User login
High-volume surgeons have best adrenalectomy outcomes
PHOENIX – There is more evidence that it’s best to go with the pros: Adrenalectomies performed by higher-volume surgeons are associated with fewer complications, lower costs, and shorter lengths of stay than are those done by surgeons who dabble in the procedure.
The findings, presented at the annual Society of Surgical Oncology Cancer Symposium, come from a cross-sectional study of outcomes on all patients who underwent unilateral, partial, or bilateral adrenalectomies in the United States over a 7-year span.
"The frequency of adrenalectomy has steadily increased in the United States within the last few years, and with improvement of diagnostic and imaging modalities it’s likely that the rate of adrenal surgery will continue to rise," said Dr. Adam Hauch, a research resident in the department of surgery at Tulane University, New Orleans.
The prospects for the growth in the procedure prompted Dr. Hauch and colleagues to look at clinical and economic outcomes following adrenalectomy, and to see how surgeon volume, diagnosis, and type of surgery might affect outcomes.
They drew on discharge data from the Healthcare Cost and Utilization Project – National Inpatient Sample (HCUP-NIS), an administrative database sponsored by the U.S. Agency for Healthcare Research and Quality.
The information included International Classification of Diseases, Ninth Revision (ICD-9) codes identifying all adult patients who underwent adrenalectomies in U.S. hospitals from 2003 through 2009. Patients were divided into benign and malignant lesion groups.
The investigators found 7,829 procedures. Mean patient age was 50 years, most of the patients (74.4%) were white, and the majority were female (58.2%) and were privately insured (58.9%). Nearly all of the patients (98.3%) had one or no comorbidities at the time of admission. Only 42 patients (0.5%) died during their hospital stays.
More than three-fourths of the procedures (79.2%) were for benign disease; the remaining 20.8% of surgeries were for malignancies.
Low-volume surgeons, defined as those who performed one or fewer adrenalectomies on average per year, performed 41.7% of all procedures, compared with 34.7% for intermediate-volume surgeons (two to five per year) and 23.6% for high-volume surgeons (more than five per year).
The vast majority (97.1%) of procedures were unilateral/partial, and approximately 95% of surgeons in each experience category performed such procedures. Procedures for malignant disease accounted for 10.6% of cases for low-volume surgeons, 6.3% for intermediate-volume docs, and 4.3% of the most prolific surgeons.
It’s complicated
Risks for any complication were significantly higher among low-volume surgeons (18.8% of their cases), compared with 14.6% for those in the middle, and 11.6% for the high-volume operators (P less than .0001). High-volume performers had significantly lower risk for cardiovascular complications (P = .0008), pulmonary complications (P = .0481), bleeding (P = .0106), and technical difficulties during surgery (P = .0024).
In an analysis adjusted for patient demographic factors, payer, primary diagnosis, obesity, comorbidities, inpatient death, admission type, hospital teaching status and volume, surgeon, and type of procedure, low-volume surgeons were nearly twice as likely as were high-volume surgeons to have complications (adjusted odds ratio [aOR] 1.822, P less than .0001), and intermediate-volume surgeons had a nearly 1.5-fold higher risk (aOR 1.479, P = .0044).
Other risk factors for complications were bilateral vs. unilateral procedures (aOR 2.165, P = .0018), and malignant vs. benign disease (aOR 1.685, P less than .0001).
Not surprisingly, complications more than doubled mean total case charges, which ranged from $33,659 for uncomplicated unilateral cases to $73,021 for complicated cases (P = .0013), and from $47,284 for bilateral cases with no complications, to $141,461 for two-sided procedures with complications (P = .0221). Charges were higher for malignant cases than for benign cases without complications (P less than .0001), but complications brought the charges for both benign and malignant cases closer together .
Charges for noncomplicated procedures performed by high-volume surgeons were a comparative bargain at $27,324, compared with $33,499 for low- and intermediate-volume surgeons combined (P = .001). However, there were no significant differences by surgeon volume when complications arose.
Similarly, lengths of stay were prolonged when complications ensued for both unilateral cases (mean 3.7 days vs. 9.3 for complicated cases, P = .0042) and for bilateral cases (9.3 vs. 19.8, P = .025).
Higher volume surgeons managed to get patients out faster, averaging 2.7 days for cases without complications, compared with 4.2 for low/intermediate-volume surgeons (P less than .0001). When complications arose, patients of higher-volume surgeons still had shorter lengths of stay (8.5 vs. 10.4 days), but this difference was not statistically significant.
Dr. Lawrence Kim, professor of surgery at the University of North Carolina, Chapel Hill, said after the presentation that the study showed the limitations of using administrative data.
He said that approximately "98% of the patients [in the study presented] had no comorbidities, which just does not mesh with the realities I have ever faced with adrenal patients."
The study was internally funded. Dr. Hauch reported having no financial disclosures.
While there are nuances to the surgical technique to remove the adrenal gland, what makes adrenal surgery unique is not necessarily the procedural aspect of it, but rather the clinical work-up and preoperative preparation of the patient. Adrenal tumors are often hormonally active. Depending on the type of hormonal activity, the needs of the patient before, during, and after surgery vary greatly. Is volume in this study really more of a marker for the patients who underwent appropriate work-up and treatment before surgery, and not a marker of the technical demands of the operation? And this study does not take into consideration the surgeon skill in advanced laparoscopy, as while some of these surgeons may be performing one or two adrenal cases a year, they also perform laparoscopic colon, kidney, pancreas, spleen, liver, or stomach surgery. These are cases with just as much, if not more, technical demands in the operating room.
And what about how the gland is removed? There are at least nine different surgical approaches to the adrenal gland. Is it open or is it minimally invasive? Are you approaching it from the front, the back, or laterally? Are you using the robot? And does it really matter if you are only doing two cases a year? While super-high-volume centers (they do way more than just five cases a year) are publishing their outcomes with using the robot and approaching the adrenal gland from the back, they also allude to the learning curve of the various procedures, as well as the progression in surgical approach acquisition. But what has yet to be determined is when should that additional approach be attempted? At what clinical volume does having eight different ways to take out the adrenal gland matter? Shouldn’t the first step be having one way to take out the adrenal gland that results in good outcomes? And how often do you need to perform each approach to ensure that you as the surgeon are at your best? And what about the fact that the anatomy for a right is completely different from the left? The combinations quickly become endless.
While we can continue to publish research showing high volume is better, we have to acknowledge that not all Americans have access to a high-volume surgeon. The barriers to accessing this care are complex, and are due to both system and patient factors. It is not just as simple as ensuring that everyone has health insurance.
Sarah Oltmann, M.D., is clinical instructor of endocrine surgery at the University of Wisconsin, Madison.
While there are nuances to the surgical technique to remove the adrenal gland, what makes adrenal surgery unique is not necessarily the procedural aspect of it, but rather the clinical work-up and preoperative preparation of the patient. Adrenal tumors are often hormonally active. Depending on the type of hormonal activity, the needs of the patient before, during, and after surgery vary greatly. Is volume in this study really more of a marker for the patients who underwent appropriate work-up and treatment before surgery, and not a marker of the technical demands of the operation? And this study does not take into consideration the surgeon skill in advanced laparoscopy, as while some of these surgeons may be performing one or two adrenal cases a year, they also perform laparoscopic colon, kidney, pancreas, spleen, liver, or stomach surgery. These are cases with just as much, if not more, technical demands in the operating room.
And what about how the gland is removed? There are at least nine different surgical approaches to the adrenal gland. Is it open or is it minimally invasive? Are you approaching it from the front, the back, or laterally? Are you using the robot? And does it really matter if you are only doing two cases a year? While super-high-volume centers (they do way more than just five cases a year) are publishing their outcomes with using the robot and approaching the adrenal gland from the back, they also allude to the learning curve of the various procedures, as well as the progression in surgical approach acquisition. But what has yet to be determined is when should that additional approach be attempted? At what clinical volume does having eight different ways to take out the adrenal gland matter? Shouldn’t the first step be having one way to take out the adrenal gland that results in good outcomes? And how often do you need to perform each approach to ensure that you as the surgeon are at your best? And what about the fact that the anatomy for a right is completely different from the left? The combinations quickly become endless.
While we can continue to publish research showing high volume is better, we have to acknowledge that not all Americans have access to a high-volume surgeon. The barriers to accessing this care are complex, and are due to both system and patient factors. It is not just as simple as ensuring that everyone has health insurance.
Sarah Oltmann, M.D., is clinical instructor of endocrine surgery at the University of Wisconsin, Madison.
While there are nuances to the surgical technique to remove the adrenal gland, what makes adrenal surgery unique is not necessarily the procedural aspect of it, but rather the clinical work-up and preoperative preparation of the patient. Adrenal tumors are often hormonally active. Depending on the type of hormonal activity, the needs of the patient before, during, and after surgery vary greatly. Is volume in this study really more of a marker for the patients who underwent appropriate work-up and treatment before surgery, and not a marker of the technical demands of the operation? And this study does not take into consideration the surgeon skill in advanced laparoscopy, as while some of these surgeons may be performing one or two adrenal cases a year, they also perform laparoscopic colon, kidney, pancreas, spleen, liver, or stomach surgery. These are cases with just as much, if not more, technical demands in the operating room.
And what about how the gland is removed? There are at least nine different surgical approaches to the adrenal gland. Is it open or is it minimally invasive? Are you approaching it from the front, the back, or laterally? Are you using the robot? And does it really matter if you are only doing two cases a year? While super-high-volume centers (they do way more than just five cases a year) are publishing their outcomes with using the robot and approaching the adrenal gland from the back, they also allude to the learning curve of the various procedures, as well as the progression in surgical approach acquisition. But what has yet to be determined is when should that additional approach be attempted? At what clinical volume does having eight different ways to take out the adrenal gland matter? Shouldn’t the first step be having one way to take out the adrenal gland that results in good outcomes? And how often do you need to perform each approach to ensure that you as the surgeon are at your best? And what about the fact that the anatomy for a right is completely different from the left? The combinations quickly become endless.
While we can continue to publish research showing high volume is better, we have to acknowledge that not all Americans have access to a high-volume surgeon. The barriers to accessing this care are complex, and are due to both system and patient factors. It is not just as simple as ensuring that everyone has health insurance.
Sarah Oltmann, M.D., is clinical instructor of endocrine surgery at the University of Wisconsin, Madison.
PHOENIX – There is more evidence that it’s best to go with the pros: Adrenalectomies performed by higher-volume surgeons are associated with fewer complications, lower costs, and shorter lengths of stay than are those done by surgeons who dabble in the procedure.
The findings, presented at the annual Society of Surgical Oncology Cancer Symposium, come from a cross-sectional study of outcomes on all patients who underwent unilateral, partial, or bilateral adrenalectomies in the United States over a 7-year span.
"The frequency of adrenalectomy has steadily increased in the United States within the last few years, and with improvement of diagnostic and imaging modalities it’s likely that the rate of adrenal surgery will continue to rise," said Dr. Adam Hauch, a research resident in the department of surgery at Tulane University, New Orleans.
The prospects for the growth in the procedure prompted Dr. Hauch and colleagues to look at clinical and economic outcomes following adrenalectomy, and to see how surgeon volume, diagnosis, and type of surgery might affect outcomes.
They drew on discharge data from the Healthcare Cost and Utilization Project – National Inpatient Sample (HCUP-NIS), an administrative database sponsored by the U.S. Agency for Healthcare Research and Quality.
The information included International Classification of Diseases, Ninth Revision (ICD-9) codes identifying all adult patients who underwent adrenalectomies in U.S. hospitals from 2003 through 2009. Patients were divided into benign and malignant lesion groups.
The investigators found 7,829 procedures. Mean patient age was 50 years, most of the patients (74.4%) were white, and the majority were female (58.2%) and were privately insured (58.9%). Nearly all of the patients (98.3%) had one or no comorbidities at the time of admission. Only 42 patients (0.5%) died during their hospital stays.
More than three-fourths of the procedures (79.2%) were for benign disease; the remaining 20.8% of surgeries were for malignancies.
Low-volume surgeons, defined as those who performed one or fewer adrenalectomies on average per year, performed 41.7% of all procedures, compared with 34.7% for intermediate-volume surgeons (two to five per year) and 23.6% for high-volume surgeons (more than five per year).
The vast majority (97.1%) of procedures were unilateral/partial, and approximately 95% of surgeons in each experience category performed such procedures. Procedures for malignant disease accounted for 10.6% of cases for low-volume surgeons, 6.3% for intermediate-volume docs, and 4.3% of the most prolific surgeons.
It’s complicated
Risks for any complication were significantly higher among low-volume surgeons (18.8% of their cases), compared with 14.6% for those in the middle, and 11.6% for the high-volume operators (P less than .0001). High-volume performers had significantly lower risk for cardiovascular complications (P = .0008), pulmonary complications (P = .0481), bleeding (P = .0106), and technical difficulties during surgery (P = .0024).
In an analysis adjusted for patient demographic factors, payer, primary diagnosis, obesity, comorbidities, inpatient death, admission type, hospital teaching status and volume, surgeon, and type of procedure, low-volume surgeons were nearly twice as likely as were high-volume surgeons to have complications (adjusted odds ratio [aOR] 1.822, P less than .0001), and intermediate-volume surgeons had a nearly 1.5-fold higher risk (aOR 1.479, P = .0044).
Other risk factors for complications were bilateral vs. unilateral procedures (aOR 2.165, P = .0018), and malignant vs. benign disease (aOR 1.685, P less than .0001).
Not surprisingly, complications more than doubled mean total case charges, which ranged from $33,659 for uncomplicated unilateral cases to $73,021 for complicated cases (P = .0013), and from $47,284 for bilateral cases with no complications, to $141,461 for two-sided procedures with complications (P = .0221). Charges were higher for malignant cases than for benign cases without complications (P less than .0001), but complications brought the charges for both benign and malignant cases closer together .
Charges for noncomplicated procedures performed by high-volume surgeons were a comparative bargain at $27,324, compared with $33,499 for low- and intermediate-volume surgeons combined (P = .001). However, there were no significant differences by surgeon volume when complications arose.
Similarly, lengths of stay were prolonged when complications ensued for both unilateral cases (mean 3.7 days vs. 9.3 for complicated cases, P = .0042) and for bilateral cases (9.3 vs. 19.8, P = .025).
