on quality of life for these patients.

Great, thank you. What is the cost structure of MR HIFU in comparison to standard of care?

Well, Hartmut, that’s an interesting question. We are still not – it’s a question that still needs to be answered completely. What I can tell you in based on our clinical trial, and also the experience of others, is that MRI scanner time is usually more expensive than CT scanner time, which is where we do the radio frequency ablation.

However, with MR HIFU we do not have the high cost of disposable equipment, such as the bone drill and the radiofrequency ablation probe. In our preliminary look at this, it seems that the estimate suggests that the cost between MR HIFU and CT guided radiofrequency ablation should be fairly similar all things being equal, but this really does need to be evaluated in a systemic way. And in our next phase trial, which is our pivotal trial of 30 patients, we will be paying special attention to the cost structure.

Excellent, thank you. Can MR HIFU replace the current standard of care treatment options and becoming a mainstream treatment modality for symptomatic osteoid osteoma in your perspective?

Yeah, let’s look back a little bit for a longer term and a historical perspective for that one. I think approximately 30 years ago if you looked at definitive therapy for osteoid osteoma, that definitive standard of care was surgical resection. Then, when radiofrequency ablation was introduced, it has gradually replaced open surgical resection, and today, that is the current standard of care.

I think that with the advantages that we have with MR HIFU once again the lack of radiation exposure, the completely non-invasive nature of the therapy, and also the fact that we can be a bit more precise with MR HIFU and RFA because we use something called MR thermometry to really show us precisely where the heating is occurring and keep it focused on the osteoid osteoma and away from the surrounding structures. I believe that this has the potential to maybe in the next decade replace radiofrequency ablation.

There are currently some challenges with device availability. But once those are sort of overcome, I think that it could very well replace needle-based ablations.

Excellent. Dr. Sharma last question – outside of osteoid osteoma therapy, what are the current endeavors and next steps of the Children’s National Hospital MR HIFU Program?

Right, so the MR HIFU team here at Children’s National is moving beyond Osteoid Osteoma to other clinical applications that are important in pediatrics, and these include metastatic bone and soft tissue tumors. Especially those that are relaxed or refractory to immerse and they don’t have any other great treatment options.

For these tumors were using not only the thermal ablation capability of HIFU, but also other HIFU modes and biomechanisms such as, hyperthermia, mild hyperthermia, to facilitate a targeted and enhanced drug delivery to the tumor, as well as a mechanism known as, histotripsy or mechanical tissue fractionation to enhance – cancer immunotherapy. We also hope to move into MR HIFU brain applications in the pediatric population to treat certain forms of epilepsy and certain brain tumors as well.

Dr. Sharma, thank you very much for this very interesting conversation. It’s really impressive to hear what you have accomplished so far at Children’s National Hospital, and that the treatment of osteoid osteoma with MR Guided high Intensity Therapeutic Ultrasound does represent a fantastic non-invasive and radiation-free alternative to the current standard of care. Thank you very much!

Thank you very much Hartmut.