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Long-acting pasireotide approved for acromegaly
A long-acting formulation of the somatostatin analogue pasireotide has been approved for treatment of acromegaly in patients “who have had an inadequate response to surgery and/or for whom surgery is not an option,” the manufacturer, Novartis, has announced.
In a Dec. 16 statement, the company said that Food and Drug Administration approval was based on two phase III studies, one that enrolled medically naive patients with the rare endocrine disorder who had surgery previously or for whom surgery was not an option, and a study of patients who were not adequately controlled on treatment with other somatostatin analogues (SSAs). Treatment was effective in both populations, based on “higher rates of full biochemical control” (mean GH level under 2.5 mcg/L and normal IGF-1 levels) among those treated with long-acting pasireotide compared with the other SSA, according to Novartis.
The most common adverse events associated with treatment, affecting at least 20% of patients, were cholelithiasis, hyperglycemia, and diabetes, according to the prescribing information, which includes a warning about the risk of hyperglycemia and diabetes, bradycardia and QT prolongation, liver test elevations, and cholelithiasis.
A regular formulation of pasireotide was approved by the FDA in 2012, for the treatment of adults with Cushing’s disease “for whom pituitary surgery is not an option or has not been curative.” It is marketed as Signifor. The long-acting formulation, administered intramuscularly once a month, will be marketed as Signifor LAR . In November 2014, it was approved in Europe for the acromegaly indication, Novartis said.
A long-acting formulation of the somatostatin analogue pasireotide has been approved for treatment of acromegaly in patients “who have had an inadequate response to surgery and/or for whom surgery is not an option,” the manufacturer, Novartis, has announced.
In a Dec. 16 statement, the company said that Food and Drug Administration approval was based on two phase III studies, one that enrolled medically naive patients with the rare endocrine disorder who had surgery previously or for whom surgery was not an option, and a study of patients who were not adequately controlled on treatment with other somatostatin analogues (SSAs). Treatment was effective in both populations, based on “higher rates of full biochemical control” (mean GH level under 2.5 mcg/L and normal IGF-1 levels) among those treated with long-acting pasireotide compared with the other SSA, according to Novartis.
The most common adverse events associated with treatment, affecting at least 20% of patients, were cholelithiasis, hyperglycemia, and diabetes, according to the prescribing information, which includes a warning about the risk of hyperglycemia and diabetes, bradycardia and QT prolongation, liver test elevations, and cholelithiasis.
A regular formulation of pasireotide was approved by the FDA in 2012, for the treatment of adults with Cushing’s disease “for whom pituitary surgery is not an option or has not been curative.” It is marketed as Signifor. The long-acting formulation, administered intramuscularly once a month, will be marketed as Signifor LAR . In November 2014, it was approved in Europe for the acromegaly indication, Novartis said.
A long-acting formulation of the somatostatin analogue pasireotide has been approved for treatment of acromegaly in patients “who have had an inadequate response to surgery and/or for whom surgery is not an option,” the manufacturer, Novartis, has announced.
In a Dec. 16 statement, the company said that Food and Drug Administration approval was based on two phase III studies, one that enrolled medically naive patients with the rare endocrine disorder who had surgery previously or for whom surgery was not an option, and a study of patients who were not adequately controlled on treatment with other somatostatin analogues (SSAs). Treatment was effective in both populations, based on “higher rates of full biochemical control” (mean GH level under 2.5 mcg/L and normal IGF-1 levels) among those treated with long-acting pasireotide compared with the other SSA, according to Novartis.
The most common adverse events associated with treatment, affecting at least 20% of patients, were cholelithiasis, hyperglycemia, and diabetes, according to the prescribing information, which includes a warning about the risk of hyperglycemia and diabetes, bradycardia and QT prolongation, liver test elevations, and cholelithiasis.
A regular formulation of pasireotide was approved by the FDA in 2012, for the treatment of adults with Cushing’s disease “for whom pituitary surgery is not an option or has not been curative.” It is marketed as Signifor. The long-acting formulation, administered intramuscularly once a month, will be marketed as Signifor LAR . In November 2014, it was approved in Europe for the acromegaly indication, Novartis said.
Autoantibodies not predictive of surgery for Graves’ disease
CORONADO, CALIF.– Measurement of thyroid antibodies had no impact on the clinical features of Graves’ disease best treated with surgery, results from a single-center retrospective study showed.
The findings are part of a larger study meant to develop ways to help patients decide between surgery and radioactive iodine for their Graves’ disease. “We know that certain clinical features make patients lean toward surgery instead of radioactive iodine, including severe ophthalmopathy and young women who have concerns about family planning,” Dr. Dawn M. Elfenbein said in an interview during the annual meeting of the American Thyroid Association. “In the long-term picture, I think that a lot of provider preferences go into this decision, but we’d like to move this to being more of a patient-centered decision. So we’re trying to see if there are biochemical factors about patients that can help us recommend one treatment versus the other.”
Dr. Elfenbein of the section of endocrine surgery in the department of surgery at the University of Wisconsin, Madison, and her associates reviewed the records of 469 patients treated with radioactive iodine (RAI) or surgery for Graves’ disease at the institution during August 2008-September 2013. They excluded patients with contraindications to RAI or those with other indications for surgery or who previously failed either treatment.
Of the 469 patients, 78% were women, and their mean age was 40 years. Most (71%) underwent RAI while 29% underwent surgery. The percentage of patients who opted for surgery increased each year of the study, from 14% in the first year to 52% in the final year.
More than half of the patients (52%) had thyroid peroxidase (TPO) measured prior to treatment, while 44% had thyroglobulin antibodies (TgAb) and 45% had either thyroid simulating immunoglobulin (TSIg) or thyrotropin receptor antibody (TRAb) measured.
Dr. Elfenbein and her associates found that clinical features such as ophthalmopathy or a compressive goiter appeared to influence a patient’s decision to choose surgery over RAI. On bivariate analysis, patients with a positive TSIg or TRAb were significantly more likely to have ophthalmopathy (41% vs. 25%) while patients with positive TgAb were significantly more likely to have goiter (71% vs. 55%). On multivariate analysis, however, antibody positivity was not predictive of ophthalmopathy or goiter.
“Surgery became the primary definitive treatment of choice over RAI for Graves’ disease at our institution over the study period, particularly for younger women,” the researchers wrote in their abstract. The concluded that measurement of thyroid-specific antibodies “does not independently predict those clinical features best treated with surgery. Clinical features and patient preferences should be considered independently from autoantibody levels.”
Dr. Elfenbein acknowledged certain limitations of the study, including its retrospective design and that fact that autoantibody levels were not measured after treatment. “What would be more helpful is to measure antibodies in everyone before they undergo treatment and measure those same antibodies after treatment to see what happens; to see if there are any differences in recurrence rates with higher antibodies,” she said. “We can be more deliberate moving forward.” She reported having no financial disclosures.
On Twitter @dougbrunk
CORONADO, CALIF.– Measurement of thyroid antibodies had no impact on the clinical features of Graves’ disease best treated with surgery, results from a single-center retrospective study showed.
The findings are part of a larger study meant to develop ways to help patients decide between surgery and radioactive iodine for their Graves’ disease. “We know that certain clinical features make patients lean toward surgery instead of radioactive iodine, including severe ophthalmopathy and young women who have concerns about family planning,” Dr. Dawn M. Elfenbein said in an interview during the annual meeting of the American Thyroid Association. “In the long-term picture, I think that a lot of provider preferences go into this decision, but we’d like to move this to being more of a patient-centered decision. So we’re trying to see if there are biochemical factors about patients that can help us recommend one treatment versus the other.”
Dr. Elfenbein of the section of endocrine surgery in the department of surgery at the University of Wisconsin, Madison, and her associates reviewed the records of 469 patients treated with radioactive iodine (RAI) or surgery for Graves’ disease at the institution during August 2008-September 2013. They excluded patients with contraindications to RAI or those with other indications for surgery or who previously failed either treatment.
Of the 469 patients, 78% were women, and their mean age was 40 years. Most (71%) underwent RAI while 29% underwent surgery. The percentage of patients who opted for surgery increased each year of the study, from 14% in the first year to 52% in the final year.
More than half of the patients (52%) had thyroid peroxidase (TPO) measured prior to treatment, while 44% had thyroglobulin antibodies (TgAb) and 45% had either thyroid simulating immunoglobulin (TSIg) or thyrotropin receptor antibody (TRAb) measured.
Dr. Elfenbein and her associates found that clinical features such as ophthalmopathy or a compressive goiter appeared to influence a patient’s decision to choose surgery over RAI. On bivariate analysis, patients with a positive TSIg or TRAb were significantly more likely to have ophthalmopathy (41% vs. 25%) while patients with positive TgAb were significantly more likely to have goiter (71% vs. 55%). On multivariate analysis, however, antibody positivity was not predictive of ophthalmopathy or goiter.
“Surgery became the primary definitive treatment of choice over RAI for Graves’ disease at our institution over the study period, particularly for younger women,” the researchers wrote in their abstract. The concluded that measurement of thyroid-specific antibodies “does not independently predict those clinical features best treated with surgery. Clinical features and patient preferences should be considered independently from autoantibody levels.”
Dr. Elfenbein acknowledged certain limitations of the study, including its retrospective design and that fact that autoantibody levels were not measured after treatment. “What would be more helpful is to measure antibodies in everyone before they undergo treatment and measure those same antibodies after treatment to see what happens; to see if there are any differences in recurrence rates with higher antibodies,” she said. “We can be more deliberate moving forward.” She reported having no financial disclosures.
On Twitter @dougbrunk
CORONADO, CALIF.– Measurement of thyroid antibodies had no impact on the clinical features of Graves’ disease best treated with surgery, results from a single-center retrospective study showed.
The findings are part of a larger study meant to develop ways to help patients decide between surgery and radioactive iodine for their Graves’ disease. “We know that certain clinical features make patients lean toward surgery instead of radioactive iodine, including severe ophthalmopathy and young women who have concerns about family planning,” Dr. Dawn M. Elfenbein said in an interview during the annual meeting of the American Thyroid Association. “In the long-term picture, I think that a lot of provider preferences go into this decision, but we’d like to move this to being more of a patient-centered decision. So we’re trying to see if there are biochemical factors about patients that can help us recommend one treatment versus the other.”
Dr. Elfenbein of the section of endocrine surgery in the department of surgery at the University of Wisconsin, Madison, and her associates reviewed the records of 469 patients treated with radioactive iodine (RAI) or surgery for Graves’ disease at the institution during August 2008-September 2013. They excluded patients with contraindications to RAI or those with other indications for surgery or who previously failed either treatment.
Of the 469 patients, 78% were women, and their mean age was 40 years. Most (71%) underwent RAI while 29% underwent surgery. The percentage of patients who opted for surgery increased each year of the study, from 14% in the first year to 52% in the final year.
More than half of the patients (52%) had thyroid peroxidase (TPO) measured prior to treatment, while 44% had thyroglobulin antibodies (TgAb) and 45% had either thyroid simulating immunoglobulin (TSIg) or thyrotropin receptor antibody (TRAb) measured.
Dr. Elfenbein and her associates found that clinical features such as ophthalmopathy or a compressive goiter appeared to influence a patient’s decision to choose surgery over RAI. On bivariate analysis, patients with a positive TSIg or TRAb were significantly more likely to have ophthalmopathy (41% vs. 25%) while patients with positive TgAb were significantly more likely to have goiter (71% vs. 55%). On multivariate analysis, however, antibody positivity was not predictive of ophthalmopathy or goiter.
“Surgery became the primary definitive treatment of choice over RAI for Graves’ disease at our institution over the study period, particularly for younger women,” the researchers wrote in their abstract. The concluded that measurement of thyroid-specific antibodies “does not independently predict those clinical features best treated with surgery. Clinical features and patient preferences should be considered independently from autoantibody levels.”
