User login
A third of follicular thyroid lesions of undetermined significance were malignant
CHICAGO – At least in some institutions, about a third of follicular thyroid lesions of undetermined significance are malignant, reported researchers from the University of Wisconsin, Madison.
That rate is a higher proportion than the 5%-15% rate estimated by the Bethesda System, a national standard for reporting thyroid cytopathology, said Dr. Juan Carlos Jaume at the joint meeting of the International Congress of Endocrinology and the Endocrine Society.
"The message here is to be aware of your local institutional rates for cancer in FLUS, because following [the Bethesda System] may mislead you and your patient" when deciding on a course of action, be it surgery, repeat biopsy, or observation, he said. "Other institutions [should be encouraged to] do similar analyses to generate more accurate local guidelines for management of FLUS," noted Dr. Jaume, senior author of the study.
Of 1,420 nodules assessed over 2 years at the thyroid clinic at the University of Wisconsin, Madison, 134 (9.4%) were reported as follicular lesions of undetermined significance (FLUS) on fine-needle aspiration. Eighty patients opted for surgery; pathology revealed that 27 (34%) actually had differentiated thyroid cancer. Cancer also was found in four more patients, but at sites different from the original fine-needle aspiration. Most of the cancers (27) were papillary, 3 were follicular, and 1 was a Hurthle cell tumor, the investigators reported.
It’s unlikely the findings were due to selection bias, with patients who were more likely to have cancer opting for surgery. More than half of the patients chose surgery after discussing risks and benefits with their providers, not because of tumor progression. Almost all the others opted for surgery because of compression symptoms or because they had a nodule larger than 4 cm.
Even if there was a bias, "the highest expectation [with Bethesda] is 15%; our rate was 34%," a large difference, Dr. Jaume said. "As soon as we had the rate available, we conveyed the information" to providers so they could more accurately counsel patients. "I think eventually we will see an increase in the number of patients deciding on surgery."
The team performed the study because providers at the university had been relying on the Bethesda estimate to guide patients, but had a hunch that their local FLUS cancer rates were higher.
The majority of the 134 FLUS patients who opted against surgery chose ultrasound monitoring. Among the 22 who chose repeat fine-needle aspiration, half were rediagnosed with benign cytology, 5 were again diagnosed with FLUS, and most of the rest were lost to follow-up.
Among the 80 surgical patients, pathology was benign in 47 and parathyroid tissue was present in 1 biopsy. Records were unavailable for the final patient.
Some cytopathologists tend to call thyroid lesions FLUS more frequently than others; possibly, that predilection has something to do with the discordance in reported cancer rates, Dr. Jaume said.
Ultimately, the solution will be genetic analysis of fine-needle aspiration samples. There is a commercial product on the market, but "we are not using [it] in our institution because the negative predictive value is high, but the positive predictive value is low," he said.
The investigators had no relevant disclosures and had no outside funding for their work.
*Correction, 8/25/2014: An earlier version of this article misspelled Dr. Jaume's name.
CHICAGO – At least in some institutions, about a third of follicular thyroid lesions of undetermined significance are malignant, reported researchers from the University of Wisconsin, Madison.
That rate is a higher proportion than the 5%-15% rate estimated by the Bethesda System, a national standard for reporting thyroid cytopathology, said Dr. Juan Carlos Jaume at the joint meeting of the International Congress of Endocrinology and the Endocrine Society.
"The message here is to be aware of your local institutional rates for cancer in FLUS, because following [the Bethesda System] may mislead you and your patient" when deciding on a course of action, be it surgery, repeat biopsy, or observation, he said. "Other institutions [should be encouraged to] do similar analyses to generate more accurate local guidelines for management of FLUS," noted Dr. Jaume, senior author of the study.
Of 1,420 nodules assessed over 2 years at the thyroid clinic at the University of Wisconsin, Madison, 134 (9.4%) were reported as follicular lesions of undetermined significance (FLUS) on fine-needle aspiration. Eighty patients opted for surgery; pathology revealed that 27 (34%) actually had differentiated thyroid cancer. Cancer also was found in four more patients, but at sites different from the original fine-needle aspiration. Most of the cancers (27) were papillary, 3 were follicular, and 1 was a Hurthle cell tumor, the investigators reported.
It’s unlikely the findings were due to selection bias, with patients who were more likely to have cancer opting for surgery. More than half of the patients chose surgery after discussing risks and benefits with their providers, not because of tumor progression. Almost all the others opted for surgery because of compression symptoms or because they had a nodule larger than 4 cm.
Even if there was a bias, "the highest expectation [with Bethesda] is 15%; our rate was 34%," a large difference, Dr. Jaume said. "As soon as we had the rate available, we conveyed the information" to providers so they could more accurately counsel patients. "I think eventually we will see an increase in the number of patients deciding on surgery."
The team performed the study because providers at the university had been relying on the Bethesda estimate to guide patients, but had a hunch that their local FLUS cancer rates were higher.
The majority of the 134 FLUS patients who opted against surgery chose ultrasound monitoring. Among the 22 who chose repeat fine-needle aspiration, half were rediagnosed with benign cytology, 5 were again diagnosed with FLUS, and most of the rest were lost to follow-up.
Among the 80 surgical patients, pathology was benign in 47 and parathyroid tissue was present in 1 biopsy. Records were unavailable for the final patient.
Some cytopathologists tend to call thyroid lesions FLUS more frequently than others; possibly, that predilection has something to do with the discordance in reported cancer rates, Dr. Jaume said.
Ultimately, the solution will be genetic analysis of fine-needle aspiration samples. There is a commercial product on the market, but "we are not using [it] in our institution because the negative predictive value is high, but the positive predictive value is low," he said.
The investigators had no relevant disclosures and had no outside funding for their work.
*Correction, 8/25/2014: An earlier version of this article misspelled Dr. Jaume's name.
CHICAGO – At least in some institutions, about a third of follicular thyroid lesions of undetermined significance are malignant, reported researchers from the University of Wisconsin, Madison.
That rate is a higher proportion than the 5%-15% rate estimated by the Bethesda System, a national standard for reporting thyroid cytopathology, said Dr. Juan Carlos Jaume at the joint meeting of the International Congress of Endocrinology and the Endocrine Society.
"The message here is to be aware of your local institutional rates for cancer in FLUS, because following [the Bethesda System] may mislead you and your patient" when deciding on a course of action, be it surgery, repeat biopsy, or observation, he said. "Other institutions [should be encouraged to] do similar analyses to generate more accurate local guidelines for management of FLUS," noted Dr. Jaume, senior author of the study.
Of 1,420 nodules assessed over 2 years at the thyroid clinic at the University of Wisconsin, Madison, 134 (9.4%) were reported as follicular lesions of undetermined significance (FLUS) on fine-needle aspiration. Eighty patients opted for surgery; pathology revealed that 27 (34%) actually had differentiated thyroid cancer. Cancer also was found in four more patients, but at sites different from the original fine-needle aspiration. Most of the cancers (27) were papillary, 3 were follicular, and 1 was a Hurthle cell tumor, the investigators reported.
It’s unlikely the findings were due to selection bias, with patients who were more likely to have cancer opting for surgery. More than half of the patients chose surgery after discussing risks and benefits with their providers, not because of tumor progression. Almost all the others opted for surgery because of compression symptoms or because they had a nodule larger than 4 cm.
Even if there was a bias, "the highest expectation [with Bethesda] is 15%; our rate was 34%," a large difference, Dr. Jaume said. "As soon as we had the rate available, we conveyed the information" to providers so they could more accurately counsel patients. "I think eventually we will see an increase in the number of patients deciding on surgery."
The team performed the study because providers at the university had been relying on the Bethesda estimate to guide patients, but had a hunch that their local FLUS cancer rates were higher.
The majority of the 134 FLUS patients who opted against surgery chose ultrasound monitoring. Among the 22 who chose repeat fine-needle aspiration, half were rediagnosed with benign cytology, 5 were again diagnosed with FLUS, and most of the rest were lost to follow-up.
Among the 80 surgical patients, pathology was benign in 47 and parathyroid tissue was present in 1 biopsy. Records were unavailable for the final patient.
Some cytopathologists tend to call thyroid lesions FLUS more frequently than others; possibly, that predilection has something to do with the discordance in reported cancer rates, Dr. Jaume said.
Ultimately, the solution will be genetic analysis of fine-needle aspiration samples. There is a commercial product on the market, but "we are not using [it] in our institution because the negative predictive value is high, but the positive predictive value is low," he said.
The investigators had no relevant disclosures and had no outside funding for their work.
*Correction, 8/25/2014: An earlier version of this article misspelled Dr. Jaume's name.
AT ICE/ENDO 2014
Key clinical point: National estimates of FLUS malignancy may not apply to your institution.
Major finding: Among 80 patients diagnosed with FLUS who opted for surgery, the lesion turned out to be differentiated thyroid cancer in 27 (34%).
Data source: Retrospective study of outcomes for 134 FLUS nodules.
Disclosures: The investigators had no disclosures and had no outside funding for their study.
Hypothyroid patients may need to surrender the car keys
CHICAGO – Hypothyroid patients exhibit objective cognitive deficits and motor slowing rendering them unsafe to operate a motor vehicle.
That’s the key take-home message from a longitudinal study in which 32 patients with thyroid cancer completed an extensive battery of neurocognitive and psychological tests as well as measured performance on a driving simulator at three time points: while euthyroid, again while temporarily hypothyroid as part of their cancer therapy and assessment, and finally while once again euthyroid after restoration of thyroid hormone therapy.
"These findings provide objective evidence warranting admonitions against operating motor vehicles for hypothyroid patients and confidence in removing such stipulations upon restoration of a euthyroid state," Dr. Kenneth B. Ain said at the joint meeting of the International Congress of Endocrinology and the Endocrine Society*.
In his own clinical practice he has long included a boxed warning against driving while hypothyroid on all of his written instructions to patients. But most physicians don’t warn their hypothyroid patients that they are driving impaired, nor do the joint practice guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists address the issue. That’s largely because there hasn’t been objective, quantitative evidence to provide firm support for such cautionary admonitions – until now, observed Dr. Ain, professor of medicine and director of the thyroid oncology program at the University of Kentucky, Lexington.
While hypothyroid, study participants experienced an 8.5% increase in braking time on a driving simulator. That’s equivalent to the degree of impairment other investigators have shown to be associated with a blood alcohol level of 82 mg/dL, which is above the legal driving limit in the United States.
"Once our study is published, a patient who is involved in an auto accident [in which] there is death or significant harm could be considered an impaired patient. And if physicians do not warn the patient of this risk, they would be considered an agent of harm. They could be liable for the consequences, the same as a neurologist who doesn’t warn a patient with a grand mal seizure disorder not to drive," Dr. Ain said.
In an interview, he noted that thyroid cancer patients undergoing thyroid hormone depletion temporarily as part of their treatment are merely a small fraction of the total impaired hypothyroid driver population. Investigators with the Framingham Heart Study have reported that 4.4% of individuals above age 60 are hypothyroid. Many of these individuals remain undiagnosed or undertreated. Plus, the noncompliance rate with levothyroxine therapy has been estimated at 17%-32%.
