Pituitary, Thyroid & Adrenal Disorders

Radioactive iodine (RAI) therapy in thyroid cancer patients does not cause such patients to get breast cancer, suggests a retrospective study of female patients from Seoul National University Hospital in South Korea.

The study enrolled 6,150 patients with thyroid cancer between 1973 and 2009, who were followed until December 2012. Of the sample, 3.691 (59%) received RAI therapy, and 99 were diagnosed with primary breast cancers during the follow-up period.

The study showed that RAI therapy did not significantly increase the incidence of breast cancer subsequent to diagnosis of thyroid cancer among patients, when a 2-year latency period was accounted for. An additional finding was that the numbers of breast cancer diagnoses made during the follow-up period for those study participants who received high doses of RAI therapy (greater than or equal to 120 mCi) and those patients who did not receive any RAI therapy were not significantly different from each other.

“The results from our study based on a large cohort of thyroid cancer patients clearly demonstrated that RAI treatment in these patients did not increase the risk of development nor worsen the recurrence of breast cancer,” Dr. Hwa Young Ahn of the department of internal medicine at Seoul National University, South Korea, and Hye Sook Min, and associates.

Read the full study in the Journal of Clinical Endocrinology & Metabolism (doi:10.1210/JC.2014-2896).

This study was supported by research grants from the Korean Foundation for Cancer Research, Seoul National University Bundang Hospital Research Grants, and the Education and Research Encouragement Fund of Seoul National University Hospital. The investigators reported having no financial conflicts of interest.

klennon@frontlinemedicalnews.com

Radioactive iodine (RAI) therapy in thyroid cancer patients does not cause such patients to get breast cancer, suggests a retrospective study of female patients from Seoul National University Hospital in South Korea.

The study enrolled 6,150 patients with thyroid cancer between 1973 and 2009, who were followed until December 2012. Of the sample, 3.691 (59%) received RAI therapy, and 99 were diagnosed with primary breast cancers during the follow-up period.

The study showed that RAI therapy did not significantly increase the incidence of breast cancer subsequent to diagnosis of thyroid cancer among patients, when a 2-year latency period was accounted for. An additional finding was that the numbers of breast cancer diagnoses made during the follow-up period for those study participants who received high doses of RAI therapy (greater than or equal to 120 mCi) and those patients who did not receive any RAI therapy were not significantly different from each other.

“The results from our study based on a large cohort of thyroid cancer patients clearly demonstrated that RAI treatment in these patients did not increase the risk of development nor worsen the recurrence of breast cancer,” Dr. Hwa Young Ahn of the department of internal medicine at Seoul National University, South Korea, and Hye Sook Min, and associates.

Read the full study in the Journal of Clinical Endocrinology & Metabolism (doi:10.1210/JC.2014-2896).

This study was supported by research grants from the Korean Foundation for Cancer Research, Seoul National University Bundang Hospital Research Grants, and the Education and Research Encouragement Fund of Seoul National University Hospital. The investigators reported having no financial conflicts of interest.

klennon@frontlinemedicalnews.com

Radioactive iodine (RAI) therapy in thyroid cancer patients does not cause such patients to get breast cancer, suggests a retrospective study of female patients from Seoul National University Hospital in South Korea.

The study enrolled 6,150 patients with thyroid cancer between 1973 and 2009, who were followed until December 2012. Of the sample, 3.691 (59%) received RAI therapy, and 99 were diagnosed with primary breast cancers during the follow-up period.

The study showed that RAI therapy did not significantly increase the incidence of breast cancer subsequent to diagnosis of thyroid cancer among patients, when a 2-year latency period was accounted for. An additional finding was that the numbers of breast cancer diagnoses made during the follow-up period for those study participants who received high doses of RAI therapy (greater than or equal to 120 mCi) and those patients who did not receive any RAI therapy were not significantly different from each other.

“The results from our study based on a large cohort of thyroid cancer patients clearly demonstrated that RAI treatment in these patients did not increase the risk of development nor worsen the recurrence of breast cancer,” Dr. Hwa Young Ahn of the department of internal medicine at Seoul National University, South Korea, and Hye Sook Min, and associates.

Read the full study in the Journal of Clinical Endocrinology & Metabolism (doi:10.1210/JC.2014-2896).

This study was supported by research grants from the Korean Foundation for Cancer Research, Seoul National University Bundang Hospital Research Grants, and the Education and Research Encouragement Fund of Seoul National University Hospital. The investigators reported having no financial conflicts of interest.

klennon@frontlinemedicalnews.com

In an outpatient study, seasonal variability did not have a significant effect on 25-hydroxy vitamin D and parathyroid hormone levels in patients with mild primary hyperparathyroidism, likely because of widespread high vitamin D supplement intake, according to research in the Journal of Clinical Endocrinology and Metabolism.

The study involved 100 people with primary hyperparathyroidism (PHPT) from the New York area who were enrolled between December 2010 and February 2014. The researchers defined vitamin D deficiency as a 25-OH vitamin D level <20 ng/mL, and vitamin D deficiency or insufficiency as a 25-OH vitamin D level <30 ng/mL, depending on the season of enrollment. The mean vitamin D intake among the participants was 1,493 ± 1,574 IU daily between diet and supplementary sources. Nearly two-thirds (65%) of participants took vitamin D supplements, according to Dr. Elaine Cong and her associates at Columbia University in New York (J. Clin. Endocrinol. Metab. [doi:10.1210/JC.2015-2105]).

Although they documented the to-be-expected seasonal differences in sun exposure, the researchers found no significant seasonal differences in levels of 25-OH vitamin D, parathyroid hormone, markers of bone turnover, or bone mineral density, or in the prevalence of 25 OH vitamin D <20 or <30 ng/mL. While supplement users had markedly better vitamin D status than nonusers (25-OH vitamin D <20 ng/mL: 8% vs. 40%, P <.0001; <30 ng/mL: 40% vs. 80%, P = .0001; ≥30 ng/mL: 60% vs. 20%, P = .0001), the researchers noted that even nonsupplement users received vitamin D through dietary means, although the nonsupplement group was more likely to be either deficient or insufficient in vitamin D.

Patients “with PHPT in the New York City metropolitan area are following secular trends and increasing their vitamin D supplement use. Most were taking over-the-counter vitamins, and it is clearly advisable for physicians who care for PHPT patients to specifically query about supplement use,” the investigators wrote.

The investigators had no relevant financial disclosures to report.

mbock@frontlinemedcom.com

In an outpatient study, seasonal variability did not have a significant effect on 25-hydroxy vitamin D and parathyroid hormone levels in patients with mild primary hyperparathyroidism, likely because of widespread high vitamin D supplement intake, according to research in the Journal of Clinical Endocrinology and Metabolism.

The study involved 100 people with primary hyperparathyroidism (PHPT) from the New York area who were enrolled between December 2010 and February 2014. The researchers defined vitamin D deficiency as a 25-OH vitamin D level <20 ng/mL, and vitamin D deficiency or insufficiency as a 25-OH vitamin D level <30 ng/mL, depending on the season of enrollment. The mean vitamin D intake among the participants was 1,493 ± 1,574 IU daily between diet and supplementary sources. Nearly two-thirds (65%) of participants took vitamin D supplements, according to Dr. Elaine Cong and her associates at Columbia University in New York (J. Clin. Endocrinol. Metab. [doi:10.1210/JC.2015-2105]).

Although they documented the to-be-expected seasonal differences in sun exposure, the researchers found no significant seasonal differences in levels of 25-OH vitamin D, parathyroid hormone, markers of bone turnover, or bone mineral density, or in the prevalence of 25 OH vitamin D <20 or <30 ng/mL. While supplement users had markedly better vitamin D status than nonusers (25-OH vitamin D <20 ng/mL: 8% vs. 40%, P <.0001; <30 ng/mL: 40% vs. 80%, P = .0001; ≥30 ng/mL: 60% vs. 20%, P = .0001), the researchers noted that even nonsupplement users received vitamin D through dietary means, although the nonsupplement group was more likely to be either deficient or insufficient in vitamin D.

Patients “with PHPT in the New York City metropolitan area are following secular trends and increasing their vitamin D supplement use. Most were taking over-the-counter vitamins, and it is clearly advisable for physicians who care for PHPT patients to specifically query about supplement use,” the investigators wrote.

The investigators had no relevant financial disclosures to report.

mbock@frontlinemedcom.com

In an outpatient study, seasonal variability did not have a significant effect on 25-hydroxy vitamin D and parathyroid hormone levels in patients with mild primary hyperparathyroidism, likely because of widespread high vitamin D supplement intake, according to research in the Journal of Clinical Endocrinology and Metabolism.

