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Held every five years 15th International Thyroid Congress
ITC: Levothyroxine may improve obstetric outcomes in women with low thyroid function
LAKE BUENA VISTA, FLA. – Normalizing maternal thyroid function early in pregnancy may improve obstetric outcomes for women with subclinical hypothyroidism.
A high level of thyroid-stimulating hormone (TSH) was associated with increased stillbirth in women who didn’t receive prenatal levothyroxine, Peter N. Taylor, Ph.D., reported at the International Thyroid Congress.
And women who were untreated for low free thyroxine (T4) were significantly more likely to need an early cesarean section than treated women, suggesting that levothyroxine could be reducing conditions leading to maternal-fetal distress.
“The good thing is that many physicians are already treating with levothyroxine anyway,” said Dr. Taylor of Cardiff (Wales) University. “There are no obvious adverse obstetric events associated with it. It seems relatively benign, and the accepted dose of 150 mcg per day seems adequate.”
He reported data from a subgroup analysis of the large Controlled Antenatal Thyroid Screening Study (N Eng J Med. 2012;366:493-501). That trial enrolled more than 21,000 mother-child pairs, and examined the effect of maternal levothyroxine treatment on the child’s IQ at 3 years. Among the children of women with hypothyroidism, the mean IQ scores were 99.2 and 100 in the treated and control groups – not significantly different. The proportions of children with an IQ of less than 85 were 12% in the treated group and 14% in the control group, also not significantly different.
Dr. Taylor’s cohort involved about 14,000 mother-child pairs from this study, all of whom were from Wales. Using national health care databases as well as study data, he was able to examine obstetric outcomes in women with low thyroid function (664) who received or did not receive levothyroxine early between 11 and 16 weeks’ gestation.
About half of the hypothyroid women (351) had TSH levels above 3.5 mU/L. The remainder had free T4 levels below 10.9 pmol/L. Each of these groups was randomized to levothyroxine treatment or placebo. The rest of the cohort had normal thyroid status.
The study’s primary endpoint was the rate of stillbirth. Secondary endpoints were cesarean section rate (both overall and early); gestational age at birth; and macrosomia.
Among the euthyroid group, the rate of stillbirth was 0.34%, similar to the national background rate. There were no stillbirths among women with high TSH who were treated. Three (1.68%) occurred in the untreated group. The TSH levels in those women before treatment were 3.63 mU/L, 3.66 mU/L, and 4.58 mU/L – not dramatically high, Dr. Taylor noted. “But they could have risen later in pregnancy as stress on the thyroid increased.”
After adjusting for maternal age, weight, parity, birth year, and smoking, stillbirths were five times more likely among the untreated women than the treated women. However, Dr. Taylor cautioned, “This is a very small number of events. But it is quite seductive to think that stillbirths could be prevented by levothyroxine.”
There were no significant associations of high TSH with macrosomia or gestational age.
Untreated low free T4 was not associated with stillbirth. However, Dr. Taylor said, it was very strongly associated with early C-section.
The overall C-section rate was similar between untreated and treated women (28%). But 5.6% of the untreated women had an early C-section, compared with none of the treated women. This hints strongly at a protective effect of levothyroxine, Dr. Taylor said. Early C-sections – between 26 and 32 weeks – are medically driven rather than driven by patient choice. This finding of fewer early interventions among treated women suggests that levothyroxine is exerting some protective effect, especially given the finding that infants of untreated mothers actually tended to be about 133 g lighter at birth.
“We would speculate this is probably due to a decrease in preeclampsia and gestational hypertension, which are more common among women with hypothyroidism.”
Infants of untreated mothers also were born slightly earlier – about half a week, he said at the meeting held by the American Thyroid Association, Asia-Oceania Thyroid Association, European Thyroid Association, and Latin American Thyroid Society.
Dr. Taylor had no financial disclosures.
LAKE BUENA VISTA, FLA. – Normalizing maternal thyroid function early in pregnancy may improve obstetric outcomes for women with subclinical hypothyroidism.
A high level of thyroid-stimulating hormone (TSH) was associated with increased stillbirth in women who didn’t receive prenatal levothyroxine, Peter N. Taylor, Ph.D., reported at the International Thyroid Congress.
And women who were untreated for low free thyroxine (T4) were significantly more likely to need an early cesarean section than treated women, suggesting that levothyroxine could be reducing conditions leading to maternal-fetal distress.
“The good thing is that many physicians are already treating with levothyroxine anyway,” said Dr. Taylor of Cardiff (Wales) University. “There are no obvious adverse obstetric events associated with it. It seems relatively benign, and the accepted dose of 150 mcg per day seems adequate.”
He reported data from a subgroup analysis of the large Controlled Antenatal Thyroid Screening Study (N Eng J Med. 2012;366:493-501). That trial enrolled more than 21,000 mother-child pairs, and examined the effect of maternal levothyroxine treatment on the child’s IQ at 3 years. Among the children of women with hypothyroidism, the mean IQ scores were 99.2 and 100 in the treated and control groups – not significantly different. The proportions of children with an IQ of less than 85 were 12% in the treated group and 14% in the control group, also not significantly different.
Dr. Taylor’s cohort involved about 14,000 mother-child pairs from this study, all of whom were from Wales. Using national health care databases as well as study data, he was able to examine obstetric outcomes in women with low thyroid function (664) who received or did not receive levothyroxine early between 11 and 16 weeks’ gestation.
About half of the hypothyroid women (351) had TSH levels above 3.5 mU/L. The remainder had free T4 levels below 10.9 pmol/L. Each of these groups was randomized to levothyroxine treatment or placebo. The rest of the cohort had normal thyroid status.
The study’s primary endpoint was the rate of stillbirth. Secondary endpoints were cesarean section rate (both overall and early); gestational age at birth; and macrosomia.
Among the euthyroid group, the rate of stillbirth was 0.34%, similar to the national background rate. There were no stillbirths among women with high TSH who were treated. Three (1.68%) occurred in the untreated group. The TSH levels in those women before treatment were 3.63 mU/L, 3.66 mU/L, and 4.58 mU/L – not dramatically high, Dr. Taylor noted. “But they could have risen later in pregnancy as stress on the thyroid increased.”
After adjusting for maternal age, weight, parity, birth year, and smoking, stillbirths were five times more likely among the untreated women than the treated women. However, Dr. Taylor cautioned, “This is a very small number of events. But it is quite seductive to think that stillbirths could be prevented by levothyroxine.”
There were no significant associations of high TSH with macrosomia or gestational age.
Untreated low free T4 was not associated with stillbirth. However, Dr. Taylor said, it was very strongly associated with early C-section.
The overall C-section rate was similar between untreated and treated women (28%). But 5.6% of the untreated women had an early C-section, compared with none of the treated women. This hints strongly at a protective effect of levothyroxine, Dr. Taylor said. Early C-sections – between 26 and 32 weeks – are medically driven rather than driven by patient choice. This finding of fewer early interventions among treated women suggests that levothyroxine is exerting some protective effect, especially given the finding that infants of untreated mothers actually tended to be about 133 g lighter at birth.
“We would speculate this is probably due to a decrease in preeclampsia and gestational hypertension, which are more common among women with hypothyroidism.”
Infants of untreated mothers also were born slightly earlier – about half a week, he said at the meeting held by the American Thyroid Association, Asia-Oceania Thyroid Association, European Thyroid Association, and Latin American Thyroid Society.
Dr. Taylor had no financial disclosures.
LAKE BUENA VISTA, FLA. – Normalizing maternal thyroid function early in pregnancy may improve obstetric outcomes for women with subclinical hypothyroidism.
A high level of thyroid-stimulating hormone (TSH) was associated with increased stillbirth in women who didn’t receive prenatal levothyroxine, Peter N. Taylor, Ph.D., reported at the International Thyroid Congress.
And women who were untreated for low free thyroxine (T4) were significantly more likely to need an early cesarean section than treated women, suggesting that levothyroxine could be reducing conditions leading to maternal-fetal distress.
“The good thing is that many physicians are already treating with levothyroxine anyway,” said Dr. Taylor of Cardiff (Wales) University. “There are no obvious adverse obstetric events associated with it. It seems relatively benign, and the accepted dose of 150 mcg per day seems adequate.”
He reported data from a subgroup analysis of the large Controlled Antenatal Thyroid Screening Study (N Eng J Med. 2012;366:493-501). That trial enrolled more than 21,000 mother-child pairs, and examined the effect of maternal levothyroxine treatment on the child’s IQ at 3 years. Among the children of women with hypothyroidism, the mean IQ scores were 99.2 and 100 in the treated and control groups – not significantly different. The proportions of children with an IQ of less than 85 were 12% in the treated group and 14% in the control group, also not significantly different.
Dr. Taylor’s cohort involved about 14,000 mother-child pairs from this study, all of whom were from Wales. Using national health care databases as well as study data, he was able to examine obstetric outcomes in women with low thyroid function (664) who received or did not receive levothyroxine early between 11 and 16 weeks’ gestation.
About half of the hypothyroid women (351) had TSH levels above 3.5 mU/L. The remainder had free T4 levels below 10.9 pmol/L. Each of these groups was randomized to levothyroxine treatment or placebo. The rest of the cohort had normal thyroid status.
The study’s primary endpoint was the rate of stillbirth. Secondary endpoints were cesarean section rate (both overall and early); gestational age at birth; and macrosomia.
Among the euthyroid group, the rate of stillbirth was 0.34%, similar to the national background rate. There were no stillbirths among women with high TSH who were treated. Three (1.68%) occurred in the untreated group. The TSH levels in those women before treatment were 3.63 mU/L, 3.66 mU/L, and 4.58 mU/L – not dramatically high, Dr. Taylor noted. “But they could have risen later in pregnancy as stress on the thyroid increased.”
After adjusting for maternal age, weight, parity, birth year, and smoking, stillbirths were five times more likely among the untreated women than the treated women. However, Dr. Taylor cautioned, “This is a very small number of events. But it is quite seductive to think that stillbirths could be prevented by levothyroxine.”
There were no significant associations of high TSH with macrosomia or gestational age.
Untreated low free T4 was not associated with stillbirth. However, Dr. Taylor said, it was very strongly associated with early C-section.
The overall C-section rate was similar between untreated and treated women (28%). But 5.6% of the untreated women had an early C-section, compared with none of the treated women. This hints strongly at a protective effect of levothyroxine, Dr. Taylor said. Early C-sections – between 26 and 32 weeks – are medically driven rather than driven by patient choice. This finding of fewer early interventions among treated women suggests that levothyroxine is exerting some protective effect, especially given the finding that infants of untreated mothers actually tended to be about 133 g lighter at birth.
“We would speculate this is probably due to a decrease in preeclampsia and gestational hypertension, which are more common among women with hypothyroidism.”
Infants of untreated mothers also were born slightly earlier – about half a week, he said at the meeting held by the American Thyroid Association, Asia-Oceania Thyroid Association, European Thyroid Association, and Latin American Thyroid Society.
Dr. Taylor had no financial disclosures.
AT ITC 2015
Key clinical point: Levothyroxine may improve obstetric outcomes in women with low thyroid function.
Major finding: Stillbirths were five times more likely among women who were untreated for high levels of thyroid-stimulating hormone during pregnancy.
Data source: The analysis comprised about 14,000 mother-child pairs.
Disclosures: Dr. Taylor had no financial disclosures.
Increased surveillance may explain post-Fukushima pediatric thyroid cancers
LAKE BUENA VISTA, FLA. – More cases of thyroid cancer are being seen in Japanese youth after the Fukushima Daiichi nuclear power plant accident, but the increased incidence may be an artifact of heightened surveillance.
“The thyroid cancers appear to have already occurred prior to radiation exposure,” said Dr. Shinichi Suzuki of the department of thyroid and endocrinology at Fukushima (Japan) Medical University. Radiation-induced thyroid cancers take about 5 years to become detectable, so physicians should just now be seeing the earliest cases of thyroid cancer related to Fukushima radiation exposure, according to Dr. Suzuki. He presented interim results of Japan’s universal screening protocol for children potentially affected by the Fukushima incident at the International Thyroid Conference.
The protocol, designed to screen everyone residing in the Fukushima prefecture and aged 19 years or younger at the time of the 2011 incident, has been highly successful, with over 80% of those eligible receiving a baseline screening that included a thyroid ultrasound exam.
Screening consisted of an initial thyroid ultrasound exam performed with a portable ultrasound device. If no cyst or nodule was found, then the patient would be seen at the next scheduled thyroid ultrasound exam, 2 years later. Patients with cysts 20 mm or less in greatest diameter or nodules 5 mm or smaller also were deferred to the next scheduled examination. Patients with cysts larger than 20 mm or nodules larger than 5 mm received confirmatory examination by detailed ultrasound examination, blood work, and fine-needle aspiration.
