Head & Neck/Thyroid Cancers

The evaluation and treatment of thyroid nodules in children should differ from evaluation and treatment in adults in that ultrasound characteristics and clinical context should be used rather than size alone to identify nodules that warrant fine-needle aspiration, according to new pediatric-specific guidelines from the American Thyroid Association.

The Management Guidelines for Children with Thyroid Nodules and Differentiated Thyroid Cancer – the first-ever guidelines for the evaluation and management of thyroid nodules and cancer in children – also note that fine-needle aspiration (FNA) in children should be performed under ultrasound guidance, that preoperative FNA of a hyperfunctioning nodule in a child is not warranted as long as the lesion is removed, that a diffusely infiltrative form of papillary thyroid cancer may occur in children and should be considered in a clinically suspicious gland, and that surgery (lobectomy plus isthmusectomy) is favored over repeat FNA for most nodules with indeterminate cytology, Dr. Gary L. Francis of Virginia Commonwealth University and Children’s Hospital of Richmond, Va., and his colleagues from the American Thyroid Association Guidelines Task Force on Pediatric Thyroid Cancer determined based on an extensive literature search.

Together this guidance with respect to thyroid nodules represents just one of 34 recommendations contained in the guidelines, which, according to the authors, represent “the current optimal care for children and adolescents with these conditions.”

The guidelines were published in the July issue of Thyroid (2015;25:716-59).

Previous guidelines were geared toward adults, but thyroid neoplasms in children differ from those in adults with respect to pathophysiology, clinical presentation, and long-term outcomes. Further, therapy that may be appropriate in adults may not be appropriate for children at low risk for death but higher risk of long-term harm from certain treatments, they said.

For example, recent studies with long-term follow-up revealed an increase in all-cause mortality for survivors of childhood differentiated thyroid cancer (DTC), primarily caused by second malignancies in children treated with radiation.

“These observations, coupled with a better understanding of the excellent prognosis associated with pediatric DTC, have now prompted the American Thyroid Association to specifically address treatment of children with benign and malignant thyroid tumors,” they wrote.

While the task force acknowledged a paucity of randomized, double-blind, controlled clinical trials involving children with DTC, they note that “retrospective analysis of therapeutic options has led to a reconsideration of the former concept that all children with DTC should be similarly treated and has provided the opportunity ... to broaden the scope of acceptable therapy in an attempt to provide aggressive therapy when warranted and to limit overtreatment to those children who are unlikely to benefit.”

In addition to addressing the evaluation and management of thyroid nodules, the guidelines also address DTC, including preoperative staging, surgical management, postoperative staging, the role of radioactive iodine therapy, and goals for thyrotropin suppression. Management algorithms are proposed, and separate recommendations for papillary and follicular thyroid cancers are provided.

The authors note that since DTC recurrence has been reported as long as 40 years after initial therapy, children with DTC should be “followed for life, albeit with decreasing intensity for those with no evidence for disease.”

The guidelines are timely, as Surveillance, Epidemiology and End Results (SEER) program data indicate that new cases of thyroid cancer in persons under the age of 20 years represent 1.8% of all thyroid malignancies diagnosed in the United States, and that the incidence appears to be increasing.

Among 15- to 19-year old adolescents, thyroid cancer is the eighth most frequently diagnosed cancer, and it is the second most common cancer among girls, the authors said, noting that adolescents have a 10-fold greater incidence than do younger children, and that there is a female to male preponderance.

The development of pediatric-specific guidelines was critical, according to guidelines coauthor, Dr. Peter Angelos, professor of surgery and surgical ethics and chief of endocrine surgery at the University of Chicago Medicine and Biological Sciences.

“As they say, ‘children are not just small adults,’ ” he said in an interview.

In addition to the guidance provided on which types of nodules should be evaluated in children (since size alone should not be used to dictate who undergoes biopsy), a highlight of the guidelines is a recommendation that children with thyroid cancer be treated by multidisciplinary teams of physician in high-volume centers, he said.