The study involved 100 people with primary hyperparathyroidism (PHPT) from the New York area who were enrolled between December 2010 and February 2014. The researchers defined vitamin D deficiency as a 25-OH vitamin D level <20 ng/mL, and vitamin D deficiency or insufficiency as a 25-OH vitamin D level <30 ng/mL, depending on the season of enrollment. The mean vitamin D intake among the participants was 1,493 ± 1,574 IU daily between diet and supplementary sources. Nearly two-thirds (65%) of participants took vitamin D supplements, according to Dr. Elaine Cong and her associates at Columbia University in New York (J. Clin. Endocrinol. Metab. [doi:10.1210/JC.2015-2105]).

Although they documented the to-be-expected seasonal differences in sun exposure, the researchers found no significant seasonal differences in levels of 25-OH vitamin D, parathyroid hormone, markers of bone turnover, or bone mineral density, or in the prevalence of 25 OH vitamin D <20 or <30 ng/mL. While supplement users had markedly better vitamin D status than nonusers (25-OH vitamin D <20 ng/mL: 8% vs. 40%, P <.0001; <30 ng/mL: 40% vs. 80%, P = .0001; ≥30 ng/mL: 60% vs. 20%, P = .0001), the researchers noted that even nonsupplement users received vitamin D through dietary means, although the nonsupplement group was more likely to be either deficient or insufficient in vitamin D.

Patients “with PHPT in the New York City metropolitan area are following secular trends and increasing their vitamin D supplement use. Most were taking over-the-counter vitamins, and it is clearly advisable for physicians who care for PHPT patients to specifically query about supplement use,” the investigators wrote.

The investigators had no relevant financial disclosures to report.

mbock@frontlinemedcom.com

An emerging market of molecular markers for thyroid cancer diagnostic and prognostic evaluation challenges current medical and surgical management; however, here is a strong word of caution; Unless the markers have been tested in the context of clinical and surgical management their true efficacy has not been accurately assessed.

We must always ask two questions before ordering these tests that can cost more than $3,000: 1) Does the use of a molecular test add any additional information that would otherwise change our recommendations; in other words, is the clinical information already known enough for appropriate clinical decision making? 2) What is the basis upon which recommendations for its use have been made; in other words, how were the studies conducted and interpreted? Are they valid?

By way of background, the gene expression clarifier (GEC) Afirma is marketed as a diagnostic tool for the differential diagnosis of indeterminate thyroid cytology (atypical cells of undetermined significance or follicular neoplasm, Bethesda categories III and IV, respectively).

Most importantly, it has been tested and is marketed as a negative predictor only. It is also only useful if used in the appropriate setting and if the test result is negative; a positive Afirma test can tell us only that the nodule is indeterminate, something, by definition, already determined by fine needle aspiration (FNA). Furthermore, any study examining its efficacy must be conducted within the context of clinical scenarios. For example, for a patient with an indeterminate lesion and a symptomatic multinodular goiter, neither a negative nor positive Afirma result would have any impact on surgical decision making and yet would have cost the patient more than $3,000. The latter patient simply needs a thyroidectomy. A patient who has a nodule that is approaching 4 cm or is increasing in size or a patient who has undergone several FNAs, ultrasounds, and endocrinology consultations similarly would likely choose surgery regardless of the GEC test result.

The only scenario in which Afirma testing is useful is in a patient with otherwise no indications for surgery except an indeterminate FNA; for instance for a patient with an asymptomatic < 4cm, stable, single nodule. In this scenario only a negative result could be helpful and would obviate the need for surgical intervention. One also must ask what is the likelihood of the patient undergoing repeat FNA, having repeat indeterminate cytology and repeat Afirma testing over the ensuing years and at what point should we consider these costs prohibitive compared with the patient undergoing a thyroidectomy instead?

Similar concerns exist with regard to somatic mutation panels, the most commonly marketed and used being Asuragen. The mutation panel consists of Ras and BRAF mutation and RET/PTC and PAX8/PPAR-gamma chromosomal rearrangement analyses. Importantly, the expanding literature on molecular markers for thyroid cancer, however, has lost track of a vast body of literature that reports Ras mutations present in up to 30% of benign thyroid nodules; RET/PTC in 24% and PAX8/PPAR-gamma in 14%, dramatically challenging the validity of the panel purported to accurately identify thyroid malignancy. We know that BRAF mutation is exclusively found in papillary thyroid cancer, but generally a BRAF-positive tumor is one in which a cytological diagnosis is already clear; it is either suspicious or definitively malignant on FNA. One might suggest that these aforementioned markers might indicate a harbinger of malignancy or identify a precancerous lesion; however, there is no study that supports this theory. Furthermore, it is important to note that even among pathology experts the diagnoses of follicular adenoma, follicular cancer, and follicular variant of papillary thyroid cancer have significant and documented inter- and intra- observer variability, thus challenging the gold standard upon which these markers have been tested.

With regard to BRAF, Ras, RET/PTC and PAX8/PPAR-gamma as prognostic markers there are many considerations, the least of which includes the differential diagnosis of follicular lesions addressed above and the known presence of these abnormalities in benign tumors. The majority of studies to date have conducted only univariate analyses without consideration of the clinical variables already available to us to make needed clinical decisions. In order to examine the usefulness of any marker panel a multivariable study is required, incorporating the available clinical variables such as size, lymph node metastases, and extra-thyroidal extension. For instance, the majority of studies examining the presence of lymph node metastases in BRAF-negative vs. BRAF-positive tumors were almost uniformly conducted on patients in whom routine lymph node dissection was not performed, thereby skewing the results. Only patients with suspicious nodes underwent a lymph node dissection; thus for those patients who had no suspicious nodes there was no information about their nodal status. Furthermore, several studies that included patients who underwent routine lymph node dissections and, importantly, included patients who underwent prophylactic dissections for whom a marker would be most useful, did not find that BRAF mutation was associated with aggressive features, including the presence of lymph node metastases. The same can be stated for a panel that includes Ras, RET/PTC, & PAX8/PPAR-gamma. “Follicular variant of papillary thyroid cancer and follicular cancer” will more likely harbor Ras and PAX8/PPAR-gamma mutations and will, by definition, include some tumors that would be considered benign by other pathologists.

There is an emerging market for molecular markers for thyroid cancer diagnosis and prognosis, but many of the studies driving this market are lacking in scientific rigor with regard to design and interpretation of results. Furthermore, the use of the marker panel requires scrutiny of its true impact on clinical management as well as its cost-effectiveness. GEC provides a negative predictor of malignancy and should be used to obviate surgery only; if the patient requires surgery its use provides no added information. BRAF is specific for thyroid cancer diagnosis, but is often not required as FNA evaluation in BRAF-positive tumors is usually already suspicious or malignant. Finally, molecular marker panels for thyroid cancer prognosis may be promising, but scrutiny for true accuracy and true clinical impact is necessary in order to make logical and useful recommendations for our patients.

Dr. Zeiger is professor of surgery, oncology, cellular, and molecular medicine, associate vice chair for faculty development, and associate dean for postdoctoral affairs at Johns Hopkins University in Baltimore. Dr. Zeiger consults for Interpace Diagnostics.

An emerging market of molecular markers for thyroid cancer diagnostic and prognostic evaluation challenges current medical and surgical management; however, here is a strong word of caution; Unless the markers have been tested in the context of clinical and surgical management their true efficacy has not been accurately assessed.

We must always ask two questions before ordering these tests that can cost more than $3,000: 1) Does the use of a molecular test add any additional information that would otherwise change our recommendations; in other words, is the clinical information already known enough for appropriate clinical decision making? 2) What is the basis upon which recommendations for its use have been made; in other words, how were the studies conducted and interpreted? Are they valid?

By way of background, the gene expression clarifier (GEC) Afirma is marketed as a diagnostic tool for the differential diagnosis of indeterminate thyroid cytology (atypical cells of undetermined significance or follicular neoplasm, Bethesda categories III and IV, respectively).

Most importantly, it has been tested and is marketed as a negative predictor only. It is also only useful if used in the appropriate setting and if the test result is negative; a positive Afirma test can tell us only that the nodule is indeterminate, something, by definition, already determined by fine needle aspiration (FNA). Furthermore, any study examining its efficacy must be conducted within the context of clinical scenarios. For example, for a patient with an indeterminate lesion and a symptomatic multinodular goiter, neither a negative nor positive Afirma result would have any impact on surgical decision making and yet would have cost the patient more than $3,000. The latter patient simply needs a thyroidectomy. A patient who has a nodule that is approaching 4 cm or is increasing in size or a patient who has undergone several FNAs, ultrasounds, and endocrinology consultations similarly would likely choose surgery regardless of the GEC test result.