Dr. Elfenbein acknowledged certain limitations of the study, including its retrospective design and that fact that autoantibody levels were not measured after treatment. “What would be more helpful is to measure antibodies in everyone before they undergo treatment and measure those same antibodies after treatment to see what happens; to see if there are any differences in recurrence rates with higher antibodies,” she said. “We can be more deliberate moving forward.” She reported having no financial disclosures.
On Twitter @dougbrunk
AT THE ATA ANNUAL MEETING
Key clinical point: Measuring thyroid antibodies adds no value in predicting clinical features of Graves’ disease best treated with surgery.
Major finding: On bivariate analysis, patients with a positive TSIg or TRAb were more likely to have ophthalmopathy (41% vs. 25%; P = .04) while patients with positive TgAb were more likely to have goiter (71% vs. 55%; P = .03). On multivariate analysis, however, antibody positivity was not predictive of ophthalmopathy or goiter.
Data source: A retrospective analysis of 469 patients treated with radioactive iodine (RAI) or surgery for Graves’ disease at the University of Wisconsin, Madison, during August 2008-September 2013.
Disclosures:Dr. Elfenbein reported having no financial disclosures.
Ultrasound bests elastography for specificity of thyroid cancer diagnosis
CORONADO, CALIF.– Compared with elastography, ultrasound predictors of malignancy were more specific for presurgical diagnosis and in differentiating between benign and malignant thyroid nodules, results from a pooled analysis showed.
“Elastography is controversial,” Dr. Parisha Bhatia said in an interview during the annual meeting of the American Thyroid Association. “Some studies have reported that it has better sensitivity and specificity, compared with conventional ultrasound, but others have found it not to be helpful.”
In an effort to compare the efficacy of elastography and ultrasound in determining benign and malignant thyroid nodules, and to determine if elastography has a complementary role to fine needle aspiration (FNA), Dr. Bhatia and her associates searched Embase and PubMed databases for articles involving more than 50 nodules using specimen histology as the reference standard. They discovered 14 prospective studies and organized them into one of two groups. Group 1 included nodules with FNA cytology–proven “benign/malignant” result. Group 2 included nodules with FNA cytology as “intermediate.” The elasticity score was compared with ultrasound features such as taller than wide, irregular margins, internal vascularity, calcification, and absence of halo to determine validity measures and likelihood ratios.
Dr. Bhatia, an endocrine surgeon at Tulane University, New Orleans, reported on findings from 2,732 nodules in the pooled analysis. Of these, 64% were benign, 25% were malignant, and 11% were indeterminate.
In group 1, elastography showed a sensitivity of 75%, a specificity of 80%, a positive predictive value (PPV) of 61%, a negative predictive value (NPV) of 89%, and a likelihood ratio of 5.7, with a higher predictive value for nodules smaller than 1 cm in diameter (PPV of 79% and NPV of 83%). The strongest ultrasound-related predictor of malignancies was “taller than wide” (a specificity of 92%, a NPV of 51%, yet a sensitivity of only 24%), followed by irregular margins (a specificity of 91%, sensitivity of 48%, and a PPV of 64%). Combination of elastography and ultrasound had the highest sensitivity (96%) and NPV (96%), yet lower specificity (46%) and PPV (46%).
In group 2, elastography yielded a higher sensitivity (90%) and NPV (92%), while ultrasound features were highly specific, with the highest values for “taller than wide” shape (85%) in these thyroid nodules.
“Ultrasound predictors of malignancy prove to be more specific for presurgical diagnosis and differentiation of benign and malignant thyroid nodules,” the researchers wrote in their abstract. “When used as an adjunct, the higher sensitivity and NPV of combination of both the techniques can lead to better selection of candidates for FNA.”
Dr. Bhatia acknowledged certain limitations of the study, including the fact that the pooled data contained little information on indeterminate thyroid nodules. She reported having no financial disclosures.
On Twitter @dougbrunk
CORONADO, CALIF.– Compared with elastography, ultrasound predictors of malignancy were more specific for presurgical diagnosis and in differentiating between benign and malignant thyroid nodules, results from a pooled analysis showed.
“Elastography is controversial,” Dr. Parisha Bhatia said in an interview during the annual meeting of the American Thyroid Association. “Some studies have reported that it has better sensitivity and specificity, compared with conventional ultrasound, but others have found it not to be helpful.”
In an effort to compare the efficacy of elastography and ultrasound in determining benign and malignant thyroid nodules, and to determine if elastography has a complementary role to fine needle aspiration (FNA), Dr. Bhatia and her associates searched Embase and PubMed databases for articles involving more than 50 nodules using specimen histology as the reference standard. They discovered 14 prospective studies and organized them into one of two groups. Group 1 included nodules with FNA cytology–proven “benign/malignant” result. Group 2 included nodules with FNA cytology as “intermediate.” The elasticity score was compared with ultrasound features such as taller than wide, irregular margins, internal vascularity, calcification, and absence of halo to determine validity measures and likelihood ratios.
Dr. Bhatia, an endocrine surgeon at Tulane University, New Orleans, reported on findings from 2,732 nodules in the pooled analysis. Of these, 64% were benign, 25% were malignant, and 11% were indeterminate.
In group 1, elastography showed a sensitivity of 75%, a specificity of 80%, a positive predictive value (PPV) of 61%, a negative predictive value (NPV) of 89%, and a likelihood ratio of 5.7, with a higher predictive value for nodules smaller than 1 cm in diameter (PPV of 79% and NPV of 83%). The strongest ultrasound-related predictor of malignancies was “taller than wide” (a specificity of 92%, a NPV of 51%, yet a sensitivity of only 24%), followed by irregular margins (a specificity of 91%, sensitivity of 48%, and a PPV of 64%). Combination of elastography and ultrasound had the highest sensitivity (96%) and NPV (96%), yet lower specificity (46%) and PPV (46%).
In group 2, elastography yielded a higher sensitivity (90%) and NPV (92%), while ultrasound features were highly specific, with the highest values for “taller than wide” shape (85%) in these thyroid nodules.
“Ultrasound predictors of malignancy prove to be more specific for presurgical diagnosis and differentiation of benign and malignant thyroid nodules,” the researchers wrote in their abstract. “When used as an adjunct, the higher sensitivity and NPV of combination of both the techniques can lead to better selection of candidates for FNA.”
Dr. Bhatia acknowledged certain limitations of the study, including the fact that the pooled data contained little information on indeterminate thyroid nodules. She reported having no financial disclosures.
On Twitter @dougbrunk
CORONADO, CALIF.– Compared with elastography, ultrasound predictors of malignancy were more specific for presurgical diagnosis and in differentiating between benign and malignant thyroid nodules, results from a pooled analysis showed.
“Elastography is controversial,” Dr. Parisha Bhatia said in an interview during the annual meeting of the American Thyroid Association. “Some studies have reported that it has better sensitivity and specificity, compared with conventional ultrasound, but others have found it not to be helpful.”
In an effort to compare the efficacy of elastography and ultrasound in determining benign and malignant thyroid nodules, and to determine if elastography has a complementary role to fine needle aspiration (FNA), Dr. Bhatia and her associates searched Embase and PubMed databases for articles involving more than 50 nodules using specimen histology as the reference standard. They discovered 14 prospective studies and organized them into one of two groups. Group 1 included nodules with FNA cytology–proven “benign/malignant” result. Group 2 included nodules with FNA cytology as “intermediate.” The elasticity score was compared with ultrasound features such as taller than wide, irregular margins, internal vascularity, calcification, and absence of halo to determine validity measures and likelihood ratios.
Dr. Bhatia, an endocrine surgeon at Tulane University, New Orleans, reported on findings from 2,732 nodules in the pooled analysis. Of these, 64% were benign, 25% were malignant, and 11% were indeterminate.
In group 1, elastography showed a sensitivity of 75%, a specificity of 80%, a positive predictive value (PPV) of 61%, a negative predictive value (NPV) of 89%, and a likelihood ratio of 5.7, with a higher predictive value for nodules smaller than 1 cm in diameter (PPV of 79% and NPV of 83%). The strongest ultrasound-related predictor of malignancies was “taller than wide” (a specificity of 92%, a NPV of 51%, yet a sensitivity of only 24%), followed by irregular margins (a specificity of 91%, sensitivity of 48%, and a PPV of 64%). Combination of elastography and ultrasound had the highest sensitivity (96%) and NPV (96%), yet lower specificity (46%) and PPV (46%).
In group 2, elastography yielded a higher sensitivity (90%) and NPV (92%), while ultrasound features were highly specific, with the highest values for “taller than wide” shape (85%) in these thyroid nodules.
“Ultrasound predictors of malignancy prove to be more specific for presurgical diagnosis and differentiation of benign and malignant thyroid nodules,” the researchers wrote in their abstract. “When used as an adjunct, the higher sensitivity and NPV of combination of both the techniques can lead to better selection of candidates for FNA.”
Dr. Bhatia acknowledged certain limitations of the study, including the fact that the pooled data contained little information on indeterminate thyroid nodules. She reported having no financial disclosures.
On Twitter @dougbrunk
AT THE ATA ANNUAL MEETING
Key clinical point: Ultrasound is more specific than elastography in helping clinicians make a presurgical diagnosis of thyroid cancer.
Major finding: Compared with elastography, ultrasound was more specific in presurgical diagnosis and in differentiating between benign and malignant thyroid nodules (specificity of 92% vs. 80%, respectively).
Data source: A pooled analysis of 14 prospective studies involving findings from 2,732 thyroid nodules.
Disclosures: Dr. Bhatia reported having no financial disclosures.
FDA issues new pregnancy/lactation drug label standards
The U.S. Food and Drug Administration has issued a final rule requiring content and format changes to pregnancy and lactation labeling information for prescription drugs and biologic products.
The long-awaited “Content and Format of Labeling for Human Prescription Drug and Biological Products; Requirements for Pregnancy and Lactation Labeling, or the Pregnancy and Lactation Labeling Rule”(PLLR) is part of broad effort by the FDA to improve the content and format of prescription drug labeling. The PLLR, which finalizes many of the provisions in a proposed rule issued in May 2008 after input from numerous stakeholders, calls for replacement of the current A, B, C, D, and X drug classification system with more detailed information about the risks and benefits of use during pregnancy and breastfeeding.
The rule will take effect June 30, 2015.
Under the PLLR, labels will be required to include three detailed subsections entitled Pregnancy, Lactation, and Females and Males of Reproductive Potential. Each will include a risk summary, a discussion of the supporting data, and relevant information to help providers make prescribing and counseling decisions, according to the FDA. If no data are available to guide decision making, this must be stated.
The Pregnancy subsection combines the existing Pregnancy and Labor and Delivery subsections, and will address use of the drug during pregnancy as well as provide information about relevant registries that collect and maintain data on the use of the product in pregnant women. The Lactation subsection replaces the existing Nursing Mothers subsection, and will include information about use of the product during breastfeeding, including the amount of drug in breast milk and potential effects on the breastfed child. The new Females and Males of Reproductive Potential subsection will address pregnancy testing, contraception, and fertility issues as they relate to use of the product.
The existing A, B, C, D, and X categories were frequently misinterpreted as a grading system, giving an over simplified view of product risk, according to Dr. Sandra Kweder, deputy director of the Office of New Drugs in the FDA’s Center for Drug Evaluation and Research.
The new, more detailed approach to labeling will better address the complex risk-benefit considerations inherent in prescribing decisions during pregnancy and lactation, she said during a press briefing.
“I’m excited because clinicians will, going forward, be able to rely on FDA-approved drug labeling for comprehensive, chronically relevant, and user-friendly information in this part of labeling – something that has been missing for many years,” she said, noting that the changes are particularly important, given that the more than 6 million women who become pregnant each year in the United States take an average of 3-5 different prescription products during the course of their pregnancy and while breastfeeding.
“It is our hope that this new system will help their health care professionals and these women as they discuss treatment options,” she said.
