ASH 2015

“Low but real” risk of myelodysplastic syndromes caused by thyroid cancer treatment

Dr Sudipto Mukherjee - Cleveland Clinic, Cleveland, USA

You’ve been commenting here, well basically your study is to look at what happens if you use radioactive iodine treatment for thyroid cancer. Can you explain to me what you were trying to do in this study, why were you looking at this issue?

So for a couple of reasons. One of them is myelodysplastic syndrome, we know now, is the most common myeloid malignancy in the US. We didn’t know this before 2001, we only came to know this since 2003. The reason is before 2001 MDS was not even considered a cancer in our cancer registry so there is no information at all outside of what is the risk of MDS in this patient population. The second thing why we looked at thyroid, why we picked thyroid cancer, is we know that the thyroid cancer incidence is going up in the United States over the last three decades; we know that most of these thyroid cancer cases that are being diagnosed are low risk because we are detecting smaller tumours. We also know from the literature that there is no clear benefit to using radioactive iodine in treating these low risk thyroid cancers.

Yes, so you’ve got an effective treatment that’s very effective when you have a tumour that’s more advanced but you’ve got the same screening problem that you go on detecting, perhaps, cancers which wouldn’t have been risky.

Yes, and maybe you do not need to treat them with radioactive iodine in the absence of any clear survival benefit.

Right. So what did you do in the study?

In this study, because of the challenges of detecting and capturing MDS cases after 2001 using the publically available SEER software, we actually had to design the programme based algorithm where we could capture as many MDS cases that occurred after.

And did you?

And we did. So we created a novel platform, search platform, called the SEERaBomb. With that we were able to capture about 100,000 thyroid cancer patients and we were able to follow them. We found about close to 50 MDS patients. Now, this number might seem low but then MDS, although it’s the most common myeloid malignancy, is still a very rare hematologic malignancy.

And it could be the tip of the iceberg?

It possibly could be. If you look at the risk evolution of MDS in this patient population the first risk happens within the first two years. Now we don’t know whether the risk is real, it could be real, or it could be that the people who got radiation, they were followed more closely by the docs.

So what have you in fact found in terms of the treatment with radioactive iodine and the outcome in terms of the risk of getting MDS?

The early risk that happens within the first two years, we are not sure why the risk is going up that quickly. So what we are trying to do is we are trying to merge the SEER Medicare claims files with the SEER registry to answer that question. What we find is clinically intriguing and probably of a little bit of concern is a trend towards increasing risk after twelve years from exposure. Now that could be a real signal but we need to wait for a little bit more follow-up. Why I say that is because in atomic bomb survivor patients, survivors, we see that the MDS risk continues to go up even after forty years of exposure. So there could be a real signal in the second rise after twelve years of exposure.

How might this knowledge influence the strategy for treating thyroid cancer, do you think?

With this finding I think that it is important that both the treating physicians and the patients have a good discussion about what could be the potential late term complications of the bone marrow in people who have otherwise low risk thyroid cancer patients. Second, in patients who have been treated and have been cured of thyroid cancer they should be under prolonged cancer surveillance. It doesn’t need to be something separate or special, just annual surveillance by their primary care doctors or their treating physicians. If you do see any blood count abnormality, please follow up on that.

So watchful waiting is a good thing to do in many of your patients?

It’s a good thing to do, yes. And it can be integrated in the annual physical check-ups, it doesn’t have to be a separate surveillance programme.

What about screening, are we doing too much screening?

I’m not a thyroid cancer doctor but what I know is that it has been a push towards doing further investigations in people who have thyroid disorders. When you use more sophisticated screening purposes like ultrasound you will pick some small nodules or tumours that may not require anything more than just surgery. Because even the American Thyroid Association guidelines do mention to use this caution that in patients who have low risk tumours you may not necessarily need to do very aggressive treatment, maybe surgery might be just enough.

Are there patients for whom no treatment would be a good option, just watchful waiting?

It would actually depend on what kind of histology you find when you do a final aspiration of those tumours because a lot will depend on the biopsy findings. Sometimes identifying risk of thyroid cancer patients not only depends upon what is the pathology of the tumour but also the age and other associated conditions.

So how would you sum up the clinical messages for doctors coming out of your report here at the American Society of Haematology?

Two, basically that there are two take-home messages. First of all is there is a low risk but a real risk of myelodysplastic syndrome in this patient population based on the study we have done so far. We do not know exactly all the reasons behind this risk but if we see it it would be prudent for the treating physician and the patient to have a very free and frank exchange of the risks and benefits of the treatment that is being offered to them right now. Definitely in patients who have high risk thyroid cancer radioactive iodine treatment is mandated because it does provide survival benefit; the case may not be that simple in low risk patients. Second, in patients who got radioactive iodine and were cured of thyroid cancer, that means they were disease free for more than five years, they should still be continued to follow with the primary care physicians. The key point is if you do notice any blood count abnormalities and you cannot find any clear reason for why these abnormalities are occurring then you have to keep this thing in mind that these people have a low but a real risk of having a bone marrow failure condition even a decade or more from their treatment.