The only scenario in which Afirma testing is useful is in a patient with otherwise no indications for surgery except an indeterminate FNA; for instance for a patient with an asymptomatic < 4cm, stable, single nodule. In this scenario only a negative result could be helpful and would obviate the need for surgical intervention. One also must ask what is the likelihood of the patient undergoing repeat FNA, having repeat indeterminate cytology and repeat Afirma testing over the ensuing years and at what point should we consider these costs prohibitive compared with the patient undergoing a thyroidectomy instead?

Similar concerns exist with regard to somatic mutation panels, the most commonly marketed and used being Asuragen. The mutation panel consists of Ras and BRAF mutation and RET/PTC and PAX8/PPAR-gamma chromosomal rearrangement analyses. Importantly, the expanding literature on molecular markers for thyroid cancer, however, has lost track of a vast body of literature that reports Ras mutations present in up to 30% of benign thyroid nodules; RET/PTC in 24% and PAX8/PPAR-gamma in 14%, dramatically challenging the validity of the panel purported to accurately identify thyroid malignancy. We know that BRAF mutation is exclusively found in papillary thyroid cancer, but generally a BRAF-positive tumor is one in which a cytological diagnosis is already clear; it is either suspicious or definitively malignant on FNA. One might suggest that these aforementioned markers might indicate a harbinger of malignancy or identify a precancerous lesion; however, there is no study that supports this theory. Furthermore, it is important to note that even among pathology experts the diagnoses of follicular adenoma, follicular cancer, and follicular variant of papillary thyroid cancer have significant and documented inter- and intra- observer variability, thus challenging the gold standard upon which these markers have been tested.

With regard to BRAF, Ras, RET/PTC and PAX8/PPAR-gamma as prognostic markers there are many considerations, the least of which includes the differential diagnosis of follicular lesions addressed above and the known presence of these abnormalities in benign tumors. The majority of studies to date have conducted only univariate analyses without consideration of the clinical variables already available to us to make needed clinical decisions. In order to examine the usefulness of any marker panel a multivariable study is required, incorporating the available clinical variables such as size, lymph node metastases, and extra-thyroidal extension. For instance, the majority of studies examining the presence of lymph node metastases in BRAF-negative vs. BRAF-positive tumors were almost uniformly conducted on patients in whom routine lymph node dissection was not performed, thereby skewing the results. Only patients with suspicious nodes underwent a lymph node dissection; thus for those patients who had no suspicious nodes there was no information about their nodal status. Furthermore, several studies that included patients who underwent routine lymph node dissections and, importantly, included patients who underwent prophylactic dissections for whom a marker would be most useful, did not find that BRAF mutation was associated with aggressive features, including the presence of lymph node metastases. The same can be stated for a panel that includes Ras, RET/PTC, & PAX8/PPAR-gamma. “Follicular variant of papillary thyroid cancer and follicular cancer” will more likely harbor Ras and PAX8/PPAR-gamma mutations and will, by definition, include some tumors that would be considered benign by other pathologists.

There is an emerging market for molecular markers for thyroid cancer diagnosis and prognosis, but many of the studies driving this market are lacking in scientific rigor with regard to design and interpretation of results. Furthermore, the use of the marker panel requires scrutiny of its true impact on clinical management as well as its cost-effectiveness. GEC provides a negative predictor of malignancy and should be used to obviate surgery only; if the patient requires surgery its use provides no added information. BRAF is specific for thyroid cancer diagnosis, but is often not required as FNA evaluation in BRAF-positive tumors is usually already suspicious or malignant. Finally, molecular marker panels for thyroid cancer prognosis may be promising, but scrutiny for true accuracy and true clinical impact is necessary in order to make logical and useful recommendations for our patients.

Dr. Zeiger is professor of surgery, oncology, cellular, and molecular medicine, associate vice chair for faculty development, and associate dean for postdoctoral affairs at Johns Hopkins University in Baltimore. Dr. Zeiger consults for Interpace Diagnostics.

An emerging market of molecular markers for thyroid cancer diagnostic and prognostic evaluation challenges current medical and surgical management; however, here is a strong word of caution; Unless the markers have been tested in the context of clinical and surgical management their true efficacy has not been accurately assessed.

We must always ask two questions before ordering these tests that can cost more than $3,000: 1) Does the use of a molecular test add any additional information that would otherwise change our recommendations; in other words, is the clinical information already known enough for appropriate clinical decision making? 2) What is the basis upon which recommendations for its use have been made; in other words, how were the studies conducted and interpreted? Are they valid?

By way of background, the gene expression clarifier (GEC) Afirma is marketed as a diagnostic tool for the differential diagnosis of indeterminate thyroid cytology (atypical cells of undetermined significance or follicular neoplasm, Bethesda categories III and IV, respectively).

Most importantly, it has been tested and is marketed as a negative predictor only. It is also only useful if used in the appropriate setting and if the test result is negative; a positive Afirma test can tell us only that the nodule is indeterminate, something, by definition, already determined by fine needle aspiration (FNA). Furthermore, any study examining its efficacy must be conducted within the context of clinical scenarios. For example, for a patient with an indeterminate lesion and a symptomatic multinodular goiter, neither a negative nor positive Afirma result would have any impact on surgical decision making and yet would have cost the patient more than $3,000. The latter patient simply needs a thyroidectomy. A patient who has a nodule that is approaching 4 cm or is increasing in size or a patient who has undergone several FNAs, ultrasounds, and endocrinology consultations similarly would likely choose surgery regardless of the GEC test result.

The only scenario in which Afirma testing is useful is in a patient with otherwise no indications for surgery except an indeterminate FNA; for instance for a patient with an asymptomatic < 4cm, stable, single nodule. In this scenario only a negative result could be helpful and would obviate the need for surgical intervention. One also must ask what is the likelihood of the patient undergoing repeat FNA, having repeat indeterminate cytology and repeat Afirma testing over the ensuing years and at what point should we consider these costs prohibitive compared with the patient undergoing a thyroidectomy instead?

Similar concerns exist with regard to somatic mutation panels, the most commonly marketed and used being Asuragen. The mutation panel consists of Ras and BRAF mutation and RET/PTC and PAX8/PPAR-gamma chromosomal rearrangement analyses. Importantly, the expanding literature on molecular markers for thyroid cancer, however, has lost track of a vast body of literature that reports Ras mutations present in up to 30% of benign thyroid nodules; RET/PTC in 24% and PAX8/PPAR-gamma in 14%, dramatically challenging the validity of the panel purported to accurately identify thyroid malignancy. We know that BRAF mutation is exclusively found in papillary thyroid cancer, but generally a BRAF-positive tumor is one in which a cytological diagnosis is already clear; it is either suspicious or definitively malignant on FNA. One might suggest that these aforementioned markers might indicate a harbinger of malignancy or identify a precancerous lesion; however, there is no study that supports this theory. Furthermore, it is important to note that even among pathology experts the diagnoses of follicular adenoma, follicular cancer, and follicular variant of papillary thyroid cancer have significant and documented inter- and intra- observer variability, thus challenging the gold standard upon which these markers have been tested.

With regard to BRAF, Ras, RET/PTC and PAX8/PPAR-gamma as prognostic markers there are many considerations, the least of which includes the differential diagnosis of follicular lesions addressed above and the known presence of these abnormalities in benign tumors. The majority of studies to date have conducted only univariate analyses without consideration of the clinical variables already available to us to make needed clinical decisions. In order to examine the usefulness of any marker panel a multivariable study is required, incorporating the available clinical variables such as size, lymph node metastases, and extra-thyroidal extension. For instance, the majority of studies examining the presence of lymph node metastases in BRAF-negative vs. BRAF-positive tumors were almost uniformly conducted on patients in whom routine lymph node dissection was not performed, thereby skewing the results. Only patients with suspicious nodes underwent a lymph node dissection; thus for those patients who had no suspicious nodes there was no information about their nodal status. Furthermore, several studies that included patients who underwent routine lymph node dissections and, importantly, included patients who underwent prophylactic dissections for whom a marker would be most useful, did not find that BRAF mutation was associated with aggressive features, including the presence of lymph node metastases. The same can be stated for a panel that includes Ras, RET/PTC, & PAX8/PPAR-gamma. “Follicular variant of papillary thyroid cancer and follicular cancer” will more likely harbor Ras and PAX8/PPAR-gamma mutations and will, by definition, include some tumors that would be considered benign by other pathologists.