Importantly, the PLLR ensures that more robust and informative data about drugs will be provided than ever before – and in a manner that speaks directly to the concerns that are common among providers, she said.
In addition to the elimination of the letter categories and the addition of the three new subsections, the use of standardized risk statement also was eliminated, as these had the same limitations as the letter categories. A section on inadvertent exposure also was eliminated due to redundancy, as the risk would be the same as with intentional exposure.
The rule also requires that labels be updated as they become outdated.
Much of the information that will be included on the new labels, which will be phased in for existing drugs and required immediately for drugs approved after June 30, 2015, was already included, but was scattered and difficult to find. The new formatting requirements provides for consistency across labels by pulling this information together in one place, Dr. Kweder said.
In an official statement, the American College of Obstetricians and Gynecologists applauded the rule for “taking needed steps to increase understanding about the effect of prescription medicine on women during pregnancy and lactation.”
“The FDA’s updated method of presenting information about both risk and benefit will improve the ability of all physicians to treat their pregnant and breastfeeding patients, as well as women who may become pregnant. It will also help more women to understand and take part in their health care decision making,” according to the ACOG statement, which also noted that the organization hopes the new content on prescription drug and biological product labels will “provide added incentives for clinical research as well as participation in patient registries.”
Christina Chambers, Ph.D., professor of pediatrics and director of clinical research for the department of pediatrics at the University of California, San Diego, also praised the new labeling rule, noting in an interview that “the final rule has been long awaited by many who work in the field of counseling pregnant and breastfeeding women about risks and safety of prescription medications, such as counselors with organizations like MotherToBaby, a service of the Organization of Teratology Information Specialists, which provides information about medication and other exposures during pregnancy and breastfeeding, and which was involved in development of the final rule.
“The MotherToBaby counselors located throughout the United States who answer questions about medication exposures for hundreds of women every day, have struggled for years with trying to explain the not-so-useful A, B, C, D, X pregnancy categories to patients and providers alike who commonly misinterpret their meaning. The new label format is much more content rich and evidence-based, and encompasses the larger picture of the safety data in the context of treatment (or lack of treatment) of the maternal condition. This is a huge step forward – and will make even more clear how critical the need is for more human pregnancy data for all medications likely to be used by women of reproductive age,” she said.
Dr. Chambers is the program director for MotherToBaby California, and director of the MotherToBaby research center at the University of California, San Diego. She reported having no relevant disclosures.
The U.S. Food and Drug Administration has issued a final rule requiring content and format changes to pregnancy and lactation labeling information for prescription drugs and biologic products.
The long-awaited “Content and Format of Labeling for Human Prescription Drug and Biological Products; Requirements for Pregnancy and Lactation Labeling, or the Pregnancy and Lactation Labeling Rule”(PLLR) is part of broad effort by the FDA to improve the content and format of prescription drug labeling. The PLLR, which finalizes many of the provisions in a proposed rule issued in May 2008 after input from numerous stakeholders, calls for replacement of the current A, B, C, D, and X drug classification system with more detailed information about the risks and benefits of use during pregnancy and breastfeeding.
The rule will take effect June 30, 2015.
Under the PLLR, labels will be required to include three detailed subsections entitled Pregnancy, Lactation, and Females and Males of Reproductive Potential. Each will include a risk summary, a discussion of the supporting data, and relevant information to help providers make prescribing and counseling decisions, according to the FDA. If no data are available to guide decision making, this must be stated.
The Pregnancy subsection combines the existing Pregnancy and Labor and Delivery subsections, and will address use of the drug during pregnancy as well as provide information about relevant registries that collect and maintain data on the use of the product in pregnant women. The Lactation subsection replaces the existing Nursing Mothers subsection, and will include information about use of the product during breastfeeding, including the amount of drug in breast milk and potential effects on the breastfed child. The new Females and Males of Reproductive Potential subsection will address pregnancy testing, contraception, and fertility issues as they relate to use of the product.
The existing A, B, C, D, and X categories were frequently misinterpreted as a grading system, giving an over simplified view of product risk, according to Dr. Sandra Kweder, deputy director of the Office of New Drugs in the FDA’s Center for Drug Evaluation and Research.
The new, more detailed approach to labeling will better address the complex risk-benefit considerations inherent in prescribing decisions during pregnancy and lactation, she said during a press briefing.
“I’m excited because clinicians will, going forward, be able to rely on FDA-approved drug labeling for comprehensive, chronically relevant, and user-friendly information in this part of labeling – something that has been missing for many years,” she said, noting that the changes are particularly important, given that the more than 6 million women who become pregnant each year in the United States take an average of 3-5 different prescription products during the course of their pregnancy and while breastfeeding.
“It is our hope that this new system will help their health care professionals and these women as they discuss treatment options,” she said.
Importantly, the PLLR ensures that more robust and informative data about drugs will be provided than ever before – and in a manner that speaks directly to the concerns that are common among providers, she said.
In addition to the elimination of the letter categories and the addition of the three new subsections, the use of standardized risk statement also was eliminated, as these had the same limitations as the letter categories. A section on inadvertent exposure also was eliminated due to redundancy, as the risk would be the same as with intentional exposure.
The rule also requires that labels be updated as they become outdated.
Much of the information that will be included on the new labels, which will be phased in for existing drugs and required immediately for drugs approved after June 30, 2015, was already included, but was scattered and difficult to find. The new formatting requirements provides for consistency across labels by pulling this information together in one place, Dr. Kweder said.
In an official statement, the American College of Obstetricians and Gynecologists applauded the rule for “taking needed steps to increase understanding about the effect of prescription medicine on women during pregnancy and lactation.”
“The FDA’s updated method of presenting information about both risk and benefit will improve the ability of all physicians to treat their pregnant and breastfeeding patients, as well as women who may become pregnant. It will also help more women to understand and take part in their health care decision making,” according to the ACOG statement, which also noted that the organization hopes the new content on prescription drug and biological product labels will “provide added incentives for clinical research as well as participation in patient registries.”
Christina Chambers, Ph.D., professor of pediatrics and director of clinical research for the department of pediatrics at the University of California, San Diego, also praised the new labeling rule, noting in an interview that “the final rule has been long awaited by many who work in the field of counseling pregnant and breastfeeding women about risks and safety of prescription medications, such as counselors with organizations like MotherToBaby, a service of the Organization of Teratology Information Specialists, which provides information about medication and other exposures during pregnancy and breastfeeding, and which was involved in development of the final rule.
“The MotherToBaby counselors located throughout the United States who answer questions about medication exposures for hundreds of women every day, have struggled for years with trying to explain the not-so-useful A, B, C, D, X pregnancy categories to patients and providers alike who commonly misinterpret their meaning. The new label format is much more content rich and evidence-based, and encompasses the larger picture of the safety data in the context of treatment (or lack of treatment) of the maternal condition. This is a huge step forward – and will make even more clear how critical the need is for more human pregnancy data for all medications likely to be used by women of reproductive age,” she said.
Dr. Chambers is the program director for MotherToBaby California, and director of the MotherToBaby research center at the University of California, San Diego. She reported having no relevant disclosures.
The U.S. Food and Drug Administration has issued a final rule requiring content and format changes to pregnancy and lactation labeling information for prescription drugs and biologic products.
The long-awaited “Content and Format of Labeling for Human Prescription Drug and Biological Products; Requirements for Pregnancy and Lactation Labeling, or the Pregnancy and Lactation Labeling Rule”(PLLR) is part of broad effort by the FDA to improve the content and format of prescription drug labeling. The PLLR, which finalizes many of the provisions in a proposed rule issued in May 2008 after input from numerous stakeholders, calls for replacement of the current A, B, C, D, and X drug classification system with more detailed information about the risks and benefits of use during pregnancy and breastfeeding.
The rule will take effect June 30, 2015.
Under the PLLR, labels will be required to include three detailed subsections entitled Pregnancy, Lactation, and Females and Males of Reproductive Potential. Each will include a risk summary, a discussion of the supporting data, and relevant information to help providers make prescribing and counseling decisions, according to the FDA. If no data are available to guide decision making, this must be stated.
The Pregnancy subsection combines the existing Pregnancy and Labor and Delivery subsections, and will address use of the drug during pregnancy as well as provide information about relevant registries that collect and maintain data on the use of the product in pregnant women. The Lactation subsection replaces the existing Nursing Mothers subsection, and will include information about use of the product during breastfeeding, including the amount of drug in breast milk and potential effects on the breastfed child. The new Females and Males of Reproductive Potential subsection will address pregnancy testing, contraception, and fertility issues as they relate to use of the product.
The existing A, B, C, D, and X categories were frequently misinterpreted as a grading system, giving an over simplified view of product risk, according to Dr. Sandra Kweder, deputy director of the Office of New Drugs in the FDA’s Center for Drug Evaluation and Research.
The new, more detailed approach to labeling will better address the complex risk-benefit considerations inherent in prescribing decisions during pregnancy and lactation, she said during a press briefing.
“I’m excited because clinicians will, going forward, be able to rely on FDA-approved drug labeling for comprehensive, chronically relevant, and user-friendly information in this part of labeling – something that has been missing for many years,” she said, noting that the changes are particularly important, given that the more than 6 million women who become pregnant each year in the United States take an average of 3-5 different prescription products during the course of their pregnancy and while breastfeeding.
“It is our hope that this new system will help their health care professionals and these women as they discuss treatment options,” she said.
Importantly, the PLLR ensures that more robust and informative data about drugs will be provided than ever before – and in a manner that speaks directly to the concerns that are common among providers, she said.
In addition to the elimination of the letter categories and the addition of the three new subsections, the use of standardized risk statement also was eliminated, as these had the same limitations as the letter categories. A section on inadvertent exposure also was eliminated due to redundancy, as the risk would be the same as with intentional exposure.
The rule also requires that labels be updated as they become outdated.
Much of the information that will be included on the new labels, which will be phased in for existing drugs and required immediately for drugs approved after June 30, 2015, was already included, but was scattered and difficult to find. The new formatting requirements provides for consistency across labels by pulling this information together in one place, Dr. Kweder said.
In an official statement, the American College of Obstetricians and Gynecologists applauded the rule for “taking needed steps to increase understanding about the effect of prescription medicine on women during pregnancy and lactation.”
“The FDA’s updated method of presenting information about both risk and benefit will improve the ability of all physicians to treat their pregnant and breastfeeding patients, as well as women who may become pregnant. It will also help more women to understand and take part in their health care decision making,” according to the ACOG statement, which also noted that the organization hopes the new content on prescription drug and biological product labels will “provide added incentives for clinical research as well as participation in patient registries.”
Christina Chambers, Ph.D., professor of pediatrics and director of clinical research for the department of pediatrics at the University of California, San Diego, also praised the new labeling rule, noting in an interview that “the final rule has been long awaited by many who work in the field of counseling pregnant and breastfeeding women about risks and safety of prescription medications, such as counselors with organizations like MotherToBaby, a service of the Organization of Teratology Information Specialists, which provides information about medication and other exposures during pregnancy and breastfeeding, and which was involved in development of the final rule.
“The MotherToBaby counselors located throughout the United States who answer questions about medication exposures for hundreds of women every day, have struggled for years with trying to explain the not-so-useful A, B, C, D, X pregnancy categories to patients and providers alike who commonly misinterpret their meaning. The new label format is much more content rich and evidence-based, and encompasses the larger picture of the safety data in the context of treatment (or lack of treatment) of the maternal condition. This is a huge step forward – and will make even more clear how critical the need is for more human pregnancy data for all medications likely to be used by women of reproductive age,” she said.
Dr. Chambers is the program director for MotherToBaby California, and director of the MotherToBaby research center at the University of California, San Diego. She reported having no relevant disclosures.
Regional lymph node mets not a risk factor for death in adrenocortical carcinoma
SAN FRANCISCO– Positive regional lymph nodes are not an independent risk factor for death from adrenocortical carcinoma, finds a cohort study presented at the annual clinical congress of the American College of Surgeons.
