RxPG News : Thyroid

Ethanol injection helps manage bone metastasis in thyroid cancer

Tue, 05 Jun 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Percutaneous ethanol injection (PEI)?an injection of ethanol (alcohol) through the skin directly into a bone tumor to kill cancer cells?may be a valuable ancillary treatment for thyroid cancer patients whose cancer has spread to the bone. Japanese researchers announced these findings during the 54th Annual Meeting of SNM, the world's largest society for molecular imaging and nuclear medicine.

PEI may be a valuable adjunctive or secondary treatment to radioiodine therapy, and it may contribute to better management of thyroid cancer patients with bone metastasis, said Kunihiro Nakada, clinical assistant professor in the Department of Radiology at Hokkaido University Hospital and the hospital chief in the Department of Radiology at LSI Sapporo Clinic, both in Japan.

Reports indicate that this year about 33,550 new cases of thyroid cancer will be diagnosed in the United States, and of those, more than 25,000 will occur in women. Thyroid cancer is a disease in which cancer (malignant) cells are found in the tissues of the thyroid gland. The thyroid gland, located at the base of the throat, makes important hormones that help the body function normally. Cancer can spread beyond that site and invade other parts of the body (metastasis), and thyroid cancer is often listed among the top most common causes of metastatic bone lesions. The primary treatment for patients with thyroid cancer is surgery, which is followed by thyroid hormone therapy. Radioactive iodine may be used to destroy thyroid cancer cells after surgical removal of the thyroid gland.

Although thyroid cancer generally has a favorable prognosis, bone metastasis can be hard to be eradicate, said Nakada. Although radioiodine therapy and/or surgery are valuable therapeutic strategies, management of bone metastasis has been challenging since it is likely that bone metastasis will show resistance to radioiodine therapy or that a tumor cannot be surgically removed, he explained.

Our study is a therapeutic approach to treat metastatic bone tumor from thyroid cancer by injecting absolute ethanol directly into the tumor, explained Nakada. Absolute ethanol induces direct necrosis (cell death) of the tissue in the area where it is distributed. Therefore, if absolute ethanol is selectively injected into a malignant tumor, selective destruction of the tumor may be expected, he added. In their study, 12 patients with radioiodine-ineffective bone metastasis from thyroid cancer underwent PEI. More than 50 percent reduction in tumor volume was achieved in all.

PEI appears effective in terms of palliation (control) of symptoms (such as pain) and tumor size reduction and does not induce significant systemic side effects, noted Nakada. In addition, PEI is a feasible treatment for radioiodine-ineffective tumors and has a potential for improving general performance or quality of life for selected patients, he added.

Additional research should be done to optimize treatment, said Nakada, including determining doses of ethanol, number of times PEI sessions should be repeated, how to predict outcome earlier and what other therapeutic options could be better combined with PEI to enhance efficacy.

Study demonstrates link between thyroid cancer and the Chornobyl accident

Thu, 06 Jul 2006 02:28:37 PST

( from http://www.rxpgnews.com ) In a study of thyroid cancer after the Chornobyl accident in 1986, researchers at Columbia University's Mailman School of Public Health report that exposure to radioactive iodine ingested through the food chain increases the risk of thyroid cancer in children and adolescents. The study is published in the July 5 issue of the Journal of the National Cancer Institute.

The 1986 accident at the Chornobyl nuclear power plant exposed large numbers of people in Belarus, Ukraine, and the Russian Federation to highly radioactive material. Numerous studies have shown that exposure to certain types of radiation increases the risk of thyroid cancer in children and adolescents. However, up until now, few studies examined the effects of exposure to radioactive iodines, which can get into the food chain, and only three studies measured cancer risk from the Chornobyl-related exposures.

The team of researchers at the Mailman School of Public Health, with colleagues, screened more than 13,000 people for thyroid cancer who were under 18 at the time of the Chornobyl accident and lived in highly contaminated areas of Ukraine. The researchers estimated each participant's individual radiation dose using thyroid radioactivity measurements made shortly after the accident and interview data obtained during screening.

The researchers found 45 cases of thyroid cancer in the screened group in comparison with the 11.2 cases expected without the accident. Subjects had a tendency toward lower risk of thyroid cancer with increasing age at the time of the exposure. The authors suggest that exposure to radioactive fallout from the Chornobyl accident increased thyroid cancer risk in those exposed as children and adolescents.

"In young children and adolescents, thyroid gland tissue requires large amounts of iodine coming primarily from food," said Geoffrey R. Howe, PhD, professor of epidemiology at the Mailman School and principal investigator. "If radioactive iodine gets into the food chain, as was the case in Chornobyl, children and adolescents accumulate large amounts of radioactive iodines in their glands. This exposes the thyroid tissues to the radiation which in turn, increases the chance of getting thyroid cancer and other diseases of the thyroid gland later in life."