Higher volume surgeons managed to get patients out faster, averaging 2.7 days for cases without complications, compared with 4.2 for low/intermediate-volume surgeons (P less than .0001). When complications arose, patients of higher-volume surgeons still had shorter lengths of stay (8.5 vs. 10.4 days), but this difference was not statistically significant.
Dr. Lawrence Kim, professor of surgery at the University of North Carolina, Chapel Hill, said after the presentation that the study showed the limitations of using administrative data.
He said that approximately "98% of the patients [in the study presented] had no comorbidities, which just does not mesh with the realities I have ever faced with adrenal patients."
The study was internally funded. Dr. Hauch reported having no financial disclosures.
PHOENIX – There is more evidence that it’s best to go with the pros: Adrenalectomies performed by higher-volume surgeons are associated with fewer complications, lower costs, and shorter lengths of stay than are those done by surgeons who dabble in the procedure.
The findings, presented at the annual Society of Surgical Oncology Cancer Symposium, come from a cross-sectional study of outcomes on all patients who underwent unilateral, partial, or bilateral adrenalectomies in the United States over a 7-year span.
"The frequency of adrenalectomy has steadily increased in the United States within the last few years, and with improvement of diagnostic and imaging modalities it’s likely that the rate of adrenal surgery will continue to rise," said Dr. Adam Hauch, a research resident in the department of surgery at Tulane University, New Orleans.
The prospects for the growth in the procedure prompted Dr. Hauch and colleagues to look at clinical and economic outcomes following adrenalectomy, and to see how surgeon volume, diagnosis, and type of surgery might affect outcomes.
They drew on discharge data from the Healthcare Cost and Utilization Project – National Inpatient Sample (HCUP-NIS), an administrative database sponsored by the U.S. Agency for Healthcare Research and Quality.
The information included International Classification of Diseases, Ninth Revision (ICD-9) codes identifying all adult patients who underwent adrenalectomies in U.S. hospitals from 2003 through 2009. Patients were divided into benign and malignant lesion groups.
The investigators found 7,829 procedures. Mean patient age was 50 years, most of the patients (74.4%) were white, and the majority were female (58.2%) and were privately insured (58.9%). Nearly all of the patients (98.3%) had one or no comorbidities at the time of admission. Only 42 patients (0.5%) died during their hospital stays.
More than three-fourths of the procedures (79.2%) were for benign disease; the remaining 20.8% of surgeries were for malignancies.
Low-volume surgeons, defined as those who performed one or fewer adrenalectomies on average per year, performed 41.7% of all procedures, compared with 34.7% for intermediate-volume surgeons (two to five per year) and 23.6% for high-volume surgeons (more than five per year).
The vast majority (97.1%) of procedures were unilateral/partial, and approximately 95% of surgeons in each experience category performed such procedures. Procedures for malignant disease accounted for 10.6% of cases for low-volume surgeons, 6.3% for intermediate-volume docs, and 4.3% of the most prolific surgeons.
It’s complicated
Risks for any complication were significantly higher among low-volume surgeons (18.8% of their cases), compared with 14.6% for those in the middle, and 11.6% for the high-volume operators (P less than .0001). High-volume performers had significantly lower risk for cardiovascular complications (P = .0008), pulmonary complications (P = .0481), bleeding (P = .0106), and technical difficulties during surgery (P = .0024).
In an analysis adjusted for patient demographic factors, payer, primary diagnosis, obesity, comorbidities, inpatient death, admission type, hospital teaching status and volume, surgeon, and type of procedure, low-volume surgeons were nearly twice as likely as were high-volume surgeons to have complications (adjusted odds ratio [aOR] 1.822, P less than .0001), and intermediate-volume surgeons had a nearly 1.5-fold higher risk (aOR 1.479, P = .0044).
Other risk factors for complications were bilateral vs. unilateral procedures (aOR 2.165, P = .0018), and malignant vs. benign disease (aOR 1.685, P less than .0001).
Not surprisingly, complications more than doubled mean total case charges, which ranged from $33,659 for uncomplicated unilateral cases to $73,021 for complicated cases (P = .0013), and from $47,284 for bilateral cases with no complications, to $141,461 for two-sided procedures with complications (P = .0221). Charges were higher for malignant cases than for benign cases without complications (P less than .0001), but complications brought the charges for both benign and malignant cases closer together .
Charges for noncomplicated procedures performed by high-volume surgeons were a comparative bargain at $27,324, compared with $33,499 for low- and intermediate-volume surgeons combined (P = .001). However, there were no significant differences by surgeon volume when complications arose.
Similarly, lengths of stay were prolonged when complications ensued for both unilateral cases (mean 3.7 days vs. 9.3 for complicated cases, P = .0042) and for bilateral cases (9.3 vs. 19.8, P = .025).
Higher volume surgeons managed to get patients out faster, averaging 2.7 days for cases without complications, compared with 4.2 for low/intermediate-volume surgeons (P less than .0001). When complications arose, patients of higher-volume surgeons still had shorter lengths of stay (8.5 vs. 10.4 days), but this difference was not statistically significant.
Dr. Lawrence Kim, professor of surgery at the University of North Carolina, Chapel Hill, said after the presentation that the study showed the limitations of using administrative data.
He said that approximately "98% of the patients [in the study presented] had no comorbidities, which just does not mesh with the realities I have ever faced with adrenal patients."
The study was internally funded. Dr. Hauch reported having no financial disclosures.
AT SSO 2014
Major finding: Patients of low-volume surgeons were nearly twice as likely as were those of high-volume surgeons to have complications following adrenalectomy (adjusted odds ratio 1.822, P less than .0001).
Data source: Cross-sectional analysis of data on 7,829 patients.
Disclosures: The study was internally funded. Dr. Hauch reported having no financial disclosures.
Younger men with goiter at higher risk for thyroid cancers
PHOENIX – More than one-fourth of men under age 50 undergoing surgery for benign goiter were found to have thyroid cancers, based on a chart review performed at the University of Pennsylvania.
The overall incidence of thyroid cancers in the patient series was 12%. Among men under age 45, the rate was "surprisingly" 28%, said Douglas R. Farquhar, a medical student at the University of Pennsylvania School of Medicine in Philadelphia.
Although thyroid goiters have traditionally been thought to be associated with a low risk for malignancy, recent studies have suggested otherwise. "In the literature we have seen published rates of up to 35%, which is much higher than we all had anticipated," Mr. Farquhar said at the annual Society of Surgical Oncology Cancer Symposium.
To get a better handle on the preoperative and patient characteristics associated with incident thyroid cancer and characterize the types of thyroid cancer discovered incidentally, Mr. Farquhar and his colleagues reviewed charts on all patients who underwent either total thyroidectomy or thyroid lobectomy for goiter at the center from 2004 through 2012.
Many cases of goiter can be medically managed, but surgery may be indicated in cases of pressure symptoms, cosmesis, or suspicion of malignancy, the investigators noted.
They excluded from their study patients with preoperative fine-needle aspiration pathology findings of Bethesda level III-VI (follicular lesion of undetermined significance, follicular neoplasm, suspicious or positive for malignancy).
Among 418 patients undergoing goiter surgery, 367 had goiter only, and 51 (12%) had an incident thyroid cancer. In all, 38 (75%) had papillary carcinomas, 10 (20%) had follicular carcinomas, 3 (6%) had Hürthle cell carcinomas, and 2 (4%) had thyroid lymphomas (two patients had multiple thyroid cancers, explaining the percentage greater than 100). An additional 67 patients (16%) were found to have micropapillary lesions.
Looking at the population as a whole, the investigators found that patients with thyroid cancer tended to be younger, with a mean age of 49.5 vs. 54.6 years (P = .012). There was a trend toward more cancers among men than women, but it was not significant.
There were no significant differences in any preoperative factors between patients with cancers and those with goiter only, including number of nodules, site of dominant nodule (right, left, or isthmus), thyroid function, thyroid weight, or fine-needle aspiration results (percentage deemed benign or nondiagnostic).
In a multivariate analysis, male sex was associated with a more than twofold risk for thyroid cancer (odds ratio, 2.39; 95% confidence interval, 1.152-4.978). There were also trends toward a lower risk of cancer with each additional decade of life, and a higher risk among patients who had undergone thyroid lobectomy, but these were nonsignificant associations.
"Knowledge of these associations may prove to be useful for both patient counseling and surgical decision making," Mr. Farquhar said.
The study was internally funded. The senior author was Dr. Douglas L. Fraker, chief of the division of endocrine and oncologic surgery at the University of Pennsylvania.
Mr. Farquhar and his coauthors reported having no relevant financial disclosures.
PHOENIX – More than one-fourth of men under age 50 undergoing surgery for benign goiter were found to have thyroid cancers, based on a chart review performed at the University of Pennsylvania.
The overall incidence of thyroid cancers in the patient series was 12%. Among men under age 45, the rate was "surprisingly" 28%, said Douglas R. Farquhar, a medical student at the University of Pennsylvania School of Medicine in Philadelphia.
Although thyroid goiters have traditionally been thought to be associated with a low risk for malignancy, recent studies have suggested otherwise. "In the literature we have seen published rates of up to 35%, which is much higher than we all had anticipated," Mr. Farquhar said at the annual Society of Surgical Oncology Cancer Symposium.
To get a better handle on the preoperative and patient characteristics associated with incident thyroid cancer and characterize the types of thyroid cancer discovered incidentally, Mr. Farquhar and his colleagues reviewed charts on all patients who underwent either total thyroidectomy or thyroid lobectomy for goiter at the center from 2004 through 2012.
Many cases of goiter can be medically managed, but surgery may be indicated in cases of pressure symptoms, cosmesis, or suspicion of malignancy, the investigators noted.
They excluded from their study patients with preoperative fine-needle aspiration pathology findings of Bethesda level III-VI (follicular lesion of undetermined significance, follicular neoplasm, suspicious or positive for malignancy).
Among 418 patients undergoing goiter surgery, 367 had goiter only, and 51 (12%) had an incident thyroid cancer. In all, 38 (75%) had papillary carcinomas, 10 (20%) had follicular carcinomas, 3 (6%) had Hürthle cell carcinomas, and 2 (4%) had thyroid lymphomas (two patients had multiple thyroid cancers, explaining the percentage greater than 100). An additional 67 patients (16%) were found to have micropapillary lesions.
Looking at the population as a whole, the investigators found that patients with thyroid cancer tended to be younger, with a mean age of 49.5 vs. 54.6 years (P = .012). There was a trend toward more cancers among men than women, but it was not significant.
There were no significant differences in any preoperative factors between patients with cancers and those with goiter only, including number of nodules, site of dominant nodule (right, left, or isthmus), thyroid function, thyroid weight, or fine-needle aspiration results (percentage deemed benign or nondiagnostic).
In a multivariate analysis, male sex was associated with a more than twofold risk for thyroid cancer (odds ratio, 2.39; 95% confidence interval, 1.152-4.978). There were also trends toward a lower risk of cancer with each additional decade of life, and a higher risk among patients who had undergone thyroid lobectomy, but these were nonsignificant associations.
"Knowledge of these associations may prove to be useful for both patient counseling and surgical decision making," Mr. Farquhar said.
The study was internally funded. The senior author was Dr. Douglas L. Fraker, chief of the division of endocrine and oncologic surgery at the University of Pennsylvania.
Mr. Farquhar and his coauthors reported having no relevant financial disclosures.
PHOENIX – More than one-fourth of men under age 50 undergoing surgery for benign goiter were found to have thyroid cancers, based on a chart review performed at the University of Pennsylvania.
The overall incidence of thyroid cancers in the patient series was 12%. Among men under age 45, the rate was "surprisingly" 28%, said Douglas R. Farquhar, a medical student at the University of Pennsylvania School of Medicine in Philadelphia.
Although thyroid goiters have traditionally been thought to be associated with a low risk for malignancy, recent studies have suggested otherwise. "In the literature we have seen published rates of up to 35%, which is much higher than we all had anticipated," Mr. Farquhar said at the annual Society of Surgical Oncology Cancer Symposium.
To get a better handle on the preoperative and patient characteristics associated with incident thyroid cancer and characterize the types of thyroid cancer discovered incidentally, Mr. Farquhar and his colleagues reviewed charts on all patients who underwent either total thyroidectomy or thyroid lobectomy for goiter at the center from 2004 through 2012.
Many cases of goiter can be medically managed, but surgery may be indicated in cases of pressure symptoms, cosmesis, or suspicion of malignancy, the investigators noted.
They excluded from their study patients with preoperative fine-needle aspiration pathology findings of Bethesda level III-VI (follicular lesion of undetermined significance, follicular neoplasm, suspicious or positive for malignancy).
Among 418 patients undergoing goiter surgery, 367 had goiter only, and 51 (12%) had an incident thyroid cancer. In all, 38 (75%) had papillary carcinomas, 10 (20%) had follicular carcinomas, 3 (6%) had Hürthle cell carcinomas, and 2 (4%) had thyroid lymphomas (two patients had multiple thyroid cancers, explaining the percentage greater than 100). An additional 67 patients (16%) were found to have micropapillary lesions.
Looking at the population as a whole, the investigators found that patients with thyroid cancer tended to be younger, with a mean age of 49.5 vs. 54.6 years (P = .012). There was a trend toward more cancers among men than women, but it was not significant.
There were no significant differences in any preoperative factors between patients with cancers and those with goiter only, including number of nodules, site of dominant nodule (right, left, or isthmus), thyroid function, thyroid weight, or fine-needle aspiration results (percentage deemed benign or nondiagnostic).
In a multivariate analysis, male sex was associated with a more than twofold risk for thyroid cancer (odds ratio, 2.39; 95% confidence interval, 1.152-4.978). There were also trends toward a lower risk of cancer with each additional decade of life, and a higher risk among patients who had undergone thyroid lobectomy, but these were nonsignificant associations.
"Knowledge of these associations may prove to be useful for both patient counseling and surgical decision making," Mr. Farquhar said.
The study was internally funded. The senior author was Dr. Douglas L. Fraker, chief of the division of endocrine and oncologic surgery at the University of Pennsylvania.
Mr. Farquhar and his coauthors reported having no relevant financial disclosures.
AT SSO 2014
Key clinical point: Men under age 50 undergoing surgery for benign goiter are at elevated risk for thyroid cancer.
