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Cancer patients with TKI-induced hypothyroidism had better survival rates
VICTORIA, B.C. – When it comes to the adverse effects of tyrosine kinase inhibitors (TKIs), hypothyroidism appears to have a bright side, according to a retrospective cohort study among patients with nonthyroid cancers.
While taking one of these targeted agents, roughly a quarter of patients became overtly hypothyroid, an adverse effect that appears to be due in part to immune destruction. Risk was higher for women and earlier in therapy.
Relative to counterparts who remained euthyroid, overtly hypothyroid patients were 44% less likely to die after other factors were taken into account.
Hypothyroidism may reflect changes in immune activation, Dr. Angell proposed. “Additional studies may be helpful, both prospectively looking at the clinical importance of this finding [of survival benefit], and also potentially mechanistically, to understand the relationship between hypothyroidism and survival in these patients.”
“This is an innovative study that looked at an interesting clinical question,” observed session cochair Angela M. Leung, MD, of the University of California, Los Angeles, and an endocrinologist at both UCLA and the VA Greater Los Angeles Healthcare System.
Thyroid dysfunction is a well-known, common side effect of TKI therapy, Dr. Angell noted. “The possible mechanisms that have been suggested for this are direct toxicity on the thyroid gland, destructive thyroiditis, increased thyroid hormone clearance, and vascular endothelial growth factor (VEGF) inhibition, among others.”
Some previous research has suggested a possible survival benefit of TKI-induced hypothyroidism. But “there are limitations in our understanding of hypothyroidism in this setting, including the timing of onset, what risk factors there may be, and the effect of additional clinical variables on the survival effect seen,” Dr. Angell pointed out.
He and his coinvestigators studied 538 adult patients with nonthyroid cancers (mostly stage III or IV) who received a first TKI during 2000-2013 and were followed up through 2017. They excluded those who had preexisting thyroid disease or were on thyroid-related medications.
During TKI therapy, 26.7% of patients developed overt hypothyroidism, and another 13.2% developed subclinical hypothyroidism.
“For a given drug, patients were less likely to develop hypothyroidism when they were given it subsequent to another TKI, as opposed to it being the initial TKI,” Dr. Angell reported. But median time to onset of hypothyroidism was about 2.5 months, regardless.
Cumulative months of all TKI exposure during cancer treatment were not significantly associated with development of hypothyroidism.
In a multivariate analysis, patients were significantly more likely to develop hypothyroidism if they were female (odds ratio, 1.99) and significantly less likely if they had a longer total time on treatment (OR, 0.98) or received a non-TKI VEGF inhibitor (OR, 0.43). Age, race, and cumulative TKI exposure did not influence the outcome.
In a second multivariate analysis, patients’ risk of death was significantly lower if they developed overt hypothyroidism (hazard ratio, 0.56; P less than .0001), but not if they developed subclinical hypothyroidism (HR, 0.79; P = .1655).
Treatment of hypothyroidism did not appear to influence survival, according to Dr. Angell. However, “there wasn’t a specific decision on who was treated, how they were treated, [or] when they were treated,” he said. “So, it is difficult within this cohort to look specifically at which cutoff would be ideal” for initiating treatment.
Similarly, thyroid function testing was not standardized in this retrospectively identified cohort, so it was not possible to determine how long patients were hypothyroid and whether that had an impact, according to Dr. Angell.
Dr. Angell had no relevant conflicts of interest.
VICTORIA, B.C. – When it comes to the adverse effects of tyrosine kinase inhibitors (TKIs), hypothyroidism appears to have a bright side, according to a retrospective cohort study among patients with nonthyroid cancers.
While taking one of these targeted agents, roughly a quarter of patients became overtly hypothyroid, an adverse effect that appears to be due in part to immune destruction. Risk was higher for women and earlier in therapy.
Relative to counterparts who remained euthyroid, overtly hypothyroid patients were 44% less likely to die after other factors were taken into account.
Hypothyroidism may reflect changes in immune activation, Dr. Angell proposed. “Additional studies may be helpful, both prospectively looking at the clinical importance of this finding [of survival benefit], and also potentially mechanistically, to understand the relationship between hypothyroidism and survival in these patients.”
“This is an innovative study that looked at an interesting clinical question,” observed session cochair Angela M. Leung, MD, of the University of California, Los Angeles, and an endocrinologist at both UCLA and the VA Greater Los Angeles Healthcare System.
Thyroid dysfunction is a well-known, common side effect of TKI therapy, Dr. Angell noted. “The possible mechanisms that have been suggested for this are direct toxicity on the thyroid gland, destructive thyroiditis, increased thyroid hormone clearance, and vascular endothelial growth factor (VEGF) inhibition, among others.”
Some previous research has suggested a possible survival benefit of TKI-induced hypothyroidism. But “there are limitations in our understanding of hypothyroidism in this setting, including the timing of onset, what risk factors there may be, and the effect of additional clinical variables on the survival effect seen,” Dr. Angell pointed out.
He and his coinvestigators studied 538 adult patients with nonthyroid cancers (mostly stage III or IV) who received a first TKI during 2000-2013 and were followed up through 2017. They excluded those who had preexisting thyroid disease or were on thyroid-related medications.
During TKI therapy, 26.7% of patients developed overt hypothyroidism, and another 13.2% developed subclinical hypothyroidism.
“For a given drug, patients were less likely to develop hypothyroidism when they were given it subsequent to another TKI, as opposed to it being the initial TKI,” Dr. Angell reported. But median time to onset of hypothyroidism was about 2.5 months, regardless.
Cumulative months of all TKI exposure during cancer treatment were not significantly associated with development of hypothyroidism.
In a multivariate analysis, patients were significantly more likely to develop hypothyroidism if they were female (odds ratio, 1.99) and significantly less likely if they had a longer total time on treatment (OR, 0.98) or received a non-TKI VEGF inhibitor (OR, 0.43). Age, race, and cumulative TKI exposure did not influence the outcome.
In a second multivariate analysis, patients’ risk of death was significantly lower if they developed overt hypothyroidism (hazard ratio, 0.56; P less than .0001), but not if they developed subclinical hypothyroidism (HR, 0.79; P = .1655).
Treatment of hypothyroidism did not appear to influence survival, according to Dr. Angell. However, “there wasn’t a specific decision on who was treated, how they were treated, [or] when they were treated,” he said. “So, it is difficult within this cohort to look specifically at which cutoff would be ideal” for initiating treatment.
Similarly, thyroid function testing was not standardized in this retrospectively identified cohort, so it was not possible to determine how long patients were hypothyroid and whether that had an impact, according to Dr. Angell.
Dr. Angell had no relevant conflicts of interest.
VICTORIA, B.C. – When it comes to the adverse effects of tyrosine kinase inhibitors (TKIs), hypothyroidism appears to have a bright side, according to a retrospective cohort study among patients with nonthyroid cancers.
While taking one of these targeted agents, roughly a quarter of patients became overtly hypothyroid, an adverse effect that appears to be due in part to immune destruction. Risk was higher for women and earlier in therapy.
Relative to counterparts who remained euthyroid, overtly hypothyroid patients were 44% less likely to die after other factors were taken into account.
Hypothyroidism may reflect changes in immune activation, Dr. Angell proposed. “Additional studies may be helpful, both prospectively looking at the clinical importance of this finding [of survival benefit], and also potentially mechanistically, to understand the relationship between hypothyroidism and survival in these patients.”
“This is an innovative study that looked at an interesting clinical question,” observed session cochair Angela M. Leung, MD, of the University of California, Los Angeles, and an endocrinologist at both UCLA and the VA Greater Los Angeles Healthcare System.
Thyroid dysfunction is a well-known, common side effect of TKI therapy, Dr. Angell noted. “The possible mechanisms that have been suggested for this are direct toxicity on the thyroid gland, destructive thyroiditis, increased thyroid hormone clearance, and vascular endothelial growth factor (VEGF) inhibition, among others.”
Some previous research has suggested a possible survival benefit of TKI-induced hypothyroidism. But “there are limitations in our understanding of hypothyroidism in this setting, including the timing of onset, what risk factors there may be, and the effect of additional clinical variables on the survival effect seen,” Dr. Angell pointed out.
He and his coinvestigators studied 538 adult patients with nonthyroid cancers (mostly stage III or IV) who received a first TKI during 2000-2013 and were followed up through 2017. They excluded those who had preexisting thyroid disease or were on thyroid-related medications.
During TKI therapy, 26.7% of patients developed overt hypothyroidism, and another 13.2% developed subclinical hypothyroidism.
“For a given drug, patients were less likely to develop hypothyroidism when they were given it subsequent to another TKI, as opposed to it being the initial TKI,” Dr. Angell reported. But median time to onset of hypothyroidism was about 2.5 months, regardless.
Cumulative months of all TKI exposure during cancer treatment were not significantly associated with development of hypothyroidism.
In a multivariate analysis, patients were significantly more likely to develop hypothyroidism if they were female (odds ratio, 1.99) and significantly less likely if they had a longer total time on treatment (OR, 0.98) or received a non-TKI VEGF inhibitor (OR, 0.43). Age, race, and cumulative TKI exposure did not influence the outcome.
In a second multivariate analysis, patients’ risk of death was significantly lower if they developed overt hypothyroidism (hazard ratio, 0.56; P less than .0001), but not if they developed subclinical hypothyroidism (HR, 0.79; P = .1655).
Treatment of hypothyroidism did not appear to influence survival, according to Dr. Angell. However, “there wasn’t a specific decision on who was treated, how they were treated, [or] when they were treated,” he said. “So, it is difficult within this cohort to look specifically at which cutoff would be ideal” for initiating treatment.
Similarly, thyroid function testing was not standardized in this retrospectively identified cohort, so it was not possible to determine how long patients were hypothyroid and whether that had an impact, according to Dr. Angell.
Dr. Angell had no relevant conflicts of interest.
AT ATA 2017
Key clinical point:
Major finding: Relative to peers who remained euthyroid, patients who developed overt hypothyroidism had a reduced risk of death (HR, 0.56; P less than .0001).
Data source: A retrospective cohort study of 538 adult patients with mainly advanced nonthyroid cancers treated with a tyrosine kinase inhibitor.
Disclosures: Dr. Angell had no relevant conflicts of interest.
Calcitonin-to-CEA ratio predicts medullary thyroid cancer survival
BOSTON – The ratio of serum calcitonin to the serum level of carcinoembryonic antigen in patients with medullary thyroid cancer can predict which patients have a better chance for survival following thyroidectomy, based on retrospective findings from 164 presurgical patients at one U.S. center.
A lower serum calcitonin–to–serum carcinoembryonic antigen (CEA) ratio following thyroidectomy is a second marker of good postsurgical survival, Tania Jaber, MD, said at the World Congress on Thyroid Cancer.
“Patients want to know whether surgery will cure them, and we have had no prognostic markers to predict this. Depending on the ratio, we can now tell patients whether or not they have a good chance of cure,” said Dr. Jaber, an endocrinological oncologist at MD Anderson in Houston. “Surgery remains the standard of care, so the ratio does not affect the decision of whether to undergo surgery, but it helps patients know what to expect” after surgery, she said in an interview.
“If their ratio is favorable it can be reassuring, and if their ratio is unfavorable it helps set expectations. We are also studying whether the ratio can be a marker for the need for systemic therapy following surgery. Right now, our prognostic tools for medullary thyroid cancer are very limited, so any additional information we can give patients based on their calcitonin-to-CEA ratio is very valuable.”
Her study included 164 patients treated at MD Anderson who had their serum drawn before thyroidectomy, and 187 patients with specimens taken 3-9 months after surgery. Median patient follow-up after surgery was 5 years. Calcitonin levels were measured as pg/mL and CEA levels as ng/mL; despite this difference in unit size the researchers calculated the ratios by a direct numerical comparison that ignored the units.
