Endocrine Cancer

BOSTON – An analysis of data from medullary thyroid cancer patients that partitioned the patients into groups with similar overall survival has spurred a rethink of the current American Joint Committee on Cancer (AJCC) staging system.

The results from researchers at Duke University, Durham, N.C., presented at the annual meeting of the Endocrine Society by Dr. Mohamed Abdelgadir Adam, are timely, as the AJCC has embarked on a reconsideration of the staging of cancers, including medullary thyroid cancer (MTC), as part revisions for the eighth edition of the staging system.

“The existing AJCC staging system for MTC appears to be less than optimal in discriminating the risk of mortality among disease stage groups,” said Dr. Adam, who discussed the findings in a video interview.

MTC, a neuroendocrine tumor that affects C cells of the thyroid, comprises 3%-5% of all cases of thyroid cancer and it can be a more aggressive disease than differentiated thyroid cancer. Yet the current AJCC MTC staging system has been extrapolated from differentiated thyroid cancer data.

“We sought to evaluate how well the current AJCC seventh edition stage groupings predict survival for patients with MTC, to suggest a possible staging revision to sharpen estimates of prognosis,” said Dr. Adam.

The researchers utilized the National Cancer Data Base, representing over 70% of incident cancer cases in the United States.

MTC patients who underwent thyroid surgery from 1998 to 2012 were identified. Patients with missing values for pathologic T, N, or M were excluded. The primary outcome in the 3,315 patients was survival.

The researchers used a form of decision-tree analysis called recursive partitioning. In general, recursive partitioning is able to classify a population by splitting subjects into subgroups, each of which is homogeneous based on the particular outcome. In this study, the subgroup allocations were based on T, N, and M stages, with the outcome being overall survival. Kaplan-Meier and adjusted survival analyses enabled survival differences among the four subgroups (groups I, II, III and IV) to be explored.

The four groups were distinct in terms of survival time and allowed more accurate risk stratification. In particular, groups I and II were markedly better distinguished from one another than is the case with the current staging system. Survival differences across the stages were more distinct with the newly created T, N, and M groupings, compared with the current AJCC staging system.

After adjustment, survival differences across TNM groups were more distinct with the newly created TNM groupings (compared to subgroup I, hazard ratio of 3.06 for subgroup II; HR, 6.79 for III; and HR, 17.03 for IV), compared with the current AJCC staging (compared to stage I, HR, 1.45 for stage II; HR, 2.17 for III; and HR, 5.33 for IV).

“The AJCC is reevaluating all staging schemas, including MTC. The current AJCC staging system could be improved with the newly identified TNM groupings suggested here for more accurate patient risk stratification and possibly treatment selection,” said Dr. Adam.

Dr. Adam had no disclosures.

BOSTON – An analysis of data from medullary thyroid cancer patients that partitioned the patients into groups with similar overall survival has spurred a rethink of the current American Joint Committee on Cancer (AJCC) staging system.

The results from researchers at Duke University, Durham, N.C., presented at the annual meeting of the Endocrine Society by Dr. Mohamed Abdelgadir Adam, are timely, as the AJCC has embarked on a reconsideration of the staging of cancers, including medullary thyroid cancer (MTC), as part revisions for the eighth edition of the staging system.

“The existing AJCC staging system for MTC appears to be less than optimal in discriminating the risk of mortality among disease stage groups,” said Dr. Adam, who discussed the findings in a video interview.

MTC, a neuroendocrine tumor that affects C cells of the thyroid, comprises 3%-5% of all cases of thyroid cancer and it can be a more aggressive disease than differentiated thyroid cancer. Yet the current AJCC MTC staging system has been extrapolated from differentiated thyroid cancer data.

“We sought to evaluate how well the current AJCC seventh edition stage groupings predict survival for patients with MTC, to suggest a possible staging revision to sharpen estimates of prognosis,” said Dr. Adam.

The researchers utilized the National Cancer Data Base, representing over 70% of incident cancer cases in the United States.

MTC patients who underwent thyroid surgery from 1998 to 2012 were identified. Patients with missing values for pathologic T, N, or M were excluded. The primary outcome in the 3,315 patients was survival.