Moreover, once a patient is newly diagnosed as being profoundly hypothyroid and receives a prescription for thyroid hormone replacement, there is a lag time involved in achieving a euthyroid state. The half-life of levothyroxine is 1 week. It takes 6-8 weeks to reach a steady state. Probably at least 2 weeks of therapy are required before there is any improvement in the neurologic impairments documented in this study, Dr. Ain speculated.
"We’re really talking here about a public health problem, one that requires a public health response and acknowledgment that this is a danger," according to the endocrinologist.
Testing during the hypothyroid phase of the study showed significant declines in measures of executive function and information-processing speed. Fine motor performance of the hands was slowed by 13%. Mean scores on the Beck Depression Inventory deteriorated from 7.9 while euthyroid to 18.9 while hypothyroid, consistent with mild bordering on moderate depression; this depression was characterized by vegetative symptoms and altered mood, but without the impaired self-esteem and sense of guilt often characteristic of other forms of depression.
Dr. Ain reported receiving a research grant from Genzyme, which funded this study.
*Correction, 7/1/2014: An earlier version of this article misstated the name of the International Congress of Endocrinology.
CHICAGO – Hypothyroid patients exhibit objective cognitive deficits and motor slowing rendering them unsafe to operate a motor vehicle.
That’s the key take-home message from a longitudinal study in which 32 patients with thyroid cancer completed an extensive battery of neurocognitive and psychological tests as well as measured performance on a driving simulator at three time points: while euthyroid, again while temporarily hypothyroid as part of their cancer therapy and assessment, and finally while once again euthyroid after restoration of thyroid hormone therapy.
"These findings provide objective evidence warranting admonitions against operating motor vehicles for hypothyroid patients and confidence in removing such stipulations upon restoration of a euthyroid state," Dr. Kenneth B. Ain said at the joint meeting of the International Congress of Endocrinology and the Endocrine Society*.
In his own clinical practice he has long included a boxed warning against driving while hypothyroid on all of his written instructions to patients. But most physicians don’t warn their hypothyroid patients that they are driving impaired, nor do the joint practice guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists address the issue. That’s largely because there hasn’t been objective, quantitative evidence to provide firm support for such cautionary admonitions – until now, observed Dr. Ain, professor of medicine and director of the thyroid oncology program at the University of Kentucky, Lexington.
While hypothyroid, study participants experienced an 8.5% increase in braking time on a driving simulator. That’s equivalent to the degree of impairment other investigators have shown to be associated with a blood alcohol level of 82 mg/dL, which is above the legal driving limit in the United States.
"Once our study is published, a patient who is involved in an auto accident [in which] there is death or significant harm could be considered an impaired patient. And if physicians do not warn the patient of this risk, they would be considered an agent of harm. They could be liable for the consequences, the same as a neurologist who doesn’t warn a patient with a grand mal seizure disorder not to drive," Dr. Ain said.
In an interview, he noted that thyroid cancer patients undergoing thyroid hormone depletion temporarily as part of their treatment are merely a small fraction of the total impaired hypothyroid driver population. Investigators with the Framingham Heart Study have reported that 4.4% of individuals above age 60 are hypothyroid. Many of these individuals remain undiagnosed or undertreated. Plus, the noncompliance rate with levothyroxine therapy has been estimated at 17%-32%.
Moreover, once a patient is newly diagnosed as being profoundly hypothyroid and receives a prescription for thyroid hormone replacement, there is a lag time involved in achieving a euthyroid state. The half-life of levothyroxine is 1 week. It takes 6-8 weeks to reach a steady state. Probably at least 2 weeks of therapy are required before there is any improvement in the neurologic impairments documented in this study, Dr. Ain speculated.
"We’re really talking here about a public health problem, one that requires a public health response and acknowledgment that this is a danger," according to the endocrinologist.
Testing during the hypothyroid phase of the study showed significant declines in measures of executive function and information-processing speed. Fine motor performance of the hands was slowed by 13%. Mean scores on the Beck Depression Inventory deteriorated from 7.9 while euthyroid to 18.9 while hypothyroid, consistent with mild bordering on moderate depression; this depression was characterized by vegetative symptoms and altered mood, but without the impaired self-esteem and sense of guilt often characteristic of other forms of depression.
Dr. Ain reported receiving a research grant from Genzyme, which funded this study.
*Correction, 7/1/2014: An earlier version of this article misstated the name of the International Congress of Endocrinology.
CHICAGO – Hypothyroid patients exhibit objective cognitive deficits and motor slowing rendering them unsafe to operate a motor vehicle.
That’s the key take-home message from a longitudinal study in which 32 patients with thyroid cancer completed an extensive battery of neurocognitive and psychological tests as well as measured performance on a driving simulator at three time points: while euthyroid, again while temporarily hypothyroid as part of their cancer therapy and assessment, and finally while once again euthyroid after restoration of thyroid hormone therapy.
"These findings provide objective evidence warranting admonitions against operating motor vehicles for hypothyroid patients and confidence in removing such stipulations upon restoration of a euthyroid state," Dr. Kenneth B. Ain said at the joint meeting of the International Congress of Endocrinology and the Endocrine Society*.
In his own clinical practice he has long included a boxed warning against driving while hypothyroid on all of his written instructions to patients. But most physicians don’t warn their hypothyroid patients that they are driving impaired, nor do the joint practice guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists address the issue. That’s largely because there hasn’t been objective, quantitative evidence to provide firm support for such cautionary admonitions – until now, observed Dr. Ain, professor of medicine and director of the thyroid oncology program at the University of Kentucky, Lexington.
While hypothyroid, study participants experienced an 8.5% increase in braking time on a driving simulator. That’s equivalent to the degree of impairment other investigators have shown to be associated with a blood alcohol level of 82 mg/dL, which is above the legal driving limit in the United States.
"Once our study is published, a patient who is involved in an auto accident [in which] there is death or significant harm could be considered an impaired patient. And if physicians do not warn the patient of this risk, they would be considered an agent of harm. They could be liable for the consequences, the same as a neurologist who doesn’t warn a patient with a grand mal seizure disorder not to drive," Dr. Ain said.
In an interview, he noted that thyroid cancer patients undergoing thyroid hormone depletion temporarily as part of their treatment are merely a small fraction of the total impaired hypothyroid driver population. Investigators with the Framingham Heart Study have reported that 4.4% of individuals above age 60 are hypothyroid. Many of these individuals remain undiagnosed or undertreated. Plus, the noncompliance rate with levothyroxine therapy has been estimated at 17%-32%.
Moreover, once a patient is newly diagnosed as being profoundly hypothyroid and receives a prescription for thyroid hormone replacement, there is a lag time involved in achieving a euthyroid state. The half-life of levothyroxine is 1 week. It takes 6-8 weeks to reach a steady state. Probably at least 2 weeks of therapy are required before there is any improvement in the neurologic impairments documented in this study, Dr. Ain speculated.
"We’re really talking here about a public health problem, one that requires a public health response and acknowledgment that this is a danger," according to the endocrinologist.
Testing during the hypothyroid phase of the study showed significant declines in measures of executive function and information-processing speed. Fine motor performance of the hands was slowed by 13%. Mean scores on the Beck Depression Inventory deteriorated from 7.9 while euthyroid to 18.9 while hypothyroid, consistent with mild bordering on moderate depression; this depression was characterized by vegetative symptoms and altered mood, but without the impaired self-esteem and sense of guilt often characteristic of other forms of depression.
Dr. Ain reported receiving a research grant from Genzyme, which funded this study.
*Correction, 7/1/2014: An earlier version of this article misstated the name of the International Congress of Endocrinology.
AT ICE/ENDO 2014
Key clinical point: Hypothyroid patients are driving impaired. Physicians need to document, firmly cautioning them to that effect, or face possible liability concerns in the event of a serious motor vehicle accident.
Major finding: Hypothyroid patients showed an increased automobile braking time on a driving simulator that was equivalent to having a blood alcohol level above the U.S. legal driving limit.
Data source: A longitudinal study in which 32 thyroid cancer patients served as their own controls. They completed an extensive neurocognitive test battery and driving simulator performance test while euthyroid, then while temporarily hypothyroid as part of their cancer-treatment regimen, and once again after restoration to the euthyroid state.
Disclosures: Dr. Ain reported receiving a research grant from Genzyme, which funded this study.
Lymph node mapping agent approval expanded to include head and neck cancer evaluation
Lymphoseek, a diagnostic imaging agent, has been approved for helping evaluate the spread of squamous cell carcinoma in patients with head and neck cancer, the Food and Drug Administration announced.
In a statement issued on June 13, the FDA said that with this approval, Lymphoseek (technetium 99m tilmanocept) injection "can now be used to guide" sentinel lymph node biopsies in patients with cancer of the head and neck, which "will allow for the option of more limited lymph node surgery in patients with sentinel nodes negative for cancer."
To use Lymphoseek, "doctors inject the drug into the tumor area and later, using a handheld radiation detector, find the sentinel lymph nodes that have taken up Lymphoseek’s radioactivity," Dr. Libero Marzella, director of the Division of Medical Imaging Products in the FDA’s Center for Drug Evaluation and Research, said in the statement.
This is a new indication for Lymphoseek, marketed by Navidea Biopharmaceuticals. In March 2013, it was approved for assisting in the localization of lymph nodes draining a primary tumor in patients with breast cancer or melanoma.
Approval of the new indication is based on a study that used Lymphoseek in the evaluation of 85 patents with squamous cell carcinoma of the lip, oral cavity, and skin, which "showed that Lymphoseek-guided sentinel lymph node biopsy accurately determined if the cancer had spread through the lymphatic system," according to the FDA. Pain and irritation at the injection site were the most common adverse effects associated with Lymphoseek in the study.
Lymphoseek, a diagnostic imaging agent, has been approved for helping evaluate the spread of squamous cell carcinoma in patients with head and neck cancer, the Food and Drug Administration announced.
In a statement issued on June 13, the FDA said that with this approval, Lymphoseek (technetium 99m tilmanocept) injection "can now be used to guide" sentinel lymph node biopsies in patients with cancer of the head and neck, which "will allow for the option of more limited lymph node surgery in patients with sentinel nodes negative for cancer."
To use Lymphoseek, "doctors inject the drug into the tumor area and later, using a handheld radiation detector, find the sentinel lymph nodes that have taken up Lymphoseek’s radioactivity," Dr. Libero Marzella, director of the Division of Medical Imaging Products in the FDA’s Center for Drug Evaluation and Research, said in the statement.
This is a new indication for Lymphoseek, marketed by Navidea Biopharmaceuticals. In March 2013, it was approved for assisting in the localization of lymph nodes draining a primary tumor in patients with breast cancer or melanoma.
Approval of the new indication is based on a study that used Lymphoseek in the evaluation of 85 patents with squamous cell carcinoma of the lip, oral cavity, and skin, which "showed that Lymphoseek-guided sentinel lymph node biopsy accurately determined if the cancer had spread through the lymphatic system," according to the FDA. Pain and irritation at the injection site were the most common adverse effects associated with Lymphoseek in the study.
