IO is not a subspecialty of IR

At ISET this year, Gary Becker, the executive director of the American Board of Radiology, prognosticated that interventional oncology would be the first subspecialty of IR. 

At SIR last month, one of the faculty was told that he could not refer to IO as a “subspecialty of IR” in the title of his talk. The reasoning for this was a little hard to follow, something solipsistic about IO being an intrinsic part of IR. (Nice to see that SIR is upholding the values of academic freedom.) 

Of course, both Gary and the SIR thought police are wrong. IO isn’t a subspecialty of IR. It’s a subspecialty of oncology, like medical, surgical, and radiation oncology. IO is a clinical discipline, requiring a broad and deep understanding of cancer, cancer treatment, and the care of cancer patients. The practitioners of IO in the US are largely interventional radiologists, though that definition is a slippery slope, given that some of our leading “ablationists” function outside the traditional IR universe. Both Nuclear Medicine and Radiation Oncology are making strides in image-guided targeted treatments for cancer, further blurring the lines. From a global perspective, IO procedures are done by many different medical specialists, reflecting practice patterns in different countries. For example, in Brasil, angiography is a surgical specialty, while non-vascular interventions are performed by radiologists. 

The evolution of IO as a clinical discipline is manifest in some leading US academic hospitals, where IO divisions have been established. This can be a service-line constructed to garner hospital resources while continuing to operate within the IR infrastructure, or a fundamentally separate division with its own staff and resources. Whether these pioneering centers reflect a new trend remains to be seen.

I mentioned this story to a Radiology department chairman, who replied with a snort, “IO is not a subspecialty of IR. If anything, it’s the other way around!”.


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Building a foundation of science or tower of Babel?

June 5, 2013 01:12 AM by Dave Liu


Dr. Arslan,


Your comments are certainly from a strong opinion and personal experience but I would like to reference the published literature as there are several factual errors in your comments:


I.  Less Filling or Taste Great?
 Your Comment: ‘I believe Resin and glass based Y90 is very different from each other. Resin based y90 is more comparable to 40 micron bland beads than the glass based y90. Its embolic effect likely has more treatment effect than the radiation it provides. That's why it probably is approved for colorectal and glass based y90 for HCC. It is definitely anecdotal but in our experience resin performs poorly in HCC and we had to retreat quite a few patients with glass to eventually get a better response.


 May be a reflection of your personal experience of which I would defer to your personal opinion and observation on but from both a clinical and scientific side, European thought leaders, including Dr. Prof Sangro and Dr. Prof Bilbo have published extensively on the following:


 Emboli effect: (this won the Abstract of the year at CIRSE)


 A)    Bilbao, J. I., de Martino, A., de Luis, E., Díaz-Dorronsoro, L., Alonso-Burgos, A., de la Cuesta, A. M., ... & de Jalón, J. A. G. (2009). Biocompatibility, inflammatory response, and recanalization characteristics of nonradioactive resin microspheres: histological findings. Cardiovascular and interventional radiology, 32(4), 727-736.


 ‘Eight-week evaluation found that the perivascular inflammatory reaction was mild. Liver cell damage, bile duct injury, and portal space fibrosis were not observed. In conclusion, resin microspheres (15–30 μm diameter) trigger virtually no inflammatory response in target tissues (liver and kidney). Clusters rather than individual microspheres were associated with a mild to moderate perivascular inflammatory reaction. There was no evidence of either a prolonged inflammatory reaction or fibrosis in the liver parenchyma following recanalization.’


 Translation: there is no terminally embolic effect associated with resin microspheres; there is essentially no response effect as a result of the physical properties. As I am sure you are aware, this is fundamentally different than DEB and TACE.


B) Simon MacKie, Suresh de Silva, Peter Aslan, Leigh Ladd, Michelle Houang, David Cade, Warwick Delprado. Super Selective Radio Embolization of the Porcine Kidney With 90Yttrium Resin Microspheres: A Feasibility, Safety and Dose Ranging Study, J Urol 2011 (volume 185 issue 1 Pages 285-290 DOI: 10.1016/j.juro.2010.09.001)



 ‘We performed super selective radio embolization with 90Y resin microspheres in 1 kidney and with an equivalent number of bland microspheres in the corresponding pole of the contralateral kidney as a control.’


Results: No discernable effects of the non radioactive microspheres in the normal porcine model, with effects of damage related directly to the amount of radiation used.


Translation: particles are too small to cause an apoptotic or hypoxic inflammatory recation.


 


 C)    Clinically, Resin for the treatment of HCC in the setting of PVT have been published refuting your comments regarding the primary embolic effect of resin microspheres for as we all know, PVT is the exact scenario in which embolic is less desirable.