Major finding: Among men under 45 undergoing goiter surgery, the rate of incidentally discovered thyroid cancers was 28%.
Data source: A case series of 418 consecutive patients undergoing surgery for goiter.
Disclosures: The study was internally funded. Mr. Farquhar and his coauthors reported having no relevant financial disclosures.
Chemoradiation offered better survival than accelerated radiation in head and neck squamous cell carcinomas
SCOTTSDALE, ARIZ. – Concurrent chemoradiation offered better overall survival and disease-free survival than accelerated radiotherapy in patients with moderately advanced squamous cell carcinomas of the head and neck, investigators reported at the Multidisciplinary Head and Neck Symposium.
Actuarial rates of 2-year overall survival and disease-free survival in patients treated with concurrent chemoradiation (CCR) were significantly better than for patients treated with accelerated radiotherapy alone, reported Dr. Krzysztof Skladowski of the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology in Gliwice, Poland.
"CCR with conventional 7 weeks of fractionation and at least two courses of high-dose cisplatin is more effective than 6 weeks of accelerated radiotherapy alone," he said.
Even if patients can tolerate only a single course of cisplatin, CCR is still superior to accelerated radiation, he added.
The findings suggest that accelerated radiation protocols should be reserved for patients with more favorable prognosis, such as those with stage T2 disease with limited nodal involvement, and those who are positive for the human papillomavirus (HPV) p16 protein, Dr. Skladowski said at the symposium cosponsored by the American Society for Radiation Oncology and the American Society of Clinical Oncology.
The findings are "concordant with data that has been emerging now over approximately 10-14 years of the value of concurrent chemoradiation in head and neck cancer for a substantial cohort of patients over radiation alone," said Dr. Paul Harari of the University of Wisconsin, Madison, and the invited discussant.
Although a previous meta-analysis (Lancet 2006; 368:843-54) suggested that accelerated or hyperfractionated radiotherapy was associated with a 3.4% advantage in overall survival, compared with conventional radiotherapy over 5 years, there have been no randomized studies comparing accelerated radiotherapy protocols with concurrent chemoradiation in this population, Dr. Skladowski said.
He and colleagues compared the two modalities in 101 patients with moderately advanced cancers of the oropharynx (46 patients), hypopharynx (19), and larynx (36).
They defined moderately advanced cancers as stage T2N1-2, T3N0-2, or T4AN0-2 if the involved nodes are not larger than 3 cm in diameter. Patients with oropharyngeal cancers were tested for expression of the human papillomavirus (HPV) p16 protein.
Patients were randomly assigned to receive either concurrent chemoradiation with intensity-modulated radiation therapy–delivered doses of 66-70 Gy divided into 33-35 daily fractions over 45-49 days plus cisplatin 100 mg/m2, delivered on days 1, 2 and 43, or to accelerated radiotherapy delivered via intensity-modulated radiation therapy in 1.8 Gy fractions 7 days/week to a total dose of 66.2-72 Gy.
Five patients in the CCR arm received only one dose of cisplatin, 30 received two doses, and 13 received the planned three doses.
At a median follow-up of 30 months, actuarial rates of 2-year overall survival of patients treated with CCR were 81%, compared with 62% for patients treated with accelerated radiation (P = .02). Disease-free survival rates were 75% and 60%, respectively (P = .05).
Acute adverse events were similar, with approximately 80% of patients in each treatment arm experiencing confluent mucositis, and about 10% having grade 3 dysphagia. There were no grade 4 toxicities.
The majority of treatment failures in each group were local, occurring in 21 of 52 patients treated with radiation alone, and in 11 of 49 patients treated with CCR (P = .03).
Significantly more deaths occurred in the radiation alone arm: 20 vs. 9 (P =.02).
The 2-year disease-free survival rate among patients in the CCR arm was dose dependent, at 60% of patients who received one course of cisplatin, 77% of those who received two courses, and 79% for those who received all three.
At the time of the analysis, all patients with oropharyngeal cancer who were positive for HPV p16 (five treated with accelerated radiation and six with CCR) were alive with no treatment failure. The overall survival rate for HPV-positive patients was 60% in the radiation only arm, and 80% in the CCR arm.
The study was supported by the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology. Dr. Skladowski reported having no financial disclosures. Dr. Harari has received research funding from Amgen.
SCOTTSDALE, ARIZ. – Concurrent chemoradiation offered better overall survival and disease-free survival than accelerated radiotherapy in patients with moderately advanced squamous cell carcinomas of the head and neck, investigators reported at the Multidisciplinary Head and Neck Symposium.
Actuarial rates of 2-year overall survival and disease-free survival in patients treated with concurrent chemoradiation (CCR) were significantly better than for patients treated with accelerated radiotherapy alone, reported Dr. Krzysztof Skladowski of the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology in Gliwice, Poland.
"CCR with conventional 7 weeks of fractionation and at least two courses of high-dose cisplatin is more effective than 6 weeks of accelerated radiotherapy alone," he said.
Even if patients can tolerate only a single course of cisplatin, CCR is still superior to accelerated radiation, he added.
The findings suggest that accelerated radiation protocols should be reserved for patients with more favorable prognosis, such as those with stage T2 disease with limited nodal involvement, and those who are positive for the human papillomavirus (HPV) p16 protein, Dr. Skladowski said at the symposium cosponsored by the American Society for Radiation Oncology and the American Society of Clinical Oncology.
The findings are "concordant with data that has been emerging now over approximately 10-14 years of the value of concurrent chemoradiation in head and neck cancer for a substantial cohort of patients over radiation alone," said Dr. Paul Harari of the University of Wisconsin, Madison, and the invited discussant.
Although a previous meta-analysis (Lancet 2006; 368:843-54) suggested that accelerated or hyperfractionated radiotherapy was associated with a 3.4% advantage in overall survival, compared with conventional radiotherapy over 5 years, there have been no randomized studies comparing accelerated radiotherapy protocols with concurrent chemoradiation in this population, Dr. Skladowski said.
He and colleagues compared the two modalities in 101 patients with moderately advanced cancers of the oropharynx (46 patients), hypopharynx (19), and larynx (36).
They defined moderately advanced cancers as stage T2N1-2, T3N0-2, or T4AN0-2 if the involved nodes are not larger than 3 cm in diameter. Patients with oropharyngeal cancers were tested for expression of the human papillomavirus (HPV) p16 protein.
Patients were randomly assigned to receive either concurrent chemoradiation with intensity-modulated radiation therapy–delivered doses of 66-70 Gy divided into 33-35 daily fractions over 45-49 days plus cisplatin 100 mg/m2, delivered on days 1, 2 and 43, or to accelerated radiotherapy delivered via intensity-modulated radiation therapy in 1.8 Gy fractions 7 days/week to a total dose of 66.2-72 Gy.
Five patients in the CCR arm received only one dose of cisplatin, 30 received two doses, and 13 received the planned three doses.
At a median follow-up of 30 months, actuarial rates of 2-year overall survival of patients treated with CCR were 81%, compared with 62% for patients treated with accelerated radiation (P = .02). Disease-free survival rates were 75% and 60%, respectively (P = .05).
Acute adverse events were similar, with approximately 80% of patients in each treatment arm experiencing confluent mucositis, and about 10% having grade 3 dysphagia. There were no grade 4 toxicities.
The majority of treatment failures in each group were local, occurring in 21 of 52 patients treated with radiation alone, and in 11 of 49 patients treated with CCR (P = .03).
Significantly more deaths occurred in the radiation alone arm: 20 vs. 9 (P =.02).
The 2-year disease-free survival rate among patients in the CCR arm was dose dependent, at 60% of patients who received one course of cisplatin, 77% of those who received two courses, and 79% for those who received all three.
At the time of the analysis, all patients with oropharyngeal cancer who were positive for HPV p16 (five treated with accelerated radiation and six with CCR) were alive with no treatment failure. The overall survival rate for HPV-positive patients was 60% in the radiation only arm, and 80% in the CCR arm.
The study was supported by the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology. Dr. Skladowski reported having no financial disclosures. Dr. Harari has received research funding from Amgen.
SCOTTSDALE, ARIZ. – Concurrent chemoradiation offered better overall survival and disease-free survival than accelerated radiotherapy in patients with moderately advanced squamous cell carcinomas of the head and neck, investigators reported at the Multidisciplinary Head and Neck Symposium.
Actuarial rates of 2-year overall survival and disease-free survival in patients treated with concurrent chemoradiation (CCR) were significantly better than for patients treated with accelerated radiotherapy alone, reported Dr. Krzysztof Skladowski of the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology in Gliwice, Poland.
"CCR with conventional 7 weeks of fractionation and at least two courses of high-dose cisplatin is more effective than 6 weeks of accelerated radiotherapy alone," he said.
Even if patients can tolerate only a single course of cisplatin, CCR is still superior to accelerated radiation, he added.
The findings suggest that accelerated radiation protocols should be reserved for patients with more favorable prognosis, such as those with stage T2 disease with limited nodal involvement, and those who are positive for the human papillomavirus (HPV) p16 protein, Dr. Skladowski said at the symposium cosponsored by the American Society for Radiation Oncology and the American Society of Clinical Oncology.
The findings are "concordant with data that has been emerging now over approximately 10-14 years of the value of concurrent chemoradiation in head and neck cancer for a substantial cohort of patients over radiation alone," said Dr. Paul Harari of the University of Wisconsin, Madison, and the invited discussant.
Although a previous meta-analysis (Lancet 2006; 368:843-54) suggested that accelerated or hyperfractionated radiotherapy was associated with a 3.4% advantage in overall survival, compared with conventional radiotherapy over 5 years, there have been no randomized studies comparing accelerated radiotherapy protocols with concurrent chemoradiation in this population, Dr. Skladowski said.
He and colleagues compared the two modalities in 101 patients with moderately advanced cancers of the oropharynx (46 patients), hypopharynx (19), and larynx (36).
They defined moderately advanced cancers as stage T2N1-2, T3N0-2, or T4AN0-2 if the involved nodes are not larger than 3 cm in diameter. Patients with oropharyngeal cancers were tested for expression of the human papillomavirus (HPV) p16 protein.
Patients were randomly assigned to receive either concurrent chemoradiation with intensity-modulated radiation therapy–delivered doses of 66-70 Gy divided into 33-35 daily fractions over 45-49 days plus cisplatin 100 mg/m2, delivered on days 1, 2 and 43, or to accelerated radiotherapy delivered via intensity-modulated radiation therapy in 1.8 Gy fractions 7 days/week to a total dose of 66.2-72 Gy.
Five patients in the CCR arm received only one dose of cisplatin, 30 received two doses, and 13 received the planned three doses.
At a median follow-up of 30 months, actuarial rates of 2-year overall survival of patients treated with CCR were 81%, compared with 62% for patients treated with accelerated radiation (P = .02). Disease-free survival rates were 75% and 60%, respectively (P = .05).
Acute adverse events were similar, with approximately 80% of patients in each treatment arm experiencing confluent mucositis, and about 10% having grade 3 dysphagia. There were no grade 4 toxicities.
The majority of treatment failures in each group were local, occurring in 21 of 52 patients treated with radiation alone, and in 11 of 49 patients treated with CCR (P = .03).
Significantly more deaths occurred in the radiation alone arm: 20 vs. 9 (P =.02).
The 2-year disease-free survival rate among patients in the CCR arm was dose dependent, at 60% of patients who received one course of cisplatin, 77% of those who received two courses, and 79% for those who received all three.
At the time of the analysis, all patients with oropharyngeal cancer who were positive for HPV p16 (five treated with accelerated radiation and six with CCR) were alive with no treatment failure. The overall survival rate for HPV-positive patients was 60% in the radiation only arm, and 80% in the CCR arm.
The study was supported by the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology. Dr. Skladowski reported having no financial disclosures. Dr. Harari has received research funding from Amgen.
AT THE HEAD AND NECK CANCER SYMPOSIUM
Major finding: At a median follow-up of 30 months, actuarial rates of 2-year overall survival of patients treated with concurrent chemoradiation were 81%, compared with 62% for patients treated with accelerated radiation.
Data source: A randomized trial comparing accelerated radiotherapy with concurrent chemoradiation with standard fractionation radiation in 101 patients with head and neck cancers.
Disclosures: The study was supported by the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology. Dr. Skladowski reported having no financial disclosures. Dr. Harari has received research funding from Amgen.
Experimental EGFR inhibitor added nothing but rash
SCOTTSDALE, ARIZ. – The addition of the experimental targeted agent zalutumumab to primary curative chemoradiation for head and neck cancers did not improve locoregional control, disease-specific survival, or overall survival at 3 years of follow-up.
The only thing that zalutumumab added to therapy was a skin rash in the large majority of patients who received it, reported Dr. Jens Overgaard, of the department of experimental clinical oncology at Aarhus University, Denmark.
Response to zalutumumab, a monoclonal antibody targeted to the epidermal growth factor receptor (EGFR), was not related to tumor human papillomavirus 16 (HPV/p16) status or to chemoradiotherapy, Dr. Overgaard reported at the Multidisciplinary Head and Neck Cancer Symposium.
The results of the DAHANCA 19 trial echo those of the RTOG (Radiation Oncology Therapy Group) trial 0522, which found no benefit from the addition of the EGFR inhibitor cetuximab (Erbitux) to accelerated cisplatin-based chemoradiotherapy, said Dr. Paul Harari, an invited discussant from the University of Wisconsin, Madison.
"Where I think we have a lot of unanswered questions is acknowledging how little we actually understand about EGFR biology, despite now 40 years of progressive knowledge," Dr. Harari said.
"We’re now seeing very clearly in molecular and clinical correlate studies that the more we suppress the EGFR, the more we see collateral overexpression of additional RTKs [receptor tyrosine kinases], including members of the HER family, such as HER-3, that enable an escape mechanism for tumors that become resistant to EGFR inhibition," he said.
Dr. Overgaard and his colleagues in the Danish Head and Neck Cancer Group conducted an open-label, phase III trial in which 619 patients with nonmetastatic squamous cell carcinomas of the larynx, oropharynx, hypopharynx, or oral cavity were randomly assigned to received 66-68 Gy of accelerated radiotherapy with or without zalutumumab 8 mg/kg weekly, with the first dose given a week before the start of radiation. The radiation was given concomitantly with the radiosensitizer nimorazole and, in patients with involved lymph nodes, cisplatin.