Among the preoperative patients and specifically among those with a low serum CEA level of less than 25 ng/ML a calcitonin-to-CEA ratio of less than 43 had the best survival rate, Dr. Jaber reported. Among preoperative patients with a CEA level of 25 ng/mL or greater a ratio of less than 18 flagged patients with the best survival rate following thyroidectomy.
Among postoperative patients the ratios that linked with better survival also depended on the CEA level. In patients with a low postoperative CEA a ratio of less than 149 linked with better survival. In patients with a high CEA level a ratio of less than 12 linked with better postoperative survival.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
BOSTON – The ratio of serum calcitonin to the serum level of carcinoembryonic antigen in patients with medullary thyroid cancer can predict which patients have a better chance for survival following thyroidectomy, based on retrospective findings from 164 presurgical patients at one U.S. center.
A lower serum calcitonin–to–serum carcinoembryonic antigen (CEA) ratio following thyroidectomy is a second marker of good postsurgical survival, Tania Jaber, MD, said at the World Congress on Thyroid Cancer.
“Patients want to know whether surgery will cure them, and we have had no prognostic markers to predict this. Depending on the ratio, we can now tell patients whether or not they have a good chance of cure,” said Dr. Jaber, an endocrinological oncologist at MD Anderson in Houston. “Surgery remains the standard of care, so the ratio does not affect the decision of whether to undergo surgery, but it helps patients know what to expect” after surgery, she said in an interview.
“If their ratio is favorable it can be reassuring, and if their ratio is unfavorable it helps set expectations. We are also studying whether the ratio can be a marker for the need for systemic therapy following surgery. Right now, our prognostic tools for medullary thyroid cancer are very limited, so any additional information we can give patients based on their calcitonin-to-CEA ratio is very valuable.”
Her study included 164 patients treated at MD Anderson who had their serum drawn before thyroidectomy, and 187 patients with specimens taken 3-9 months after surgery. Median patient follow-up after surgery was 5 years. Calcitonin levels were measured as pg/mL and CEA levels as ng/mL; despite this difference in unit size the researchers calculated the ratios by a direct numerical comparison that ignored the units.
Among the preoperative patients and specifically among those with a low serum CEA level of less than 25 ng/ML a calcitonin-to-CEA ratio of less than 43 had the best survival rate, Dr. Jaber reported. Among preoperative patients with a CEA level of 25 ng/mL or greater a ratio of less than 18 flagged patients with the best survival rate following thyroidectomy.
Among postoperative patients the ratios that linked with better survival also depended on the CEA level. In patients with a low postoperative CEA a ratio of less than 149 linked with better survival. In patients with a high CEA level a ratio of less than 12 linked with better postoperative survival.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
BOSTON – The ratio of serum calcitonin to the serum level of carcinoembryonic antigen in patients with medullary thyroid cancer can predict which patients have a better chance for survival following thyroidectomy, based on retrospective findings from 164 presurgical patients at one U.S. center.
A lower serum calcitonin–to–serum carcinoembryonic antigen (CEA) ratio following thyroidectomy is a second marker of good postsurgical survival, Tania Jaber, MD, said at the World Congress on Thyroid Cancer.
“Patients want to know whether surgery will cure them, and we have had no prognostic markers to predict this. Depending on the ratio, we can now tell patients whether or not they have a good chance of cure,” said Dr. Jaber, an endocrinological oncologist at MD Anderson in Houston. “Surgery remains the standard of care, so the ratio does not affect the decision of whether to undergo surgery, but it helps patients know what to expect” after surgery, she said in an interview.
“If their ratio is favorable it can be reassuring, and if their ratio is unfavorable it helps set expectations. We are also studying whether the ratio can be a marker for the need for systemic therapy following surgery. Right now, our prognostic tools for medullary thyroid cancer are very limited, so any additional information we can give patients based on their calcitonin-to-CEA ratio is very valuable.”
Her study included 164 patients treated at MD Anderson who had their serum drawn before thyroidectomy, and 187 patients with specimens taken 3-9 months after surgery. Median patient follow-up after surgery was 5 years. Calcitonin levels were measured as pg/mL and CEA levels as ng/mL; despite this difference in unit size the researchers calculated the ratios by a direct numerical comparison that ignored the units.
Among the preoperative patients and specifically among those with a low serum CEA level of less than 25 ng/ML a calcitonin-to-CEA ratio of less than 43 had the best survival rate, Dr. Jaber reported. Among preoperative patients with a CEA level of 25 ng/mL or greater a ratio of less than 18 flagged patients with the best survival rate following thyroidectomy.
Among postoperative patients the ratios that linked with better survival also depended on the CEA level. In patients with a low postoperative CEA a ratio of less than 149 linked with better survival. In patients with a high CEA level a ratio of less than 12 linked with better postoperative survival.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
AT WCTC 2017
Key clinical point:
Major finding: Presurgery, a calcitonin-to-CEA ratio below 18 was linked with superior survival in patients whose CEA was at least 25 ng/Ml.
Data source: A single-center, retrospective study with 164 patients assessed before thyroidectomy and 187 assessed after surgery.
Disclosures: Dr. Jaber had no disclosures.
Big changes coming for thyroid cancer staging
BOSTON – When the American Joint Committee on Cancer’s Eighth Edition Cancer Staging Manual becomes effective for U.S. practice on Jan. 1, 2018, substantially more patients with thyroid cancer will meet the definition for stage I disease, but their survival prognosis will remain as good as it was for the smaller slice of patients defined with stage I thyroid cancer by the seventh edition, Bryan R. Haugen, MD, predicted during a talk at the World Congress on Thyroid Cancer.
Under current stage definitions in the seventh edition, roughly 60% of thyroid cancer patients have stage I disease, but this will kick up to about 80% under the eighth edition, said Dr. Haugen, professor of medicine and head of the division of endocrinology, metabolism, and diabetes at the University of Colorado in Aurora. Despite this influx of more patients, “survival rates in stage I patients haven’t changed,” with a disease-specific survival (DSS) of 98%-100% for stage I patients in the eighth edition compared with 97%-100% in the seventh edition, he noted.
Dr. Haugen credited this apparent paradox to the revised staging system’s superior discrimination among various grades of disease progression. “The eighth edition better separates patients based on their projected survival.” As more patients fit stage I classification with its highest level of projected survival, fewer patients will classify with more advanced disease and its worse projected survival.
For example, in the seventh edition patients with stage IV disease had a projected DSS rate of 50%-75%; in the eighth edition that rate is now less than 50%. The projected DSS rate for patients with stage II disease has down shifted from 97%-100% in the seventh edition to 85%-95% in the eighth. For patients with stage III thyroid cancer the DSS rate of 88%-95% in the seventh edition became 60%-70% in the eighth edition.
‘The new system will take some getting used to,” Dr. Haugen admitted, and it involves even more “big” changes, he warned. These include:
• Changing the cutpoint separating younger from older patients to 55 years of age in the eighth edition, a rise from the 45-year-old cutpoint in the seventh edition.
• Allowing tumors classified as stage I to be as large as 4 cm, up from the 2 cm or less defining stage I in the seventh edition.
• Reserving stage II designation for patients with tumors larger than 4 cm. In the seventh edition tumors had to be 2-4 cm in size.
• Expanding stage II disease to include not only patients with disease confined to their thyroid, but also patients with N1 lymph node spread or gross extrathyroidal extension. In the seventh edition tumor spread like this put patients into stage III.
• Specifying in the eighth edition that stage III disease must feature gross extrathyroidal extension into the larynx, trachea, esophagus, or recurrent laryngial nerve. To qualify for stage IV in the eighth edition, spread must extend into prevertebral fascia or encase major vessels, for stage IVA, or involve distant metastases for stage IVB.
• Paring down three stage IV subgroups, A, B, and C, in the seventh edition to just an A or B subgroup in the eighth edition.
Dr. Haugen coauthored a recent editorial that laid out an assessment of the eighth edition in greater detail (Thyroid. 2017 Jun;27[6]:751-6).
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
BOSTON – When the American Joint Committee on Cancer’s Eighth Edition Cancer Staging Manual becomes effective for U.S. practice on Jan. 1, 2018, substantially more patients with thyroid cancer will meet the definition for stage I disease, but their survival prognosis will remain as good as it was for the smaller slice of patients defined with stage I thyroid cancer by the seventh edition, Bryan R. Haugen, MD, predicted during a talk at the World Congress on Thyroid Cancer.
Under current stage definitions in the seventh edition, roughly 60% of thyroid cancer patients have stage I disease, but this will kick up to about 80% under the eighth edition, said Dr. Haugen, professor of medicine and head of the division of endocrinology, metabolism, and diabetes at the University of Colorado in Aurora. Despite this influx of more patients, “survival rates in stage I patients haven’t changed,” with a disease-specific survival (DSS) of 98%-100% for stage I patients in the eighth edition compared with 97%-100% in the seventh edition, he noted.
Dr. Haugen credited this apparent paradox to the revised staging system’s superior discrimination among various grades of disease progression. “The eighth edition better separates patients based on their projected survival.” As more patients fit stage I classification with its highest level of projected survival, fewer patients will classify with more advanced disease and its worse projected survival.
For example, in the seventh edition patients with stage IV disease had a projected DSS rate of 50%-75%; in the eighth edition that rate is now less than 50%. The projected DSS rate for patients with stage II disease has down shifted from 97%-100% in the seventh edition to 85%-95% in the eighth. For patients with stage III thyroid cancer the DSS rate of 88%-95% in the seventh edition became 60%-70% in the eighth edition.
‘The new system will take some getting used to,” Dr. Haugen admitted, and it involves even more “big” changes, he warned. These include:
• Changing the cutpoint separating younger from older patients to 55 years of age in the eighth edition, a rise from the 45-year-old cutpoint in the seventh edition.
• Allowing tumors classified as stage I to be as large as 4 cm, up from the 2 cm or less defining stage I in the seventh edition.
• Reserving stage II designation for patients with tumors larger than 4 cm. In the seventh edition tumors had to be 2-4 cm in size.
• Expanding stage II disease to include not only patients with disease confined to their thyroid, but also patients with N1 lymph node spread or gross extrathyroidal extension. In the seventh edition tumor spread like this put patients into stage III.
• Specifying in the eighth edition that stage III disease must feature gross extrathyroidal extension into the larynx, trachea, esophagus, or recurrent laryngial nerve. To qualify for stage IV in the eighth edition, spread must extend into prevertebral fascia or encase major vessels, for stage IVA, or involve distant metastases for stage IVB.
• Paring down three stage IV subgroups, A, B, and C, in the seventh edition to just an A or B subgroup in the eighth edition.
Dr. Haugen coauthored a recent editorial that laid out an assessment of the eighth edition in greater detail (Thyroid. 2017 Jun;27[6]:751-6).
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
BOSTON – When the American Joint Committee on Cancer’s Eighth Edition Cancer Staging Manual becomes effective for U.S. practice on Jan. 1, 2018, substantially more patients with thyroid cancer will meet the definition for stage I disease, but their survival prognosis will remain as good as it was for the smaller slice of patients defined with stage I thyroid cancer by the seventh edition, Bryan R. Haugen, MD, predicted during a talk at the World Congress on Thyroid Cancer.
Under current stage definitions in the seventh edition, roughly 60% of thyroid cancer patients have stage I disease, but this will kick up to about 80% under the eighth edition, said Dr. Haugen, professor of medicine and head of the division of endocrinology, metabolism, and diabetes at the University of Colorado in Aurora. Despite this influx of more patients, “survival rates in stage I patients haven’t changed,” with a disease-specific survival (DSS) of 98%-100% for stage I patients in the eighth edition compared with 97%-100% in the seventh edition, he noted.
Dr. Haugen credited this apparent paradox to the revised staging system’s superior discrimination among various grades of disease progression. “The eighth edition better separates patients based on their projected survival.” As more patients fit stage I classification with its highest level of projected survival, fewer patients will classify with more advanced disease and its worse projected survival.