Lymphoseek, a diagnostic imaging agent, has been approved for helping evaluate the spread of squamous cell carcinoma in patients with head and neck cancer, the Food and Drug Administration announced.
In a statement issued on June 13, the FDA said that with this approval, Lymphoseek (technetium 99m tilmanocept) injection "can now be used to guide" sentinel lymph node biopsies in patients with cancer of the head and neck, which "will allow for the option of more limited lymph node surgery in patients with sentinel nodes negative for cancer."
To use Lymphoseek, "doctors inject the drug into the tumor area and later, using a handheld radiation detector, find the sentinel lymph nodes that have taken up Lymphoseek’s radioactivity," Dr. Libero Marzella, director of the Division of Medical Imaging Products in the FDA’s Center for Drug Evaluation and Research, said in the statement.
This is a new indication for Lymphoseek, marketed by Navidea Biopharmaceuticals. In March 2013, it was approved for assisting in the localization of lymph nodes draining a primary tumor in patients with breast cancer or melanoma.
Approval of the new indication is based on a study that used Lymphoseek in the evaluation of 85 patents with squamous cell carcinoma of the lip, oral cavity, and skin, which "showed that Lymphoseek-guided sentinel lymph node biopsy accurately determined if the cancer had spread through the lymphatic system," according to the FDA. Pain and irritation at the injection site were the most common adverse effects associated with Lymphoseek in the study.
Insomnia with very short sleep duration is a risk factor for cancer
MINNEAPOLIS – People who have the type of insomnia characterized by a sharply shortened duration of sleep are at increased risk for cancer, a longitudinal cohort study showed.
In the study of more than 1,600 adults from the general population, those who reported insomnia and slept 5 hours or less per night as determined by polysomnography had more than double the adjusted cancer risk of their insomnia-free counterparts who slept longer. But the association was no longer significant after depression was controlled for.
"Insomnia with severe short sleep duration is associated with increased risk of cancer, particularly in those with comorbid depression," commented first author Julio Fernandez-Mendoza, Ph.D., of the sleep research and treatment center, department of psychiatry, Penn State College of Medicine, Hershey.
Previous research has established a dose-response relationship between objectively measured sleep duration and other adverse health outcomes, he noted. "For us, basically, objective sleep duration is a biomarker, is an assay, is the best we have right now. ... These findings expand on our previous studies, and it appears that we can continue using this assay to explore the medical morbidity associated with this insomnia phenotype."
In an interview, session cochair Dr. Ruth M. Benca, director of the center for sleep medicine and sleep research at the University of Wisconsin–Madison, commented, "The whole connection between sleep and cancer has now come to the fore with some of the recent studies showing, for example, that sleep apnea seems to be a risk factor for the ultimate development of cancer. And these new data suggest that insomnia, or insomnia and depression, may also play a role. We need more mechanistic studies to understand how those links may work."
The picture is complicated by overlaps between apnea and insomnia, she noted. "People with apnea can have high rates of insomnia, and both insomnia and apnea can be associated with fragmented sleep or insufficient sleep. So is it the insufficient sleep that’s a problem? Do hypoxemia and apnea also contribute? There are some animal studies that suggest that hypoxemia is related to cancer progression."
In the study, the investigators analyzed data from 1,620 individuals in the Penn State cohort who had no history of cancer at baseline. Insomnia was defined as self-reported insomnia present for at least 1 year, and very short sleep duration was defined as 5 hours or less as determined by polysomnography.
After a follow-up of about 15 years, 12.3% of the individuals experienced incident cancer, defined as a cancer diagnosis or death from the disease.
In an analysis adjusted for traditional confounders (sex, age, race, apnea-hypopnea index, body mass index, diabetes, and hypertension), relative to noninsomniacs who slept more than 5 hours nightly, insomniacs who slept 5 hours or less had significant 2.73-fold higher odds of incident cancer.
However, the association was no longer significant after additional adjustment for depression. "This makes sense because we do know very well two things: the strong association of depression with cancer, and second, the strong association of insomnia with depression. They have a lot in common, particularly inflammation. They have in common fatigue also," Dr. Fernandez-Mendoza said at the annual meeting of the Associated Professional Sleep Societies.
Similarly, the association was not significant after additional adjustment for smoking and alcohol use. "That was primarily driven by something that we learned from our natural history papers: Because these are basically behavioral factors, many insomniacs stop smoking or stop using so much alcohol, just related to the sleep hygiene thing," he commented.
The investigators have not yet assessed whether insomnia with very short sleep duration is associated with specific types of cancer, according to Dr. Fernandez-Mendoza.
Of note, insomniacs who slept more than 5 hours did not have elevated odds of cancer. Nor did noninsomniacs who slept 5 hours or less.
Dr. Fernandez-Mendoza disclosed no relevant conflicts of interest.
MINNEAPOLIS – People who have the type of insomnia characterized by a sharply shortened duration of sleep are at increased risk for cancer, a longitudinal cohort study showed.
In the study of more than 1,600 adults from the general population, those who reported insomnia and slept 5 hours or less per night as determined by polysomnography had more than double the adjusted cancer risk of their insomnia-free counterparts who slept longer. But the association was no longer significant after depression was controlled for.
"Insomnia with severe short sleep duration is associated with increased risk of cancer, particularly in those with comorbid depression," commented first author Julio Fernandez-Mendoza, Ph.D., of the sleep research and treatment center, department of psychiatry, Penn State College of Medicine, Hershey.
Previous research has established a dose-response relationship between objectively measured sleep duration and other adverse health outcomes, he noted. "For us, basically, objective sleep duration is a biomarker, is an assay, is the best we have right now. ... These findings expand on our previous studies, and it appears that we can continue using this assay to explore the medical morbidity associated with this insomnia phenotype."
In an interview, session cochair Dr. Ruth M. Benca, director of the center for sleep medicine and sleep research at the University of Wisconsin–Madison, commented, "The whole connection between sleep and cancer has now come to the fore with some of the recent studies showing, for example, that sleep apnea seems to be a risk factor for the ultimate development of cancer. And these new data suggest that insomnia, or insomnia and depression, may also play a role. We need more mechanistic studies to understand how those links may work."
The picture is complicated by overlaps between apnea and insomnia, she noted. "People with apnea can have high rates of insomnia, and both insomnia and apnea can be associated with fragmented sleep or insufficient sleep. So is it the insufficient sleep that’s a problem? Do hypoxemia and apnea also contribute? There are some animal studies that suggest that hypoxemia is related to cancer progression."
In the study, the investigators analyzed data from 1,620 individuals in the Penn State cohort who had no history of cancer at baseline. Insomnia was defined as self-reported insomnia present for at least 1 year, and very short sleep duration was defined as 5 hours or less as determined by polysomnography.
After a follow-up of about 15 years, 12.3% of the individuals experienced incident cancer, defined as a cancer diagnosis or death from the disease.
In an analysis adjusted for traditional confounders (sex, age, race, apnea-hypopnea index, body mass index, diabetes, and hypertension), relative to noninsomniacs who slept more than 5 hours nightly, insomniacs who slept 5 hours or less had significant 2.73-fold higher odds of incident cancer.
However, the association was no longer significant after additional adjustment for depression. "This makes sense because we do know very well two things: the strong association of depression with cancer, and second, the strong association of insomnia with depression. They have a lot in common, particularly inflammation. They have in common fatigue also," Dr. Fernandez-Mendoza said at the annual meeting of the Associated Professional Sleep Societies.
Similarly, the association was not significant after additional adjustment for smoking and alcohol use. "That was primarily driven by something that we learned from our natural history papers: Because these are basically behavioral factors, many insomniacs stop smoking or stop using so much alcohol, just related to the sleep hygiene thing," he commented.
The investigators have not yet assessed whether insomnia with very short sleep duration is associated with specific types of cancer, according to Dr. Fernandez-Mendoza.
Of note, insomniacs who slept more than 5 hours did not have elevated odds of cancer. Nor did noninsomniacs who slept 5 hours or less.
Dr. Fernandez-Mendoza disclosed no relevant conflicts of interest.
MINNEAPOLIS – People who have the type of insomnia characterized by a sharply shortened duration of sleep are at increased risk for cancer, a longitudinal cohort study showed.
In the study of more than 1,600 adults from the general population, those who reported insomnia and slept 5 hours or less per night as determined by polysomnography had more than double the adjusted cancer risk of their insomnia-free counterparts who slept longer. But the association was no longer significant after depression was controlled for.
"Insomnia with severe short sleep duration is associated with increased risk of cancer, particularly in those with comorbid depression," commented first author Julio Fernandez-Mendoza, Ph.D., of the sleep research and treatment center, department of psychiatry, Penn State College of Medicine, Hershey.
Previous research has established a dose-response relationship between objectively measured sleep duration and other adverse health outcomes, he noted. "For us, basically, objective sleep duration is a biomarker, is an assay, is the best we have right now. ... These findings expand on our previous studies, and it appears that we can continue using this assay to explore the medical morbidity associated with this insomnia phenotype."
In an interview, session cochair Dr. Ruth M. Benca, director of the center for sleep medicine and sleep research at the University of Wisconsin–Madison, commented, "The whole connection between sleep and cancer has now come to the fore with some of the recent studies showing, for example, that sleep apnea seems to be a risk factor for the ultimate development of cancer. And these new data suggest that insomnia, or insomnia and depression, may also play a role. We need more mechanistic studies to understand how those links may work."
The picture is complicated by overlaps between apnea and insomnia, she noted. "People with apnea can have high rates of insomnia, and both insomnia and apnea can be associated with fragmented sleep or insufficient sleep. So is it the insufficient sleep that’s a problem? Do hypoxemia and apnea also contribute? There are some animal studies that suggest that hypoxemia is related to cancer progression."
In the study, the investigators analyzed data from 1,620 individuals in the Penn State cohort who had no history of cancer at baseline. Insomnia was defined as self-reported insomnia present for at least 1 year, and very short sleep duration was defined as 5 hours or less as determined by polysomnography.
After a follow-up of about 15 years, 12.3% of the individuals experienced incident cancer, defined as a cancer diagnosis or death from the disease.
In an analysis adjusted for traditional confounders (sex, age, race, apnea-hypopnea index, body mass index, diabetes, and hypertension), relative to noninsomniacs who slept more than 5 hours nightly, insomniacs who slept 5 hours or less had significant 2.73-fold higher odds of incident cancer.
However, the association was no longer significant after additional adjustment for depression. "This makes sense because we do know very well two things: the strong association of depression with cancer, and second, the strong association of insomnia with depression. They have a lot in common, particularly inflammation. They have in common fatigue also," Dr. Fernandez-Mendoza said at the annual meeting of the Associated Professional Sleep Societies.
Similarly, the association was not significant after additional adjustment for smoking and alcohol use. "That was primarily driven by something that we learned from our natural history papers: Because these are basically behavioral factors, many insomniacs stop smoking or stop using so much alcohol, just related to the sleep hygiene thing," he commented.
The investigators have not yet assessed whether insomnia with very short sleep duration is associated with specific types of cancer, according to Dr. Fernandez-Mendoza.
