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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
Moderate THST linked to improved survival in thyroid cancer
CORONADO, CALIF.– In an analysis of primary treatments for all stages of differentiated thyroid carcinoma, only thyroid hormone suppressive therapy was associated with both improved overall survival and disease-free survival.
Further, when examining the degree of thyroid hormone suppressive therapy (THST), aggressive THST conferred no additional survival benefit when compared with moderate THST, even when limiting the analysis to patients with distant metastatic disease, results from a long-term analysis of registry showed.
Those are key findings from an updated analysis of data from the National Thyroid Cancer Treatment Cooperative Study Group Registry, which were presented by lead study author Dr. Aubrey Carhill during the annual meeting of the American Thyroid Association.
“To date there are no prospective studies evaluating the longitudinal outcomes of initial long-term therapies in differentiated thyroid carcinoma,” said Dr. Carhill of MD Anderson Cancer Center, Houston. “In the absence of prospective trials, there has been significant reliance on retrospective studies with limited numbers of patients and low event rates as well as significant reliance on expert opinion to guide clinical practice.”
For example, current ATA guidelines for TSH suppression suggest that in long-term follow-up of patients with differentiated thyroid cancer, “those with persistent disease should have TSH levels suppressed to undetectable levels and maintained indefinitely,” Dr. Carhill said, while disease-free, higher-risk patients “should be suppressed to low-moderate levels continued between 5 and 10 years and low-risk patients should be maintained in the low-normal range. Similar levels of evidence exist to support the use of radioactive iodine and the degree of surgical extent.”
The challenge for clinicians, she continued, becomes balancing the potential risks of more aggressive therapies, such as aggressive thyroid hormone suppression, and the risks associated with long-term thyrotoxicosis with the potential benefits of treatment. “This is not always clear, especially in patients who are at very low risk for cancer-specific mortality,” she said. “There remains a need for accurate prognostication in order to identify which patients will benefit from different treatment modalities because current staging systems have limited ability to predict response to treatment.”
Formed in 1987, the National Thyroid Treatment Cooperative Study Group is a multi-institutional effort to assess long-term management of outcomes on patients with differentiated thyroid cancer. The purpose of the present study was to provide a more current analysis of the prospectively collected data, which was last analyzed in 2001. All staging is tracked according to the registry’s staging system, which is very similar to that of the American Joint Committee on Cancer’s TNM Staging System. Therapies analyzed included total/near total thyroidectomy (T/NTT) vs. a lesser extent of surgery; radioactive iodine (RAI) vs. no RAI; and increasing degrees of THST over time.
Dr. Carhill presented findings from an analysis of the effects of initial therapies in 4,941 patients treated at 11 centers in North America between 1987 and 2012. The median length of follow-up was 6 years, which translated to 34,631 person-years of documented follow-up time. The researchers used univariate and multivariate analyses to assess overall and disease-free survival. Moderate THST was defined as TSH maintained in subnormal or normal levels, while aggressive THST was defined as that maintained in undetectable or subnormal levels.
Improved overall survival was observed in stage III patients who received RAI (risk ratio, 0.66; P = .04) and in stage IV patients who received T/NTT and RAI (RR, 0.66 and 0.70, respectively; combined P = .049). Moderate but not aggressive THST was associated with significantly improved overall survival in all stages (RR, 0.13 in stage I, 0.09 in stage II, 0.13 in stage III, and 0.33 in stage IV), as well as with improved disease-free survival (RR, 0.52 in stage I, 0.40 in stage II, 0.18 in stage III, and no RR in stage IV).
In stage I patients, RAI conferred worse disease-free survival (RR, 1.79; P = .0005). “However, further propensity analysis demonstrated that there was no difference in disease-free survival when patients were stratified according to their propensity to receive radioactive iodine,” Dr. Carhill said.
To evaluate the optimal duration of THST, the researchers examined the effect of continuing degrees of suppression beyond 1, 3, and 5 years of follow-up. After 1 and 3 years of follow-up, both initial stage and moderate TSH suppression were independently predictive of improved overall survival (RR, 0.31 and 0.29, respectively). However, after 5 years of follow-up, “although initial stage remained independently predictive, there was no further benefit with any subsequent degree of TSH suppression,” Dr. Carhill said.
The study “confirms prior registry findings of a survival benefit in high-risk groups treated with T/NTT and RAI, and there is no disease-free survival benefit in low-risk groups receiving postoperative RAI,” she concluded. “We also report for the first time that in multivariate analysis of primary treatments for DTC [differentiated thyroid cancer], in all stages, only THST was associated with both improved overall survival and disease-free survival. When examining the degree of THST, aggressive THST confers no additional survival advantage as compared with moderate THST, even in patients with distant metastatic disease, which remains particularly relevant given the risks associated with long-term thyrotoxicosis.” She acknowledged certain limitations of the study, including the potential for institutional bias. “However, we feel that this is somewhat offset due to the size of the registry cohort and the number of sites involved” Dr. Carhill said.
The registry has received support from Genzyme and Pfizer. Dr. Carhill reported having no financial disclosures.
On Twitter @dougbrunk
CORONADO, CALIF.– In an analysis of primary treatments for all stages of differentiated thyroid carcinoma, only thyroid hormone suppressive therapy was associated with both improved overall survival and disease-free survival.
Further, when examining the degree of thyroid hormone suppressive therapy (THST), aggressive THST conferred no additional survival benefit when compared with moderate THST, even when limiting the analysis to patients with distant metastatic disease, results from a long-term analysis of registry showed.
Those are key findings from an updated analysis of data from the National Thyroid Cancer Treatment Cooperative Study Group Registry, which were presented by lead study author Dr. Aubrey Carhill during the annual meeting of the American Thyroid Association.
“To date there are no prospective studies evaluating the longitudinal outcomes of initial long-term therapies in differentiated thyroid carcinoma,” said Dr. Carhill of MD Anderson Cancer Center, Houston. “In the absence of prospective trials, there has been significant reliance on retrospective studies with limited numbers of patients and low event rates as well as significant reliance on expert opinion to guide clinical practice.”
For example, current ATA guidelines for TSH suppression suggest that in long-term follow-up of patients with differentiated thyroid cancer, “those with persistent disease should have TSH levels suppressed to undetectable levels and maintained indefinitely,” Dr. Carhill said, while disease-free, higher-risk patients “should be suppressed to low-moderate levels continued between 5 and 10 years and low-risk patients should be maintained in the low-normal range. Similar levels of evidence exist to support the use of radioactive iodine and the degree of surgical extent.”
The challenge for clinicians, she continued, becomes balancing the potential risks of more aggressive therapies, such as aggressive thyroid hormone suppression, and the risks associated with long-term thyrotoxicosis with the potential benefits of treatment. “This is not always clear, especially in patients who are at very low risk for cancer-specific mortality,” she said. “There remains a need for accurate prognostication in order to identify which patients will benefit from different treatment modalities because current staging systems have limited ability to predict response to treatment.”
Formed in 1987, the National Thyroid Treatment Cooperative Study Group is a multi-institutional effort to assess long-term management of outcomes on patients with differentiated thyroid cancer. The purpose of the present study was to provide a more current analysis of the prospectively collected data, which was last analyzed in 2001. All staging is tracked according to the registry’s staging system, which is very similar to that of the American Joint Committee on Cancer’s TNM Staging System. Therapies analyzed included total/near total thyroidectomy (T/NTT) vs. a lesser extent of surgery; radioactive iodine (RAI) vs. no RAI; and increasing degrees of THST over time.
Dr. Carhill presented findings from an analysis of the effects of initial therapies in 4,941 patients treated at 11 centers in North America between 1987 and 2012. The median length of follow-up was 6 years, which translated to 34,631 person-years of documented follow-up time. The researchers used univariate and multivariate analyses to assess overall and disease-free survival. Moderate THST was defined as TSH maintained in subnormal or normal levels, while aggressive THST was defined as that maintained in undetectable or subnormal levels.
Improved overall survival was observed in stage III patients who received RAI (risk ratio, 0.66; P = .04) and in stage IV patients who received T/NTT and RAI (RR, 0.66 and 0.70, respectively; combined P = .049). Moderate but not aggressive THST was associated with significantly improved overall survival in all stages (RR, 0.13 in stage I, 0.09 in stage II, 0.13 in stage III, and 0.33 in stage IV), as well as with improved disease-free survival (RR, 0.52 in stage I, 0.40 in stage II, 0.18 in stage III, and no RR in stage IV).
In stage I patients, RAI conferred worse disease-free survival (RR, 1.79; P = .0005). “However, further propensity analysis demonstrated that there was no difference in disease-free survival when patients were stratified according to their propensity to receive radioactive iodine,” Dr. Carhill said.