For example, in the seventh edition patients with stage IV disease had a projected DSS rate of 50%-75%; in the eighth edition that rate is now less than 50%. The projected DSS rate for patients with stage II disease has down shifted from 97%-100% in the seventh edition to 85%-95% in the eighth. For patients with stage III thyroid cancer the DSS rate of 88%-95% in the seventh edition became 60%-70% in the eighth edition.
‘The new system will take some getting used to,” Dr. Haugen admitted, and it involves even more “big” changes, he warned. These include:
• Changing the cutpoint separating younger from older patients to 55 years of age in the eighth edition, a rise from the 45-year-old cutpoint in the seventh edition.
• Allowing tumors classified as stage I to be as large as 4 cm, up from the 2 cm or less defining stage I in the seventh edition.
• Reserving stage II designation for patients with tumors larger than 4 cm. In the seventh edition tumors had to be 2-4 cm in size.
• Expanding stage II disease to include not only patients with disease confined to their thyroid, but also patients with N1 lymph node spread or gross extrathyroidal extension. In the seventh edition tumor spread like this put patients into stage III.
• Specifying in the eighth edition that stage III disease must feature gross extrathyroidal extension into the larynx, trachea, esophagus, or recurrent laryngial nerve. To qualify for stage IV in the eighth edition, spread must extend into prevertebral fascia or encase major vessels, for stage IVA, or involve distant metastases for stage IVB.
• Paring down three stage IV subgroups, A, B, and C, in the seventh edition to just an A or B subgroup in the eighth edition.
Dr. Haugen coauthored a recent editorial that laid out an assessment of the eighth edition in greater detail (Thyroid. 2017 Jun;27[6]:751-6).
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
EXPERT ANALYSIS FROM WCTC 2017
Contralateral nodal thyroid metastases show slow progression
BOSTON – More than a third of 63 patients with unilateral papillary thyroid carcinoma and ipsilateral lymph node metastases also had occult, contralateral, lateral-neck lymph nodes with metastases, but the low reported rate of contralateral neck recurrence has raised the question of whether routine resection of these contralateral lymph nodes benefits patients.
“Prophylactic contralateral lateral-neck dissection may not be relevant for patients with unilateral N1b tumors,” Dana Hartl, MD, PhD, said at the World Congress on Thyroid Cancer.
She envisioned a more targeted approach to using surgical resection of contralateral, lateral-neck lymph nodes. “We would still do this surgery for patients with lots of big, bulky nodules; it just takes an additional 10-20 minutes. It’s not that long or morbid. For patients with lots of [affected] nodes, you’ve got to clear it out. But for a patient with a small, level III node on one side I will no longer do [prophylactic, contralateral, lateral-neck lymph node removal].”
Dr. Hartl and her associates reviewed records for 63 patients with unilateral, unifocal papillary thyroid carcinoma who underwent prophylactic, contralateral, lymph node removal during 1997-2016. They ranged from 11-84 years old, and 60% had extrathyroidal extension of their primary tumor. The patients averaged having four lymph nodes with metastatic cells in the ipsilateral lateral neck, an average of five affected lymph nodes in the ipsilateral central neck, and an average of two affected lymph nodes in the contralateral central neck.
Among the 63 patients, 23 (37%) had metastases-containing lymph nodes at levels III and IV in the contralateral lateral neck, with a range of 1-17 metastases per node. All nodes were less than 1 cm in diameter. Extracapsular spread had occurred in 11 of the 23 cases.
The relatively frequent presence of metastases in the contralateral, lateral-neck lymph nodes contrasted with the reported low 5%-15% rate of recurrence in these lymph nodes in patients with N1b disease, Dr. Hartl said.
The analysis identified two factors that significantly linked with having contralateral, lateral-neck metastases: having a bilateral tumor with contralateral microcancer, or having at least four lymph nodes positive for metastases in the ipsilateral central compartment, she reported. When patients had fewer than five positive lymph nodes in the ipsilateral central neck, their risk for occult metastases in contralateral lymph nodes was 26%.
“It’s not very strong data; we were a little disappointed” with the results, Dr. Hartl said.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
The finding reported by Dr. Hartl is consistent with recent experience with other tumor types, like prostate cancer, that often show low aggressiveness. The need to routinely resect what may be indolent microscopic metastases remains a big open question.
The dilemma for thyroid cancer was nicely summarized by Gilbert Welch, MD, and his associates who highlighted the risk of overdiagnosing thyroid cancer with aggressive screening. In South Korea, this resulted in a 15-fold increase in thyroid cancer diagnoses between 1993 and 2011, which led to substantial increases in the rates of thyroidectomy including patients with tumors too small to warrant surgery (N Engl J Med. 2014 Nov 6;371[19]:1765-7).
Pamela Hartzband, MD , is an endocrinologist at Beth Israel Deaconess Medical Center in Boston. She had no disclosures. She made these comments in an interview.
The finding reported by Dr. Hartl is consistent with recent experience with other tumor types, like prostate cancer, that often show low aggressiveness. The need to routinely resect what may be indolent microscopic metastases remains a big open question.
The dilemma for thyroid cancer was nicely summarized by Gilbert Welch, MD, and his associates who highlighted the risk of overdiagnosing thyroid cancer with aggressive screening. In South Korea, this resulted in a 15-fold increase in thyroid cancer diagnoses between 1993 and 2011, which led to substantial increases in the rates of thyroidectomy including patients with tumors too small to warrant surgery (N Engl J Med. 2014 Nov 6;371[19]:1765-7).
Pamela Hartzband, MD , is an endocrinologist at Beth Israel Deaconess Medical Center in Boston. She had no disclosures. She made these comments in an interview.
The finding reported by Dr. Hartl is consistent with recent experience with other tumor types, like prostate cancer, that often show low aggressiveness. The need to routinely resect what may be indolent microscopic metastases remains a big open question.
The dilemma for thyroid cancer was nicely summarized by Gilbert Welch, MD, and his associates who highlighted the risk of overdiagnosing thyroid cancer with aggressive screening. In South Korea, this resulted in a 15-fold increase in thyroid cancer diagnoses between 1993 and 2011, which led to substantial increases in the rates of thyroidectomy including patients with tumors too small to warrant surgery (N Engl J Med. 2014 Nov 6;371[19]:1765-7).
Pamela Hartzband, MD , is an endocrinologist at Beth Israel Deaconess Medical Center in Boston. She had no disclosures. She made these comments in an interview.
BOSTON – More than a third of 63 patients with unilateral papillary thyroid carcinoma and ipsilateral lymph node metastases also had occult, contralateral, lateral-neck lymph nodes with metastases, but the low reported rate of contralateral neck recurrence has raised the question of whether routine resection of these contralateral lymph nodes benefits patients.
“Prophylactic contralateral lateral-neck dissection may not be relevant for patients with unilateral N1b tumors,” Dana Hartl, MD, PhD, said at the World Congress on Thyroid Cancer.
She envisioned a more targeted approach to using surgical resection of contralateral, lateral-neck lymph nodes. “We would still do this surgery for patients with lots of big, bulky nodules; it just takes an additional 10-20 minutes. It’s not that long or morbid. For patients with lots of [affected] nodes, you’ve got to clear it out. But for a patient with a small, level III node on one side I will no longer do [prophylactic, contralateral, lateral-neck lymph node removal].”
Dr. Hartl and her associates reviewed records for 63 patients with unilateral, unifocal papillary thyroid carcinoma who underwent prophylactic, contralateral, lymph node removal during 1997-2016. They ranged from 11-84 years old, and 60% had extrathyroidal extension of their primary tumor. The patients averaged having four lymph nodes with metastatic cells in the ipsilateral lateral neck, an average of five affected lymph nodes in the ipsilateral central neck, and an average of two affected lymph nodes in the contralateral central neck.
Among the 63 patients, 23 (37%) had metastases-containing lymph nodes at levels III and IV in the contralateral lateral neck, with a range of 1-17 metastases per node. All nodes were less than 1 cm in diameter. Extracapsular spread had occurred in 11 of the 23 cases.
The relatively frequent presence of metastases in the contralateral, lateral-neck lymph nodes contrasted with the reported low 5%-15% rate of recurrence in these lymph nodes in patients with N1b disease, Dr. Hartl said.
The analysis identified two factors that significantly linked with having contralateral, lateral-neck metastases: having a bilateral tumor with contralateral microcancer, or having at least four lymph nodes positive for metastases in the ipsilateral central compartment, she reported. When patients had fewer than five positive lymph nodes in the ipsilateral central neck, their risk for occult metastases in contralateral lymph nodes was 26%.
“It’s not very strong data; we were a little disappointed” with the results, Dr. Hartl said.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
BOSTON – More than a third of 63 patients with unilateral papillary thyroid carcinoma and ipsilateral lymph node metastases also had occult, contralateral, lateral-neck lymph nodes with metastases, but the low reported rate of contralateral neck recurrence has raised the question of whether routine resection of these contralateral lymph nodes benefits patients.
“Prophylactic contralateral lateral-neck dissection may not be relevant for patients with unilateral N1b tumors,” Dana Hartl, MD, PhD, said at the World Congress on Thyroid Cancer.
She envisioned a more targeted approach to using surgical resection of contralateral, lateral-neck lymph nodes. “We would still do this surgery for patients with lots of big, bulky nodules; it just takes an additional 10-20 minutes. It’s not that long or morbid. For patients with lots of [affected] nodes, you’ve got to clear it out. But for a patient with a small, level III node on one side I will no longer do [prophylactic, contralateral, lateral-neck lymph node removal].”
Dr. Hartl and her associates reviewed records for 63 patients with unilateral, unifocal papillary thyroid carcinoma who underwent prophylactic, contralateral, lymph node removal during 1997-2016. They ranged from 11-84 years old, and 60% had extrathyroidal extension of their primary tumor. The patients averaged having four lymph nodes with metastatic cells in the ipsilateral lateral neck, an average of five affected lymph nodes in the ipsilateral central neck, and an average of two affected lymph nodes in the contralateral central neck.
Among the 63 patients, 23 (37%) had metastases-containing lymph nodes at levels III and IV in the contralateral lateral neck, with a range of 1-17 metastases per node. All nodes were less than 1 cm in diameter. Extracapsular spread had occurred in 11 of the 23 cases.
The relatively frequent presence of metastases in the contralateral, lateral-neck lymph nodes contrasted with the reported low 5%-15% rate of recurrence in these lymph nodes in patients with N1b disease, Dr. Hartl said.
The analysis identified two factors that significantly linked with having contralateral, lateral-neck metastases: having a bilateral tumor with contralateral microcancer, or having at least four lymph nodes positive for metastases in the ipsilateral central compartment, she reported. When patients had fewer than five positive lymph nodes in the ipsilateral central neck, their risk for occult metastases in contralateral lymph nodes was 26%.
“It’s not very strong data; we were a little disappointed” with the results, Dr. Hartl said.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
AT WCTC 2017
Key clinical point:
Major finding: Thirty-seven percent of patients with unilateral N1b thyroid tumors also had metastases in their contralateral lateral-neck lymph nodes.
Data source: Review of 63 patients treated at a single French center during a 20-year period.
Disclosures: Dr. Hartl had no disclosures.
Revised thyroid Bethesda System resets malignant risks
BOSTON – Under the newly revised Bethesda System for Reporting Thyroid Cytology, slated for official release in October 2017, the six cytology-based diagnostic categories for thyroid lesions stay exactly the same as in the 10-year-old first edition, but some associated malignancy risks have changed.
Important changes include molecular testing to further assess malignancy risk in thyroid nodules and the introduction of lobectomy as a treatment option, “which really wasn’t an option 10 years ago,” in the first iteration of the Bethesda System (New York: Springer US, 2010), its coauthor Edmund S. Cibas, MD, said at the World Congress on Thyroid Cancer.
An Endocrine Pathology Society working group created the NIFTP designation in 2016 to describe an encapsulated follicular variant of papillary thyroid carcinoma that is characterized by lack of invasion, a follicular growth pattern, and nuclear features of papillary thyroid carcinoma with a very low risk of an adverse outcome (JAMA Oncology. 2016 Aug;2[8]:1023-9) (Cancer Cytopathol. 2016 Sep;124[9]:616-20).