There is an emerging market for molecular markers for thyroid cancer diagnosis and prognosis, but many of the studies driving this market are lacking in scientific rigor with regard to design and interpretation of results. Furthermore, the use of the marker panel requires scrutiny of its true impact on clinical management as well as its cost-effectiveness. GEC provides a negative predictor of malignancy and should be used to obviate surgery only; if the patient requires surgery its use provides no added information. BRAF is specific for thyroid cancer diagnosis, but is often not required as FNA evaluation in BRAF-positive tumors is usually already suspicious or malignant. Finally, molecular marker panels for thyroid cancer prognosis may be promising, but scrutiny for true accuracy and true clinical impact is necessary in order to make logical and useful recommendations for our patients.

Dr. Zeiger is professor of surgery, oncology, cellular, and molecular medicine, associate vice chair for faculty development, and associate dean for postdoctoral affairs at Johns Hopkins University in Baltimore. Dr. Zeiger consults for Interpace Diagnostics.

Increased amygdala activity after testosterone administration is bound to social threat approach, not social threat avoidance, a newly published research article shows.

Sina Radke, Ph.D., of Radboud University Nijmegen in the Netherlands and associates enrolled 54 female volunteers aged 18 to 30 in a double-blind, randomized, placebo-controlled study. The participants received either a single dose of 0.5 mg of testosterone (n = 26) or a matched placebo (n = 28), then completed a task where they were shown visually presented emotional facial expressions, and responded by either pulling a joystick toward their bodies (approach movement) or pushing it away from their bodies (avoidance movement).

Compared to placebo, testosterone administration increased left amygdala activity during approach trials at trend level (P = 0.10), and decreased it during avoidance trials (P = 0.01). In addition, left amygdala activity significantly differed between approach and avoidance of angry faces after testosterone administration (P = 0.034) but not after placebo (P = 0.23).

“By differentiating between approach and avoidance, we showed that testosterone modulates amygdala reactivity according to current motivational demands and not according to the emotional or action context per se,” the authors wrote. “This motivation-specific mechanism converges with approach-enhancing effects of testosterone observed during social challenges.”

Read the entire article here: Sci. Adv. 2015 (doi: 10.1126/sciadv.1400074)

mbock@frontlinemedcom.com

Increased amygdala activity after testosterone administration is bound to social threat approach, not social threat avoidance, a newly published research article shows.

Sina Radke, Ph.D., of Radboud University Nijmegen in the Netherlands and associates enrolled 54 female volunteers aged 18 to 30 in a double-blind, randomized, placebo-controlled study. The participants received either a single dose of 0.5 mg of testosterone (n = 26) or a matched placebo (n = 28), then completed a task where they were shown visually presented emotional facial expressions, and responded by either pulling a joystick toward their bodies (approach movement) or pushing it away from their bodies (avoidance movement).

Compared to placebo, testosterone administration increased left amygdala activity during approach trials at trend level (P = 0.10), and decreased it during avoidance trials (P = 0.01). In addition, left amygdala activity significantly differed between approach and avoidance of angry faces after testosterone administration (P = 0.034) but not after placebo (P = 0.23).

“By differentiating between approach and avoidance, we showed that testosterone modulates amygdala reactivity according to current motivational demands and not according to the emotional or action context per se,” the authors wrote. “This motivation-specific mechanism converges with approach-enhancing effects of testosterone observed during social challenges.”

Read the entire article here: Sci. Adv. 2015 (doi: 10.1126/sciadv.1400074)

mbock@frontlinemedcom.com

Increased amygdala activity after testosterone administration is bound to social threat approach, not social threat avoidance, a newly published research article shows.

Sina Radke, Ph.D., of Radboud University Nijmegen in the Netherlands and associates enrolled 54 female volunteers aged 18 to 30 in a double-blind, randomized, placebo-controlled study. The participants received either a single dose of 0.5 mg of testosterone (n = 26) or a matched placebo (n = 28), then completed a task where they were shown visually presented emotional facial expressions, and responded by either pulling a joystick toward their bodies (approach movement) or pushing it away from their bodies (avoidance movement).

Compared to placebo, testosterone administration increased left amygdala activity during approach trials at trend level (P = 0.10), and decreased it during avoidance trials (P = 0.01). In addition, left amygdala activity significantly differed between approach and avoidance of angry faces after testosterone administration (P = 0.034) but not after placebo (P = 0.23).

“By differentiating between approach and avoidance, we showed that testosterone modulates amygdala reactivity according to current motivational demands and not according to the emotional or action context per se,” the authors wrote. “This motivation-specific mechanism converges with approach-enhancing effects of testosterone observed during social challenges.”

Read the entire article here: Sci. Adv. 2015 (doi: 10.1126/sciadv.1400074)

mbock@frontlinemedcom.com

In patients with indeterminate thyroid nodules, routine gene expression classifier testing may not meet standard definitions of cost efficacy relative to conventional care at many treatment centers, according to a decision-tree analysis performed with data from a tertiary treatment center.

In this analysis, gene expression classifier (GEC) testing was associated with a small gain in health benefits, measured in quality adjusted life-years (QALY), but at a much higher cost than conventional care, according to Dr. James X. Wu of the University of California, Los Angeles. The data were presented at the annual meeting of the American Association of Endocrine Surgeons (AAES).

Management of thyroid nodules indeterminate for malignancy after fine needle aspiration, which occurs in up to 30% of patients, is a challenge, according to Dr. Wu. Cancer rates in these patients can be as high as 30%, and often benign and malignant indeterminate nodules are indistinguishable. Conventionally, surgical resection is recommended to avoid missing a cancer diagnosis. However, uniform thyroid lobectomy means that 70% or more of lesions excised will be benign.

GEC testing is a relatively new molecular test that helps guide therapy in these individuals. The high negative predictive value of this test allows the test to reliably predict when patients have benign disease, giving them the option of being observed rather than undergoing surgery, explained Dr. Wu. In this study, the goal was to determine whether GEC testing has the potential to be cost effective, defined as a ratio of added cost to QALYs gained of less than $100,000/QALY relative to conventional treatment.

The decision-tree model was constructed on 2 years of GEC testing performance data prospectively collected at UCLA. In this model, the assumption was made that patients would be observed if the GEC test was negative but would undergo thyroid resection if the gene expression classifier test was suspicious.

Applying the UCLA dataset to the model, the expected cost for conventional management in the reference scenario was $11,119 to produce 22.15 QALYs, according to Dr. Wu. Routine GEC testing produced an additional 0.01 QALY but cost $1,197 more. This translated into an incremental cost-effectiveness ratio of $119,700/QALY, which exceeded the common $100,000/QALY threshold for cost efficacy.

The main determinants of cost effectiveness were the cost of the gene expression classifier test, the rate of malignancy in patients with indeterminate thyroid nodules, and cost of thyroid lobectomy.

More favorable costs for gene expression testing could be generated by plausible alterations of key clinical factors. This included lowering the cost of the GEC test itself or raising the cost of thyroid lobectomy. For example, the GEC testing became cost effective with the parameters used if the test was less than $2,460 or the cost of thyroid lobectomy exceeded $12,160.

In addition, malignancy rates influenced the relative cost efficacy of gene expression classifier testing. Centers with lower rates of cancer get more value from routine GEC testing than do centers with high rates of cancer, because more patients avoid surgery with testing. At UCLA, the malignancy rate was 24%, and could pay as much as $2,460 per test to remain cost-effective. Institutions with a malignancy rate less than 24% would have a higher cost threshold.

Indeed, even though routine gene expression classifier testing was not found to be cost effective using the assumptions of this study and data from UCLA, on probabilistic sensitivity analysis, it was found to be cost effective in 53.2% of simulations. Dr. Wu suggested the same analyses should be performed at centers using their own data to accurately assess cost effectiveness. Given the wide variation in important variables, particularly the malignancy rate in indeterminate nodules, the results from one institution cannot reliably predict the cost effectiveness at a separate treatment facility.

“Our conclusion is that every center needs to audit themselves to find out whether it’s truly cost effective and not blindly trust that it’s 100% cost effective across the board.” Dr. Wu reported. He noted that gene expression classifier testing, which has been used for 2 years at UCLA, is likely to be continued to be used but with a focus on making the test more cost effective by finding ways to use it more selectively.

In patients with indeterminate thyroid nodules, routine gene expression classifier testing may not meet standard definitions of cost efficacy relative to conventional care at many treatment centers, according to a decision-tree analysis performed with data from a tertiary treatment center.

In this analysis, gene expression classifier (GEC) testing was associated with a small gain in health benefits, measured in quality adjusted life-years (QALY), but at a much higher cost than conventional care, according to Dr. James X. Wu of the University of California, Los Angeles. The data were presented at the annual meeting of the American Association of Endocrine Surgeons (AAES).

Management of thyroid nodules indeterminate for malignancy after fine needle aspiration, which occurs in up to 30% of patients, is a challenge, according to Dr. Wu. Cancer rates in these patients can be as high as 30%, and often benign and malignant indeterminate nodules are indistinguishable. Conventionally, surgical resection is recommended to avoid missing a cancer diagnosis. However, uniform thyroid lobectomy means that 70% or more of lesions excised will be benign.

