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New Treatments for Thyroid Cancer

Thyroid cancer is most frequently going to present as a solitary thyroid nodule. These are by no means uncommon findings. In the Framingham study, just the health surveillance study, the prevalence of these nodules was close to 10% in women. The important figure that I tell my patients when I first see them is that the a priori odds of a solitary thyroid nodule being a cancer.

Clinical risk factors: the important risk factors, issues that would make one highly suspicious, a nodule that is growing rapidly. Say, over a period of weeks to months. A family history of a familial syndrome, multiple endocrine neoplasia or perhaps medullary thyroid cancer. Not by any means a common situation and in fact I would hope not to be seeing anybody with that history at this point, for reasons that weíll discuss.

So with that, letís talk a little bit about thyroid cancer itself. A variety of different types. Differentiated cancers arising from thyroid follicular cells are of course papillary or follicular cancers. The less differentiated is the anaplastic, which fortunately we see very rarely. Arising from an embryologically distinct population of C cells is medullary thyroid cancer. Iíll talk very briefly about it towards the end. I donít know if the speakers, when they were talking about some of the other islet cell neoplasms, discussed this at all or not. Finally, there are sort of non-thyroid thyroid things. Non-Hodgkinís lymphoma can present as a goiter or a thyroid nodule.

The most common form of thyroid cancer that we see in this country, and in general in areas of iodine sufficiency, is papillary thyroid cancer. Probably accounts for 80-85% of the thyroid cancers that we see in the United States. Papillary thyroid cancer can be noted as an incidental finding. Occasionally one will undergo a thyroidectomy and a microscopic focus or maybe several microscopic foci of papillary thyroid cancer will be found almost as an incidental finding.

Risk factors for papillary cancer; thyroid irradiation. Papillary cancer is seen with increased frequency as a second malignancy in individuals with a history of childhood cancer. This in part may be related to the irradiation issue. It may be in part related to general genetic factors with regard to tumor predisposition. There is some argument as to whether or not Graveís disease, because of its sort of the endogenous thyroid stimulation is a risk factor.

Letís talk just very briefly about thyroid irradiation. Potential sources for thyroid irradiation include external beam irradiation or radioiodine fallout. There was a lot of childhood irradiation being done back in the 40ís and 50ís and there were many many cases of thyroid cancer noted in the adults of children who were exposed, for reasons that would certainly not be considered medically appropriate uses of radiation in this day and age. It is clear to me that children are more radio-sensitive than adults. Now we have radioactive fallout. Catastrophe; Iím sure many of you remember this. This was shortly after the Chernobyl reactor accident, and it truly has been a catastrophe in any number of different ways.

Familial syndromes associated with papillary thyroid cancer: there are familial papillary thyroid cancer syndromes but a specific familial papillary gene has not been identified. Papillary cancer is seen in increased frequency with some GI syndromes, Gardenerís syndrome, familial polyposis, Cowden syndrome. Carney complex is the combination of myxomas, nodular adrenal cortical disease, Sertoli cell, testicular carcinomas and thyroid malignancies are also seen with increased frequency in that. A couple of pathologic variants of papillary thyroid cancer.

Follicular thyroid cancer accounts for about 15% of the thyroid cancer in the United States, and as I mentioned, more common in areas of chronic iodine deficiency. We touched on the issue that follicular carcinoma cannot be distinguished from follicular adenoma by aspiration, and so if that quandary remains, in general I will recommend surgery to the patient.

For the rest of the talk Iím really going to treat papillary and follicular carcinomas together as far as treatment decisions are concerned. The prognostic factors are similar for staging, and although it has traditionally been said that the outcome in follicular cancer is worse than the outcome in papillary cancer, oftentimes itís not clear if it relates to the difference in the tumor type or if itís more properly accounted for by these risk factors. But important prognostic risk factors, in terms of staging or particularly patient age.

There have been several staging systems that have been popularized for papillary thyroid cancer. Itís sort of one of these things about standards now. Everybody likes standards so much, and thatís why they make so many different ones. I counted at least eight different papillary thyroid staging systems. Iím just going to mention two of them. Certainly a TNM staging system has been widely adopted. I think that the important thing to look at here is that it covers all different forms of thyroid cancer, including medullary and anaplastic. Youíll notice that for differentiated follicular cancer, for patients less than 45, the only differentiating factor.

What about the treatment factors, in terms of the outcome for treatment in thyroid cancer? I think the take home message from the staging system is that we can identify a group of patients who are at fairly low risk - those at young age with small or moderate size tumors who are going to do quite well - and we can identify another higher risk group - those who are older, those who have evidence of multifocality or spread. What about frequent factors? Delay in treatment - Iím not going to talk about - but Masoferreís document.

The next thing, following surgery and assuming that a total thyroidectomy has been done, the next thing is going to be radioiodine ablation. Basically what is done here is the patient is allowed to become hypothyroid, their TSH rises and they then are given a tracer dose of 131 iodine which typically will show uptake in the neck, because even a total thyroidectomy, surgically complete, is rarely complete at the level of radioiodine uptake. Assuming that there is a remnant, then that is going to be ablated with 131 iodine.

This is a xiphoid marker here, some residual iodine in the Ö the lung uptake is actually this over here. So that patient was given a therapeutic dose of 131 iodine, probably in that case 200 microcuries of iodine were given. And this is a scan that was done a year or two later. At this time the patient was again withdrawn from thyroxine, the TSH was again allowed to rise and they were again given a tracer dose of radioiodine. There is still this appropriate uptake into the salivary glands, but you can see now the neck and the chest are now clear.

And this again is just some data from Masoferreís studies on recurrence and death rate again in patients with intermediate stage II and III disease in the absence or presence of radioiodine. And you can see that there were no deaths in the radioiodine treated group and a substantial decrease in the risk of recurrence as well.

Finally, the surveillance data. Weíve already sort of alluded to that. There are two major components to surveillance. One is the measurement of thyroglobulin, the thyroglobulin which is a normal thyroid product should be undetectably low in patients who have undergone total thyroidectomy and radioiodine ablation who are disease free. So a rising thyroglobulin is a marker of a return of thyroid tissue, obviously very suspicious for thyroid cancer. The other major surveillance tool that I alluded to is the use of the whole body metastatic survey.

This is an example of the utility of thyroglobulin. This is a patient who had surgery and 131 iodine ablation over here. The thyroglobulin level was initially around 5 at the time they were off suppression. They were started on thyroxin suppression. Their TSH was brought low and their thyroglobulin declined. A year later their thyroxin was stopped, TSH went back up, there was a slight increase in the thyroglobulin levels but the 131 iodine scan was negative, so they were put back on suppression. Several months after that their thyroglobulin, even while on suppression, started to rise and then when they were taken off suppression there was a considerably greater increment in their thyroglobulin, and the scan at that time was positive showing recurrent disease with pulmonary mets, which was treated with a second treatment with radioiodine.

Finally, as far as the other treatment issue that is available is the question of what one should do as far as thyroxine suppression. This is just some data from a recent, retrospective study, in which patients were scaled regarding the degree of thyroxine suppression. There were some patients who had essentially undetectable TSHís and other patients whose TSH was not quite fully suppressed. What this is showing is that in patients with - this is going back to a TNM staging - TNM stage I or II disease, that there was not very much of an impact on recurrence.