The researchers used a form of decision-tree analysis called recursive partitioning. In general, recursive partitioning is able to classify a population by splitting subjects into subgroups, each of which is homogeneous based on the particular outcome. In this study, the subgroup allocations were based on T, N, and M stages, with the outcome being overall survival. Kaplan-Meier and adjusted survival analyses enabled survival differences among the four subgroups (groups I, II, III and IV) to be explored.

The four groups were distinct in terms of survival time and allowed more accurate risk stratification. In particular, groups I and II were markedly better distinguished from one another than is the case with the current staging system. Survival differences across the stages were more distinct with the newly created T, N, and M groupings, compared with the current AJCC staging system.

After adjustment, survival differences across TNM groups were more distinct with the newly created TNM groupings (compared to subgroup I, hazard ratio of 3.06 for subgroup II; HR, 6.79 for III; and HR, 17.03 for IV), compared with the current AJCC staging (compared to stage I, HR, 1.45 for stage II; HR, 2.17 for III; and HR, 5.33 for IV).

“The AJCC is reevaluating all staging schemas, including MTC. The current AJCC staging system could be improved with the newly identified TNM groupings suggested here for more accurate patient risk stratification and possibly treatment selection,” said Dr. Adam.

Dr. Adam had no disclosures.

BOSTON – An analysis of data from medullary thyroid cancer patients that partitioned the patients into groups with similar overall survival has spurred a rethink of the current American Joint Committee on Cancer (AJCC) staging system.

The results from researchers at Duke University, Durham, N.C., presented at the annual meeting of the Endocrine Society by Dr. Mohamed Abdelgadir Adam, are timely, as the AJCC has embarked on a reconsideration of the staging of cancers, including medullary thyroid cancer (MTC), as part revisions for the eighth edition of the staging system.

“The existing AJCC staging system for MTC appears to be less than optimal in discriminating the risk of mortality among disease stage groups,” said Dr. Adam, who discussed the findings in a video interview.

MTC, a neuroendocrine tumor that affects C cells of the thyroid, comprises 3%-5% of all cases of thyroid cancer and it can be a more aggressive disease than differentiated thyroid cancer. Yet the current AJCC MTC staging system has been extrapolated from differentiated thyroid cancer data.

“We sought to evaluate how well the current AJCC seventh edition stage groupings predict survival for patients with MTC, to suggest a possible staging revision to sharpen estimates of prognosis,” said Dr. Adam.

The researchers utilized the National Cancer Data Base, representing over 70% of incident cancer cases in the United States.

MTC patients who underwent thyroid surgery from 1998 to 2012 were identified. Patients with missing values for pathologic T, N, or M were excluded. The primary outcome in the 3,315 patients was survival.

The researchers used a form of decision-tree analysis called recursive partitioning. In general, recursive partitioning is able to classify a population by splitting subjects into subgroups, each of which is homogeneous based on the particular outcome. In this study, the subgroup allocations were based on T, N, and M stages, with the outcome being overall survival. Kaplan-Meier and adjusted survival analyses enabled survival differences among the four subgroups (groups I, II, III and IV) to be explored.

The four groups were distinct in terms of survival time and allowed more accurate risk stratification. In particular, groups I and II were markedly better distinguished from one another than is the case with the current staging system. Survival differences across the stages were more distinct with the newly created T, N, and M groupings, compared with the current AJCC staging system.

After adjustment, survival differences across TNM groups were more distinct with the newly created TNM groupings (compared to subgroup I, hazard ratio of 3.06 for subgroup II; HR, 6.79 for III; and HR, 17.03 for IV), compared with the current AJCC staging (compared to stage I, HR, 1.45 for stage II; HR, 2.17 for III; and HR, 5.33 for IV).

“The AJCC is reevaluating all staging schemas, including MTC. The current AJCC staging system could be improved with the newly identified TNM groupings suggested here for more accurate patient risk stratification and possibly treatment selection,” said Dr. Adam.

Dr. Adam had no disclosures.

Oncologists should take an individualized approach when making decisions about adjuvant endocrine therapies for premenopausal hormone receptor–positive, HER2-negative early breast cancer, suggests an analysis of a pair of randomized phase III trials published online in the Journal of Clinical Oncology.

Investigators led by Meredith M. Regan, Sc.D., of Dana-Farber Cancer Institute in Boston, analyzed data from the TEXT (Tamoxifen and Exemestane Trial) and SOFT (Suppression of Ovarian Function Trial) trials of adjuvant endocrine therapies, comprising a total of nearly 5,000 women.

