- [Nick] Good morning everyone. My name's Nick Kurup, I'm from Mayo Clinic. And I'd just like to thank Kristin and the leadership for inviting me to speak. I'm gonna be talking about bone ablation for local tumor control, and these are my disclosures, research stuff,
and writing about this subject. So I'm mostly gonna focus on the why. Why do we do bone ablation for local tumor control and I'll talk about a rationale for focal therapy in these patients, a little bit about technique,
and then some evidence supporting ablation for these patients. So there's been an evolution in our understanding of patients with metastatic disease. Starting in the late 1800s with Dr Halsted, he described the orderly and contiguous understanding
of metastatic spread in the case of breast cancer. So the primary tumor moving through the lymphatics to the lymph nodes before spreading systemically. And he used this as justification for patients undergoing mastectomy or radiation therapy to the breast.
Another understanding of metastatic disease is that it's always widely disseminated. So if we have a patient like this that has a melanoma metastasis to the liver, if we only had more sensitive imaging techniques could really see what's going on,
we would see that there's not only the single metastasis, but really a host of other metastases, and these patients all have micrometastasis, cats out of the bag, there's nothing to do focally for these patients.
However, in 1995 Drs. Welchselbaum and Hellman
wrote an opinion paper called Oligometastases and then rewrote on this subject in 2011 about the concept of oligometastasis, and they really described this as a distinct state in which tumors have an intermediate metastatic potential. So these patients have a limited number
and site of metastases, and these are variably defined in the literature, but usually people will say up to five metastases. And in these patients it makes sense to do focal therapy rather than systemic therapy. These patients do not have all of the changes
that are required to have distant metastatic spread.
So is there any cellular or biologic basis for this understanding? Well over the last couple of decades really, there's been a lot of scientific study into tumors on a genomic basis.
And we find that tumors really have a lot of heterogeneity. So this clump of cells that are multicolored here represent the tumor and really, we see that the metastases that develop from this to the brain, liver, and lungs, and spread from different parts of that tumor.
And each of these parts of the tumor may develop different mutations. And even the tumors that spread, like that green metastasis to the liver, then may develop further mutations that allow it to spread further.
And so if we find patients who have a limited amount of metastatic spread, potentially those patients have a single mutation as a more homogeneous tumor. In which case, we could potentially have a therapeutic window in which we can
prevent them from having spread elsewhere. So if we take this example, patient who has a colon cancer and the colon cancer had spread to the liver, those metastases then develop further mutations that spread to the lung and the bone and then the bone metastasis further spreads to the brain,
we could potentially, if we find a patient who only has a liver metastasis and a bone metastasis, if we actually treat those areas focally potentially we can limit their metastatic progression, improve survival.
So what are the focal therapies we could use?
Well surgery's been used for years, and there's certainly clinical evidence for this in a number of scenarios. Pts who have colorectal metastases to the liver. They undergo a partial liver resection and they live longer. They are long-term survivors from that.
Same thing with resection of lung metastases, even adrenal metastases. Radiation therapy is certainly used for this in certain areas, particularly of the spine. Embolization is certainly used as a local regional therapy
for metastatic disease, particularly into the liver, and currently it's being used in patients who have more than oligometastasis, several metastases. Focus ultrasound is being used, it's really in the experimental stage now for actually developing local control,
not just in the uterine fibroid here or benign tumor, but in bone metastases.
But I'm really gonna focus on percutaneous ablation because it's particularly well suited to this application, minimally invasive for these potentially frail and elderly patients,
as well as high kill rate with tumors of many different histologies. So when we're choosing, this is the technique, so how do we do it? If we were facing a metastasis in the scapula like this, we can treat it with heat,
radiofrequency, or microwave ablation, or we can treat it with cryoablation, extreme cold temperatures, extreme cold or extreme heat, they'll both kill the tumor. How do we decide? Well, if we compare cryoablation versus microwave ablation
or radiofrequency ablation, ease of use, the heat-based therapies are certainly easier to use. They're generally faster, so the procedure duration is quite a bit shorter, but the energy transmission into bone is better with cryoablation.
It'll go through the cortex, whereas heat is limited in that regard. The predictability of the ablation zone, the cryoablation. As you can see in that scapular picture, we can actually see the edge of the ablation with several different modalities, CTMR and ultrasound.
Our ability to monitor that ablation then and prevent it from escaping into adjacent collateral structures. And then the ablation zone size, we can usually treat a larger area with cryoablation, and patient tolerance, their pain scores are generally less
after a cryoablation than a heat-based therapy. So in general, most of us who are treating for local tumor control would use cryoablation. These factors are a little less true these days where there are newer bipolar radiofrequency devices that are designed specifically for bone
so have better ability to control tumors within these sites.
So when we're doing this technique, what do we need before we get started? We need adequate preprocedural imaging. So if we're seeing this tumor that's in a bit of a scary location in the proximal femur,
sometimes if we treat that too aggressively that can fracture, but this looks like it's isolated into the medullary cavity. But these patients have multiple imaging modalities and these help. So if we have functional imaging, in this case a PET scan,
we can see it's actually a bilobe lesion that actually is a little bit higher than we might just suspect from the CT alone. And so when we're ablating we make sure to cover that entire territory when we're in this indication
of trying to locally control that disease. Likewise, if we have a patient like this who has sclerotic metastases, prostate or breast cancer, they've been treated. It's a little bit hard to know which of these are actually active disease.