To evaluate the optimal duration of THST, the researchers examined the effect of continuing degrees of suppression beyond 1, 3, and 5 years of follow-up. After 1 and 3 years of follow-up, both initial stage and moderate TSH suppression were independently predictive of improved overall survival (RR, 0.31 and 0.29, respectively). However, after 5 years of follow-up, “although initial stage remained independently predictive, there was no further benefit with any subsequent degree of TSH suppression,” Dr. Carhill said.
The study “confirms prior registry findings of a survival benefit in high-risk groups treated with T/NTT and RAI, and there is no disease-free survival benefit in low-risk groups receiving postoperative RAI,” she concluded. “We also report for the first time that in multivariate analysis of primary treatments for DTC [differentiated thyroid cancer], in all stages, only THST was associated with both improved overall survival and disease-free survival. When examining the degree of THST, aggressive THST confers no additional survival advantage as compared with moderate THST, even in patients with distant metastatic disease, which remains particularly relevant given the risks associated with long-term thyrotoxicosis.” She acknowledged certain limitations of the study, including the potential for institutional bias. “However, we feel that this is somewhat offset due to the size of the registry cohort and the number of sites involved” Dr. Carhill said.
The registry has received support from Genzyme and Pfizer. Dr. Carhill reported having no financial disclosures.
On Twitter @dougbrunk
CORONADO, CALIF.– In an analysis of primary treatments for all stages of differentiated thyroid carcinoma, only thyroid hormone suppressive therapy was associated with both improved overall survival and disease-free survival.
Further, when examining the degree of thyroid hormone suppressive therapy (THST), aggressive THST conferred no additional survival benefit when compared with moderate THST, even when limiting the analysis to patients with distant metastatic disease, results from a long-term analysis of registry showed.
Those are key findings from an updated analysis of data from the National Thyroid Cancer Treatment Cooperative Study Group Registry, which were presented by lead study author Dr. Aubrey Carhill during the annual meeting of the American Thyroid Association.
“To date there are no prospective studies evaluating the longitudinal outcomes of initial long-term therapies in differentiated thyroid carcinoma,” said Dr. Carhill of MD Anderson Cancer Center, Houston. “In the absence of prospective trials, there has been significant reliance on retrospective studies with limited numbers of patients and low event rates as well as significant reliance on expert opinion to guide clinical practice.”
For example, current ATA guidelines for TSH suppression suggest that in long-term follow-up of patients with differentiated thyroid cancer, “those with persistent disease should have TSH levels suppressed to undetectable levels and maintained indefinitely,” Dr. Carhill said, while disease-free, higher-risk patients “should be suppressed to low-moderate levels continued between 5 and 10 years and low-risk patients should be maintained in the low-normal range. Similar levels of evidence exist to support the use of radioactive iodine and the degree of surgical extent.”
The challenge for clinicians, she continued, becomes balancing the potential risks of more aggressive therapies, such as aggressive thyroid hormone suppression, and the risks associated with long-term thyrotoxicosis with the potential benefits of treatment. “This is not always clear, especially in patients who are at very low risk for cancer-specific mortality,” she said. “There remains a need for accurate prognostication in order to identify which patients will benefit from different treatment modalities because current staging systems have limited ability to predict response to treatment.”
Formed in 1987, the National Thyroid Treatment Cooperative Study Group is a multi-institutional effort to assess long-term management of outcomes on patients with differentiated thyroid cancer. The purpose of the present study was to provide a more current analysis of the prospectively collected data, which was last analyzed in 2001. All staging is tracked according to the registry’s staging system, which is very similar to that of the American Joint Committee on Cancer’s TNM Staging System. Therapies analyzed included total/near total thyroidectomy (T/NTT) vs. a lesser extent of surgery; radioactive iodine (RAI) vs. no RAI; and increasing degrees of THST over time.
Dr. Carhill presented findings from an analysis of the effects of initial therapies in 4,941 patients treated at 11 centers in North America between 1987 and 2012. The median length of follow-up was 6 years, which translated to 34,631 person-years of documented follow-up time. The researchers used univariate and multivariate analyses to assess overall and disease-free survival. Moderate THST was defined as TSH maintained in subnormal or normal levels, while aggressive THST was defined as that maintained in undetectable or subnormal levels.
Improved overall survival was observed in stage III patients who received RAI (risk ratio, 0.66; P = .04) and in stage IV patients who received T/NTT and RAI (RR, 0.66 and 0.70, respectively; combined P = .049). Moderate but not aggressive THST was associated with significantly improved overall survival in all stages (RR, 0.13 in stage I, 0.09 in stage II, 0.13 in stage III, and 0.33 in stage IV), as well as with improved disease-free survival (RR, 0.52 in stage I, 0.40 in stage II, 0.18 in stage III, and no RR in stage IV).
In stage I patients, RAI conferred worse disease-free survival (RR, 1.79; P = .0005). “However, further propensity analysis demonstrated that there was no difference in disease-free survival when patients were stratified according to their propensity to receive radioactive iodine,” Dr. Carhill said.
To evaluate the optimal duration of THST, the researchers examined the effect of continuing degrees of suppression beyond 1, 3, and 5 years of follow-up. After 1 and 3 years of follow-up, both initial stage and moderate TSH suppression were independently predictive of improved overall survival (RR, 0.31 and 0.29, respectively). However, after 5 years of follow-up, “although initial stage remained independently predictive, there was no further benefit with any subsequent degree of TSH suppression,” Dr. Carhill said.
The study “confirms prior registry findings of a survival benefit in high-risk groups treated with T/NTT and RAI, and there is no disease-free survival benefit in low-risk groups receiving postoperative RAI,” she concluded. “We also report for the first time that in multivariate analysis of primary treatments for DTC [differentiated thyroid cancer], in all stages, only THST was associated with both improved overall survival and disease-free survival. When examining the degree of THST, aggressive THST confers no additional survival advantage as compared with moderate THST, even in patients with distant metastatic disease, which remains particularly relevant given the risks associated with long-term thyrotoxicosis.” She acknowledged certain limitations of the study, including the potential for institutional bias. “However, we feel that this is somewhat offset due to the size of the registry cohort and the number of sites involved” Dr. Carhill said.
The registry has received support from Genzyme and Pfizer. Dr. Carhill reported having no financial disclosures.
On Twitter @dougbrunk
AT THE ATA ANNUAL MEETING
Key clinical point: Only moderate thyroid hormone suppressive therapy is associated with better outcomes in all stages of differentiated thyroid cancer.
Major finding: Moderate, but not aggressive, THST was linked with significantly improved overall survival in all stages of differentiated thyroid cancer (RR, .13 in stage I, .09 in stage II, .13 in stage III, and .33 in stage IV).
Data source: An analysis of the effects of initial therapies in 4,941 patients from the National Thyroid Cancer Treatment Cooperative Study Group Registry who were treated at 11 centers in North America between 1987 and 2012.
Disclosures:The registry has received support from Genzyme and Pfizer. Dr. Carhill reported having no financial disclosures.
No survival benefit of RAI seen in early-stage thyroid cancer
CORONADO, CALIF. – In a large cohort of patients with differentiated thyroid cancer, the use of radioactive iodine was associated with improved disease-specific survival in those with advanced disease but not in those with papillary thyroid microcarcinoma.
“Everything in medicine is a risk-benefit balance,” lead author Dr. Ryan K. Orosco said in an interview in advance of the annual meeting of the American Thyroid Association, where the work was presented. “Any two patients that receive radioactive iodine (RAI) for differentiated thyroid cancer are likely to have different survival benefit from that therapy. This study provides a quantitative comparison of the impact of RAI in various patient subgroups.”
In one of the largest studies of its kind, Dr. Orosco of the division of head and neck surgery at the University of California, San Diego, and his associates identified 85,740 patients with differentiated thyroid carcinoma from the Surveillance, Epidemiology, and End Results database from 1973 through 2009. They used multivariate analyses to explore the association between RAI and cancer-specific survival in 149 population subgroups, controlling for age, decade of diagnosis, race, gender, tumor type, nodal involvement, metastasis stage, and RAI therapy.
More than three-quarters of the patients (78%) were female, 68% were white, their mean age at diagnosis was 46 years, and the median follow-up time was 85 months. The researchers found that nearly half of patients (43%) received RAI. By American Joint Committee on Cancer stage, RAI was used in 55% of stage I patients, 41% of stage II patients, 94% of stage III patients, and 85% of stage IV patients. In addition, 42% of patients with T1a disease and 88% of those with T4 disease received RAI.
Use of RAI was positively associated with survival in the overall cohort (hazard ratio 1.3; P = .002), while statistically significant HRs for RAI were observed in 49 population subgroups. In patients with metastatic disease, use of RAI was associated with a decreased risk for disease-specific mortality (HR range of 2.28-3.82). Protective effects of RAI were also observed in patients with regional metastases (HR 1.4-1.9), those with T3-positive tumors (HR 1.36-1.39), those with T4 tumors (HR 1.85), and in those with stage IV disease (HR 1.47-1.73).
