Newly Established I-131 Principles Bring Multidisciplinary Collaboration to Thyroid Cancer Community

R. Michael Tuttle, MD

R. Michael Tuttle, MD

Recommendations for radioactive iodine (I-131) published in 2015 by the American Thyroid Association (ATA) ignited major disagreements between the nuclear medicine community and endocrinologists, explained R. Michael Tuttle, MD. However, experts in both fields across 8 countries recently came together in an effort to restore mutual understanding of the disease and the role of radioactive iodine therapy in differentiated thyroid cancer.

Held in Martinique, France in January 2018, the 2-day interactive meeting brought together experts from the European Association of Nuclear Medicine (EANM), the Society of Nuclear Medicine and Molecular Imaging (SNMMI), the European Thyroid Association (ETA), and the ATA. Collaboration at the meeting resulted in the development and publication of the Martinique Principles, a set of 9 principles designed to integrate the different understandings in the field of thyroid cancer regarding treatment and beyond.

As the biology of thyroid cancer has changed over time, the ATA saw that the treatment guidelines must change as well. A large proportion of patients now present with small, low-risk thyroid cancers that may not require surgery or an aggressive therapy such as radioactive iodine. By the end of the meeting, experts from the United States and Europe were able to define factors that should be evaluated for each patient presenting with thyroid cancer in order to decide if radioactive iodine is the right treatment option. These factors are included in the 9 principles, recently published inThyroid.

“It is clear from the paper that we haven’t agreed to agree on everything, but at least we are talking and moving in the right direction,” said Tuttle, a member of the ATA Board of Directors and lead author of the paper. “This gives me hope that in the future, these discussions will keep going and we will be able to, in a logical and evidence-based way, identify where we agree, where we don’t agree, and more importantly, areas of research where we can work together.”

In an interview withTargeted Oncology,Tuttle, an endocrinologist at Memorial Sloan Kettering Cancer Center, discussed the Martinique meeting and the 9 principles published following the meeting. He also highlighted the importance of continuing meetings like this in order to identify and develop optimal treatment options for patients with thyroid cancer.

TARGETED ONCOLOGY:What was the rationale behind conducting this meeting?

Tuttle:This was started after the ATA published its 2015 guidelines, and there were several folks in the nuclear medicine community that weren’t thrilled with all of our recommendations. That led to meetings, discussions, and arguments at national and international meetings. Finally, some of the doctors from Martinique said it would probably be helpful if we put everyone together in a room. They got together with the EANM, SNMMI, ETA, and the ATA. They put us all in a room about a year ago and wouldn’t let us leave until we played nice with each other. That became the start of this discussion and to really try and integrate all 4 organizations. I doubt we will ever be able to make 1 big set of guidelines, but at least we have a better understanding of how each of the organizations view thyroid cancer and the use of radioactive iodine in thyroid cancers.

TARGETED ONCOLOGY:Why is the use of radioactive iodine a controversial topic in thyroid cancer?

Tuttle:It is partly because times are changing. In the old days, thyroid cancer was always found with your hands, and it was big nodules that often spread to the lymph nodes of the neck. Surgery, lymph node surgery, and radioactive iodine made a lot of sense, but in the last 15 years, we have seen a dramatic increase in really small thyroid cancers.

Now, a large proportion of our patients are really low-risk thyroid cancers that are probably treated by removing just half of the thyroid. It’s been this shift in the type of thyroid cancers we see that made us question if it is really necessary to do that very aggressive treatment of taking the whole thyroid out and giving radioactive iodine in these low-risk patients.

The ATA responded to that by saying we recognize there are a lot of these low-risk patients, and the data is just not strong enough that they need aggressive surgeries or radioactive iodine. In fact, some of these really small thyroid cancers don’t even need surgery, so we are now doing active surveillance in papillary cancers less than 1 cm rather than rushing to surgery. The change was not because of tons of new data; the change was asking if all these aggressive management approaches really apply to this low-risk disease that we are seeing today.

TARGETED ONCOLOGY:What came out of the discussions at the Martinique meeting?

Tuttle:What really came out of it is that in some respects, we agreed to disagree. I think that’s important at a big organizational level. Now, I don’t think all of us are saying the other side is completely wrong; we recognize that, as in principle 1, the principles really being a charter to say how we are going to play together in the sandbox. The first principle was recognizing that we are going to have differences in opinion, and that it’s not so black and white who needs radioactive iodine versus who doesn’t. There’s a lot of patients that we are just going to disagree on. We may disagree because of patient preference or it may be because of where we work, or because there may be a different approach in Europe versus the United States versus South America. There’s lots of reasons that go into why someone may or may not need radioactive iodine for follow-up, and there is more to it than just what’s the size of the tumor and if there are any metastases.

I think the big thing is we better understood how the nuclear medicine doctors were reading the exact same literature we were reading but interpreting it slightly differently. It made us open up to a different point of view. On 1 of the principles, number 6, we actually said we can’t really tell you what exactly is the right dose of radioactive iodine for adjuvant therapy. Nuclear medicine guys had an opinion, endocrine guys had an opinion, but if we honestly looked at the data, there just wasn’t enough data to give us an exact dose, so we wrote that. I think that is a nice step forward; it doesn’t mean I’m wrong or they are wrong, it just means that the best data we have can be interpreted a couple different ways.