NIFTP is not an overt malignancy. The revised Bethesda System “limits malignancy to cases with features of classic malignant papillary thyroid carcinoma,” explained Dr. Cibas, professor of pathology at Harvard Medical School and director of cytopathology at Brigham and Women’s Hospital, both in Boston.
Because the Bethesda System categories link to specific management recommendations, the new edition orients patients toward more conservative management decisions, specifically lobectomies instead of total thyroidectomies, he said in an interview.
The International Cytology Congress held a symposium during its meeting in Yokohama, Japan, in 2016, which resulted in the second edition of the Bethesda System (ACTA Cytol. 2016 Sep-Oct; 60[5]:399-405).
The changes in risk of malignancy occurred primarily in two categories, either “atypia of undetermined significance” (AUS) or “follicular lesions of undetermined significance” (FLUS). The risk of malignancy jumped from 5%-15% in the Bethesda System first edition up to 10%-30% in the revision. A smaller bump-up hit the category of “follicular neoplasm” or “suspicious for follicular neoplasm,” in which the risk of malignancy increased from 20%-30% in the first edition to 25%-40% in the revision. And, in the suspicion of malignancy category, the risk of malignancy actually lowered modestly, easing from 60%-75% in the first edition to 50%-75% in the revision.
Dr. Cibas highlighted the AUS/FLUS category with further notable features. The limit on laboratories reporting this category increased to 10% of total reports, up from 7% in the first edition. Management changed from the single options of a repeat fine-needle aspiration specimen to either that or molecular testing. Also, “the first edition was not clear that AUS and FLUS are synonyms. That will be a lot clearer” in the second edition, Dr. Cibas promised. The revision “will encourage labs that currently use [the terms] AUS and FLUS to mean two different things to make a choice between them.”
Another quirk of the AUS and FLUS category is that the risk of malignancy estimates are based on what Dr. Cibas called “flawed” data from only the selected subset of AUS or FLUS patients who have their nodule resected. “The reality is that most of the nodules are not resected” from patients with AUS or FLUS, so conclusions about the risk of malignancy come from a subset with considerable selection bias.
The definition of “follicular neoplasm” or “suspicious for follicular neoplasm” category also added “mild nuclear changes,” which can include increased nuclear size, contour irregularity, or chromatin clearing. The “suspicious for malignancy” category made a modest tweak to the risk of malignancy. Plus, “some of these patients will now undergo lobectomy rather than total thyroidectomy, which has been usual management.
The “suspicious for malignant” and “malignant” categories had little change aside from wider use of lobectomy, now feasible for any patient except those with metastatic disease, Dr. Cibas said.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
BOSTON – Under the newly revised Bethesda System for Reporting Thyroid Cytology, slated for official release in October 2017, the six cytology-based diagnostic categories for thyroid lesions stay exactly the same as in the 10-year-old first edition, but some associated malignancy risks have changed.
Important changes include molecular testing to further assess malignancy risk in thyroid nodules and the introduction of lobectomy as a treatment option, “which really wasn’t an option 10 years ago,” in the first iteration of the Bethesda System (New York: Springer US, 2010), its coauthor Edmund S. Cibas, MD, said at the World Congress on Thyroid Cancer.
An Endocrine Pathology Society working group created the NIFTP designation in 2016 to describe an encapsulated follicular variant of papillary thyroid carcinoma that is characterized by lack of invasion, a follicular growth pattern, and nuclear features of papillary thyroid carcinoma with a very low risk of an adverse outcome (JAMA Oncology. 2016 Aug;2[8]:1023-9) (Cancer Cytopathol. 2016 Sep;124[9]:616-20).
NIFTP is not an overt malignancy. The revised Bethesda System “limits malignancy to cases with features of classic malignant papillary thyroid carcinoma,” explained Dr. Cibas, professor of pathology at Harvard Medical School and director of cytopathology at Brigham and Women’s Hospital, both in Boston.
Because the Bethesda System categories link to specific management recommendations, the new edition orients patients toward more conservative management decisions, specifically lobectomies instead of total thyroidectomies, he said in an interview.
The International Cytology Congress held a symposium during its meeting in Yokohama, Japan, in 2016, which resulted in the second edition of the Bethesda System (ACTA Cytol. 2016 Sep-Oct; 60[5]:399-405).
The changes in risk of malignancy occurred primarily in two categories, either “atypia of undetermined significance” (AUS) or “follicular lesions of undetermined significance” (FLUS). The risk of malignancy jumped from 5%-15% in the Bethesda System first edition up to 10%-30% in the revision. A smaller bump-up hit the category of “follicular neoplasm” or “suspicious for follicular neoplasm,” in which the risk of malignancy increased from 20%-30% in the first edition to 25%-40% in the revision. And, in the suspicion of malignancy category, the risk of malignancy actually lowered modestly, easing from 60%-75% in the first edition to 50%-75% in the revision.
Dr. Cibas highlighted the AUS/FLUS category with further notable features. The limit on laboratories reporting this category increased to 10% of total reports, up from 7% in the first edition. Management changed from the single options of a repeat fine-needle aspiration specimen to either that or molecular testing. Also, “the first edition was not clear that AUS and FLUS are synonyms. That will be a lot clearer” in the second edition, Dr. Cibas promised. The revision “will encourage labs that currently use [the terms] AUS and FLUS to mean two different things to make a choice between them.”
Another quirk of the AUS and FLUS category is that the risk of malignancy estimates are based on what Dr. Cibas called “flawed” data from only the selected subset of AUS or FLUS patients who have their nodule resected. “The reality is that most of the nodules are not resected” from patients with AUS or FLUS, so conclusions about the risk of malignancy come from a subset with considerable selection bias.
The definition of “follicular neoplasm” or “suspicious for follicular neoplasm” category also added “mild nuclear changes,” which can include increased nuclear size, contour irregularity, or chromatin clearing. The “suspicious for malignancy” category made a modest tweak to the risk of malignancy. Plus, “some of these patients will now undergo lobectomy rather than total thyroidectomy, which has been usual management.
The “suspicious for malignant” and “malignant” categories had little change aside from wider use of lobectomy, now feasible for any patient except those with metastatic disease, Dr. Cibas said.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
BOSTON – Under the newly revised Bethesda System for Reporting Thyroid Cytology, slated for official release in October 2017, the six cytology-based diagnostic categories for thyroid lesions stay exactly the same as in the 10-year-old first edition, but some associated malignancy risks have changed.
Important changes include molecular testing to further assess malignancy risk in thyroid nodules and the introduction of lobectomy as a treatment option, “which really wasn’t an option 10 years ago,” in the first iteration of the Bethesda System (New York: Springer US, 2010), its coauthor Edmund S. Cibas, MD, said at the World Congress on Thyroid Cancer.
An Endocrine Pathology Society working group created the NIFTP designation in 2016 to describe an encapsulated follicular variant of papillary thyroid carcinoma that is characterized by lack of invasion, a follicular growth pattern, and nuclear features of papillary thyroid carcinoma with a very low risk of an adverse outcome (JAMA Oncology. 2016 Aug;2[8]:1023-9) (Cancer Cytopathol. 2016 Sep;124[9]:616-20).
NIFTP is not an overt malignancy. The revised Bethesda System “limits malignancy to cases with features of classic malignant papillary thyroid carcinoma,” explained Dr. Cibas, professor of pathology at Harvard Medical School and director of cytopathology at Brigham and Women’s Hospital, both in Boston.
Because the Bethesda System categories link to specific management recommendations, the new edition orients patients toward more conservative management decisions, specifically lobectomies instead of total thyroidectomies, he said in an interview.
The International Cytology Congress held a symposium during its meeting in Yokohama, Japan, in 2016, which resulted in the second edition of the Bethesda System (ACTA Cytol. 2016 Sep-Oct; 60[5]:399-405).
The changes in risk of malignancy occurred primarily in two categories, either “atypia of undetermined significance” (AUS) or “follicular lesions of undetermined significance” (FLUS). The risk of malignancy jumped from 5%-15% in the Bethesda System first edition up to 10%-30% in the revision. A smaller bump-up hit the category of “follicular neoplasm” or “suspicious for follicular neoplasm,” in which the risk of malignancy increased from 20%-30% in the first edition to 25%-40% in the revision. And, in the suspicion of malignancy category, the risk of malignancy actually lowered modestly, easing from 60%-75% in the first edition to 50%-75% in the revision.
Dr. Cibas highlighted the AUS/FLUS category with further notable features. The limit on laboratories reporting this category increased to 10% of total reports, up from 7% in the first edition. Management changed from the single options of a repeat fine-needle aspiration specimen to either that or molecular testing. Also, “the first edition was not clear that AUS and FLUS are synonyms. That will be a lot clearer” in the second edition, Dr. Cibas promised. The revision “will encourage labs that currently use [the terms] AUS and FLUS to mean two different things to make a choice between them.”
Another quirk of the AUS and FLUS category is that the risk of malignancy estimates are based on what Dr. Cibas called “flawed” data from only the selected subset of AUS or FLUS patients who have their nodule resected. “The reality is that most of the nodules are not resected” from patients with AUS or FLUS, so conclusions about the risk of malignancy come from a subset with considerable selection bias.
The definition of “follicular neoplasm” or “suspicious for follicular neoplasm” category also added “mild nuclear changes,” which can include increased nuclear size, contour irregularity, or chromatin clearing. The “suspicious for malignancy” category made a modest tweak to the risk of malignancy. Plus, “some of these patients will now undergo lobectomy rather than total thyroidectomy, which has been usual management.
The “suspicious for malignant” and “malignant” categories had little change aside from wider use of lobectomy, now feasible for any patient except those with metastatic disease, Dr. Cibas said.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
EXPERT ANALYSIS FROM WCTC 2017
VIDEO: Lenvatinib’s real-world thyroid cancer performance matches trial
BOSTON – Lenvatinib’s real-world performance treating advanced, radio-iodine refractory, differentiated thyroid cancer closely followed the efficacy and adverse effect profiles the drug showed in its pivotal trial.
Lenvatinib showed good efficacy in 75 French registry patients, while also producing adverse effects in virtually every patient, but with the possibility to resolve the adverse effects with dose reductions or short-term treatment discontinuations, Martin Schlumberger, MD, said at the World Congress on Thyroid Cancer.
“Lenvatinib is toxic, but the toxicity can be managed in almost all patients by drug withholding or by reducing the dosage, and with symptomatic treatments,” Dr. Schlumberger said in a video interview. But adverse events are a “major problem” for the drug, so patients receiving lenvatinib “should be seen very frequently, and as soon as toxicity appears it should be treated,” said Dr. Schlumberger, professor of medicine and chairman of nuclear medicine and endocrine oncology at Gustave Roussy in Paris.
But lenvatinib’s efficacy makes it a first-line option despite the frequent adverse effects it causes.
“Without doubt it is the most effective drug” for treating advanced, rapidly progressing, radio-iodine refractory thyroid cancer, he said. “When patients really need systemic therapy they should get lenvatinib. It’s a balance of risk and benefit, and the risk from not being treated is higher than the risk from adverse effects.”
A similar pattern of adverse effects and efficacy was seen for lenvatinib in the pivotal Study of Lenvatinib in Differentiated Cancer of the Thyroid (SELECT) trial, which reported a median 18-month progression-free survival rate among patients treated with the drug compared with a median 4-month progression-free survival rate in placebo-treated patients (N Engl J Med. 2015 Feb 12;372[7]:621-30).
Among the 75 patients enrolled in the French registry, the median time of progression-free survival was 10 months, with 8 patients on continued therapy without progression. The response rate in the registry was 31% compared with 65% in the SELECT trial (and 2% in placebo-treated patients in SELECT), but the registry included many patients with advanced disease, comorbidities, and pretreatment, Dr. Schlumberger reported. Just 17 of the registry patients (23%) would have met the enrollment criteria for SELECT. Among this subset the response rate to lenvatinib was 47%.