Of the 300,476 patients who received the preliminary baseline survey, 2,294 (0.8%) had an abnormality that warranted confirmatory examination and 91.9% of patients went on to have the confirmatory exams. Of these, 113 were assessed as malignant or suspicious for malignancy. Ninety-nine patients had surgery, with findings of 98 cases of thyroid cancer and one benign tumor.
Patients examined after April 2014 were part of an expanded protocol. Under this protocol, 169,455 patients (44.7% participation) were examined and 1,223 patients (0.8%) had suspicious findings on thyroid ultrasound exam. Participation rate for confirmatory testing for this group was 62.7%, with 25 patients’ thyroids having malignant or potentially malignant findings. Six of these patients had surgery, and thyroid cancer was found in all six cases.
Pooling data from the 138 malignant or suspicious cases from the two groups, 105 patients in total have had surgery, 13 patients with small, noninvasive masses are being watched, and a further 20 are awaiting surgery, Dr. Suzuki said at the meeting held by the American Thyroid Association, Asia-Oceania Thyroid Association, European Thyroid Association, and Latin American Thyroid Society.
Of the 97 patients with thyroid cancer who were treated at Fukushima University, 61 were female. The mean patient age at the time of the disaster was 14.8 ± 2.7 years (range, 6-18 years), while the mean age at diagnosis was 17.4 ± 2.8 years (range, 9-22 years). All patients were asymptomatic.
Tumors were unilateral in all but two patients. Mean tumor size was 15.1 ± 0.8 mm (range, 5-53 mm). Nearly all of the tumors (94/97) were papillary thyroid carcinoma, with 86 of those being classical-type papillary thyroid carcinoma. Three patients had poorly differentiated thyroid carcinoma. Fifty-eight patients (60%) had some intraglandular spread, while 71 (73%) had calcifications.
Dr. Suzuki and his collaborators compared these 97 cases with 37 cases of pediatric thyroid cancer in an historical Japanese cohort and to the 26 cases seen in a cohort from Belarus following the Chernobyl disaster. The Fukushima patients were significantly older than either comparison group, with mean age of 11.9 years for the historical Japanese cohort and 10.6 years for the children from Belarus. Tumor size was smaller than the historical Japanese cohort’s mean of 4.1 cm but about the same as that seen in Belarus (1.4 cm). Pulmonary metastases were more common in the historical Japanese cohort (19% vs. 4% in Belarus and 2% in Fukushima).
To have reference data that use similar techniques on a similar population, Japanese researchers are conducting thyroid ultrasound examsaccording to the Fukushima protocol concurrently in three other Japanese prefectures. This is especially important, Dr. Suzuki said, because rapid technological advances in ultrasound imaging mean that screening is much more likely to detect small abnormalities in the thyroid than would have been the case even a few years ago. For this reason, and also because much more radiation was released at the site of the Chernobyl nuclear disaster, only limited comparisons can be made between pediatric thyroid cancer rates from the two nuclear accidents.
Thyroid ultrasound exam “has the ability to detect a lot of thyroid cancers,” he said, so care must be taken to avoid overdiagnosis and overtreatment in this group of young people. Information to date from the Fukushima surveillance project does not yet “give us the clear view about the influence of radiation exposure after the accident on thyroid cancer occurrence,” he said.
Dr. Suzuki reported no relevant disclosures.
On Twitter @karioakes
LAKE BUENA VISTA, FLA. – More cases of thyroid cancer are being seen in Japanese youth after the Fukushima Daiichi nuclear power plant accident, but the increased incidence may be an artifact of heightened surveillance.
“The thyroid cancers appear to have already occurred prior to radiation exposure,” said Dr. Shinichi Suzuki of the department of thyroid and endocrinology at Fukushima (Japan) Medical University. Radiation-induced thyroid cancers take about 5 years to become detectable, so physicians should just now be seeing the earliest cases of thyroid cancer related to Fukushima radiation exposure, according to Dr. Suzuki. He presented interim results of Japan’s universal screening protocol for children potentially affected by the Fukushima incident at the International Thyroid Conference.
The protocol, designed to screen everyone residing in the Fukushima prefecture and aged 19 years or younger at the time of the 2011 incident, has been highly successful, with over 80% of those eligible receiving a baseline screening that included a thyroid ultrasound exam.
Screening consisted of an initial thyroid ultrasound exam performed with a portable ultrasound device. If no cyst or nodule was found, then the patient would be seen at the next scheduled thyroid ultrasound exam, 2 years later. Patients with cysts 20 mm or less in greatest diameter or nodules 5 mm or smaller also were deferred to the next scheduled examination. Patients with cysts larger than 20 mm or nodules larger than 5 mm received confirmatory examination by detailed ultrasound examination, blood work, and fine-needle aspiration.
Of the 300,476 patients who received the preliminary baseline survey, 2,294 (0.8%) had an abnormality that warranted confirmatory examination and 91.9% of patients went on to have the confirmatory exams. Of these, 113 were assessed as malignant or suspicious for malignancy. Ninety-nine patients had surgery, with findings of 98 cases of thyroid cancer and one benign tumor.
Patients examined after April 2014 were part of an expanded protocol. Under this protocol, 169,455 patients (44.7% participation) were examined and 1,223 patients (0.8%) had suspicious findings on thyroid ultrasound exam. Participation rate for confirmatory testing for this group was 62.7%, with 25 patients’ thyroids having malignant or potentially malignant findings. Six of these patients had surgery, and thyroid cancer was found in all six cases.
Pooling data from the 138 malignant or suspicious cases from the two groups, 105 patients in total have had surgery, 13 patients with small, noninvasive masses are being watched, and a further 20 are awaiting surgery, Dr. Suzuki said at the meeting held by the American Thyroid Association, Asia-Oceania Thyroid Association, European Thyroid Association, and Latin American Thyroid Society.
Of the 97 patients with thyroid cancer who were treated at Fukushima University, 61 were female. The mean patient age at the time of the disaster was 14.8 ± 2.7 years (range, 6-18 years), while the mean age at diagnosis was 17.4 ± 2.8 years (range, 9-22 years). All patients were asymptomatic.
Tumors were unilateral in all but two patients. Mean tumor size was 15.1 ± 0.8 mm (range, 5-53 mm). Nearly all of the tumors (94/97) were papillary thyroid carcinoma, with 86 of those being classical-type papillary thyroid carcinoma. Three patients had poorly differentiated thyroid carcinoma. Fifty-eight patients (60%) had some intraglandular spread, while 71 (73%) had calcifications.
Dr. Suzuki and his collaborators compared these 97 cases with 37 cases of pediatric thyroid cancer in an historical Japanese cohort and to the 26 cases seen in a cohort from Belarus following the Chernobyl disaster. The Fukushima patients were significantly older than either comparison group, with mean age of 11.9 years for the historical Japanese cohort and 10.6 years for the children from Belarus. Tumor size was smaller than the historical Japanese cohort’s mean of 4.1 cm but about the same as that seen in Belarus (1.4 cm). Pulmonary metastases were more common in the historical Japanese cohort (19% vs. 4% in Belarus and 2% in Fukushima).
To have reference data that use similar techniques on a similar population, Japanese researchers are conducting thyroid ultrasound examsaccording to the Fukushima protocol concurrently in three other Japanese prefectures. This is especially important, Dr. Suzuki said, because rapid technological advances in ultrasound imaging mean that screening is much more likely to detect small abnormalities in the thyroid than would have been the case even a few years ago. For this reason, and also because much more radiation was released at the site of the Chernobyl nuclear disaster, only limited comparisons can be made between pediatric thyroid cancer rates from the two nuclear accidents.
Thyroid ultrasound exam “has the ability to detect a lot of thyroid cancers,” he said, so care must be taken to avoid overdiagnosis and overtreatment in this group of young people. Information to date from the Fukushima surveillance project does not yet “give us the clear view about the influence of radiation exposure after the accident on thyroid cancer occurrence,” he said.
Dr. Suzuki reported no relevant disclosures.
On Twitter @karioakes
LAKE BUENA VISTA, FLA. – More cases of thyroid cancer are being seen in Japanese youth after the Fukushima Daiichi nuclear power plant accident, but the increased incidence may be an artifact of heightened surveillance.
“The thyroid cancers appear to have already occurred prior to radiation exposure,” said Dr. Shinichi Suzuki of the department of thyroid and endocrinology at Fukushima (Japan) Medical University. Radiation-induced thyroid cancers take about 5 years to become detectable, so physicians should just now be seeing the earliest cases of thyroid cancer related to Fukushima radiation exposure, according to Dr. Suzuki. He presented interim results of Japan’s universal screening protocol for children potentially affected by the Fukushima incident at the International Thyroid Conference.
The protocol, designed to screen everyone residing in the Fukushima prefecture and aged 19 years or younger at the time of the 2011 incident, has been highly successful, with over 80% of those eligible receiving a baseline screening that included a thyroid ultrasound exam.
Screening consisted of an initial thyroid ultrasound exam performed with a portable ultrasound device. If no cyst or nodule was found, then the patient would be seen at the next scheduled thyroid ultrasound exam, 2 years later. Patients with cysts 20 mm or less in greatest diameter or nodules 5 mm or smaller also were deferred to the next scheduled examination. Patients with cysts larger than 20 mm or nodules larger than 5 mm received confirmatory examination by detailed ultrasound examination, blood work, and fine-needle aspiration.
Of the 300,476 patients who received the preliminary baseline survey, 2,294 (0.8%) had an abnormality that warranted confirmatory examination and 91.9% of patients went on to have the confirmatory exams. Of these, 113 were assessed as malignant or suspicious for malignancy. Ninety-nine patients had surgery, with findings of 98 cases of thyroid cancer and one benign tumor.
Patients examined after April 2014 were part of an expanded protocol. Under this protocol, 169,455 patients (44.7% participation) were examined and 1,223 patients (0.8%) had suspicious findings on thyroid ultrasound exam. Participation rate for confirmatory testing for this group was 62.7%, with 25 patients’ thyroids having malignant or potentially malignant findings. Six of these patients had surgery, and thyroid cancer was found in all six cases.
Pooling data from the 138 malignant or suspicious cases from the two groups, 105 patients in total have had surgery, 13 patients with small, noninvasive masses are being watched, and a further 20 are awaiting surgery, Dr. Suzuki said at the meeting held by the American Thyroid Association, Asia-Oceania Thyroid Association, European Thyroid Association, and Latin American Thyroid Society.
Of the 97 patients with thyroid cancer who were treated at Fukushima University, 61 were female. The mean patient age at the time of the disaster was 14.8 ± 2.7 years (range, 6-18 years), while the mean age at diagnosis was 17.4 ± 2.8 years (range, 9-22 years). All patients were asymptomatic.
Tumors were unilateral in all but two patients. Mean tumor size was 15.1 ± 0.8 mm (range, 5-53 mm). Nearly all of the tumors (94/97) were papillary thyroid carcinoma, with 86 of those being classical-type papillary thyroid carcinoma. Three patients had poorly differentiated thyroid carcinoma. Fifty-eight patients (60%) had some intraglandular spread, while 71 (73%) had calcifications.
Dr. Suzuki and his collaborators compared these 97 cases with 37 cases of pediatric thyroid cancer in an historical Japanese cohort and to the 26 cases seen in a cohort from Belarus following the Chernobyl disaster. The Fukushima patients were significantly older than either comparison group, with mean age of 11.9 years for the historical Japanese cohort and 10.6 years for the children from Belarus. Tumor size was smaller than the historical Japanese cohort’s mean of 4.1 cm but about the same as that seen in Belarus (1.4 cm). Pulmonary metastases were more common in the historical Japanese cohort (19% vs. 4% in Belarus and 2% in Fukushima).
To have reference data that use similar techniques on a similar population, Japanese researchers are conducting thyroid ultrasound examsaccording to the Fukushima protocol concurrently in three other Japanese prefectures. This is especially important, Dr. Suzuki said, because rapid technological advances in ultrasound imaging mean that screening is much more likely to detect small abnormalities in the thyroid than would have been the case even a few years ago. For this reason, and also because much more radiation was released at the site of the Chernobyl nuclear disaster, only limited comparisons can be made between pediatric thyroid cancer rates from the two nuclear accidents.
Thyroid ultrasound exam “has the ability to detect a lot of thyroid cancers,” he said, so care must be taken to avoid overdiagnosis and overtreatment in this group of young people. Information to date from the Fukushima surveillance project does not yet “give us the clear view about the influence of radiation exposure after the accident on thyroid cancer occurrence,” he said.
Dr. Suzuki reported no relevant disclosures.
On Twitter @karioakes
AT ITC 2015
Key clinical point: The increased incidence of thyroid cancers in Japanese youth after the Fukushima nuclear accident may be an artifact of increased surveillance.
Major finding: A total of 138 thyroid cancers have been found when screening 469,931 children in Fukushima after the 2011 nuclear power plant accident.
Data source: Universal screening for thyroid cancer among individuals who were aged 18 years or younger and resident in Fukushima at the time of the accident.