The researchers estimate that 75% of the thyroid cancer cases would have been avoided in the absence of radiation. "This estimate demonstrates a substantial contribution of radioactive iodines to the excess of thyroid cancer that followed the Chornobyl accident," observed Dr. Howe.

Recombinant TSH therapy promises better quality of life for thyroid cancer patients

Sun, 22 Jan 2006 22:32:37 PST

( from http://www.rxpgnews.com ) A multicenter international study, including Johns Hopkins, has found that after surgery for thyroid cancer, giving genetically engineered human thyroid-stimulating hormone (rhTSH) before radioiodine treatment avoids the previous need to stop thyroid replacement therapy and the miserable side effects that go with it.

The study, led by Paul Ladenson, M.D., director of the Division of Endocrinology at The Johns Hopkins University School of Medicine, and Furio Pacini at the University of Siena in Italy, was reported in the December online edition of the Journal of Clinical Endocrinology and Metabolism.

Typically, radioiodine treatment for cancer of the thyroid gland requires temporary discontinuation of thyroid hormone replacement for several weeks, leading to weight gain, constipation, fatigue, slowed thinking, depressed mood, muscle cramps, intolerance of cold temperatures and other symptoms. This study shows that patients who use a recombinant form of TSH can continue their thyroid replacement therapy and enjoy a better quality of life during their cancer treatment, Ladenson says.

Thyroid cancer is first treated by surgical removal of the gland in the neck, often followed by radioactive iodine treatment to remove any remaining thyroid tissue.

Once the thyroid is diseased or removed, it no longer produces the hormones T4 (thyroxine) and T3 (triiodothyronine), which help regulate heart rate, blood pressure, body temperature and weight. Therefore, it is essential to add back the thyroid hormone L-thyroxine to keep the body functioning normally. Paradoxically, for radioiodine treatment to be effective, thyroid hormone treatments previously had to be suspended, according to Ladenson. Suspending hormone treatments stimulates the pituitary gland to produce thyroid-stimulating hormone (TSH). TSH stimulates any remaining thyroid tissue to concentrate the radioiodine, which can then eliminate remaining thyroid tissue. Once inside the cell, radioiodine emits beta particles that damage the DNA in thyroid cells without affecting surrounding tissues, according to Ladenson.

TSH made by the pituitary gland and rhTSH produce equivalent biological actions, according to Ladenson, and there are only slight structural differences.

This multi-institutional study proved that rhTSH is just as effective as the TSH produced by the body in destroying these remaining thyroid cells, Ladenson says.

This randomized, controlled, study involved 60 patients from four centers in Europe and five in North America. The first patient was enrolled on Dec. 17, 2001, and the last patient completed the final study visit on Sept. 26, 2003.

Within 14 days after surgical removal of the thyroid, 32 of these patients were randomized to a group that received their thyroid hormone treatment, L-thyroxine, without interruption and rhTSH for four to six weeks prior to radioiodine treatment. Twenty-eight were randomized to a group that did not receive L-thyroxine or rhTSH and were then treated after hypothyroidism prompted their own pituitary glands to make TSH. Quality of life was tested during this period and symptoms were assessed using the Billewicz scale -- an observer-rated evaluation of 14 symptoms and signs exhibited by patients who have a lack of thyroid hormone in their system. Patients then underwent radioiodine treatment. Eight months after this treatment, doctors performed a scan to determine if there was any remaining thyroid tissue.

Before radioiodine treatment, Billewicz scores revealed both groups to be comparable -- with mild and transient symptoms reported by only eight patients in each group. As they were prepared for radioiodine treatment, the group denied thyroid hormone therapy had significantly higher total symptom scores at weeks two and four. The most common complaints of patients who were denied thyroid hormone therapy, vs. patients who received thyroid hormone therapy and rhTSH, were cold intolerance (50 percent vs. 21 percent), weight increase (60 percent vs. 21 percent), constipation (43 percent vs. 3 percent), lethargy (50 percent vs. 12 percent), cold skin (47 percent vs. 12 percent), and puffiness around the eyes (50 percent vs. 0 percent).

Eight months after radioiodine therapy, tests showed that remaining thyroid cells had been successfully destroyed in all patients in both groups, according to the study.

These results clearly indicate that rhTSH combined with radiation therapy successfully destroys remaining thyroid tissue without the need to discontinue thyroid hormones, thus reducing the unpleasant side effects generally associated with this treatment, Ladenson says.