A multivariate analysis identified three factors that significantly linked with drug responses, Dr. Schlumberger said: pretreatment, more advanced disease, and comorbidities.
Treatment-related adverse effects occurred in 71 of the registry patients (95%), with half of these grade 3 or higher. Twelve patients (16%) discontinued treatment because of an adverse effect. Hypertension was the most common adverse effect, occurring in 50 patients (67%), with 26 having grade 3 or higher hypertension. Other common adverse effects were fatigue, weight loss, diarrhea, and anorexia.
The 75 patients began treatment with lenvatinib for advanced thyroid cancer at any of 24 French centers during April 2015–June 2016. This marked the first year when lenvatinib was available in France for routine use, which roughly coincided with its U.S. introduction after lenvatinib received Food and Drug Administration marketing approval for advanced thyroid cancer in February 2015. Fifty-four patients (72%) began treatment on the labeled dosage of 24 mg/day; the remaining patients started the drug at a lower dosage.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
Because of its efficacy lenvatinib is absolutely the top thymidine kinase inhibitor to use today to treat patients with radio-iodine-resistant, progressive, differentiated thyroid cancer. Although comparing drugs across trials is unreliable, the activity of lenvatinib in the SELECT trial (N Engl J Med. 2015 Feb 12;372[7]:621-30) was better than the activity of sorafenib in the DECISION trial (Lancet. 2014 July 26;384[9940]:319-28). There was enough of a difference between lenvatinib and sorafenib in the SELECT and DECISION trials to convince me that lenvatinib is the better drug.
Many of the patients enrolled in the French registry would not have qualified to enter the SELECT trial, so I’m not surprised that there was a lower response rate in the registry. We know that lenvatinib works better when the tumor burden is low, and some of the registry patients had a high tumor burden. In addition, a fraction of the registry patients did not receive a dosage of 24 mg/day, and data from the SELECT trial suggests that dosage size matters. The full dosage of 24 mg/day should be used as the starting dosage for lenvatinib, but that isn’t always possible for elderly patients or those with comorbidities.
A rise in blood pressure with lenvatinib treatment is not a completely bad outcome, because our experience with lenvatinib shows that this adverse effect actually links with a survival benefit. A spike in a patient’s blood pressure in response to lenvatinib is a sign that the drug is working and the patient will have a good treatment response, an association that we’ve seen with other tumor types and with other thymidine kinase inhibitors.
Unfortunately, a good response to lenvatinib is usually not enough in the long run. Experience shows that even when advanced thyroid cancer responds to lenvatinib or to another thymidine kinase inhibitor, eventually the disease will progress despite this treatment.
Lori J. Wirth, MD , is medical director of the Center for Head and Neck Cancers at Massachusetts General Hospital in Boston. She has been a consultant to Eisai, Blueprint Medicines, Loxo, and Merck. She made these comments in an interview.
Because of its efficacy lenvatinib is absolutely the top thymidine kinase inhibitor to use today to treat patients with radio-iodine-resistant, progressive, differentiated thyroid cancer. Although comparing drugs across trials is unreliable, the activity of lenvatinib in the SELECT trial (N Engl J Med. 2015 Feb 12;372[7]:621-30) was better than the activity of sorafenib in the DECISION trial (Lancet. 2014 July 26;384[9940]:319-28). There was enough of a difference between lenvatinib and sorafenib in the SELECT and DECISION trials to convince me that lenvatinib is the better drug.
Many of the patients enrolled in the French registry would not have qualified to enter the SELECT trial, so I’m not surprised that there was a lower response rate in the registry. We know that lenvatinib works better when the tumor burden is low, and some of the registry patients had a high tumor burden. In addition, a fraction of the registry patients did not receive a dosage of 24 mg/day, and data from the SELECT trial suggests that dosage size matters. The full dosage of 24 mg/day should be used as the starting dosage for lenvatinib, but that isn’t always possible for elderly patients or those with comorbidities.
A rise in blood pressure with lenvatinib treatment is not a completely bad outcome, because our experience with lenvatinib shows that this adverse effect actually links with a survival benefit. A spike in a patient’s blood pressure in response to lenvatinib is a sign that the drug is working and the patient will have a good treatment response, an association that we’ve seen with other tumor types and with other thymidine kinase inhibitors.
Unfortunately, a good response to lenvatinib is usually not enough in the long run. Experience shows that even when advanced thyroid cancer responds to lenvatinib or to another thymidine kinase inhibitor, eventually the disease will progress despite this treatment.
Lori J. Wirth, MD , is medical director of the Center for Head and Neck Cancers at Massachusetts General Hospital in Boston. She has been a consultant to Eisai, Blueprint Medicines, Loxo, and Merck. She made these comments in an interview.
Because of its efficacy lenvatinib is absolutely the top thymidine kinase inhibitor to use today to treat patients with radio-iodine-resistant, progressive, differentiated thyroid cancer. Although comparing drugs across trials is unreliable, the activity of lenvatinib in the SELECT trial (N Engl J Med. 2015 Feb 12;372[7]:621-30) was better than the activity of sorafenib in the DECISION trial (Lancet. 2014 July 26;384[9940]:319-28). There was enough of a difference between lenvatinib and sorafenib in the SELECT and DECISION trials to convince me that lenvatinib is the better drug.
Many of the patients enrolled in the French registry would not have qualified to enter the SELECT trial, so I’m not surprised that there was a lower response rate in the registry. We know that lenvatinib works better when the tumor burden is low, and some of the registry patients had a high tumor burden. In addition, a fraction of the registry patients did not receive a dosage of 24 mg/day, and data from the SELECT trial suggests that dosage size matters. The full dosage of 24 mg/day should be used as the starting dosage for lenvatinib, but that isn’t always possible for elderly patients or those with comorbidities.
A rise in blood pressure with lenvatinib treatment is not a completely bad outcome, because our experience with lenvatinib shows that this adverse effect actually links with a survival benefit. A spike in a patient’s blood pressure in response to lenvatinib is a sign that the drug is working and the patient will have a good treatment response, an association that we’ve seen with other tumor types and with other thymidine kinase inhibitors.
Unfortunately, a good response to lenvatinib is usually not enough in the long run. Experience shows that even when advanced thyroid cancer responds to lenvatinib or to another thymidine kinase inhibitor, eventually the disease will progress despite this treatment.
Lori J. Wirth, MD , is medical director of the Center for Head and Neck Cancers at Massachusetts General Hospital in Boston. She has been a consultant to Eisai, Blueprint Medicines, Loxo, and Merck. She made these comments in an interview.
BOSTON – Lenvatinib’s real-world performance treating advanced, radio-iodine refractory, differentiated thyroid cancer closely followed the efficacy and adverse effect profiles the drug showed in its pivotal trial.
Lenvatinib showed good efficacy in 75 French registry patients, while also producing adverse effects in virtually every patient, but with the possibility to resolve the adverse effects with dose reductions or short-term treatment discontinuations, Martin Schlumberger, MD, said at the World Congress on Thyroid Cancer.
“Lenvatinib is toxic, but the toxicity can be managed in almost all patients by drug withholding or by reducing the dosage, and with symptomatic treatments,” Dr. Schlumberger said in a video interview. But adverse events are a “major problem” for the drug, so patients receiving lenvatinib “should be seen very frequently, and as soon as toxicity appears it should be treated,” said Dr. Schlumberger, professor of medicine and chairman of nuclear medicine and endocrine oncology at Gustave Roussy in Paris.
But lenvatinib’s efficacy makes it a first-line option despite the frequent adverse effects it causes.
“Without doubt it is the most effective drug” for treating advanced, rapidly progressing, radio-iodine refractory thyroid cancer, he said. “When patients really need systemic therapy they should get lenvatinib. It’s a balance of risk and benefit, and the risk from not being treated is higher than the risk from adverse effects.”
A similar pattern of adverse effects and efficacy was seen for lenvatinib in the pivotal Study of Lenvatinib in Differentiated Cancer of the Thyroid (SELECT) trial, which reported a median 18-month progression-free survival rate among patients treated with the drug compared with a median 4-month progression-free survival rate in placebo-treated patients (N Engl J Med. 2015 Feb 12;372[7]:621-30).
Among the 75 patients enrolled in the French registry, the median time of progression-free survival was 10 months, with 8 patients on continued therapy without progression. The response rate in the registry was 31% compared with 65% in the SELECT trial (and 2% in placebo-treated patients in SELECT), but the registry included many patients with advanced disease, comorbidities, and pretreatment, Dr. Schlumberger reported. Just 17 of the registry patients (23%) would have met the enrollment criteria for SELECT. Among this subset the response rate to lenvatinib was 47%.
A multivariate analysis identified three factors that significantly linked with drug responses, Dr. Schlumberger said: pretreatment, more advanced disease, and comorbidities.
Treatment-related adverse effects occurred in 71 of the registry patients (95%), with half of these grade 3 or higher. Twelve patients (16%) discontinued treatment because of an adverse effect. Hypertension was the most common adverse effect, occurring in 50 patients (67%), with 26 having grade 3 or higher hypertension. Other common adverse effects were fatigue, weight loss, diarrhea, and anorexia.
The 75 patients began treatment with lenvatinib for advanced thyroid cancer at any of 24 French centers during April 2015–June 2016. This marked the first year when lenvatinib was available in France for routine use, which roughly coincided with its U.S. introduction after lenvatinib received Food and Drug Administration marketing approval for advanced thyroid cancer in February 2015. Fifty-four patients (72%) began treatment on the labeled dosage of 24 mg/day; the remaining patients started the drug at a lower dosage.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
BOSTON – Lenvatinib’s real-world performance treating advanced, radio-iodine refractory, differentiated thyroid cancer closely followed the efficacy and adverse effect profiles the drug showed in its pivotal trial.
Lenvatinib showed good efficacy in 75 French registry patients, while also producing adverse effects in virtually every patient, but with the possibility to resolve the adverse effects with dose reductions or short-term treatment discontinuations, Martin Schlumberger, MD, said at the World Congress on Thyroid Cancer.
“Lenvatinib is toxic, but the toxicity can be managed in almost all patients by drug withholding or by reducing the dosage, and with symptomatic treatments,” Dr. Schlumberger said in a video interview. But adverse events are a “major problem” for the drug, so patients receiving lenvatinib “should be seen very frequently, and as soon as toxicity appears it should be treated,” said Dr. Schlumberger, professor of medicine and chairman of nuclear medicine and endocrine oncology at Gustave Roussy in Paris.
But lenvatinib’s efficacy makes it a first-line option despite the frequent adverse effects it causes.
“Without doubt it is the most effective drug” for treating advanced, rapidly progressing, radio-iodine refractory thyroid cancer, he said. “When patients really need systemic therapy they should get lenvatinib. It’s a balance of risk and benefit, and the risk from not being treated is higher than the risk from adverse effects.”
A similar pattern of adverse effects and efficacy was seen for lenvatinib in the pivotal Study of Lenvatinib in Differentiated Cancer of the Thyroid (SELECT) trial, which reported a median 18-month progression-free survival rate among patients treated with the drug compared with a median 4-month progression-free survival rate in placebo-treated patients (N Engl J Med. 2015 Feb 12;372[7]:621-30).
Among the 75 patients enrolled in the French registry, the median time of progression-free survival was 10 months, with 8 patients on continued therapy without progression. The response rate in the registry was 31% compared with 65% in the SELECT trial (and 2% in placebo-treated patients in SELECT), but the registry included many patients with advanced disease, comorbidities, and pretreatment, Dr. Schlumberger reported. Just 17 of the registry patients (23%) would have met the enrollment criteria for SELECT. Among this subset the response rate to lenvatinib was 47%.
A multivariate analysis identified three factors that significantly linked with drug responses, Dr. Schlumberger said: pretreatment, more advanced disease, and comorbidities.
Treatment-related adverse effects occurred in 71 of the registry patients (95%), with half of these grade 3 or higher. Twelve patients (16%) discontinued treatment because of an adverse effect. Hypertension was the most common adverse effect, occurring in 50 patients (67%), with 26 having grade 3 or higher hypertension. Other common adverse effects were fatigue, weight loss, diarrhea, and anorexia.