Articles from Pamplona with resin and PVT:


 Inarrairaegui, M., K. G. Thurston, et al. (2010). "Radioembolization with use of yttrium-90 resin microspheres in patients with hepatocellular carcinoma and portal vein thrombosis." Journal of vascular and interventional radiology: JVIR 21(8): 1205-1212.


 ‘Radioembolization of unresectable HCC and branch or main PVT with (90)Y resin microspheres was associated with minimal toxicity and a favorable median survival time. Further prospective studies are warranted to validate the findings in this clinically challenging patient population.’


i. Article from Pamplona with resin and PVT:


Lau, W. Y., B. Sangro, et al. (2013). "Treatment for hepatocellular carcinoma with portal vein tumor thrombosis: the emerging role for radioembolization using yttrium-90." Oncology 84(5): 311-318.


 ‘Transarterial radioembolization (TARE) with yttrium-90 microspheres is emerging as a valuable strategy. A wider range of patients with PVTT are suitable for this procedure compared to TACE. TARE is as effective as TACE in HCC and has quality-of-life advantages. Conclusion: In patients with HCC with PVTT, medical evidence suggests that TARE is a good choice of treatment.’


ii. Article from Singapore with resin and PVT:


Burgmans, M. C., F. G. Irani, et al. (2012). "Radioembolization after portal vein embolization in a patient with multifocal hepatocellular carcinoma." Cardiovascular and interventional radiology 35(6): 1519-1523.


 ‘Radioembolization is an effective locoregional therapy for patients with intermediate or advanced stage hepatocellular carcinoma (HCC). It has been shown that radioembolization is safe in patients with portal vein thrombosis....describes safe radioembolization after portal vein embolization in a patient with multifocal HCC.’



II. Will More Radiation Cook a Tumor ‘Dead’er’?


Your comment: ‘Figuring out dosimetry is important, but let's face it by lowering the existing dose increasing efficacy is quite unlikely. If there is room to improve efficacy, beyond more targeted delivery it will be by genetic profiling of the tumor to see if they are more sensitive to radiation and mainly by increasing the radiation dose as long as it is within safety limits.’


The comments are interesting as I would like to know what your thoughts are on the common practice of using Glass EX ‘dosimetry’ and lowering the partition model ‘dose’ to 80Gy. Many high volume and experienced institutions do this on a regular basis in order to improve tumor coverage.  I would assume that would mean that you do not believe or do EX treatments?



III. How Many Fairies Fit on the Head of a Pin?


Your comment: With resin based I doubt there is much more room to increase the radiation dose as you will not be able to achieve it in most cases due to reflux, but with glass based there is that potential. Additionally resin based beads are not only less radioactive but also slightly larger in average diameter (5 micron?). That does not help either.


Dating back to 1957 with the seminal paper by Breedis and Young, with the initial descriptions of hepatic tumor vascularization and subsequent work by Ackerman and Lein in the 1970’s the hypervascular rim that constitutes the target of carrier based deliver mechanisms are in the range (I emphasize range) of 30-70um.  5um is 1/10 the width of a human hair, half the size of a red blood cell and closer to the size of a bacterium…


Targeted embolic therapy (bland) has been effective in the 100-300 and sub 100 um range; that data has been very well published and validated by the Memorial Sloan Kettering group over the last 15 years.


Proximal embolization to increase AUC and diffusion/dwell time for lipiodol tace is in the 300-500um range, demonstrated by the Hopkins group a few years ago.


Anything bigger than 500um can result in collateralization and reconstitution of flow. This has been demonstrated in gelfoam  embolization dog studies in the 1980’s


In summary the scale you are referring to of 5um is irrelevant based on published literature (and as mentioned is the size of a single bacterium), current knowledge of angiogenesis and physical property when it comes to tumor vasculature.


Regarding increasing the radiation dose, please define what you mean by dose? If you mean activity (i.e. GBq) that is the whole point of the discussion and would encourage a review of the previous postings and intellectually rewarding discussions with Dr. Prof Lam on the exact topic….



IV. IN SUMMARY, to which I will reiterate:


I JUST HEAR FROM TOO MANY PEOPLE THAT ‘MORE ACTIVITY NEEDS TO BE ADMINISTERED’ RATHER THAN ‘BETTER DISTRIBUTION OF ACTIVITY NEEDS TO BE PLANNED’ and without an understanding of 3D crossfire, isodose cloud distribution, microclustering and microdosimetry, the discussion cannot be effective or productive as it will reduce down to an argument of  ‘I like this better because I do…’

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