“Thyroid cancer in children is different than in adults in that children have much higher rates of involved lymph nodes, but their overall prognosis is excellent despite the frequency of involved nodes. This confluence of findings pushes surgeons to do more aggressive operations to clear lymph nodes. This is a good thing, but unfortunately, can lead to higher complication rates (things such as permanently low calcium levels in the blood),” he said, adding that “the implications of finding a high-volume thyroid cancer surgeon with experience in thyroid cancer surgery on children are very significant and the guidelines make some recommendations about how many operations are necessary to constitute high volume.”

The push to limit the use of radioactive iodine in children further underscores the need for an experienced surgeon, he said.

“In an effort to avoid exposing children to radiation, surgeons are further pushed to be more aggressive in the operating room. Thus, it becomes even more important to see an experienced surgeon so that complications can be minimized. Even a seemingly ‘mild’ complication can be devastating for a child who will likely have to live with that complication for decades to come since the prognosis for thyroid cancer is so good,” he said.

An important potential benefit of treatment at centers with multidisciplinary interest and expertise is facilitation of additional research, particularly in areas of uncertainty, including the proper use of ¹³¹I, the interpretation of thyroglobulin (Tg) and TgAb (antibody) levels, the role of prospective ultrasound monitoring in presymptomatic children at risk for thyroid neoplasia, the use of novel targeted therapies for advanced disease that fails to respond to ¹³¹I, and the long-term psychosocial impacts of the disease on children and their families, the guideline authors said.

“These areas require well-designed long-term, multicenter studies that will be difficult to perform because of the rarity of pediatric DTC and the prolonged follow-up required to reach meaningful endpoints. Further research should be facilitated by ensuring that children with DTC are treated when possible at centers with multidisciplinary interest and expertise in this disease,” they concluded.

The guidelines were funded by the American Thyroid Association and ThyCa: Thyroid Cancer Survivors’ Association. Dr. Francis reported serving as an adviser to ThyCa and receiving research support from Grifols, Novo Nordisk, and the Juvenile Diabetes Research Foundation. Other authors reported relationships (consulting, receiving research support, and/or serving as a speaker) with Akrimax, IBSA Institut Biochimique, Pfizer, Novo Nordisk, Eli Lilly, AstraZeneca, Bayer Healthcare, Genzyme, Sobi, Henning, and Merck, and ThyCa.

[email protected]

The evaluation and treatment of thyroid nodules in children should differ from evaluation and treatment in adults in that ultrasound characteristics and clinical context should be used rather than size alone to identify nodules that warrant fine-needle aspiration, according to new pediatric-specific guidelines from the American Thyroid Association.

The Management Guidelines for Children with Thyroid Nodules and Differentiated Thyroid Cancer – the first-ever guidelines for the evaluation and management of thyroid nodules and cancer in children – also note that fine-needle aspiration (FNA) in children should be performed under ultrasound guidance, that preoperative FNA of a hyperfunctioning nodule in a child is not warranted as long as the lesion is removed, that a diffusely infiltrative form of papillary thyroid cancer may occur in children and should be considered in a clinically suspicious gland, and that surgery (lobectomy plus isthmusectomy) is favored over repeat FNA for most nodules with indeterminate cytology, Dr. Gary L. Francis of Virginia Commonwealth University and Children’s Hospital of Richmond, Va., and his colleagues from the American Thyroid Association Guidelines Task Force on Pediatric Thyroid Cancer determined based on an extensive literature search.

Together this guidance with respect to thyroid nodules represents just one of 34 recommendations contained in the guidelines, which, according to the authors, represent “the current optimal care for children and adolescents with these conditions.”

The guidelines were published in the July issue of Thyroid (2015;25:716-59).

Previous guidelines were geared toward adults, but thyroid neoplasms in children differ from those in adults with respect to pathophysiology, clinical presentation, and long-term outcomes. Further, therapy that may be appropriate in adults may not be appropriate for children at low risk for death but higher risk of long-term harm from certain treatments, they said.

For example, recent studies with long-term follow-up revealed an increase in all-cause mortality for survivors of childhood differentiated thyroid cancer (DTC), primarily caused by second malignancies in children treated with radiation.