Disclosures: Dr. Suzuki reported no relevant disclosures.
Surgical options for Graves orbitopathy can be vision saving
LAKE BUENA VISTA, FLA. – In the face of serious – even vision-threatening – complications, endocrinologists treating patients with Graves orbitopathy should understand when and how surgical options should be considered, according to Dr. Peter J. Dolman, speaking at the 15th International Thyroid Congress.
For most patients, the course of Graves orbitopathy (GO) is likely to follow “Rundle’s curve,” with a rapid progression to the most severe symptoms, and a more gradual abatement of eye symptoms that usually does not return to baseline. About one-third of patients with GO will develop more severe disease, will need intensive medical management, and may require surgical referral. The VISA system, which Dr. Dolman helped develop, classifies thyroid eye disease according to the four criteria of vision/optic neuropathy, inflammation/congestion, strabismus/motility, and appearance/exposure.
During early disease stages, medical management is usually the most effective in quieting the disease course. “The earlier you can treat the patient, the fewer consequences to the orbit,” he said. Later surgical treatment can work to restore alignment, lower the lids, and reduce proptosis. However, when disease severity threatens vision, earlier surgical referral can be needed, said Dr. Dolman, clinical professor in the department of ophthalmology and visual sciences at the University of British Columbia in Vancouver.
Using the VISA assessment system, the first major area of concern is optic neuropathy. This usually happens in the context of pronounced inflammation of retro-orbital contents and also of the eye muscles. In this circumstance, the inflammation crowds and compresses the optic nerve. Decreased color perception can be an early symptom, noted by the patient well before central vision loss, said Dr. Dolman. If compression is unilateral, an afferent pupil defect may be noted. A CT scan will show apical compression of the optic nerve. Clinical activity scores may not rise significantly, so physicians must have a high index of suspicion for optic neuropathy.
In his practice, 85% of patients with GO complicated by optic neuropathy show some improvement on steroids, but Dr. Dolman still performs orbital decompressions on 80% of these patients overall. Radiotherapy may be effective over time as well. Complications of orbital decompression can include CSF leak, intracranial hemorrhage, increased strabismus (experienced by 54% of patients in one study), and the chance of relapse with vision loss (in 8% of patients). Even after surgery, disease progresses in about 30% of patients; therefore, “It’s wise to continue with steroids and radiotherapy after surgery.”
Inflammation and congestion represent the “I” in VISA. In addition to the local inflammatory response, local tissue edema can increase vasocongestion by mechanical means when venules and veins are compressed. The resulting chemosis can exacerbate pain and irritation and make lid closure even more difficult, increasing the risk of corneal damage. Steroids may help relieve chronic congestion and may be useful in those patients in whom exposure is not compromising corneal integrity. But orbital decompression may be needed when the patient’s stabilized GO picture still has a significant congestive component.
Strabismus and eye motility impairment can present a significant impediment in patients’ daily lives. Diplopia can preclude driving, impair reading ability, and even affect ambulation. Initial treatment with steroids and/or radiotherapy during the initial phase may alleviate the tissue inflammation and edema that are impairing muscle function; eye patching should also be used when helpful. Once GO has stabilized, visual correction with prisms may help less severe strabismus, while some patients will need eye muscle surgery to correct alignment.
Eye appearance and risk for corneal damage from exposure are the final considerations in the VISA system. Proptosis may be severe enough that patients cannot fully blink or close their eyes enough to eliminate the palpebral fissure during sleep, risking corneal integrity. If initial treatment with steroids and radiotherapy is not effective – as it will not be in 40%-50% of patients – then surgery should be considered. Options include performing a temporary tarsorrhaphy or an orbit decompression with lid narrowing. Because the surgical approach is different when decompression is performed for proptosis, “complications of decompression are much less common for proptosis than for optic neuropathy,” said Dr. Dolman.
On Twitter @karioakes
LAKE BUENA VISTA, FLA. – In the face of serious – even vision-threatening – complications, endocrinologists treating patients with Graves orbitopathy should understand when and how surgical options should be considered, according to Dr. Peter J. Dolman, speaking at the 15th International Thyroid Congress.
For most patients, the course of Graves orbitopathy (GO) is likely to follow “Rundle’s curve,” with a rapid progression to the most severe symptoms, and a more gradual abatement of eye symptoms that usually does not return to baseline. About one-third of patients with GO will develop more severe disease, will need intensive medical management, and may require surgical referral. The VISA system, which Dr. Dolman helped develop, classifies thyroid eye disease according to the four criteria of vision/optic neuropathy, inflammation/congestion, strabismus/motility, and appearance/exposure.
During early disease stages, medical management is usually the most effective in quieting the disease course. “The earlier you can treat the patient, the fewer consequences to the orbit,” he said. Later surgical treatment can work to restore alignment, lower the lids, and reduce proptosis. However, when disease severity threatens vision, earlier surgical referral can be needed, said Dr. Dolman, clinical professor in the department of ophthalmology and visual sciences at the University of British Columbia in Vancouver.
Using the VISA assessment system, the first major area of concern is optic neuropathy. This usually happens in the context of pronounced inflammation of retro-orbital contents and also of the eye muscles. In this circumstance, the inflammation crowds and compresses the optic nerve. Decreased color perception can be an early symptom, noted by the patient well before central vision loss, said Dr. Dolman. If compression is unilateral, an afferent pupil defect may be noted. A CT scan will show apical compression of the optic nerve. Clinical activity scores may not rise significantly, so physicians must have a high index of suspicion for optic neuropathy.
In his practice, 85% of patients with GO complicated by optic neuropathy show some improvement on steroids, but Dr. Dolman still performs orbital decompressions on 80% of these patients overall. Radiotherapy may be effective over time as well. Complications of orbital decompression can include CSF leak, intracranial hemorrhage, increased strabismus (experienced by 54% of patients in one study), and the chance of relapse with vision loss (in 8% of patients). Even after surgery, disease progresses in about 30% of patients; therefore, “It’s wise to continue with steroids and radiotherapy after surgery.”
Inflammation and congestion represent the “I” in VISA. In addition to the local inflammatory response, local tissue edema can increase vasocongestion by mechanical means when venules and veins are compressed. The resulting chemosis can exacerbate pain and irritation and make lid closure even more difficult, increasing the risk of corneal damage. Steroids may help relieve chronic congestion and may be useful in those patients in whom exposure is not compromising corneal integrity. But orbital decompression may be needed when the patient’s stabilized GO picture still has a significant congestive component.
Strabismus and eye motility impairment can present a significant impediment in patients’ daily lives. Diplopia can preclude driving, impair reading ability, and even affect ambulation. Initial treatment with steroids and/or radiotherapy during the initial phase may alleviate the tissue inflammation and edema that are impairing muscle function; eye patching should also be used when helpful. Once GO has stabilized, visual correction with prisms may help less severe strabismus, while some patients will need eye muscle surgery to correct alignment.
Eye appearance and risk for corneal damage from exposure are the final considerations in the VISA system. Proptosis may be severe enough that patients cannot fully blink or close their eyes enough to eliminate the palpebral fissure during sleep, risking corneal integrity. If initial treatment with steroids and radiotherapy is not effective – as it will not be in 40%-50% of patients – then surgery should be considered. Options include performing a temporary tarsorrhaphy or an orbit decompression with lid narrowing. Because the surgical approach is different when decompression is performed for proptosis, “complications of decompression are much less common for proptosis than for optic neuropathy,” said Dr. Dolman.
On Twitter @karioakes
LAKE BUENA VISTA, FLA. – In the face of serious – even vision-threatening – complications, endocrinologists treating patients with Graves orbitopathy should understand when and how surgical options should be considered, according to Dr. Peter J. Dolman, speaking at the 15th International Thyroid Congress.
For most patients, the course of Graves orbitopathy (GO) is likely to follow “Rundle’s curve,” with a rapid progression to the most severe symptoms, and a more gradual abatement of eye symptoms that usually does not return to baseline. About one-third of patients with GO will develop more severe disease, will need intensive medical management, and may require surgical referral. The VISA system, which Dr. Dolman helped develop, classifies thyroid eye disease according to the four criteria of vision/optic neuropathy, inflammation/congestion, strabismus/motility, and appearance/exposure.
During early disease stages, medical management is usually the most effective in quieting the disease course. “The earlier you can treat the patient, the fewer consequences to the orbit,” he said. Later surgical treatment can work to restore alignment, lower the lids, and reduce proptosis. However, when disease severity threatens vision, earlier surgical referral can be needed, said Dr. Dolman, clinical professor in the department of ophthalmology and visual sciences at the University of British Columbia in Vancouver.
Using the VISA assessment system, the first major area of concern is optic neuropathy. This usually happens in the context of pronounced inflammation of retro-orbital contents and also of the eye muscles. In this circumstance, the inflammation crowds and compresses the optic nerve. Decreased color perception can be an early symptom, noted by the patient well before central vision loss, said Dr. Dolman. If compression is unilateral, an afferent pupil defect may be noted. A CT scan will show apical compression of the optic nerve. Clinical activity scores may not rise significantly, so physicians must have a high index of suspicion for optic neuropathy.
In his practice, 85% of patients with GO complicated by optic neuropathy show some improvement on steroids, but Dr. Dolman still performs orbital decompressions on 80% of these patients overall. Radiotherapy may be effective over time as well. Complications of orbital decompression can include CSF leak, intracranial hemorrhage, increased strabismus (experienced by 54% of patients in one study), and the chance of relapse with vision loss (in 8% of patients). Even after surgery, disease progresses in about 30% of patients; therefore, “It’s wise to continue with steroids and radiotherapy after surgery.”
Inflammation and congestion represent the “I” in VISA. In addition to the local inflammatory response, local tissue edema can increase vasocongestion by mechanical means when venules and veins are compressed. The resulting chemosis can exacerbate pain and irritation and make lid closure even more difficult, increasing the risk of corneal damage. Steroids may help relieve chronic congestion and may be useful in those patients in whom exposure is not compromising corneal integrity. But orbital decompression may be needed when the patient’s stabilized GO picture still has a significant congestive component.
Strabismus and eye motility impairment can present a significant impediment in patients’ daily lives. Diplopia can preclude driving, impair reading ability, and even affect ambulation. Initial treatment with steroids and/or radiotherapy during the initial phase may alleviate the tissue inflammation and edema that are impairing muscle function; eye patching should also be used when helpful. Once GO has stabilized, visual correction with prisms may help less severe strabismus, while some patients will need eye muscle surgery to correct alignment.
Eye appearance and risk for corneal damage from exposure are the final considerations in the VISA system. Proptosis may be severe enough that patients cannot fully blink or close their eyes enough to eliminate the palpebral fissure during sleep, risking corneal integrity. If initial treatment with steroids and radiotherapy is not effective – as it will not be in 40%-50% of patients – then surgery should be considered. Options include performing a temporary tarsorrhaphy or an orbit decompression with lid narrowing. Because the surgical approach is different when decompression is performed for proptosis, “complications of decompression are much less common for proptosis than for optic neuropathy,” said Dr. Dolman.
On Twitter @karioakes
EXPERT ANALYSIS FROM THE ITC 2015
Early A-bomb radiation not linked to thyroid function
LAKE BUENA VISTA, FLA. – No link was found between atomic bomb radiation exposure in childhood and autoimmune thyroid disease or thyroid dysfunction in a study of nearly 2,700 Hiroshima and Nagasaki atomic bomb survivors.
Exposure among the 2,668 survivors included in the survey occurred prior to age 10 years, with follow-up more than 60 years later. The prevalence of anti–thyroid peroxidase (anti-TPO) positivity and/or antithyroglobulin (anti-Tg) antibodies, hypothyroidism, and hyperthyroidism was 21.5%, 4.8%, and 1.2%, respectively, when measured between October 2007 and October 2011, Dr. Misa Imaizumi of the Radiation Effects Research Foundation, Nagasaki, Japan, reported at the International Thyroid Congress.
All patients with hyperthyroidism had Graves disease, and the prevalence of anti–thyroid antibody–positive and –negative hypothyroidism was 2.1% and 2.7%, respectively, she said at the meeting held by the American Thyroid Association, Asia-Oceania Thyroid Association, European Thyroid Association, and Latin American Thyroid Society.
An analysis showed no significant dose-response relationship between radiation exposure and any thyroid disease (P greater than .1). This remained true when additional analyses were performed using alternative definitions of hypothyroidism and hyperthyroidism, such as subclinical, antibody-positive, and antibody-negative disease, she noted.
Study subjects included 1,213 men and 1,455 women with known atomic bomb thyroid radiation doses during childhood (mean thyroid dose, 0.182 Gy; median dose, 0.018 Gy).