TARGETED ONCOLOGY:Can you provide some background to the 9 principles in this paper and the meaning behind them?

Tuttle:The 9 principles grew out after we first got together at the start of our 2-day meeting; we didn’t really have the idea that we were going to have principles. We just had really good and honest discussions. These were people in the room that were experts from all the different fields, and they were the senior people from the different organizations. It really was just the chance to be able to have frank discussions without an audience and all that stuff. As we talked for a day and a half, some of us realized we were starting to agree on a few certain things, and toward the end of the second day, we began to write down some things to see what we agreed on. That became the Martinique principles, where number 1 really was that we really have to work together. We can’t write guidelines without nuclear medicine and without endocrinologists; we need to figure out a way to do this together, and we need to figure out a way to do this internationally because countries all over the world read the ATA Guidelines.

We also realized we needed to work on some definitions. We were using the same words differently in terms of ablation, adjuvant therapy, and therapy. It turns out that with some of the differences we were having, we were saying the same words and meaning different things. Principle number 2 said we need to speak a common language and agree on these definitions.

Principles 3, 4, 5, and 6 got to the heart of who needs radioactive iodine, what dose we should use, and how we do the decision making. We talked about all the different factors that went in to when you are sitting in a room with somebody making the decision for their particular case about whether or not they needed radioactive iodine. While we didn’t all agree on who needs it, we did agree on the factors that need to be evaluated and incorporated.

The last big thing that we dealt with was in Martinique principles numbers 7 and 8. It’s this whole concept that we call the radioactive iodine-refractory. When do we say radioactive iodine doesn’t work anymore? That’s really important because when radioactive iodine works, it works, and it works very well. When it doesn’t work, there are a whole bunch of tyrosine kinase inhibitors that we now have that are FDA approved to treat these patients, but you don’t want to use any of those pills until you’re certain that the radioactive iodine has stopped working. There’s a long discussion in the principles that look at how to define if somebody is radioactive iodine-refractory and what things you need to think about because it is such an important decision in how we take care of these patients. That was the third big piece to the puzzle that we worked on. I think it is going to help people work through these issues.

TARGETED ONCOLOGY:Are there any next steps planned to continue this progress?

Tuttle:I think that moving forward, the 4 organizations have to proactively work together. This is above the heads of any one of us that happened to be sitting at the table. They are doing that; the 4 organizations are talking and being proactive at having meetings and such. I think that is really important.

The second thing is to identify the next set of topics that are controversial between the specialties of the endocrinologists and the nuclear medicine doctors, not necessarily between Europe and the United States. There are lots of topics we can deal with, including benign thyroid disease and thyroid cancer. I think we started down the thyroid cancer pathway, we started down radioactive iodine therapy in the cancer pathway, as that was the most controversial, but when you begin talking with colleagues, you realize there are some other ideas that we could achieve consensus on. I hope that going forward this meeting keeps happening every year or 2 and that the 4 organizations identify important topics that endocrinologists and nuclear medicine doctors need to discuss. With each subsequent meeting, they will invite the appropriate specialists. I only deal with thyroid cancer so I’m no good at talking about nodules or follow-up of graves’ disease or that stuff, so we need different members of the ATA. I think this provides a forum, and it provides an interactive place to really look at our differences and to look where we agree. I think it allows us to have really productive discussions.

TARGETED ONCOLOGY:What were the key takeaways from this meeting?

Tuttle:The key points are that anybody writing guidelines or management recommendations needs to make sure they have a multidisciplinary team that’s involved in the development of that and to make sure to get all the voices at the table that you need to hear, not just the ones that you like; you must include the ones that you may not necessarily like or understand. At the big macroscopic level, it’s just making sure you have the appropriate people at the table when you are doing that.

On a positive note, this has been a very positive experience. I learned a lot from my colleagues in Europe, both the European nuclear medicine doctors and the endocrinologists, about how they practice medicine, what their patients are like, what their follow-ups are like. That made me think if I was practicing in another country, would I would be doing something differently? I think all of that is important for learning different ways to do things. I think the real take home message is getting the right people at the table and providing a forum where you can have a frank, open, safe discussion in which you can air your differences and what you agree on. That allows us to leverage the expertise of all the different experts to really come closer to a single, unified management approach as best we can.

TARGETED ONCOLOGY:Is there anything else that you would like to add?

Tuttle:The centerpiece is really those Martinique Principles, and the general theme that is instead of 4 different societies going about and talking bad about each other, to be adult enough to say we are going to sit down in a room and iron this out. At least, this is the first time a paper has been published from all 4 societies. It is clear from the paper that we haven’t agreed to agree on everything, but at least we are talking and moving in the right direction.

This gives me hope that in the future, these discussions will keep going, and we will be able to, in a logical and evidence-based way, identify where we agree, where we don’t agree, and more importantly, areas of research where we can work together. Instead of saying we just don’t have the information, [we can say] what is it that we as a world community need to do and what studies we need to do to make that information that we need available.

Reference:

Tuttle M, Ahuja S, Avram A, et al. Controversies, Consensus, and Collaboration in the Use of I-131 Therapy in Differentiated Thyroid Cancer: A Joint Statement from the American Thyroid Association, the European Association of Nuclear Medicine, the Society of Nuclear Medicine and Molecular Imaging, and the European Thyroid Association.Thyroid. 2019; 29(4). doi: 10.1089/thy/2018.0597.