“These observations, coupled with a better understanding of the excellent prognosis associated with pediatric DTC, have now prompted the American Thyroid Association to specifically address treatment of children with benign and malignant thyroid tumors,” they wrote.

While the task force acknowledged a paucity of randomized, double-blind, controlled clinical trials involving children with DTC, they note that “retrospective analysis of therapeutic options has led to a reconsideration of the former concept that all children with DTC should be similarly treated and has provided the opportunity ... to broaden the scope of acceptable therapy in an attempt to provide aggressive therapy when warranted and to limit overtreatment to those children who are unlikely to benefit.”

In addition to addressing the evaluation and management of thyroid nodules, the guidelines also address DTC, including preoperative staging, surgical management, postoperative staging, the role of radioactive iodine therapy, and goals for thyrotropin suppression. Management algorithms are proposed, and separate recommendations for papillary and follicular thyroid cancers are provided.

The authors note that since DTC recurrence has been reported as long as 40 years after initial therapy, children with DTC should be “followed for life, albeit with decreasing intensity for those with no evidence for disease.”

The guidelines are timely, as Surveillance, Epidemiology and End Results (SEER) program data indicate that new cases of thyroid cancer in persons under the age of 20 years represent 1.8% of all thyroid malignancies diagnosed in the United States, and that the incidence appears to be increasing.

Among 15- to 19-year old adolescents, thyroid cancer is the eighth most frequently diagnosed cancer, and it is the second most common cancer among girls, the authors said, noting that adolescents have a 10-fold greater incidence than do younger children, and that there is a female to male preponderance.

The development of pediatric-specific guidelines was critical, according to guidelines coauthor, Dr. Peter Angelos, professor of surgery and surgical ethics and chief of endocrine surgery at the University of Chicago Medicine and Biological Sciences.

“As they say, ‘children are not just small adults,’ ” he said in an interview.

In addition to the guidance provided on which types of nodules should be evaluated in children (since size alone should not be used to dictate who undergoes biopsy), a highlight of the guidelines is a recommendation that children with thyroid cancer be treated by multidisciplinary teams of physician in high-volume centers, he said.

“Thyroid cancer in children is different than in adults in that children have much higher rates of involved lymph nodes, but their overall prognosis is excellent despite the frequency of involved nodes. This confluence of findings pushes surgeons to do more aggressive operations to clear lymph nodes. This is a good thing, but unfortunately, can lead to higher complication rates (things such as permanently low calcium levels in the blood),” he said, adding that “the implications of finding a high-volume thyroid cancer surgeon with experience in thyroid cancer surgery on children are very significant and the guidelines make some recommendations about how many operations are necessary to constitute high volume.”

The push to limit the use of radioactive iodine in children further underscores the need for an experienced surgeon, he said.

“In an effort to avoid exposing children to radiation, surgeons are further pushed to be more aggressive in the operating room. Thus, it becomes even more important to see an experienced surgeon so that complications can be minimized. Even a seemingly ‘mild’ complication can be devastating for a child who will likely have to live with that complication for decades to come since the prognosis for thyroid cancer is so good,” he said.

An important potential benefit of treatment at centers with multidisciplinary interest and expertise is facilitation of additional research, particularly in areas of uncertainty, including the proper use of ¹³¹I, the interpretation of thyroglobulin (Tg) and TgAb (antibody) levels, the role of prospective ultrasound monitoring in presymptomatic children at risk for thyroid neoplasia, the use of novel targeted therapies for advanced disease that fails to respond to ¹³¹I, and the long-term psychosocial impacts of the disease on children and their families, the guideline authors said.

“These areas require well-designed long-term, multicenter studies that will be difficult to perform because of the rarity of pediatric DTC and the prolonged follow-up required to reach meaningful endpoints. Further research should be facilitated by ensuring that children with DTC are treated when possible at centers with multidisciplinary interest and expertise in this disease,” they concluded.