Dr. Orosco and his associates observed a negative effect of RAI in patients with macropapillary carcinoma. Specifically, those with T1a disease had an increased likelihood of thyroid cancer–specific mortality (HR .13; P less than .001), while similar associations were seen in multiple subgroups of patients with T1a disease (HR 0.04-0.25). No statistically significant effects of RAI were observed in patients with T1b or T2 tumors.
“RAI appears to offer the best survival impact in patients with advanced differentiated thyroid carcinoma,” Dr. Orosco said. “Its use in early-stage patients should be carefully considered.”
In their abstract, the researchers noted that the findings “might help clinicians personalize RAI therapy to specific differentiated thyroid cancer populations – offering treatment in patients most likely to benefit, and sparing others unnecessary costs and potential side effects.”
Dr. Orosco acknowledged certain limitations of the study, including the fact that the SEER database does not contain details about each patient’s surgery, the dose of RAI used, other comorbidities, or data on cancer recurrence. “This study does not attempt to explore the reasons behind the apparent survival disadvantage seen in patients with T1a disease,” he said. “We don’t know exactly why early-stage patients have an increased risk of disease-specific mortality when RAI is used. Additional work is needed to explore this further.”
Dr. Orosco reported having no financial disclosures.
On Twitter @dougbrunk
CORONADO, CALIF. – In a large cohort of patients with differentiated thyroid cancer, the use of radioactive iodine was associated with improved disease-specific survival in those with advanced disease but not in those with papillary thyroid microcarcinoma.
“Everything in medicine is a risk-benefit balance,” lead author Dr. Ryan K. Orosco said in an interview in advance of the annual meeting of the American Thyroid Association, where the work was presented. “Any two patients that receive radioactive iodine (RAI) for differentiated thyroid cancer are likely to have different survival benefit from that therapy. This study provides a quantitative comparison of the impact of RAI in various patient subgroups.”
In one of the largest studies of its kind, Dr. Orosco of the division of head and neck surgery at the University of California, San Diego, and his associates identified 85,740 patients with differentiated thyroid carcinoma from the Surveillance, Epidemiology, and End Results database from 1973 through 2009. They used multivariate analyses to explore the association between RAI and cancer-specific survival in 149 population subgroups, controlling for age, decade of diagnosis, race, gender, tumor type, nodal involvement, metastasis stage, and RAI therapy.
More than three-quarters of the patients (78%) were female, 68% were white, their mean age at diagnosis was 46 years, and the median follow-up time was 85 months. The researchers found that nearly half of patients (43%) received RAI. By American Joint Committee on Cancer stage, RAI was used in 55% of stage I patients, 41% of stage II patients, 94% of stage III patients, and 85% of stage IV patients. In addition, 42% of patients with T1a disease and 88% of those with T4 disease received RAI.
Use of RAI was positively associated with survival in the overall cohort (hazard ratio 1.3; P = .002), while statistically significant HRs for RAI were observed in 49 population subgroups. In patients with metastatic disease, use of RAI was associated with a decreased risk for disease-specific mortality (HR range of 2.28-3.82). Protective effects of RAI were also observed in patients with regional metastases (HR 1.4-1.9), those with T3-positive tumors (HR 1.36-1.39), those with T4 tumors (HR 1.85), and in those with stage IV disease (HR 1.47-1.73).
Dr. Orosco and his associates observed a negative effect of RAI in patients with macropapillary carcinoma. Specifically, those with T1a disease had an increased likelihood of thyroid cancer–specific mortality (HR .13; P less than .001), while similar associations were seen in multiple subgroups of patients with T1a disease (HR 0.04-0.25). No statistically significant effects of RAI were observed in patients with T1b or T2 tumors.
“RAI appears to offer the best survival impact in patients with advanced differentiated thyroid carcinoma,” Dr. Orosco said. “Its use in early-stage patients should be carefully considered.”
In their abstract, the researchers noted that the findings “might help clinicians personalize RAI therapy to specific differentiated thyroid cancer populations – offering treatment in patients most likely to benefit, and sparing others unnecessary costs and potential side effects.”
Dr. Orosco acknowledged certain limitations of the study, including the fact that the SEER database does not contain details about each patient’s surgery, the dose of RAI used, other comorbidities, or data on cancer recurrence. “This study does not attempt to explore the reasons behind the apparent survival disadvantage seen in patients with T1a disease,” he said. “We don’t know exactly why early-stage patients have an increased risk of disease-specific mortality when RAI is used. Additional work is needed to explore this further.”
Dr. Orosco reported having no financial disclosures.
On Twitter @dougbrunk
CORONADO, CALIF. – In a large cohort of patients with differentiated thyroid cancer, the use of radioactive iodine was associated with improved disease-specific survival in those with advanced disease but not in those with papillary thyroid microcarcinoma.
“Everything in medicine is a risk-benefit balance,” lead author Dr. Ryan K. Orosco said in an interview in advance of the annual meeting of the American Thyroid Association, where the work was presented. “Any two patients that receive radioactive iodine (RAI) for differentiated thyroid cancer are likely to have different survival benefit from that therapy. This study provides a quantitative comparison of the impact of RAI in various patient subgroups.”
In one of the largest studies of its kind, Dr. Orosco of the division of head and neck surgery at the University of California, San Diego, and his associates identified 85,740 patients with differentiated thyroid carcinoma from the Surveillance, Epidemiology, and End Results database from 1973 through 2009. They used multivariate analyses to explore the association between RAI and cancer-specific survival in 149 population subgroups, controlling for age, decade of diagnosis, race, gender, tumor type, nodal involvement, metastasis stage, and RAI therapy.
More than three-quarters of the patients (78%) were female, 68% were white, their mean age at diagnosis was 46 years, and the median follow-up time was 85 months. The researchers found that nearly half of patients (43%) received RAI. By American Joint Committee on Cancer stage, RAI was used in 55% of stage I patients, 41% of stage II patients, 94% of stage III patients, and 85% of stage IV patients. In addition, 42% of patients with T1a disease and 88% of those with T4 disease received RAI.
Use of RAI was positively associated with survival in the overall cohort (hazard ratio 1.3; P = .002), while statistically significant HRs for RAI were observed in 49 population subgroups. In patients with metastatic disease, use of RAI was associated with a decreased risk for disease-specific mortality (HR range of 2.28-3.82). Protective effects of RAI were also observed in patients with regional metastases (HR 1.4-1.9), those with T3-positive tumors (HR 1.36-1.39), those with T4 tumors (HR 1.85), and in those with stage IV disease (HR 1.47-1.73).
Dr. Orosco and his associates observed a negative effect of RAI in patients with macropapillary carcinoma. Specifically, those with T1a disease had an increased likelihood of thyroid cancer–specific mortality (HR .13; P less than .001), while similar associations were seen in multiple subgroups of patients with T1a disease (HR 0.04-0.25). No statistically significant effects of RAI were observed in patients with T1b or T2 tumors.
“RAI appears to offer the best survival impact in patients with advanced differentiated thyroid carcinoma,” Dr. Orosco said. “Its use in early-stage patients should be carefully considered.”
In their abstract, the researchers noted that the findings “might help clinicians personalize RAI therapy to specific differentiated thyroid cancer populations – offering treatment in patients most likely to benefit, and sparing others unnecessary costs and potential side effects.”
Dr. Orosco acknowledged certain limitations of the study, including the fact that the SEER database does not contain details about each patient’s surgery, the dose of RAI used, other comorbidities, or data on cancer recurrence. “This study does not attempt to explore the reasons behind the apparent survival disadvantage seen in patients with T1a disease,” he said. “We don’t know exactly why early-stage patients have an increased risk of disease-specific mortality when RAI is used. Additional work is needed to explore this further.”
Dr. Orosco reported having no financial disclosures.
On Twitter @dougbrunk
AT THE ATA ANNUAL MEETING
Key clinical point: Radioactive iodine appears to offer the best survival impact in patients with advanced differentiated thyroid carcinoma.
Major finding: In patients with metastatic disease, use of RAI was associated with a decreased risk for disease-specific mortality (HR range of 2.28-3.82). However, those with T1a disease had an increased likelihood of thyroid cancer-specific mortality (HR .13; P less than .001), while similar associations were seen in multiple subgroups of patients with T1a disease (HR .04-.25).
Data source: An analysis of 85,740 patients with differentiated thyroid carcinoma from the Surveillance, Epidemiology, and End Results database from 1973 through 2009.
Disclosures: Dr. Orosco reported having no financial disclosures.