“High tumor grade and distant metastasis were the only independent prognostic factors,” reported lead researcher Dr. Kun-Tai Hsu, a surgical resident formerly with the University of Wisconsin–Madison and currently at Michigan State University in East Lansing.
“While regional lymph node metastasis was not associated with worse outcome, it was associated with local tumor invasion. More importantly, regional lymph node status and local tumor invasion had equivalent impact on disease-specific mortality, but lymph node status was not a marker for local tumor invasion,” he added.
Using the Surveillance, Epidemiology, and End Results (SEER) database, the researchers analyzed data for 1,202 adults who underwent surgery for unilateral adrenocortical carcinoma between 1973 and 2010. A total of 10% had regional lymph node metastases, as ascertained by sampling, imaging, or both.
Median survival was 46 months for the cohort overall, and the 5-year rate of disease-specific mortality was 55%, Dr. Hsu reported. Patients with regional lymph node metastases had higher significantly disease-specific mortality in unadjusted analyses but not in adjusted analysis. However, high tumor grade and distant metastases were both strong independent risk factors (hazard ratios, 2.37 and 2.87).
Patients were more likely to have regional lymph node metastases if they had local invasion. When peers having neither of these factors were the comparator, risk was elevated for patients with only positive lymph nodes (HR, 9.9) and for patients with only local invasion (HR, 6.7), and most for patients having both factors (HR, 18.0).
“The effect appears to be additive rather than a true interaction,” commented Dr. Hsu, who disclosed that he had no conflicts of interest relevant to the research. “Therefore, there was no synergistic interaction between local tumor invasion and regional lymph node metastases: these two disease factors equally predict disease-specific mortality and are not simply a marker of one another.”
“We are aware that there are several limitations of the SEER database,” he acknowledged. “Nevertheless, given the rare nature of adrenocortical carcinoma, SEER provided enough data to have the statistical power and objectivity not available from single-institution studies.”
In an interview, session comoderator Dr. Amelia C. Grover of the Department of Surgery’s division of surgical oncology, Virginia Commonwealth University in Richmond, said that the findings reinforce earlier research on this cancer. “The problem is, adrenocortical carcinoma is such a uncommon disease, it makes drawing a large enough group difficult. So the SEER database was a great resource,” she agreed. “However, because of its limitations, it makes it hard to draw any significant conclusions, again stressing that for these unusual endocrine neoplasms, it’s really great to have collaborative efforts from multiple institutions in driving that research forward and collecting that data so that we can better care for those patients.”
SAN FRANCISCO– Positive regional lymph nodes are not an independent risk factor for death from adrenocortical carcinoma, finds a cohort study presented at the annual clinical congress of the American College of Surgeons.
“High tumor grade and distant metastasis were the only independent prognostic factors,” reported lead researcher Dr. Kun-Tai Hsu, a surgical resident formerly with the University of Wisconsin–Madison and currently at Michigan State University in East Lansing.
“While regional lymph node metastasis was not associated with worse outcome, it was associated with local tumor invasion. More importantly, regional lymph node status and local tumor invasion had equivalent impact on disease-specific mortality, but lymph node status was not a marker for local tumor invasion,” he added.
Using the Surveillance, Epidemiology, and End Results (SEER) database, the researchers analyzed data for 1,202 adults who underwent surgery for unilateral adrenocortical carcinoma between 1973 and 2010. A total of 10% had regional lymph node metastases, as ascertained by sampling, imaging, or both.
Median survival was 46 months for the cohort overall, and the 5-year rate of disease-specific mortality was 55%, Dr. Hsu reported. Patients with regional lymph node metastases had higher significantly disease-specific mortality in unadjusted analyses but not in adjusted analysis. However, high tumor grade and distant metastases were both strong independent risk factors (hazard ratios, 2.37 and 2.87).
Patients were more likely to have regional lymph node metastases if they had local invasion. When peers having neither of these factors were the comparator, risk was elevated for patients with only positive lymph nodes (HR, 9.9) and for patients with only local invasion (HR, 6.7), and most for patients having both factors (HR, 18.0).
“The effect appears to be additive rather than a true interaction,” commented Dr. Hsu, who disclosed that he had no conflicts of interest relevant to the research. “Therefore, there was no synergistic interaction between local tumor invasion and regional lymph node metastases: these two disease factors equally predict disease-specific mortality and are not simply a marker of one another.”
“We are aware that there are several limitations of the SEER database,” he acknowledged. “Nevertheless, given the rare nature of adrenocortical carcinoma, SEER provided enough data to have the statistical power and objectivity not available from single-institution studies.”
In an interview, session comoderator Dr. Amelia C. Grover of the Department of Surgery’s division of surgical oncology, Virginia Commonwealth University in Richmond, said that the findings reinforce earlier research on this cancer. “The problem is, adrenocortical carcinoma is such a uncommon disease, it makes drawing a large enough group difficult. So the SEER database was a great resource,” she agreed. “However, because of its limitations, it makes it hard to draw any significant conclusions, again stressing that for these unusual endocrine neoplasms, it’s really great to have collaborative efforts from multiple institutions in driving that research forward and collecting that data so that we can better care for those patients.”
SAN FRANCISCO– Positive regional lymph nodes are not an independent risk factor for death from adrenocortical carcinoma, finds a cohort study presented at the annual clinical congress of the American College of Surgeons.
“High tumor grade and distant metastasis were the only independent prognostic factors,” reported lead researcher Dr. Kun-Tai Hsu, a surgical resident formerly with the University of Wisconsin–Madison and currently at Michigan State University in East Lansing.
“While regional lymph node metastasis was not associated with worse outcome, it was associated with local tumor invasion. More importantly, regional lymph node status and local tumor invasion had equivalent impact on disease-specific mortality, but lymph node status was not a marker for local tumor invasion,” he added.
Using the Surveillance, Epidemiology, and End Results (SEER) database, the researchers analyzed data for 1,202 adults who underwent surgery for unilateral adrenocortical carcinoma between 1973 and 2010. A total of 10% had regional lymph node metastases, as ascertained by sampling, imaging, or both.
Median survival was 46 months for the cohort overall, and the 5-year rate of disease-specific mortality was 55%, Dr. Hsu reported. Patients with regional lymph node metastases had higher significantly disease-specific mortality in unadjusted analyses but not in adjusted analysis. However, high tumor grade and distant metastases were both strong independent risk factors (hazard ratios, 2.37 and 2.87).
Patients were more likely to have regional lymph node metastases if they had local invasion. When peers having neither of these factors were the comparator, risk was elevated for patients with only positive lymph nodes (HR, 9.9) and for patients with only local invasion (HR, 6.7), and most for patients having both factors (HR, 18.0).
“The effect appears to be additive rather than a true interaction,” commented Dr. Hsu, who disclosed that he had no conflicts of interest relevant to the research. “Therefore, there was no synergistic interaction between local tumor invasion and regional lymph node metastases: these two disease factors equally predict disease-specific mortality and are not simply a marker of one another.”
“We are aware that there are several limitations of the SEER database,” he acknowledged. “Nevertheless, given the rare nature of adrenocortical carcinoma, SEER provided enough data to have the statistical power and objectivity not available from single-institution studies.”
In an interview, session comoderator Dr. Amelia C. Grover of the Department of Surgery’s division of surgical oncology, Virginia Commonwealth University in Richmond, said that the findings reinforce earlier research on this cancer. “The problem is, adrenocortical carcinoma is such a uncommon disease, it makes drawing a large enough group difficult. So the SEER database was a great resource,” she agreed. “However, because of its limitations, it makes it hard to draw any significant conclusions, again stressing that for these unusual endocrine neoplasms, it’s really great to have collaborative efforts from multiple institutions in driving that research forward and collecting that data so that we can better care for those patients.”
AT THE ACS CLINICAL CONGRESS
Key clinical point: Regional lymph node metastasis does not independently predict disease-specific mortality.
Major finding: Patients with involved regional nodes were not more likely to die from their cancer after other factors were taken in account.
Data source: A retrospective cohort study of 1,202 adults who had surgery for unilateral adrenocortical carcinoma.
Disclosures: Dr. Hsu disclosed that he had no relevant conflicts of interest.
High failure rate seen with limited parathyroidectomy in patients with MEN-1
SAN FRANCISCO – Patients with hyperparathyroidism due to multiple endocrine neoplasia type 1 (MEN-1) have a 4 in 10 chance of persistent hyperparathyroidism if they undergo surgery that leaves at least one gland in place, according to a retrospective cohort study presented at the annual clinical congress of the American College of Surgeons.
“Limited initial parathyroidectomy in patients with MEN-1–associated primary hyperparathyroidism results in a high failure rate. Additional enlarged contralateral parathyroid glands are frequently missed by preoperative localizing studies,” commented lead investigator Dr. Naris Nilubol, a staff clinician with the endocrine oncology branch of the Center for Cancer Research, National Cancer Institute, Bethesda, Md.
“We conclude that limited parathyroidectomy in MEN-1 guided by preoperative localizing studies is associated with high failure rates and therefore should not be performed,” he maintained.
In an interview, session comoderator Dr. Marybeth S. Hughes, a staff clinician with the thoracic and gastrointestinal oncology branch, Center for Cancer Research, National Cancer Institute, commented, “In general, I would say that the data presented just reiterates the standard of care, that MEN-1 patients should have bilateral neck exploration with [removal of] three and half glands, or four glands with autotransplantation. So it just basically solidifies what is being done standardly. I don’t think there is a compelling argument to change the standard.”
Dr. Nilubol and colleagues reviewed the charts of 99 patients with MEN-1 who underwent at least one parathyroidectomy at the National Institutes of Health (NIH).
Of the 64 patients who had initial surgery at NIH and had preoperative localizing studies done, 32 had only a single enlarged gland identified by the tests, suggesting they would be good candidates for limited surgery, according to Dr. Nilubol. Bilateral neck dissection at the time of parathyroidectomy showed that in 22 (69%) of these 32 patients, the studies had correctly identified the largest gland; however, in 19 (87%) of those 22, it missed another enlarged gland on the contralateral side. Furthermore, in 5 (16%) of the 32, the largest gland was found on the contralateral side.
With a median follow-up of 23 months, the risk of persistent hyperparathyroidism was 41% for patients who had limited parathyroidectomy (three or fewer glands removed) at initial surgery, significantly and sharply higher than the 6% seen in patients who had subtotal parathyroidectomy or more extensive surgery (at least three and a half glands removed).
Looking at the cumulative number of glands removed during initial and subsequent surgeries, 57% of patients having two or fewer glands removed and 45% of those having two and a half to three glands removed had persistent hyperparathyroidism – both significantly higher than the 5% of patients having at least three and a half glands removed.
Regarding complications, 10% of the patients who had their initial surgery at NIH developed permanent hypoparathyroidism, reported Dr. Nilubol, who disclosed that he had no relevant conflicts of interest.
Session attendees asked about the use of parathyroid hormone levels intraoperatively to guide surgery and what strategy surgeons follow at his institution in this patient population.
Previous research has suggested that intraoperative parathyroid hormone levels do not add any information that would change the operative plan, Dr. Nilubol replied. “Everybody at NIH has preop localizing studies as part of the clinical investigation, but it doesn’t change the way we approach it. Everybody gets a bilateral neck exploration and three and a half–gland removal,” provided all glands can be found, he said.
Session attendee Dr. Michael J. Campbell, a surgeon at the University California, Davis, commented, “A 10% permanent hypoparathyroidism rate in these patients – and they have a tendency to be young, most of them in their late teens, early 20s – that’s a major complication. So could you take your data and make exactly the opposite argument, that maybe you should be doing less to these patients to limit that fairly life-altering complication?” Permanent hypothyroidism at that age is “a significant medical problem,” Dr. Nilubol agreed. However, “at the NIH, we don’t operate on everybody just because they have primary hyperparathyroidism. They have to fulfill metabolic complications before we choose to operate on them. We want to delay the surgeries and [time] between the surgeries because if they live long enough, it will recur, so we want to operate when we can make the most difference, meaning [addressing] kidney stone, bone loss, etc. The most common reason for young patients is they have kidney stones, which leads to surgery.”