The guidelines were funded by the American Thyroid Association and ThyCa: Thyroid Cancer Survivors’ Association. Dr. Francis reported serving as an adviser to ThyCa and receiving research support from Grifols, Novo Nordisk, and the Juvenile Diabetes Research Foundation. Other authors reported relationships (consulting, receiving research support, and/or serving as a speaker) with Akrimax, IBSA Institut Biochimique, Pfizer, Novo Nordisk, Eli Lilly, AstraZeneca, Bayer Healthcare, Genzyme, Sobi, Henning, and Merck, and ThyCa.

[email protected]

The evaluation and treatment of thyroid nodules in children should differ from evaluation and treatment in adults in that ultrasound characteristics and clinical context should be used rather than size alone to identify nodules that warrant fine-needle aspiration, according to new pediatric-specific guidelines from the American Thyroid Association.

The Management Guidelines for Children with Thyroid Nodules and Differentiated Thyroid Cancer – the first-ever guidelines for the evaluation and management of thyroid nodules and cancer in children – also note that fine-needle aspiration (FNA) in children should be performed under ultrasound guidance, that preoperative FNA of a hyperfunctioning nodule in a child is not warranted as long as the lesion is removed, that a diffusely infiltrative form of papillary thyroid cancer may occur in children and should be considered in a clinically suspicious gland, and that surgery (lobectomy plus isthmusectomy) is favored over repeat FNA for most nodules with indeterminate cytology, Dr. Gary L. Francis of Virginia Commonwealth University and Children’s Hospital of Richmond, Va., and his colleagues from the American Thyroid Association Guidelines Task Force on Pediatric Thyroid Cancer determined based on an extensive literature search.

Together this guidance with respect to thyroid nodules represents just one of 34 recommendations contained in the guidelines, which, according to the authors, represent “the current optimal care for children and adolescents with these conditions.”

The guidelines were published in the July issue of Thyroid (2015;25:716-59).

Previous guidelines were geared toward adults, but thyroid neoplasms in children differ from those in adults with respect to pathophysiology, clinical presentation, and long-term outcomes. Further, therapy that may be appropriate in adults may not be appropriate for children at low risk for death but higher risk of long-term harm from certain treatments, they said.

For example, recent studies with long-term follow-up revealed an increase in all-cause mortality for survivors of childhood differentiated thyroid cancer (DTC), primarily caused by second malignancies in children treated with radiation.

“These observations, coupled with a better understanding of the excellent prognosis associated with pediatric DTC, have now prompted the American Thyroid Association to specifically address treatment of children with benign and malignant thyroid tumors,” they wrote.

While the task force acknowledged a paucity of randomized, double-blind, controlled clinical trials involving children with DTC, they note that “retrospective analysis of therapeutic options has led to a reconsideration of the former concept that all children with DTC should be similarly treated and has provided the opportunity ... to broaden the scope of acceptable therapy in an attempt to provide aggressive therapy when warranted and to limit overtreatment to those children who are unlikely to benefit.”

In addition to addressing the evaluation and management of thyroid nodules, the guidelines also address DTC, including preoperative staging, surgical management, postoperative staging, the role of radioactive iodine therapy, and goals for thyrotropin suppression. Management algorithms are proposed, and separate recommendations for papillary and follicular thyroid cancers are provided.

The authors note that since DTC recurrence has been reported as long as 40 years after initial therapy, children with DTC should be “followed for life, albeit with decreasing intensity for those with no evidence for disease.”

The guidelines are timely, as Surveillance, Epidemiology and End Results (SEER) program data indicate that new cases of thyroid cancer in persons under the age of 20 years represent 1.8% of all thyroid malignancies diagnosed in the United States, and that the incidence appears to be increasing.

Among 15- to 19-year old adolescents, thyroid cancer is the eighth most frequently diagnosed cancer, and it is the second most common cancer among girls, the authors said, noting that adolescents have a 10-fold greater incidence than do younger children, and that there is a female to male preponderance.

The development of pediatric-specific guidelines was critical, according to guidelines coauthor, Dr. Peter Angelos, professor of surgery and surgical ethics and chief of endocrine surgery at the University of Chicago Medicine and Biological Sciences.