“As you know, the risk of thyroid cancer increases by radiation exposure, and an increased risk of thyroid cancer has been observed in atomic bomb survivors. It is also well-known that high-dose radiation exposure – several 10s of gray – induces hypothyroidism, but the influence of radiation exposure by low to moderate doses – less than 5 gray – on thyroid dysfunction has been debated, and [studies of] the effects of atomic bomb radiation have been inconclusive,” Dr. Imaizumi said.
Because the radiation sensitivity of the thyroid is believed to be higher in children than in adults, she and her colleagues at the Radiation Effects Research Foundation – a Japan/U.S. collaboration that studies the effects of atomic bomb radiation for peaceful purposes – investigated the effects of childhood exposure on later thyroid dysfunction. Evaluations were conducted between October 2007 and October 2011; patients had a mean age of 68 years at the time of evaluation.
Information about previous thyroid diseases was obtained by questionnaire and by measurement of T4, thyroid-stimulating hormone, anti-TPO antibody, and anti-Tg antibody levels.
“In conclusion, associations between radiation exposure and thyroid dysfunction and other thyroid disease were not found in atomic bomb survivors 60 years after exposure in childhood,” she said.
Dr. Imaizumi reported having no relevant financial disclosures.
LAKE BUENA VISTA, FLA. – No link was found between atomic bomb radiation exposure in childhood and autoimmune thyroid disease or thyroid dysfunction in a study of nearly 2,700 Hiroshima and Nagasaki atomic bomb survivors.
Exposure among the 2,668 survivors included in the survey occurred prior to age 10 years, with follow-up more than 60 years later. The prevalence of anti–thyroid peroxidase (anti-TPO) positivity and/or antithyroglobulin (anti-Tg) antibodies, hypothyroidism, and hyperthyroidism was 21.5%, 4.8%, and 1.2%, respectively, when measured between October 2007 and October 2011, Dr. Misa Imaizumi of the Radiation Effects Research Foundation, Nagasaki, Japan, reported at the International Thyroid Congress.
All patients with hyperthyroidism had Graves disease, and the prevalence of anti–thyroid antibody–positive and –negative hypothyroidism was 2.1% and 2.7%, respectively, she said at the meeting held by the American Thyroid Association, Asia-Oceania Thyroid Association, European Thyroid Association, and Latin American Thyroid Society.
An analysis showed no significant dose-response relationship between radiation exposure and any thyroid disease (P greater than .1). This remained true when additional analyses were performed using alternative definitions of hypothyroidism and hyperthyroidism, such as subclinical, antibody-positive, and antibody-negative disease, she noted.
Study subjects included 1,213 men and 1,455 women with known atomic bomb thyroid radiation doses during childhood (mean thyroid dose, 0.182 Gy; median dose, 0.018 Gy).
“As you know, the risk of thyroid cancer increases by radiation exposure, and an increased risk of thyroid cancer has been observed in atomic bomb survivors. It is also well-known that high-dose radiation exposure – several 10s of gray – induces hypothyroidism, but the influence of radiation exposure by low to moderate doses – less than 5 gray – on thyroid dysfunction has been debated, and [studies of] the effects of atomic bomb radiation have been inconclusive,” Dr. Imaizumi said.
Because the radiation sensitivity of the thyroid is believed to be higher in children than in adults, she and her colleagues at the Radiation Effects Research Foundation – a Japan/U.S. collaboration that studies the effects of atomic bomb radiation for peaceful purposes – investigated the effects of childhood exposure on later thyroid dysfunction. Evaluations were conducted between October 2007 and October 2011; patients had a mean age of 68 years at the time of evaluation.
Information about previous thyroid diseases was obtained by questionnaire and by measurement of T4, thyroid-stimulating hormone, anti-TPO antibody, and anti-Tg antibody levels.
“In conclusion, associations between radiation exposure and thyroid dysfunction and other thyroid disease were not found in atomic bomb survivors 60 years after exposure in childhood,” she said.
Dr. Imaizumi reported having no relevant financial disclosures.
LAKE BUENA VISTA, FLA. – No link was found between atomic bomb radiation exposure in childhood and autoimmune thyroid disease or thyroid dysfunction in a study of nearly 2,700 Hiroshima and Nagasaki atomic bomb survivors.
Exposure among the 2,668 survivors included in the survey occurred prior to age 10 years, with follow-up more than 60 years later. The prevalence of anti–thyroid peroxidase (anti-TPO) positivity and/or antithyroglobulin (anti-Tg) antibodies, hypothyroidism, and hyperthyroidism was 21.5%, 4.8%, and 1.2%, respectively, when measured between October 2007 and October 2011, Dr. Misa Imaizumi of the Radiation Effects Research Foundation, Nagasaki, Japan, reported at the International Thyroid Congress.
All patients with hyperthyroidism had Graves disease, and the prevalence of anti–thyroid antibody–positive and –negative hypothyroidism was 2.1% and 2.7%, respectively, she said at the meeting held by the American Thyroid Association, Asia-Oceania Thyroid Association, European Thyroid Association, and Latin American Thyroid Society.
An analysis showed no significant dose-response relationship between radiation exposure and any thyroid disease (P greater than .1). This remained true when additional analyses were performed using alternative definitions of hypothyroidism and hyperthyroidism, such as subclinical, antibody-positive, and antibody-negative disease, she noted.
Study subjects included 1,213 men and 1,455 women with known atomic bomb thyroid radiation doses during childhood (mean thyroid dose, 0.182 Gy; median dose, 0.018 Gy).
“As you know, the risk of thyroid cancer increases by radiation exposure, and an increased risk of thyroid cancer has been observed in atomic bomb survivors. It is also well-known that high-dose radiation exposure – several 10s of gray – induces hypothyroidism, but the influence of radiation exposure by low to moderate doses – less than 5 gray – on thyroid dysfunction has been debated, and [studies of] the effects of atomic bomb radiation have been inconclusive,” Dr. Imaizumi said.
Because the radiation sensitivity of the thyroid is believed to be higher in children than in adults, she and her colleagues at the Radiation Effects Research Foundation – a Japan/U.S. collaboration that studies the effects of atomic bomb radiation for peaceful purposes – investigated the effects of childhood exposure on later thyroid dysfunction. Evaluations were conducted between October 2007 and October 2011; patients had a mean age of 68 years at the time of evaluation.
Information about previous thyroid diseases was obtained by questionnaire and by measurement of T4, thyroid-stimulating hormone, anti-TPO antibody, and anti-Tg antibody levels.
“In conclusion, associations between radiation exposure and thyroid dysfunction and other thyroid disease were not found in atomic bomb survivors 60 years after exposure in childhood,” she said.
Dr. Imaizumi reported having no relevant financial disclosures.
AT THE INTERNATIONAL THYROID CONGRESS
Key clinical point: No link was found between atomic bomb radiation exposure in childhood and autoimmune thyroid disease or thyroid dysfunction in a study of nearly 2,700 Hiroshima and Nagasaki atomic bomb survivors.
Major finding: A dose-response analysis showed no significant dose-response relationship between radiation exposure and any thyroid disease (P greater than .1).
Data source: A survey and evaluation of 2,668 subjects.
Disclosures: Dr. Imaizumi reported having no relevant financial disclosures.
Percutaneous ethanol effective for small papillary thyroid cancers
LAKE BUENA VISTA, FLA. – An outpatient procedure may represent an efficacious and safe alternative to surgery for those patients with small papillary thyroid cancers who prefer definitive treatment over the “wait and watch” approach. Further, at one institution, the cost-effective alternative to surgery saved almost $40,000 per patient.
Ultrasound-guided percutaneous ethanol injection (UPEA) of small (cT1N0) intrathyroidal papillary thyroid cancer (SIPC) successfully reduced tumor volume by a median of 92%, eliminated tumor blood flow, and was very well tolerated by a series of 13 patients who received UPEA at the Mayo Clinic, Rochester, Minn.
Dr. Ian D. Hay, a consultant in Mayo’s division of endocrinology, diabetes, metabolism, and nutrition, presented the findings during a poster session at the International Thyroid Congress.
Dr. Hay and his colleagues treated 13 patients with a total of 15 tumors with injections of percutaneous ethanol. The first patient received just one injection; the remaining patients received one injection to each tumor site on each of 2 consecutive days. Five of the tumor foci had less than a 50% reduction in tumor volume at the first follow-up visit, so those tumors were injected a third time.
Patients in the series ranged from 38 to 86 years old (median 45), and five patients had significant comorbidities: one had congestive heart failure and the other four had concomitant unrelated cancers. Tumors were a median 8 mm in size, with volumes ranging from 25 to 676 mm3 (median 140 mm3).
All of the injections were performed under ultrasound guidance, and a median of 0.9 cc of ethanol was injected into each tumor. Ultrasound examination was performed at each follow-up visit to evaluate tumor volume and blood flow. Dr. Hay reported that the procedure was well tolerated: Local neck tenderness resolved within a day or two, and there were no reports of hoarseness or laryngeal nerve palsy.
Patients were followed for a mean 2.0 years (range, 0.4-5.7 years), with a median tumor reduction of 92% (range 46%-100%). For the nine tumors that were still identifiable on ultrasound at the time of reporting, the mean volume had decreased by 73%. Six tumor foci had completely disappeared, and no tumor had detectable blood flow on Doppler exam. Tumor thyroglobulin levels remained stable in all patients, and no nodal metastases were identified, Dr. Hay reported at the meeting, which was held by the American Thyroid Association, Asia-Oceania Thyroid Association, European Thyroid Association, and Latin American Thyroid Society.
Internationally, the approach to managing SIPC varies from lobectomy to near-total thyroidectomy to active surveillance. For patients who prefer definitive management of their tumors but are reluctant to have surgery or who may have significant comorbidities, UPEA may represent a safe alternative, and at significant cost savings compared to surgery: Dr. Hay and his colleagues reported that they estimated the average cost savings at their institution to be over $38,000 per patient. “If prospective trials of observation vs. surgery for SIPC are to occur in the USA, perhaps it could be included as a ‘third arm’ in such trials,” Dr. Hay and his colleagues said.
On Twitter @karioakes
LAKE BUENA VISTA, FLA. – An outpatient procedure may represent an efficacious and safe alternative to surgery for those patients with small papillary thyroid cancers who prefer definitive treatment over the “wait and watch” approach. Further, at one institution, the cost-effective alternative to surgery saved almost $40,000 per patient.
Ultrasound-guided percutaneous ethanol injection (UPEA) of small (cT1N0) intrathyroidal papillary thyroid cancer (SIPC) successfully reduced tumor volume by a median of 92%, eliminated tumor blood flow, and was very well tolerated by a series of 13 patients who received UPEA at the Mayo Clinic, Rochester, Minn.
Dr. Ian D. Hay, a consultant in Mayo’s division of endocrinology, diabetes, metabolism, and nutrition, presented the findings during a poster session at the International Thyroid Congress.
Dr. Hay and his colleagues treated 13 patients with a total of 15 tumors with injections of percutaneous ethanol. The first patient received just one injection; the remaining patients received one injection to each tumor site on each of 2 consecutive days. Five of the tumor foci had less than a 50% reduction in tumor volume at the first follow-up visit, so those tumors were injected a third time.
Patients in the series ranged from 38 to 86 years old (median 45), and five patients had significant comorbidities: one had congestive heart failure and the other four had concomitant unrelated cancers. Tumors were a median 8 mm in size, with volumes ranging from 25 to 676 mm3 (median 140 mm3).
All of the injections were performed under ultrasound guidance, and a median of 0.9 cc of ethanol was injected into each tumor. Ultrasound examination was performed at each follow-up visit to evaluate tumor volume and blood flow. Dr. Hay reported that the procedure was well tolerated: Local neck tenderness resolved within a day or two, and there were no reports of hoarseness or laryngeal nerve palsy.
Patients were followed for a mean 2.0 years (range, 0.4-5.7 years), with a median tumor reduction of 92% (range 46%-100%). For the nine tumors that were still identifiable on ultrasound at the time of reporting, the mean volume had decreased by 73%. Six tumor foci had completely disappeared, and no tumor had detectable blood flow on Doppler exam. Tumor thyroglobulin levels remained stable in all patients, and no nodal metastases were identified, Dr. Hay reported at the meeting, which was held by the American Thyroid Association, Asia-Oceania Thyroid Association, European Thyroid Association, and Latin American Thyroid Society.
Internationally, the approach to managing SIPC varies from lobectomy to near-total thyroidectomy to active surveillance. For patients who prefer definitive management of their tumors but are reluctant to have surgery or who may have significant comorbidities, UPEA may represent a safe alternative, and at significant cost savings compared to surgery: Dr. Hay and his colleagues reported that they estimated the average cost savings at their institution to be over $38,000 per patient. “If prospective trials of observation vs. surgery for SIPC are to occur in the USA, perhaps it could be included as a ‘third arm’ in such trials,” Dr. Hay and his colleagues said.