The 75 patients began treatment with lenvatinib for advanced thyroid cancer at any of 24 French centers during April 2015–June 2016. This marked the first year when lenvatinib was available in France for routine use, which roughly coincided with its U.S. introduction after lenvatinib received Food and Drug Administration marketing approval for advanced thyroid cancer in February 2015. Fifty-four patients (72%) began treatment on the labeled dosage of 24 mg/day; the remaining patients started the drug at a lower dosage.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
AT WCTC 2017
Key clinical point:
Major finding: The median time of progression-free survival was 10 months in the registry and 18 months in the pivotal trial.
Data source: A retrospective review of the first 75 French patients with advanced differentiated thyroid cancer who received lenvatinib following its marketing approval.
Disclosures: Dr. Schlumberger has received research funding from Eisai, the company that markets lenvatinib (Lenvima). He has also received research support and honoraria from AstraZeneca, Bayer, and Excelixis.
VIDEO: Less follow-up proposed for low-risk thyroid cancer
BOSTON – , Bryan R. Haugen, MD, suggested in a keynote lecture during the World Congress on Thyroid Cancer.
Traditionally, thyroid cancer specialists have monitored these patients for persistent or recurrent disease as often as every 6 or 12 months. “But what we’ve realized with recent assessments of response to treatment is that some patients do well without a recurrence over many years; so, the concept of doing less monitoring and less imaging, especially in patients with an excellent response [to their initial treatment], is being studied,” Dr. Haugen said in a video interview following his talk.
He estimated that perhaps two-thirds or as many as three-quarters of patients with differentiated thyroid cancer fall into the category of having low- or intermediate-risk disease with an excellent or good response to treatment, and hence they are potential candidates for eventually transitioning to less frequent follow-up.
During his talk, Dr. Haugen suggested that after several years with no sign of disease recurrence, lower-risk patients with an excellent treatment response may be able to stop undergoing regular monitoring, and those with a good treatment response may be able to safely have their monitoring intervals extended.
According to the most recent (2015) guidelines for differentiated thyroid cancer management from the American Thyroid Association, lower-risk patients with an excellent treatment response should have their serum thyroglobulin measured every 12-24 months and undergo an ultrasound examination every 3-5 years, while patients with a good response are targeted for serum thyroglobulin measurement annually with an ultrasound every 1-3 years (Thyroid. 2016 Jan;26[1]:1-133). Dr. Haugen chaired the expert panel that wrote these guidelines.
In another provocative suggestion, Dr. Haugen proposed that once well-responsive, lower-risk patients have remained disease free for several years, their less frequent follow-up monitoring could be continued by a primary care physician or another less specialized clinician.
At some time in the future, “a patient’s primary care physician could follow a simple tumor marker, thyroglobulin, maybe once every 5 years,” said Dr. Haugen, professor of medicine and head of the division of endocrinology, metabolism, and diabetes at the University of Colorado in Aurora. “At the University of Colorado, we use advanced-practice providers to do long-term follow-up” for lower-risk, treatment-responsive patients, he said.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @mitchelzoler
BOSTON – , Bryan R. Haugen, MD, suggested in a keynote lecture during the World Congress on Thyroid Cancer.
Traditionally, thyroid cancer specialists have monitored these patients for persistent or recurrent disease as often as every 6 or 12 months. “But what we’ve realized with recent assessments of response to treatment is that some patients do well without a recurrence over many years; so, the concept of doing less monitoring and less imaging, especially in patients with an excellent response [to their initial treatment], is being studied,” Dr. Haugen said in a video interview following his talk.
He estimated that perhaps two-thirds or as many as three-quarters of patients with differentiated thyroid cancer fall into the category of having low- or intermediate-risk disease with an excellent or good response to treatment, and hence they are potential candidates for eventually transitioning to less frequent follow-up.
During his talk, Dr. Haugen suggested that after several years with no sign of disease recurrence, lower-risk patients with an excellent treatment response may be able to stop undergoing regular monitoring, and those with a good treatment response may be able to safely have their monitoring intervals extended.
According to the most recent (2015) guidelines for differentiated thyroid cancer management from the American Thyroid Association, lower-risk patients with an excellent treatment response should have their serum thyroglobulin measured every 12-24 months and undergo an ultrasound examination every 3-5 years, while patients with a good response are targeted for serum thyroglobulin measurement annually with an ultrasound every 1-3 years (Thyroid. 2016 Jan;26[1]:1-133). Dr. Haugen chaired the expert panel that wrote these guidelines.
In another provocative suggestion, Dr. Haugen proposed that once well-responsive, lower-risk patients have remained disease free for several years, their less frequent follow-up monitoring could be continued by a primary care physician or another less specialized clinician.
At some time in the future, “a patient’s primary care physician could follow a simple tumor marker, thyroglobulin, maybe once every 5 years,” said Dr. Haugen, professor of medicine and head of the division of endocrinology, metabolism, and diabetes at the University of Colorado in Aurora. “At the University of Colorado, we use advanced-practice providers to do long-term follow-up” for lower-risk, treatment-responsive patients, he said.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @mitchelzoler
BOSTON – , Bryan R. Haugen, MD, suggested in a keynote lecture during the World Congress on Thyroid Cancer.
Traditionally, thyroid cancer specialists have monitored these patients for persistent or recurrent disease as often as every 6 or 12 months. “But what we’ve realized with recent assessments of response to treatment is that some patients do well without a recurrence over many years; so, the concept of doing less monitoring and less imaging, especially in patients with an excellent response [to their initial treatment], is being studied,” Dr. Haugen said in a video interview following his talk.
He estimated that perhaps two-thirds or as many as three-quarters of patients with differentiated thyroid cancer fall into the category of having low- or intermediate-risk disease with an excellent or good response to treatment, and hence they are potential candidates for eventually transitioning to less frequent follow-up.
During his talk, Dr. Haugen suggested that after several years with no sign of disease recurrence, lower-risk patients with an excellent treatment response may be able to stop undergoing regular monitoring, and those with a good treatment response may be able to safely have their monitoring intervals extended.
According to the most recent (2015) guidelines for differentiated thyroid cancer management from the American Thyroid Association, lower-risk patients with an excellent treatment response should have their serum thyroglobulin measured every 12-24 months and undergo an ultrasound examination every 3-5 years, while patients with a good response are targeted for serum thyroglobulin measurement annually with an ultrasound every 1-3 years (Thyroid. 2016 Jan;26[1]:1-133). Dr. Haugen chaired the expert panel that wrote these guidelines.
In another provocative suggestion, Dr. Haugen proposed that once well-responsive, lower-risk patients have remained disease free for several years, their less frequent follow-up monitoring could be continued by a primary care physician or another less specialized clinician.
At some time in the future, “a patient’s primary care physician could follow a simple tumor marker, thyroglobulin, maybe once every 5 years,” said Dr. Haugen, professor of medicine and head of the division of endocrinology, metabolism, and diabetes at the University of Colorado in Aurora. “At the University of Colorado, we use advanced-practice providers to do long-term follow-up” for lower-risk, treatment-responsive patients, he said.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @mitchelzoler
AT WCTC 2017
USPSTF: No thyroid cancer screening for asymptomatic adults
The U.S. Preventive Services Task Force recommends against screening asymptomatic adults for thyroid cancer, because the harms of such screening outweigh the benefits, according to a recommendation statement published May 9 in JAMA.
The USPSTF makes recommendations about the effectiveness of specific health care services for patients who don’t have related signs or symptoms. In this case, the recommendation statement addresses screening of adults who have no signs or symptoms of thyroid cancer by using neck palpation or ultrasonography, said Kirsten Bibbins-Domingo, MD, PhD, chair of the organization and lead author of the recommendation statement, and her associates (JAMA. 2017 May 9;317[18]:1882-7).
This document is an update of the previous USPSTF recommendation statement issued in 1996 and was undertaken because there have been several major advances related to the disease since that time.
However, despite a comprehensive review of the current literature, the group found no direct evidence supporting a change to their original advice against such screening.
They emphasized that this applies only to asymptomatic adults, not to those who have hoarseness, throat pain, difficulty swallowing, lumps in the neck, swelling, or asymmetry of the neck; nor to those who have a history of exposure to ionizing radiation, a family history of thyroid cancer, or a genetic susceptibility to the disease.
The results of the literature review were summarized in an evidence report by Jennifer S. Lin, MD, of Kaiser Permanente Center for Health Research, Portland, Ore., and her associates. They examined 67 studies involving nearly 584,000 patients, including 10 studies that addressed screening test performance, 3 that addressed the possible harms of screening, 2 that addressed treatment benefits, and 52 that addressed treatment harms.
No good-quality studies assessed the net benefit of thyroid cancer screening, nor whether “early” treatment of screen-detected cancers improved patient outcomes. However, the preponderance of evidence suggested that most thyroid cancers detected by screening are indolent.
So, treatment is likely unnecessary but exposes patients to “nontrivial” harms, including an increased risk of second primary malignancy, permanent adverse effects on the salivary glands, laryngeal nerve injury, hypoparathyroidism, and the need for lifelong thyroid replacement therapy and monitoring for cancer recurrence, Dr. Lin and her associates said in their evidence report (JAMA. 2017 May 9;317[18]:1888-1903).
The task force noted that no professional medical society currently recommends population-based screening for thyroid cancer. The American Cancer Society, American Thyroid Association, American Association of Clinical Endocrinologists, and American College of Endocrinology all have no specific recommendations for screening asymptomatic patients, while the American Academy of Family Physicians recommends against such screening, said Dr. Bibbins-Domingo, who is also a professor of medicine at the University of California, San Francisco, and her associates.
Further information regarding the recommendation statement and the evidence report is available at www.uspreventiveservicestaskforce.org.
The USPSTF is an independent voluntary group supported by the Agency for Healthcare Research and Quality. The authors’ conflict of interest disclosures are available at www.uspreventiveservicestaskforce.org.
The rationale for recommending against screening asymptomatic people for thyroid cancer is compelling, and the evidence clearly points to the harms outweighing the benefits.
But that doesn’t mean that the conversation about screening should stop. What the field needs is not a better means to detect thyroid nodules, but a noninvasive measure to distinguish nodules whose cells will leave the thyroid capsule and cause morbidity from nodules whose cells will not. That will spare patients with indolent cancers from unnecessary treatment, while steering the minority of patients with more aggressive cancers to early treatment.
Anne R. Cappola, MD, is in the division of endocrinology, diabetes, and metabolism at the University of Pennsylvania, Philadelphia, and is an associate editor of JAMA. She reported having no relevant financial disclosures. Dr. Cappola made these remarks in an editorial accompanying the recommendation statement and the evidence report (JAMA. 2017 May 9;317[18]:1840-1).
The rationale for recommending against screening asymptomatic people for thyroid cancer is compelling, and the evidence clearly points to the harms outweighing the benefits.
But that doesn’t mean that the conversation about screening should stop. What the field needs is not a better means to detect thyroid nodules, but a noninvasive measure to distinguish nodules whose cells will leave the thyroid capsule and cause morbidity from nodules whose cells will not. That will spare patients with indolent cancers from unnecessary treatment, while steering the minority of patients with more aggressive cancers to early treatment.
Anne R. Cappola, MD, is in the division of endocrinology, diabetes, and metabolism at the University of Pennsylvania, Philadelphia, and is an associate editor of JAMA. She reported having no relevant financial disclosures. Dr. Cappola made these remarks in an editorial accompanying the recommendation statement and the evidence report (JAMA. 2017 May 9;317[18]:1840-1).
The rationale for recommending against screening asymptomatic people for thyroid cancer is compelling, and the evidence clearly points to the harms outweighing the benefits.