Results suggested that the absolute improvement in the 5-year breast cancer–free interval rate with exemestane plus ovarian function suppression (OFS) versus tamoxifen with or without OFS ranged from less than 1% in women with a lowest recurrence risk based on clinicopathologic factors to 10%-15% in women with a highest risk.

“TEXT and SOFT demonstrated that premenopausal women with hormone receptor–positive disease benefit, on average, from exemestane plus OFS versus tamoxifen with or without OFS. However, individualized treatment decisions should weigh the benefits against the adverse effects and costs of these therapy options,” the investigators wrote.

“In the absence of predictive biomarkers, consideration of a patient’s prognosis, as illustrated by STEPP [Subpopulation Treatment Effect Pattern Plot] analysis of a composite measure of recurrence risk in the TEXT and SOFT populations, is integral to this decision making,” they added.

In the SOFT trial, women were randomized to 5 years of tamoxifen alone (as an active comparator), tamoxifen plus OFS, or exemestane (Aromasin) plus OFS. In the TEXT trial, women were randomized to 5 years of exemestane plus OFS or of tamoxifen plus OFS.

Dr. Regan and colleagues based their analyses on a total of 4,891 women. They assessed each patient’s composite recurrence risk from a Cox model that included a set of conventional clinicopathologic factors: age, nodal status, tumor size and grade, and estrogen receptor, progesterone receptor, and Ki-67 expression levels. And they used STEPP methodology to assess the impact of endocrine therapy across groups having different risk.

The median duration of follow-up was 5.6 years in the SOFT trial and 6 years in the TEXT trial. Results showed that the 5-year breast cancer–free interval rate was 90.8% for the study cohort as a whole. But it ranged considerably from 98.6% for patients with composite risk in the lowest quartile to 77.5% for patients with composite risk in the highest quartiles, the investigators reported (J Clin Oncol. 2016. doi: 10.1200/JCO.2015.64.3171).

In the SOFT population, patients who remained premenopausal after neoadjuvant or adjuvant chemotherapy had an absolute improvement of 5% or more in the 5-year breast cancer–free interval rate with exemestane plus OFS, compared with tamoxifen plus OFS or tamoxifen alone. The difference was 10%-15% for the subset at intermediate to high risk for recurrence.

In addition, a benefit of tamoxifen plus OFS over tamoxifen alone was evident in patients having the highest composite risk.

Among patients who were not given chemotherapy, who on average had the lowest composite recurrence risk, the 5-year breast cancer–free interval rate was excellent regardless of the endocrine therapy received.

In the TEXT trial population, the benefit of exemestane plus OFS over tamoxifen plus OFS in 5-year breast cancer–free interval rate ranged from 5% to 15%. Again, the patients who were not given chemotherapy, who had the lowest composite recurrence risk, fared well regardless of which endocrine therapy they received.

These findings should help guide clinical decisions in premenopausal women with hormone receptor–positive, HER2-negative breast cancer, both at the extremes of risk and in the scenario of intermediate risk, where factors such as patient preference, tolerance, and cost play a greater role, according to the investigators.

“Further follow-up of TEXT and SOFT patients is essential to guide patient care,” they concluded.

Oncologists should take an individualized approach when making decisions about adjuvant endocrine therapies for premenopausal hormone receptor–positive, HER2-negative early breast cancer, suggests an analysis of a pair of randomized phase III trials published online in the Journal of Clinical Oncology.

Investigators led by Meredith M. Regan, Sc.D., of Dana-Farber Cancer Institute in Boston, analyzed data from the TEXT (Tamoxifen and Exemestane Trial) and SOFT (Suppression of Ovarian Function Trial) trials of adjuvant endocrine therapies, comprising a total of nearly 5,000 women.

Results suggested that the absolute improvement in the 5-year breast cancer–free interval rate with exemestane plus ovarian function suppression (OFS) versus tamoxifen with or without OFS ranged from less than 1% in women with a lowest recurrence risk based on clinicopathologic factors to 10%-15% in women with a highest risk.

“TEXT and SOFT demonstrated that premenopausal women with hormone receptor–positive disease benefit, on average, from exemestane plus OFS versus tamoxifen with or without OFS. However, individualized treatment decisions should weigh the benefits against the adverse effects and costs of these therapy options,” the investigators wrote.