On Twitter @karioakes
LAKE BUENA VISTA, FLA. – An outpatient procedure may represent an efficacious and safe alternative to surgery for those patients with small papillary thyroid cancers who prefer definitive treatment over the “wait and watch” approach. Further, at one institution, the cost-effective alternative to surgery saved almost $40,000 per patient.
Ultrasound-guided percutaneous ethanol injection (UPEA) of small (cT1N0) intrathyroidal papillary thyroid cancer (SIPC) successfully reduced tumor volume by a median of 92%, eliminated tumor blood flow, and was very well tolerated by a series of 13 patients who received UPEA at the Mayo Clinic, Rochester, Minn.
Dr. Ian D. Hay, a consultant in Mayo’s division of endocrinology, diabetes, metabolism, and nutrition, presented the findings during a poster session at the International Thyroid Congress.
Dr. Hay and his colleagues treated 13 patients with a total of 15 tumors with injections of percutaneous ethanol. The first patient received just one injection; the remaining patients received one injection to each tumor site on each of 2 consecutive days. Five of the tumor foci had less than a 50% reduction in tumor volume at the first follow-up visit, so those tumors were injected a third time.
Patients in the series ranged from 38 to 86 years old (median 45), and five patients had significant comorbidities: one had congestive heart failure and the other four had concomitant unrelated cancers. Tumors were a median 8 mm in size, with volumes ranging from 25 to 676 mm3 (median 140 mm3).
All of the injections were performed under ultrasound guidance, and a median of 0.9 cc of ethanol was injected into each tumor. Ultrasound examination was performed at each follow-up visit to evaluate tumor volume and blood flow. Dr. Hay reported that the procedure was well tolerated: Local neck tenderness resolved within a day or two, and there were no reports of hoarseness or laryngeal nerve palsy.
Patients were followed for a mean 2.0 years (range, 0.4-5.7 years), with a median tumor reduction of 92% (range 46%-100%). For the nine tumors that were still identifiable on ultrasound at the time of reporting, the mean volume had decreased by 73%. Six tumor foci had completely disappeared, and no tumor had detectable blood flow on Doppler exam. Tumor thyroglobulin levels remained stable in all patients, and no nodal metastases were identified, Dr. Hay reported at the meeting, which was held by the American Thyroid Association, Asia-Oceania Thyroid Association, European Thyroid Association, and Latin American Thyroid Society.
Internationally, the approach to managing SIPC varies from lobectomy to near-total thyroidectomy to active surveillance. For patients who prefer definitive management of their tumors but are reluctant to have surgery or who may have significant comorbidities, UPEA may represent a safe alternative, and at significant cost savings compared to surgery: Dr. Hay and his colleagues reported that they estimated the average cost savings at their institution to be over $38,000 per patient. “If prospective trials of observation vs. surgery for SIPC are to occur in the USA, perhaps it could be included as a ‘third arm’ in such trials,” Dr. Hay and his colleagues said.
On Twitter @karioakes
AT ITC 2015
Key clinical point: Ultrasound-guided percutaneous ethanol ablation (UPEA) is an efficacious, cost-effective, and noninvasive definitive treatment for small papillary thyroid cancers.
Major finding: Fifteen tumors in 13 patients were successfully treated with UPEA with a mean 92% reduction in tumor volume and no complications or metastasis at a mean 2-year follow-up.
Data source: Series of 13 patients with 15 tumors treated at the Mayo Clinic for small intrathyroidal papillary cancers.
Disclosures: No disclosures were identified.
RFA, ethanol ablation equally effective for thyroid nodules
LAKE BUENA VISTA, FLA. – Ethanol ablation is just as effective as radiofrequency ablation for cystic thyroid nodules, resulting in similar volume reduction and similarly improving symptomatic and cosmetic outcomes at 6 months.
Radiofrequnecy ablation (RFA) did have a slight edge over ethanol injection (EA) in therapeutic response, Dr. Hye Sun Park said at the International Thyroid Conference. But because ethanol ablation is easier and less expensive, she recommended that it be considered as first-line therapy for these lesions.
Dr. Park of the University of Ulsan, Asan Medical Center in Seoul, South Korea, reported a trial of 46 patients, mean age 50 years old, with benign cystic thyroid nodules who were randomized to the two treatments. Patients randomized to ethanol, however, had significantly larger-volume lesions (14.7 vs. 8.6 mL), and symptom scores. Cosmetic scores and nodule vascularity were similar.
RFA was performed with an 18-gauge monopolar, internally cooled electrode with a 1-cm active tip, using the moving shot technique. Patients undergoing EA first had fluid removed from the nodules using a 16-gauge needle. Ablation consisted of an injection of 99% ethanol into the cystic space, which was removed after 2 minutes.
The primary outcome was nodule volume at 6 months. Secondary outcomes were postprocedural pain and complications, Dr. Park said at the meeting held by the American Thyroid Association, Asia-Oceania Thyroid Association , European Thyroid Association, and Latin American Thyroid Society.
At follow-up, the volume reductions were similar in RFA and EA (87.5 vs. 82.4 ml). The therapeutic success rate was 100% for patients who had RFA and 92% for those who had EA. Two patients in the EA group had major bleeding from the nodule, which interrupted the procedure; they later had a successful RFA. There were no complications in the RFA group.
There was only one major complication during follow-up: One patient who received EA complained of voice change, which resolved spontaneously by 2 months after ablation.
Dr. Park had no financial disclosures.
LAKE BUENA VISTA, FLA. – Ethanol ablation is just as effective as radiofrequency ablation for cystic thyroid nodules, resulting in similar volume reduction and similarly improving symptomatic and cosmetic outcomes at 6 months.
Radiofrequnecy ablation (RFA) did have a slight edge over ethanol injection (EA) in therapeutic response, Dr. Hye Sun Park said at the International Thyroid Conference. But because ethanol ablation is easier and less expensive, she recommended that it be considered as first-line therapy for these lesions.
Dr. Park of the University of Ulsan, Asan Medical Center in Seoul, South Korea, reported a trial of 46 patients, mean age 50 years old, with benign cystic thyroid nodules who were randomized to the two treatments. Patients randomized to ethanol, however, had significantly larger-volume lesions (14.7 vs. 8.6 mL), and symptom scores. Cosmetic scores and nodule vascularity were similar.
RFA was performed with an 18-gauge monopolar, internally cooled electrode with a 1-cm active tip, using the moving shot technique. Patients undergoing EA first had fluid removed from the nodules using a 16-gauge needle. Ablation consisted of an injection of 99% ethanol into the cystic space, which was removed after 2 minutes.
The primary outcome was nodule volume at 6 months. Secondary outcomes were postprocedural pain and complications, Dr. Park said at the meeting held by the American Thyroid Association, Asia-Oceania Thyroid Association , European Thyroid Association, and Latin American Thyroid Society.
At follow-up, the volume reductions were similar in RFA and EA (87.5 vs. 82.4 ml). The therapeutic success rate was 100% for patients who had RFA and 92% for those who had EA. Two patients in the EA group had major bleeding from the nodule, which interrupted the procedure; they later had a successful RFA. There were no complications in the RFA group.
There was only one major complication during follow-up: One patient who received EA complained of voice change, which resolved spontaneously by 2 months after ablation.
Dr. Park had no financial disclosures.
LAKE BUENA VISTA, FLA. – Ethanol ablation is just as effective as radiofrequency ablation for cystic thyroid nodules, resulting in similar volume reduction and similarly improving symptomatic and cosmetic outcomes at 6 months.
Radiofrequnecy ablation (RFA) did have a slight edge over ethanol injection (EA) in therapeutic response, Dr. Hye Sun Park said at the International Thyroid Conference. But because ethanol ablation is easier and less expensive, she recommended that it be considered as first-line therapy for these lesions.
Dr. Park of the University of Ulsan, Asan Medical Center in Seoul, South Korea, reported a trial of 46 patients, mean age 50 years old, with benign cystic thyroid nodules who were randomized to the two treatments. Patients randomized to ethanol, however, had significantly larger-volume lesions (14.7 vs. 8.6 mL), and symptom scores. Cosmetic scores and nodule vascularity were similar.
RFA was performed with an 18-gauge monopolar, internally cooled electrode with a 1-cm active tip, using the moving shot technique. Patients undergoing EA first had fluid removed from the nodules using a 16-gauge needle. Ablation consisted of an injection of 99% ethanol into the cystic space, which was removed after 2 minutes.
The primary outcome was nodule volume at 6 months. Secondary outcomes were postprocedural pain and complications, Dr. Park said at the meeting held by the American Thyroid Association, Asia-Oceania Thyroid Association , European Thyroid Association, and Latin American Thyroid Society.
At follow-up, the volume reductions were similar in RFA and EA (87.5 vs. 82.4 ml). The therapeutic success rate was 100% for patients who had RFA and 92% for those who had EA. Two patients in the EA group had major bleeding from the nodule, which interrupted the procedure; they later had a successful RFA. There were no complications in the RFA group.
There was only one major complication during follow-up: One patient who received EA complained of voice change, which resolved spontaneously by 2 months after ablation.
Dr. Park had no financial disclosures.
AT ITC 2015
Key clinical point: Radiofrequency ablation and ethanol ablation were similarly effective in treating cystic thyroid nodules.
Major finding: At 6 months, radiofrequency ablation and ethanol ablation achieved similar reductions in the volume of benign cystic thyroid nodules (87.5 vs. 82.4 mL).
Data source: The randomized study comprised 46 patients.
Disclosures: Dr Hye Sun Park had no financial disclosures.
ITC: SELECT trial: Lenvatinib effects similar regardless of site, number of metastases
LAKE BUENA VISTA, FLA. – Outcomes in patients with radioiodine-refractory differentiated thyroid cancer treated with lenvatinib did not differ based on metastatic site, according to a subanalysis of data from the phase 3, randomized, double-blind SELECT trial.
The overall response rate in 257 patients from that trial (the Study of Lenvatinib in Differentiated Cancer of the Thyroid) who had one or more metastatic sites of radioiodine-refractory differentiated thyroid cancer (RR-DTC) was more than 50% (vs. 1.6% or less in 131 treated with placebo) regardless of the number of metastatic sites at baseline and regardless of the site, Dr. Mouhammed Amir Habra reported in a poster at the International Thyroid Congress.
Further, the overall response rate did not differ significantly between those with zero to one vs. two or more metastatic sites, said Dr. Habra of the University of Texas MD Anderson Cancer Center, Houston.
For common sites of metastasis, including bone, liver, lungs, and lymph nodes, median progression-free survival (PFS) was significantly prolonged with lenvatinib vs. placebo. The median was not estimable for those with one or no metastatic sites who were treated with lenvatinib and was 3.7 months for those who received placebo. The corresponding values for those with two or more metastatic sites were 15.9 vs. 3.6 months.
An exception was in those with brain metastasis, who had PFS of 8.8 vs. 3.7 months with lenvatinib vs. placebo, respectively, but this subgroup included only 16 patients, Dr. Habra noted.
Time to first objective response was also similar between metastatic groups (1.9, 3.6, 3.5, and 2 months in those with brain, bone, liver, and lung metastases at baseline, respectively). The median duration of objective response was 6.9 months in those with brain metastases and 9.2 months in those with liver metastases at baseline. The duration of objective response was not reached in those with bone and lung metastases at baseline.
In the pivotal SELECT trial, the oral multikinase inhibitor lenvatinib significantly prolonged PFS in patients with RR-DTC vs. placebo (median PFS of 18.3 vs. 3.6 months).
“These [current] findings suggest a treatment benefit vs. placebo with lenvatinib regardless of number and type of metastatic sites at baseline,” Dr. Habra concluded at the meeting held by the American Thyroid Association, Asia-Oceania Thyroid Association, European Thyroid Association, and Latin American Thyroid Society.
The study was funded by Eisai, and additional support was provided by Oxford PharmaGenesis.
LAKE BUENA VISTA, FLA. – Outcomes in patients with radioiodine-refractory differentiated thyroid cancer treated with lenvatinib did not differ based on metastatic site, according to a subanalysis of data from the phase 3, randomized, double-blind SELECT trial.
The overall response rate in 257 patients from that trial (the Study of Lenvatinib in Differentiated Cancer of the Thyroid) who had one or more metastatic sites of radioiodine-refractory differentiated thyroid cancer (RR-DTC) was more than 50% (vs. 1.6% or less in 131 treated with placebo) regardless of the number of metastatic sites at baseline and regardless of the site, Dr. Mouhammed Amir Habra reported in a poster at the International Thyroid Congress.
Further, the overall response rate did not differ significantly between those with zero to one vs. two or more metastatic sites, said Dr. Habra of the University of Texas MD Anderson Cancer Center, Houston.
For common sites of metastasis, including bone, liver, lungs, and lymph nodes, median progression-free survival (PFS) was significantly prolonged with lenvatinib vs. placebo. The median was not estimable for those with one or no metastatic sites who were treated with lenvatinib and was 3.7 months for those who received placebo. The corresponding values for those with two or more metastatic sites were 15.9 vs. 3.6 months.
