Radioimmunotherapy for solid tumors?

[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 oncology and nuclear medicine.

I read about the success Zevalin and Bexxar have had in converting partial responses to R-CHOP in NHL to complete ones, at a low rate of ADRs, so I'm very interested in RIT.

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.

So the tumor will be killed by both alpha radiation and ADCC.

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

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

Thanks!

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[carrigallen]

While drug-antibody conjugates are certainly the way of the future, there is big downside to uptake of radioimmunotherapy in the US. The main problem is that administration of radioimmunotherapy requires special certification in radiation safety practices for infusion center, Radioactive Materials License for the pharmacy. Other problems are high overhead to float, competing treatment options, staff training, which physician to administer it. Thus it is not cost-effective for most community infusion centers. You can spend a billion developing an active drug, but if no one uses it, it is a bust. For example, Bexxar was approved in 2003 but GSK recently stopped manufacture because no one was using it.

 

[TSDentSurg]

You have a good point. Although one of the benefits of RIT is that you can administer it as a single injection. Perhaps they should have an advanced fellowship so med oncs can acquire the skills needed for an NRC license. Or a med onc could partner with a NMT.

I think that nuclear radiologists and IRs should be the ones administering RIT as of now.

However, wouldn't you agree that someone with cancer would better be taken care of in a major medical center, than in a community center?

Until we get this sorted out, we should invest more money in researching oncolytic viruses, CDEPT, and immunotoxins.

I also think the emerging technology of DNA aptamers could make molecular targeting of oncocytes much easier, as they are a) much smaller, and b) can be evolved via error-prone PCR.

Zevalin is still in use, though.