“In the absence of predictive biomarkers, consideration of a patient’s prognosis, as illustrated by STEPP [Subpopulation Treatment Effect Pattern Plot] analysis of a composite measure of recurrence risk in the TEXT and SOFT populations, is integral to this decision making,” they added.

In the SOFT trial, women were randomized to 5 years of tamoxifen alone (as an active comparator), tamoxifen plus OFS, or exemestane (Aromasin) plus OFS. In the TEXT trial, women were randomized to 5 years of exemestane plus OFS or of tamoxifen plus OFS.

Dr. Regan and colleagues based their analyses on a total of 4,891 women. They assessed each patient’s composite recurrence risk from a Cox model that included a set of conventional clinicopathologic factors: age, nodal status, tumor size and grade, and estrogen receptor, progesterone receptor, and Ki-67 expression levels. And they used STEPP methodology to assess the impact of endocrine therapy across groups having different risk.

The median duration of follow-up was 5.6 years in the SOFT trial and 6 years in the TEXT trial. Results showed that the 5-year breast cancer–free interval rate was 90.8% for the study cohort as a whole. But it ranged considerably from 98.6% for patients with composite risk in the lowest quartile to 77.5% for patients with composite risk in the highest quartiles, the investigators reported (J Clin Oncol. 2016. doi: 10.1200/JCO.2015.64.3171).

In the SOFT population, patients who remained premenopausal after neoadjuvant or adjuvant chemotherapy had an absolute improvement of 5% or more in the 5-year breast cancer–free interval rate with exemestane plus OFS, compared with tamoxifen plus OFS or tamoxifen alone. The difference was 10%-15% for the subset at intermediate to high risk for recurrence.

In addition, a benefit of tamoxifen plus OFS over tamoxifen alone was evident in patients having the highest composite risk.

Among patients who were not given chemotherapy, who on average had the lowest composite recurrence risk, the 5-year breast cancer–free interval rate was excellent regardless of the endocrine therapy received.

In the TEXT trial population, the benefit of exemestane plus OFS over tamoxifen plus OFS in 5-year breast cancer–free interval rate ranged from 5% to 15%. Again, the patients who were not given chemotherapy, who had the lowest composite recurrence risk, fared well regardless of which endocrine therapy they received.

These findings should help guide clinical decisions in premenopausal women with hormone receptor–positive, HER2-negative breast cancer, both at the extremes of risk and in the scenario of intermediate risk, where factors such as patient preference, tolerance, and cost play a greater role, according to the investigators.

“Further follow-up of TEXT and SOFT patients is essential to guide patient care,” they concluded.

Oncologists should take an individualized approach when making decisions about adjuvant endocrine therapies for premenopausal hormone receptor–positive, HER2-negative early breast cancer, suggests an analysis of a pair of randomized phase III trials published online in the Journal of Clinical Oncology.

Investigators led by Meredith M. Regan, Sc.D., of Dana-Farber Cancer Institute in Boston, analyzed data from the TEXT (Tamoxifen and Exemestane Trial) and SOFT (Suppression of Ovarian Function Trial) trials of adjuvant endocrine therapies, comprising a total of nearly 5,000 women.

Results suggested that the absolute improvement in the 5-year breast cancer–free interval rate with exemestane plus ovarian function suppression (OFS) versus tamoxifen with or without OFS ranged from less than 1% in women with a lowest recurrence risk based on clinicopathologic factors to 10%-15% in women with a highest risk.

“TEXT and SOFT demonstrated that premenopausal women with hormone receptor–positive disease benefit, on average, from exemestane plus OFS versus tamoxifen with or without OFS. However, individualized treatment decisions should weigh the benefits against the adverse effects and costs of these therapy options,” the investigators wrote.

“In the absence of predictive biomarkers, consideration of a patient’s prognosis, as illustrated by STEPP [Subpopulation Treatment Effect Pattern Plot] analysis of a composite measure of recurrence risk in the TEXT and SOFT populations, is integral to this decision making,” they added.

In the SOFT trial, women were randomized to 5 years of tamoxifen alone (as an active comparator), tamoxifen plus OFS, or exemestane (Aromasin) plus OFS. In the TEXT trial, women were randomized to 5 years of exemestane plus OFS or of tamoxifen plus OFS.

