Interventional treatments for oral cancer?

[TSDentSurg]

Hi guys!

I'm a dental student, and I'm strongly interested in specializing in academic oral-maxillofacial surgical oncology. I enjoy keeping myself informed on recent advances in related fields, such as interventional radiology and nuclear medicine.

I just got done reading these two very interesting articles:

1. Ophthalmic artery chemosurgery for retinoblastoma: http://www.retinalphysician.com/articleviewer.aspx?articleID=107657

2. Alpha radioimmunotherapy for radio- and chemoresistant NHL:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3712568/

So, I have an interesting theory on how to treat tongue SCC:

1. Perform dosimetric calculations to determine the dose of Bi-213 needed to deliver 80Gy to the tumor.

2. Conjugate anti-SCCA mAbs to Bi-213.

3. Do a selective lingual angiogram to determine the tumor vascular anatomy.

4. Inject the mAb conjugate into the tumor feeder arteries.

5. Do PET scan 1 day post-op to determine if the alpha radiation has rendered the tumor metabolically inactive.

The lingual artery catheterization will ensure the therapy will be localized to the tongue, the SCCA mAbs will ensure the radionuclide will only be delivered to the SCC cells, and using the alpha-emitter Bi-213 will maximize tumorcidal radiation while minimizing radiation to nearby healthy cells.

This seems like a promising treatment idea. I wonder if anyone has tried irreversible electroporation in oral cancer.

Interventional radiology seems to be limited in the field of H&N to performing pre-op tumor embolization; I wonder why?

Thanks!

---

Members don't see this ad.

 

[resxn]

So I'm no academician and pretty much do very little cancer and certainly do zero XRT. However, no one has responded and so I feel bad for you. Certain questions are raised by your points. Great idea that may be harder than the theory, some questions to consider from a very lowbrow perspective.

1 - why 80Gy to an oral cancer? Seems to be a boat load. More than is typically delivered to OSCCa by IMRT.
2 - that's a Holy Grail Ab, isn't it? Do we have selective anti-SCCa mAbs? What about for moderate and high-grade tumors?
4 - mAB injection into the feeder arteries, while feasible, does not preclude retrograde delivery outside of the tumor area. How to control for spread away from primary target?
5 - No way a 1 day post-op PET is going to give you jack squat. Assuming the procedure worked, you're going to get an inflammed mass in the oral cavity for months depending on T stage. You might be able to do a PET at 3 months, but doing it on Day 1 is not realistic.

According to Wikipedia the following are trials for irreversible electroporation (no mention of oral SCCa in it although I'm sure this isn't an exhaustive list as this kind of research is probably occurring and not yet announced somewhere):

None of the potential organ systems, which may be treated for various conditions and tumors, are covered by randomized multicenter trials or long-term follow-ups. In a nonrandomized prospective study, the only observed adverse event directly related to IRE was transient ventricular arrhythmia.[18]

Non-controlled clinical trials have been carried out on the prostate,[19] kidney,[20] liver,[21] pancreas[22] [23] and lung.[24]

Clinical trials for the use of irreversible electroporation for the treatment of pancreatic[25] and liver cancer[26] are currently being run.

I applaud your ideas and thoughts. You should pursue your thoughts with an H&N surgeon at your academic center. It's guys like you who will come up with the next great thing.

 

[DrBodacious]

To the OP: great questions. Keep exploring these ideas. It will take a while to understand the disease and it's potential treatments and limitations.

When I was a MS4, I remember considering why we couldn't use image navigation systems for expirtative surgery. (There are multiple reasons why this isn't practical). One reason is that during surgery, the oral cavity tissues are very pliable and mobile (they move around and sort of slept open and fall away from each other as you operate). This is also one theory why XRT is generally less effective than surgery for oral cavity primaries compared to oropharynx, which are going to be more reliably positioned with the use of a face mask. (There are other potential and legitimate reasons).

Likewise, targeting a tongue cancer volume with angiography is not going to be extremely clean, or reliably effective from patient to patient. Even though you are doing an ECA treatment, there are going to be significant risks of backflow and I CA delivery with brain sequelae. I have unfortunately seen this with glomus tumor embolization.