GEC testing is a relatively new molecular test that helps guide therapy in these individuals. The high negative predictive value of this test allows the test to reliably predict when patients have benign disease, giving them the option of being observed rather than undergoing surgery, explained Dr. Wu. In this study, the goal was to determine whether GEC testing has the potential to be cost effective, defined as a ratio of added cost to QALYs gained of less than $100,000/QALY relative to conventional treatment.

The decision-tree model was constructed on 2 years of GEC testing performance data prospectively collected at UCLA. In this model, the assumption was made that patients would be observed if the GEC test was negative but would undergo thyroid resection if the gene expression classifier test was suspicious.

Applying the UCLA dataset to the model, the expected cost for conventional management in the reference scenario was $11,119 to produce 22.15 QALYs, according to Dr. Wu. Routine GEC testing produced an additional 0.01 QALY but cost $1,197 more. This translated into an incremental cost-effectiveness ratio of $119,700/QALY, which exceeded the common $100,000/QALY threshold for cost efficacy.

The main determinants of cost effectiveness were the cost of the gene expression classifier test, the rate of malignancy in patients with indeterminate thyroid nodules, and cost of thyroid lobectomy.

More favorable costs for gene expression testing could be generated by plausible alterations of key clinical factors. This included lowering the cost of the GEC test itself or raising the cost of thyroid lobectomy. For example, the GEC testing became cost effective with the parameters used if the test was less than $2,460 or the cost of thyroid lobectomy exceeded $12,160.

In addition, malignancy rates influenced the relative cost efficacy of gene expression classifier testing. Centers with lower rates of cancer get more value from routine GEC testing than do centers with high rates of cancer, because more patients avoid surgery with testing. At UCLA, the malignancy rate was 24%, and could pay as much as $2,460 per test to remain cost-effective. Institutions with a malignancy rate less than 24% would have a higher cost threshold.

Indeed, even though routine gene expression classifier testing was not found to be cost effective using the assumptions of this study and data from UCLA, on probabilistic sensitivity analysis, it was found to be cost effective in 53.2% of simulations. Dr. Wu suggested the same analyses should be performed at centers using their own data to accurately assess cost effectiveness. Given the wide variation in important variables, particularly the malignancy rate in indeterminate nodules, the results from one institution cannot reliably predict the cost effectiveness at a separate treatment facility.

“Our conclusion is that every center needs to audit themselves to find out whether it’s truly cost effective and not blindly trust that it’s 100% cost effective across the board.” Dr. Wu reported. He noted that gene expression classifier testing, which has been used for 2 years at UCLA, is likely to be continued to be used but with a focus on making the test more cost effective by finding ways to use it more selectively.

In patients with indeterminate thyroid nodules, routine gene expression classifier testing may not meet standard definitions of cost efficacy relative to conventional care at many treatment centers, according to a decision-tree analysis performed with data from a tertiary treatment center.

In this analysis, gene expression classifier (GEC) testing was associated with a small gain in health benefits, measured in quality adjusted life-years (QALY), but at a much higher cost than conventional care, according to Dr. James X. Wu of the University of California, Los Angeles. The data were presented at the annual meeting of the American Association of Endocrine Surgeons (AAES).

Management of thyroid nodules indeterminate for malignancy after fine needle aspiration, which occurs in up to 30% of patients, is a challenge, according to Dr. Wu. Cancer rates in these patients can be as high as 30%, and often benign and malignant indeterminate nodules are indistinguishable. Conventionally, surgical resection is recommended to avoid missing a cancer diagnosis. However, uniform thyroid lobectomy means that 70% or more of lesions excised will be benign.

GEC testing is a relatively new molecular test that helps guide therapy in these individuals. The high negative predictive value of this test allows the test to reliably predict when patients have benign disease, giving them the option of being observed rather than undergoing surgery, explained Dr. Wu. In this study, the goal was to determine whether GEC testing has the potential to be cost effective, defined as a ratio of added cost to QALYs gained of less than $100,000/QALY relative to conventional treatment.

The decision-tree model was constructed on 2 years of GEC testing performance data prospectively collected at UCLA. In this model, the assumption was made that patients would be observed if the GEC test was negative but would undergo thyroid resection if the gene expression classifier test was suspicious.

Applying the UCLA dataset to the model, the expected cost for conventional management in the reference scenario was $11,119 to produce 22.15 QALYs, according to Dr. Wu. Routine GEC testing produced an additional 0.01 QALY but cost $1,197 more. This translated into an incremental cost-effectiveness ratio of $119,700/QALY, which exceeded the common $100,000/QALY threshold for cost efficacy.

The main determinants of cost effectiveness were the cost of the gene expression classifier test, the rate of malignancy in patients with indeterminate thyroid nodules, and cost of thyroid lobectomy.

More favorable costs for gene expression testing could be generated by plausible alterations of key clinical factors. This included lowering the cost of the GEC test itself or raising the cost of thyroid lobectomy. For example, the GEC testing became cost effective with the parameters used if the test was less than $2,460 or the cost of thyroid lobectomy exceeded $12,160.

In addition, malignancy rates influenced the relative cost efficacy of gene expression classifier testing. Centers with lower rates of cancer get more value from routine GEC testing than do centers with high rates of cancer, because more patients avoid surgery with testing. At UCLA, the malignancy rate was 24%, and could pay as much as $2,460 per test to remain cost-effective. Institutions with a malignancy rate less than 24% would have a higher cost threshold.

Indeed, even though routine gene expression classifier testing was not found to be cost effective using the assumptions of this study and data from UCLA, on probabilistic sensitivity analysis, it was found to be cost effective in 53.2% of simulations. Dr. Wu suggested the same analyses should be performed at centers using their own data to accurately assess cost effectiveness. Given the wide variation in important variables, particularly the malignancy rate in indeterminate nodules, the results from one institution cannot reliably predict the cost effectiveness at a separate treatment facility.

“Our conclusion is that every center needs to audit themselves to find out whether it’s truly cost effective and not blindly trust that it’s 100% cost effective across the board.” Dr. Wu reported. He noted that gene expression classifier testing, which has been used for 2 years at UCLA, is likely to be continued to be used but with a focus on making the test more cost effective by finding ways to use it more selectively.

Thyroid dysfunction was associated with an increased risk of mortality in patients with heart failure due to idiopathic dilated cardiomyopathy (IDCM), according to research reported in the Journal of Clinical Endocrinology and Metabolism.

Lead author Wenyao Wang of the Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, and associates gathered data from 458 consecutive patients with IDCM who were admitted to the National Center of Cardiovascular diseases in Beijing, and then evaluated their risk of mortality based on levels of free T₃ and TSH and the whole thyroid function profile.

Hypothyroidism was the strongest predictor of mortality (hazard ratio, 4.189; 95% confidence interval, 2.118-8.283), followed by low-T₃ syndrome (HR, 3.147; 95% CI, 1.558-6.355) and subclinical hypothyroidism (HR, 2.869; 95% CI, 1.817-4.532); subclinical hyperthyroidism did not have a significant impact on mortality. The most common forms of thyroid dysfunction were subclinical hypothyroidism (n = 41, 9%), followed by subclinical hyperthyroidism (n = 35, 7%), low-T3 syndrome (n = 17, 4%), and overt hypothyroidism (n = 12, 3%).

“Monitoring thyroid function is necessary for patients with IDCM, and further study is warranted to investigate whether reversing low thyroid function can benefit these patients,” the investigators noted.

Read the full article here: (J. Clin. Endocrinol. Metab. 2015 [doi:10.1210/jc.2014-4159]).

The investigators reported that they had no financial disclosures to make.

mbock@frontlinemedcom.com

Thyroid dysfunction was associated with an increased risk of mortality in patients with heart failure due to idiopathic dilated cardiomyopathy (IDCM), according to research reported in the Journal of Clinical Endocrinology and Metabolism.

Lead author Wenyao Wang of the Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, and associates gathered data from 458 consecutive patients with IDCM who were admitted to the National Center of Cardiovascular diseases in Beijing, and then evaluated their risk of mortality based on levels of free T₃ and TSH and the whole thyroid function profile.

Hypothyroidism was the strongest predictor of mortality (hazard ratio, 4.189; 95% confidence interval, 2.118-8.283), followed by low-T₃ syndrome (HR, 3.147; 95% CI, 1.558-6.355) and subclinical hypothyroidism (HR, 2.869; 95% CI, 1.817-4.532); subclinical hyperthyroidism did not have a significant impact on mortality. The most common forms of thyroid dysfunction were subclinical hypothyroidism (n = 41, 9%), followed by subclinical hyperthyroidism (n = 35, 7%), low-T3 syndrome (n = 17, 4%), and overt hypothyroidism (n = 12, 3%).