Of note, insomniacs who slept more than 5 hours did not have elevated odds of cancer. Nor did noninsomniacs who slept 5 hours or less.
Dr. Fernandez-Mendoza disclosed no relevant conflicts of interest.
AT SLEEP 2014
Key clinical point: Short sleep duration increases risk of cancer.
Major finding: Insomniacs who slept 5 hours or less nightly had 2.73-fold higher adjusted odds of cancer when compared with noninsomniacs who slept more than 5 hours.
Data source: A longitudinal cohort study of 1,620 individuals from the general population.
Disclosures: Dr. Fernandez-Mendoza disclosed no relevant conflicts of interest.
Low-dose IMRT may be safe for patients with HPV-positive head and neck cancer
CHICAGO – Lower-dose radiation therapy may be safe for some patients with human papillomavirus (HPV)-positive oropharyngeal cancer, decreasing the risk of often long-term side effects, such as trouble swallowing, dry mouth, loss of taste, neck stiffness, and thyroid problems, investigators reported at the annual meeting of the American Society of Clinical Oncology.
Two-year overall survival and progression-free survival were 93% and 80%, respectively, among 62 patients with operable stage III/IVA HPV-positive oropharyngeal squamous carcinoma who received lower-dose intensity-modulated radiation therapy (IMRT) after clinical complete response to induction chemotherapy, reported Dr. Anthony Cmelak, professor of radiation oncology at Vanderbilt University, Nashville, Tenn., and medical director of the Vanderbilt-Ingram Cancer Center at Franklin.
Overall, the phase II study enrolled 90 patients, median age 57 years, who all received induction chemotherapy with paclitaxel, cisplatin, and cetuximab. The response to induction chemotherapy determined IMRT dose. The 62 patients who had a complete clinical response received a reduced dose (54 Gy) of IMRT, and the rest of the patients received standard dose IMRT (70 Gy). All patients received standard cetuximab along with radiation.
Two-year overall survival and progression-free survival for the higher-risk patients who received the standard dose of IMRT were 87% and 65% respectively. Among those patients receiving low-dose IMRT, survival was slightly higher for those with less than 10 pack-years of smoking and earlier-stage disease; in those patients 2-year progression-free and overall survival were 92% and 97%, respectively.
However, Dr. Cmelak does not yet recommend modifying regimens for patients with HPV-positive disease. "I don’t recommend using lower doses now, off study. Ultimately, we will need a large randomized trial," he said. "This study represents one more piece of evidence that we need to look at the optimal regimen for both chemotherapy and radiation technique and dosage to minimize toxicities," he added.
"We are not at the point where we know exactly how to treat patients with HPV-positive cancers. What we do know now is that there is a different biology to their tumors," commented Dr. Gregory A. Masters, of the Helen F. Graham Cancer Center, Newark, Del., who attended the briefing but was not involved with the study. However, the study represents progress toward precision medicine, he said. "Most of what we have been doing over the last 49 years in oncology is escalating dosages. This is not necessarily always the right answer," he added.
The research was supported by the National Institutes of Health. Dr. Cmelak reported a consultancy role and honoraria from Bristol-Myers Squibb. Dr. Masters reported no disclosures.
On Twitter @nikolaideslaura
CHICAGO – Lower-dose radiation therapy may be safe for some patients with human papillomavirus (HPV)-positive oropharyngeal cancer, decreasing the risk of often long-term side effects, such as trouble swallowing, dry mouth, loss of taste, neck stiffness, and thyroid problems, investigators reported at the annual meeting of the American Society of Clinical Oncology.
Two-year overall survival and progression-free survival were 93% and 80%, respectively, among 62 patients with operable stage III/IVA HPV-positive oropharyngeal squamous carcinoma who received lower-dose intensity-modulated radiation therapy (IMRT) after clinical complete response to induction chemotherapy, reported Dr. Anthony Cmelak, professor of radiation oncology at Vanderbilt University, Nashville, Tenn., and medical director of the Vanderbilt-Ingram Cancer Center at Franklin.
Overall, the phase II study enrolled 90 patients, median age 57 years, who all received induction chemotherapy with paclitaxel, cisplatin, and cetuximab. The response to induction chemotherapy determined IMRT dose. The 62 patients who had a complete clinical response received a reduced dose (54 Gy) of IMRT, and the rest of the patients received standard dose IMRT (70 Gy). All patients received standard cetuximab along with radiation.
Two-year overall survival and progression-free survival for the higher-risk patients who received the standard dose of IMRT were 87% and 65% respectively. Among those patients receiving low-dose IMRT, survival was slightly higher for those with less than 10 pack-years of smoking and earlier-stage disease; in those patients 2-year progression-free and overall survival were 92% and 97%, respectively.
However, Dr. Cmelak does not yet recommend modifying regimens for patients with HPV-positive disease. "I don’t recommend using lower doses now, off study. Ultimately, we will need a large randomized trial," he said. "This study represents one more piece of evidence that we need to look at the optimal regimen for both chemotherapy and radiation technique and dosage to minimize toxicities," he added.
"We are not at the point where we know exactly how to treat patients with HPV-positive cancers. What we do know now is that there is a different biology to their tumors," commented Dr. Gregory A. Masters, of the Helen F. Graham Cancer Center, Newark, Del., who attended the briefing but was not involved with the study. However, the study represents progress toward precision medicine, he said. "Most of what we have been doing over the last 49 years in oncology is escalating dosages. This is not necessarily always the right answer," he added.
The research was supported by the National Institutes of Health. Dr. Cmelak reported a consultancy role and honoraria from Bristol-Myers Squibb. Dr. Masters reported no disclosures.
On Twitter @nikolaideslaura
CHICAGO – Lower-dose radiation therapy may be safe for some patients with human papillomavirus (HPV)-positive oropharyngeal cancer, decreasing the risk of often long-term side effects, such as trouble swallowing, dry mouth, loss of taste, neck stiffness, and thyroid problems, investigators reported at the annual meeting of the American Society of Clinical Oncology.
Two-year overall survival and progression-free survival were 93% and 80%, respectively, among 62 patients with operable stage III/IVA HPV-positive oropharyngeal squamous carcinoma who received lower-dose intensity-modulated radiation therapy (IMRT) after clinical complete response to induction chemotherapy, reported Dr. Anthony Cmelak, professor of radiation oncology at Vanderbilt University, Nashville, Tenn., and medical director of the Vanderbilt-Ingram Cancer Center at Franklin.
Overall, the phase II study enrolled 90 patients, median age 57 years, who all received induction chemotherapy with paclitaxel, cisplatin, and cetuximab. The response to induction chemotherapy determined IMRT dose. The 62 patients who had a complete clinical response received a reduced dose (54 Gy) of IMRT, and the rest of the patients received standard dose IMRT (70 Gy). All patients received standard cetuximab along with radiation.
Two-year overall survival and progression-free survival for the higher-risk patients who received the standard dose of IMRT were 87% and 65% respectively. Among those patients receiving low-dose IMRT, survival was slightly higher for those with less than 10 pack-years of smoking and earlier-stage disease; in those patients 2-year progression-free and overall survival were 92% and 97%, respectively.
However, Dr. Cmelak does not yet recommend modifying regimens for patients with HPV-positive disease. "I don’t recommend using lower doses now, off study. Ultimately, we will need a large randomized trial," he said. "This study represents one more piece of evidence that we need to look at the optimal regimen for both chemotherapy and radiation technique and dosage to minimize toxicities," he added.
"We are not at the point where we know exactly how to treat patients with HPV-positive cancers. What we do know now is that there is a different biology to their tumors," commented Dr. Gregory A. Masters, of the Helen F. Graham Cancer Center, Newark, Del., who attended the briefing but was not involved with the study. However, the study represents progress toward precision medicine, he said. "Most of what we have been doing over the last 49 years in oncology is escalating dosages. This is not necessarily always the right answer," he added.
The research was supported by the National Institutes of Health. Dr. Cmelak reported a consultancy role and honoraria from Bristol-Myers Squibb. Dr. Masters reported no disclosures.
On Twitter @nikolaideslaura
AT THE ASCO ANNUAL MEETING 2014
Key clinical finding: Some patients with HPV-positive oropharyngeal cancer may be able to avoid possible long-term side effects by receiving lower-dose radiation therapy, though a randomized trial is needed.
Major finding: Two-year overall survival and progression-free survival were 93% and 80%, respectively, among patients with operable stage III/IVA HPV-positive oropharyngeal squamous carcinoma who received lower-dose IMRT after clinical complete response to induction.
Data source: Phase II study of 90 patients with operable stage III/IVA HPV-positive oropharyngeal squamous carcinoma who received either lower-dose IMRT or standard-dose IMRT based on their response after induction chemotherapy.
Disclosures: The research was supported by the National Institutes of Health. Dr. Cmelak reported a consultancy role and honoraria from Bristol-Myers Squibb. Dr. Masters reported no disclosures.
VIDEO: Lenvatinib ups PFS in thyroid cancer
CHICAGO – Lenvatinib significantly prolonged progression-free survival and produced high response rates compared with placebo in patients with relapsed iodine-refractory differentiated thyroid cancer. We catch up with study coauthor Dr. Lori C. Wirth, medical director of the Center for Head and Neck Cancers at Massachusetts General Hospital, Boston, to discuss the promising results at the annual meeting of the American Society of Clinical Oncology.
The study was funded by Eisai. Dr. Wirth reported no financial disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
CHICAGO – Lenvatinib significantly prolonged progression-free survival and produced high response rates compared with placebo in patients with relapsed iodine-refractory differentiated thyroid cancer. We catch up with study coauthor Dr. Lori C. Wirth, medical director of the Center for Head and Neck Cancers at Massachusetts General Hospital, Boston, to discuss the promising results at the annual meeting of the American Society of Clinical Oncology.
The study was funded by Eisai. Dr. Wirth reported no financial disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
CHICAGO – Lenvatinib significantly prolonged progression-free survival and produced high response rates compared with placebo in patients with relapsed iodine-refractory differentiated thyroid cancer. We catch up with study coauthor Dr. Lori C. Wirth, medical director of the Center for Head and Neck Cancers at Massachusetts General Hospital, Boston, to discuss the promising results at the annual meeting of the American Society of Clinical Oncology.
The study was funded by Eisai. Dr. Wirth reported no financial disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT THE ASCO ANNUAL MEETING 2014
Experimental lenvatinib extends PFS in iodine-refractory relapsed thyroid cancer
CHICAGO – The investigational drug lenvatinib significantly prolonged progression-free survival and produced high response rates compared with placebo in patients with iodine-refractory differentiated thyroid cancer.
In a randomized trial, the median progression-free survival (PFS) among patients assigned to lenvatinib was 18.3 months, compared with 3.6 months for placebo. The hazard ratio for lenvatinib was 0.21 (P less than .0001), Dr. Martin Schlumberger reported at the annual meeting of the American Society of Clinical Oncology.
"We had a high objective response rate – about 65% – with some complete responses. Interestingly, the time to objective response was only 2 months, so responses occur very quickly after the first treatment," Dr. Schlumberger, a professor of oncology at the University Paris-Sud, France, said at a media briefing prior to his presentation of the data in a plenary session.