SAN FRANCISCO – Patients with hyperparathyroidism due to multiple endocrine neoplasia type 1 (MEN-1) have a 4 in 10 chance of persistent hyperparathyroidism if they undergo surgery that leaves at least one gland in place, according to a retrospective cohort study presented at the annual clinical congress of the American College of Surgeons.
“Limited initial parathyroidectomy in patients with MEN-1–associated primary hyperparathyroidism results in a high failure rate. Additional enlarged contralateral parathyroid glands are frequently missed by preoperative localizing studies,” commented lead investigator Dr. Naris Nilubol, a staff clinician with the endocrine oncology branch of the Center for Cancer Research, National Cancer Institute, Bethesda, Md.
“We conclude that limited parathyroidectomy in MEN-1 guided by preoperative localizing studies is associated with high failure rates and therefore should not be performed,” he maintained.
In an interview, session comoderator Dr. Marybeth S. Hughes, a staff clinician with the thoracic and gastrointestinal oncology branch, Center for Cancer Research, National Cancer Institute, commented, “In general, I would say that the data presented just reiterates the standard of care, that MEN-1 patients should have bilateral neck exploration with [removal of] three and half glands, or four glands with autotransplantation. So it just basically solidifies what is being done standardly. I don’t think there is a compelling argument to change the standard.”
Dr. Nilubol and colleagues reviewed the charts of 99 patients with MEN-1 who underwent at least one parathyroidectomy at the National Institutes of Health (NIH).
Of the 64 patients who had initial surgery at NIH and had preoperative localizing studies done, 32 had only a single enlarged gland identified by the tests, suggesting they would be good candidates for limited surgery, according to Dr. Nilubol. Bilateral neck dissection at the time of parathyroidectomy showed that in 22 (69%) of these 32 patients, the studies had correctly identified the largest gland; however, in 19 (87%) of those 22, it missed another enlarged gland on the contralateral side. Furthermore, in 5 (16%) of the 32, the largest gland was found on the contralateral side.
With a median follow-up of 23 months, the risk of persistent hyperparathyroidism was 41% for patients who had limited parathyroidectomy (three or fewer glands removed) at initial surgery, significantly and sharply higher than the 6% seen in patients who had subtotal parathyroidectomy or more extensive surgery (at least three and a half glands removed).
Looking at the cumulative number of glands removed during initial and subsequent surgeries, 57% of patients having two or fewer glands removed and 45% of those having two and a half to three glands removed had persistent hyperparathyroidism – both significantly higher than the 5% of patients having at least three and a half glands removed.
Regarding complications, 10% of the patients who had their initial surgery at NIH developed permanent hypoparathyroidism, reported Dr. Nilubol, who disclosed that he had no relevant conflicts of interest.
Session attendees asked about the use of parathyroid hormone levels intraoperatively to guide surgery and what strategy surgeons follow at his institution in this patient population.
Previous research has suggested that intraoperative parathyroid hormone levels do not add any information that would change the operative plan, Dr. Nilubol replied. “Everybody at NIH has preop localizing studies as part of the clinical investigation, but it doesn’t change the way we approach it. Everybody gets a bilateral neck exploration and three and a half–gland removal,” provided all glands can be found, he said.
Session attendee Dr. Michael J. Campbell, a surgeon at the University California, Davis, commented, “A 10% permanent hypoparathyroidism rate in these patients – and they have a tendency to be young, most of them in their late teens, early 20s – that’s a major complication. So could you take your data and make exactly the opposite argument, that maybe you should be doing less to these patients to limit that fairly life-altering complication?” Permanent hypothyroidism at that age is “a significant medical problem,” Dr. Nilubol agreed. However, “at the NIH, we don’t operate on everybody just because they have primary hyperparathyroidism. They have to fulfill metabolic complications before we choose to operate on them. We want to delay the surgeries and [time] between the surgeries because if they live long enough, it will recur, so we want to operate when we can make the most difference, meaning [addressing] kidney stone, bone loss, etc. The most common reason for young patients is they have kidney stones, which leads to surgery.”
SAN FRANCISCO – Patients with hyperparathyroidism due to multiple endocrine neoplasia type 1 (MEN-1) have a 4 in 10 chance of persistent hyperparathyroidism if they undergo surgery that leaves at least one gland in place, according to a retrospective cohort study presented at the annual clinical congress of the American College of Surgeons.
“Limited initial parathyroidectomy in patients with MEN-1–associated primary hyperparathyroidism results in a high failure rate. Additional enlarged contralateral parathyroid glands are frequently missed by preoperative localizing studies,” commented lead investigator Dr. Naris Nilubol, a staff clinician with the endocrine oncology branch of the Center for Cancer Research, National Cancer Institute, Bethesda, Md.
“We conclude that limited parathyroidectomy in MEN-1 guided by preoperative localizing studies is associated with high failure rates and therefore should not be performed,” he maintained.
In an interview, session comoderator Dr. Marybeth S. Hughes, a staff clinician with the thoracic and gastrointestinal oncology branch, Center for Cancer Research, National Cancer Institute, commented, “In general, I would say that the data presented just reiterates the standard of care, that MEN-1 patients should have bilateral neck exploration with [removal of] three and half glands, or four glands with autotransplantation. So it just basically solidifies what is being done standardly. I don’t think there is a compelling argument to change the standard.”
Dr. Nilubol and colleagues reviewed the charts of 99 patients with MEN-1 who underwent at least one parathyroidectomy at the National Institutes of Health (NIH).
Of the 64 patients who had initial surgery at NIH and had preoperative localizing studies done, 32 had only a single enlarged gland identified by the tests, suggesting they would be good candidates for limited surgery, according to Dr. Nilubol. Bilateral neck dissection at the time of parathyroidectomy showed that in 22 (69%) of these 32 patients, the studies had correctly identified the largest gland; however, in 19 (87%) of those 22, it missed another enlarged gland on the contralateral side. Furthermore, in 5 (16%) of the 32, the largest gland was found on the contralateral side.
With a median follow-up of 23 months, the risk of persistent hyperparathyroidism was 41% for patients who had limited parathyroidectomy (three or fewer glands removed) at initial surgery, significantly and sharply higher than the 6% seen in patients who had subtotal parathyroidectomy or more extensive surgery (at least three and a half glands removed).
Looking at the cumulative number of glands removed during initial and subsequent surgeries, 57% of patients having two or fewer glands removed and 45% of those having two and a half to three glands removed had persistent hyperparathyroidism – both significantly higher than the 5% of patients having at least three and a half glands removed.
Regarding complications, 10% of the patients who had their initial surgery at NIH developed permanent hypoparathyroidism, reported Dr. Nilubol, who disclosed that he had no relevant conflicts of interest.
Session attendees asked about the use of parathyroid hormone levels intraoperatively to guide surgery and what strategy surgeons follow at his institution in this patient population.
Previous research has suggested that intraoperative parathyroid hormone levels do not add any information that would change the operative plan, Dr. Nilubol replied. “Everybody at NIH has preop localizing studies as part of the clinical investigation, but it doesn’t change the way we approach it. Everybody gets a bilateral neck exploration and three and a half–gland removal,” provided all glands can be found, he said.
Session attendee Dr. Michael J. Campbell, a surgeon at the University California, Davis, commented, “A 10% permanent hypoparathyroidism rate in these patients – and they have a tendency to be young, most of them in their late teens, early 20s – that’s a major complication. So could you take your data and make exactly the opposite argument, that maybe you should be doing less to these patients to limit that fairly life-altering complication?” Permanent hypothyroidism at that age is “a significant medical problem,” Dr. Nilubol agreed. However, “at the NIH, we don’t operate on everybody just because they have primary hyperparathyroidism. They have to fulfill metabolic complications before we choose to operate on them. We want to delay the surgeries and [time] between the surgeries because if they live long enough, it will recur, so we want to operate when we can make the most difference, meaning [addressing] kidney stone, bone loss, etc. The most common reason for young patients is they have kidney stones, which leads to surgery.”
AT THE ACS CLINICAL CONGRESS
Key clinical point: Patients are more likely to have persistent hyperparathyroidism if a gland is left behind.
Major finding: The failure rate after initial parathyroidectomy was 41% with limited surgery versus 6% with subtotal or more extensive surgery.
Data source: A retrospective chart review of 99 patients with MEN-1–associated hyperparathyroidism.
Disclosures: Dr. Nilubol disclosed that he had no relevant conflicts of interest.
Shoulder morbidity common after thyroid cancer surgery
CORONADO, CALIF. – More than 50% of patients who underwent surgery for differentiated thyroid cancer experienced shoulder morbidity up to 10 years after the procedure, results from a Dutch study showed.
“What’s causing the pain?” Dr. Romana T. Netea-Maier asked in an interview at the annual meeting of the American Thyroid Association. “It may be that the spinal accessory nerve or other nerves have been injured during the surgery. We don’t know.”
In what she said is the first study of its kind, Dr. Netea-Maier and her associates compared the prevalence of shoulder morbidity and its relation to clinical characteristics and quality of life in 109 patients who underwent surgery for differentiated thyroid cancer at Radboud University Medical Center, Nijmegen, the Netherlands, with a group of 81 healthy controls and a group of 59 patients who underwent surgery for benign thyroid pathology. Main outcome measures were the prevalence of shoulder complaints based on results of the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire and the European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire-C-30 (EORTC QLQ-C30).
Dr. Netea-Maier, of the department of medicine at the university, reported that the mean age of patients in the two surgery groups was 46 years, and 73% were women. During an average of 10 years following surgery, 59% of patients in the thyroid cancer group and 49% of patients in the benign thyroid pathology group reported shoulder morbidity, compared with 14% of controls (P < .01). The chief complaints among patients in the thyroid cancer group were pain (25%), muscle weakness (8%), and tingling (8%), while the main complaints among those with benign thyroid pathology were pain (38%), and tingling (7%).
Compared with healthy controls, patients in the thyroid cancer group scored worse on all subscales of the DASH and the EORTC QLQ-C30. On bivariate analysis, level V neck dissection, spinal accessory nerve damage, and employment status were associated with the prevalence of shoulder complaints and DASH scores, while the prevalence of shoulder complaints and DASH scores correlated significantly with EORTC QLQ-C30 scores.
The researchers found that only 12% of patients in the thyroid cancer group received preoperative information on the potential for shoulder morbidity and 35% received additional care for postoperative shoulder complaints.
“The take-home message would be to inform your patients of the potential for shoulder comorbidity, because what we have shown here is that patients do not recall being informed about this possible complication before the surgery,” Dr. Netea-Maier said. “If they have complaints, start with physiotherapy early on.”
Dr. Netea-Maier reported having no financial disclosures.
On Twitter @dougbrunk
CORONADO, CALIF. – More than 50% of patients who underwent surgery for differentiated thyroid cancer experienced shoulder morbidity up to 10 years after the procedure, results from a Dutch study showed.
“What’s causing the pain?” Dr. Romana T. Netea-Maier asked in an interview at the annual meeting of the American Thyroid Association. “It may be that the spinal accessory nerve or other nerves have been injured during the surgery. We don’t know.”
In what she said is the first study of its kind, Dr. Netea-Maier and her associates compared the prevalence of shoulder morbidity and its relation to clinical characteristics and quality of life in 109 patients who underwent surgery for differentiated thyroid cancer at Radboud University Medical Center, Nijmegen, the Netherlands, with a group of 81 healthy controls and a group of 59 patients who underwent surgery for benign thyroid pathology. Main outcome measures were the prevalence of shoulder complaints based on results of the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire and the European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire-C-30 (EORTC QLQ-C30).