“As they say, ‘children are not just small adults,’ ” he said in an interview.

In addition to the guidance provided on which types of nodules should be evaluated in children (since size alone should not be used to dictate who undergoes biopsy), a highlight of the guidelines is a recommendation that children with thyroid cancer be treated by multidisciplinary teams of physician in high-volume centers, he said.

“Thyroid cancer in children is different than in adults in that children have much higher rates of involved lymph nodes, but their overall prognosis is excellent despite the frequency of involved nodes. This confluence of findings pushes surgeons to do more aggressive operations to clear lymph nodes. This is a good thing, but unfortunately, can lead to higher complication rates (things such as permanently low calcium levels in the blood),” he said, adding that “the implications of finding a high-volume thyroid cancer surgeon with experience in thyroid cancer surgery on children are very significant and the guidelines make some recommendations about how many operations are necessary to constitute high volume.”

The push to limit the use of radioactive iodine in children further underscores the need for an experienced surgeon, he said.

“In an effort to avoid exposing children to radiation, surgeons are further pushed to be more aggressive in the operating room. Thus, it becomes even more important to see an experienced surgeon so that complications can be minimized. Even a seemingly ‘mild’ complication can be devastating for a child who will likely have to live with that complication for decades to come since the prognosis for thyroid cancer is so good,” he said.

An important potential benefit of treatment at centers with multidisciplinary interest and expertise is facilitation of additional research, particularly in areas of uncertainty, including the proper use of ¹³¹I, the interpretation of thyroglobulin (Tg) and TgAb (antibody) levels, the role of prospective ultrasound monitoring in presymptomatic children at risk for thyroid neoplasia, the use of novel targeted therapies for advanced disease that fails to respond to ¹³¹I, and the long-term psychosocial impacts of the disease on children and their families, the guideline authors said.

“These areas require well-designed long-term, multicenter studies that will be difficult to perform because of the rarity of pediatric DTC and the prolonged follow-up required to reach meaningful endpoints. Further research should be facilitated by ensuring that children with DTC are treated when possible at centers with multidisciplinary interest and expertise in this disease,” they concluded.

The guidelines were funded by the American Thyroid Association and ThyCa: Thyroid Cancer Survivors’ Association. Dr. Francis reported serving as an adviser to ThyCa and receiving research support from Grifols, Novo Nordisk, and the Juvenile Diabetes Research Foundation. Other authors reported relationships (consulting, receiving research support, and/or serving as a speaker) with Akrimax, IBSA Institut Biochimique, Pfizer, Novo Nordisk, Eli Lilly, AstraZeneca, Bayer Healthcare, Genzyme, Sobi, Henning, and Merck, and ThyCa.

[email protected]

Molecular profiling may be useful to thyroid surgeons in a variety of scenarios, but results should be interpreted with proper knowledge of cancer prevalence at the clinician’s institution, report Dr. Robert L. Ferris and coauthors of the University of Pittsburgh Cancer Institute.

A large, prospective single-center study examined seven-gene mutational panel performance, and found that for the AUS/FLUS cytologic category, mutation identification had a positive predictive value of 88% for histologic cancers, with a false-positive rate of 12%, the authors said.

©Sebastian Kaulitzki/Fotolia.com

Results from two analyses of the gene expression classifier (GEC) test emphasized the importance of cancer prevalence at the institution in interpretation of negative predictive value (NPV) and positive predictive value (PPV). In the first study, though the overall calculated sensitivity for GEC was 94%, the high malignancy rate at the institution resulted in a lower estimated NPV of 90%. The second study found an estimated sensitivity and specificity to be 83% and 10%, respectively, and decreases in estimated NPV (94%) and PPV (16%), Dr. Ferris and his colleagues reported.

“Given the well established and frequently dramatic variations in cancer prevalence in thyroid cytology specimens, clinicians are urged to be aware of the prevalence of disease by cytologic category in their tested patients and carefully consider how local disease prevalence may change PPV and NPV of molecular diagnostic tests when applied to their unique clinical practice,” the authors said in the report.