An exception was in those with brain metastasis, who had PFS of 8.8 vs. 3.7 months with lenvatinib vs. placebo, respectively, but this subgroup included only 16 patients, Dr. Habra noted.
Time to first objective response was also similar between metastatic groups (1.9, 3.6, 3.5, and 2 months in those with brain, bone, liver, and lung metastases at baseline, respectively). The median duration of objective response was 6.9 months in those with brain metastases and 9.2 months in those with liver metastases at baseline. The duration of objective response was not reached in those with bone and lung metastases at baseline.
In the pivotal SELECT trial, the oral multikinase inhibitor lenvatinib significantly prolonged PFS in patients with RR-DTC vs. placebo (median PFS of 18.3 vs. 3.6 months).
“These [current] findings suggest a treatment benefit vs. placebo with lenvatinib regardless of number and type of metastatic sites at baseline,” Dr. Habra concluded at the meeting held by the American Thyroid Association, Asia-Oceania Thyroid Association, European Thyroid Association, and Latin American Thyroid Society.
The study was funded by Eisai, and additional support was provided by Oxford PharmaGenesis.
LAKE BUENA VISTA, FLA. – Outcomes in patients with radioiodine-refractory differentiated thyroid cancer treated with lenvatinib did not differ based on metastatic site, according to a subanalysis of data from the phase 3, randomized, double-blind SELECT trial.
The overall response rate in 257 patients from that trial (the Study of Lenvatinib in Differentiated Cancer of the Thyroid) who had one or more metastatic sites of radioiodine-refractory differentiated thyroid cancer (RR-DTC) was more than 50% (vs. 1.6% or less in 131 treated with placebo) regardless of the number of metastatic sites at baseline and regardless of the site, Dr. Mouhammed Amir Habra reported in a poster at the International Thyroid Congress.
Further, the overall response rate did not differ significantly between those with zero to one vs. two or more metastatic sites, said Dr. Habra of the University of Texas MD Anderson Cancer Center, Houston.
For common sites of metastasis, including bone, liver, lungs, and lymph nodes, median progression-free survival (PFS) was significantly prolonged with lenvatinib vs. placebo. The median was not estimable for those with one or no metastatic sites who were treated with lenvatinib and was 3.7 months for those who received placebo. The corresponding values for those with two or more metastatic sites were 15.9 vs. 3.6 months.
An exception was in those with brain metastasis, who had PFS of 8.8 vs. 3.7 months with lenvatinib vs. placebo, respectively, but this subgroup included only 16 patients, Dr. Habra noted.
Time to first objective response was also similar between metastatic groups (1.9, 3.6, 3.5, and 2 months in those with brain, bone, liver, and lung metastases at baseline, respectively). The median duration of objective response was 6.9 months in those with brain metastases and 9.2 months in those with liver metastases at baseline. The duration of objective response was not reached in those with bone and lung metastases at baseline.
In the pivotal SELECT trial, the oral multikinase inhibitor lenvatinib significantly prolonged PFS in patients with RR-DTC vs. placebo (median PFS of 18.3 vs. 3.6 months).
“These [current] findings suggest a treatment benefit vs. placebo with lenvatinib regardless of number and type of metastatic sites at baseline,” Dr. Habra concluded at the meeting held by the American Thyroid Association, Asia-Oceania Thyroid Association, European Thyroid Association, and Latin American Thyroid Society.
The study was funded by Eisai, and additional support was provided by Oxford PharmaGenesis.
AT ITC 2015
Key clinical point: Outcomes in patients with radioiodine-refractory differentiated thyroid cancer treated with lenvatinib did not differ based on metastatic site, according to a subanalysis of data from the phase III, randomized, double-blind SELECT trial.
Major finding: The overall response rate in patients with at least one metastatic site was more than 50%, regardless of the number of metastatic sites at baseline of the site.
Data source: An analysis of data for 388 patients from the phase III SELECT trial.
Disclosures: The study was funded by Eisai, and additional support was provided by Oxford PharmaGenesis.
Study finds no link between thyroid autoimmunity, breast cancer outcomes
LAKE BUENA VISTA, FLA. – In contrast with at least two prior small studies, thyroid peroxidase autoantibodies were not associated with breast cancer outcomes in a large cohort of patients.
Stored serum samples from 1,974 patients with lymph node–positive or high-risk lymph node–negative breast cancer who were enrolled in the TACT (Taxotere as Adjuvant Chemotherapy for Early Breast Cancer) trial were tested, and investigators assessed the prognostic significance of thyroid peroxidase autoantibodies (TPOAb) and thyroid function for disease-free survival (DFS), overall survival (OS), and time to recurrence (TTR).
At a median follow-up of 97.5 months, investigators found no evidence of a difference in outcomes, either on univariate or multivariable analysis, for any of those outcomes based on free thyroxine (FT4) or thyroid-stimulating hormone (TSH) levels alone or in combination as hypo- or hyperthyroidism, Dr. Ilaria Muller, of Cardiff (England) University reported at the International Thyroid Congress.
For example, the unadjusted hazard ratios for DFS, OS, and TTR based on TPOAb-positive vs. TPOAb-negative status were 0.97, 0.86, and 0.97, respectively, Dr. Muller said.
An explorative multivariable analysis of the impact of TPOab status and thyroid function on breast cancer DFS, OS, and TTR also showed no evidence of a difference (HR, 1 and 0.97 for TPOAb-negative and TPOAb-positive status; HR, 1 and 1.27 for euthyroid and hypothyroid status), Dr. Muller said.
Similarly, no evidence of a difference in outcomes was seen based on an explorative analysis of TPOAb status in clinical subgroups based on age, nodal status, tumor grade, tumor size, type of surgery, estrogen receptor (ER)-positive status, human epidermal growth factor receptor 2 (HER2)-positive status, and molecular subgroup, she noted.
Serum samples used in the study were from patients who had undergone breast cancer surgery a mean of 15.5 months prior and were mainly taken during/after adjuvant treatments for breast cancer. All had received chemotherapy: 88.4% received radiotherapy, 98.7% of ER-positive patients received hormonal therapy, and trastuzumab was given in 11.8% of HER2-positive patients.
About a fifth (20.6%) of patients were TPOAb-positive, 89.16% were euthyroid, 4.86% were hypothyroid, and 5.97% were hyperthyroid.
The TPOAb-positive and -negative patients were largely comparable, except the TPOAb-positive women were slightly older.
A sensitivity analysis performed in 123 patients with blood taken after surgery but before any adjuvant therapy for breast cancer also showed no evidence of TPOAb prognostic ability, Dr. Muller said.
Despite an ongoing debate aabout a possible association between breast cancer and thyroid autoimmunity, findings have been conflicting. Two small studies correlated TPOAb positivity with improved breast cancer outcomes, but a third did not confirm the findings.
“As a possible explanation, we hypothesized an immune response to shared thyroid/breast antigens. We recently reported that TPO is expressed in breast cancer tissue,” Dr. Muller wrote.
However, the findings of the current study – the largest retrospective study to date investigating the prognostic role of TPOAb in breast cancer – suggest that TPOAb and thyroid function are not prognostic markers in breast cancer.
“Effects of chemotherapy and/or radiotherapy for breast cancer are currently under debate. Tamoxifen exerts an antithyroid effect. However, confounding due to breast cancer adjuvant treatment is unlikely to alter significantly any results, as suggested by our sensitivity analysis performed on 123 patients,” she said at the meeting held by the American Thyroid Association, Asia-Oceania Thyroid Association , European Thyroid Association, and Latin American Thyroid Society.
This study was supported by a Tenovus Innovation Grant from Tenovus Cancer Care. TACT was funded by Cancer Research UK. Dr. Muller reported having no disclosures.
LAKE BUENA VISTA, FLA. – In contrast with at least two prior small studies, thyroid peroxidase autoantibodies were not associated with breast cancer outcomes in a large cohort of patients.
Stored serum samples from 1,974 patients with lymph node–positive or high-risk lymph node–negative breast cancer who were enrolled in the TACT (Taxotere as Adjuvant Chemotherapy for Early Breast Cancer) trial were tested, and investigators assessed the prognostic significance of thyroid peroxidase autoantibodies (TPOAb) and thyroid function for disease-free survival (DFS), overall survival (OS), and time to recurrence (TTR).
At a median follow-up of 97.5 months, investigators found no evidence of a difference in outcomes, either on univariate or multivariable analysis, for any of those outcomes based on free thyroxine (FT4) or thyroid-stimulating hormone (TSH) levels alone or in combination as hypo- or hyperthyroidism, Dr. Ilaria Muller, of Cardiff (England) University reported at the International Thyroid Congress.
For example, the unadjusted hazard ratios for DFS, OS, and TTR based on TPOAb-positive vs. TPOAb-negative status were 0.97, 0.86, and 0.97, respectively, Dr. Muller said.
An explorative multivariable analysis of the impact of TPOab status and thyroid function on breast cancer DFS, OS, and TTR also showed no evidence of a difference (HR, 1 and 0.97 for TPOAb-negative and TPOAb-positive status; HR, 1 and 1.27 for euthyroid and hypothyroid status), Dr. Muller said.
Similarly, no evidence of a difference in outcomes was seen based on an explorative analysis of TPOAb status in clinical subgroups based on age, nodal status, tumor grade, tumor size, type of surgery, estrogen receptor (ER)-positive status, human epidermal growth factor receptor 2 (HER2)-positive status, and molecular subgroup, she noted.
Serum samples used in the study were from patients who had undergone breast cancer surgery a mean of 15.5 months prior and were mainly taken during/after adjuvant treatments for breast cancer. All had received chemotherapy: 88.4% received radiotherapy, 98.7% of ER-positive patients received hormonal therapy, and trastuzumab was given in 11.8% of HER2-positive patients.
About a fifth (20.6%) of patients were TPOAb-positive, 89.16% were euthyroid, 4.86% were hypothyroid, and 5.97% were hyperthyroid.
The TPOAb-positive and -negative patients were largely comparable, except the TPOAb-positive women were slightly older.
A sensitivity analysis performed in 123 patients with blood taken after surgery but before any adjuvant therapy for breast cancer also showed no evidence of TPOAb prognostic ability, Dr. Muller said.
Despite an ongoing debate aabout a possible association between breast cancer and thyroid autoimmunity, findings have been conflicting. Two small studies correlated TPOAb positivity with improved breast cancer outcomes, but a third did not confirm the findings.
“As a possible explanation, we hypothesized an immune response to shared thyroid/breast antigens. We recently reported that TPO is expressed in breast cancer tissue,” Dr. Muller wrote.
However, the findings of the current study – the largest retrospective study to date investigating the prognostic role of TPOAb in breast cancer – suggest that TPOAb and thyroid function are not prognostic markers in breast cancer.
“Effects of chemotherapy and/or radiotherapy for breast cancer are currently under debate. Tamoxifen exerts an antithyroid effect. However, confounding due to breast cancer adjuvant treatment is unlikely to alter significantly any results, as suggested by our sensitivity analysis performed on 123 patients,” she said at the meeting held by the American Thyroid Association, Asia-Oceania Thyroid Association , European Thyroid Association, and Latin American Thyroid Society.
This study was supported by a Tenovus Innovation Grant from Tenovus Cancer Care. TACT was funded by Cancer Research UK. Dr. Muller reported having no disclosures.
LAKE BUENA VISTA, FLA. – In contrast with at least two prior small studies, thyroid peroxidase autoantibodies were not associated with breast cancer outcomes in a large cohort of patients.
Stored serum samples from 1,974 patients with lymph node–positive or high-risk lymph node–negative breast cancer who were enrolled in the TACT (Taxotere as Adjuvant Chemotherapy for Early Breast Cancer) trial were tested, and investigators assessed the prognostic significance of thyroid peroxidase autoantibodies (TPOAb) and thyroid function for disease-free survival (DFS), overall survival (OS), and time to recurrence (TTR).
At a median follow-up of 97.5 months, investigators found no evidence of a difference in outcomes, either on univariate or multivariable analysis, for any of those outcomes based on free thyroxine (FT4) or thyroid-stimulating hormone (TSH) levels alone or in combination as hypo- or hyperthyroidism, Dr. Ilaria Muller, of Cardiff (England) University reported at the International Thyroid Congress.
For example, the unadjusted hazard ratios for DFS, OS, and TTR based on TPOAb-positive vs. TPOAb-negative status were 0.97, 0.86, and 0.97, respectively, Dr. Muller said.
An explorative multivariable analysis of the impact of TPOab status and thyroid function on breast cancer DFS, OS, and TTR also showed no evidence of a difference (HR, 1 and 0.97 for TPOAb-negative and TPOAb-positive status; HR, 1 and 1.27 for euthyroid and hypothyroid status), Dr. Muller said.