Anticoagulants sharply increase hematoma risk after thyroid, parathyroid surgery
SAN FRANCISCO – Patients undergoing thyroid or parathyroid surgery have a sharply higher risk of postoperative hematoma if they are on clopidogrel or anticoagulants – even if these agents are stopped in advance – researchers reported at the annual clinical congress of the American College of Surgeons.
“Patients with multiple factors considered high risk for postoperative hematoma formation after parathyroid or thyroid surgery should probably undergo a period of observation,” recommended lead investigator Dr. Sarah C. Oltmann, who at the time of the study was the director of endocrine surgery at Parkland Memorial Hospital, University of Texas Southwestern Medical Center, Dallas.
“The need specifically for anticoagulation in the perioperative period should really be carefully assessed, and decisions regarding their use in the perioperative period need to be made very cautiously,” she added. “This is particularly important when considering the need for an injectable bridge [anticoagulant], and discussions with the patient’s primary care provider or cardiologist should be prompted because obviously a hematoma risk of 11% [seen with injectable anticoagulants] is not insignificant.”
The researchers retrospectively studied 4,514 patients who underwent thyroid or parathyroid surgery at the center between 1994 and 2013. Most of the operations were performed by high-volume surgeons.
Overall, 25% of patients were using an antiplatelet agent and 3% were using an anticoagulant agent, defined in the study as current use or use up to 5-7 days before surgery. “We felt that there may be some alteration of hemostasis both at the time of surgery and in the days following surgery if they were resumed on their home meds,” explained Dr. Oltmann, who is now a clinical instructor of surgery at the University of Wisconsin–Madison.
Overall, 0.5% of patients developed a postoperative hematoma, with the majority of these events occurring in the first 24 hours. Three-fourths of the affected patients had to undergo repeat surgery.
In multivariate analyses, clopidogrel (Plavix) users had 5.6 times the odds of developing a hematoma. But neither lower-dose aspirin (less than 325 mg daily) alone nor higher-dose aspirin alone was associated with this complication.
Hematoma odds were elevated by an even greater extent, 7.5 and 29.5 times, for patients using oral and injectable anticoagulants, respectively. (Subcutaneous heparin was not included among injectable anticoagulants because surgeons at the center seldom use it in this setting, according to Dr. Oltmann.)
Patients also had increased odds of hematoma if they underwent thyroid surgery as compared with parathyroid surgery (odds ratio, 7.9), and had a bilateral procedure as compared with a unilateral one (OR, 4.9).
“Additional studies are needed to better clarify both the risk-benefit ratio of injectable anticoagulation in this patient population and potentially being able to better risk-stratify which patients would be better served with a period of overnight observation,” Dr. Oltmann concluded.
Invited discussant Dr. Raymon H. Grogan, director of the endocrine surgery research program at University of Chicago Medicine, commented, “I think this work represents a level of detail and granularity in regard to anticoagulants that we haven’t seen before in this literature, so it’s really important for us to see these data.
“We tend to get lulled into a false sense of security when we talk about complications related to thyroidectomy because they are so rare. But the truth of the matter is that this is a complication that causes deaths. A recent Nationwide Inpatient Sample study showed that about 1.3% of people who developed a hematoma will actually die in the United States, which is not an insignificant number of people who will die from a complication that’s directly caused by something we’ve done as surgeons,” he said.
Patients often have other risk factors for hematoma, Dr. Grogan noted. Therefore, he wondered, “Who can actually be sent home as a same-day patient after thyroidectomy? … When you combine your … people on these medications, along with all these other risk factors, as well as the risk of significant hypocalcemia postop, it starts to get to the point where, is it really safe to send anyone home the same day after thyroidectomy, given this overwhelming number of different factors that could cause problems?”
“That’s something we all struggle with to a certain degree, trying to be able to best determine who is safe to go home at night and who is not,” Dr. Oltmann replied, noting that risk in the study was greatest for the small proportion of patients on anticoagulants. “So I think a patient who is on some form of anticoagulant, I would definitely have significant reservations about sending home on the same day. They would be somebody I would at least want to keep overnight.”
“As far as the other variables – Graves disease, the size of the tumor, some people would also argue smoking and poorly controlled hypertension – it really becomes a conversation between the surgeon and the patient to know how reliable is the patient, how do you feel the operation went. … Hopefully, the next step is being able to find a way to weigh these different factors to be able to figure out, well, if my patient has A, B, and C, I must observe versus if they don’t, this might be somebody I can send home.”
Another attendee asked, “How do you [handle] aspirin use, given that it’s low risk as seen in your data set? How do you preop the patients, [do you] ask them to stop any low-risk agents, such as aspirin, or if they take the combination of aspirin and Plavix, which one do you hold and which do you continue in your practice?”
“After kind of combing through this data and becoming very familiar with it, I feel very comfortable with continuing aspirin use through the perioperative period,” Dr. Oltmann commented.
“For Plavix, obviously, you just have to juggle the risk-benefit ratio of why they are on that medication,” she said. “I think the most compelling situation is for our patients with atrial fibrillation, with the primary care provider wanting to … have them done on a Lovenox [enoxaparin] bridge, and now having some sort of objective data to get back with them and say, ‘Listen, they have an 11% risk of this really bad complication. Do you really think their risk of stroke trumps that?’ In most patients, that’s not the case, and I think [these data are] finally going to be able to give us some ammunition in that particular battle.”
Dr. Oltmann disclosed that she had no relevant conflicts of interest.
SAN FRANCISCO – Patients undergoing thyroid or parathyroid surgery have a sharply higher risk of postoperative hematoma if they are on clopidogrel or anticoagulants – even if these agents are stopped in advance – researchers reported at the annual clinical congress of the American College of Surgeons.
“Patients with multiple factors considered high risk for postoperative hematoma formation after parathyroid or thyroid surgery should probably undergo a period of observation,” recommended lead investigator Dr. Sarah C. Oltmann, who at the time of the study was the director of endocrine surgery at Parkland Memorial Hospital, University of Texas Southwestern Medical Center, Dallas.
“The need specifically for anticoagulation in the perioperative period should really be carefully assessed, and decisions regarding their use in the perioperative period need to be made very cautiously,” she added. “This is particularly important when considering the need for an injectable bridge [anticoagulant], and discussions with the patient’s primary care provider or cardiologist should be prompted because obviously a hematoma risk of 11% [seen with injectable anticoagulants] is not insignificant.”
The researchers retrospectively studied 4,514 patients who underwent thyroid or parathyroid surgery at the center between 1994 and 2013. Most of the operations were performed by high-volume surgeons.
Overall, 25% of patients were using an antiplatelet agent and 3% were using an anticoagulant agent, defined in the study as current use or use up to 5-7 days before surgery. “We felt that there may be some alteration of hemostasis both at the time of surgery and in the days following surgery if they were resumed on their home meds,” explained Dr. Oltmann, who is now a clinical instructor of surgery at the University of Wisconsin–Madison.
Overall, 0.5% of patients developed a postoperative hematoma, with the majority of these events occurring in the first 24 hours. Three-fourths of the affected patients had to undergo repeat surgery.
In multivariate analyses, clopidogrel (Plavix) users had 5.6 times the odds of developing a hematoma. But neither lower-dose aspirin (less than 325 mg daily) alone nor higher-dose aspirin alone was associated with this complication.
Hematoma odds were elevated by an even greater extent, 7.5 and 29.5 times, for patients using oral and injectable anticoagulants, respectively. (Subcutaneous heparin was not included among injectable anticoagulants because surgeons at the center seldom use it in this setting, according to Dr. Oltmann.)
Patients also had increased odds of hematoma if they underwent thyroid surgery as compared with parathyroid surgery (odds ratio, 7.9), and had a bilateral procedure as compared with a unilateral one (OR, 4.9).
“Additional studies are needed to better clarify both the risk-benefit ratio of injectable anticoagulation in this patient population and potentially being able to better risk-stratify which patients would be better served with a period of overnight observation,” Dr. Oltmann concluded.
Invited discussant Dr. Raymon H. Grogan, director of the endocrine surgery research program at University of Chicago Medicine, commented, “I think this work represents a level of detail and granularity in regard to anticoagulants that we haven’t seen before in this literature, so it’s really important for us to see these data.
“We tend to get lulled into a false sense of security when we talk about complications related to thyroidectomy because they are so rare. But the truth of the matter is that this is a complication that causes deaths. A recent Nationwide Inpatient Sample study showed that about 1.3% of people who developed a hematoma will actually die in the United States, which is not an insignificant number of people who will die from a complication that’s directly caused by something we’ve done as surgeons,” he said.