A novel molecular diagnostic tool to assess risk for patients with papillary thyroid cancer

Sat, 07 Jan 2006 17:45:37 PST

( from http://www.rxpgnews.com ) Scientists at Johns Hopkins have found that a mutation in the gene that triggers production of a tumor growth protein is linked to poorer outcomes for patients with papillary thyroid cancer (PTC). A report on the study is published in the December issue of The Journal of Clinical Endocrinology and Metabolism.

Mingzhao Xing, M.D., Ph.D., an assistant professor in the Division of Endocrinology and Metabolism at The Johns Hopkins University School of Medicine, led the multi-center study. This discovery should help physicians rate risk levels for patients with PTC, he says.

The gene, called BRAF, is part of a signaling pathway that, when activated, is known to cause tumor growth, and mutations in BRAF have been linked to a variety of human cancers, the researchers say.

For the study, Xing and colleagues looked at information from 219 PTC patients from 1990 to 2004. The relationship among BRAF mutations, initial tumor characteristics, cancer recurrence and clinical outcomes was analyzed.

Results showed a significant association between BRAF mutation and spread of the cancer from the thyroid, lymph node metastasis, and advanced tumor stage at the time of surgery to remove the cancerous thyroid gland. The thyroid, a gland located beneath the voice box (larynx) that produces thyroid hormone, helps regulate body cell growth and metabolism. Results also showed that, given an average follow-up of three to four years, 25 percent of patients with BRAF mutations experienced tumor recurrence compared to 9 percent without evidence of BRAF mutations.

BRAF mutation was also an independent predictor of recurrence in patients with early disease, with 22 percent recurrence in those who had BRAF mutations versus only 5 percent in patients without the mutation.

Finally, BRAF mutation was more frequently associated with treatment failure in recurrent disease, according to the study.

By illustrating a higher risk of poorer outcomes and recurrence, these results should help physicians perform better risk analysis of patients with PTC, which in turn will lead to more tailored treatment of the disease, Xing said.

PTC is the most common thyroid cancer, accounting for 80 percent or more of thyroid malignancies. Although PTC is usually curable with surgical removal of the gland, often followed by radioiodine treatment, many cases recur and are fatal.

The ability to predict outcome has traditionally been based on such factors as patient age and gender, tumor size and the nature of the spread of disease. However, these criteria often leave uncertainty regarding the risk of tumor progression and recurrence.

What we have is a novel molecular diagnostic tool that will improve existing clinical efforts, Xing said.
The study patients were recruited from The Johns Hopkins University School of Medicine; The Yale University School of Medicine; The Hospital for Endocrine Surgery in Kiev, Ukraine; and The University of Bologna Hospital in Bologna, Italy.

Other contributors from Hopkins include William H. Westra, M.D., professor in the Department of Pathology; Ralph P. Tufano, M.D, assistant professor in the Department of Otolaryngology -- Head and Neck Surgery; David Sidransky, M.D., professor in the Department of Otolaryngology -- Head and Neck Surgery, and Paul W. Ladenson, M.D., director of the Division of Endocrinology and Metabolism.

The study was supported by grants from the National Institutes of Health and the Flight Attendant Medical Research Institute.

Gene Activity can Differentiate Follicular Adenoma from Follicular Thyroid Cancer

Sat, 26 Mar 2005 16:18:38 PST

( from http://www.rxpgnews.com ) New research suggests that physicians can distinguish between a type of thyroid cancer and an identical-looking, non-cancerous thyroid condition by simply determining the activity of three genes.

The findings could lead to a test that will prevent the needless loss of the thyroid gland in people with the noncancerous condition.
Charis Eng

The study, led by researchers at The Ohio State University Comprehensive Cancer Center Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, indicates that the activity levels of three genes cyclin D2, PCSK2 (for protein convertase 2) and PLAB (prostate differentiation factor) -- might distinguish the noncancerous condition known as follicular adenoma (FA) from follicular thyroid cancer (FTC).

The findings, published online by the Journal of Clinical Endocrinology and Metabolism, also provide insight into the genetic changes that occur in those cases when FA becomes FTC.

Presently, doctors cannot distinguish between these two conditions without surgical removal of the thyroid, even though only about 10 percent of cases prove to be cancerous, says principal investigator Charis Eng, director of OSUs clinical cancer genetics program. Follicular adenoma often does not require surgery, and certainly not as extensive as for a cancer.
Presently, doctors cannot distinguish between these two conditions without surgical removal of the thyroid, even though only about 10 percent of cases prove to be cancerous.

This is the first step in determining whether we can use these three genes as an objective way to tell whether a patient has cancer or simply a benign adenoma before sending that person to surgery, says Eng, holder of the Klotz Chair in Cancer Research and a recipient of the Doris Duke Distinguished Clinical Scientist Award.