“Monitoring thyroid function is necessary for patients with IDCM, and further study is warranted to investigate whether reversing low thyroid function can benefit these patients,” the investigators noted.

Read the full article here: (J. Clin. Endocrinol. Metab. 2015 [doi:10.1210/jc.2014-4159]).

The investigators reported that they had no financial disclosures to make.

mbock@frontlinemedcom.com

Thyroid dysfunction was associated with an increased risk of mortality in patients with heart failure due to idiopathic dilated cardiomyopathy (IDCM), according to research reported in the Journal of Clinical Endocrinology and Metabolism.

Lead author Wenyao Wang of the Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, and associates gathered data from 458 consecutive patients with IDCM who were admitted to the National Center of Cardiovascular diseases in Beijing, and then evaluated their risk of mortality based on levels of free T₃ and TSH and the whole thyroid function profile.

Hypothyroidism was the strongest predictor of mortality (hazard ratio, 4.189; 95% confidence interval, 2.118-8.283), followed by low-T₃ syndrome (HR, 3.147; 95% CI, 1.558-6.355) and subclinical hypothyroidism (HR, 2.869; 95% CI, 1.817-4.532); subclinical hyperthyroidism did not have a significant impact on mortality. The most common forms of thyroid dysfunction were subclinical hypothyroidism (n = 41, 9%), followed by subclinical hyperthyroidism (n = 35, 7%), low-T3 syndrome (n = 17, 4%), and overt hypothyroidism (n = 12, 3%).

“Monitoring thyroid function is necessary for patients with IDCM, and further study is warranted to investigate whether reversing low thyroid function can benefit these patients,” the investigators noted.

Read the full article here: (J. Clin. Endocrinol. Metab. 2015 [doi:10.1210/jc.2014-4159]).

The investigators reported that they had no financial disclosures to make.

mbock@frontlinemedcom.com

African American and Hispanic adolescents and adults under the age of 40 years were more likely to die from differentiated thyroid cancer than were non-Hispanic whites from the same age range, said the authors of a newly published study in Thyroid.

Lead author Theresa H.M. Keegan, Ph.D., of Stanford (Calif.) University and her associates used the California Cancer Registry to obtain data on 16,827 adolescents and young adults who had a diagnosis of differentiated thyroid cancer between 1988 and 2010. Older young adults aged 35-39 years (versus 15- to 29-year-olds), men (hazard ratio, 2.77; 95% confidence interval, 1.62-4.72), and adolescents and young adults of African American or Hispanic race/ethnicity (versus non-Hispanic whites) had worse thyroid cancer–specific survival than did non-Hispanic whites, judging from findings of multivariate analyses using Cox proportional hazards regression.

In addition, residence in low-socioeconomic-status neighborhoods (HR, 3.11; 95% CI, 1.28-7.56) and nonmetropolitan areas (HR, 5.53; 95% CI, 2.07-14.78) was associated with worse thyroid cancer–specific survival among adolescent and young adult men but not adolescent and young adult women.

“Our study is one of the first to simultaneously consider the impact of small-area neighborhood [socioeconomic status], health insurance, marital status, diagnosis of subsequent cancers, and a number of tumor characteristics on survival after” differentiated thyroid cancer in adolescents and young adults, the authors noted.

Read the full article here (Thyroid 2015;25:635-48 [doi:10.1089/thy.2015.0021]).

The authors reported that they did not have any competing financial interests.

mbock@frontlinemedcom.com

African American and Hispanic adolescents and adults under the age of 40 years were more likely to die from differentiated thyroid cancer than were non-Hispanic whites from the same age range, said the authors of a newly published study in Thyroid.

Lead author Theresa H.M. Keegan, Ph.D., of Stanford (Calif.) University and her associates used the California Cancer Registry to obtain data on 16,827 adolescents and young adults who had a diagnosis of differentiated thyroid cancer between 1988 and 2010. Older young adults aged 35-39 years (versus 15- to 29-year-olds), men (hazard ratio, 2.77; 95% confidence interval, 1.62-4.72), and adolescents and young adults of African American or Hispanic race/ethnicity (versus non-Hispanic whites) had worse thyroid cancer–specific survival than did non-Hispanic whites, judging from findings of multivariate analyses using Cox proportional hazards regression.

In addition, residence in low-socioeconomic-status neighborhoods (HR, 3.11; 95% CI, 1.28-7.56) and nonmetropolitan areas (HR, 5.53; 95% CI, 2.07-14.78) was associated with worse thyroid cancer–specific survival among adolescent and young adult men but not adolescent and young adult women.

“Our study is one of the first to simultaneously consider the impact of small-area neighborhood [socioeconomic status], health insurance, marital status, diagnosis of subsequent cancers, and a number of tumor characteristics on survival after” differentiated thyroid cancer in adolescents and young adults, the authors noted.

Read the full article here (Thyroid 2015;25:635-48 [doi:10.1089/thy.2015.0021]).

The authors reported that they did not have any competing financial interests.

mbock@frontlinemedcom.com

African American and Hispanic adolescents and adults under the age of 40 years were more likely to die from differentiated thyroid cancer than were non-Hispanic whites from the same age range, said the authors of a newly published study in Thyroid.

Lead author Theresa H.M. Keegan, Ph.D., of Stanford (Calif.) University and her associates used the California Cancer Registry to obtain data on 16,827 adolescents and young adults who had a diagnosis of differentiated thyroid cancer between 1988 and 2010. Older young adults aged 35-39 years (versus 15- to 29-year-olds), men (hazard ratio, 2.77; 95% confidence interval, 1.62-4.72), and adolescents and young adults of African American or Hispanic race/ethnicity (versus non-Hispanic whites) had worse thyroid cancer–specific survival than did non-Hispanic whites, judging from findings of multivariate analyses using Cox proportional hazards regression.

In addition, residence in low-socioeconomic-status neighborhoods (HR, 3.11; 95% CI, 1.28-7.56) and nonmetropolitan areas (HR, 5.53; 95% CI, 2.07-14.78) was associated with worse thyroid cancer–specific survival among adolescent and young adult men but not adolescent and young adult women.

“Our study is one of the first to simultaneously consider the impact of small-area neighborhood [socioeconomic status], health insurance, marital status, diagnosis of subsequent cancers, and a number of tumor characteristics on survival after” differentiated thyroid cancer in adolescents and young adults, the authors noted.

Read the full article here (Thyroid 2015;25:635-48 [doi:10.1089/thy.2015.0021]).

The authors reported that they did not have any competing financial interests.

mbock@frontlinemedcom.com

SAN DIEGO – Routine preoperative use of genetic testing to detect mutations implicated in thyroid carcinogenesis can help guide perioperative decision making, though risks associated with mutations are not always clear-cut.

For individuals with thyroid cancer (TC), the presence of certain mutations was associated with higher risk of early recurrence of cancer as well as distant metastases, according to a recent study presented by Dr. Linwah Yip at the annual meeting of the American Surgical Association. She and her colleagues at the University of Pittsburgh built on their previous work to characterize how thyroid cancer genotype relates both to cancer histology and to disease-related outcomes.

Using data from the electronic medical record of a single institution, Dr. Yip and her colleagues examined data from consecutive patients who had initial surgery for histologically confirmed TC. Of the 1,510 patients in the study cohort, 77% were women, and patients had a mean age of 49 years. All of the cancers in the study were tested for mutations in seven genes known to be associated with thyroid carcinogenesis. Mutation testing was a routine part of preoperative care for thyroid cancer patients, often performed on preoperative fine needle aspiration (FNA) biopsy.

Outcomes tracked in the study, Dr. Yip said, included the type and stage of thyroid cancer identified and whether the cancer recurred.

Mutations were found in 1,039 patients (69%), and no more than one mutation was found in any one tumor. No tumor genotype was specifically associated with tumor size or whether the tumor was multifocal.

Overall, BRAF V600E was the most common mutation associated with TC, and patients with this mutation were the ones most likely to have a recurrence (P = .001). However, Dr. Yip noted that there is phenotypic heterogeneity in how the recurrences present. More distant metastatic disease and lateral lymph node metastases were most likely with RET/PTC1 and three mutations (P = .02).

By contrast, about 25% of thyroid cancers in the study showed mutations in RAS, PAX8/PPARG, or BRAF K601E. These mutations were associated with a more indolent disease course, with more encapsulated tumors and an overall disease-free survival of nearly 100% at 5 years after diagnosis. Dr. Yip said, “However, RAS variations can be associated with any histologic type of thyroid cancer, including anaplastic.”