Patients often have other risk factors for hematoma, Dr. Grogan noted. Therefore, he wondered, “Who can actually be sent home as a same-day patient after thyroidectomy? … When you combine your … people on these medications, along with all these other risk factors, as well as the risk of significant hypocalcemia postop, it starts to get to the point where, is it really safe to send anyone home the same day after thyroidectomy, given this overwhelming number of different factors that could cause problems?”
“That’s something we all struggle with to a certain degree, trying to be able to best determine who is safe to go home at night and who is not,” Dr. Oltmann replied, noting that risk in the study was greatest for the small proportion of patients on anticoagulants. “So I think a patient who is on some form of anticoagulant, I would definitely have significant reservations about sending home on the same day. They would be somebody I would at least want to keep overnight.”
“As far as the other variables – Graves disease, the size of the tumor, some people would also argue smoking and poorly controlled hypertension – it really becomes a conversation between the surgeon and the patient to know how reliable is the patient, how do you feel the operation went. … Hopefully, the next step is being able to find a way to weigh these different factors to be able to figure out, well, if my patient has A, B, and C, I must observe versus if they don’t, this might be somebody I can send home.”
Another attendee asked, “How do you [handle] aspirin use, given that it’s low risk as seen in your data set? How do you preop the patients, [do you] ask them to stop any low-risk agents, such as aspirin, or if they take the combination of aspirin and Plavix, which one do you hold and which do you continue in your practice?”
“After kind of combing through this data and becoming very familiar with it, I feel very comfortable with continuing aspirin use through the perioperative period,” Dr. Oltmann commented.
“For Plavix, obviously, you just have to juggle the risk-benefit ratio of why they are on that medication,” she said. “I think the most compelling situation is for our patients with atrial fibrillation, with the primary care provider wanting to … have them done on a Lovenox [enoxaparin] bridge, and now having some sort of objective data to get back with them and say, ‘Listen, they have an 11% risk of this really bad complication. Do you really think their risk of stroke trumps that?’ In most patients, that’s not the case, and I think [these data are] finally going to be able to give us some ammunition in that particular battle.”
Dr. Oltmann disclosed that she had no relevant conflicts of interest.
SAN FRANCISCO – Patients undergoing thyroid or parathyroid surgery have a sharply higher risk of postoperative hematoma if they are on clopidogrel or anticoagulants – even if these agents are stopped in advance – researchers reported at the annual clinical congress of the American College of Surgeons.
“Patients with multiple factors considered high risk for postoperative hematoma formation after parathyroid or thyroid surgery should probably undergo a period of observation,” recommended lead investigator Dr. Sarah C. Oltmann, who at the time of the study was the director of endocrine surgery at Parkland Memorial Hospital, University of Texas Southwestern Medical Center, Dallas.
“The need specifically for anticoagulation in the perioperative period should really be carefully assessed, and decisions regarding their use in the perioperative period need to be made very cautiously,” she added. “This is particularly important when considering the need for an injectable bridge [anticoagulant], and discussions with the patient’s primary care provider or cardiologist should be prompted because obviously a hematoma risk of 11% [seen with injectable anticoagulants] is not insignificant.”
The researchers retrospectively studied 4,514 patients who underwent thyroid or parathyroid surgery at the center between 1994 and 2013. Most of the operations were performed by high-volume surgeons.
Overall, 25% of patients were using an antiplatelet agent and 3% were using an anticoagulant agent, defined in the study as current use or use up to 5-7 days before surgery. “We felt that there may be some alteration of hemostasis both at the time of surgery and in the days following surgery if they were resumed on their home meds,” explained Dr. Oltmann, who is now a clinical instructor of surgery at the University of Wisconsin–Madison.
Overall, 0.5% of patients developed a postoperative hematoma, with the majority of these events occurring in the first 24 hours. Three-fourths of the affected patients had to undergo repeat surgery.
In multivariate analyses, clopidogrel (Plavix) users had 5.6 times the odds of developing a hematoma. But neither lower-dose aspirin (less than 325 mg daily) alone nor higher-dose aspirin alone was associated with this complication.
Hematoma odds were elevated by an even greater extent, 7.5 and 29.5 times, for patients using oral and injectable anticoagulants, respectively. (Subcutaneous heparin was not included among injectable anticoagulants because surgeons at the center seldom use it in this setting, according to Dr. Oltmann.)
Patients also had increased odds of hematoma if they underwent thyroid surgery as compared with parathyroid surgery (odds ratio, 7.9), and had a bilateral procedure as compared with a unilateral one (OR, 4.9).
“Additional studies are needed to better clarify both the risk-benefit ratio of injectable anticoagulation in this patient population and potentially being able to better risk-stratify which patients would be better served with a period of overnight observation,” Dr. Oltmann concluded.
Invited discussant Dr. Raymon H. Grogan, director of the endocrine surgery research program at University of Chicago Medicine, commented, “I think this work represents a level of detail and granularity in regard to anticoagulants that we haven’t seen before in this literature, so it’s really important for us to see these data.
“We tend to get lulled into a false sense of security when we talk about complications related to thyroidectomy because they are so rare. But the truth of the matter is that this is a complication that causes deaths. A recent Nationwide Inpatient Sample study showed that about 1.3% of people who developed a hematoma will actually die in the United States, which is not an insignificant number of people who will die from a complication that’s directly caused by something we’ve done as surgeons,” he said.
Patients often have other risk factors for hematoma, Dr. Grogan noted. Therefore, he wondered, “Who can actually be sent home as a same-day patient after thyroidectomy? … When you combine your … people on these medications, along with all these other risk factors, as well as the risk of significant hypocalcemia postop, it starts to get to the point where, is it really safe to send anyone home the same day after thyroidectomy, given this overwhelming number of different factors that could cause problems?”
“That’s something we all struggle with to a certain degree, trying to be able to best determine who is safe to go home at night and who is not,” Dr. Oltmann replied, noting that risk in the study was greatest for the small proportion of patients on anticoagulants. “So I think a patient who is on some form of anticoagulant, I would definitely have significant reservations about sending home on the same day. They would be somebody I would at least want to keep overnight.”
“As far as the other variables – Graves disease, the size of the tumor, some people would also argue smoking and poorly controlled hypertension – it really becomes a conversation between the surgeon and the patient to know how reliable is the patient, how do you feel the operation went. … Hopefully, the next step is being able to find a way to weigh these different factors to be able to figure out, well, if my patient has A, B, and C, I must observe versus if they don’t, this might be somebody I can send home.”
Another attendee asked, “How do you [handle] aspirin use, given that it’s low risk as seen in your data set? How do you preop the patients, [do you] ask them to stop any low-risk agents, such as aspirin, or if they take the combination of aspirin and Plavix, which one do you hold and which do you continue in your practice?”
“After kind of combing through this data and becoming very familiar with it, I feel very comfortable with continuing aspirin use through the perioperative period,” Dr. Oltmann commented.
“For Plavix, obviously, you just have to juggle the risk-benefit ratio of why they are on that medication,” she said. “I think the most compelling situation is for our patients with atrial fibrillation, with the primary care provider wanting to … have them done on a Lovenox [enoxaparin] bridge, and now having some sort of objective data to get back with them and say, ‘Listen, they have an 11% risk of this really bad complication. Do you really think their risk of stroke trumps that?’ In most patients, that’s not the case, and I think [these data are] finally going to be able to give us some ammunition in that particular battle.”
Dr. Oltmann disclosed that she had no relevant conflicts of interest.
AT THE ACS CLINICAL CONGRESS
Key clinical point: Clopidogrel and anticoagulants are risk factors for hematoma after thyroid or parathyroid surgery.
Major finding: The odds of hematoma were 5.6 times higher with clopidogrel use and 7.5 and 29.5 times higher with oral and injectable anticoagulant use, respectively.
Data source: A retrospective study of 4,514 patients undergoing thyroid or parathyroid surgery.
Disclosures: Dr. Oltmann disclosed that she had no relevant conflicts of interest.
Tests pinpoint primary sources of neuroendocrine bowel, pancreatic metastases
BOSTON – With a little chemical or genetic snooping, or both, clinicians may be able to pinpoint the source of nearly all metastatic neuroendocrine tumors of the small bowel or pancreas.
By looking at expression patterns of four genes, investigators were able to determine that a surgically obtained metastatic neuroendocrine tumor (NET) originated in the small bowel with more than 96% accuracy, and, with the use of an immunohistochemistry algorithm, they identified the pancreas as the primary source of metastases in 10 of 10 cases.
"All the NETs that were misclassified by one method were correctly identified by the other method," said Dr. Jessica Maxwell of the department of surgery at the University of Iowa Hospitals and Clinics in Iowa City.
In about 15%-20% of cases of metastatic NETs, the primary tumor site is unknown, but is most likely to be in the small bowel or pancreas. Failure to identify the primary tumor site, despite optimal work-up, could delay referral for surgery or complicate choice of systemic medical therapies, she said at the annual meeting of the American Association of Endocrine Surgeons.