"It’s really rewarding to see another active drug in this disease, where a year ago we really had no active therapy," commented Dr. Gregory A. Masters from the Helen F. Graham Cancer Center in Newark, Delaware.
Dr. Masters moderated the briefing but was not involved in the study.
Patients with relapsed or refractory differentiated thyroid cancer that is resistant to treatment with iodine-131 (131I) have few treatment choices and a 10-year survival rate of just 10%, Dr. Schlumberger noted.
There is evidence, however, showing that vascular endothelial growth factor (VEGF) signaling is associated with aggressive thyroid cancer and its propensity for metastasis, prompting researchers to explore VEGF-receptor inhibitors.
Lenvatinib is an oral multi–tyrosine kinase inhibitor of VEGF receptors 1-3, fibroblast growth factor receptors 1-4, platelet-derived growth factor receptor–alpha, and the RET and KIT kinases.
In a phase II study, the drug showed clinical activity against 131I-refractory differentiated thyroid cancer, prompting investigators to launch the phase III SELECT trial (Study of E7080 Lenvatinib in Differentiated Cancer of the Thyroid) in this population.
They enrolled 392 patients with measurable disease and evidence of progression within the previous 13 months of treatment, which could include one prior VEGF or VEGF-receptor inhibitor.
The patients were randomized on a 2:1 basis to either oral lenvatinib 24 mg daily or placebo, with treatment continuing until disease progression according to RECIST (Response Evaluation Criteria in Solid Tumor) criteria. At the time of confirmed disease progression, patients originally assigned to placebo could be crossed over to the active drug.
As noted above, median PFS was significantly better for the 261 patients assigned to lenvatinib, at 18.3 months, vs. 3.6 months for the 121 assigned to placebo. The median PFS for patients who had previously received another VEGF inhibitor was 15.1 months, compared with 18.7 months for those who had not been treated with an anti-VEGF agent (P value not shown). Median overall survival has not yet been reached.
The overall response rates were 65% for lenvatinib, versus 2% for placebo (P less than .0001). In the lenvatinib group, there were 4 complete responses, 165 partial responses, 40 cases with stable disease of at least 23 weeks’ duration, and 18 cases of progressive disease. Among placebo-treated patients, there were no complete responses, 2 partial responses, 39 cases of stable disease, and 52 of progressive disease. Only 1.5% of patients, all in the lenvatinib group, had a complete response, compared with none in the placebo group.
The median time to an objective response was 2 months. The median duration of response had not been reached by the last analysis. Approximately 75% of responders had an objective response last for more than 9.4 months, Dr. Schlumberger said.
As is common with other VEGF inhibitors, treatment-emergent adverse events were common, occurring in 97% of patients treated with lenvatinib, compared with 60% of patients on placebo.
The most common events were hypertension, occurring in 68% of patients vs. 9% on placebo, diarrhea (60% vs. 8%), fatigue/asthenia (59% vs. 28%), decreased appetite (50% vs. 12%), and nausea/vomiting (51% vs. 24%).
Adverse events requiring dose reductions occurred in 68% of patients on lenvatinib, dose interruptions in 82%, and discontinuation in 14%. In contrast, only 5% of patients on placebo had a dose reduction, 18% had an interruption, and 5% discontinued therapy.
Also of concern to investigators was the fact that of the 20 patients on lenvatinib who died during the trial, 6 of the deaths were determined by investigators to be treatment related. One of these patients died from a hemorrhagic stroke, one from a pulmonary embolism, and four from general health deterioration.
Hematologic complications are a class effect of the anti-VEGF tyrosine kinase inhibitors, said coauthor Dr. Lori Wirth, medical director of the center for head and neck cancers at Massachusetts General Hospital, Boston.
"The other thing about the toxicity profile overall is that it’s an extremely important thing to consider in patients with thyroid cancer, because many patients do have quite indolent disease. But the patients who were enrolled in the placebo arm had a progression-free survival of less than 4 months, and these are the people who go on to die from their disease when it’s that rapidly progressive. So we do need effective treatments that, unfortunately, do come with some toxicities," she said in an interview.
Although the toxicities of therapy were "considerable," most could be managed through either dose adjustment or additional medications, Dr. Schlumberger said.
The study was sponsored by Eisai. Dr. Schlumberger disclosed receiving honoraria and research funding and acting in an advisory role to the company. Dr. Masters and Dr. Wirth reported having no relevant relationships to disclose.
CHICAGO – The investigational drug lenvatinib significantly prolonged progression-free survival and produced high response rates compared with placebo in patients with iodine-refractory differentiated thyroid cancer.
In a randomized trial, the median progression-free survival (PFS) among patients assigned to lenvatinib was 18.3 months, compared with 3.6 months for placebo. The hazard ratio for lenvatinib was 0.21 (P less than .0001), Dr. Martin Schlumberger reported at the annual meeting of the American Society of Clinical Oncology.
"We had a high objective response rate – about 65% – with some complete responses. Interestingly, the time to objective response was only 2 months, so responses occur very quickly after the first treatment," Dr. Schlumberger, a professor of oncology at the University Paris-Sud, France, said at a media briefing prior to his presentation of the data in a plenary session.
"It’s really rewarding to see another active drug in this disease, where a year ago we really had no active therapy," commented Dr. Gregory A. Masters from the Helen F. Graham Cancer Center in Newark, Delaware.
Dr. Masters moderated the briefing but was not involved in the study.
Patients with relapsed or refractory differentiated thyroid cancer that is resistant to treatment with iodine-131 (131I) have few treatment choices and a 10-year survival rate of just 10%, Dr. Schlumberger noted.
There is evidence, however, showing that vascular endothelial growth factor (VEGF) signaling is associated with aggressive thyroid cancer and its propensity for metastasis, prompting researchers to explore VEGF-receptor inhibitors.
Lenvatinib is an oral multi–tyrosine kinase inhibitor of VEGF receptors 1-3, fibroblast growth factor receptors 1-4, platelet-derived growth factor receptor–alpha, and the RET and KIT kinases.
In a phase II study, the drug showed clinical activity against 131I-refractory differentiated thyroid cancer, prompting investigators to launch the phase III SELECT trial (Study of E7080 Lenvatinib in Differentiated Cancer of the Thyroid) in this population.
They enrolled 392 patients with measurable disease and evidence of progression within the previous 13 months of treatment, which could include one prior VEGF or VEGF-receptor inhibitor.
The patients were randomized on a 2:1 basis to either oral lenvatinib 24 mg daily or placebo, with treatment continuing until disease progression according to RECIST (Response Evaluation Criteria in Solid Tumor) criteria. At the time of confirmed disease progression, patients originally assigned to placebo could be crossed over to the active drug.
As noted above, median PFS was significantly better for the 261 patients assigned to lenvatinib, at 18.3 months, vs. 3.6 months for the 121 assigned to placebo. The median PFS for patients who had previously received another VEGF inhibitor was 15.1 months, compared with 18.7 months for those who had not been treated with an anti-VEGF agent (P value not shown). Median overall survival has not yet been reached.
The overall response rates were 65% for lenvatinib, versus 2% for placebo (P less than .0001). In the lenvatinib group, there were 4 complete responses, 165 partial responses, 40 cases with stable disease of at least 23 weeks’ duration, and 18 cases of progressive disease. Among placebo-treated patients, there were no complete responses, 2 partial responses, 39 cases of stable disease, and 52 of progressive disease. Only 1.5% of patients, all in the lenvatinib group, had a complete response, compared with none in the placebo group.
The median time to an objective response was 2 months. The median duration of response had not been reached by the last analysis. Approximately 75% of responders had an objective response last for more than 9.4 months, Dr. Schlumberger said.
As is common with other VEGF inhibitors, treatment-emergent adverse events were common, occurring in 97% of patients treated with lenvatinib, compared with 60% of patients on placebo.
The most common events were hypertension, occurring in 68% of patients vs. 9% on placebo, diarrhea (60% vs. 8%), fatigue/asthenia (59% vs. 28%), decreased appetite (50% vs. 12%), and nausea/vomiting (51% vs. 24%).
Adverse events requiring dose reductions occurred in 68% of patients on lenvatinib, dose interruptions in 82%, and discontinuation in 14%. In contrast, only 5% of patients on placebo had a dose reduction, 18% had an interruption, and 5% discontinued therapy.
Also of concern to investigators was the fact that of the 20 patients on lenvatinib who died during the trial, 6 of the deaths were determined by investigators to be treatment related. One of these patients died from a hemorrhagic stroke, one from a pulmonary embolism, and four from general health deterioration.
Hematologic complications are a class effect of the anti-VEGF tyrosine kinase inhibitors, said coauthor Dr. Lori Wirth, medical director of the center for head and neck cancers at Massachusetts General Hospital, Boston.
"The other thing about the toxicity profile overall is that it’s an extremely important thing to consider in patients with thyroid cancer, because many patients do have quite indolent disease. But the patients who were enrolled in the placebo arm had a progression-free survival of less than 4 months, and these are the people who go on to die from their disease when it’s that rapidly progressive. So we do need effective treatments that, unfortunately, do come with some toxicities," she said in an interview.
Although the toxicities of therapy were "considerable," most could be managed through either dose adjustment or additional medications, Dr. Schlumberger said.
The study was sponsored by Eisai. Dr. Schlumberger disclosed receiving honoraria and research funding and acting in an advisory role to the company. Dr. Masters and Dr. Wirth reported having no relevant relationships to disclose.
CHICAGO – The investigational drug lenvatinib significantly prolonged progression-free survival and produced high response rates compared with placebo in patients with iodine-refractory differentiated thyroid cancer.
In a randomized trial, the median progression-free survival (PFS) among patients assigned to lenvatinib was 18.3 months, compared with 3.6 months for placebo. The hazard ratio for lenvatinib was 0.21 (P less than .0001), Dr. Martin Schlumberger reported at the annual meeting of the American Society of Clinical Oncology.
"We had a high objective response rate – about 65% – with some complete responses. Interestingly, the time to objective response was only 2 months, so responses occur very quickly after the first treatment," Dr. Schlumberger, a professor of oncology at the University Paris-Sud, France, said at a media briefing prior to his presentation of the data in a plenary session.
"It’s really rewarding to see another active drug in this disease, where a year ago we really had no active therapy," commented Dr. Gregory A. Masters from the Helen F. Graham Cancer Center in Newark, Delaware.
Dr. Masters moderated the briefing but was not involved in the study.
Patients with relapsed or refractory differentiated thyroid cancer that is resistant to treatment with iodine-131 (131I) have few treatment choices and a 10-year survival rate of just 10%, Dr. Schlumberger noted.
There is evidence, however, showing that vascular endothelial growth factor (VEGF) signaling is associated with aggressive thyroid cancer and its propensity for metastasis, prompting researchers to explore VEGF-receptor inhibitors.
Lenvatinib is an oral multi–tyrosine kinase inhibitor of VEGF receptors 1-3, fibroblast growth factor receptors 1-4, platelet-derived growth factor receptor–alpha, and the RET and KIT kinases.