Dr. Yip said that clinicians should consider conducting perioperative neck ultrasound with lymph node mapping if BRAF V600E or RET/PTC mutations are found. Her recommendation for these patients was a total thyroidectomy, with consideration of a central compartment neck dissection performed prophylactically, in light of the > 50% chance for lymph node involvement. Additionally, surveillance for distant metastases in the form of a chest CT should be considered when tumors are REC/PTC positive.

Study limitations include its retrospective nature and the fact that the treating physicians were not blinded to mutation testing results. Additionally, Dr. Yip noted, in patients with multifocal disease, only the most aggressive tumor was included.

Dr. Chris McHenry of Case Western Reserve University, Cleveland, noted in discussion that disease-specific survival was not related to mutation testing in this study. For patients with advanced thyroid cancer who have limited treatment options, however, mutation testing may help direct specific adjuvant therapies based on risk.

Dr. Nikiforov is a consultant for Quest Diagnostics. The others reported no disclosures.

The complete manuscript of this study and its presentation at the American Surgical Association’s 135th Annual Meeting, April 2015, in San Diego, California, are anticipated to be published in the Annals of Surgery pending editorial review.

SAN DIEGO – Routine preoperative use of genetic testing to detect mutations implicated in thyroid carcinogenesis can help guide perioperative decision making, though risks associated with mutations are not always clear-cut.

For individuals with thyroid cancer (TC), the presence of certain mutations was associated with higher risk of early recurrence of cancer as well as distant metastases, according to a recent study presented by Dr. Linwah Yip at the annual meeting of the American Surgical Association. She and her colleagues at the University of Pittsburgh built on their previous work to characterize how thyroid cancer genotype relates both to cancer histology and to disease-related outcomes.

Using data from the electronic medical record of a single institution, Dr. Yip and her colleagues examined data from consecutive patients who had initial surgery for histologically confirmed TC. Of the 1,510 patients in the study cohort, 77% were women, and patients had a mean age of 49 years. All of the cancers in the study were tested for mutations in seven genes known to be associated with thyroid carcinogenesis. Mutation testing was a routine part of preoperative care for thyroid cancer patients, often performed on preoperative fine needle aspiration (FNA) biopsy.

Outcomes tracked in the study, Dr. Yip said, included the type and stage of thyroid cancer identified and whether the cancer recurred.

Mutations were found in 1,039 patients (69%), and no more than one mutation was found in any one tumor. No tumor genotype was specifically associated with tumor size or whether the tumor was multifocal.

Overall, BRAF V600E was the most common mutation associated with TC, and patients with this mutation were the ones most likely to have a recurrence (P = .001). However, Dr. Yip noted that there is phenotypic heterogeneity in how the recurrences present. More distant metastatic disease and lateral lymph node metastases were most likely with RET/PTC1 and three mutations (P = .02).

By contrast, about 25% of thyroid cancers in the study showed mutations in RAS, PAX8/PPARG, or BRAF K601E. These mutations were associated with a more indolent disease course, with more encapsulated tumors and an overall disease-free survival of nearly 100% at 5 years after diagnosis. Dr. Yip said, “However, RAS variations can be associated with any histologic type of thyroid cancer, including anaplastic.”

Dr. Yip said that clinicians should consider conducting perioperative neck ultrasound with lymph node mapping if BRAF V600E or RET/PTC mutations are found. Her recommendation for these patients was a total thyroidectomy, with consideration of a central compartment neck dissection performed prophylactically, in light of the > 50% chance for lymph node involvement. Additionally, surveillance for distant metastases in the form of a chest CT should be considered when tumors are REC/PTC positive.

Study limitations include its retrospective nature and the fact that the treating physicians were not blinded to mutation testing results. Additionally, Dr. Yip noted, in patients with multifocal disease, only the most aggressive tumor was included.

Dr. Chris McHenry of Case Western Reserve University, Cleveland, noted in discussion that disease-specific survival was not related to mutation testing in this study. For patients with advanced thyroid cancer who have limited treatment options, however, mutation testing may help direct specific adjuvant therapies based on risk.

Dr. Nikiforov is a consultant for Quest Diagnostics. The others reported no disclosures.

The complete manuscript of this study and its presentation at the American Surgical Association’s 135th Annual Meeting, April 2015, in San Diego, California, are anticipated to be published in the Annals of Surgery pending editorial review.

SAN DIEGO – Routine preoperative use of genetic testing to detect mutations implicated in thyroid carcinogenesis can help guide perioperative decision making, though risks associated with mutations are not always clear-cut.

For individuals with thyroid cancer (TC), the presence of certain mutations was associated with higher risk of early recurrence of cancer as well as distant metastases, according to a recent study presented by Dr. Linwah Yip at the annual meeting of the American Surgical Association. She and her colleagues at the University of Pittsburgh built on their previous work to characterize how thyroid cancer genotype relates both to cancer histology and to disease-related outcomes.

Using data from the electronic medical record of a single institution, Dr. Yip and her colleagues examined data from consecutive patients who had initial surgery for histologically confirmed TC. Of the 1,510 patients in the study cohort, 77% were women, and patients had a mean age of 49 years. All of the cancers in the study were tested for mutations in seven genes known to be associated with thyroid carcinogenesis. Mutation testing was a routine part of preoperative care for thyroid cancer patients, often performed on preoperative fine needle aspiration (FNA) biopsy.

Outcomes tracked in the study, Dr. Yip said, included the type and stage of thyroid cancer identified and whether the cancer recurred.

Mutations were found in 1,039 patients (69%), and no more than one mutation was found in any one tumor. No tumor genotype was specifically associated with tumor size or whether the tumor was multifocal.

Overall, BRAF V600E was the most common mutation associated with TC, and patients with this mutation were the ones most likely to have a recurrence (P = .001). However, Dr. Yip noted that there is phenotypic heterogeneity in how the recurrences present. More distant metastatic disease and lateral lymph node metastases were most likely with RET/PTC1 and three mutations (P = .02).

By contrast, about 25% of thyroid cancers in the study showed mutations in RAS, PAX8/PPARG, or BRAF K601E. These mutations were associated with a more indolent disease course, with more encapsulated tumors and an overall disease-free survival of nearly 100% at 5 years after diagnosis. Dr. Yip said, “However, RAS variations can be associated with any histologic type of thyroid cancer, including anaplastic.”

Dr. Yip said that clinicians should consider conducting perioperative neck ultrasound with lymph node mapping if BRAF V600E or RET/PTC mutations are found. Her recommendation for these patients was a total thyroidectomy, with consideration of a central compartment neck dissection performed prophylactically, in light of the > 50% chance for lymph node involvement. Additionally, surveillance for distant metastases in the form of a chest CT should be considered when tumors are REC/PTC positive.

Study limitations include its retrospective nature and the fact that the treating physicians were not blinded to mutation testing results. Additionally, Dr. Yip noted, in patients with multifocal disease, only the most aggressive tumor was included.

Dr. Chris McHenry of Case Western Reserve University, Cleveland, noted in discussion that disease-specific survival was not related to mutation testing in this study. For patients with advanced thyroid cancer who have limited treatment options, however, mutation testing may help direct specific adjuvant therapies based on risk.

Dr. Nikiforov is a consultant for Quest Diagnostics. The others reported no disclosures.

The complete manuscript of this study and its presentation at the American Surgical Association’s 135th Annual Meeting, April 2015, in San Diego, California, are anticipated to be published in the Annals of Surgery pending editorial review.

NASHVILLE – Endocrinologists dealing with adult patients who survived cancer during childhood should ensure that they have an adequate understanding of the elevated risk that such patients are at for various endocrine conditions, such as hypogonadism, hypopituitarism, and ovarian failure.

This is according to the findings of a survey study presented at the annual meeting of the American Association of Clinical Endocrinologists by Dr. Sripriya Raman of Children’s Mercy Hospital and Clinics in Kansas City, Missouri.

“Incidences of childhood cancer have crept up from 1975 to 1995, but mortality has gone down, thanks to advancements in cancer therapy,” explained Dr. Raman. “Even among ethnic groups – whites, Hispanics, African Americans, and Asians – cancer incidence rates have either stabilized or increased slightly, which means we’re seeing more and more of these types of patients at our clinics.”

Dr. Raman and coinvestigators developed a survey of 19 questions: 10 questions on provider characteristics, 5 on demographic data, and 4 questions derived from two clinical vignettes. This survey was then sent to 294 endocrinologists belonging to either the Pediatric Endocrine Society (PES) or the AACE between October and December 2014; 274 surveys were returned either complete or near complete. Of those, 231 (84%) were from pediatric endocrinologists (PE) and 43 (16%) were from adult endocrinologists (AE).