Dr. Regan and colleagues based their analyses on a total of 4,891 women. They assessed each patient’s composite recurrence risk from a Cox model that included a set of conventional clinicopathologic factors: age, nodal status, tumor size and grade, and estrogen receptor, progesterone receptor, and Ki-67 expression levels. And they used STEPP methodology to assess the impact of endocrine therapy across groups having different risk.

The median duration of follow-up was 5.6 years in the SOFT trial and 6 years in the TEXT trial. Results showed that the 5-year breast cancer–free interval rate was 90.8% for the study cohort as a whole. But it ranged considerably from 98.6% for patients with composite risk in the lowest quartile to 77.5% for patients with composite risk in the highest quartiles, the investigators reported (J Clin Oncol. 2016. doi: 10.1200/JCO.2015.64.3171).

In the SOFT population, patients who remained premenopausal after neoadjuvant or adjuvant chemotherapy had an absolute improvement of 5% or more in the 5-year breast cancer–free interval rate with exemestane plus OFS, compared with tamoxifen plus OFS or tamoxifen alone. The difference was 10%-15% for the subset at intermediate to high risk for recurrence.

In addition, a benefit of tamoxifen plus OFS over tamoxifen alone was evident in patients having the highest composite risk.

Among patients who were not given chemotherapy, who on average had the lowest composite recurrence risk, the 5-year breast cancer–free interval rate was excellent regardless of the endocrine therapy received.

In the TEXT trial population, the benefit of exemestane plus OFS over tamoxifen plus OFS in 5-year breast cancer–free interval rate ranged from 5% to 15%. Again, the patients who were not given chemotherapy, who had the lowest composite recurrence risk, fared well regardless of which endocrine therapy they received.

These findings should help guide clinical decisions in premenopausal women with hormone receptor–positive, HER2-negative breast cancer, both at the extremes of risk and in the scenario of intermediate risk, where factors such as patient preference, tolerance, and cost play a greater role, according to the investigators.

“Further follow-up of TEXT and SOFT patients is essential to guide patient care,” they concluded.

SAN DIEGO – Endometrial pathology findings at 3 months predicted response to levonorgestrel-releasing IUD treatment for complex atypical hyperplasia or grade 1 endometrial cancer at the MD Anderson Cancer Center in Houston.

Twenty-nine of 32 women (91%) who responded by 12 months showed stromal, glandular, or other endometrial changes indicating an effect at 3 months, vs. only 3 of 9 nonresponders (33%) (P less than .001). There were no differences in responders versus nonresponders in median age (47 vs. 56 years, P = .2) or body mass index (45 vs. 55 kg/m², P = .16).

The finding addresses an “unmet need” for markers of response to levonorgestrel-releasing IUD therapy. “You can look at [early] pathology” and have an idea how patients will do, Dr. Shannon Westin, a study investigator who is with the department of gynecologic oncology at MD Anderson, said at the annual meeting of the Society of Gynecologic Oncology.

Twenty-seven of 29 women (93%) with complex atypical hyperplasia (CAH) responded completely to the IUD, meaning they had normal endometrium or hyperplasia without atypia at 12 months. The response rate for endometrial cancer was 67%; 7 of 12 women had a complete response, and an 8th was diagnosed at 12 months with CAH, indicating a partial response. The rest of the patients remained stable or progressed.

Endometrial biopsies were performed every 3 months; the team also did molecular testing on tumors from 20 patients. Baseline protein Ki67 – a marker of proliferation – was significantly higher in nonresponders. Expression of several estrogen-induced genes was higher in responders.

Patients opted for the IUD to retain fertility or because obesity or comorbidities precluded surgery. Exclusion criteria included prior treatment for CAH or endometrial cancer, evidence of extrauterine spread, or levonorgestrel IUD contraindications, such as uterine infection.

Adverse events – primarily irregular bleeding and cramping – were mild and tended to resolve by 12 months. Treatment had little effect on measures of social, mental, and physical function. About half of the patients were white, a third were Hispanic, and most of the remaining patients were black.

There was no external funding for the work. Dr. Westin is a consultant for AstraZeneca, Medivation, Roche, Ovation, and Vermillion, and reported receiving research funding from AstraZeneca, Critical Outcomes Technologies, and Novartis.