In a phase II study, the drug showed clinical activity against 131I-refractory differentiated thyroid cancer, prompting investigators to launch the phase III SELECT trial (Study of E7080 Lenvatinib in Differentiated Cancer of the Thyroid) in this population.
They enrolled 392 patients with measurable disease and evidence of progression within the previous 13 months of treatment, which could include one prior VEGF or VEGF-receptor inhibitor.
The patients were randomized on a 2:1 basis to either oral lenvatinib 24 mg daily or placebo, with treatment continuing until disease progression according to RECIST (Response Evaluation Criteria in Solid Tumor) criteria. At the time of confirmed disease progression, patients originally assigned to placebo could be crossed over to the active drug.
As noted above, median PFS was significantly better for the 261 patients assigned to lenvatinib, at 18.3 months, vs. 3.6 months for the 121 assigned to placebo. The median PFS for patients who had previously received another VEGF inhibitor was 15.1 months, compared with 18.7 months for those who had not been treated with an anti-VEGF agent (P value not shown). Median overall survival has not yet been reached.
The overall response rates were 65% for lenvatinib, versus 2% for placebo (P less than .0001). In the lenvatinib group, there were 4 complete responses, 165 partial responses, 40 cases with stable disease of at least 23 weeks’ duration, and 18 cases of progressive disease. Among placebo-treated patients, there were no complete responses, 2 partial responses, 39 cases of stable disease, and 52 of progressive disease. Only 1.5% of patients, all in the lenvatinib group, had a complete response, compared with none in the placebo group.
The median time to an objective response was 2 months. The median duration of response had not been reached by the last analysis. Approximately 75% of responders had an objective response last for more than 9.4 months, Dr. Schlumberger said.
As is common with other VEGF inhibitors, treatment-emergent adverse events were common, occurring in 97% of patients treated with lenvatinib, compared with 60% of patients on placebo.
The most common events were hypertension, occurring in 68% of patients vs. 9% on placebo, diarrhea (60% vs. 8%), fatigue/asthenia (59% vs. 28%), decreased appetite (50% vs. 12%), and nausea/vomiting (51% vs. 24%).
Adverse events requiring dose reductions occurred in 68% of patients on lenvatinib, dose interruptions in 82%, and discontinuation in 14%. In contrast, only 5% of patients on placebo had a dose reduction, 18% had an interruption, and 5% discontinued therapy.
Also of concern to investigators was the fact that of the 20 patients on lenvatinib who died during the trial, 6 of the deaths were determined by investigators to be treatment related. One of these patients died from a hemorrhagic stroke, one from a pulmonary embolism, and four from general health deterioration.
Hematologic complications are a class effect of the anti-VEGF tyrosine kinase inhibitors, said coauthor Dr. Lori Wirth, medical director of the center for head and neck cancers at Massachusetts General Hospital, Boston.
"The other thing about the toxicity profile overall is that it’s an extremely important thing to consider in patients with thyroid cancer, because many patients do have quite indolent disease. But the patients who were enrolled in the placebo arm had a progression-free survival of less than 4 months, and these are the people who go on to die from their disease when it’s that rapidly progressive. So we do need effective treatments that, unfortunately, do come with some toxicities," she said in an interview.
Although the toxicities of therapy were "considerable," most could be managed through either dose adjustment or additional medications, Dr. Schlumberger said.
The study was sponsored by Eisai. Dr. Schlumberger disclosed receiving honoraria and research funding and acting in an advisory role to the company. Dr. Masters and Dr. Wirth reported having no relevant relationships to disclose.
AT THE ASCO ANNUAL MEETING 2014
Key clinical finding: The investigational drug lenvatinib significantly prolonged progression-free survival and produced high response rates compared with placebo in patients with iodine-refractory differentiated thyroid cancer.
Major finding: Median progression-free survival for patients with relapsed iodine-refractory differentiated thyroid cancer was 18.3 months, compared with 3.6 months for patients on placebo.
Data source: Randomized, doubled-blind, placebo-controlled trial in 392 patients.
Disclosures: The study was sponsored by Eisai. Dr. Schlumberger disclosed receiving honoraria and research funding and acting in an advisory role to the company. Dr. Masters and Dr. Wirth reported having no relevant relationships to disclose.
Lobectomy suffices for surgery of small papillary thyroid cancers
BOSTON – Extensive surgery beyond lobectomy offers no survival advantage for small papillary thyroid cancers, according to a large database analysis.
Total thyroidectomy was not associated with an overall survival benefit over lobectomy for papillary thyroid cancers sized 1-2 cm (hazard ratio, 1.05; P = .61) or 2.1-4.0 cm (HR, 0.89; P = .21), even after adjusting for multiple patient and pathologic factors.
"Despite guidelines, our results call into question whether tumor size 1-4 cm should be an absolute determinant for extent of surgery," Dr. Mohamed Abdelgadir Adam said at the annual meeting of the American Surgical Association.
Current American Thyroid Association guidelines recommend lobectomy for tumors less than 1 cm in size and total thyroidectomy for those exceeding 1 cm.
"Using total thyroidectomy based on tumor size alone may unnecessarily subject patients to increased risks of complications without a survival benefit," he said. "In addition to tumor size up to 4 cm, other factors are important for determining extent of surgery such as nodal and distant metastases and patient preference."
The extent of surgery for papillary thyroid cancer, however, remains controversial. Recent analyses (Arch. Otolaryngol. Head Neck Surg. 2010;136:1055-61) have shown no survival difference between lobectomy and total thyroidectomy, while an earlier landmark study found improved overall survival with total thyroidectomy for tumors 1 cm or more (Ann. Surg. 2007;246;375-81). The latter study, however, has been criticized because it did not take into account patient comorbidities, multifocality, extrathyroidal extension, or completeness of resection, said Dr. Adam of Duke University School of Medicine, Durham, N.C.
The current analysis adjusted for age, gender, race, annual income, insurance status, hospital volume, patient comorbidities, tumor multifocality, extrathyroidal extension, lymph node involvement, metastases, surgical margins, and radioactive iodine ablation.
Discussant Dr. Blake Cady, professor emeritus of surgery at Harvard Medical School and Massachusetts General Hospital in Boston, said the current report is an important contribution to the controversy. It also supports his own bias against overtreatment of these mostly young patients with total thyroidectomy, which necessitates long-term medication and is accompanied by almost routine use of radioactive iodine, despite no evidence it improves outcomes in low-risk patients.
"In no other human cancer with a 99% 20-year survival is a policy of routine total primary organ removal practiced and routine systemic therapy used," he said. "Therefore, this report may help to scale back toward a more measured balance between treatment and morbidity."
Study coauthor Dr. Julie Ann Sosa, chief of endocrine surgery at Duke, challenged the audience to promote the growing body of evidence supporting equivalence in overall survival, such as a recent study described as coming the closest to a head-to-head comparison and having the longest follow-up at 18 years. It showed equivalence between lobectomy, without radioactive iodine, and total thyroidectomy for overall, progression-free, and disease-specific survival and risk of recurrence in tumors 40 mm or less (World J. Surg. 2014;38:68-79.
"In light of these data, I think it is probably high time for guidelines to potentially reconsider this issue," she said, noting that the American Thyroid Association will issue new guidelines later this spring or summer.
Dr. Sosa also advocated for "a more sophisticated approach" to preoperative evaluation and risk stratification for papillary thyroid cancer that distinguishes between low-, medium-, and high-risk tumors. The Duke study did not exclude most high-risk tumors, but rather adjusted for high-risk characteristics such as extrathyroidal extension, lymph node involvement, and distant metastases.
"When you adjust for these high-risk characteristics, the afforded overall survival benefit disappears," she said. "So what I think we would argue is that there is equivalence in outcome for the majority of patients for low- and medium-risk tumors. But for those patients who have high-risk tumors, as defined by some of these high-risk characteristics, then I think all of us would agree that total thyroidectomy, with or without radioactive iodine, would be indicated."
The study involved 61,775 patients in the National Cancer Database who underwent total thyroidectomy (n = 54,926) or lobectomy with or without isthmusectomy (n = 6,849) for papillary thyroid cancer from 1998 to 2006. Compared with the lobectomy group, the thyroidectomy group had more tumor multifocality (44% vs. 29%), positive surgical margins (27% vs. 7%), distant metastases (1% vs. 0.4%), and radioactive iodine (65% vs. 33%; P value less than .01 for all).
In multivariable analysis, nodal and distant metastases were associated with compromised survival, Dr. Adam said.
The complete manuscript of this study and its presentation at the American Surgical Association’s 134th Annual Meeting, April 2014 in Boston, is anticipated to be published in the Annals of Surgery, pending editorial review.
The authors reported no conflicting interests
This excellent study by Adam et al. contributes to a growing body of literature supporting thyroid lobectomy for low risk, small, differentiated thyroid tumors. I should say this represents a shift back toward lobectomy. Total thyroidectomy became the procedure of choice for nearly all differentiated thyroid tumors over the last 2-3 decades in part because of the landmark study by Bilimoria et al. (Surgery 2007;142:906-14).
Now the tide is shifting back the other direction.
I do not mean to imply that passing trends drive how we treat thyroid cancer. Mortality rates from differentiated thyroid cancer remain extremely low. This makes measuring any differences in mortality challenging. The outcome can differ depending on the cohort and the other variables included in the modeling. Recurrence is the real driver of morbidity in thyroid cancer, with anywhere from 10%-30% of patients experiencing a recurrence. Unfortunately, large national cancer registries do not capture recurrence very well.
This study controlled for many tumor features that will also impact disease specific survival apart from just the treatment received. The follow-up time is also impressive. So, if we are to undertake a more nuanced and stratified approach to determining the extent of surgery, there are a few things to consider. The first is patient selection.
In this study and in a growing body of retrospective, single institution studies looking at lobectomy for low-risk cancers, one must remember that these patients are selected based on other tumor features (multifocality, extrathyroidal extension, etc.) and not just size alone. Remember that 30%-40% of patients with papillary thyroid cancer will have multifocal disease.
The second is that successfully treating thyroid cancer patients with lobectomy requires buy-in from all parties involved - surgeons, endocrinologists, and, most importantly, the patient. Everyone must be comfortable with omitting radioactive iodine, detectable thyroglobulin levels, and following the remaining lobe with ultrasound. Some patients will not be comfortable with this and may choose to undergo total thyroidectomy. Even if we surgeons agree to shift back toward less aggressive surgery, we cannot do so in isolation.
Dr. David F. Schneider is an associate professor and the director of endocrine surgery research in the department of surgery, University of Wisconsin, Madison. He has no conflicts to disclose.
This excellent study by Adam et al. contributes to a growing body of literature supporting thyroid lobectomy for low risk, small, differentiated thyroid tumors. I should say this represents a shift back toward lobectomy. Total thyroidectomy became the procedure of choice for nearly all differentiated thyroid tumors over the last 2-3 decades in part because of the landmark study by Bilimoria et al. (Surgery 2007;142:906-14).
Now the tide is shifting back the other direction.