An estimated 25,690 Americans will be diagnosed with thyroid cancer this year, and an estimated 2,370 people will die of the disease. The great majority of thyroid cancers begin as thyroid nodules, which develop in about 7 percent of adult Americans (about 275,000 people in 1999).

To determine if thyroid nodules are cancerous, doctors typically withdraw cells from the nodules using a procedure known as a fine-needle aspiration biopsy. A pathologist then examines the cells to determine if they are noncancerous (benign) or cancerous.

But if the nodules consist of the thyroids follicular cells, Eng says, it is often impossible to tell if they are benign or cancerous.

So the person is sent to surgery, and the entire thyroid is often removed. Ultimately, however, only 10-20 percent of these cases are actually cancerous. The great majority of patients therefore undergo unnecessary surgery and thyroid loss.

These patients must then take synthetic thyroid-hormone tablets daily for life, with regular testing to adjust the dosage.

For this study, Eng and her colleagues used gene chip technology to compare gene activity levels in nodules from 12 patients with FA and 12 patients with FTC. The comparison included four cases of early (i.e., minimally invasive) FTCs.

Gene-chip analysis compares activity levels of tens of thousands of genes in this case, 33,000 genes in a sample at one time.

The researchers focused on the three genes that showed the greatest differences in activity. One gene was almost 145 times more active, a second was eight times more active and the third was 12 times less active in FTC cells compared with FA cells.

The researchers confirmed the gene-chip findings on two additional sets of tissue samples using two other measures of gene activity a form of polymerase chain reaction (PCR) and immunohistochemistry. The validation tests showed that the three genes could distinguish FTC from FA with an accuracy of 96.7 percent.

Next, the investigators will confirm their findings using fresh thyroid follicular nodule tissue obtained by fine-needle aspiration. This work is under way.

Cincinnati study of Chernobyl residents uncovers new cause of thyroid cancer

Tue, 04 Jan 2005 19:17:38 PST

( from http://www.rxpgnews.com ) Cincinnati University scientists studying papillary thyroid cancer in Chernobyl residents following the 1986 nuclear plant accident have identified a novel genetic mutation event that occurs as a result of their exposure to high levels of radioiodide.

Yuri E. Nukiforov led a team of researchers from both Cincinnati University and the University of Munich in identifying a novel oncogene (a mutated and/or overproduced version of a normal gene that alone or together with other changes can convert a cell into a tumor cell) in papillary thyroid carcinomas that developed in patients exposed to radiation at Chernobyl. Their results are published in the January 3 issue of the Journal of Clinical Investigation.

Mutations of the genes BRAF, RET, or RAS are found in 70% of all cases of papillary thyroid tumors. In sporadic tumors (where patients have not been exposed to high levels of radiation), the most common genetic mutational event occurs within the BRAF gene. In contrast, mutations observed in radiation-induced tumors most commonly involve fusion of one end of the RET gene to the opposite end of various other genes to create a "chimeric oncogene." The two most common gene rearrangement types are called RET/PTC1 and RET/PTC3. Both types of mutations promote transformation of normal cells into malignant cells.

In their current study, Nukiforov and colleagues identified a novel oncogene in Chernobyl residents with papillary thyroid cancer. This oncogene resulted from fusion of part of the AKAP9 gene with one end of the BRAF gene; both genes are present within chromosome 7. The intrachromosomal AKAP9-BRAF fusion event resulted in the loss of portions of the BRAF protein that normally inhibit the kinase activity of BRAF. BRAF is then able to transmit uncontrolled signals to normal cells that promote their division and transformation into malignant tumor cells.

In an accompanying commentary, Alfredo Fusco and colleagues from Università degli Studi di Napoli "Federico II", in Naples, state that this study "provides further evidence supporting the concept that chromosomal inversions represent the most typical molecular lesion in tumors occurring in Belarus and the surrounding region after the Chernobyl accident.the peculiar susceptibility of thyroid follicular cells to chromosomal rearrangement is remarkable."

This study represents a major breakthrough in our knowledge of the genetic events involved in papillary thyroid initiation. It demonstrates that while BRAF activation is a common feature of both sporadic and post-Chernobyl thyroid cancers, it is the genetic event underlying BRAF activation that can differentiate between the two types of tumors, with a higher proportion of point mutations occurring in sporadic thyroid cancers and intrachromosomal inversion responsible for a larger percentage of radiation-induced tumors. At this stage, the signaling pathway activated as a result of these mutational events (known as the MAPK pathway) is the most attractive target for new drugs that may intervene in the development of human papillary thyroid carcinomas.