Additionally, “the use of molecular profiling in cytologic indeterminate categories should be interpreted judiciously and with discretion by the clinician, who must be aware of institutional cytopathologic performance results, as well as the individual clinical and sonographic factors for each patient,” they concluded.

Read the full article in Thyroid (doi/pdf/10.1089/thy.2014.0502).

Molecular profiling may be useful to thyroid surgeons in a variety of scenarios, but results should be interpreted with proper knowledge of cancer prevalence at the clinician’s institution, report Dr. Robert L. Ferris and coauthors of the University of Pittsburgh Cancer Institute.

A large, prospective single-center study examined seven-gene mutational panel performance, and found that for the AUS/FLUS cytologic category, mutation identification had a positive predictive value of 88% for histologic cancers, with a false-positive rate of 12%, the authors said.

©Sebastian Kaulitzki/Fotolia.com

Results from two analyses of the gene expression classifier (GEC) test emphasized the importance of cancer prevalence at the institution in interpretation of negative predictive value (NPV) and positive predictive value (PPV). In the first study, though the overall calculated sensitivity for GEC was 94%, the high malignancy rate at the institution resulted in a lower estimated NPV of 90%. The second study found an estimated sensitivity and specificity to be 83% and 10%, respectively, and decreases in estimated NPV (94%) and PPV (16%), Dr. Ferris and his colleagues reported.

“Given the well established and frequently dramatic variations in cancer prevalence in thyroid cytology specimens, clinicians are urged to be aware of the prevalence of disease by cytologic category in their tested patients and carefully consider how local disease prevalence may change PPV and NPV of molecular diagnostic tests when applied to their unique clinical practice,” the authors said in the report.

Additionally, “the use of molecular profiling in cytologic indeterminate categories should be interpreted judiciously and with discretion by the clinician, who must be aware of institutional cytopathologic performance results, as well as the individual clinical and sonographic factors for each patient,” they concluded.

Read the full article in Thyroid (doi/pdf/10.1089/thy.2014.0502).

Molecular profiling may be useful to thyroid surgeons in a variety of scenarios, but results should be interpreted with proper knowledge of cancer prevalence at the clinician’s institution, report Dr. Robert L. Ferris and coauthors of the University of Pittsburgh Cancer Institute.

A large, prospective single-center study examined seven-gene mutational panel performance, and found that for the AUS/FLUS cytologic category, mutation identification had a positive predictive value of 88% for histologic cancers, with a false-positive rate of 12%, the authors said.

©Sebastian Kaulitzki/Fotolia.com

Results from two analyses of the gene expression classifier (GEC) test emphasized the importance of cancer prevalence at the institution in interpretation of negative predictive value (NPV) and positive predictive value (PPV). In the first study, though the overall calculated sensitivity for GEC was 94%, the high malignancy rate at the institution resulted in a lower estimated NPV of 90%. The second study found an estimated sensitivity and specificity to be 83% and 10%, respectively, and decreases in estimated NPV (94%) and PPV (16%), Dr. Ferris and his colleagues reported.

“Given the well established and frequently dramatic variations in cancer prevalence in thyroid cytology specimens, clinicians are urged to be aware of the prevalence of disease by cytologic category in their tested patients and carefully consider how local disease prevalence may change PPV and NPV of molecular diagnostic tests when applied to their unique clinical practice,” the authors said in the report.

Additionally, “the use of molecular profiling in cytologic indeterminate categories should be interpreted judiciously and with discretion by the clinician, who must be aware of institutional cytopathologic performance results, as well as the individual clinical and sonographic factors for each patient,” they concluded.

Read the full article in Thyroid (doi/pdf/10.1089/thy.2014.0502).

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

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

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

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

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

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

[email protected]

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

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

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

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

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

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

[email protected]

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

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

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

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

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

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

[email protected]

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[email protected]

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

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

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

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

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

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

[email protected]

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

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

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

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

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

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

[email protected]

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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