Have they already been treated? Because they'll look like this for the rest of their life. And we do a PET scan and we actually see there's really only one tumor that has FDG uptake or choline uptake and is actually active disease, and so we actually target that tumor.
When we're treating these tumors for local tumor control we're really aggressive in ablating them. So we have a rib metastasis here, and we won't just put one probe in it and call it a day. We have to make sure that we have adequate cold temperatures surrounding the entire tumor with margin
to make sure that we can provide a long-lasting effect for these patients, rather than this case in which patient has a spinal metastasis, we put one probe in part of it and leave a little corner of tumor
when our goal is local tumor control that's not really adequate. And local recurrence really matters so in this study this is one example study of a patient who had surgical replacement of renal cell carcinoma, bone metastases.
And in this study they show that threefold higher hazard ratio of death in patients who develop local tumor recurrence at the site of the resection. So if we can, extrapolating that surgical data to ablation we wanna make sure we get that local control.
Unfortunately as we treat aggressively we are more at risk for developing complications. In this large metastasis that's in the supra-acetabulum here we try to be very cautious that we don't actually have that ice ball encroach upon the femoral head,
as opposed to this equally large metastasis in the supra-acetabulum where we actually have the ice that if you extrapolate those into that femoral head and then several months later the patient develops femoral head collapse and fracture, and their pain recurs.
So let's just talk briefly about the evidence and I'll use metastatic renal cell carcinoma as a model case. Different tumor histologies will have different evidence and different studies to support them. So in this case of a patient who has a right renal mass
and develop this renal metastasis and we ablate that with the ice ball you can see very well. So does this oligometastatic state even occur in renal cell carcinoma met, patients? Well, it does. Most patients actually present
with limited metastatic disease. More than half the patients, when they present with metastases, have just a single site of disease, and that proportion actually increases as patients age. So the patients who are the most elderly,
the most frail, the least suited to surgery, actually are the most likely to have a single site of disease to treat. Is there a survival benefit from surgery if we extrapolate those data? Well, if patients have a wide or radical surgical resection
as opposed to a marginal, they're just pinning that metastasis, those patients do better who have a wide radical surgery. And if patients at the end of their surgery actually are free of disease, they don't have other sites of metastasis,
if we can actually treat all of their disease, they live longer.
So what about if patients have more than just one renal cell carcinoma metastasis? What if they have multiple. So in this study from my institution,
the urology team looked at patients who had all of their tumors resected as opposed to patients who had any of their tumors resected compared to those who had none of them resected. And there was a survival benefit for each of those patients. And these authors wrote a really nice statement
I like in this scenario. And they said limited data exists on the outcomes of these types of patients, and we believe this may result in an unnecessary therapeutic anilism, whereby patients who have multiple lesions
are excluded from an aggressive approach. They're just put onto systemic therapy or comfort care. And why is the literature limited in this case? It's due to the morbidity of surgical resection. So really ablation in these minimally invasive IR techniques provide an opportunity to help this patient population.
So we've looked at our experience in treating musculoskeletal limited metastatic disease for complete remission, and we looked at 52 metastases in 40 patients. A quarter of them were renal cell in this case. Had about two years followup,
and 87% were able to achieve local tumor control. And these patients live a long time. The median survival of these patients was almost four years with two years survival of 84% with acceptable complication rate. We looked at specifically in renal cell carcinoma,
treating those in multiple different sites. And you know, most of these patients did have locations in bone and soft tissue. So if we used those data to say is there evidence to support this? Well, in these 82 tumors the recurrence
resurvival was very high in 94%, and the patient's overall survival 83% were still alive two years later. In our local tumor control about 88% with an acceptable complication rate. So it is possible to treat these patients
and continue to have them live a long time without systemic therapy. Others have certainly looked at this. This is a group in Detroit that's looked at the same thing, renal cell carcinoma metastasis ablation, and they found the same thing,
median survival over two years in this group. And they actually did a little bit of a cost analysis and said what's the estimated cost even if we have to ablate these people twice and their cost per life year gained was $26,000, which is very reasonable
and compares favorably to systemic therapy, these patients who are put on systemic therapy, the cost is 30 to 45,000 in their study. I've seen estimates over $60,000 for a year. So it's certainly reasonable to do that. This is a busy chart that just shows
that there's a lot of evidence for treating musculoskeletal tumors for local tumor control for a variety of histologies from lung cancer to renal cell cancer to a mixed populations, and breast cancer, whether it's in the spine or other areas in the bone,
a variety of ablation modalities, cryoablation versus heat and the local tumor control rates are reasonable, 70 to 98% depending on the patient population we're looking at. And these data have been compelling enough that the National Cancer Care Network's guidelines
had been revised for patients with stage four renal cell carcinoma. Now that if they are not surgical candidates, ablative techniques in these metastases should be considered.
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