Dr. Netea-Maier, of the department of medicine at the university, reported that the mean age of patients in the two surgery groups was 46 years, and 73% were women. During an average of 10 years following surgery, 59% of patients in the thyroid cancer group and 49% of patients in the benign thyroid pathology group reported shoulder morbidity, compared with 14% of controls (P < .01). The chief complaints among patients in the thyroid cancer group were pain (25%), muscle weakness (8%), and tingling (8%), while the main complaints among those with benign thyroid pathology were pain (38%), and tingling (7%).
Compared with healthy controls, patients in the thyroid cancer group scored worse on all subscales of the DASH and the EORTC QLQ-C30. On bivariate analysis, level V neck dissection, spinal accessory nerve damage, and employment status were associated with the prevalence of shoulder complaints and DASH scores, while the prevalence of shoulder complaints and DASH scores correlated significantly with EORTC QLQ-C30 scores.
The researchers found that only 12% of patients in the thyroid cancer group received preoperative information on the potential for shoulder morbidity and 35% received additional care for postoperative shoulder complaints.
“The take-home message would be to inform your patients of the potential for shoulder comorbidity, because what we have shown here is that patients do not recall being informed about this possible complication before the surgery,” Dr. Netea-Maier said. “If they have complaints, start with physiotherapy early on.”
Dr. Netea-Maier reported having no financial disclosures.
On Twitter @dougbrunk
CORONADO, CALIF. – More than 50% of patients who underwent surgery for differentiated thyroid cancer experienced shoulder morbidity up to 10 years after the procedure, results from a Dutch study showed.
“What’s causing the pain?” Dr. Romana T. Netea-Maier asked in an interview at the annual meeting of the American Thyroid Association. “It may be that the spinal accessory nerve or other nerves have been injured during the surgery. We don’t know.”
In what she said is the first study of its kind, Dr. Netea-Maier and her associates compared the prevalence of shoulder morbidity and its relation to clinical characteristics and quality of life in 109 patients who underwent surgery for differentiated thyroid cancer at Radboud University Medical Center, Nijmegen, the Netherlands, with a group of 81 healthy controls and a group of 59 patients who underwent surgery for benign thyroid pathology. Main outcome measures were the prevalence of shoulder complaints based on results of the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire and the European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire-C-30 (EORTC QLQ-C30).
Dr. Netea-Maier, of the department of medicine at the university, reported that the mean age of patients in the two surgery groups was 46 years, and 73% were women. During an average of 10 years following surgery, 59% of patients in the thyroid cancer group and 49% of patients in the benign thyroid pathology group reported shoulder morbidity, compared with 14% of controls (P < .01). The chief complaints among patients in the thyroid cancer group were pain (25%), muscle weakness (8%), and tingling (8%), while the main complaints among those with benign thyroid pathology were pain (38%), and tingling (7%).
Compared with healthy controls, patients in the thyroid cancer group scored worse on all subscales of the DASH and the EORTC QLQ-C30. On bivariate analysis, level V neck dissection, spinal accessory nerve damage, and employment status were associated with the prevalence of shoulder complaints and DASH scores, while the prevalence of shoulder complaints and DASH scores correlated significantly with EORTC QLQ-C30 scores.
The researchers found that only 12% of patients in the thyroid cancer group received preoperative information on the potential for shoulder morbidity and 35% received additional care for postoperative shoulder complaints.
“The take-home message would be to inform your patients of the potential for shoulder comorbidity, because what we have shown here is that patients do not recall being informed about this possible complication before the surgery,” Dr. Netea-Maier said. “If they have complaints, start with physiotherapy early on.”
Dr. Netea-Maier reported having no financial disclosures.
On Twitter @dougbrunk
AT THE ATA ANNUAL MEETING
Key clinical point: Postoperative shoulder morbidity is highly prevalent in patients who undergo surgery for thyroid cancer.
Major finding: During an average of 10 years following surgery, 59% of patients in the thyroid cancer group and 49% of patients in the benign thyroid pathology group reported shoulder morbidity, compared with 14% of controls (P < .01).
Data source: A Dutch study of 109 patients who underwent surgery for differentiated thyroid cancer, compared with 81 healthy controls and 59 patients who underwent surgery for benign thyroid pathology.
Disclosures: Dr. Netea-Maier reported having no financial disclosures.
Radioactive iodine may boost survival in papillary thyroid cancer
CORONADO, CALIF. – The use of radioactive iodine in patients with papillary thyroid cancer showed a small but statistically significant survival benefit for all tumor size categories, a long-term analysis of national data suggested.
“The incidence of papillary thyroid carcinoma is rapidly rising, but the survival advantage of radioactive iodine ablation has not been confirmed,” Dr. Paritosh Suman said at the annual meeting of the American Thyroid Association.
To investigate the effect of radioactive iodine (RAI) on papillary thyroid cancer mortality, Dr. Suman and his associates identified 108,565 patients from the National Cancer Data Base who were diagnosed with papillary thyroid cancer and underwent total or near total thyroidectomy between 1998 and 2006.
The investigators classified tumors into one of four groups by diameter size: 10 mm or less, 11-20 mm, 21-40 mm, and greater than 40 mm. The study researchers used Cox regression analysis to quantify the effect of radioactive iodine, adjusting for clinicopathologic, demographic, and socioeconomic variables. A total of 52% of the patients were older than 45 years, 77% were female, and 54% received RAI.
Factors predicting the use of RAI were being male, having positive margins, having cervical lymph node involvement, and having a tumor size greater than 4 cm in diameter, said Dr. Suman, an endocrinology surgery fellow at North Shore University Health System in Evanston, Ill. The 10-year overall survival rate was 90% in those who received RAI, compared with 87.4% among those who did not, for a small but statistically significant survival advantage (P < .0001).
Among patients who received RAI, the 10-year survival advantage by diameter of tumor was 3.4% for those with tumors 10 mm or less; 2.8% with 11-20 mm; 3.3% with 21-40 mm, and 5.7% with greater than 40 mm.
Age also played a factor, with a 10-year survival advantage of 0.5% for those aged 18-35 years; 1.5% for those aged 36-45 years; 0.9% for those aged 46-55 years; 0.6% for those aged 56-65 years; and 2.1% for those older than 65 years. Both men and women who received RAI had a statistically significant survival advantage at 10 years (3.9% and 1.6%, respectively).
When the researchers assessed the 10-year survival advantage by lymph node category of patients who received RAI, the rates were 2.9% for N-0, 4.2% for N-1, 5.2% for N-1A, and 5.8% for N-1B. By margin status, the 10-year survival advantage was 3.1% for negative margins, 3.6% for positive margins, 3.5% for microscopic margins, and 8.8% for gross margins.
In an analysis of all patients with very low-risk, low-risk, and high-risk papillary thyroid carcinoma according to ATA guidelines for the use of RAI, the study authors found a 10-year survival advantage of RAI in each of the three categories.
Among patients with very low-risk papillary thyroid carcinoma, the rate of 10-year survival was 92.2% among those who received RAI, compared with 89% among those who did not (hazard ratio, 0.74). Similar associations were observed in those with low-risk carcinoma (91.8% vs. 89%; HR, 0.80) and in those with high-risk carcinoma (86.2% vs. 79.2%; HR, 0.71).
“RAI is associated with a statistically significant but small overall survival advantage for most patients,” Dr. Suman said. “High-risk patients, defined by large tumor size, lymph node involvement, and gross margins, achieve the greatest benefit with RAI ablation.”
Dr. Suman reported having no relevant financial disclosures.
On Twitter @dougbrunk
CORONADO, CALIF. – The use of radioactive iodine in patients with papillary thyroid cancer showed a small but statistically significant survival benefit for all tumor size categories, a long-term analysis of national data suggested.
“The incidence of papillary thyroid carcinoma is rapidly rising, but the survival advantage of radioactive iodine ablation has not been confirmed,” Dr. Paritosh Suman said at the annual meeting of the American Thyroid Association.
To investigate the effect of radioactive iodine (RAI) on papillary thyroid cancer mortality, Dr. Suman and his associates identified 108,565 patients from the National Cancer Data Base who were diagnosed with papillary thyroid cancer and underwent total or near total thyroidectomy between 1998 and 2006.
The investigators classified tumors into one of four groups by diameter size: 10 mm or less, 11-20 mm, 21-40 mm, and greater than 40 mm. The study researchers used Cox regression analysis to quantify the effect of radioactive iodine, adjusting for clinicopathologic, demographic, and socioeconomic variables. A total of 52% of the patients were older than 45 years, 77% were female, and 54% received RAI.
Factors predicting the use of RAI were being male, having positive margins, having cervical lymph node involvement, and having a tumor size greater than 4 cm in diameter, said Dr. Suman, an endocrinology surgery fellow at North Shore University Health System in Evanston, Ill. The 10-year overall survival rate was 90% in those who received RAI, compared with 87.4% among those who did not, for a small but statistically significant survival advantage (P < .0001).
Among patients who received RAI, the 10-year survival advantage by diameter of tumor was 3.4% for those with tumors 10 mm or less; 2.8% with 11-20 mm; 3.3% with 21-40 mm, and 5.7% with greater than 40 mm.
Age also played a factor, with a 10-year survival advantage of 0.5% for those aged 18-35 years; 1.5% for those aged 36-45 years; 0.9% for those aged 46-55 years; 0.6% for those aged 56-65 years; and 2.1% for those older than 65 years. Both men and women who received RAI had a statistically significant survival advantage at 10 years (3.9% and 1.6%, respectively).
When the researchers assessed the 10-year survival advantage by lymph node category of patients who received RAI, the rates were 2.9% for N-0, 4.2% for N-1, 5.2% for N-1A, and 5.8% for N-1B. By margin status, the 10-year survival advantage was 3.1% for negative margins, 3.6% for positive margins, 3.5% for microscopic margins, and 8.8% for gross margins.
In an analysis of all patients with very low-risk, low-risk, and high-risk papillary thyroid carcinoma according to ATA guidelines for the use of RAI, the study authors found a 10-year survival advantage of RAI in each of the three categories.
Among patients with very low-risk papillary thyroid carcinoma, the rate of 10-year survival was 92.2% among those who received RAI, compared with 89% among those who did not (hazard ratio, 0.74). Similar associations were observed in those with low-risk carcinoma (91.8% vs. 89%; HR, 0.80) and in those with high-risk carcinoma (86.2% vs. 79.2%; HR, 0.71).
“RAI is associated with a statistically significant but small overall survival advantage for most patients,” Dr. Suman said. “High-risk patients, defined by large tumor size, lymph node involvement, and gross margins, achieve the greatest benefit with RAI ablation.”
Dr. Suman reported having no relevant financial disclosures.
On Twitter @dougbrunk
CORONADO, CALIF. – The use of radioactive iodine in patients with papillary thyroid cancer showed a small but statistically significant survival benefit for all tumor size categories, a long-term analysis of national data suggested.
“The incidence of papillary thyroid carcinoma is rapidly rising, but the survival advantage of radioactive iodine ablation has not been confirmed,” Dr. Paritosh Suman said at the annual meeting of the American Thyroid Association.
To investigate the effect of radioactive iodine (RAI) on papillary thyroid cancer mortality, Dr. Suman and his associates identified 108,565 patients from the National Cancer Data Base who were diagnosed with papillary thyroid cancer and underwent total or near total thyroidectomy between 1998 and 2006.
The investigators classified tumors into one of four groups by diameter size: 10 mm or less, 11-20 mm, 21-40 mm, and greater than 40 mm. The study researchers used Cox regression analysis to quantify the effect of radioactive iodine, adjusting for clinicopathologic, demographic, and socioeconomic variables. A total of 52% of the patients were older than 45 years, 77% were female, and 54% received RAI.