Although, there are folks out there doing intraarterial chemotherapy for challenging head and neck tumors (e.g. sinus malignancies), where definitely double and sometimes triple modality treatment can be an institutional strategy. You could do a search on intraarterial chemotherapy to find out more. I heard someone talk about doing this as a radiosensitizing treatment concurrent with xrt, although I don't recall the details. This stuff hasn't, to my knowledge, gained much more use just in more run of the mill oral cavity primaries yet, and I can't tell you why, exactly, other than the practicality issues I just alluded to.

 

[DrBodacious]

Also, I second resxns points, all very good points.

 

[TSDentSurg]

Thanks for your responses.

I made a mistake: since we're using alpha radiation, we need only 4 Gy, due to alpha radiation having weighting factor of 20. So we'd have an effective dose of 80 Sv. Gy and Sv are effectively equivalent for beta and gamma radiation, as they both have a weighting factor of 1.

Lesson here is you can't use the dosimetry for XRT for alpha RIT. You'd seriously overdose, as resxn pointed out.

Using DNA aptamers as the delivery mechanism would make things much easier, as we could simply use error-prone PCR to evolve an aptamer specific for SCCA.

The Bi-213-aptamer conjugate could be injected intratumorally, instead of messing with angiography.

Or, we could conjugate the aptamer to streptavidin, inject that into the tumor or it's feeder arteries, and then give a systemic injection of a Bi-213-biotin conjugate. This is called pre-targeting, and should reduce the risk of irradiating something we don't want to.

Also, using the longer-lived Ac-225 radioisotope would make treatment logistics easier, as it's half-life is 10 days, and it would double the radiation dose, as it's daughter is Bi-213.

Perhaps encapsulating the radioisotope in a liposome, and then injecting spores of recombinant Clostridium novyi that secretes liposomase into the tumor would be an alternative. The radioisotope would only be released from its fatty prison in the presence of the enzyme, which would only be produced in the hypoxic tumor, where the obligate anaerobe is replicating.

Interventional oncology is so exciting!

 

[DrBodacious]

Sounds like we are developing a good Michael Crichton book, now. I'm not saying that use of anaerobic bacteria is not possible, but not practical, and a long way off after decades if not centuries of testing with animal models, etc.

For a good nonfiction read, check out the book "king of hearts" about some of the crazy animal studies and early attempts at open heart surgery. Research was much more exciting /inhumane ~80 years ago, but today's regulations make rapid breakthroughs unlikely.

 

[TSDentSurg]

It's a well-researched area that's shown good results in animal models as recent as 2008: http://www.ncbi.nlm.nih.gov/pubmed/18829557

 

[DrBodacious]

I have oral boards in a couple weeks, so I don't have time to read up on this too much. The article you linked is interesting, but seems to offer pretty basic results/conclusions. I don't see anywhere that they achieved the test results in any more than one mouse... Having done some basic science research, I know how that goes. I am sure there is a lot more work that has been done that I don't know about.

I am not trying to discourage you, but there are a lot of smart people thinking about these things all the time... I still think it is a decent analogy that you are taking this from pointlessly cloning sheep to cloning extinct dinosaurs.

Also, you have to ask what you are trying to gain. Decent results are achieved with conventional treatment modalities, so any new method will have to beat current methods with regards to efficacy, safety and (for everyone's sake) hopefully cost.

 

[TSDentSurg]

I agree it's far too early to tell whether these lab results will translate clinically.

What would you say about transarterial ethanol ablation for H&N SCC? It's shown good results in HCC: http://www.ncbi.nlm.nih.gov/m/pubmed/18192473/

You could use it to debulk the tumor, and then treat the residual tumor and micrometases with systemic pre-targeted alpha RIT or a MMAE-SCCA mAb conjugate.

The latter immunotoxin has shown amazing results in remitting refractory lymphoma: http://adcreview.com/m/blogpost?id=6613470:BlogPost:2474

 

[Dunce]

sounds a lot like RADPLAT

the mAb part is interesting though

 

[DrBodacious]

RADPLAT, yes, this is what I was talking about above. I forgot the term for it. I haven't heard an update on this for the last year and a half or so...