Browse Tag: chemotherapy

The utility of thyroglobulin

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 TSH’s 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 related to the degree of thyroxin suppression but that in these higher risk patients with stage III disease, particularly, that the patients who were more fully suppressed had a lower risk of recurrence. So again, certainly in some of the patients who might be at a higher a priori risk there’s justification in treating them with sufficient thyroxine to keep their TSH suppressed, I feel that to an undetectable level at least for the first several years after treatment.

What about the patients who, in a way, I suppose you might be more likely to see, or the ones we need to call for additional help on, are those with differentiated radioiodine resistant thyroid cancer. A couple of potential treatment options; there is a role for external beam irradiation in these patients.

Chemotherapy has been, I’d say, disappointing at best, but there still may be a role for it. The most commonly used drug has been Adriamycin, either by itself or in combination with cisplatin, with other agents. There are a variety of kind of interesting approaches being tried right now. In addition I believe there is a Taxol trial going on, although I haven’t seen any results on it. There has also been this interest in redifferentiation, in trying to treat the tumor in such a way as to lessen its radioiodine resistance and enable it to be more effective in taking up radioiodine. Retinoic acid and its congeners has been used and there has also been this interesting finding that occasionally in patients treated with Adriamycin as chemotherapy, that if you repeat the scan after they have gone through a couple of treatment cycles, that there have been some patients who have then been shown to take up radioiodine.

Suggesting that in some way there was some type of redifferentiation that took place. But clearly, these patients who get to a stage of radioresistant disease are a very very troubling group to treat.

My approach, in terms of these patients, is; the question is whether they have progressive disease and whether they are symptomatic. If they are not symptomatic – and many many patients, even with extensive thyroid cancer, may not be – or maybe minimally symptomatic, there is certainly reason to simply continue to follow those patients. If there are significant symptoms taking place, which may frequently relate to bony metastases, then I think the important issue is to localize the disease. If the disease if very focal, if it involves an isolated or bony matter or a large soft tissue lesion, then there is certainly a role for external beam irradiation and/or surgery, depending on the locations involved. If the patient is progressing, has diffuse disease, then I think that might be the situation in which there would be a role for systemic chemotherapy, using either Adriamycin or some combination of agents. Then as I mentioned, consider at least not giving up totally on radioiodine but consider another scan maybe after a few cycles to see if there might have been some redifferentiation issue.

Just to give you an idea of what types of responses you can have

Just to give you an idea of what types of responses you can have. This is a 52-year-old man, presented with a huge mass in his right temporal parietal lobe. This was found on biopsy to be a CNS lymphoma and after two cycles on a regimen that we use, consisting of high dose methotrexate, cyclophosphamide and vincristine, after two cycles this was his scan. This is before radiation therapy. So again a very satisfying disease to treat.

There remain a number of questions of primary CNS lymphoma relative to chemotherapy, such as who benefits from chemotherapy? We talked about the issue of immunocompetent versus immunodeficient patients. Prognostic factors seem to make a difference, with age being the most important. That elderly patients do not tolerate the chemotherapy as well or they don’t tolerate the chemotherapy side effects, and indeed they do not appear to benefit as much as younger patients. But what the age cut-off is and why this should be the case remains totally unknown. Issues relative to performance status, pathology and extent of disease appear to be less significant, at least for immunocompetent patients being treated with chemotherapy. There also continue to be significant and growing questions about the appropriate role for radiotherapy, such as what is the optimal dose and fractionation scheme, since combining chemotherapy and radiation now patients are living longer, one begins to have to worry about long term neuro-cognitive sequelae. One is beginning to question, with optimal chemotherapy, does one even need to use radiation therapy. So these are questions that still remain outstanding in primary CNS lymphoma. Again, a difficult problem in answering these questions given the relative rarity of the disease.

I’d like to just finish up by talking a little bit about, and mentioning a few of the recent developments, in the treatment of brain metastasis. A problem that medical oncologists obviously see quite frequently. The reason for that is that 20-40% of all cancer patients will develop brain metastases, accounting for 170,000 cases per year. The majority of these patients have lung cancer. Most of the metastases occur in the gray white matter, of which 80% is supratentorial. The few tumor types that can metastasize to the dura are breast and prostate, while the two tumor types that appear as hyperdense lesions without contrast are renal cell carcinoma, melanoma and actually sarcoma. But most of the other metastases appearing as hypo or iso-dense lesions.

How about the use of standard chemotherapy

Well, if we are going to use chemotherapy, particularly for those with anaplastic astrocytomas where we do believe that there is a role for post-radiation chemotherapy, what are the optimal drugs?

Well, there are very few data out there that gives us a lead. The best, or the only data that’s really out there, comes from a randomized trial conducted by NCOG published in 1990. It took patients with high grade astrocytomas, following external beam radiation therapy and randomized them to treatment with either treatment with single agent with BCNU or PCV. If you looked at the groups as a whole there was no significant survival advantage of time to tumor progression difference between these two treatment regimens. However, when a subgroup analysis was done they looked at the minority of patients with anaplastic astrocytoma there appeared to be a very significant survival advantage for patients treated with PCV over BCNU. And hence, the standard recommendation for patients with anaplastic gliomas to be treated with the three drug combination of procarbazine, CCNU and vincristine following standard external beam radiation. It’s important to understand that this is really the only hard data that suggests that PCV is better than BCNU. This is a subgroup analysis and it consisted of only approximately 30-40 patients, and that’s whether in fact this truly is true at this point remains unclear. Nevertheless, it’s unlikely this trial is going to be reproduced so this is the data that we are stuck with.

How about the use of standard chemotherapy at the time of recurrence? Well, if you look through the literature you will see various reports of various combinations, single agent chemotherapy trials and combination chemotherapy that give relatively high response rates. It’s important to understand that the reporting of these response rates are often very over-inflated for a number of reasons. One of the major reasons is that response criteria in the neuro-oncology community have not been agreed upon and for instance, stable disease is often considered a response in most of the literature. Canadian viagra online is a successful way to fight male impotence problems. And stable disease is often not even defined by duration of stable disease. Furthermore, many of the older trials did not have imaging modalities that were accurate. They used old brain scans or some of the older data for some of the older agents only used clinical exam as a way of assessing response.

Many of these trials did not control for steroid dose and we know steroids can certainly affect the clinical symptoms of patients as well as their imaging.

As a matter of fact, I think one has to be very critical, particularly looking at the older data in neuro-oncology. It is clear regardless of what the response rate is, that for most agents, standard chemotherapy agents in the treatment of recurrent high grade gliomas that whatever responses there are tend to be very short. Although the responders may live longer than non-responders, whatever that means, there is clearly no overall survival prolongation in patients treated with chemotherapy. Furthermore, there are few if any significant quality of life studies to suggest the role of chemotherapy. I think the one potential contradiction to this is the recent demonstration that a new drug, temozolomide, has a relatively high – approximately 37% – response rate in patients with anaplastic gliomas treated at the time of recurrence who’ve had one or fewer previous chemotherapy regimens. So temozolomide for recurrent glioma probably offers something to these patients.