A total of 301 patients who received zalutumumab and 307 controls were included in the final intention-to-treat analysis.
At 3-year follow-up, there were no significant differences in either the primary endpoint of locoregional control (76% in zalutumumab-treated patients and 77% of controls) or in the secondary endpoints of disease-specific survival (82% and 85%, respectively) or overall survival (72% and 79%), Dr. Overgaard reported at the symposium, cosponsored by the American Society for Radiation Oncology and the American Society of Clinical Oncology.
Overall, patients who were positive for the HPV/p16 biomarker fared better than p16-negative patients, with an odds ratio for the probability of local control in negative patients of 0.52 (95% confidence interval, 0.36-0.73; P value not reported).
However, regardless of HPV 16 status, the addition of zalutumumab made no difference in the primary endpoint.
In a proportional hazard analysis, factors significantly associated with worse outcomes included worse World Health Organization performance status, higher disease stage, nodal involvement, and HPV/p16 negative status.
Although zalutumumab was generally well tolerated, 94% of patients who received it developed a rash, and of this group, 29% had grade 3 or 4 rash. In all, 11% of patients assigned to zalutumumab had to stop the drug because of rash.
The trial was sponsored by the Danish Head and Neck Cancer Group. Dr. Overgaard reported having no financial disclosures. Dr. Harari has received research funding from Amgen.
SCOTTSDALE, ARIZ. – The addition of the experimental targeted agent zalutumumab to primary curative chemoradiation for head and neck cancers did not improve locoregional control, disease-specific survival, or overall survival at 3 years of follow-up.
The only thing that zalutumumab added to therapy was a skin rash in the large majority of patients who received it, reported Dr. Jens Overgaard, of the department of experimental clinical oncology at Aarhus University, Denmark.
Response to zalutumumab, a monoclonal antibody targeted to the epidermal growth factor receptor (EGFR), was not related to tumor human papillomavirus 16 (HPV/p16) status or to chemoradiotherapy, Dr. Overgaard reported at the Multidisciplinary Head and Neck Cancer Symposium.
The results of the DAHANCA 19 trial echo those of the RTOG (Radiation Oncology Therapy Group) trial 0522, which found no benefit from the addition of the EGFR inhibitor cetuximab (Erbitux) to accelerated cisplatin-based chemoradiotherapy, said Dr. Paul Harari, an invited discussant from the University of Wisconsin, Madison.
"Where I think we have a lot of unanswered questions is acknowledging how little we actually understand about EGFR biology, despite now 40 years of progressive knowledge," Dr. Harari said.
"We’re now seeing very clearly in molecular and clinical correlate studies that the more we suppress the EGFR, the more we see collateral overexpression of additional RTKs [receptor tyrosine kinases], including members of the HER family, such as HER-3, that enable an escape mechanism for tumors that become resistant to EGFR inhibition," he said.
Dr. Overgaard and his colleagues in the Danish Head and Neck Cancer Group conducted an open-label, phase III trial in which 619 patients with nonmetastatic squamous cell carcinomas of the larynx, oropharynx, hypopharynx, or oral cavity were randomly assigned to received 66-68 Gy of accelerated radiotherapy with or without zalutumumab 8 mg/kg weekly, with the first dose given a week before the start of radiation. The radiation was given concomitantly with the radiosensitizer nimorazole and, in patients with involved lymph nodes, cisplatin.
A total of 301 patients who received zalutumumab and 307 controls were included in the final intention-to-treat analysis.
At 3-year follow-up, there were no significant differences in either the primary endpoint of locoregional control (76% in zalutumumab-treated patients and 77% of controls) or in the secondary endpoints of disease-specific survival (82% and 85%, respectively) or overall survival (72% and 79%), Dr. Overgaard reported at the symposium, cosponsored by the American Society for Radiation Oncology and the American Society of Clinical Oncology.
Overall, patients who were positive for the HPV/p16 biomarker fared better than p16-negative patients, with an odds ratio for the probability of local control in negative patients of 0.52 (95% confidence interval, 0.36-0.73; P value not reported).
However, regardless of HPV 16 status, the addition of zalutumumab made no difference in the primary endpoint.
In a proportional hazard analysis, factors significantly associated with worse outcomes included worse World Health Organization performance status, higher disease stage, nodal involvement, and HPV/p16 negative status.
Although zalutumumab was generally well tolerated, 94% of patients who received it developed a rash, and of this group, 29% had grade 3 or 4 rash. In all, 11% of patients assigned to zalutumumab had to stop the drug because of rash.
The trial was sponsored by the Danish Head and Neck Cancer Group. Dr. Overgaard reported having no financial disclosures. Dr. Harari has received research funding from Amgen.
SCOTTSDALE, ARIZ. – The addition of the experimental targeted agent zalutumumab to primary curative chemoradiation for head and neck cancers did not improve locoregional control, disease-specific survival, or overall survival at 3 years of follow-up.
The only thing that zalutumumab added to therapy was a skin rash in the large majority of patients who received it, reported Dr. Jens Overgaard, of the department of experimental clinical oncology at Aarhus University, Denmark.
Response to zalutumumab, a monoclonal antibody targeted to the epidermal growth factor receptor (EGFR), was not related to tumor human papillomavirus 16 (HPV/p16) status or to chemoradiotherapy, Dr. Overgaard reported at the Multidisciplinary Head and Neck Cancer Symposium.
The results of the DAHANCA 19 trial echo those of the RTOG (Radiation Oncology Therapy Group) trial 0522, which found no benefit from the addition of the EGFR inhibitor cetuximab (Erbitux) to accelerated cisplatin-based chemoradiotherapy, said Dr. Paul Harari, an invited discussant from the University of Wisconsin, Madison.
"Where I think we have a lot of unanswered questions is acknowledging how little we actually understand about EGFR biology, despite now 40 years of progressive knowledge," Dr. Harari said.
"We’re now seeing very clearly in molecular and clinical correlate studies that the more we suppress the EGFR, the more we see collateral overexpression of additional RTKs [receptor tyrosine kinases], including members of the HER family, such as HER-3, that enable an escape mechanism for tumors that become resistant to EGFR inhibition," he said.
Dr. Overgaard and his colleagues in the Danish Head and Neck Cancer Group conducted an open-label, phase III trial in which 619 patients with nonmetastatic squamous cell carcinomas of the larynx, oropharynx, hypopharynx, or oral cavity were randomly assigned to received 66-68 Gy of accelerated radiotherapy with or without zalutumumab 8 mg/kg weekly, with the first dose given a week before the start of radiation. The radiation was given concomitantly with the radiosensitizer nimorazole and, in patients with involved lymph nodes, cisplatin.
A total of 301 patients who received zalutumumab and 307 controls were included in the final intention-to-treat analysis.
At 3-year follow-up, there were no significant differences in either the primary endpoint of locoregional control (76% in zalutumumab-treated patients and 77% of controls) or in the secondary endpoints of disease-specific survival (82% and 85%, respectively) or overall survival (72% and 79%), Dr. Overgaard reported at the symposium, cosponsored by the American Society for Radiation Oncology and the American Society of Clinical Oncology.
Overall, patients who were positive for the HPV/p16 biomarker fared better than p16-negative patients, with an odds ratio for the probability of local control in negative patients of 0.52 (95% confidence interval, 0.36-0.73; P value not reported).
However, regardless of HPV 16 status, the addition of zalutumumab made no difference in the primary endpoint.
In a proportional hazard analysis, factors significantly associated with worse outcomes included worse World Health Organization performance status, higher disease stage, nodal involvement, and HPV/p16 negative status.
Although zalutumumab was generally well tolerated, 94% of patients who received it developed a rash, and of this group, 29% had grade 3 or 4 rash. In all, 11% of patients assigned to zalutumumab had to stop the drug because of rash.
The trial was sponsored by the Danish Head and Neck Cancer Group. Dr. Overgaard reported having no financial disclosures. Dr. Harari has received research funding from Amgen.
AT THE HEAD AND NECK CANCER SYMPOSIUM
Major finding: There were no significant differences in locoregional control, disease-specific survival, or overall survival at 3 years with the addition of zalutumumab to accelerated chemoradiotherapy.
Data source: Open-label, randomized, phase III trial in 619 patients with squamous cell cancers of the head and neck.
Disclosures: The trial was sponsored by the Danish Head and Neck Cancer Group. Dr. Overgaard reported having no financial disclosures. Dr. Harari has received research funding from Amgen.
The push for smaller, smarter cancer trials
The American Society of Clinical Oncology is pressing cancer researchers to rethink the design of future clinical trials to achieve larger gains in four common cancers.
The final recommendations, which come after months of deliberations and public comment, try to hit the sweet spot between proposing guidelines that are not obtainable, and thus ignored, and having ambitious yet realistic goals.
For pancreatic cancer, for example, the experts recommended that clinical trials seek to improve median overall survival by 50%, or 4-5 months, for patients eligible for FOLFIRINOX (leucovorin, fluorouracil, irinotecan, and oxaliplatin) and by 3-4 months for those eligible for gemcitabine (Gemzar) with or without nab-paclitaxel (Abraxane).
Overall survival (OS) was selected over progression-free survival as the primary endpoint, although it was acknowledged that OS poses challenges such as the need for longer follow-up, the potential confounding effect of post-study therapies, and use of second-line therapies for secondary mutations identified after progression during first-line targeted therapy.
Ultimately, an improvement in median OS of 2.5-6 months, depending on the setting, was identified as the minimum incremental improvement over standard therapy that would define a clinically meaningful outcome.
The recommendations, published March 17 in the Journal of Clinical Oncology (J. Clin. Oncol. 2014 Mar. 17 [doi:10.1200/JCO.2013.53.8009]), also note that incremental improvements should be accompanied by little to no added toxicity over current treatments, and that a highly toxic regimen should produce the greatest OS gains to be considered clinically meaningful.
"We expect that sponsors will appreciate the need for raising the bar with regard to clinical trial goals, but that they will be conservative in their adoption of the recommendations," Dr. Lee M. Ellis, committee chair and professor of surgery at the University of Texas M.D. Anderson Cancer Center, Houston, said in an interview. "Trials designed with less ambitious goals may still be of benefit to individual patients if trial endpoints are met and if we can develop methods to identify patients most likely to benefit from the intervention."
Achieving the "smaller and smarter" trials envisioned by the committee rests on the ability to select patients for targeted therapy based on the molecular drivers of their tumors, rather than enrolling all comers. Unfortunately, in many cases, targeted agents continue to be developed without complete understanding of the drug target and, therefore, companion diagnostics to aid in patient selection, the experts observed.
"It is difficult to hit a target when it is not certain where it is or if it is valid," agreed Dr. David M. Dilts, codirector of the Center for Management Research in Healthcare, Oregon Health & Science University, Portland, in an accompanying editorial (J. Clin. Oncol. 2014 Mar. 17 [doi:10.1200/JCO.2013.54.5277]). "This, not insubstantial risk, should be ameliorated in the near future as major clinical research organizations are banking specimens, some of which are highly annotated, and as technology to analyze such specimens becomes faster, better, and cheaper."
To further this goal, the expert committee calls on trial sponsors to develop comprehensive biospecimen banks for each trial.
"Obstacles to developing these banks include cost and the willingness and ability of trial sponsors to foot the bill," Dr. Ellis said. "However, we believe the investment will pay off in increasing our ability to understand the molecular drivers of cancer and, as a result, more appropriate targeted therapies for people with cancer."
QOL
Though quality of life was a common theme that arose in all working group discussions, the recommendations lack hard targets in this area. Instead, the working groups cited the 2011 approval of the Janus kinase 1 and 2 inhibitor ruxolitinib (Jakavi) for myelofibrosis as an example of how serial assessment of specific cancer-related symptoms can define a clinically meaningful outcome for patients.
"It is not enough to just mention how important quality of life is. A clinical trial must be designed with a suite of thoughtful, feasible, validated patient-reported outcome measures that capture clinical benefit," Ms. Musa Mayer, a long-time advocate for patients with metastatic breast cancer, said in an interview. "Observed adverse events can never fully account for the lived experience of a given treatment."
Breast cancer
For breast cancer, the committee selected metastatic triple-negative breast cancer that was previously untreated for metastatic disease. They recommend clinical trials aim for an increase in OS of 4.5-6 months, although it was noted that consensus was not achieved by the breast cancer group on the magnitude of the benefit that would be considered clinically meaningful. The current median overall survival in this poor-prognosis population is 18 months.
Lung cancer
The committee addressed two lung cancer populations: nonsquamous cell carcinoma and squamous cell carcinoma. They recommend clinical trials seek to improve OS by 3.25-4 months and by 2.5-3 months, respectively. Current baseline median OS in these groups is 13 and 10 months.
Colon cancer
The recommendations for colon cancer target patients with disease progression with all prior therapies, or who are not candidates for standard second- or third-line options. Here, the goal is to improve OS by 3-5 months over the current baseline median OS of 4-6 months.
Notably, the cost of delivering the recommended targets for all four cancers was not addressed by the committee. The ASCO Value of Cancer Care Task Force, however, is already tasked with evaluating the efficacy, toxicity, and cost of specific oncology treatments.
"The working group provided thoughtful recommendations for the topics considered, although the specific recommendations were limited," Ms. Patricia Haugen, breast cancer survivor and current member and previous chair of the Department of Defense Congressionally Directed Breast Cancer Research Program Integration Panel, said in an interview.
She is hopeful that the new recommendations will be followed, but said there needs to be broad support and commitment to changes that produce more meaningful clinical benefit. "That commitment must be real and must come from all parties involved in the clinical trials process, so that clinical trials that do not meet a high bar are not considered, funded, nor implemented," she said.
Editorialist Dr. Dilts agreed that advocates from many areas are needed if the recommended goals are to be reached and suggested what might be required is "a more DARPA [Defense Advanced Research Projects Agency] approach, where answering high-risk questions are fostered and supported."
Dr. Ellis reported a consultant/advisory role with Genentech, Roche, Imclone, Eli Lilly, and Amgen. Ms. Mayer, Ms. Haugen, and Dr. Dilts reported no potential conflicts of interest.
The American Society of Clinical Oncology is pressing cancer researchers to rethink the design of future clinical trials to achieve larger gains in four common cancers.
The final recommendations, which come after months of deliberations and public comment, try to hit the sweet spot between proposing guidelines that are not obtainable, and thus ignored, and having ambitious yet realistic goals.