[email protected]

SAN DIEGO – Endometrial pathology findings at 3 months predicted response to levonorgestrel-releasing IUD treatment for complex atypical hyperplasia or grade 1 endometrial cancer at the MD Anderson Cancer Center in Houston.

Twenty-nine of 32 women (91%) who responded by 12 months showed stromal, glandular, or other endometrial changes indicating an effect at 3 months, vs. only 3 of 9 nonresponders (33%) (P less than .001). There were no differences in responders versus nonresponders in median age (47 vs. 56 years, P = .2) or body mass index (45 vs. 55 kg/m², P = .16).

The finding addresses an “unmet need” for markers of response to levonorgestrel-releasing IUD therapy. “You can look at [early] pathology” and have an idea how patients will do, Dr. Shannon Westin, a study investigator who is with the department of gynecologic oncology at MD Anderson, said at the annual meeting of the Society of Gynecologic Oncology.

Twenty-seven of 29 women (93%) with complex atypical hyperplasia (CAH) responded completely to the IUD, meaning they had normal endometrium or hyperplasia without atypia at 12 months. The response rate for endometrial cancer was 67%; 7 of 12 women had a complete response, and an 8th was diagnosed at 12 months with CAH, indicating a partial response. The rest of the patients remained stable or progressed.

Endometrial biopsies were performed every 3 months; the team also did molecular testing on tumors from 20 patients. Baseline protein Ki67 – a marker of proliferation – was significantly higher in nonresponders. Expression of several estrogen-induced genes was higher in responders.

Patients opted for the IUD to retain fertility or because obesity or comorbidities precluded surgery. Exclusion criteria included prior treatment for CAH or endometrial cancer, evidence of extrauterine spread, or levonorgestrel IUD contraindications, such as uterine infection.

Adverse events – primarily irregular bleeding and cramping – were mild and tended to resolve by 12 months. Treatment had little effect on measures of social, mental, and physical function. About half of the patients were white, a third were Hispanic, and most of the remaining patients were black.

There was no external funding for the work. Dr. Westin is a consultant for AstraZeneca, Medivation, Roche, Ovation, and Vermillion, and reported receiving research funding from AstraZeneca, Critical Outcomes Technologies, and Novartis.

[email protected]

SAN DIEGO – Endometrial pathology findings at 3 months predicted response to levonorgestrel-releasing IUD treatment for complex atypical hyperplasia or grade 1 endometrial cancer at the MD Anderson Cancer Center in Houston.

Twenty-nine of 32 women (91%) who responded by 12 months showed stromal, glandular, or other endometrial changes indicating an effect at 3 months, vs. only 3 of 9 nonresponders (33%) (P less than .001). There were no differences in responders versus nonresponders in median age (47 vs. 56 years, P = .2) or body mass index (45 vs. 55 kg/m², P = .16).

The finding addresses an “unmet need” for markers of response to levonorgestrel-releasing IUD therapy. “You can look at [early] pathology” and have an idea how patients will do, Dr. Shannon Westin, a study investigator who is with the department of gynecologic oncology at MD Anderson, said at the annual meeting of the Society of Gynecologic Oncology.

Twenty-seven of 29 women (93%) with complex atypical hyperplasia (CAH) responded completely to the IUD, meaning they had normal endometrium or hyperplasia without atypia at 12 months. The response rate for endometrial cancer was 67%; 7 of 12 women had a complete response, and an 8th was diagnosed at 12 months with CAH, indicating a partial response. The rest of the patients remained stable or progressed.

Endometrial biopsies were performed every 3 months; the team also did molecular testing on tumors from 20 patients. Baseline protein Ki67 – a marker of proliferation – was significantly higher in nonresponders. Expression of several estrogen-induced genes was higher in responders.

Patients opted for the IUD to retain fertility or because obesity or comorbidities precluded surgery. Exclusion criteria included prior treatment for CAH or endometrial cancer, evidence of extrauterine spread, or levonorgestrel IUD contraindications, such as uterine infection.

Adverse events – primarily irregular bleeding and cramping – were mild and tended to resolve by 12 months. Treatment had little effect on measures of social, mental, and physical function. About half of the patients were white, a third were Hispanic, and most of the remaining patients were black.

There was no external funding for the work. Dr. Westin is a consultant for AstraZeneca, Medivation, Roche, Ovation, and Vermillion, and reported receiving research funding from AstraZeneca, Critical Outcomes Technologies, and Novartis.