Factors predicting the use of RAI were being male, having positive margins, having cervical lymph node involvement, and having a tumor size greater than 4 cm in diameter, said Dr. Suman, an endocrinology surgery fellow at North Shore University Health System in Evanston, Ill. The 10-year overall survival rate was 90% in those who received RAI, compared with 87.4% among those who did not, for a small but statistically significant survival advantage (P < .0001).
Among patients who received RAI, the 10-year survival advantage by diameter of tumor was 3.4% for those with tumors 10 mm or less; 2.8% with 11-20 mm; 3.3% with 21-40 mm, and 5.7% with greater than 40 mm.
Age also played a factor, with a 10-year survival advantage of 0.5% for those aged 18-35 years; 1.5% for those aged 36-45 years; 0.9% for those aged 46-55 years; 0.6% for those aged 56-65 years; and 2.1% for those older than 65 years. Both men and women who received RAI had a statistically significant survival advantage at 10 years (3.9% and 1.6%, respectively).
When the researchers assessed the 10-year survival advantage by lymph node category of patients who received RAI, the rates were 2.9% for N-0, 4.2% for N-1, 5.2% for N-1A, and 5.8% for N-1B. By margin status, the 10-year survival advantage was 3.1% for negative margins, 3.6% for positive margins, 3.5% for microscopic margins, and 8.8% for gross margins.
In an analysis of all patients with very low-risk, low-risk, and high-risk papillary thyroid carcinoma according to ATA guidelines for the use of RAI, the study authors found a 10-year survival advantage of RAI in each of the three categories.
Among patients with very low-risk papillary thyroid carcinoma, the rate of 10-year survival was 92.2% among those who received RAI, compared with 89% among those who did not (hazard ratio, 0.74). Similar associations were observed in those with low-risk carcinoma (91.8% vs. 89%; HR, 0.80) and in those with high-risk carcinoma (86.2% vs. 79.2%; HR, 0.71).
“RAI is associated with a statistically significant but small overall survival advantage for most patients,” Dr. Suman said. “High-risk patients, defined by large tumor size, lymph node involvement, and gross margins, achieve the greatest benefit with RAI ablation.”
Dr. Suman reported having no relevant financial disclosures.
On Twitter @dougbrunk
AT THE ATA ANNUAL MEETING
Key clinical point: The use of radioactive iodine is associated with a small but statistically significant increase in overall survival in most patients with papillary thyroid carcinoma.
Major finding: The 10-year overall survival rate was 90% in patients who received RAI, compared with 87.4% among those who did not, a small but statistically significant difference (P < .0001).
Data source: An analysis of 108,565 patients from the National Cancer Data Base who were diagnosed with papillary thyroid cancer and underwent total or near total thyroidectomy between 1998 and 2006.
Disclosures: Dr. Suman reported having no relevant financial disclosures.
Total thyroidectomy more likely with younger thyroid cancer patients
CORONADO, CALIF. – Patients with differentiated thyroid cancer who were younger than age 45 years were more likely to undergo total or near-total thyroidectomy and to receive radioactive iodine, compared with their older counterparts, a large registry analysis demonstrated.
In addition, younger patients were more likely to be Hispanic and female and to have papillary carcinoma, lead study author Dr. Thomas J. Semrad reported during the annual meeting of the American Thyroid Association.
“Not much is known about how treatment administration differs between younger and older patients with thyroid cancer,” Dr. Semrad of the division of hematology/oncology at the University of California, Davis, Comprehensive Cancer Center, Sacramento, said in an interview. “Some data suggest that perhaps patients younger than age 15 years may respond better to radioactive iodine and may present with more advanced disease. But not much is known about how they’re treated.”
To find out, Dr. Semrad and his associates used the California Cancer Registry to identify 23,629 patients who were diagnosed with differentiated thyroid cancer between 2004 and 2011. They divided the patients into two cohorts: younger (defined as those younger than 45 years) and older (those 45 years or older). Treatment variables of interest included total or near-total thyroidectomy, other types of thyroid surgery, and the administration of radioactive iodine (RAI). The researchers compared the descriptive statistics between the two groups and used univariate and multivariate logistic regression to identify predictors of the treatment administered.
Compared with older patients, younger patients were significantly more likely to be Hispanic (33% vs. 22%), to be female (83% vs. 75%), to have papillary carcinoma (93% vs. 91%), and to have lymph node involvement (32% vs. 20%, all P < .0001).
Overall, the majority of patients (86%) underwent total or near-total thyroidectomy, but the surgery was slightly and significantly more common in younger patients, compared with their older counterparts (88% vs. 85%, P < .0001). Younger patients also were significantly more likely to receive RAI (55% vs. 49%, P < .0001).
On multivariate analysis, statistically significant predictors of total thyroidectomy, compared with other thyroid surgery, included younger age (odds ratio, 1.193); higher socioeconomic status (OR, 1.263, for higher-middle SES and OR, 1.325, for highest SES); higher T stage (OR, 1.848, for T2; OR, 2.473, for T3; and OR, 2.908, for T4); and papillary histology (OR, 0.349).
At the same time, statistically significant predictors of RAI administration included younger age (OR, 1.116); higher SES (OR, 1.410, for higher-middle SES and OR, 1.307, for highest SES); more advanced T stage (OR, 2.194 for T2; OR, 2.084, for T3; and OR, 1.527, for T4); node positivity (OR, 0.481), and total thyroidectomy (OR, 3.76).
“As we expected, the younger population was more likely to be female, but we did find that the younger population was also more likely to be Hispanic,” Dr. Semrad said. “We don’t know if they were native Hispanics or if it has something to do with immigration rates.”
Dr. Semrad acknowledged certain limitations of the study, including the risk of misclassification bias in registry data, the lack of details about surgical procedures performed, and the fact that the radioiodine dose was not captured.
“We have data regarding the T stage, the nodal stage, and the number of lymph nodes examined, but we don’t have some of the finer histology data,” he said.
Even so, he characterized the findings as “provocative in suggesting that perhaps our treatment patterns in younger patients are different. With more aggressive surgery and more use of radioactive iodine, that can have potential implications in terms of long-term side effects and follow-up.”
The researchers said they plan to use linked administrative data to analyze initial and subsequent thyroid surgical procedures in this patient population.
The study was supported by a grant from the National Institutes of Health. Dr. Semrad reported having no relevant financial disclosures.
On Twitter @dougbrunk
CORONADO, CALIF. – Patients with differentiated thyroid cancer who were younger than age 45 years were more likely to undergo total or near-total thyroidectomy and to receive radioactive iodine, compared with their older counterparts, a large registry analysis demonstrated.
In addition, younger patients were more likely to be Hispanic and female and to have papillary carcinoma, lead study author Dr. Thomas J. Semrad reported during the annual meeting of the American Thyroid Association.
“Not much is known about how treatment administration differs between younger and older patients with thyroid cancer,” Dr. Semrad of the division of hematology/oncology at the University of California, Davis, Comprehensive Cancer Center, Sacramento, said in an interview. “Some data suggest that perhaps patients younger than age 15 years may respond better to radioactive iodine and may present with more advanced disease. But not much is known about how they’re treated.”
To find out, Dr. Semrad and his associates used the California Cancer Registry to identify 23,629 patients who were diagnosed with differentiated thyroid cancer between 2004 and 2011. They divided the patients into two cohorts: younger (defined as those younger than 45 years) and older (those 45 years or older). Treatment variables of interest included total or near-total thyroidectomy, other types of thyroid surgery, and the administration of radioactive iodine (RAI). The researchers compared the descriptive statistics between the two groups and used univariate and multivariate logistic regression to identify predictors of the treatment administered.
Compared with older patients, younger patients were significantly more likely to be Hispanic (33% vs. 22%), to be female (83% vs. 75%), to have papillary carcinoma (93% vs. 91%), and to have lymph node involvement (32% vs. 20%, all P < .0001).
Overall, the majority of patients (86%) underwent total or near-total thyroidectomy, but the surgery was slightly and significantly more common in younger patients, compared with their older counterparts (88% vs. 85%, P < .0001). Younger patients also were significantly more likely to receive RAI (55% vs. 49%, P < .0001).
On multivariate analysis, statistically significant predictors of total thyroidectomy, compared with other thyroid surgery, included younger age (odds ratio, 1.193); higher socioeconomic status (OR, 1.263, for higher-middle SES and OR, 1.325, for highest SES); higher T stage (OR, 1.848, for T2; OR, 2.473, for T3; and OR, 2.908, for T4); and papillary histology (OR, 0.349).
At the same time, statistically significant predictors of RAI administration included younger age (OR, 1.116); higher SES (OR, 1.410, for higher-middle SES and OR, 1.307, for highest SES); more advanced T stage (OR, 2.194 for T2; OR, 2.084, for T3; and OR, 1.527, for T4); node positivity (OR, 0.481), and total thyroidectomy (OR, 3.76).
“As we expected, the younger population was more likely to be female, but we did find that the younger population was also more likely to be Hispanic,” Dr. Semrad said. “We don’t know if they were native Hispanics or if it has something to do with immigration rates.”
Dr. Semrad acknowledged certain limitations of the study, including the risk of misclassification bias in registry data, the lack of details about surgical procedures performed, and the fact that the radioiodine dose was not captured.
“We have data regarding the T stage, the nodal stage, and the number of lymph nodes examined, but we don’t have some of the finer histology data,” he said.
Even so, he characterized the findings as “provocative in suggesting that perhaps our treatment patterns in younger patients are different. With more aggressive surgery and more use of radioactive iodine, that can have potential implications in terms of long-term side effects and follow-up.”
The researchers said they plan to use linked administrative data to analyze initial and subsequent thyroid surgical procedures in this patient population.
The study was supported by a grant from the National Institutes of Health. Dr. Semrad reported having no relevant financial disclosures.
On Twitter @dougbrunk
CORONADO, CALIF. – Patients with differentiated thyroid cancer who were younger than age 45 years were more likely to undergo total or near-total thyroidectomy and to receive radioactive iodine, compared with their older counterparts, a large registry analysis demonstrated.
In addition, younger patients were more likely to be Hispanic and female and to have papillary carcinoma, lead study author Dr. Thomas J. Semrad reported during the annual meeting of the American Thyroid Association.
“Not much is known about how treatment administration differs between younger and older patients with thyroid cancer,” Dr. Semrad of the division of hematology/oncology at the University of California, Davis, Comprehensive Cancer Center, Sacramento, said in an interview. “Some data suggest that perhaps patients younger than age 15 years may respond better to radioactive iodine and may present with more advanced disease. But not much is known about how they’re treated.”
To find out, Dr. Semrad and his associates used the California Cancer Registry to identify 23,629 patients who were diagnosed with differentiated thyroid cancer between 2004 and 2011. They divided the patients into two cohorts: younger (defined as those younger than 45 years) and older (those 45 years or older). Treatment variables of interest included total or near-total thyroidectomy, other types of thyroid surgery, and the administration of radioactive iodine (RAI). The researchers compared the descriptive statistics between the two groups and used univariate and multivariate logistic regression to identify predictors of the treatment administered.
Compared with older patients, younger patients were significantly more likely to be Hispanic (33% vs. 22%), to be female (83% vs. 75%), to have papillary carcinoma (93% vs. 91%), and to have lymph node involvement (32% vs. 20%, all P < .0001).
Overall, the majority of patients (86%) underwent total or near-total thyroidectomy, but the surgery was slightly and significantly more common in younger patients, compared with their older counterparts (88% vs. 85%, P < .0001). Younger patients also were significantly more likely to receive RAI (55% vs. 49%, P < .0001).
On multivariate analysis, statistically significant predictors of total thyroidectomy, compared with other thyroid surgery, included younger age (odds ratio, 1.193); higher socioeconomic status (OR, 1.263, for higher-middle SES and OR, 1.325, for highest SES); higher T stage (OR, 1.848, for T2; OR, 2.473, for T3; and OR, 2.908, for T4); and papillary histology (OR, 0.349).