I do not mean to imply that passing trends drive how we treat thyroid cancer. Mortality rates from differentiated thyroid cancer remain extremely low. This makes measuring any differences in mortality challenging. The outcome can differ depending on the cohort and the other variables included in the modeling. Recurrence is the real driver of morbidity in thyroid cancer, with anywhere from 10%-30% of patients experiencing a recurrence. Unfortunately, large national cancer registries do not capture recurrence very well.
This study controlled for many tumor features that will also impact disease specific survival apart from just the treatment received. The follow-up time is also impressive. So, if we are to undertake a more nuanced and stratified approach to determining the extent of surgery, there are a few things to consider. The first is patient selection.
In this study and in a growing body of retrospective, single institution studies looking at lobectomy for low-risk cancers, one must remember that these patients are selected based on other tumor features (multifocality, extrathyroidal extension, etc.) and not just size alone. Remember that 30%-40% of patients with papillary thyroid cancer will have multifocal disease.
The second is that successfully treating thyroid cancer patients with lobectomy requires buy-in from all parties involved - surgeons, endocrinologists, and, most importantly, the patient. Everyone must be comfortable with omitting radioactive iodine, detectable thyroglobulin levels, and following the remaining lobe with ultrasound. Some patients will not be comfortable with this and may choose to undergo total thyroidectomy. Even if we surgeons agree to shift back toward less aggressive surgery, we cannot do so in isolation.
Dr. David F. Schneider is an associate professor and the director of endocrine surgery research in the department of surgery, University of Wisconsin, Madison. He has no conflicts to disclose.
This excellent study by Adam et al. contributes to a growing body of literature supporting thyroid lobectomy for low risk, small, differentiated thyroid tumors. I should say this represents a shift back toward lobectomy. Total thyroidectomy became the procedure of choice for nearly all differentiated thyroid tumors over the last 2-3 decades in part because of the landmark study by Bilimoria et al. (Surgery 2007;142:906-14).
Now the tide is shifting back the other direction.
I do not mean to imply that passing trends drive how we treat thyroid cancer. Mortality rates from differentiated thyroid cancer remain extremely low. This makes measuring any differences in mortality challenging. The outcome can differ depending on the cohort and the other variables included in the modeling. Recurrence is the real driver of morbidity in thyroid cancer, with anywhere from 10%-30% of patients experiencing a recurrence. Unfortunately, large national cancer registries do not capture recurrence very well.
This study controlled for many tumor features that will also impact disease specific survival apart from just the treatment received. The follow-up time is also impressive. So, if we are to undertake a more nuanced and stratified approach to determining the extent of surgery, there are a few things to consider. The first is patient selection.
In this study and in a growing body of retrospective, single institution studies looking at lobectomy for low-risk cancers, one must remember that these patients are selected based on other tumor features (multifocality, extrathyroidal extension, etc.) and not just size alone. Remember that 30%-40% of patients with papillary thyroid cancer will have multifocal disease.
The second is that successfully treating thyroid cancer patients with lobectomy requires buy-in from all parties involved - surgeons, endocrinologists, and, most importantly, the patient. Everyone must be comfortable with omitting radioactive iodine, detectable thyroglobulin levels, and following the remaining lobe with ultrasound. Some patients will not be comfortable with this and may choose to undergo total thyroidectomy. Even if we surgeons agree to shift back toward less aggressive surgery, we cannot do so in isolation.
Dr. David F. Schneider is an associate professor and the director of endocrine surgery research in the department of surgery, University of Wisconsin, Madison. He has no conflicts to disclose.
BOSTON – Extensive surgery beyond lobectomy offers no survival advantage for small papillary thyroid cancers, according to a large database analysis.
Total thyroidectomy was not associated with an overall survival benefit over lobectomy for papillary thyroid cancers sized 1-2 cm (hazard ratio, 1.05; P = .61) or 2.1-4.0 cm (HR, 0.89; P = .21), even after adjusting for multiple patient and pathologic factors.
"Despite guidelines, our results call into question whether tumor size 1-4 cm should be an absolute determinant for extent of surgery," Dr. Mohamed Abdelgadir Adam said at the annual meeting of the American Surgical Association.
Current American Thyroid Association guidelines recommend lobectomy for tumors less than 1 cm in size and total thyroidectomy for those exceeding 1 cm.
"Using total thyroidectomy based on tumor size alone may unnecessarily subject patients to increased risks of complications without a survival benefit," he said. "In addition to tumor size up to 4 cm, other factors are important for determining extent of surgery such as nodal and distant metastases and patient preference."
The extent of surgery for papillary thyroid cancer, however, remains controversial. Recent analyses (Arch. Otolaryngol. Head Neck Surg. 2010;136:1055-61) have shown no survival difference between lobectomy and total thyroidectomy, while an earlier landmark study found improved overall survival with total thyroidectomy for tumors 1 cm or more (Ann. Surg. 2007;246;375-81). The latter study, however, has been criticized because it did not take into account patient comorbidities, multifocality, extrathyroidal extension, or completeness of resection, said Dr. Adam of Duke University School of Medicine, Durham, N.C.
The current analysis adjusted for age, gender, race, annual income, insurance status, hospital volume, patient comorbidities, tumor multifocality, extrathyroidal extension, lymph node involvement, metastases, surgical margins, and radioactive iodine ablation.
Discussant Dr. Blake Cady, professor emeritus of surgery at Harvard Medical School and Massachusetts General Hospital in Boston, said the current report is an important contribution to the controversy. It also supports his own bias against overtreatment of these mostly young patients with total thyroidectomy, which necessitates long-term medication and is accompanied by almost routine use of radioactive iodine, despite no evidence it improves outcomes in low-risk patients.
"In no other human cancer with a 99% 20-year survival is a policy of routine total primary organ removal practiced and routine systemic therapy used," he said. "Therefore, this report may help to scale back toward a more measured balance between treatment and morbidity."
Study coauthor Dr. Julie Ann Sosa, chief of endocrine surgery at Duke, challenged the audience to promote the growing body of evidence supporting equivalence in overall survival, such as a recent study described as coming the closest to a head-to-head comparison and having the longest follow-up at 18 years. It showed equivalence between lobectomy, without radioactive iodine, and total thyroidectomy for overall, progression-free, and disease-specific survival and risk of recurrence in tumors 40 mm or less (World J. Surg. 2014;38:68-79.
"In light of these data, I think it is probably high time for guidelines to potentially reconsider this issue," she said, noting that the American Thyroid Association will issue new guidelines later this spring or summer.
Dr. Sosa also advocated for "a more sophisticated approach" to preoperative evaluation and risk stratification for papillary thyroid cancer that distinguishes between low-, medium-, and high-risk tumors. The Duke study did not exclude most high-risk tumors, but rather adjusted for high-risk characteristics such as extrathyroidal extension, lymph node involvement, and distant metastases.
"When you adjust for these high-risk characteristics, the afforded overall survival benefit disappears," she said. "So what I think we would argue is that there is equivalence in outcome for the majority of patients for low- and medium-risk tumors. But for those patients who have high-risk tumors, as defined by some of these high-risk characteristics, then I think all of us would agree that total thyroidectomy, with or without radioactive iodine, would be indicated."
The study involved 61,775 patients in the National Cancer Database who underwent total thyroidectomy (n = 54,926) or lobectomy with or without isthmusectomy (n = 6,849) for papillary thyroid cancer from 1998 to 2006. Compared with the lobectomy group, the thyroidectomy group had more tumor multifocality (44% vs. 29%), positive surgical margins (27% vs. 7%), distant metastases (1% vs. 0.4%), and radioactive iodine (65% vs. 33%; P value less than .01 for all).
In multivariable analysis, nodal and distant metastases were associated with compromised survival, Dr. Adam said.
The complete manuscript of this study and its presentation at the American Surgical Association’s 134th Annual Meeting, April 2014 in Boston, is anticipated to be published in the Annals of Surgery, pending editorial review.
The authors reported no conflicting interests
BOSTON – Extensive surgery beyond lobectomy offers no survival advantage for small papillary thyroid cancers, according to a large database analysis.
Total thyroidectomy was not associated with an overall survival benefit over lobectomy for papillary thyroid cancers sized 1-2 cm (hazard ratio, 1.05; P = .61) or 2.1-4.0 cm (HR, 0.89; P = .21), even after adjusting for multiple patient and pathologic factors.
"Despite guidelines, our results call into question whether tumor size 1-4 cm should be an absolute determinant for extent of surgery," Dr. Mohamed Abdelgadir Adam said at the annual meeting of the American Surgical Association.
Current American Thyroid Association guidelines recommend lobectomy for tumors less than 1 cm in size and total thyroidectomy for those exceeding 1 cm.
"Using total thyroidectomy based on tumor size alone may unnecessarily subject patients to increased risks of complications without a survival benefit," he said. "In addition to tumor size up to 4 cm, other factors are important for determining extent of surgery such as nodal and distant metastases and patient preference."
The extent of surgery for papillary thyroid cancer, however, remains controversial. Recent analyses (Arch. Otolaryngol. Head Neck Surg. 2010;136:1055-61) have shown no survival difference between lobectomy and total thyroidectomy, while an earlier landmark study found improved overall survival with total thyroidectomy for tumors 1 cm or more (Ann. Surg. 2007;246;375-81). The latter study, however, has been criticized because it did not take into account patient comorbidities, multifocality, extrathyroidal extension, or completeness of resection, said Dr. Adam of Duke University School of Medicine, Durham, N.C.
The current analysis adjusted for age, gender, race, annual income, insurance status, hospital volume, patient comorbidities, tumor multifocality, extrathyroidal extension, lymph node involvement, metastases, surgical margins, and radioactive iodine ablation.
Discussant Dr. Blake Cady, professor emeritus of surgery at Harvard Medical School and Massachusetts General Hospital in Boston, said the current report is an important contribution to the controversy. It also supports his own bias against overtreatment of these mostly young patients with total thyroidectomy, which necessitates long-term medication and is accompanied by almost routine use of radioactive iodine, despite no evidence it improves outcomes in low-risk patients.
"In no other human cancer with a 99% 20-year survival is a policy of routine total primary organ removal practiced and routine systemic therapy used," he said. "Therefore, this report may help to scale back toward a more measured balance between treatment and morbidity."
Study coauthor Dr. Julie Ann Sosa, chief of endocrine surgery at Duke, challenged the audience to promote the growing body of evidence supporting equivalence in overall survival, such as a recent study described as coming the closest to a head-to-head comparison and having the longest follow-up at 18 years. It showed equivalence between lobectomy, without radioactive iodine, and total thyroidectomy for overall, progression-free, and disease-specific survival and risk of recurrence in tumors 40 mm or less (World J. Surg. 2014;38:68-79.
"In light of these data, I think it is probably high time for guidelines to potentially reconsider this issue," she said, noting that the American Thyroid Association will issue new guidelines later this spring or summer.
Dr. Sosa also advocated for "a more sophisticated approach" to preoperative evaluation and risk stratification for papillary thyroid cancer that distinguishes between low-, medium-, and high-risk tumors. The Duke study did not exclude most high-risk tumors, but rather adjusted for high-risk characteristics such as extrathyroidal extension, lymph node involvement, and distant metastases.