[email protected]

SAN ANTONIO – A definitive phase III randomized controlled trial of statin therapy during adjuvant endocrine therapy for breast cancer is warranted in light of recent encouraging evidence pointing to a protective effect against disease recurrence, Melissa L. Bondy, Ph.D., said at the San Antonio Breast Cancer Symposium.

“The next phase of research in this area is to learn whether we can improve survival in breast cancer patients by having them take cholesterol-lowering medication. We really need to have a phase III trial in the adjuvant setting that includes these cholesterol-lowering drugs,” said Dr. Bondy, professor of cancer prevention and population sciences at Baylor Medical College, Houston.

Her call for a formal, randomized trial came while serving as discussant for two positive reports of an apparent beneficial effect of statins on breast cancer recurrence-free survival: one from the BIG 1-98 trial of adjuvant endocrine therapy for early-stage breast cancer, the other a meta-analysis of 12 published studies totaling 72,774 breast cancer patients.

Dr. Bondy found particularly compelling the Breast International Group (BIG) 1-98 study results presented by Dr. Signe Borgquist, an oncologist at Lund (Sweden) University. This secondary analysis of the impact of cholesterol-lowering medication included 7,963 postmenopausal women with early-stage, estrogen receptor–positive invasive breast cancer who were randomized to 5 years of tamoxifen, the aromatase inhibitor letrozole (Femara), or the two drugs in sequence. Serum total cholesterol levels and the use of cholesterol-lowering medications – a decision left up to individual physicians and patients – were assessed at baseline and again every 6 months for 5.5 years.

With a median 8 years of prospective follow-up, during which 1,432 patients experienced breast cancer recurrence, the disease-free survival rate was 18% higher in the 637 patients already on cholesterol-lowering medication – mainly statins – at enrollment, compared with those who were not. The distant recurrence-free interval was 19% better as well, with both analyses adjusted for their form of endocrine therapy, tumor size and grade, nodal status, local therapy, peritumoral vascular invasion, and other potential confounders.

Another 697 BIG 1-98 participants initiated cholesterol-lowering medication during their adjuvant endocrine therapy. In multivariate adjusted analyses, their disease-free survival rate was 21% greater and distant recurrence-free interval was 26% better than in participants not on a statin or other cholesterol-lowering medication during the trial.

As a possible mechanism by which statins might exert anticancer effects, Dr. Borgquist proposed that lowering cholesterol levels may deprive tumor cells of the ability to satisfy their increased demand for cholesterol uptake. This is a result of attenuated signaling through the estrogen receptor by the cholesterol metabolite 27-hydroxycholesterol, levels of which correlate with systemic total cholesterol.

Dr. Bondy offered another possible explanation for the reduced risk of breast cancer recurrence seen in women on cholesterol-lowering medication in BIG 1-98: “Many groups have shown that LDL affects the immune system by binding and inactivating all kinds of microorganisms and their toxic products. In other words, statins appear to affect the microbiome.”

She commented that, although the use of statins was nonrandomized in BIG 1-98, she was favorably impressed by the 8-year follow-up and careful monitoring of total cholesterol levels at 6-month intervals throughout the 5 years of adjuvant endocrine therapy.

Dr. Bondy noted that other studies – again, nonrandomized – suggest statins also interrupt the growth of colorectal cancer and other malignancies.

Dr. Sashidhar Manthravadi presented a meta-analysis of the 12 published studies that have reported data on the association of statins with recurrence-free and/or overall survival in breast cancer patients. Statin use was associated with a significant 34% improvement in recurrence-free survival.

Moreover, this benefit was confined to breast cancer patients on the lipophilic statins atorvastatin and simvastatin; the use of hydrophilic statins was not associated with a significant improvement in recurrence-free survival, according to Dr. Manthravadi, an internal medicine resident at the University of Missouri, Kansas City.

The use of statins also was associated with a 27% improvement in breast cancer–specific survival and a 33% improvement in overall survival, compared with statin nonusers; however, neither of these results achieved statistical significance, he added.

Dr. Bondy cautioned against making too much of the apparent distinction between lipophilic and hydrophilic statin in terms of protection against breast cancer recurrence, given the inherent limitations of a meta-analysis.