None of the AE clinics reported having a focus clinic for childhood cancer survivors in their practices, compared with 54% of PE practices that reported having such a focus clinic (P < .001). Furthermore, 84% of practices that reported a general lack of adequate training, confidence, and general awareness of the long-term follow-up guidelines for treating childhood cancer survivors were AE, compared with 16% PE (P < .001).

Overall, 53% of practices reported receiving cancer treatment summaries for their patients on a consistent basis. Regarding the training they’ve received on how to treat childhood cancer survivors, 65% reported receiving “somewhat adequate training” but 22% reported receiving either very little or no training all. While 67% of practices reported feeling “somewhat confident” in their ability to properly treat childhood cancer survivors, 10% reported feeling either very little or no confidence. Infertility and growth hormone deficiency were the most commonly cited conditions reported by AE clinics that responded to the survey.

Of PE practices, 64% reported following at least six patients who were childhood cancer survivors, while only 19% of AE practices reported the same (P < .001). Regarding the clinical vignettes, PE practices scored higher than their AE counterparts on identifying childhood cancer survivors’ susceptibility to cranial radiation (76% vs. 50%; P = .001) and ovarian failure (28% vs. 13%; P = .048), but there was “no significant difference” in scores on the topics of hypopituitarism and hypogonadism.

Nearly 1 out of every 640 young adults in the United States are childhood cancer survivors, and roughly 40% of those will experience at least one endocrine disorder at some point in their adult life. To solve the issue of insufficient experience or preparation regarding treatment of these patients, Dr. Raman suggested that practices create personalized management plans with specific protocols derived from clinical guidelines and expert opinions. These protocols could either be cancer center based, community based, or a hybrid of the two, which would involve care at a community site along with “close collaboration with [a] cancer center.”

“There are no treatment guidelines specifically for endocrinologists,” said Dr. Raman. “There are screening guidelines, which are more guided towards oncologists [and] family practitioners who would be seeing these patients with the idea that they would be referred to endocrinologists once they identify a problem.”

Dr. Raman did not report any relevant financial disclosures.

dchitnis@frontlinemedcom.com

NASHVILLE – Endocrinologists dealing with adult patients who survived cancer during childhood should ensure that they have an adequate understanding of the elevated risk that such patients are at for various endocrine conditions, such as hypogonadism, hypopituitarism, and ovarian failure.

This is according to the findings of a survey study presented at the annual meeting of the American Association of Clinical Endocrinologists by Dr. Sripriya Raman of Children’s Mercy Hospital and Clinics in Kansas City, Missouri.

“Incidences of childhood cancer have crept up from 1975 to 1995, but mortality has gone down, thanks to advancements in cancer therapy,” explained Dr. Raman. “Even among ethnic groups – whites, Hispanics, African Americans, and Asians – cancer incidence rates have either stabilized or increased slightly, which means we’re seeing more and more of these types of patients at our clinics.”

Dr. Raman and coinvestigators developed a survey of 19 questions: 10 questions on provider characteristics, 5 on demographic data, and 4 questions derived from two clinical vignettes. This survey was then sent to 294 endocrinologists belonging to either the Pediatric Endocrine Society (PES) or the AACE between October and December 2014; 274 surveys were returned either complete or near complete. Of those, 231 (84%) were from pediatric endocrinologists (PE) and 43 (16%) were from adult endocrinologists (AE).

None of the AE clinics reported having a focus clinic for childhood cancer survivors in their practices, compared with 54% of PE practices that reported having such a focus clinic (P < .001). Furthermore, 84% of practices that reported a general lack of adequate training, confidence, and general awareness of the long-term follow-up guidelines for treating childhood cancer survivors were AE, compared with 16% PE (P < .001).

Overall, 53% of practices reported receiving cancer treatment summaries for their patients on a consistent basis. Regarding the training they’ve received on how to treat childhood cancer survivors, 65% reported receiving “somewhat adequate training” but 22% reported receiving either very little or no training all. While 67% of practices reported feeling “somewhat confident” in their ability to properly treat childhood cancer survivors, 10% reported feeling either very little or no confidence. Infertility and growth hormone deficiency were the most commonly cited conditions reported by AE clinics that responded to the survey.

Of PE practices, 64% reported following at least six patients who were childhood cancer survivors, while only 19% of AE practices reported the same (P < .001). Regarding the clinical vignettes, PE practices scored higher than their AE counterparts on identifying childhood cancer survivors’ susceptibility to cranial radiation (76% vs. 50%; P = .001) and ovarian failure (28% vs. 13%; P = .048), but there was “no significant difference” in scores on the topics of hypopituitarism and hypogonadism.

Nearly 1 out of every 640 young adults in the United States are childhood cancer survivors, and roughly 40% of those will experience at least one endocrine disorder at some point in their adult life. To solve the issue of insufficient experience or preparation regarding treatment of these patients, Dr. Raman suggested that practices create personalized management plans with specific protocols derived from clinical guidelines and expert opinions. These protocols could either be cancer center based, community based, or a hybrid of the two, which would involve care at a community site along with “close collaboration with [a] cancer center.”

“There are no treatment guidelines specifically for endocrinologists,” said Dr. Raman. “There are screening guidelines, which are more guided towards oncologists [and] family practitioners who would be seeing these patients with the idea that they would be referred to endocrinologists once they identify a problem.”

Dr. Raman did not report any relevant financial disclosures.

dchitnis@frontlinemedcom.com

NASHVILLE – Endocrinologists dealing with adult patients who survived cancer during childhood should ensure that they have an adequate understanding of the elevated risk that such patients are at for various endocrine conditions, such as hypogonadism, hypopituitarism, and ovarian failure.

This is according to the findings of a survey study presented at the annual meeting of the American Association of Clinical Endocrinologists by Dr. Sripriya Raman of Children’s Mercy Hospital and Clinics in Kansas City, Missouri.

“Incidences of childhood cancer have crept up from 1975 to 1995, but mortality has gone down, thanks to advancements in cancer therapy,” explained Dr. Raman. “Even among ethnic groups – whites, Hispanics, African Americans, and Asians – cancer incidence rates have either stabilized or increased slightly, which means we’re seeing more and more of these types of patients at our clinics.”

Dr. Raman and coinvestigators developed a survey of 19 questions: 10 questions on provider characteristics, 5 on demographic data, and 4 questions derived from two clinical vignettes. This survey was then sent to 294 endocrinologists belonging to either the Pediatric Endocrine Society (PES) or the AACE between October and December 2014; 274 surveys were returned either complete or near complete. Of those, 231 (84%) were from pediatric endocrinologists (PE) and 43 (16%) were from adult endocrinologists (AE).

None of the AE clinics reported having a focus clinic for childhood cancer survivors in their practices, compared with 54% of PE practices that reported having such a focus clinic (P < .001). Furthermore, 84% of practices that reported a general lack of adequate training, confidence, and general awareness of the long-term follow-up guidelines for treating childhood cancer survivors were AE, compared with 16% PE (P < .001).

Overall, 53% of practices reported receiving cancer treatment summaries for their patients on a consistent basis. Regarding the training they’ve received on how to treat childhood cancer survivors, 65% reported receiving “somewhat adequate training” but 22% reported receiving either very little or no training all. While 67% of practices reported feeling “somewhat confident” in their ability to properly treat childhood cancer survivors, 10% reported feeling either very little or no confidence. Infertility and growth hormone deficiency were the most commonly cited conditions reported by AE clinics that responded to the survey.

Of PE practices, 64% reported following at least six patients who were childhood cancer survivors, while only 19% of AE practices reported the same (P < .001). Regarding the clinical vignettes, PE practices scored higher than their AE counterparts on identifying childhood cancer survivors’ susceptibility to cranial radiation (76% vs. 50%; P = .001) and ovarian failure (28% vs. 13%; P = .048), but there was “no significant difference” in scores on the topics of hypopituitarism and hypogonadism.

Nearly 1 out of every 640 young adults in the United States are childhood cancer survivors, and roughly 40% of those will experience at least one endocrine disorder at some point in their adult life. To solve the issue of insufficient experience or preparation regarding treatment of these patients, Dr. Raman suggested that practices create personalized management plans with specific protocols derived from clinical guidelines and expert opinions. These protocols could either be cancer center based, community based, or a hybrid of the two, which would involve care at a community site along with “close collaboration with [a] cancer center.”

“There are no treatment guidelines specifically for endocrinologists,” said Dr. Raman. “There are screening guidelines, which are more guided towards oncologists [and] family practitioners who would be seeing these patients with the idea that they would be referred to endocrinologists once they identify a problem.”

Dr. Raman did not report any relevant financial disclosures.

dchitnis@frontlinemedcom.com