For pancreatic cancer, for example, the experts recommended that clinical trials seek to improve median overall survival by 50%, or 4-5 months, for patients eligible for FOLFIRINOX (leucovorin, fluorouracil, irinotecan, and oxaliplatin) and by 3-4 months for those eligible for gemcitabine (Gemzar) with or without nab-paclitaxel (Abraxane).
Overall survival (OS) was selected over progression-free survival as the primary endpoint, although it was acknowledged that OS poses challenges such as the need for longer follow-up, the potential confounding effect of post-study therapies, and use of second-line therapies for secondary mutations identified after progression during first-line targeted therapy.
Ultimately, an improvement in median OS of 2.5-6 months, depending on the setting, was identified as the minimum incremental improvement over standard therapy that would define a clinically meaningful outcome.
The recommendations, published March 17 in the Journal of Clinical Oncology (J. Clin. Oncol. 2014 Mar. 17 [doi:10.1200/JCO.2013.53.8009]), also note that incremental improvements should be accompanied by little to no added toxicity over current treatments, and that a highly toxic regimen should produce the greatest OS gains to be considered clinically meaningful.
"We expect that sponsors will appreciate the need for raising the bar with regard to clinical trial goals, but that they will be conservative in their adoption of the recommendations," Dr. Lee M. Ellis, committee chair and professor of surgery at the University of Texas M.D. Anderson Cancer Center, Houston, said in an interview. "Trials designed with less ambitious goals may still be of benefit to individual patients if trial endpoints are met and if we can develop methods to identify patients most likely to benefit from the intervention."
Achieving the "smaller and smarter" trials envisioned by the committee rests on the ability to select patients for targeted therapy based on the molecular drivers of their tumors, rather than enrolling all comers. Unfortunately, in many cases, targeted agents continue to be developed without complete understanding of the drug target and, therefore, companion diagnostics to aid in patient selection, the experts observed.
"It is difficult to hit a target when it is not certain where it is or if it is valid," agreed Dr. David M. Dilts, codirector of the Center for Management Research in Healthcare, Oregon Health & Science University, Portland, in an accompanying editorial (J. Clin. Oncol. 2014 Mar. 17 [doi:10.1200/JCO.2013.54.5277]). "This, not insubstantial risk, should be ameliorated in the near future as major clinical research organizations are banking specimens, some of which are highly annotated, and as technology to analyze such specimens becomes faster, better, and cheaper."
To further this goal, the expert committee calls on trial sponsors to develop comprehensive biospecimen banks for each trial.
"Obstacles to developing these banks include cost and the willingness and ability of trial sponsors to foot the bill," Dr. Ellis said. "However, we believe the investment will pay off in increasing our ability to understand the molecular drivers of cancer and, as a result, more appropriate targeted therapies for people with cancer."
QOL
Though quality of life was a common theme that arose in all working group discussions, the recommendations lack hard targets in this area. Instead, the working groups cited the 2011 approval of the Janus kinase 1 and 2 inhibitor ruxolitinib (Jakavi) for myelofibrosis as an example of how serial assessment of specific cancer-related symptoms can define a clinically meaningful outcome for patients.
"It is not enough to just mention how important quality of life is. A clinical trial must be designed with a suite of thoughtful, feasible, validated patient-reported outcome measures that capture clinical benefit," Ms. Musa Mayer, a long-time advocate for patients with metastatic breast cancer, said in an interview. "Observed adverse events can never fully account for the lived experience of a given treatment."
Breast cancer
For breast cancer, the committee selected metastatic triple-negative breast cancer that was previously untreated for metastatic disease. They recommend clinical trials aim for an increase in OS of 4.5-6 months, although it was noted that consensus was not achieved by the breast cancer group on the magnitude of the benefit that would be considered clinically meaningful. The current median overall survival in this poor-prognosis population is 18 months.
Lung cancer
The committee addressed two lung cancer populations: nonsquamous cell carcinoma and squamous cell carcinoma. They recommend clinical trials seek to improve OS by 3.25-4 months and by 2.5-3 months, respectively. Current baseline median OS in these groups is 13 and 10 months.
Colon cancer
The recommendations for colon cancer target patients with disease progression with all prior therapies, or who are not candidates for standard second- or third-line options. Here, the goal is to improve OS by 3-5 months over the current baseline median OS of 4-6 months.
Notably, the cost of delivering the recommended targets for all four cancers was not addressed by the committee. The ASCO Value of Cancer Care Task Force, however, is already tasked with evaluating the efficacy, toxicity, and cost of specific oncology treatments.
"The working group provided thoughtful recommendations for the topics considered, although the specific recommendations were limited," Ms. Patricia Haugen, breast cancer survivor and current member and previous chair of the Department of Defense Congressionally Directed Breast Cancer Research Program Integration Panel, said in an interview.
She is hopeful that the new recommendations will be followed, but said there needs to be broad support and commitment to changes that produce more meaningful clinical benefit. "That commitment must be real and must come from all parties involved in the clinical trials process, so that clinical trials that do not meet a high bar are not considered, funded, nor implemented," she said.
Editorialist Dr. Dilts agreed that advocates from many areas are needed if the recommended goals are to be reached and suggested what might be required is "a more DARPA [Defense Advanced Research Projects Agency] approach, where answering high-risk questions are fostered and supported."
Dr. Ellis reported a consultant/advisory role with Genentech, Roche, Imclone, Eli Lilly, and Amgen. Ms. Mayer, Ms. Haugen, and Dr. Dilts reported no potential conflicts of interest.
The American Society of Clinical Oncology is pressing cancer researchers to rethink the design of future clinical trials to achieve larger gains in four common cancers.
The final recommendations, which come after months of deliberations and public comment, try to hit the sweet spot between proposing guidelines that are not obtainable, and thus ignored, and having ambitious yet realistic goals.
For pancreatic cancer, for example, the experts recommended that clinical trials seek to improve median overall survival by 50%, or 4-5 months, for patients eligible for FOLFIRINOX (leucovorin, fluorouracil, irinotecan, and oxaliplatin) and by 3-4 months for those eligible for gemcitabine (Gemzar) with or without nab-paclitaxel (Abraxane).
Overall survival (OS) was selected over progression-free survival as the primary endpoint, although it was acknowledged that OS poses challenges such as the need for longer follow-up, the potential confounding effect of post-study therapies, and use of second-line therapies for secondary mutations identified after progression during first-line targeted therapy.
Ultimately, an improvement in median OS of 2.5-6 months, depending on the setting, was identified as the minimum incremental improvement over standard therapy that would define a clinically meaningful outcome.
The recommendations, published March 17 in the Journal of Clinical Oncology (J. Clin. Oncol. 2014 Mar. 17 [doi:10.1200/JCO.2013.53.8009]), also note that incremental improvements should be accompanied by little to no added toxicity over current treatments, and that a highly toxic regimen should produce the greatest OS gains to be considered clinically meaningful.
"We expect that sponsors will appreciate the need for raising the bar with regard to clinical trial goals, but that they will be conservative in their adoption of the recommendations," Dr. Lee M. Ellis, committee chair and professor of surgery at the University of Texas M.D. Anderson Cancer Center, Houston, said in an interview. "Trials designed with less ambitious goals may still be of benefit to individual patients if trial endpoints are met and if we can develop methods to identify patients most likely to benefit from the intervention."
Achieving the "smaller and smarter" trials envisioned by the committee rests on the ability to select patients for targeted therapy based on the molecular drivers of their tumors, rather than enrolling all comers. Unfortunately, in many cases, targeted agents continue to be developed without complete understanding of the drug target and, therefore, companion diagnostics to aid in patient selection, the experts observed.
"It is difficult to hit a target when it is not certain where it is or if it is valid," agreed Dr. David M. Dilts, codirector of the Center for Management Research in Healthcare, Oregon Health & Science University, Portland, in an accompanying editorial (J. Clin. Oncol. 2014 Mar. 17 [doi:10.1200/JCO.2013.54.5277]). "This, not insubstantial risk, should be ameliorated in the near future as major clinical research organizations are banking specimens, some of which are highly annotated, and as technology to analyze such specimens becomes faster, better, and cheaper."
To further this goal, the expert committee calls on trial sponsors to develop comprehensive biospecimen banks for each trial.
"Obstacles to developing these banks include cost and the willingness and ability of trial sponsors to foot the bill," Dr. Ellis said. "However, we believe the investment will pay off in increasing our ability to understand the molecular drivers of cancer and, as a result, more appropriate targeted therapies for people with cancer."
QOL
Though quality of life was a common theme that arose in all working group discussions, the recommendations lack hard targets in this area. Instead, the working groups cited the 2011 approval of the Janus kinase 1 and 2 inhibitor ruxolitinib (Jakavi) for myelofibrosis as an example of how serial assessment of specific cancer-related symptoms can define a clinically meaningful outcome for patients.
"It is not enough to just mention how important quality of life is. A clinical trial must be designed with a suite of thoughtful, feasible, validated patient-reported outcome measures that capture clinical benefit," Ms. Musa Mayer, a long-time advocate for patients with metastatic breast cancer, said in an interview. "Observed adverse events can never fully account for the lived experience of a given treatment."
Breast cancer
For breast cancer, the committee selected metastatic triple-negative breast cancer that was previously untreated for metastatic disease. They recommend clinical trials aim for an increase in OS of 4.5-6 months, although it was noted that consensus was not achieved by the breast cancer group on the magnitude of the benefit that would be considered clinically meaningful. The current median overall survival in this poor-prognosis population is 18 months.
Lung cancer
The committee addressed two lung cancer populations: nonsquamous cell carcinoma and squamous cell carcinoma. They recommend clinical trials seek to improve OS by 3.25-4 months and by 2.5-3 months, respectively. Current baseline median OS in these groups is 13 and 10 months.
Colon cancer
The recommendations for colon cancer target patients with disease progression with all prior therapies, or who are not candidates for standard second- or third-line options. Here, the goal is to improve OS by 3-5 months over the current baseline median OS of 4-6 months.
Notably, the cost of delivering the recommended targets for all four cancers was not addressed by the committee. The ASCO Value of Cancer Care Task Force, however, is already tasked with evaluating the efficacy, toxicity, and cost of specific oncology treatments.
"The working group provided thoughtful recommendations for the topics considered, although the specific recommendations were limited," Ms. Patricia Haugen, breast cancer survivor and current member and previous chair of the Department of Defense Congressionally Directed Breast Cancer Research Program Integration Panel, said in an interview.
She is hopeful that the new recommendations will be followed, but said there needs to be broad support and commitment to changes that produce more meaningful clinical benefit. "That commitment must be real and must come from all parties involved in the clinical trials process, so that clinical trials that do not meet a high bar are not considered, funded, nor implemented," she said.
Editorialist Dr. Dilts agreed that advocates from many areas are needed if the recommended goals are to be reached and suggested what might be required is "a more DARPA [Defense Advanced Research Projects Agency] approach, where answering high-risk questions are fostered and supported."
Dr. Ellis reported a consultant/advisory role with Genentech, Roche, Imclone, Eli Lilly, and Amgen. Ms. Mayer, Ms. Haugen, and Dr. Dilts reported no potential conflicts of interest.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Overall survival from recurrent head and neck cancer double among HPV+ patients
SCOTTSDALE, ARIZ. – Patients positive for the human papillomavirus have nearly twice the overall survival rate from recurrent oropharyngeal cancers as HPV-negative patients, Dr. Carole Fakhry reported at the 2014 Multidisciplinary Head and Neck Cancer Symposium.
Two years after a diagnosis of recurrence, 54.6% of HPV-positive patients were alive, compared with 27.6% of HPV-negative patients (P less than .001), according to a retrospective analysis of data from two clinical trials of 181 patients with stage III-IV oropharyngeal squamous cell carcinomas and known HPV status (measured by p16 protein expression).
"Tumor p16 status is independently associated with overall survival among oropharyngeal cancer patients with disease progression," said Dr. Fakhry of Johns Hopkins Medicine in Baltimore.
The analysis shows that "unquestionably, HPV-positive patients have a different molecular disease than their HPV-negative, tobacco-related counterparts. They are different with respect to specific tumor suppressor genes, and they are different in respect to specific activating oncogenes," noted Dr. Ezra Cohen of the University of California San Diego Moores Cancer Center, who was the invited discussant.
Dr. Fakhry and her colleagues looked at data on patients treated in the RTOG 0129 and 0522 trials.
Median time to progression was similar between the groups (8.2 months for HPV+ patients and 7.3 months for HPV–; P = .67), with the majority of disease progressions occurring within the first year (65% and 63%, respectively), reported Dr. Fakhry at the symposium, cosponsored by the American Society for Radiation Oncology and American Society of Clinical Oncology.
Factors associated with better overall survival in multivariate analysis included HPV+ status, salvage surgery, local-regional vs. distant progression, lower T stage at enrollment, and less than 20 smoking pack-years.
The study was supported by the National Cancer Institute and Bristol-Myers Squibb. Dr. Fakhry reported having no financial disclosures. Dr. Cohen disclosed serving as a consultant and adviser to BMS.
SCOTTSDALE, ARIZ. – Patients positive for the human papillomavirus have nearly twice the overall survival rate from recurrent oropharyngeal cancers as HPV-negative patients, Dr. Carole Fakhry reported at the 2014 Multidisciplinary Head and Neck Cancer Symposium.
Two years after a diagnosis of recurrence, 54.6% of HPV-positive patients were alive, compared with 27.6% of HPV-negative patients (P less than .001), according to a retrospective analysis of data from two clinical trials of 181 patients with stage III-IV oropharyngeal squamous cell carcinomas and known HPV status (measured by p16 protein expression).
"Tumor p16 status is independently associated with overall survival among oropharyngeal cancer patients with disease progression," said Dr. Fakhry of Johns Hopkins Medicine in Baltimore.
The analysis shows that "unquestionably, HPV-positive patients have a different molecular disease than their HPV-negative, tobacco-related counterparts. They are different with respect to specific tumor suppressor genes, and they are different in respect to specific activating oncogenes," noted Dr. Ezra Cohen of the University of California San Diego Moores Cancer Center, who was the invited discussant.
Dr. Fakhry and her colleagues looked at data on patients treated in the RTOG 0129 and 0522 trials.