But that doesn’t mean that the conversation about screening should stop. What the field needs is not a better means to detect thyroid nodules, but a noninvasive measure to distinguish nodules whose cells will leave the thyroid capsule and cause morbidity from nodules whose cells will not. That will spare patients with indolent cancers from unnecessary treatment, while steering the minority of patients with more aggressive cancers to early treatment.
Anne R. Cappola, MD, is in the division of endocrinology, diabetes, and metabolism at the University of Pennsylvania, Philadelphia, and is an associate editor of JAMA. She reported having no relevant financial disclosures. Dr. Cappola made these remarks in an editorial accompanying the recommendation statement and the evidence report (JAMA. 2017 May 9;317[18]:1840-1).
The U.S. Preventive Services Task Force recommends against screening asymptomatic adults for thyroid cancer, because the harms of such screening outweigh the benefits, according to a recommendation statement published May 9 in JAMA.
The USPSTF makes recommendations about the effectiveness of specific health care services for patients who don’t have related signs or symptoms. In this case, the recommendation statement addresses screening of adults who have no signs or symptoms of thyroid cancer by using neck palpation or ultrasonography, said Kirsten Bibbins-Domingo, MD, PhD, chair of the organization and lead author of the recommendation statement, and her associates (JAMA. 2017 May 9;317[18]:1882-7).
This document is an update of the previous USPSTF recommendation statement issued in 1996 and was undertaken because there have been several major advances related to the disease since that time.
However, despite a comprehensive review of the current literature, the group found no direct evidence supporting a change to their original advice against such screening.
They emphasized that this applies only to asymptomatic adults, not to those who have hoarseness, throat pain, difficulty swallowing, lumps in the neck, swelling, or asymmetry of the neck; nor to those who have a history of exposure to ionizing radiation, a family history of thyroid cancer, or a genetic susceptibility to the disease.
The results of the literature review were summarized in an evidence report by Jennifer S. Lin, MD, of Kaiser Permanente Center for Health Research, Portland, Ore., and her associates. They examined 67 studies involving nearly 584,000 patients, including 10 studies that addressed screening test performance, 3 that addressed the possible harms of screening, 2 that addressed treatment benefits, and 52 that addressed treatment harms.
No good-quality studies assessed the net benefit of thyroid cancer screening, nor whether “early” treatment of screen-detected cancers improved patient outcomes. However, the preponderance of evidence suggested that most thyroid cancers detected by screening are indolent.
So, treatment is likely unnecessary but exposes patients to “nontrivial” harms, including an increased risk of second primary malignancy, permanent adverse effects on the salivary glands, laryngeal nerve injury, hypoparathyroidism, and the need for lifelong thyroid replacement therapy and monitoring for cancer recurrence, Dr. Lin and her associates said in their evidence report (JAMA. 2017 May 9;317[18]:1888-1903).
The task force noted that no professional medical society currently recommends population-based screening for thyroid cancer. The American Cancer Society, American Thyroid Association, American Association of Clinical Endocrinologists, and American College of Endocrinology all have no specific recommendations for screening asymptomatic patients, while the American Academy of Family Physicians recommends against such screening, said Dr. Bibbins-Domingo, who is also a professor of medicine at the University of California, San Francisco, and her associates.
Further information regarding the recommendation statement and the evidence report is available at www.uspreventiveservicestaskforce.org.
The USPSTF is an independent voluntary group supported by the Agency for Healthcare Research and Quality. The authors’ conflict of interest disclosures are available at www.uspreventiveservicestaskforce.org.
The U.S. Preventive Services Task Force recommends against screening asymptomatic adults for thyroid cancer, because the harms of such screening outweigh the benefits, according to a recommendation statement published May 9 in JAMA.
The USPSTF makes recommendations about the effectiveness of specific health care services for patients who don’t have related signs or symptoms. In this case, the recommendation statement addresses screening of adults who have no signs or symptoms of thyroid cancer by using neck palpation or ultrasonography, said Kirsten Bibbins-Domingo, MD, PhD, chair of the organization and lead author of the recommendation statement, and her associates (JAMA. 2017 May 9;317[18]:1882-7).
This document is an update of the previous USPSTF recommendation statement issued in 1996 and was undertaken because there have been several major advances related to the disease since that time.
However, despite a comprehensive review of the current literature, the group found no direct evidence supporting a change to their original advice against such screening.
They emphasized that this applies only to asymptomatic adults, not to those who have hoarseness, throat pain, difficulty swallowing, lumps in the neck, swelling, or asymmetry of the neck; nor to those who have a history of exposure to ionizing radiation, a family history of thyroid cancer, or a genetic susceptibility to the disease.
The results of the literature review were summarized in an evidence report by Jennifer S. Lin, MD, of Kaiser Permanente Center for Health Research, Portland, Ore., and her associates. They examined 67 studies involving nearly 584,000 patients, including 10 studies that addressed screening test performance, 3 that addressed the possible harms of screening, 2 that addressed treatment benefits, and 52 that addressed treatment harms.
No good-quality studies assessed the net benefit of thyroid cancer screening, nor whether “early” treatment of screen-detected cancers improved patient outcomes. However, the preponderance of evidence suggested that most thyroid cancers detected by screening are indolent.
So, treatment is likely unnecessary but exposes patients to “nontrivial” harms, including an increased risk of second primary malignancy, permanent adverse effects on the salivary glands, laryngeal nerve injury, hypoparathyroidism, and the need for lifelong thyroid replacement therapy and monitoring for cancer recurrence, Dr. Lin and her associates said in their evidence report (JAMA. 2017 May 9;317[18]:1888-1903).
The task force noted that no professional medical society currently recommends population-based screening for thyroid cancer. The American Cancer Society, American Thyroid Association, American Association of Clinical Endocrinologists, and American College of Endocrinology all have no specific recommendations for screening asymptomatic patients, while the American Academy of Family Physicians recommends against such screening, said Dr. Bibbins-Domingo, who is also a professor of medicine at the University of California, San Francisco, and her associates.
Further information regarding the recommendation statement and the evidence report is available at www.uspreventiveservicestaskforce.org.
The USPSTF is an independent voluntary group supported by the Agency for Healthcare Research and Quality. The authors’ conflict of interest disclosures are available at www.uspreventiveservicestaskforce.org.
FROM JAMA
Key clinical point: The USPSTF recommends against screening asymptomatic adults for thyroid cancer because the harms outweigh the benefits.
Major finding: None of the 67 studies reviewed in the evidence report directly assessed the net benefit of thyroid cancer screening, nor whether “early” treatment of screen-detected cancers improved patient outcomes.
Data source: A recommendation statement based on a review of 67 studies published during 1996-2016 involving 583,914 patients.
Disclosures: The USPSTF is an independent voluntary group supported by the Agency for Healthcare Research and Quality. The authors’ conflict of interest disclosures are available at www.uspreventiveservicestaskforce.org.
Metformin linked with better survival in RCC patients with diabetes
Metformin use was associated with better survival for patients with renal cell carcinoma and diabetes in a meta-analysis, investigators report.
Yang Li, MD, and associates at Chongqing (China) Medical University, performed a pooled analysis of data from 254,329 patients with both localized and metastatic renal cell carcinoma, and found the risk of mortality was reduced in patients exposed to metformin (hazard ratio, 0.41; P less than .001).
However, there was significant heterogeneity among the eight eligible studies included in the meta-analysis, Dr. Li and associates reported (Int Urol Nephrol. 2017 Mar 7. doi: 10.1007/s11255-017-1548-4).
In a subgroup analysis, the association held in patients with localized disease, but was not significant in those with metastatic disease.
The current meta-analysis suggests that the use of metformin could improve the survival of kidney cancer patients, particularly those with localized disease; however, further studies are needed, the investigators conclude.
The authors declared that they had no conflicts of interest.
Metformin use was associated with better survival for patients with renal cell carcinoma and diabetes in a meta-analysis, investigators report.
Yang Li, MD, and associates at Chongqing (China) Medical University, performed a pooled analysis of data from 254,329 patients with both localized and metastatic renal cell carcinoma, and found the risk of mortality was reduced in patients exposed to metformin (hazard ratio, 0.41; P less than .001).
However, there was significant heterogeneity among the eight eligible studies included in the meta-analysis, Dr. Li and associates reported (Int Urol Nephrol. 2017 Mar 7. doi: 10.1007/s11255-017-1548-4).
In a subgroup analysis, the association held in patients with localized disease, but was not significant in those with metastatic disease.
The current meta-analysis suggests that the use of metformin could improve the survival of kidney cancer patients, particularly those with localized disease; however, further studies are needed, the investigators conclude.
The authors declared that they had no conflicts of interest.
Metformin use was associated with better survival for patients with renal cell carcinoma and diabetes in a meta-analysis, investigators report.
Yang Li, MD, and associates at Chongqing (China) Medical University, performed a pooled analysis of data from 254,329 patients with both localized and metastatic renal cell carcinoma, and found the risk of mortality was reduced in patients exposed to metformin (hazard ratio, 0.41; P less than .001).
However, there was significant heterogeneity among the eight eligible studies included in the meta-analysis, Dr. Li and associates reported (Int Urol Nephrol. 2017 Mar 7. doi: 10.1007/s11255-017-1548-4).
In a subgroup analysis, the association held in patients with localized disease, but was not significant in those with metastatic disease.
The current meta-analysis suggests that the use of metformin could improve the survival of kidney cancer patients, particularly those with localized disease; however, further studies are needed, the investigators conclude.
The authors declared that they had no conflicts of interest.
Key clinical point:
Major finding: In a pooled analysis of data from eight studies, the risk of mortality was reduced in patients exposed to metformin (hazard ratio, 0.41; P less than .001).
Data source: A meta-analysis of eight studies including 254,329 patients with renal cell carcinoma.
Disclosures: The authors declared that they had no conflicts of interest.
Temozolomide may help half of patients with aggressive pituitary tumors
ORLANDO – Temozolomide, an alkylating agent approved for glioblastoma, improved long-term survival in about half of patients who took it for aggressive pituitary tumors, a retrospective study has determined.
The study, conducted by members of the French Society of Endocrinology, comprised 43 patients. Of the 51% who responded to the treatment, the median overall survival time was 44 months, compared to just 16 months for patients who didn’t respond, Gérald Raverot, MD, said at the annual meeting of the Endocrine Society.
“Despite the very good response we saw in some patients, we also saw a high risk of recurrence, with a median of about 30 months,” for relapse, he noted. “And a second course of temozolomide always failed.”
When used for aggressive pituitary tumors, temozolomide is usually given in a conventional scheme of up to 12 cycles. It’s typically reserved for tumors that have responded poorly to other treatment regimens, Dr. Raverot said.
The drug has not been widely studied in patients with aggressive pituitary tumors, although there have been a number of case reports suggesting that can be beneficial. Data on about 90 patients have been published. The largest series to date appeared in 2015 and comprised 24 patients. It found about a 50% response rate to the drug. Two patients had a complete regression and seven patients had a partial regression of tumor mass. Tumor mass shrunk to less than 30% in three patients, less than 50% in three, and less than 75% in one.
Because of both the promise temozolomide shows in these very tough cases, and the paucity of descriptive and clinical data, Dr. Raverot and his colleagues conducted a multi-center study that spanned 21 facilities in France and comprised 43 patients who were treated from 2006-2016. The intent was to evaluate efficacy at the end of treatment, or at last follow-up in the case of those who were still being treated. Tumor response was defined as a decrease of more than 30% in the largest tumor diameter; hormonal response was more than a 50% decrease in baseline hormone levels. The endpoint was overall survival and relapse-free survival.
Of the 43 patients, 29 were men. The group’s mean age at diagnosis was 43 years, and the mean age at temozolomide treatment, 53 years. Fourteen of the tumors were carcinomas and 12 were silent or initially silent.
About half of the tumors (23) were adrenocorticotropic hormone-producing. Other tumor types were prolactin-secreting (13) and growth hormone-secreting (3); an additional three tumors secreted both prolactin and growth hormone.
Most patients (36) underwent a typical temozolomide protocol. This consisted of at least one 5-day cycle of 150 mg/m2/day every 28 days, followed by 250 mg/m2/day thereafter. The median number of cycles was 6.5, but this ranged from 1-24 cycles.