Similarly, no evidence of a difference in outcomes was seen based on an explorative analysis of TPOAb status in clinical subgroups based on age, nodal status, tumor grade, tumor size, type of surgery, estrogen receptor (ER)-positive status, human epidermal growth factor receptor 2 (HER2)-positive status, and molecular subgroup, she noted.
Serum samples used in the study were from patients who had undergone breast cancer surgery a mean of 15.5 months prior and were mainly taken during/after adjuvant treatments for breast cancer. All had received chemotherapy: 88.4% received radiotherapy, 98.7% of ER-positive patients received hormonal therapy, and trastuzumab was given in 11.8% of HER2-positive patients.
About a fifth (20.6%) of patients were TPOAb-positive, 89.16% were euthyroid, 4.86% were hypothyroid, and 5.97% were hyperthyroid.
The TPOAb-positive and -negative patients were largely comparable, except the TPOAb-positive women were slightly older.
A sensitivity analysis performed in 123 patients with blood taken after surgery but before any adjuvant therapy for breast cancer also showed no evidence of TPOAb prognostic ability, Dr. Muller said.
Despite an ongoing debate aabout a possible association between breast cancer and thyroid autoimmunity, findings have been conflicting. Two small studies correlated TPOAb positivity with improved breast cancer outcomes, but a third did not confirm the findings.
“As a possible explanation, we hypothesized an immune response to shared thyroid/breast antigens. We recently reported that TPO is expressed in breast cancer tissue,” Dr. Muller wrote.
However, the findings of the current study – the largest retrospective study to date investigating the prognostic role of TPOAb in breast cancer – suggest that TPOAb and thyroid function are not prognostic markers in breast cancer.
“Effects of chemotherapy and/or radiotherapy for breast cancer are currently under debate. Tamoxifen exerts an antithyroid effect. However, confounding due to breast cancer adjuvant treatment is unlikely to alter significantly any results, as suggested by our sensitivity analysis performed on 123 patients,” she said at the meeting held by the American Thyroid Association, Asia-Oceania Thyroid Association , European Thyroid Association, and Latin American Thyroid Society.
This study was supported by a Tenovus Innovation Grant from Tenovus Cancer Care. TACT was funded by Cancer Research UK. Dr. Muller reported having no disclosures.
At ITC 2015
Key clinical point: In contrast with at least two prior small studies, thyroid peroxidase autoantibodies were not associated with breast cancer outcomes in a large cohort of patients.
Major finding: An explorative multivariable analysis showed no impact of TPOab status and thyroid function on breast cancer DFS, OS, and TTR (hazard ratios, 1.00 and 0.97 for TPOAb-negative and TPOAb-positive status, and 1.00 and 1.27 for euthyroid and hypothyroid status).
Data source: An analysis of serum samples from 1,974 TACT trial participants.
Disclosures: This study was supported by a Tenovus Innovation Grant from Tenovus Cancer Care. TACT was funded by Cancer Research UK. Dr. Muller reported having no disclosures.
Thyroglobulin can’t predict pazopanib response in differentiated thyroid cancer
Lake BUENA VISTA, FLA. – Pazopanib is an effective therapy for advanced thyroid cancer, but at present, there seems to be no way to predict which patients will respond to it.
An investigation into the predictive value of thyroglobulin found that the level during treatment did change, but it did so in parallel with response; there was no way to use the protein to parse out which patients would do well, Dr. Keith Bible said at the International Thyroid Congress.
“We had hoped that it might be a predictor as early as 4 weeks, so we could assign patients into categories of response and perhaps stop treatment earlier,” said Dr. Bible of the Mayo Clinic, Rochester, Minn. “Unfortunately, there was no way to do that.”
Pazopanib (Votrient) is a tyrosine kinase inhibitor of vascular endothelial growth factor receptors. It is approved for advanced soft tissue sarcoma and advanced renal cell carcinoma. The Mayo Clinic Consortium has been investigating pazopanib in phase II trials for advanced differentiated and medullary thyroid cancers. In a 2010 report, it was shown to induce at least a partial response in about half of the patients who received it (Lancet Oncol. 2010 Oct;11[10]:962-72).
Last year, it was also shown to be effective in advanced medullary thyroid cancer. Five of 35 patients attained partial Response Evaluation Criteria In Solid Tumors (RECIST) responses (14%) (J Clin Endocrinol Metab. 2014 May;99[5]:1687-93).
The drug has not been successful in treating advanced anaplastic thyroid cancer, however.
Because of pazopanib’s proclivity to induce sometimes-severe hypertension, investigators were hoping for some way to stratify potential responders. Thyroglobulin levels could be one marker, Dr. Bible said at the meeting, which was held by the American Thyroid Association, Asia-Oceania Thyroid Association, European Thyroid Association, and Latin American Thyroid Society.
He and the consortium investigators examined how thyroglobulin levels correlated with RECIST scores in 60 patients with metastatic differentiated thyroid cancers. The patients received a median of 10 cycles, but the range was wide (1-53 cycles). Most of them (92%) had already received systemic therapy, including a tyrosine kinase inhibitor and/or radioactive iodine.
The most common side effect was hypertension, which occurred in 75% patients, and was severe in 23%. Of those with a severe reaction, 53% required a new prescription for an antihypertensive medication. No one left the study or required a pazopanib dose reduction because of a blood pressure elevation, however. “We responded with a aggressive treatment, but it was a prominent issue,” Dr. Bible said.
Other adverse events were fatigue (83%; 8% severe); decrease in neutrophils (47%; 8% severe); diarrhea (78%; 7% severe); hand-foot syndrome (17%; 7% severe); and elevations of liver enzymes (53%; 6% severe). There were no deaths related to the study drug.
Partial RECIST responses occurred in 22 patients (37%). Thyroglobulin change did not differ by response after cycle 1, although its nadir was lower among patients who attained a partial response than among those who maintained disease stability (–87% vs. –69%).
“There was this correlation of nadir with maximum RECIST response, but this occurred in parallel with the response, so it was not capable of providing a prediction of response,” Dr. Bible said.
Prior therapy also was not a response predictor, he added.
Genomic profiling was available for 16 patients; of these, 11 had mutations of BRAF, p53, JAK3 or HRAS. Thyroglobulin change and response to treatment was not significantly correlated with any of these mutations. Nor did it correlate with any type of prior tumor therapy.
The finding that pazopanib can benefit patients previously treated with a kinase inhibitor is an interesting one, Dr. Bible noted.
“Most kinase inhibitors are very promiscuous – they work on a number of pathways and have a footprint which is very messy. Most of them seem to have some activity in differentiated thyroid cancer, but we are still struggling to understand how that footprint varies. In theory they are all targeting VEGF receptors, but it’s striking that we can go from one kinase inhibitor to the next and still get a response.”
Dr. Bible had no financial declarations.
On Twitter @Alz_Gal
Lake BUENA VISTA, FLA. – Pazopanib is an effective therapy for advanced thyroid cancer, but at present, there seems to be no way to predict which patients will respond to it.
An investigation into the predictive value of thyroglobulin found that the level during treatment did change, but it did so in parallel with response; there was no way to use the protein to parse out which patients would do well, Dr. Keith Bible said at the International Thyroid Congress.
“We had hoped that it might be a predictor as early as 4 weeks, so we could assign patients into categories of response and perhaps stop treatment earlier,” said Dr. Bible of the Mayo Clinic, Rochester, Minn. “Unfortunately, there was no way to do that.”
Pazopanib (Votrient) is a tyrosine kinase inhibitor of vascular endothelial growth factor receptors. It is approved for advanced soft tissue sarcoma and advanced renal cell carcinoma. The Mayo Clinic Consortium has been investigating pazopanib in phase II trials for advanced differentiated and medullary thyroid cancers. In a 2010 report, it was shown to induce at least a partial response in about half of the patients who received it (Lancet Oncol. 2010 Oct;11[10]:962-72).
Last year, it was also shown to be effective in advanced medullary thyroid cancer. Five of 35 patients attained partial Response Evaluation Criteria In Solid Tumors (RECIST) responses (14%) (J Clin Endocrinol Metab. 2014 May;99[5]:1687-93).
The drug has not been successful in treating advanced anaplastic thyroid cancer, however.
Because of pazopanib’s proclivity to induce sometimes-severe hypertension, investigators were hoping for some way to stratify potential responders. Thyroglobulin levels could be one marker, Dr. Bible said at the meeting, which was held by the American Thyroid Association, Asia-Oceania Thyroid Association, European Thyroid Association, and Latin American Thyroid Society.
He and the consortium investigators examined how thyroglobulin levels correlated with RECIST scores in 60 patients with metastatic differentiated thyroid cancers. The patients received a median of 10 cycles, but the range was wide (1-53 cycles). Most of them (92%) had already received systemic therapy, including a tyrosine kinase inhibitor and/or radioactive iodine.
The most common side effect was hypertension, which occurred in 75% patients, and was severe in 23%. Of those with a severe reaction, 53% required a new prescription for an antihypertensive medication. No one left the study or required a pazopanib dose reduction because of a blood pressure elevation, however. “We responded with a aggressive treatment, but it was a prominent issue,” Dr. Bible said.
Other adverse events were fatigue (83%; 8% severe); decrease in neutrophils (47%; 8% severe); diarrhea (78%; 7% severe); hand-foot syndrome (17%; 7% severe); and elevations of liver enzymes (53%; 6% severe). There were no deaths related to the study drug.
Partial RECIST responses occurred in 22 patients (37%). Thyroglobulin change did not differ by response after cycle 1, although its nadir was lower among patients who attained a partial response than among those who maintained disease stability (–87% vs. –69%).
“There was this correlation of nadir with maximum RECIST response, but this occurred in parallel with the response, so it was not capable of providing a prediction of response,” Dr. Bible said.
Prior therapy also was not a response predictor, he added.
Genomic profiling was available for 16 patients; of these, 11 had mutations of BRAF, p53, JAK3 or HRAS. Thyroglobulin change and response to treatment was not significantly correlated with any of these mutations. Nor did it correlate with any type of prior tumor therapy.
The finding that pazopanib can benefit patients previously treated with a kinase inhibitor is an interesting one, Dr. Bible noted.
“Most kinase inhibitors are very promiscuous – they work on a number of pathways and have a footprint which is very messy. Most of them seem to have some activity in differentiated thyroid cancer, but we are still struggling to understand how that footprint varies. In theory they are all targeting VEGF receptors, but it’s striking that we can go from one kinase inhibitor to the next and still get a response.”
Dr. Bible had no financial declarations.
On Twitter @Alz_Gal
Lake BUENA VISTA, FLA. – Pazopanib is an effective therapy for advanced thyroid cancer, but at present, there seems to be no way to predict which patients will respond to it.
An investigation into the predictive value of thyroglobulin found that the level during treatment did change, but it did so in parallel with response; there was no way to use the protein to parse out which patients would do well, Dr. Keith Bible said at the International Thyroid Congress.
“We had hoped that it might be a predictor as early as 4 weeks, so we could assign patients into categories of response and perhaps stop treatment earlier,” said Dr. Bible of the Mayo Clinic, Rochester, Minn. “Unfortunately, there was no way to do that.”
Pazopanib (Votrient) is a tyrosine kinase inhibitor of vascular endothelial growth factor receptors. It is approved for advanced soft tissue sarcoma and advanced renal cell carcinoma. The Mayo Clinic Consortium has been investigating pazopanib in phase II trials for advanced differentiated and medullary thyroid cancers. In a 2010 report, it was shown to induce at least a partial response in about half of the patients who received it (Lancet Oncol. 2010 Oct;11[10]:962-72).
Last year, it was also shown to be effective in advanced medullary thyroid cancer. Five of 35 patients attained partial Response Evaluation Criteria In Solid Tumors (RECIST) responses (14%) (J Clin Endocrinol Metab. 2014 May;99[5]:1687-93).
The drug has not been successful in treating advanced anaplastic thyroid cancer, however.
Because of pazopanib’s proclivity to induce sometimes-severe hypertension, investigators were hoping for some way to stratify potential responders. Thyroglobulin levels could be one marker, Dr. Bible said at the meeting, which was held by the American Thyroid Association, Asia-Oceania Thyroid Association, European Thyroid Association, and Latin American Thyroid Society.
He and the consortium investigators examined how thyroglobulin levels correlated with RECIST scores in 60 patients with metastatic differentiated thyroid cancers. The patients received a median of 10 cycles, but the range was wide (1-53 cycles). Most of them (92%) had already received systemic therapy, including a tyrosine kinase inhibitor and/or radioactive iodine.
The most common side effect was hypertension, which occurred in 75% patients, and was severe in 23%. Of those with a severe reaction, 53% required a new prescription for an antihypertensive medication. No one left the study or required a pazopanib dose reduction because of a blood pressure elevation, however. “We responded with a aggressive treatment, but it was a prominent issue,” Dr. Bible said.