Median time to progression was similar between the groups (8.2 months for HPV+ patients and 7.3 months for HPV–; P = .67), with the majority of disease progressions occurring within the first year (65% and 63%, respectively), reported Dr. Fakhry at the symposium, cosponsored by the American Society for Radiation Oncology and American Society of Clinical Oncology.
Factors associated with better overall survival in multivariate analysis included HPV+ status, salvage surgery, local-regional vs. distant progression, lower T stage at enrollment, and less than 20 smoking pack-years.
The study was supported by the National Cancer Institute and Bristol-Myers Squibb. Dr. Fakhry reported having no financial disclosures. Dr. Cohen disclosed serving as a consultant and adviser to BMS.
SCOTTSDALE, ARIZ. – Patients positive for the human papillomavirus have nearly twice the overall survival rate from recurrent oropharyngeal cancers as HPV-negative patients, Dr. Carole Fakhry reported at the 2014 Multidisciplinary Head and Neck Cancer Symposium.
Two years after a diagnosis of recurrence, 54.6% of HPV-positive patients were alive, compared with 27.6% of HPV-negative patients (P less than .001), according to a retrospective analysis of data from two clinical trials of 181 patients with stage III-IV oropharyngeal squamous cell carcinomas and known HPV status (measured by p16 protein expression).
"Tumor p16 status is independently associated with overall survival among oropharyngeal cancer patients with disease progression," said Dr. Fakhry of Johns Hopkins Medicine in Baltimore.
The analysis shows that "unquestionably, HPV-positive patients have a different molecular disease than their HPV-negative, tobacco-related counterparts. They are different with respect to specific tumor suppressor genes, and they are different in respect to specific activating oncogenes," noted Dr. Ezra Cohen of the University of California San Diego Moores Cancer Center, who was the invited discussant.
Dr. Fakhry and her colleagues looked at data on patients treated in the RTOG 0129 and 0522 trials.
Median time to progression was similar between the groups (8.2 months for HPV+ patients and 7.3 months for HPV–; P = .67), with the majority of disease progressions occurring within the first year (65% and 63%, respectively), reported Dr. Fakhry at the symposium, cosponsored by the American Society for Radiation Oncology and American Society of Clinical Oncology.
Factors associated with better overall survival in multivariate analysis included HPV+ status, salvage surgery, local-regional vs. distant progression, lower T stage at enrollment, and less than 20 smoking pack-years.
The study was supported by the National Cancer Institute and Bristol-Myers Squibb. Dr. Fakhry reported having no financial disclosures. Dr. Cohen disclosed serving as a consultant and adviser to BMS.
AT THE 2014 HEAD AND NECK CANCER SYMPOSIUM
Major finding: Two years after a diagnosis of recurrence of oropharyngeal cancer, 54.6% of HPV-positive patients were alive, compared with 27.6% of HPV-negative patients
Data source: Retrospective analysis of 181 patients with known HPV status in the RTOG 0129 and 0522 trials.
Disclosures: The study was supported by the National Cancer Institute and Bristol-Myers Squibb. Dr. Fakhry reported having no financial disclosures. Dr. Cohen disclosed serving as a consultant and adviser to BMS.
Humidification mitigates radiation-induced mucositis, but compliance is a problem
SCOTTSDALE, ARIZ. – A home humidification device can reduce the symptom burden of mucositis in patients undergoing radiation for head and neck cancers, but the technology only works when patients actually use it, reported investigators at the Multidisciplinary Head and Neck Cancer Symposium.
In a randomized phase III trial, patients assigned to daily humidification of the mouth and throat beginning on the first day of radiation had a 45% reduction in risk for acute hospitalization and had about half the symptom-related hospital days of patients who did not receive daily humidification, reported Dr. Andrew Macann from Auckland (New Zealand) City Hospital.
However, compliance with the humidification protocol was spotty, with only 42% of patients assigned to the therapy using it according to study protocol, Dr. Macann noted.
"The efficacy signals were seen across clinician-reported, independent, and patient-reported outcomes, and although in the main these signals were seen in the per-protocol analysis, the result which is perhaps most influential in considering whether domiciliary humidification could be cost effective, was the reduction in inpatient hospital days, where there was significant reduction in both the intention-to-treat and per protocol analyses," he said at the symposium, cosponsored by the American Society for Radiation Oncology and the American Society of Clinical Oncology .
The device used in the study was a humidifier/flow generator with a plastic face apparatus that delivered 44 mg of water per liter of air at a rate of 30 L/min. The flow was designed to slightly exceed inspiratory flow so that there was no entrainment of nonhumidified air.
In the trial, conducted by the Trans Tasman Radiation Oncology Group, 210 patients with cancers of the nasopharynx, oropharynx, oral cavity, larynx or hypopharynx were randomly assigned to receive humidification plus the institutional standard of care for mucositis management, or standard of care alone. Patients assigned to humidification were supposed to continue on the protocol until resolution of the ulcerative component of clinical mucositis.
A total of 103 patients assigned to humidification and 100 controls were available for the intention-to-treat (ITT) analysis.
Humidification compliance was electronically recorded, with full compliance consisting of more than 4 hours of daily use. The investigators calculated compliance ratios based on the number of full compliance days divided by the total days from the start of therapy to resolution of ulcerative mucositis. They determined high compliance to be a ratio greater than 0.67, and medium compliance to be a ratio of 0.34-0.66. High and medium compliers (23 and 20 patients, respectively) were included in the per-protocol analysis.
Although the humidification protocol did not meet the primary endpoint (area under the curve for a clinical mucositis score of 2 or greater according to Common Terminology Criteria for Adverse Events) in either the ITT or per-protocol analysis, there was a significant reduction in clinician-assessed functional mucositis symptom burden among the compliant patients (P = .009).
Additionally, total days in hospital were significantly lower among patients on the experimental protocol in both the ITT and per-protocol analyses. Control patients spent a geometric mean 4.10 days in hospital compared with 2.32 in ITT (P = .017), and 1.65 in per-protocol (P = .006). The investigators calculated that all patients treated with humidification spent only 57% of the hospital days of controls, and that compliant patients spent only 40% of those days.
Compliant patients were also significantly less likely than controls to require a feeding tube, with an odds ratio for never needing a tube of 2.50 (P = .035).
Patient-reported impression of symptom burden as rated on the McMaster University Head and Neck Questionnaire trended toward favoring the humidification protocol but there were no significant differences between the groups.
Simple strategies such as humidification can add value to head and neck cancer therapy, commented Dr. Paul M. Harari of the University of Wisconsin, Madison.
"I would love to see this humidification developed in a way that would be more compliant for patients, because I have no doubt that it could be valuable," he said.
The study was funded by the New Zealand Ministry of Science and Innovation, Fisher and Paykel Healthcare, Baxter Healthcare, and Auckland Hospital Charitable Trust. Dr. Macann and Dr. Harari reported having no conflicts of interest.
SCOTTSDALE, ARIZ. – A home humidification device can reduce the symptom burden of mucositis in patients undergoing radiation for head and neck cancers, but the technology only works when patients actually use it, reported investigators at the Multidisciplinary Head and Neck Cancer Symposium.
In a randomized phase III trial, patients assigned to daily humidification of the mouth and throat beginning on the first day of radiation had a 45% reduction in risk for acute hospitalization and had about half the symptom-related hospital days of patients who did not receive daily humidification, reported Dr. Andrew Macann from Auckland (New Zealand) City Hospital.
However, compliance with the humidification protocol was spotty, with only 42% of patients assigned to the therapy using it according to study protocol, Dr. Macann noted.
"The efficacy signals were seen across clinician-reported, independent, and patient-reported outcomes, and although in the main these signals were seen in the per-protocol analysis, the result which is perhaps most influential in considering whether domiciliary humidification could be cost effective, was the reduction in inpatient hospital days, where there was significant reduction in both the intention-to-treat and per protocol analyses," he said at the symposium, cosponsored by the American Society for Radiation Oncology and the American Society of Clinical Oncology .
The device used in the study was a humidifier/flow generator with a plastic face apparatus that delivered 44 mg of water per liter of air at a rate of 30 L/min. The flow was designed to slightly exceed inspiratory flow so that there was no entrainment of nonhumidified air.
In the trial, conducted by the Trans Tasman Radiation Oncology Group, 210 patients with cancers of the nasopharynx, oropharynx, oral cavity, larynx or hypopharynx were randomly assigned to receive humidification plus the institutional standard of care for mucositis management, or standard of care alone. Patients assigned to humidification were supposed to continue on the protocol until resolution of the ulcerative component of clinical mucositis.
A total of 103 patients assigned to humidification and 100 controls were available for the intention-to-treat (ITT) analysis.
Humidification compliance was electronically recorded, with full compliance consisting of more than 4 hours of daily use. The investigators calculated compliance ratios based on the number of full compliance days divided by the total days from the start of therapy to resolution of ulcerative mucositis. They determined high compliance to be a ratio greater than 0.67, and medium compliance to be a ratio of 0.34-0.66. High and medium compliers (23 and 20 patients, respectively) were included in the per-protocol analysis.
Although the humidification protocol did not meet the primary endpoint (area under the curve for a clinical mucositis score of 2 or greater according to Common Terminology Criteria for Adverse Events) in either the ITT or per-protocol analysis, there was a significant reduction in clinician-assessed functional mucositis symptom burden among the compliant patients (P = .009).
Additionally, total days in hospital were significantly lower among patients on the experimental protocol in both the ITT and per-protocol analyses. Control patients spent a geometric mean 4.10 days in hospital compared with 2.32 in ITT (P = .017), and 1.65 in per-protocol (P = .006). The investigators calculated that all patients treated with humidification spent only 57% of the hospital days of controls, and that compliant patients spent only 40% of those days.
Compliant patients were also significantly less likely than controls to require a feeding tube, with an odds ratio for never needing a tube of 2.50 (P = .035).
Patient-reported impression of symptom burden as rated on the McMaster University Head and Neck Questionnaire trended toward favoring the humidification protocol but there were no significant differences between the groups.
Simple strategies such as humidification can add value to head and neck cancer therapy, commented Dr. Paul M. Harari of the University of Wisconsin, Madison.
"I would love to see this humidification developed in a way that would be more compliant for patients, because I have no doubt that it could be valuable," he said.
The study was funded by the New Zealand Ministry of Science and Innovation, Fisher and Paykel Healthcare, Baxter Healthcare, and Auckland Hospital Charitable Trust. Dr. Macann and Dr. Harari reported having no conflicts of interest.
SCOTTSDALE, ARIZ. – A home humidification device can reduce the symptom burden of mucositis in patients undergoing radiation for head and neck cancers, but the technology only works when patients actually use it, reported investigators at the Multidisciplinary Head and Neck Cancer Symposium.
In a randomized phase III trial, patients assigned to daily humidification of the mouth and throat beginning on the first day of radiation had a 45% reduction in risk for acute hospitalization and had about half the symptom-related hospital days of patients who did not receive daily humidification, reported Dr. Andrew Macann from Auckland (New Zealand) City Hospital.
However, compliance with the humidification protocol was spotty, with only 42% of patients assigned to the therapy using it according to study protocol, Dr. Macann noted.
"The efficacy signals were seen across clinician-reported, independent, and patient-reported outcomes, and although in the main these signals were seen in the per-protocol analysis, the result which is perhaps most influential in considering whether domiciliary humidification could be cost effective, was the reduction in inpatient hospital days, where there was significant reduction in both the intention-to-treat and per protocol analyses," he said at the symposium, cosponsored by the American Society for Radiation Oncology and the American Society of Clinical Oncology .
The device used in the study was a humidifier/flow generator with a plastic face apparatus that delivered 44 mg of water per liter of air at a rate of 30 L/min. The flow was designed to slightly exceed inspiratory flow so that there was no entrainment of nonhumidified air.
In the trial, conducted by the Trans Tasman Radiation Oncology Group, 210 patients with cancers of the nasopharynx, oropharynx, oral cavity, larynx or hypopharynx were randomly assigned to receive humidification plus the institutional standard of care for mucositis management, or standard of care alone. Patients assigned to humidification were supposed to continue on the protocol until resolution of the ulcerative component of clinical mucositis.
A total of 103 patients assigned to humidification and 100 controls were available for the intention-to-treat (ITT) analysis.
Humidification compliance was electronically recorded, with full compliance consisting of more than 4 hours of daily use. The investigators calculated compliance ratios based on the number of full compliance days divided by the total days from the start of therapy to resolution of ulcerative mucositis. They determined high compliance to be a ratio greater than 0.67, and medium compliance to be a ratio of 0.34-0.66. High and medium compliers (23 and 20 patients, respectively) were included in the per-protocol analysis.
Although the humidification protocol did not meet the primary endpoint (area under the curve for a clinical mucositis score of 2 or greater according to Common Terminology Criteria for Adverse Events) in either the ITT or per-protocol analysis, there was a significant reduction in clinician-assessed functional mucositis symptom burden among the compliant patients (P = .009).
Additionally, total days in hospital were significantly lower among patients on the experimental protocol in both the ITT and per-protocol analyses. Control patients spent a geometric mean 4.10 days in hospital compared with 2.32 in ITT (P = .017), and 1.65 in per-protocol (P = .006). The investigators calculated that all patients treated with humidification spent only 57% of the hospital days of controls, and that compliant patients spent only 40% of those days.
Compliant patients were also significantly less likely than controls to require a feeding tube, with an odds ratio for never needing a tube of 2.50 (P = .035).
Patient-reported impression of symptom burden as rated on the McMaster University Head and Neck Questionnaire trended toward favoring the humidification protocol but there were no significant differences between the groups.
Simple strategies such as humidification can add value to head and neck cancer therapy, commented Dr. Paul M. Harari of the University of Wisconsin, Madison.
"I would love to see this humidification developed in a way that would be more compliant for patients, because I have no doubt that it could be valuable," he said.
The study was funded by the New Zealand Ministry of Science and Innovation, Fisher and Paykel Healthcare, Baxter Healthcare, and Auckland Hospital Charitable Trust. Dr. Macann and Dr. Harari reported having no conflicts of interest.
AT THE HEAD AND NECK CANCER SYMPOSIUM
Major finding: Patients with radiation-treated head and neck cancers who received daily humidification had approximately half of the hospital days for mucositis of controls treated with standard care.
