The State of the Fight: Thyroid Cancerby Douglas Ball, M.D.
Thyroid cancer is the fifth most common cancer diagnosed in U.S. women. Overall, female patients outnumber men by about 3:1. The number of new cases of thyroid cancer is increasing, and much of this increase appears to stem from a rise in medical imaging. Scans conducted for unrelated reasons are now sometimes causing doctors to discover small thyroid gland nodules that probably would not have been found otherwise. Only small minorities of thyroid nodules prove to be cancer when biopsied. The combination of a lot of new cases, often in young adults, and excellent survival rates adds up to a huge survivorship population. Hundreds of thousands of Americans are now living as thyroid cancer survivors.
The mainstay of thyroid cancer treatment is surgery. Some patients get additional treatment with radioiodine - the decision to do this depends on the type of thyroid cancer, its size, and whether lymph nodes are involved. The five year survival rate for thyroid cancer at the beginning of the 21st century was 97 percent. This is among the best for any solid tumor, but understates the scope of the thyroid cancer problem. In addition to the approximately 1,800 Americans who die every year from advanced thyroid cancer, there is a much larger number living with persistent thyroid cancer, some of which is low-level and indolent, but some of which is progressing.
There is natural fear among people discovered to have thyroid gland nodules that they might have a serious cancer. However, the actual chance of a serious thyroid cancer is extremely small. Fewer than 5 percent of thyroid nodules are cancerous, and for those that are malignant, most patients will respond well to surgery and, sometimes, radioiodine.
A second misconception I still occasionally see among doctors and patients relates to more advanced cases of thyroid cancer. There is a tendency to view radioiodine as a ‘magic bullet.’ Unfortunately, the bad cases of thyroid cancer are often refractory to radioiodine. It’s important to appropriately use blood tests and other imaging to identify this subset of thyroid cancer patients, and not rely excessively on radioiodine scans. The vast majority of doctors who treat thyroid cancer patients now understand this.
For the majority of patients with early stage thyroid cancer, there has been incremental progress including more accurate imaging and better surgical techniques, along with more efficient post-operative surveillance. For patients with advanced thyroid cancer, there’s been a major paradigm shift. Doctors are recognizing the shortcomings of radioiodine, and are beginning to apply lessons from molecular genetics to treat the disease. A class of drugs, called ultikinase inhibitors (MKIs) is showing excellent activity in clinical trials of advanced thyroid cancer. Earlier this year, the Food and Drug Administration approved vandetanib - the first new thyroid cancer drug in over 30 years. This drug is specifically designed for a subtype called medullary thyroid cancer. Discovery of the characteristic mutation in medullary thyroid cancer in 1993 was critical in the successful development of this drug. Other MKIs are showing great promise in the more common kinds of advanced thyroid cancer.
While we are not seeing long term complete responses yet, we do see excellent partial shrinkages of tumors, and in some cases, prolonged progression-free survival. Because these oral chemotherapy drugs can have significant side effects, the appropriate situations for treatment are still under investigation. It’s critical for patients with advanced thyroid cancer to have access to clinical trials.
Cancer biology and cancer translational research has excited me for the past 20 years. I’m clinically trained as an endocrinologist, so my focus is on the principal endocrine cancer, thyroid cancer. I’m really lucky to have one foot planted with an outstanding endocrine group, and the other in the cancer center, with all its resources and excitement of discovery. Johns Hopkins is a superb place to be for this kind of multidisciplinary work. I collaborate with scientists to study the effect of drugs that target different activated signaling pathways in thyroid cancer cells. We’ve stewarded some of these promising results from the lab into clinical trials. I lead or share a number of thyroid cancer clinical trials at Hopkins. We’ve focused so far on oral chemotherapy approaches, using MKIs and inhibitors of the “MAP kinase” and “PI 3 kinase” signaling pathways. The clinical trials depend on collaborations with pharmaceutical companies, the National Comprehensive Cancer Network, and a group of thyroid cancer investigators called the International Thyroid Oncology Group (ITOG). Multi-institutional and interdisciplinary cooperation is critical to progress in this cancer, as well as in any other.
There’s a big need for genetic discovery - thoroughly sequencing the genomes of the different types of thyroid cancer, combined with analysis of epigenetic changes that affect the expression of genes. At Johns Hopkins, we’re excited about these genetic and epigenetic studies that are now underway. These findings could lead to a more personalized approach to drug therapy. A more novel approach involving immune therapy could also be promising.
I think that the future is in personalized treatment, based on the genetic, epigenetic, and signaling changes in individual cancers. In advanced thyroid cancer, we’ve reached an early stage of progress with MKIs. Moving forward is a challenge, since these drugs hit a number of targets, and we have limited means to test the effectiveness in order to optimize their use. In the short term, we need to understand why some people respond well to these drugs and others don’t. In the medium term, I’m hopeful that genetic discovery will provide us with new targets. Because tumors evolve and adapt to treatment pressure, I suspect that we may need a multidrug approach, in analogy to strategies that have worked well for TB and HIV. Crafting such a multidrug combination to be selective for cancer and have acceptable toxicity will be a supreme challenge.
Thyroid cancer is believed to be largely unpreventable. The main risk factor is radiation exposure during childhood. Children receiving radiation therapy should be carefully followed throughout their lives. However, routine medical and dental X-ray’s don’t seem to cause thyroid cancer. The serious nuclear accidents at Chernobyl, and now in Fukushima, Japan raise the risk of pediatric thyroid cancer in those areas. Five to 25 percent of thyroid cancers are heritable, depending on the type. Readers with a family history of thyroid cancer should share this information with their physicians. In some cases, screening tests are appropriate, especially if more than one family member is affected. Family history of other thyroid diseases, such as thyroid underactivity or overactivity is not a risk factor for thyroid cancer. Sometimes benign multinodular goiters can also be familial as well.
The most important take home lesson is that thyroid nodules are incredibly common, and usually benign. People should have thyroid exams as part of periodic medical check-ups. Often, gynecologists are skilled and conscientious in performing thyroid exams. Discovery of a nodule in the thyroid deserves an evaluation, but isn’t a cause for excessive concern. In most cases, an ultrasound-guided biopsy of the thyroid nodule will settle the issue. It’s a case of better to be safe than sorry.