"When you adjust for these high-risk characteristics, the afforded overall survival benefit disappears," she said. "So what I think we would argue is that there is equivalence in outcome for the majority of patients for low- and medium-risk tumors. But for those patients who have high-risk tumors, as defined by some of these high-risk characteristics, then I think all of us would agree that total thyroidectomy, with or without radioactive iodine, would be indicated."
The study involved 61,775 patients in the National Cancer Database who underwent total thyroidectomy (n = 54,926) or lobectomy with or without isthmusectomy (n = 6,849) for papillary thyroid cancer from 1998 to 2006. Compared with the lobectomy group, the thyroidectomy group had more tumor multifocality (44% vs. 29%), positive surgical margins (27% vs. 7%), distant metastases (1% vs. 0.4%), and radioactive iodine (65% vs. 33%; P value less than .01 for all).
In multivariable analysis, nodal and distant metastases were associated with compromised survival, Dr. Adam said.
The complete manuscript of this study and its presentation at the American Surgical Association’s 134th Annual Meeting, April 2014 in Boston, is anticipated to be published in the Annals of Surgery, pending editorial review.
The authors reported no conflicting interests
AT THE ASA ANNUAL MEETING
Major finding: After adjustment, total thyroidectomy did not improve overall survival over lobectomy for tumors 1-2 cm (HR, 1.05; P = .61) or 2.1-4.0 cm (HR, 0.89; P = .21).
Data source: A retrospective database analysis of 61,775 papillary thyroid cancers.
Disclosures: The authors reported no conflicting interests.
Keep an eye on the HPV p16 protein in head and neck cancer
Click on the PDF icon at the top of this introduction to read the full article.
Click on the PDF icon at the top of this introduction to read the full article.
Click on the PDF icon at the top of this introduction to read the full article.
Thyroglobulin washout boosts diagnostic sensitivity in recurrent thyroid cancer
PHOENIX – In patients with recurrent papillary thyroid cancer, fine-needle aspiration cytology and thyroglobulin washout was a highly sensitive and specific means of detecting metastatic disease, according to a retrospective analysis.
Surgeon-performed FNA-Tg washout appears to increase the diagnostic accuracy in detecting metastatic disease in this patient population. Routine performance of the combined modalities should be considered in patients with suspicious metastatic lymphadenopathies, said Dr. Hossam Mohamed of the division of endocrine and oncological surgery in the department of surgery at Tulane University, New Orleans.
In a retrospective study of 117 patients with recurrent papillary thyroid cancer, the combination of surgeon-performed fine-needle aspiration cytology (FNAC) with fine-needle aspiration thyroglobulin washout (FNA-Tg) had a 100% specificity, 94.9% sensitivity, and negative predictive value of 93.75%, with a diagnostic accuracy of 97.1%, he said.
"Cervical lymph node involvement has been reported to be up to 46% at initial diagnosis, hence ultrasonography and fine-needle aspiration have been standard diagnostic modalities used to detect and evaluate cervical lymph nodes in patients with thyroid malignancies," he said at the annual Society of Surgical Oncology Cancer Symposium.
His team hypothesized that by adding surgeon-performed ultrasonography with Tg washout to FNAC for the management of patients with suspicious lymphadenopathies, they might be able to increase the accuracy of the combined tests for detecting metastatic disease in patients with recurrent papillary thyroid cancers.
In a retrospective study, they looked at results for patients who underwent preoperative FNAC and FNA-Tg washout followed by selective neck dissection. All dissections were performed by senior author Dr. Emad Kandil, chief of the endocrine surgery section at Tulane University.
They correlated the test results with the final pathology results of the dissected lymph nodes, and compared the sensitivity and specificity of the combined modalities to those of standard FNAC alone.
Of the 117 patients, 76% were female, and mean age was 52 years. Nearly half of the patients (47.6%) had cervical lymph node dissections, 39.7% had modified radical lymph node dissections, 6.35% had combined modified-radical, and 12.7% had combined modified-radical and cervical resections. Half of the group required second resections.
When the researchers compared the individual modalities to the final pathology results, they found that the respective sensitivity of FNAC, FNA-Tg, and the two combined were 84.6%, 89.4%, and 94.9%. They found the respective specificities to be 100%, 96.8%, and 100%.
The negative predictive value of FNAC was 87.1%. and of FNA-Tg was 85.7%. When the two diagnostic methods were used together, they ruled out metastases with 93.75% accuracy.
"Only one patient had a negative lymph node pathology with a positive FNA-Tg washout, which we couldn’t find an explanation for," Dr. Mohamed said.
Two patients who had negative FNA-Tg washout levels had evidence of atypical cells on FNAC and elevated serum Tg levels. These patients were therefore taken to surgery, and were found to have metastatic disease on final pathology, he said.
The study was internally funded. Dr. Mohamed reported having no financial disclosures.
PHOENIX – In patients with recurrent papillary thyroid cancer, fine-needle aspiration cytology and thyroglobulin washout was a highly sensitive and specific means of detecting metastatic disease, according to a retrospective analysis.
Surgeon-performed FNA-Tg washout appears to increase the diagnostic accuracy in detecting metastatic disease in this patient population. Routine performance of the combined modalities should be considered in patients with suspicious metastatic lymphadenopathies, said Dr. Hossam Mohamed of the division of endocrine and oncological surgery in the department of surgery at Tulane University, New Orleans.
In a retrospective study of 117 patients with recurrent papillary thyroid cancer, the combination of surgeon-performed fine-needle aspiration cytology (FNAC) with fine-needle aspiration thyroglobulin washout (FNA-Tg) had a 100% specificity, 94.9% sensitivity, and negative predictive value of 93.75%, with a diagnostic accuracy of 97.1%, he said.
"Cervical lymph node involvement has been reported to be up to 46% at initial diagnosis, hence ultrasonography and fine-needle aspiration have been standard diagnostic modalities used to detect and evaluate cervical lymph nodes in patients with thyroid malignancies," he said at the annual Society of Surgical Oncology Cancer Symposium.
His team hypothesized that by adding surgeon-performed ultrasonography with Tg washout to FNAC for the management of patients with suspicious lymphadenopathies, they might be able to increase the accuracy of the combined tests for detecting metastatic disease in patients with recurrent papillary thyroid cancers.
In a retrospective study, they looked at results for patients who underwent preoperative FNAC and FNA-Tg washout followed by selective neck dissection. All dissections were performed by senior author Dr. Emad Kandil, chief of the endocrine surgery section at Tulane University.
They correlated the test results with the final pathology results of the dissected lymph nodes, and compared the sensitivity and specificity of the combined modalities to those of standard FNAC alone.
Of the 117 patients, 76% were female, and mean age was 52 years. Nearly half of the patients (47.6%) had cervical lymph node dissections, 39.7% had modified radical lymph node dissections, 6.35% had combined modified-radical, and 12.7% had combined modified-radical and cervical resections. Half of the group required second resections.
When the researchers compared the individual modalities to the final pathology results, they found that the respective sensitivity of FNAC, FNA-Tg, and the two combined were 84.6%, 89.4%, and 94.9%. They found the respective specificities to be 100%, 96.8%, and 100%.
The negative predictive value of FNAC was 87.1%. and of FNA-Tg was 85.7%. When the two diagnostic methods were used together, they ruled out metastases with 93.75% accuracy.
"Only one patient had a negative lymph node pathology with a positive FNA-Tg washout, which we couldn’t find an explanation for," Dr. Mohamed said.
Two patients who had negative FNA-Tg washout levels had evidence of atypical cells on FNAC and elevated serum Tg levels. These patients were therefore taken to surgery, and were found to have metastatic disease on final pathology, he said.
The study was internally funded. Dr. Mohamed reported having no financial disclosures.
PHOENIX – In patients with recurrent papillary thyroid cancer, fine-needle aspiration cytology and thyroglobulin washout was a highly sensitive and specific means of detecting metastatic disease, according to a retrospective analysis.
Surgeon-performed FNA-Tg washout appears to increase the diagnostic accuracy in detecting metastatic disease in this patient population. Routine performance of the combined modalities should be considered in patients with suspicious metastatic lymphadenopathies, said Dr. Hossam Mohamed of the division of endocrine and oncological surgery in the department of surgery at Tulane University, New Orleans.
In a retrospective study of 117 patients with recurrent papillary thyroid cancer, the combination of surgeon-performed fine-needle aspiration cytology (FNAC) with fine-needle aspiration thyroglobulin washout (FNA-Tg) had a 100% specificity, 94.9% sensitivity, and negative predictive value of 93.75%, with a diagnostic accuracy of 97.1%, he said.
"Cervical lymph node involvement has been reported to be up to 46% at initial diagnosis, hence ultrasonography and fine-needle aspiration have been standard diagnostic modalities used to detect and evaluate cervical lymph nodes in patients with thyroid malignancies," he said at the annual Society of Surgical Oncology Cancer Symposium.
His team hypothesized that by adding surgeon-performed ultrasonography with Tg washout to FNAC for the management of patients with suspicious lymphadenopathies, they might be able to increase the accuracy of the combined tests for detecting metastatic disease in patients with recurrent papillary thyroid cancers.
In a retrospective study, they looked at results for patients who underwent preoperative FNAC and FNA-Tg washout followed by selective neck dissection. All dissections were performed by senior author Dr. Emad Kandil, chief of the endocrine surgery section at Tulane University.
They correlated the test results with the final pathology results of the dissected lymph nodes, and compared the sensitivity and specificity of the combined modalities to those of standard FNAC alone.
Of the 117 patients, 76% were female, and mean age was 52 years. Nearly half of the patients (47.6%) had cervical lymph node dissections, 39.7% had modified radical lymph node dissections, 6.35% had combined modified-radical, and 12.7% had combined modified-radical and cervical resections. Half of the group required second resections.
When the researchers compared the individual modalities to the final pathology results, they found that the respective sensitivity of FNAC, FNA-Tg, and the two combined were 84.6%, 89.4%, and 94.9%. They found the respective specificities to be 100%, 96.8%, and 100%.
The negative predictive value of FNAC was 87.1%. and of FNA-Tg was 85.7%. When the two diagnostic methods were used together, they ruled out metastases with 93.75% accuracy.
"Only one patient had a negative lymph node pathology with a positive FNA-Tg washout, which we couldn’t find an explanation for," Dr. Mohamed said.
Two patients who had negative FNA-Tg washout levels had evidence of atypical cells on FNAC and elevated serum Tg levels. These patients were therefore taken to surgery, and were found to have metastatic disease on final pathology, he said.
The study was internally funded. Dr. Mohamed reported having no financial disclosures.
AT SSO 2014
Key clinical point: Adding surgeon-performed ultrasonography with thyroglobulin washout to fine-needle aspiration cytology increases the accuracy of detecting metastatic disease in patients with recurrent papillary thyroid cancers.
Major finding: The negative predictive value of fine-needle aspiration cytology (FNAC) with fine-needle aspiration thyroglobulin washout (FNA-Tg) was 93.75%.
Data source: Review of prospectively collected data on 117 patients with recurrent papillary thyroid cancer.
Disclosures: The study was internally funded. Dr. Mohamed reported having no financial disclosures.