Data source: Randomized phase III trial of 203 patients treated with radiation for head and neck cancers.
Disclosures: The study was funded by the New Zealand Ministry of Science & Innovation, Fisher and Paykel Healthcare, Baxter Healthcare, and Auckland Hospital Charitable Trust. Dr. Macann and Dr. Harari reported having no conflicts of interest.
Gland-sparing technique safe in tonsillar, tongue cancers
SCOTTSDALE, ARIZ. – Although radiation oncologists have typically worried that, in patients with oral cancers, leaving contralateral submandibular glands untreated could lead to tumor involvement of nearby lymph nodes, those worries may soon be put to rest, suggest results of a small retrospective study.
Among 71 patients with locally advanced cancers of the tongue base or tonsils who underwent radiation therapy that avoided targeting the contralateral submandibular glands, there were no cancer recurrences in contralateral level 1B nodes after a median 27.3 months of follow-up, reported Dr. Tyler Robin of the University of Colorado at Denver, Aurora.
"We’re interested in sparing the contralateral submandibular gland because we’re interested in minimizing xerostomia. Xerostomia is a significant morbidity of head and neck cancer radiotherapy, and it has substantial impact on patient quality of life," Dr. Robin said at the Multidisciplinary Head and Neck Cancer Symposium.
Intensity-modulated radiation therapy (IMRT) allows treatment beams to be shaped to avoid the parotid glands with no subsequent increase in regional lymph node failures and preservation of parotid salivary flow. But patient-reported xerostomia and quality-of-life outcomes with parotid-sparing techniques have been mixed, Dr. Robin said.
"Interestingly, an earlier study looking at predictors of xerostomia found that dose to the submandibular gland was a stronger predictor of xerostomia than dose to the parotids, and this may be because of the role of the submandibular gland in unstimulated salivary flow," he said.
The submandibular gland is located near level IB lymph nodes, but the risk of contralateral level IB involvement in oropharyngeal (OP) cancers is low, on the order of 0%-2%. Gland-sparing therapy with IMRT has previously been shown to mitigate xerostomia and to be safe, but primarily in patients with early-stage disease, prompting the investigators to examine whether it would also be safe and effective in patients with locally advanced tumors.
The question is particularly relevant at a time when the epidemiology of OP cancers is shifting toward patients who are positive for the human papillomavirus, who are more likely to have good therapeutic outcomes and who may live for many decades beyond an initial diagnosis, Dr. Robin said at the symposium cosponsored by the American Society for Radiation Oncology and the American Society of Clinical Oncology.
His team reviewed records of 71 patients treated for primary OP cancers at the University of Colorado and at Memorial Sloan-Kettering Cancer Center in New York.
In all, 40 patients had tonsillar cancers, 28 had base-of-tongue lesions, and 3 had cancers involving both sites.
They considered gland-sparing procedures as those in which total doses delivered to the contralateral submandibular gland during bilateral neck radiotherapy were not more than 39 Gy.
Of the 71 patients, 61 (85.9%) had stage IVA disease, 6 (8.5%) had stage III cancers, and 3 (4.2%) had stage IVB disease. The majority of patients had significant nodal involvement, with 46 (64.8%) having stage N2b; 7 (9.9%) N2c; and 3 (4.2%) having staging N3 disease.
The respective mean and median doses to the contralateral glands were 33.04 and 34.21 Gy.
At median follow-up of 27.3 months, there were 12 treatment failures: 1 local, 6 regional, and 5 distant failures. However, there were no cases of disease recurrence in contralateral level IB nodes, the investigators found. There was, however, one documented case of recurrence in contralateral level IIa lymph nodes.
"We believe this is evidence that contralateral submandibular gland sparing can be feasible and safe even in advanced node-positive head and neck cancers, including base- of-tongue lesions," Dr. Robin said,
The data suggest the need for a large prospective trial specifically addressing the safety and efficacy of contralateral submandibular gland-sparing therapy in patients with locally advanced head and neck cancers. Such studies should incorporate existing xerostomia-based quality-of-life assessments and formal sialometry studies, he added.
While the study shows that contralateral submandibular gland sparing is feasible, it raises the question of whether the technique might increase the dose to the muscles of the floor of the mouth, said Dr. Harry Quon of Johns Hopkins University in Baltimore, the invited discussant.
"There is emerging data that our chemoradiation approaches, with long-term follow-up maybe increases [patients’] risk of death, and one hypothesis that has been put forward is chronic aspiration with secondary injury to the lungs," he said.
Radiation injury to the floor-of-mouth muscles appears to be a significant risk factor for aspiration, indicating that future conformal approaches to treating cancers of the tonsils and tongue base should attempt to avoid delivering excessive doses to the midline mucosa, Dr. Quon said.
The study was internally funded. Dr. Robin and Dr. Quon reported having no financial disclosures.
SCOTTSDALE, ARIZ. – Although radiation oncologists have typically worried that, in patients with oral cancers, leaving contralateral submandibular glands untreated could lead to tumor involvement of nearby lymph nodes, those worries may soon be put to rest, suggest results of a small retrospective study.
Among 71 patients with locally advanced cancers of the tongue base or tonsils who underwent radiation therapy that avoided targeting the contralateral submandibular glands, there were no cancer recurrences in contralateral level 1B nodes after a median 27.3 months of follow-up, reported Dr. Tyler Robin of the University of Colorado at Denver, Aurora.
"We’re interested in sparing the contralateral submandibular gland because we’re interested in minimizing xerostomia. Xerostomia is a significant morbidity of head and neck cancer radiotherapy, and it has substantial impact on patient quality of life," Dr. Robin said at the Multidisciplinary Head and Neck Cancer Symposium.
Intensity-modulated radiation therapy (IMRT) allows treatment beams to be shaped to avoid the parotid glands with no subsequent increase in regional lymph node failures and preservation of parotid salivary flow. But patient-reported xerostomia and quality-of-life outcomes with parotid-sparing techniques have been mixed, Dr. Robin said.
"Interestingly, an earlier study looking at predictors of xerostomia found that dose to the submandibular gland was a stronger predictor of xerostomia than dose to the parotids, and this may be because of the role of the submandibular gland in unstimulated salivary flow," he said.
The submandibular gland is located near level IB lymph nodes, but the risk of contralateral level IB involvement in oropharyngeal (OP) cancers is low, on the order of 0%-2%. Gland-sparing therapy with IMRT has previously been shown to mitigate xerostomia and to be safe, but primarily in patients with early-stage disease, prompting the investigators to examine whether it would also be safe and effective in patients with locally advanced tumors.
The question is particularly relevant at a time when the epidemiology of OP cancers is shifting toward patients who are positive for the human papillomavirus, who are more likely to have good therapeutic outcomes and who may live for many decades beyond an initial diagnosis, Dr. Robin said at the symposium cosponsored by the American Society for Radiation Oncology and the American Society of Clinical Oncology.
His team reviewed records of 71 patients treated for primary OP cancers at the University of Colorado and at Memorial Sloan-Kettering Cancer Center in New York.
In all, 40 patients had tonsillar cancers, 28 had base-of-tongue lesions, and 3 had cancers involving both sites.
They considered gland-sparing procedures as those in which total doses delivered to the contralateral submandibular gland during bilateral neck radiotherapy were not more than 39 Gy.
Of the 71 patients, 61 (85.9%) had stage IVA disease, 6 (8.5%) had stage III cancers, and 3 (4.2%) had stage IVB disease. The majority of patients had significant nodal involvement, with 46 (64.8%) having stage N2b; 7 (9.9%) N2c; and 3 (4.2%) having staging N3 disease.
The respective mean and median doses to the contralateral glands were 33.04 and 34.21 Gy.
At median follow-up of 27.3 months, there were 12 treatment failures: 1 local, 6 regional, and 5 distant failures. However, there were no cases of disease recurrence in contralateral level IB nodes, the investigators found. There was, however, one documented case of recurrence in contralateral level IIa lymph nodes.
"We believe this is evidence that contralateral submandibular gland sparing can be feasible and safe even in advanced node-positive head and neck cancers, including base- of-tongue lesions," Dr. Robin said,
The data suggest the need for a large prospective trial specifically addressing the safety and efficacy of contralateral submandibular gland-sparing therapy in patients with locally advanced head and neck cancers. Such studies should incorporate existing xerostomia-based quality-of-life assessments and formal sialometry studies, he added.
While the study shows that contralateral submandibular gland sparing is feasible, it raises the question of whether the technique might increase the dose to the muscles of the floor of the mouth, said Dr. Harry Quon of Johns Hopkins University in Baltimore, the invited discussant.
"There is emerging data that our chemoradiation approaches, with long-term follow-up maybe increases [patients’] risk of death, and one hypothesis that has been put forward is chronic aspiration with secondary injury to the lungs," he said.
Radiation injury to the floor-of-mouth muscles appears to be a significant risk factor for aspiration, indicating that future conformal approaches to treating cancers of the tonsils and tongue base should attempt to avoid delivering excessive doses to the midline mucosa, Dr. Quon said.
The study was internally funded. Dr. Robin and Dr. Quon reported having no financial disclosures.
SCOTTSDALE, ARIZ. – Although radiation oncologists have typically worried that, in patients with oral cancers, leaving contralateral submandibular glands untreated could lead to tumor involvement of nearby lymph nodes, those worries may soon be put to rest, suggest results of a small retrospective study.
Among 71 patients with locally advanced cancers of the tongue base or tonsils who underwent radiation therapy that avoided targeting the contralateral submandibular glands, there were no cancer recurrences in contralateral level 1B nodes after a median 27.3 months of follow-up, reported Dr. Tyler Robin of the University of Colorado at Denver, Aurora.
"We’re interested in sparing the contralateral submandibular gland because we’re interested in minimizing xerostomia. Xerostomia is a significant morbidity of head and neck cancer radiotherapy, and it has substantial impact on patient quality of life," Dr. Robin said at the Multidisciplinary Head and Neck Cancer Symposium.
Intensity-modulated radiation therapy (IMRT) allows treatment beams to be shaped to avoid the parotid glands with no subsequent increase in regional lymph node failures and preservation of parotid salivary flow. But patient-reported xerostomia and quality-of-life outcomes with parotid-sparing techniques have been mixed, Dr. Robin said.
"Interestingly, an earlier study looking at predictors of xerostomia found that dose to the submandibular gland was a stronger predictor of xerostomia than dose to the parotids, and this may be because of the role of the submandibular gland in unstimulated salivary flow," he said.
The submandibular gland is located near level IB lymph nodes, but the risk of contralateral level IB involvement in oropharyngeal (OP) cancers is low, on the order of 0%-2%. Gland-sparing therapy with IMRT has previously been shown to mitigate xerostomia and to be safe, but primarily in patients with early-stage disease, prompting the investigators to examine whether it would also be safe and effective in patients with locally advanced tumors.
The question is particularly relevant at a time when the epidemiology of OP cancers is shifting toward patients who are positive for the human papillomavirus, who are more likely to have good therapeutic outcomes and who may live for many decades beyond an initial diagnosis, Dr. Robin said at the symposium cosponsored by the American Society for Radiation Oncology and the American Society of Clinical Oncology.
His team reviewed records of 71 patients treated for primary OP cancers at the University of Colorado and at Memorial Sloan-Kettering Cancer Center in New York.
In all, 40 patients had tonsillar cancers, 28 had base-of-tongue lesions, and 3 had cancers involving both sites.
They considered gland-sparing procedures as those in which total doses delivered to the contralateral submandibular gland during bilateral neck radiotherapy were not more than 39 Gy.
Of the 71 patients, 61 (85.9%) had stage IVA disease, 6 (8.5%) had stage III cancers, and 3 (4.2%) had stage IVB disease. The majority of patients had significant nodal involvement, with 46 (64.8%) having stage N2b; 7 (9.9%) N2c; and 3 (4.2%) having staging N3 disease.
The respective mean and median doses to the contralateral glands were 33.04 and 34.21 Gy.
At median follow-up of 27.3 months, there were 12 treatment failures: 1 local, 6 regional, and 5 distant failures. However, there were no cases of disease recurrence in contralateral level IB nodes, the investigators found. There was, however, one documented case of recurrence in contralateral level IIa lymph nodes.
"We believe this is evidence that contralateral submandibular gland sparing can be feasible and safe even in advanced node-positive head and neck cancers, including base- of-tongue lesions," Dr. Robin said,
The data suggest the need for a large prospective trial specifically addressing the safety and efficacy of contralateral submandibular gland-sparing therapy in patients with locally advanced head and neck cancers. Such studies should incorporate existing xerostomia-based quality-of-life assessments and formal sialometry studies, he added.
While the study shows that contralateral submandibular gland sparing is feasible, it raises the question of whether the technique might increase the dose to the muscles of the floor of the mouth, said Dr. Harry Quon of Johns Hopkins University in Baltimore, the invited discussant.
"There is emerging data that our chemoradiation approaches, with long-term follow-up maybe increases [patients’] risk of death, and one hypothesis that has been put forward is chronic aspiration with secondary injury to the lungs," he said.
Radiation injury to the floor-of-mouth muscles appears to be a significant risk factor for aspiration, indicating that future conformal approaches to treating cancers of the tonsils and tongue base should attempt to avoid delivering excessive doses to the midline mucosa, Dr. Quon said.
The study was internally funded. Dr. Robin and Dr. Quon reported having no financial disclosures.
AT THE HEAD AND NECK CANCER SYMPOSIUM
Major finding: Among patients with oropharyngeal cancers treated with conformal radiation sparing the contralateral submandibular gland, there were no contralateral lymph node recurrences.
Data source: Retrospective analysis of 71 patients.
Disclosures: The study was internally funded. Dr. Robin and Dr. Quon reported having no financial disclosures.
Thyroid cancer rise mostly overdiagnosis
The incidence of thyroid cancer has nearly tripled in the United States since the 1970s. However, this is mainly an epidemic of diagnosis, researchers reported.
Small papillary cancers are not likely to cause death or disease, and women are four times more likely to receive a diagnosis than men, even though autopsy findings show that these cancers occur more frequently in men.
For the research, published online Feb. 20 in JAMA Otolaryngology–Head & Neck Surgery, Dr. Louise Davies and Dr. H. Gilbert Welch reviewed diagnostic trends from the population-based Surveillance, Epidemiology, and End Results (SEER) 9 program, which covers four large U.S. metropolitan areas along with five states. They also reviewed mortality records from the National Vital Statistics System between 1975 and 2009 for the same areas, reported Dr. Davies of the Veterans Affairs Medical Center in White River Junction, Vt., and Dr. Welch of the Dartmouth Institute for Health Policy and Clinical Practice in Hanover, N.H.