Other adverse events were fatigue (83%; 8% severe); decrease in neutrophils (47%; 8% severe); diarrhea (78%; 7% severe); hand-foot syndrome (17%; 7% severe); and elevations of liver enzymes (53%; 6% severe). There were no deaths related to the study drug.
Partial RECIST responses occurred in 22 patients (37%). Thyroglobulin change did not differ by response after cycle 1, although its nadir was lower among patients who attained a partial response than among those who maintained disease stability (–87% vs. –69%).
“There was this correlation of nadir with maximum RECIST response, but this occurred in parallel with the response, so it was not capable of providing a prediction of response,” Dr. Bible said.
Prior therapy also was not a response predictor, he added.
Genomic profiling was available for 16 patients; of these, 11 had mutations of BRAF, p53, JAK3 or HRAS. Thyroglobulin change and response to treatment was not significantly correlated with any of these mutations. Nor did it correlate with any type of prior tumor therapy.
The finding that pazopanib can benefit patients previously treated with a kinase inhibitor is an interesting one, Dr. Bible noted.
“Most kinase inhibitors are very promiscuous – they work on a number of pathways and have a footprint which is very messy. Most of them seem to have some activity in differentiated thyroid cancer, but we are still struggling to understand how that footprint varies. In theory they are all targeting VEGF receptors, but it’s striking that we can go from one kinase inhibitor to the next and still get a response.”
Dr. Bible had no financial declarations.
On Twitter @Alz_Gal
AT ITC 2015
Key clinical point: Falling thyroglobulin levels cannot predict early response to pazopanib in differentiated thyroid cancers.
Major finding: There was a 37% response rate for patients taking pazopanib for differentiated thyroid cancer, but thyroglobulin decline was not an early predictor of response.
Data source: A prospective study of 60 patients.
Disclosures: Dr. Bible had no financial disclosures.
Cabozantinib shows promise in refractory differentiated thyroid cancer
LAKE BUENA VISTA, FLA. – Most patients with differentiated thyroid cancer who had shown progression on previous courses of targeted chemotherapy either maintained stable disease or responded to the oral multikinase inhibitor cabozantinib (Cometriq), according to a small multicenter phase II trial presented at the International Thyroid Congress.
This is important, according to Dr. Manisha H. Shah, because there has been no standard of care for patients with differentiated thyroid cancer whose cancer progresses on first- or second-line vascular endothelial growth factor receptor (VEGFR) inhibitors.
Nine of the 25 enrolled patients (36%; 95% confidence interval, 18%-57%) showed confirmed partial response, 12 patients (48%) had stable disease, and one patient had disease progression, according to Dr. Shah, director of the neuroendocrine tumor program at Ohio State University’s Wexner Medical Center. The trial enrolled patients with radioiodine–refractory differentiated thyroid cancer who had progression of their disease after one or two previous VEGFR agents.
Cabozantinib targets VEGFR and MET and is approved as first-line treatment for medullary thyroid cancer. The majority of the response to cabozantinib occurs in the first several months of treatment, so the study used a Simon minimax two-stage design, enrolling an initial 16 patients, then opening enrollment to an additional 9 when at least 2 of the initial cohort showed partial or complete response within the first 6 months.
The primary outcome measure was the number of patients showing objective response (partial or complete response) within the first 6 months of therapy.
Median patient age was 64 years, and 64% of patients were male. Just over half of the patients previously had been treated with sorafenib, and just over a quarter had received pazopanib. Five patients had received two previous VEGFR-targeted therapies, while the remaining 20 had received one.
Nine patients (36%) had papillary thyroid cancer, seven (28%) had poorly differentiated thyroid cancer, five (20%) had Hurthle cell cancer, and four (16%) had follicular thyroid cancer. The most common metastasis sites were lymph node, bone, and lung.
Patients received continuous treatment until they showed disease progression, had an unacceptable adverse event or an illness precluding further treatment, or withdrew consent.
Disease progression was measured by serum tumor markers and CT or MRI scan every 8 weeks while in the study; patients also received bone scans and 18F-FDG and 18F-fluoride PET scans before the study and while in the study.
Side effects were common and generally mild, with two instances each of grade 3 events related to fatigue, hand-foot skin reactions, and diarrhea. One death occurred and was adjudicated as possibly study related; there were no grade 4 events, and no grade 3 bleeding events.
Dr. Shah noted that the starting cabozantinib dose of 60 mg/day was considerably lower than that used in previous trials for thyroid cancer. With time, investigators have learned that the sometimes debilitating side effects of cabozantinib are somewhat dose dependent, she noted. The study design permitted dose escalation to 80 mg for nonresponders to the lower dose, and permitted a decrease to 40 or 20 mg/day as needed to manage side effects. Investigators were able to tell the patients what to expect, and to be proactive in anticipating side effects. “We have learned to manage these drugs much better with time,” she said.
“Cabozantinib was effective in inducing a durable partial response,” said Dr. Shah. Future directions, in addition to phase III clinical trials, may include combining cabozantinib with immune checkpoint–targeted therapies such as lenvatinib, a strategy that has been effective for other cancers, she said at the meeting, which was held by the American Thyroid Association, Asia-Oceania Thyroid Association, European Thyroid Association, and Latin American Thyroid Society.
The multisite study was sponsored by the National Cancer Institute with participation by eight International Thyroid Oncology Group centers. Dr. Shah reported being on the advisory board for Exelixis and Eisai, and receiving research funding from those two organizations and Bayer.
On Twitter @karioakes
LAKE BUENA VISTA, FLA. – Most patients with differentiated thyroid cancer who had shown progression on previous courses of targeted chemotherapy either maintained stable disease or responded to the oral multikinase inhibitor cabozantinib (Cometriq), according to a small multicenter phase II trial presented at the International Thyroid Congress.
This is important, according to Dr. Manisha H. Shah, because there has been no standard of care for patients with differentiated thyroid cancer whose cancer progresses on first- or second-line vascular endothelial growth factor receptor (VEGFR) inhibitors.
Nine of the 25 enrolled patients (36%; 95% confidence interval, 18%-57%) showed confirmed partial response, 12 patients (48%) had stable disease, and one patient had disease progression, according to Dr. Shah, director of the neuroendocrine tumor program at Ohio State University’s Wexner Medical Center. The trial enrolled patients with radioiodine–refractory differentiated thyroid cancer who had progression of their disease after one or two previous VEGFR agents.
Cabozantinib targets VEGFR and MET and is approved as first-line treatment for medullary thyroid cancer. The majority of the response to cabozantinib occurs in the first several months of treatment, so the study used a Simon minimax two-stage design, enrolling an initial 16 patients, then opening enrollment to an additional 9 when at least 2 of the initial cohort showed partial or complete response within the first 6 months.
The primary outcome measure was the number of patients showing objective response (partial or complete response) within the first 6 months of therapy.
Median patient age was 64 years, and 64% of patients were male. Just over half of the patients previously had been treated with sorafenib, and just over a quarter had received pazopanib. Five patients had received two previous VEGFR-targeted therapies, while the remaining 20 had received one.
Nine patients (36%) had papillary thyroid cancer, seven (28%) had poorly differentiated thyroid cancer, five (20%) had Hurthle cell cancer, and four (16%) had follicular thyroid cancer. The most common metastasis sites were lymph node, bone, and lung.
Patients received continuous treatment until they showed disease progression, had an unacceptable adverse event or an illness precluding further treatment, or withdrew consent.
Disease progression was measured by serum tumor markers and CT or MRI scan every 8 weeks while in the study; patients also received bone scans and 18F-FDG and 18F-fluoride PET scans before the study and while in the study.
Side effects were common and generally mild, with two instances each of grade 3 events related to fatigue, hand-foot skin reactions, and diarrhea. One death occurred and was adjudicated as possibly study related; there were no grade 4 events, and no grade 3 bleeding events.
Dr. Shah noted that the starting cabozantinib dose of 60 mg/day was considerably lower than that used in previous trials for thyroid cancer. With time, investigators have learned that the sometimes debilitating side effects of cabozantinib are somewhat dose dependent, she noted. The study design permitted dose escalation to 80 mg for nonresponders to the lower dose, and permitted a decrease to 40 or 20 mg/day as needed to manage side effects. Investigators were able to tell the patients what to expect, and to be proactive in anticipating side effects. “We have learned to manage these drugs much better with time,” she said.
“Cabozantinib was effective in inducing a durable partial response,” said Dr. Shah. Future directions, in addition to phase III clinical trials, may include combining cabozantinib with immune checkpoint–targeted therapies such as lenvatinib, a strategy that has been effective for other cancers, she said at the meeting, which was held by the American Thyroid Association, Asia-Oceania Thyroid Association, European Thyroid Association, and Latin American Thyroid Society.
The multisite study was sponsored by the National Cancer Institute with participation by eight International Thyroid Oncology Group centers. Dr. Shah reported being on the advisory board for Exelixis and Eisai, and receiving research funding from those two organizations and Bayer.
On Twitter @karioakes
LAKE BUENA VISTA, FLA. – Most patients with differentiated thyroid cancer who had shown progression on previous courses of targeted chemotherapy either maintained stable disease or responded to the oral multikinase inhibitor cabozantinib (Cometriq), according to a small multicenter phase II trial presented at the International Thyroid Congress.
This is important, according to Dr. Manisha H. Shah, because there has been no standard of care for patients with differentiated thyroid cancer whose cancer progresses on first- or second-line vascular endothelial growth factor receptor (VEGFR) inhibitors.
Nine of the 25 enrolled patients (36%; 95% confidence interval, 18%-57%) showed confirmed partial response, 12 patients (48%) had stable disease, and one patient had disease progression, according to Dr. Shah, director of the neuroendocrine tumor program at Ohio State University’s Wexner Medical Center. The trial enrolled patients with radioiodine–refractory differentiated thyroid cancer who had progression of their disease after one or two previous VEGFR agents.
Cabozantinib targets VEGFR and MET and is approved as first-line treatment for medullary thyroid cancer. The majority of the response to cabozantinib occurs in the first several months of treatment, so the study used a Simon minimax two-stage design, enrolling an initial 16 patients, then opening enrollment to an additional 9 when at least 2 of the initial cohort showed partial or complete response within the first 6 months.
The primary outcome measure was the number of patients showing objective response (partial or complete response) within the first 6 months of therapy.
Median patient age was 64 years, and 64% of patients were male. Just over half of the patients previously had been treated with sorafenib, and just over a quarter had received pazopanib. Five patients had received two previous VEGFR-targeted therapies, while the remaining 20 had received one.
Nine patients (36%) had papillary thyroid cancer, seven (28%) had poorly differentiated thyroid cancer, five (20%) had Hurthle cell cancer, and four (16%) had follicular thyroid cancer. The most common metastasis sites were lymph node, bone, and lung.
Patients received continuous treatment until they showed disease progression, had an unacceptable adverse event or an illness precluding further treatment, or withdrew consent.
Disease progression was measured by serum tumor markers and CT or MRI scan every 8 weeks while in the study; patients also received bone scans and 18F-FDG and 18F-fluoride PET scans before the study and while in the study.
Side effects were common and generally mild, with two instances each of grade 3 events related to fatigue, hand-foot skin reactions, and diarrhea. One death occurred and was adjudicated as possibly study related; there were no grade 4 events, and no grade 3 bleeding events.
Dr. Shah noted that the starting cabozantinib dose of 60 mg/day was considerably lower than that used in previous trials for thyroid cancer. With time, investigators have learned that the sometimes debilitating side effects of cabozantinib are somewhat dose dependent, she noted. The study design permitted dose escalation to 80 mg for nonresponders to the lower dose, and permitted a decrease to 40 or 20 mg/day as needed to manage side effects. Investigators were able to tell the patients what to expect, and to be proactive in anticipating side effects. “We have learned to manage these drugs much better with time,” she said.
“Cabozantinib was effective in inducing a durable partial response,” said Dr. Shah. Future directions, in addition to phase III clinical trials, may include combining cabozantinib with immune checkpoint–targeted therapies such as lenvatinib, a strategy that has been effective for other cancers, she said at the meeting, which was held by the American Thyroid Association, Asia-Oceania Thyroid Association, European Thyroid Association, and Latin American Thyroid Society.
The multisite study was sponsored by the National Cancer Institute with participation by eight International Thyroid Oncology Group centers. Dr. Shah reported being on the advisory board for Exelixis and Eisai, and receiving research funding from those two organizations and Bayer.
On Twitter @karioakes
AT ITC 2015
Key clinical point: Cabozantinib shows promise for refractory differentiated thyroid cancer.
Major finding: Twenty-one of 25 patients with differentiated thyroid cancer showed stable disease or partial response to cabozantinib after disease progression on previous targeted therapies.
Data source: Multisite, open-label phase II clinical trial of 25 patients.
Disclosures: The study was sponsored by the National Cancer Institute with participation by eight International Thyroid Oncology Group centers. Dr. Shah reported being on the advisory board for Exelixis and Eisai, and receiving research funding from those two organizations and Bayer.