The authors tested the mettle of immunohistochemistry and gene expression classification (GEC) methods on 136 metastatic NETs collected intraoperatively from 97 patients with small-bowel NETs (38 with metastases to liver and 59 with metastases to lymph nodes) and 39 with pancreatic NETs (17 liver and 22 lymph node metastases).
The GEC uses quantitative or "real-time" polymerase chain reaction (qPCR) to evaluate expression of four key genes, encoding for the secretin receptor (SCTR), oxytocin receptor (OXTR), bombesin-like receptor-3 (BRS3), and opioid receptor kappa-1 (OPRK1).
The differential patterns of gene expression mark the metastases as originating either in the pancreas or small bowel.
They also tested a two-tiered immunohistochemistry algorithm using the markers CDX2, PAX6, and ISLET1 for tier 1, and PrAP, PRm NESP55, and PDX1 in tier 2. They tested the algorithm on six primary tumors and validated their findings on 37 metastases.
The immunohistochemistry method can identify a primary tumor site with as few as three markers, but if the findings are indeterminate, the addition of the four tier 2 markers can help to nail down the tumor site, Dr. Maxwell said.
They found that the GEC accurately identified 94 of 97 small bowel NETs (96.9%), and 34 of 39 pancreatic NETS (87.2%).
In contrast, the immunohistochemistry algorithm correctly identified the primary site in 23 of 27 small bowel metastases (85.2%), and in 10 of 10 (100%) pancreatic metastases.
When the methods were compared head to head in 27 metastases, GEC had a 96.2% overall accuracy and immunohistochemistry an 85.2% accuracy.
As noted before, the methods were complementary, with all NETs misclassified by one method called accurately by the other.
The investigators suggest that because the methods are highly accurate and complementary, they may best be used sequentially, starting with immunohistochemistry which is both inexpensive and widely available, and if immunohistochemistry fails, moving on to GEC.
"Sequential use allows for identification of nearly all metastatic neuroendocrine tumors from small bowel or pancreatic sites," Dr. Maxwell said.
In the discussion, Dr. Eren Berber of the Center for Endocrine Surgery at the Cleveland Clinic, who was not involved in the study, questioned whether knowing the primary site had any practical implications for surgeons.
Dr. Maxwell noted that some pancreatic NETs are not detected by preoperative studies and that given the risks of pancreatectomy or pancreaticoduodenectomy, accurately identifying the source of an NET may be helpful for patient counseling and preoperative planning.
The study was supported by a grant from the National Institutes of Health. Dr. Maxwell and Dr. Berber reported having no financial disclosures.
BOSTON – With a little chemical or genetic snooping, or both, clinicians may be able to pinpoint the source of nearly all metastatic neuroendocrine tumors of the small bowel or pancreas.
By looking at expression patterns of four genes, investigators were able to determine that a surgically obtained metastatic neuroendocrine tumor (NET) originated in the small bowel with more than 96% accuracy, and, with the use of an immunohistochemistry algorithm, they identified the pancreas as the primary source of metastases in 10 of 10 cases.
"All the NETs that were misclassified by one method were correctly identified by the other method," said Dr. Jessica Maxwell of the department of surgery at the University of Iowa Hospitals and Clinics in Iowa City.
In about 15%-20% of cases of metastatic NETs, the primary tumor site is unknown, but is most likely to be in the small bowel or pancreas. Failure to identify the primary tumor site, despite optimal work-up, could delay referral for surgery or complicate choice of systemic medical therapies, she said at the annual meeting of the American Association of Endocrine Surgeons.
The authors tested the mettle of immunohistochemistry and gene expression classification (GEC) methods on 136 metastatic NETs collected intraoperatively from 97 patients with small-bowel NETs (38 with metastases to liver and 59 with metastases to lymph nodes) and 39 with pancreatic NETs (17 liver and 22 lymph node metastases).
The GEC uses quantitative or "real-time" polymerase chain reaction (qPCR) to evaluate expression of four key genes, encoding for the secretin receptor (SCTR), oxytocin receptor (OXTR), bombesin-like receptor-3 (BRS3), and opioid receptor kappa-1 (OPRK1).
The differential patterns of gene expression mark the metastases as originating either in the pancreas or small bowel.
They also tested a two-tiered immunohistochemistry algorithm using the markers CDX2, PAX6, and ISLET1 for tier 1, and PrAP, PRm NESP55, and PDX1 in tier 2. They tested the algorithm on six primary tumors and validated their findings on 37 metastases.
The immunohistochemistry method can identify a primary tumor site with as few as three markers, but if the findings are indeterminate, the addition of the four tier 2 markers can help to nail down the tumor site, Dr. Maxwell said.
They found that the GEC accurately identified 94 of 97 small bowel NETs (96.9%), and 34 of 39 pancreatic NETS (87.2%).
In contrast, the immunohistochemistry algorithm correctly identified the primary site in 23 of 27 small bowel metastases (85.2%), and in 10 of 10 (100%) pancreatic metastases.
When the methods were compared head to head in 27 metastases, GEC had a 96.2% overall accuracy and immunohistochemistry an 85.2% accuracy.
As noted before, the methods were complementary, with all NETs misclassified by one method called accurately by the other.
The investigators suggest that because the methods are highly accurate and complementary, they may best be used sequentially, starting with immunohistochemistry which is both inexpensive and widely available, and if immunohistochemistry fails, moving on to GEC.
"Sequential use allows for identification of nearly all metastatic neuroendocrine tumors from small bowel or pancreatic sites," Dr. Maxwell said.
In the discussion, Dr. Eren Berber of the Center for Endocrine Surgery at the Cleveland Clinic, who was not involved in the study, questioned whether knowing the primary site had any practical implications for surgeons.
Dr. Maxwell noted that some pancreatic NETs are not detected by preoperative studies and that given the risks of pancreatectomy or pancreaticoduodenectomy, accurately identifying the source of an NET may be helpful for patient counseling and preoperative planning.
The study was supported by a grant from the National Institutes of Health. Dr. Maxwell and Dr. Berber reported having no financial disclosures.
BOSTON – With a little chemical or genetic snooping, or both, clinicians may be able to pinpoint the source of nearly all metastatic neuroendocrine tumors of the small bowel or pancreas.
By looking at expression patterns of four genes, investigators were able to determine that a surgically obtained metastatic neuroendocrine tumor (NET) originated in the small bowel with more than 96% accuracy, and, with the use of an immunohistochemistry algorithm, they identified the pancreas as the primary source of metastases in 10 of 10 cases.
"All the NETs that were misclassified by one method were correctly identified by the other method," said Dr. Jessica Maxwell of the department of surgery at the University of Iowa Hospitals and Clinics in Iowa City.
In about 15%-20% of cases of metastatic NETs, the primary tumor site is unknown, but is most likely to be in the small bowel or pancreas. Failure to identify the primary tumor site, despite optimal work-up, could delay referral for surgery or complicate choice of systemic medical therapies, she said at the annual meeting of the American Association of Endocrine Surgeons.
The authors tested the mettle of immunohistochemistry and gene expression classification (GEC) methods on 136 metastatic NETs collected intraoperatively from 97 patients with small-bowel NETs (38 with metastases to liver and 59 with metastases to lymph nodes) and 39 with pancreatic NETs (17 liver and 22 lymph node metastases).
The GEC uses quantitative or "real-time" polymerase chain reaction (qPCR) to evaluate expression of four key genes, encoding for the secretin receptor (SCTR), oxytocin receptor (OXTR), bombesin-like receptor-3 (BRS3), and opioid receptor kappa-1 (OPRK1).
The differential patterns of gene expression mark the metastases as originating either in the pancreas or small bowel.
They also tested a two-tiered immunohistochemistry algorithm using the markers CDX2, PAX6, and ISLET1 for tier 1, and PrAP, PRm NESP55, and PDX1 in tier 2. They tested the algorithm on six primary tumors and validated their findings on 37 metastases.
The immunohistochemistry method can identify a primary tumor site with as few as three markers, but if the findings are indeterminate, the addition of the four tier 2 markers can help to nail down the tumor site, Dr. Maxwell said.
They found that the GEC accurately identified 94 of 97 small bowel NETs (96.9%), and 34 of 39 pancreatic NETS (87.2%).
In contrast, the immunohistochemistry algorithm correctly identified the primary site in 23 of 27 small bowel metastases (85.2%), and in 10 of 10 (100%) pancreatic metastases.
When the methods were compared head to head in 27 metastases, GEC had a 96.2% overall accuracy and immunohistochemistry an 85.2% accuracy.
As noted before, the methods were complementary, with all NETs misclassified by one method called accurately by the other.