The researchers found that thyroid cancer incidence nearly tripled, from 4.9 to 14.3 per 100,000 individuals, in that time period (relative rate, 2.9) and that nearly all of the increase was attributable to diagnoses of small papillary cancers, the least aggressive form of thyroid cancer. The mortality rate from thyroid cancer remained stable – at 0.5 deaths per 100,000 – during the same time, Dr. Davies and Dr. Welch reported (JAMA Otolaryngol. Head Neck Surg. 2014 Feb. 20 [doi: 10.1001/jamaoto.2014.1]).
The investigators saw a much greater absolute increase in thyroid cancer in women, at 3.3-fold (from 6.5 to 21.4 cases per 100,000), than in men, at 2.2-fold (from 3.1 to 6.9), during the study period, which suggests that the burden of overdiagnosis fell heavily on women, they wrote.
Moreover, most thyroid cancers are treated "as though they are destined to cause real problems for the people who have them," Dr. Davies and Dr. Welch wrote, usually with total thyroidectomy, radiation, or both, putting patients at risk for complications and secondary cancers.
Patients – particularly women – might be better served with a less intensive diagnostic and treatment approach to these cancers, and even by relabeling them using a term other than cancer. Clinicians should take care to advise patients of the uncertainty surrounding the small papillary cancers and encourage them to consider the risks of treatment compared with active surveillance, the researchers said.
Dr. Davies and Dr. Welch received support from their institutions for their research; neither declared conflicts of interest.
This is an interesting and important study, but one that is difficult to interpret. We don't yet know which of these cancers, no matter what size, will ultimately prove to be important. Once a diagnosis of cancer is made, it is difficult for patients and doctors to simply continue to observe the cancer. Most patients and doctors are uncomfortable with that.
In addition, the follow-up itself becomes burdensome, with annual ultrasounds and, possibly, multiple needle biopsies over time. Although much of this increased incidence seems related to increased use of imaging studies, several authors have also reported an absolute increase in the incidence of thyroid cancer.
Other issues related to this topic are the extent of surgery that is necessary for these small early cancers. The authors point out that many surgeons perform total thyroidectomy and postoperative radioactive iodine ablation, but there are some who advocate for lesser surgery. This becomes problematic when patients have other smaller nodules in the opposite lobe of the thyroid of uncertain significance. Some national guidelines recommend total or near-total thyroidectomy for T1 and T2 well-differentiated thyroid cancers, and it is difficult to go against these guidelines. What is really needed are better molecular and genetic tests to better define which well-differentiated thyroid cancers are likely to act in a more aggressive manner, and which are not.
Mark C. Weissler, M.D., FACS, is the J.P. Riddle Distinguished Professor of Otolaryngology-Head and Neck Surgery at the University of North Carolina, Chapel Hill. Dr. Weissler had no disclosures.
This is an interesting and important study, but one that is difficult to interpret. We don't yet know which of these cancers, no matter what size, will ultimately prove to be important. Once a diagnosis of cancer is made, it is difficult for patients and doctors to simply continue to observe the cancer. Most patients and doctors are uncomfortable with that.
In addition, the follow-up itself becomes burdensome, with annual ultrasounds and, possibly, multiple needle biopsies over time. Although much of this increased incidence seems related to increased use of imaging studies, several authors have also reported an absolute increase in the incidence of thyroid cancer.
Other issues related to this topic are the extent of surgery that is necessary for these small early cancers. The authors point out that many surgeons perform total thyroidectomy and postoperative radioactive iodine ablation, but there are some who advocate for lesser surgery. This becomes problematic when patients have other smaller nodules in the opposite lobe of the thyroid of uncertain significance. Some national guidelines recommend total or near-total thyroidectomy for T1 and T2 well-differentiated thyroid cancers, and it is difficult to go against these guidelines. What is really needed are better molecular and genetic tests to better define which well-differentiated thyroid cancers are likely to act in a more aggressive manner, and which are not.
Mark C. Weissler, M.D., FACS, is the J.P. Riddle Distinguished Professor of Otolaryngology-Head and Neck Surgery at the University of North Carolina, Chapel Hill. Dr. Weissler had no disclosures.
This is an interesting and important study, but one that is difficult to interpret. We don't yet know which of these cancers, no matter what size, will ultimately prove to be important. Once a diagnosis of cancer is made, it is difficult for patients and doctors to simply continue to observe the cancer. Most patients and doctors are uncomfortable with that.
In addition, the follow-up itself becomes burdensome, with annual ultrasounds and, possibly, multiple needle biopsies over time. Although much of this increased incidence seems related to increased use of imaging studies, several authors have also reported an absolute increase in the incidence of thyroid cancer.
Other issues related to this topic are the extent of surgery that is necessary for these small early cancers. The authors point out that many surgeons perform total thyroidectomy and postoperative radioactive iodine ablation, but there are some who advocate for lesser surgery. This becomes problematic when patients have other smaller nodules in the opposite lobe of the thyroid of uncertain significance. Some national guidelines recommend total or near-total thyroidectomy for T1 and T2 well-differentiated thyroid cancers, and it is difficult to go against these guidelines. What is really needed are better molecular and genetic tests to better define which well-differentiated thyroid cancers are likely to act in a more aggressive manner, and which are not.
Mark C. Weissler, M.D., FACS, is the J.P. Riddle Distinguished Professor of Otolaryngology-Head and Neck Surgery at the University of North Carolina, Chapel Hill. Dr. Weissler had no disclosures.
The incidence of thyroid cancer has nearly tripled in the United States since the 1970s. However, this is mainly an epidemic of diagnosis, researchers reported.
Small papillary cancers are not likely to cause death or disease, and women are four times more likely to receive a diagnosis than men, even though autopsy findings show that these cancers occur more frequently in men.
For the research, published online Feb. 20 in JAMA Otolaryngology–Head & Neck Surgery, Dr. Louise Davies and Dr. H. Gilbert Welch reviewed diagnostic trends from the population-based Surveillance, Epidemiology, and End Results (SEER) 9 program, which covers four large U.S. metropolitan areas along with five states. They also reviewed mortality records from the National Vital Statistics System between 1975 and 2009 for the same areas, reported Dr. Davies of the Veterans Affairs Medical Center in White River Junction, Vt., and Dr. Welch of the Dartmouth Institute for Health Policy and Clinical Practice in Hanover, N.H.
The researchers found that thyroid cancer incidence nearly tripled, from 4.9 to 14.3 per 100,000 individuals, in that time period (relative rate, 2.9) and that nearly all of the increase was attributable to diagnoses of small papillary cancers, the least aggressive form of thyroid cancer. The mortality rate from thyroid cancer remained stable – at 0.5 deaths per 100,000 – during the same time, Dr. Davies and Dr. Welch reported (JAMA Otolaryngol. Head Neck Surg. 2014 Feb. 20 [doi: 10.1001/jamaoto.2014.1]).
The investigators saw a much greater absolute increase in thyroid cancer in women, at 3.3-fold (from 6.5 to 21.4 cases per 100,000), than in men, at 2.2-fold (from 3.1 to 6.9), during the study period, which suggests that the burden of overdiagnosis fell heavily on women, they wrote.
Moreover, most thyroid cancers are treated "as though they are destined to cause real problems for the people who have them," Dr. Davies and Dr. Welch wrote, usually with total thyroidectomy, radiation, or both, putting patients at risk for complications and secondary cancers.
Patients – particularly women – might be better served with a less intensive diagnostic and treatment approach to these cancers, and even by relabeling them using a term other than cancer. Clinicians should take care to advise patients of the uncertainty surrounding the small papillary cancers and encourage them to consider the risks of treatment compared with active surveillance, the researchers said.
Dr. Davies and Dr. Welch received support from their institutions for their research; neither declared conflicts of interest.
The incidence of thyroid cancer has nearly tripled in the United States since the 1970s. However, this is mainly an epidemic of diagnosis, researchers reported.
Small papillary cancers are not likely to cause death or disease, and women are four times more likely to receive a diagnosis than men, even though autopsy findings show that these cancers occur more frequently in men.
For the research, published online Feb. 20 in JAMA Otolaryngology–Head & Neck Surgery, Dr. Louise Davies and Dr. H. Gilbert Welch reviewed diagnostic trends from the population-based Surveillance, Epidemiology, and End Results (SEER) 9 program, which covers four large U.S. metropolitan areas along with five states. They also reviewed mortality records from the National Vital Statistics System between 1975 and 2009 for the same areas, reported Dr. Davies of the Veterans Affairs Medical Center in White River Junction, Vt., and Dr. Welch of the Dartmouth Institute for Health Policy and Clinical Practice in Hanover, N.H.
The researchers found that thyroid cancer incidence nearly tripled, from 4.9 to 14.3 per 100,000 individuals, in that time period (relative rate, 2.9) and that nearly all of the increase was attributable to diagnoses of small papillary cancers, the least aggressive form of thyroid cancer. The mortality rate from thyroid cancer remained stable – at 0.5 deaths per 100,000 – during the same time, Dr. Davies and Dr. Welch reported (JAMA Otolaryngol. Head Neck Surg. 2014 Feb. 20 [doi: 10.1001/jamaoto.2014.1]).
The investigators saw a much greater absolute increase in thyroid cancer in women, at 3.3-fold (from 6.5 to 21.4 cases per 100,000), than in men, at 2.2-fold (from 3.1 to 6.9), during the study period, which suggests that the burden of overdiagnosis fell heavily on women, they wrote.
Moreover, most thyroid cancers are treated "as though they are destined to cause real problems for the people who have them," Dr. Davies and Dr. Welch wrote, usually with total thyroidectomy, radiation, or both, putting patients at risk for complications and secondary cancers.
Patients – particularly women – might be better served with a less intensive diagnostic and treatment approach to these cancers, and even by relabeling them using a term other than cancer. Clinicians should take care to advise patients of the uncertainty surrounding the small papillary cancers and encourage them to consider the risks of treatment compared with active surveillance, the researchers said.
Dr. Davies and Dr. Welch received support from their institutions for their research; neither declared conflicts of interest.
FROM JAMA OTOLARYNGOLOGY – HEAD & NECK SURGERY
Sorafenib approval now includes late-stage thyroid cancer
Sorafenib’s approval has been expanded to include late-stage differentiated thyroid cancer, the Food and Drug Administration announced on Nov. 22.
The kinase inhibitor was approved for the treatment of "locally recurrent or metastatic, progressive, differentiated thyroid carcinoma refractory to radioactive iodine treatment," according to the prescribing information.
The expedited approval –completed in 6 months – was based on a study of 417 people with locally recurrent or metastatic, progressive differentiated thyroid cancer that had not responded to radioactive iodine treatment. Subjects were randomized to 400 mg of sorafenib twice a day or placebo. The median progression-free survival was 10.8 months among those on sorafenib and 5.8 months among those on placebo, a statistically significant 41% difference.
Diarrhea, fatigue, infection, alopecia, hand-foot skin reaction, rash, weight loss, decreased appetite, nausea, gastrointestinal and abdominal pains, and hypertension were among the most common adverse effects associated with treatment, according to the FDA. In addition, thyroid stimulating hormone, which can promote thyroid cancer, "is more likely to become elevated while on treatment with Nexavar, requiring adjustment of thyroid hormone replacement therapy," the statement said.
Sorafenib, marketed as Nexavar by Bayer HealthCare Pharmaceuticals was approved for treating advanced renal cell carcinoma in 2005 and for unresectable hepatocellular carcinoma in 2007.
Sorafenib’s approval has been expanded to include late-stage differentiated thyroid cancer, the Food and Drug Administration announced on Nov. 22.
The kinase inhibitor was approved for the treatment of "locally recurrent or metastatic, progressive, differentiated thyroid carcinoma refractory to radioactive iodine treatment," according to the prescribing information.
The expedited approval –completed in 6 months – was based on a study of 417 people with locally recurrent or metastatic, progressive differentiated thyroid cancer that had not responded to radioactive iodine treatment. Subjects were randomized to 400 mg of sorafenib twice a day or placebo. The median progression-free survival was 10.8 months among those on sorafenib and 5.8 months among those on placebo, a statistically significant 41% difference.
Diarrhea, fatigue, infection, alopecia, hand-foot skin reaction, rash, weight loss, decreased appetite, nausea, gastrointestinal and abdominal pains, and hypertension were among the most common adverse effects associated with treatment, according to the FDA. In addition, thyroid stimulating hormone, which can promote thyroid cancer, "is more likely to become elevated while on treatment with Nexavar, requiring adjustment of thyroid hormone replacement therapy," the statement said.
Sorafenib, marketed as Nexavar by Bayer HealthCare Pharmaceuticals was approved for treating advanced renal cell carcinoma in 2005 and for unresectable hepatocellular carcinoma in 2007.
Sorafenib’s approval has been expanded to include late-stage differentiated thyroid cancer, the Food and Drug Administration announced on Nov. 22.
The kinase inhibitor was approved for the treatment of "locally recurrent or metastatic, progressive, differentiated thyroid carcinoma refractory to radioactive iodine treatment," according to the prescribing information.
The expedited approval –completed in 6 months – was based on a study of 417 people with locally recurrent or metastatic, progressive differentiated thyroid cancer that had not responded to radioactive iodine treatment. Subjects were randomized to 400 mg of sorafenib twice a day or placebo. The median progression-free survival was 10.8 months among those on sorafenib and 5.8 months among those on placebo, a statistically significant 41% difference.
Diarrhea, fatigue, infection, alopecia, hand-foot skin reaction, rash, weight loss, decreased appetite, nausea, gastrointestinal and abdominal pains, and hypertension were among the most common adverse effects associated with treatment, according to the FDA. In addition, thyroid stimulating hormone, which can promote thyroid cancer, "is more likely to become elevated while on treatment with Nexavar, requiring adjustment of thyroid hormone replacement therapy," the statement said.
Sorafenib, marketed as Nexavar by Bayer HealthCare Pharmaceuticals was approved for treating advanced renal cell carcinoma in 2005 and for unresectable hepatocellular carcinoma in 2007.