At the same time, statistically significant predictors of RAI administration included younger age (OR, 1.116); higher SES (OR, 1.410, for higher-middle SES and OR, 1.307, for highest SES); more advanced T stage (OR, 2.194 for T2; OR, 2.084, for T3; and OR, 1.527, for T4); node positivity (OR, 0.481), and total thyroidectomy (OR, 3.76).
“As we expected, the younger population was more likely to be female, but we did find that the younger population was also more likely to be Hispanic,” Dr. Semrad said. “We don’t know if they were native Hispanics or if it has something to do with immigration rates.”
Dr. Semrad acknowledged certain limitations of the study, including the risk of misclassification bias in registry data, the lack of details about surgical procedures performed, and the fact that the radioiodine dose was not captured.
“We have data regarding the T stage, the nodal stage, and the number of lymph nodes examined, but we don’t have some of the finer histology data,” he said.
Even so, he characterized the findings as “provocative in suggesting that perhaps our treatment patterns in younger patients are different. With more aggressive surgery and more use of radioactive iodine, that can have potential implications in terms of long-term side effects and follow-up.”
The researchers said they plan to use linked administrative data to analyze initial and subsequent thyroid surgical procedures in this patient population.
The study was supported by a grant from the National Institutes of Health. Dr. Semrad reported having no relevant financial disclosures.
On Twitter @dougbrunk
AT THE ATA ANNUAL MEETING
Key clinical point: Younger patients with differentiated thyroid cancer were more likely to undergo total thyroidectomy and receive radioactive iodine.
Major finding: Total or near-total thyroidectomy was slightly more common in patients younger than age 45 years, compared with their older counterparts (88% vs. 85%, P < .0001). Younger patients were also more likely to receive RAI (55% vs. 49%, P < .0001).
Data source: A study of 23,629 patients from the California Cancer Registry who were diagnosed with differentiated thyroid cancer between 2004 and 2011.
Disclosures: The study was supported by a grant from the National Institutes of Health. Dr. Semrad reported having no relevant financial disclosures.
Enhanced thyroid cancer guidelines expected in 2015
CORONADO, CALIF. – Expect significant enhancements to the updated thyroid cancer management guidelines from the American Thyroid Association, due to be released in early 2015.
Last updated in 2009, the goal of the new guidelines is to “be evidence based and helpful,” guidelines task force chair Dr. Bryan R. Haugen said at the annual meeting of the American Thyroid Association. For example, the new guidelines will contain 101 recommendations, up from 80 in the 2009 version; 175 subrecommendations, up from 103; and 998 references, up from 437. “Still, 59 of the existing 80 recommendations are not substantially changed, showing a general stability in our field over the past 5 to 6 years,” he said.
One enhancement is a definition of risk of structural disease recurrence in patients without structurally identifiable disease after initial therapy for thyroid cancer. Low risk is defined as intrathyroidal differentiated thyroid cancer involving up to five metastases less than 0.2 cm in size. Intermediate risk is defined as the presence of aggressive histology, minor extrathyroidal extension, vascular invasion, or more than five involved lymph nodes with metastases 0.2-0.3 cm in size. High risk is defined as the presence of gross extrathyroidal extension, incomplete tumor resection, distant metastases, or lymph node metastases greater than 3 cm in size.
The guidelines also include a table that defines a patient’s response to therapy as a dynamic risk assessment. “This best applies to the low- to intermediate-risk patients, although it definitely applies to high risk as well,” said Dr. Haugen, who heads the division of endocrinology, metabolism, and diabetes at the University of Colorado Health Sciences Center, Denver. “It’s [a] strong recommendation based on low-quality evidence to use this risk-based response to therapy. A lot of this data is generated from patients who’ve had a thyroidectomy and have received radioiodine. So we’re on a bit more shaky ground right now in a patient who’s had a thyroidectomy but no radioiodine, or a patient who’s had a lobectomy.”
Other changes include the concept that it’s not necessary to biopsy every nodule more than 1 cm in size. “We’re going to be guided by the sonographic pattern in who we biopsy and how we monitor them,” Dr. Haugen explained. “A new recommendation adds follow-up guidance for nodules that do not meet FNA [fine-needle aspiration] criteria. We’re also recommending use of the Bethesda Cytology Classification System for cytology.”
Changes in the initial management of thyroid cancer include a recommendation for cross-sectional imaging with contrast for higher-risk disease and the consideration of lobectomy for some patients with tumors 1-4 cm in size. “This is a controversial recommendation,” Dr. Haugen said. “We got some feedback from members asking if you do it, what’s the TSH target? Should we give them synthetic levothyroxine? We are revising the guidelines based on this feedback to help guide clinicians.”
The new guidelines also call for more detailed/standardized pathology reports, with inclusion of lymph node size, extranodal invasion, and the number of invaded vessels. “I’ve talked to a number of pathologists and clinicians who are very happy about this guidance,” he said. “We also need to look at tumor stage, recurrence risk, and response to therapy in our patients, and the use of selective radioiodine. There is some more information on considering lower administered activities, especially in the lower-risk patients.”
For the first time, the guidelines include a section on radioiodine treatment for refractory differentiated thyroid cancer, including tips on directed therapy, clinical trials, systemic therapy, and bone-specific therapy.
Dr. Haugen disclosed that he has received grants and research support from Veracyte and Genzyme.
On Twitter @dougbrunk
CORONADO, CALIF. – Expect significant enhancements to the updated thyroid cancer management guidelines from the American Thyroid Association, due to be released in early 2015.
Last updated in 2009, the goal of the new guidelines is to “be evidence based and helpful,” guidelines task force chair Dr. Bryan R. Haugen said at the annual meeting of the American Thyroid Association. For example, the new guidelines will contain 101 recommendations, up from 80 in the 2009 version; 175 subrecommendations, up from 103; and 998 references, up from 437. “Still, 59 of the existing 80 recommendations are not substantially changed, showing a general stability in our field over the past 5 to 6 years,” he said.
One enhancement is a definition of risk of structural disease recurrence in patients without structurally identifiable disease after initial therapy for thyroid cancer. Low risk is defined as intrathyroidal differentiated thyroid cancer involving up to five metastases less than 0.2 cm in size. Intermediate risk is defined as the presence of aggressive histology, minor extrathyroidal extension, vascular invasion, or more than five involved lymph nodes with metastases 0.2-0.3 cm in size. High risk is defined as the presence of gross extrathyroidal extension, incomplete tumor resection, distant metastases, or lymph node metastases greater than 3 cm in size.
The guidelines also include a table that defines a patient’s response to therapy as a dynamic risk assessment. “This best applies to the low- to intermediate-risk patients, although it definitely applies to high risk as well,” said Dr. Haugen, who heads the division of endocrinology, metabolism, and diabetes at the University of Colorado Health Sciences Center, Denver. “It’s [a] strong recommendation based on low-quality evidence to use this risk-based response to therapy. A lot of this data is generated from patients who’ve had a thyroidectomy and have received radioiodine. So we’re on a bit more shaky ground right now in a patient who’s had a thyroidectomy but no radioiodine, or a patient who’s had a lobectomy.”
Other changes include the concept that it’s not necessary to biopsy every nodule more than 1 cm in size. “We’re going to be guided by the sonographic pattern in who we biopsy and how we monitor them,” Dr. Haugen explained. “A new recommendation adds follow-up guidance for nodules that do not meet FNA [fine-needle aspiration] criteria. We’re also recommending use of the Bethesda Cytology Classification System for cytology.”
Changes in the initial management of thyroid cancer include a recommendation for cross-sectional imaging with contrast for higher-risk disease and the consideration of lobectomy for some patients with tumors 1-4 cm in size. “This is a controversial recommendation,” Dr. Haugen said. “We got some feedback from members asking if you do it, what’s the TSH target? Should we give them synthetic levothyroxine? We are revising the guidelines based on this feedback to help guide clinicians.”
The new guidelines also call for more detailed/standardized pathology reports, with inclusion of lymph node size, extranodal invasion, and the number of invaded vessels. “I’ve talked to a number of pathologists and clinicians who are very happy about this guidance,” he said. “We also need to look at tumor stage, recurrence risk, and response to therapy in our patients, and the use of selective radioiodine. There is some more information on considering lower administered activities, especially in the lower-risk patients.”
For the first time, the guidelines include a section on radioiodine treatment for refractory differentiated thyroid cancer, including tips on directed therapy, clinical trials, systemic therapy, and bone-specific therapy.
Dr. Haugen disclosed that he has received grants and research support from Veracyte and Genzyme.
On Twitter @dougbrunk
CORONADO, CALIF. – Expect significant enhancements to the updated thyroid cancer management guidelines from the American Thyroid Association, due to be released in early 2015.
Last updated in 2009, the goal of the new guidelines is to “be evidence based and helpful,” guidelines task force chair Dr. Bryan R. Haugen said at the annual meeting of the American Thyroid Association. For example, the new guidelines will contain 101 recommendations, up from 80 in the 2009 version; 175 subrecommendations, up from 103; and 998 references, up from 437. “Still, 59 of the existing 80 recommendations are not substantially changed, showing a general stability in our field over the past 5 to 6 years,” he said.
One enhancement is a definition of risk of structural disease recurrence in patients without structurally identifiable disease after initial therapy for thyroid cancer. Low risk is defined as intrathyroidal differentiated thyroid cancer involving up to five metastases less than 0.2 cm in size. Intermediate risk is defined as the presence of aggressive histology, minor extrathyroidal extension, vascular invasion, or more than five involved lymph nodes with metastases 0.2-0.3 cm in size. High risk is defined as the presence of gross extrathyroidal extension, incomplete tumor resection, distant metastases, or lymph node metastases greater than 3 cm in size.
The guidelines also include a table that defines a patient’s response to therapy as a dynamic risk assessment. “This best applies to the low- to intermediate-risk patients, although it definitely applies to high risk as well,” said Dr. Haugen, who heads the division of endocrinology, metabolism, and diabetes at the University of Colorado Health Sciences Center, Denver. “It’s [a] strong recommendation based on low-quality evidence to use this risk-based response to therapy. A lot of this data is generated from patients who’ve had a thyroidectomy and have received radioiodine. So we’re on a bit more shaky ground right now in a patient who’s had a thyroidectomy but no radioiodine, or a patient who’s had a lobectomy.”
Other changes include the concept that it’s not necessary to biopsy every nodule more than 1 cm in size. “We’re going to be guided by the sonographic pattern in who we biopsy and how we monitor them,” Dr. Haugen explained. “A new recommendation adds follow-up guidance for nodules that do not meet FNA [fine-needle aspiration] criteria. We’re also recommending use of the Bethesda Cytology Classification System for cytology.”
Changes in the initial management of thyroid cancer include a recommendation for cross-sectional imaging with contrast for higher-risk disease and the consideration of lobectomy for some patients with tumors 1-4 cm in size. “This is a controversial recommendation,” Dr. Haugen said. “We got some feedback from members asking if you do it, what’s the TSH target? Should we give them synthetic levothyroxine? We are revising the guidelines based on this feedback to help guide clinicians.”
The new guidelines also call for more detailed/standardized pathology reports, with inclusion of lymph node size, extranodal invasion, and the number of invaded vessels. “I’ve talked to a number of pathologists and clinicians who are very happy about this guidance,” he said. “We also need to look at tumor stage, recurrence risk, and response to therapy in our patients, and the use of selective radioiodine. There is some more information on considering lower administered activities, especially in the lower-risk patients.”
For the first time, the guidelines include a section on radioiodine treatment for refractory differentiated thyroid cancer, including tips on directed therapy, clinical trials, systemic therapy, and bone-specific therapy.
Dr. Haugen disclosed that he has received grants and research support from Veracyte and Genzyme.
On Twitter @dougbrunk
EXPERT ANALYSIS FROM THE ATA ANNUAL MEETING