The investigators suggest that because the methods are highly accurate and complementary, they may best be used sequentially, starting with immunohistochemistry which is both inexpensive and widely available, and if immunohistochemistry fails, moving on to GEC.
"Sequential use allows for identification of nearly all metastatic neuroendocrine tumors from small bowel or pancreatic sites," Dr. Maxwell said.
In the discussion, Dr. Eren Berber of the Center for Endocrine Surgery at the Cleveland Clinic, who was not involved in the study, questioned whether knowing the primary site had any practical implications for surgeons.
Dr. Maxwell noted that some pancreatic NETs are not detected by preoperative studies and that given the risks of pancreatectomy or pancreaticoduodenectomy, accurately identifying the source of an NET may be helpful for patient counseling and preoperative planning.
The study was supported by a grant from the National Institutes of Health. Dr. Maxwell and Dr. Berber reported having no financial disclosures.
AT AAES 2014
Key clinical point: Gene expression can be used to identify the primary source of neuroendocrine small bowel and pancreatic metastases.
Major finding: Gene expression classification accurately identified the primary source of 94 of 97 small bowel neuroendocrine tumor metastases, (96.9%), and 34 of 39 pancreatic metastases (87.2%).
Data source: Retrospective single institution study of metastases from 136 patients with neuroendocrine tumors.
Disclosures: The study was supported by a grant from the National Institutes of Health. Dr. Maxwell and Dr. Berber reported having no financial disclosures.
Experimental lenvatinib extends PFS in iodine-refractory relapsed thyroid cancer
CHICAGO – The investigational drug lenvatinib significantly prolonged progression-free survival and produced high response rates compared with placebo in patients with iodine-refractory differentiated thyroid cancer.
In a randomized trial, the median progression-free survival (PFS) among patients assigned to lenvatinib was 18.3 months, compared with 3.6 months for placebo. The hazard ratio for lenvatinib was 0.21 (P less than .0001), Dr. Martin Schlumberger reported at the annual meeting of the American Society of Clinical Oncology.
"We had a high objective response rate – about 65% – with some complete responses. Interestingly, the time to objective response was only 2 months, so responses occur very quickly after the first treatment," Dr. Schlumberger, a professor of oncology at the University Paris-Sud, France, said at a media briefing prior to his presentation of the data in a plenary session.
"It’s really rewarding to see another active drug in this disease, where a year ago we really had no active therapy," commented Dr. Gregory A. Masters from the Helen F. Graham Cancer Center in Newark, Delaware.
Dr. Masters moderated the briefing but was not involved in the study.
Patients with relapsed or refractory differentiated thyroid cancer that is resistant to treatment with iodine-131 (131I) have few treatment choices and a 10-year survival rate of just 10%, Dr. Schlumberger noted.
There is evidence, however, showing that vascular endothelial growth factor (VEGF) signaling is associated with aggressive thyroid cancer and its propensity for metastasis, prompting researchers to explore VEGF-receptor inhibitors.
Lenvatinib is an oral multi–tyrosine kinase inhibitor of VEGF receptors 1-3, fibroblast growth factor receptors 1-4, platelet-derived growth factor receptor–alpha, and the RET and KIT kinases.
In a phase II study, the drug showed clinical activity against 131I-refractory differentiated thyroid cancer, prompting investigators to launch the phase III SELECT trial (Study of E7080 Lenvatinib in Differentiated Cancer of the Thyroid) in this population.
They enrolled 392 patients with measurable disease and evidence of progression within the previous 13 months of treatment, which could include one prior VEGF or VEGF-receptor inhibitor.
The patients were randomized on a 2:1 basis to either oral lenvatinib 24 mg daily or placebo, with treatment continuing until disease progression according to RECIST (Response Evaluation Criteria in Solid Tumor) criteria. At the time of confirmed disease progression, patients originally assigned to placebo could be crossed over to the active drug.
As noted above, median PFS was significantly better for the 261 patients assigned to lenvatinib, at 18.3 months, vs. 3.6 months for the 121 assigned to placebo. The median PFS for patients who had previously received another VEGF inhibitor was 15.1 months, compared with 18.7 months for those who had not been treated with an anti-VEGF agent (P value not shown). Median overall survival has not yet been reached.
The overall response rates were 65% for lenvatinib, versus 2% for placebo (P less than .0001). In the lenvatinib group, there were 4 complete responses, 165 partial responses, 40 cases with stable disease of at least 23 weeks’ duration, and 18 cases of progressive disease. Among placebo-treated patients, there were no complete responses, 2 partial responses, 39 cases of stable disease, and 52 of progressive disease. Only 1.5% of patients, all in the lenvatinib group, had a complete response, compared with none in the placebo group.
The median time to an objective response was 2 months. The median duration of response had not been reached by the last analysis. Approximately 75% of responders had an objective response last for more than 9.4 months, Dr. Schlumberger said.
As is common with other VEGF inhibitors, treatment-emergent adverse events were common, occurring in 97% of patients treated with lenvatinib, compared with 60% of patients on placebo.
The most common events were hypertension, occurring in 68% of patients vs. 9% on placebo, diarrhea (60% vs. 8%), fatigue/asthenia (59% vs. 28%), decreased appetite (50% vs. 12%), and nausea/vomiting (51% vs. 24%).
Adverse events requiring dose reductions occurred in 68% of patients on lenvatinib, dose interruptions in 82%, and discontinuation in 14%. In contrast, only 5% of patients on placebo had a dose reduction, 18% had an interruption, and 5% discontinued therapy.
Also of concern to investigators was the fact that of the 20 patients on lenvatinib who died during the trial, 6 of the deaths were determined by investigators to be treatment related. One of these patients died from a hemorrhagic stroke, one from a pulmonary embolism, and four from general health deterioration.
Hematologic complications are a class effect of the anti-VEGF tyrosine kinase inhibitors, said coauthor Dr. Lori Wirth, medical director of the center for head and neck cancers at Massachusetts General Hospital, Boston.
"The other thing about the toxicity profile overall is that it’s an extremely important thing to consider in patients with thyroid cancer, because many patients do have quite indolent disease. But the patients who were enrolled in the placebo arm had a progression-free survival of less than 4 months, and these are the people who go on to die from their disease when it’s that rapidly progressive. So we do need effective treatments that, unfortunately, do come with some toxicities," she said in an interview.
Although the toxicities of therapy were "considerable," most could be managed through either dose adjustment or additional medications, Dr. Schlumberger said.
The study was sponsored by Eisai. Dr. Schlumberger disclosed receiving honoraria and research funding and acting in an advisory role to the company. Dr. Masters and Dr. Wirth reported having no relevant relationships to disclose.
CHICAGO – The investigational drug lenvatinib significantly prolonged progression-free survival and produced high response rates compared with placebo in patients with iodine-refractory differentiated thyroid cancer.
In a randomized trial, the median progression-free survival (PFS) among patients assigned to lenvatinib was 18.3 months, compared with 3.6 months for placebo. The hazard ratio for lenvatinib was 0.21 (P less than .0001), Dr. Martin Schlumberger reported at the annual meeting of the American Society of Clinical Oncology.
"We had a high objective response rate – about 65% – with some complete responses. Interestingly, the time to objective response was only 2 months, so responses occur very quickly after the first treatment," Dr. Schlumberger, a professor of oncology at the University Paris-Sud, France, said at a media briefing prior to his presentation of the data in a plenary session.
"It’s really rewarding to see another active drug in this disease, where a year ago we really had no active therapy," commented Dr. Gregory A. Masters from the Helen F. Graham Cancer Center in Newark, Delaware.
Dr. Masters moderated the briefing but was not involved in the study.
Patients with relapsed or refractory differentiated thyroid cancer that is resistant to treatment with iodine-131 (131I) have few treatment choices and a 10-year survival rate of just 10%, Dr. Schlumberger noted.
There is evidence, however, showing that vascular endothelial growth factor (VEGF) signaling is associated with aggressive thyroid cancer and its propensity for metastasis, prompting researchers to explore VEGF-receptor inhibitors.
Lenvatinib is an oral multi–tyrosine kinase inhibitor of VEGF receptors 1-3, fibroblast growth factor receptors 1-4, platelet-derived growth factor receptor–alpha, and the RET and KIT kinases.
In a phase II study, the drug showed clinical activity against 131I-refractory differentiated thyroid cancer, prompting investigators to launch the phase III SELECT trial (Study of E7080 Lenvatinib in Differentiated Cancer of the Thyroid) in this population.
They enrolled 392 patients with measurable disease and evidence of progression within the previous 13 months of treatment, which could include one prior VEGF or VEGF-receptor inhibitor.
The patients were randomized on a 2:1 basis to either oral lenvatinib 24 mg daily or placebo, with treatment continuing until disease progression according to RECIST (Response Evaluation Criteria in Solid Tumor) criteria. At the time of confirmed disease progression, patients originally assigned to placebo could be crossed over to the active drug.