Six patients were treated according to the Stupp protocol for temozolomide in glioblastoma. This consists of daily temozolomide 75 mg/m2 with concomitant radiotherapy for 6 weeks, followed by a standard temozolomide protocol. Four patients underwent 6 cycles; one patient 12 cycles, and one patient, 17 cycles.
An additional four patients had concomitant radiotherapy within 4 months of their temozolomide treatment.
The overall response rate was 51% (22 patients). Dr. Raverot attempted to identify clinical characteristics predictive of response. There was no association with gender, age at diagnosis or age at temozolomide treatment, tumor type, whether or not the tumor was a carcinoma, or what type of hormone it secreted. Nor was there a response associated with hypermethylation of the O6-methylguanine-DNA-methyltransferase (MGMT) gene.
Dr. Raverot found only one positive association with response. Tumors that were silent or initially silent (12) were much less likely to respond than secreting tumors. Of the 21 nonresponsive tumors, 10 were silent (45%). Of the 22 responsive tumors, only 2 were silent (9%).
Dr. Raverot also analyzed response by protocol and found intriguing results. Of the 10 patients who had concomitant radiotherapy, seven responded and three did not. Patients who underwent the Stupp protocol also tended to do better, he said. “Of the six who had this, five responded, so this is interesting.”
However, he cautioned, both of these positive associations are based on such small numbers that it’s impossible to draw firm conclusions.
Dr. Raverot had survival data on 38 patients with a median follow-up of 16 months after the end of treatment. Of these, 20 were responders and 18 were non-responders. Death had occurred in 13 of the nonresponders and five responders.
Of the 20 responders, 10 were still controlled at the time of last follow-up, and 10 had relapsed at a median of 5 months after treatment cessation. Five of these patients had a second course of temozolomide, but none of them responded to it, Dr. Raverot said. Three of these patients have died and two are still living.
“We looked at other salvage treatments for them, but none of these therapies could control the disease. Unfortunately, we just don’t have good treatment options for these patients. And even among those with good treatment response, there is a risk of early recurrence, with a median time of 30 months to relapse. The second course of temozolomide always fails. So we have now some questions about who we should maintain on treatment. We don’t have this answered yet, and we need to.”
Dr. Raverot had no financial disclosures.
msullivan@frontlinemedcom.com
On Twitter @Alz_gal
ORLANDO – Temozolomide, an alkylating agent approved for glioblastoma, improved long-term survival in about half of patients who took it for aggressive pituitary tumors, a retrospective study has determined.
The study, conducted by members of the French Society of Endocrinology, comprised 43 patients. Of the 51% who responded to the treatment, the median overall survival time was 44 months, compared to just 16 months for patients who didn’t respond, Gérald Raverot, MD, said at the annual meeting of the Endocrine Society.
“Despite the very good response we saw in some patients, we also saw a high risk of recurrence, with a median of about 30 months,” for relapse, he noted. “And a second course of temozolomide always failed.”
When used for aggressive pituitary tumors, temozolomide is usually given in a conventional scheme of up to 12 cycles. It’s typically reserved for tumors that have responded poorly to other treatment regimens, Dr. Raverot said.
The drug has not been widely studied in patients with aggressive pituitary tumors, although there have been a number of case reports suggesting that can be beneficial. Data on about 90 patients have been published. The largest series to date appeared in 2015 and comprised 24 patients. It found about a 50% response rate to the drug. Two patients had a complete regression and seven patients had a partial regression of tumor mass. Tumor mass shrunk to less than 30% in three patients, less than 50% in three, and less than 75% in one.
Because of both the promise temozolomide shows in these very tough cases, and the paucity of descriptive and clinical data, Dr. Raverot and his colleagues conducted a multi-center study that spanned 21 facilities in France and comprised 43 patients who were treated from 2006-2016. The intent was to evaluate efficacy at the end of treatment, or at last follow-up in the case of those who were still being treated. Tumor response was defined as a decrease of more than 30% in the largest tumor diameter; hormonal response was more than a 50% decrease in baseline hormone levels. The endpoint was overall survival and relapse-free survival.
Of the 43 patients, 29 were men. The group’s mean age at diagnosis was 43 years, and the mean age at temozolomide treatment, 53 years. Fourteen of the tumors were carcinomas and 12 were silent or initially silent.
About half of the tumors (23) were adrenocorticotropic hormone-producing. Other tumor types were prolactin-secreting (13) and growth hormone-secreting (3); an additional three tumors secreted both prolactin and growth hormone.
Most patients (36) underwent a typical temozolomide protocol. This consisted of at least one 5-day cycle of 150 mg/m2/day every 28 days, followed by 250 mg/m2/day thereafter. The median number of cycles was 6.5, but this ranged from 1-24 cycles.
Six patients were treated according to the Stupp protocol for temozolomide in glioblastoma. This consists of daily temozolomide 75 mg/m2 with concomitant radiotherapy for 6 weeks, followed by a standard temozolomide protocol. Four patients underwent 6 cycles; one patient 12 cycles, and one patient, 17 cycles.
An additional four patients had concomitant radiotherapy within 4 months of their temozolomide treatment.
The overall response rate was 51% (22 patients). Dr. Raverot attempted to identify clinical characteristics predictive of response. There was no association with gender, age at diagnosis or age at temozolomide treatment, tumor type, whether or not the tumor was a carcinoma, or what type of hormone it secreted. Nor was there a response associated with hypermethylation of the O6-methylguanine-DNA-methyltransferase (MGMT) gene.
Dr. Raverot found only one positive association with response. Tumors that were silent or initially silent (12) were much less likely to respond than secreting tumors. Of the 21 nonresponsive tumors, 10 were silent (45%). Of the 22 responsive tumors, only 2 were silent (9%).
Dr. Raverot also analyzed response by protocol and found intriguing results. Of the 10 patients who had concomitant radiotherapy, seven responded and three did not. Patients who underwent the Stupp protocol also tended to do better, he said. “Of the six who had this, five responded, so this is interesting.”
However, he cautioned, both of these positive associations are based on such small numbers that it’s impossible to draw firm conclusions.
Dr. Raverot had survival data on 38 patients with a median follow-up of 16 months after the end of treatment. Of these, 20 were responders and 18 were non-responders. Death had occurred in 13 of the nonresponders and five responders.
Of the 20 responders, 10 were still controlled at the time of last follow-up, and 10 had relapsed at a median of 5 months after treatment cessation. Five of these patients had a second course of temozolomide, but none of them responded to it, Dr. Raverot said. Three of these patients have died and two are still living.
“We looked at other salvage treatments for them, but none of these therapies could control the disease. Unfortunately, we just don’t have good treatment options for these patients. And even among those with good treatment response, there is a risk of early recurrence, with a median time of 30 months to relapse. The second course of temozolomide always fails. So we have now some questions about who we should maintain on treatment. We don’t have this answered yet, and we need to.”
Dr. Raverot had no financial disclosures.
msullivan@frontlinemedcom.com
On Twitter @Alz_gal
ORLANDO – Temozolomide, an alkylating agent approved for glioblastoma, improved long-term survival in about half of patients who took it for aggressive pituitary tumors, a retrospective study has determined.
The study, conducted by members of the French Society of Endocrinology, comprised 43 patients. Of the 51% who responded to the treatment, the median overall survival time was 44 months, compared to just 16 months for patients who didn’t respond, Gérald Raverot, MD, said at the annual meeting of the Endocrine Society.
“Despite the very good response we saw in some patients, we also saw a high risk of recurrence, with a median of about 30 months,” for relapse, he noted. “And a second course of temozolomide always failed.”
When used for aggressive pituitary tumors, temozolomide is usually given in a conventional scheme of up to 12 cycles. It’s typically reserved for tumors that have responded poorly to other treatment regimens, Dr. Raverot said.
The drug has not been widely studied in patients with aggressive pituitary tumors, although there have been a number of case reports suggesting that can be beneficial. Data on about 90 patients have been published. The largest series to date appeared in 2015 and comprised 24 patients. It found about a 50% response rate to the drug. Two patients had a complete regression and seven patients had a partial regression of tumor mass. Tumor mass shrunk to less than 30% in three patients, less than 50% in three, and less than 75% in one.
Because of both the promise temozolomide shows in these very tough cases, and the paucity of descriptive and clinical data, Dr. Raverot and his colleagues conducted a multi-center study that spanned 21 facilities in France and comprised 43 patients who were treated from 2006-2016. The intent was to evaluate efficacy at the end of treatment, or at last follow-up in the case of those who were still being treated. Tumor response was defined as a decrease of more than 30% in the largest tumor diameter; hormonal response was more than a 50% decrease in baseline hormone levels. The endpoint was overall survival and relapse-free survival.
Of the 43 patients, 29 were men. The group’s mean age at diagnosis was 43 years, and the mean age at temozolomide treatment, 53 years. Fourteen of the tumors were carcinomas and 12 were silent or initially silent.
About half of the tumors (23) were adrenocorticotropic hormone-producing. Other tumor types were prolactin-secreting (13) and growth hormone-secreting (3); an additional three tumors secreted both prolactin and growth hormone.
Most patients (36) underwent a typical temozolomide protocol. This consisted of at least one 5-day cycle of 150 mg/m2/day every 28 days, followed by 250 mg/m2/day thereafter. The median number of cycles was 6.5, but this ranged from 1-24 cycles.
Six patients were treated according to the Stupp protocol for temozolomide in glioblastoma. This consists of daily temozolomide 75 mg/m2 with concomitant radiotherapy for 6 weeks, followed by a standard temozolomide protocol. Four patients underwent 6 cycles; one patient 12 cycles, and one patient, 17 cycles.
An additional four patients had concomitant radiotherapy within 4 months of their temozolomide treatment.
The overall response rate was 51% (22 patients). Dr. Raverot attempted to identify clinical characteristics predictive of response. There was no association with gender, age at diagnosis or age at temozolomide treatment, tumor type, whether or not the tumor was a carcinoma, or what type of hormone it secreted. Nor was there a response associated with hypermethylation of the O6-methylguanine-DNA-methyltransferase (MGMT) gene.
Dr. Raverot found only one positive association with response. Tumors that were silent or initially silent (12) were much less likely to respond than secreting tumors. Of the 21 nonresponsive tumors, 10 were silent (45%). Of the 22 responsive tumors, only 2 were silent (9%).
Dr. Raverot also analyzed response by protocol and found intriguing results. Of the 10 patients who had concomitant radiotherapy, seven responded and three did not. Patients who underwent the Stupp protocol also tended to do better, he said. “Of the six who had this, five responded, so this is interesting.”
However, he cautioned, both of these positive associations are based on such small numbers that it’s impossible to draw firm conclusions.
Dr. Raverot had survival data on 38 patients with a median follow-up of 16 months after the end of treatment. Of these, 20 were responders and 18 were non-responders. Death had occurred in 13 of the nonresponders and five responders.
Of the 20 responders, 10 were still controlled at the time of last follow-up, and 10 had relapsed at a median of 5 months after treatment cessation. Five of these patients had a second course of temozolomide, but none of them responded to it, Dr. Raverot said. Three of these patients have died and two are still living.
“We looked at other salvage treatments for them, but none of these therapies could control the disease. Unfortunately, we just don’t have good treatment options for these patients. And even among those with good treatment response, there is a risk of early recurrence, with a median time of 30 months to relapse. The second course of temozolomide always fails. So we have now some questions about who we should maintain on treatment. We don’t have this answered yet, and we need to.”
Dr. Raverot had no financial disclosures.
msullivan@frontlinemedcom.com
On Twitter @Alz_gal
AT ENDO 2017
Key clinical point:
Major finding: Of the 51% who responded to the treatment, the median overall survival time was 44 months, compared to just 16 months for patients who didn’t respond.
Data source: The retrospective study comprised 43 patients treated in France.
Disclosures: Dr. Raverot had no financial disclosures.