As noted above, median PFS was significantly better for the 261 patients assigned to lenvatinib, at 18.3 months, vs. 3.6 months for the 121 assigned to placebo. The median PFS for patients who had previously received another VEGF inhibitor was 15.1 months, compared with 18.7 months for those who had not been treated with an anti-VEGF agent (P value not shown). Median overall survival has not yet been reached.
The overall response rates were 65% for lenvatinib, versus 2% for placebo (P less than .0001). In the lenvatinib group, there were 4 complete responses, 165 partial responses, 40 cases with stable disease of at least 23 weeks’ duration, and 18 cases of progressive disease. Among placebo-treated patients, there were no complete responses, 2 partial responses, 39 cases of stable disease, and 52 of progressive disease. Only 1.5% of patients, all in the lenvatinib group, had a complete response, compared with none in the placebo group.
The median time to an objective response was 2 months. The median duration of response had not been reached by the last analysis. Approximately 75% of responders had an objective response last for more than 9.4 months, Dr. Schlumberger said.
As is common with other VEGF inhibitors, treatment-emergent adverse events were common, occurring in 97% of patients treated with lenvatinib, compared with 60% of patients on placebo.
The most common events were hypertension, occurring in 68% of patients vs. 9% on placebo, diarrhea (60% vs. 8%), fatigue/asthenia (59% vs. 28%), decreased appetite (50% vs. 12%), and nausea/vomiting (51% vs. 24%).
Adverse events requiring dose reductions occurred in 68% of patients on lenvatinib, dose interruptions in 82%, and discontinuation in 14%. In contrast, only 5% of patients on placebo had a dose reduction, 18% had an interruption, and 5% discontinued therapy.
Also of concern to investigators was the fact that of the 20 patients on lenvatinib who died during the trial, 6 of the deaths were determined by investigators to be treatment related. One of these patients died from a hemorrhagic stroke, one from a pulmonary embolism, and four from general health deterioration.
Hematologic complications are a class effect of the anti-VEGF tyrosine kinase inhibitors, said coauthor Dr. Lori Wirth, medical director of the center for head and neck cancers at Massachusetts General Hospital, Boston.
"The other thing about the toxicity profile overall is that it’s an extremely important thing to consider in patients with thyroid cancer, because many patients do have quite indolent disease. But the patients who were enrolled in the placebo arm had a progression-free survival of less than 4 months, and these are the people who go on to die from their disease when it’s that rapidly progressive. So we do need effective treatments that, unfortunately, do come with some toxicities," she said in an interview.
Although the toxicities of therapy were "considerable," most could be managed through either dose adjustment or additional medications, Dr. Schlumberger said.
The study was sponsored by Eisai. Dr. Schlumberger disclosed receiving honoraria and research funding and acting in an advisory role to the company. Dr. Masters and Dr. Wirth reported having no relevant relationships to disclose.
CHICAGO – The investigational drug lenvatinib significantly prolonged progression-free survival and produced high response rates compared with placebo in patients with iodine-refractory differentiated thyroid cancer.
In a randomized trial, the median progression-free survival (PFS) among patients assigned to lenvatinib was 18.3 months, compared with 3.6 months for placebo. The hazard ratio for lenvatinib was 0.21 (P less than .0001), Dr. Martin Schlumberger reported at the annual meeting of the American Society of Clinical Oncology.
"We had a high objective response rate – about 65% – with some complete responses. Interestingly, the time to objective response was only 2 months, so responses occur very quickly after the first treatment," Dr. Schlumberger, a professor of oncology at the University Paris-Sud, France, said at a media briefing prior to his presentation of the data in a plenary session.
"It’s really rewarding to see another active drug in this disease, where a year ago we really had no active therapy," commented Dr. Gregory A. Masters from the Helen F. Graham Cancer Center in Newark, Delaware.
Dr. Masters moderated the briefing but was not involved in the study.
Patients with relapsed or refractory differentiated thyroid cancer that is resistant to treatment with iodine-131 (131I) have few treatment choices and a 10-year survival rate of just 10%, Dr. Schlumberger noted.
There is evidence, however, showing that vascular endothelial growth factor (VEGF) signaling is associated with aggressive thyroid cancer and its propensity for metastasis, prompting researchers to explore VEGF-receptor inhibitors.
Lenvatinib is an oral multi–tyrosine kinase inhibitor of VEGF receptors 1-3, fibroblast growth factor receptors 1-4, platelet-derived growth factor receptor–alpha, and the RET and KIT kinases.
In a phase II study, the drug showed clinical activity against 131I-refractory differentiated thyroid cancer, prompting investigators to launch the phase III SELECT trial (Study of E7080 Lenvatinib in Differentiated Cancer of the Thyroid) in this population.
They enrolled 392 patients with measurable disease and evidence of progression within the previous 13 months of treatment, which could include one prior VEGF or VEGF-receptor inhibitor.
The patients were randomized on a 2:1 basis to either oral lenvatinib 24 mg daily or placebo, with treatment continuing until disease progression according to RECIST (Response Evaluation Criteria in Solid Tumor) criteria. At the time of confirmed disease progression, patients originally assigned to placebo could be crossed over to the active drug.
As noted above, median PFS was significantly better for the 261 patients assigned to lenvatinib, at 18.3 months, vs. 3.6 months for the 121 assigned to placebo. The median PFS for patients who had previously received another VEGF inhibitor was 15.1 months, compared with 18.7 months for those who had not been treated with an anti-VEGF agent (P value not shown). Median overall survival has not yet been reached.
The overall response rates were 65% for lenvatinib, versus 2% for placebo (P less than .0001). In the lenvatinib group, there were 4 complete responses, 165 partial responses, 40 cases with stable disease of at least 23 weeks’ duration, and 18 cases of progressive disease. Among placebo-treated patients, there were no complete responses, 2 partial responses, 39 cases of stable disease, and 52 of progressive disease. Only 1.5% of patients, all in the lenvatinib group, had a complete response, compared with none in the placebo group.
The median time to an objective response was 2 months. The median duration of response had not been reached by the last analysis. Approximately 75% of responders had an objective response last for more than 9.4 months, Dr. Schlumberger said.
As is common with other VEGF inhibitors, treatment-emergent adverse events were common, occurring in 97% of patients treated with lenvatinib, compared with 60% of patients on placebo.
The most common events were hypertension, occurring in 68% of patients vs. 9% on placebo, diarrhea (60% vs. 8%), fatigue/asthenia (59% vs. 28%), decreased appetite (50% vs. 12%), and nausea/vomiting (51% vs. 24%).
Adverse events requiring dose reductions occurred in 68% of patients on lenvatinib, dose interruptions in 82%, and discontinuation in 14%. In contrast, only 5% of patients on placebo had a dose reduction, 18% had an interruption, and 5% discontinued therapy.
Also of concern to investigators was the fact that of the 20 patients on lenvatinib who died during the trial, 6 of the deaths were determined by investigators to be treatment related. One of these patients died from a hemorrhagic stroke, one from a pulmonary embolism, and four from general health deterioration.
Hematologic complications are a class effect of the anti-VEGF tyrosine kinase inhibitors, said coauthor Dr. Lori Wirth, medical director of the center for head and neck cancers at Massachusetts General Hospital, Boston.
"The other thing about the toxicity profile overall is that it’s an extremely important thing to consider in patients with thyroid cancer, because many patients do have quite indolent disease. But the patients who were enrolled in the placebo arm had a progression-free survival of less than 4 months, and these are the people who go on to die from their disease when it’s that rapidly progressive. So we do need effective treatments that, unfortunately, do come with some toxicities," she said in an interview.
Although the toxicities of therapy were "considerable," most could be managed through either dose adjustment or additional medications, Dr. Schlumberger said.
The study was sponsored by Eisai. Dr. Schlumberger disclosed receiving honoraria and research funding and acting in an advisory role to the company. Dr. Masters and Dr. Wirth reported having no relevant relationships to disclose.
AT THE ASCO ANNUAL MEETING 2014
Key clinical finding: The investigational drug lenvatinib significantly prolonged progression-free survival and produced high response rates compared with placebo in patients with iodine-refractory differentiated thyroid cancer.
Major finding: Median progression-free survival for patients with relapsed iodine-refractory differentiated thyroid cancer was 18.3 months, compared with 3.6 months for patients on placebo.
Data source: Randomized, doubled-blind, placebo-controlled trial in 392 patients.
Disclosures: The study was sponsored by Eisai. Dr. Schlumberger disclosed receiving honoraria and research funding and acting in an advisory role to the company. Dr. Masters and Dr. Wirth reported having no relevant relationships to disclose.