“There’s always a lot of missing information, as well as a failure to adjust for comorbidities. And follow-up times in these 12 studies ranged from 2.5 to 11.5 years,” she noted.

The ongoing BIG 1-98 trial is sponsored by the International Breast Cancer Study Group. Dr. Borgquist, Dr. Bondy, and Dr. Manthravadi reported having no financial conflicts of interest.

[email protected]

SAN ANTONIO – A definitive phase III randomized controlled trial of statin therapy during adjuvant endocrine therapy for breast cancer is warranted in light of recent encouraging evidence pointing to a protective effect against disease recurrence, Melissa L. Bondy, Ph.D., said at the San Antonio Breast Cancer Symposium.

“The next phase of research in this area is to learn whether we can improve survival in breast cancer patients by having them take cholesterol-lowering medication. We really need to have a phase III trial in the adjuvant setting that includes these cholesterol-lowering drugs,” said Dr. Bondy, professor of cancer prevention and population sciences at Baylor Medical College, Houston.

Her call for a formal, randomized trial came while serving as discussant for two positive reports of an apparent beneficial effect of statins on breast cancer recurrence-free survival: one from the BIG 1-98 trial of adjuvant endocrine therapy for early-stage breast cancer, the other a meta-analysis of 12 published studies totaling 72,774 breast cancer patients.

Dr. Bondy found particularly compelling the Breast International Group (BIG) 1-98 study results presented by Dr. Signe Borgquist, an oncologist at Lund (Sweden) University. This secondary analysis of the impact of cholesterol-lowering medication included 7,963 postmenopausal women with early-stage, estrogen receptor–positive invasive breast cancer who were randomized to 5 years of tamoxifen, the aromatase inhibitor letrozole (Femara), or the two drugs in sequence. Serum total cholesterol levels and the use of cholesterol-lowering medications – a decision left up to individual physicians and patients – were assessed at baseline and again every 6 months for 5.5 years.

With a median 8 years of prospective follow-up, during which 1,432 patients experienced breast cancer recurrence, the disease-free survival rate was 18% higher in the 637 patients already on cholesterol-lowering medication – mainly statins – at enrollment, compared with those who were not. The distant recurrence-free interval was 19% better as well, with both analyses adjusted for their form of endocrine therapy, tumor size and grade, nodal status, local therapy, peritumoral vascular invasion, and other potential confounders.

Another 697 BIG 1-98 participants initiated cholesterol-lowering medication during their adjuvant endocrine therapy. In multivariate adjusted analyses, their disease-free survival rate was 21% greater and distant recurrence-free interval was 26% better than in participants not on a statin or other cholesterol-lowering medication during the trial.

As a possible mechanism by which statins might exert anticancer effects, Dr. Borgquist proposed that lowering cholesterol levels may deprive tumor cells of the ability to satisfy their increased demand for cholesterol uptake. This is a result of attenuated signaling through the estrogen receptor by the cholesterol metabolite 27-hydroxycholesterol, levels of which correlate with systemic total cholesterol.

Dr. Bondy offered another possible explanation for the reduced risk of breast cancer recurrence seen in women on cholesterol-lowering medication in BIG 1-98: “Many groups have shown that LDL affects the immune system by binding and inactivating all kinds of microorganisms and their toxic products. In other words, statins appear to affect the microbiome.”

She commented that, although the use of statins was nonrandomized in BIG 1-98, she was favorably impressed by the 8-year follow-up and careful monitoring of total cholesterol levels at 6-month intervals throughout the 5 years of adjuvant endocrine therapy.

Dr. Bondy noted that other studies – again, nonrandomized – suggest statins also interrupt the growth of colorectal cancer and other malignancies.

Dr. Sashidhar Manthravadi presented a meta-analysis of the 12 published studies that have reported data on the association of statins with recurrence-free and/or overall survival in breast cancer patients. Statin use was associated with a significant 34% improvement in recurrence-free survival.

Moreover, this benefit was confined to breast cancer patients on the lipophilic statins atorvastatin and simvastatin; the use of hydrophilic statins was not associated with a significant improvement in recurrence-free survival, according to Dr. Manthravadi, an internal medicine resident at the University of Missouri, Kansas City.

The use of statins also was associated with a 27% improvement in breast cancer–specific survival and a 33% improvement in overall survival, compared with statin nonusers; however, neither of these results achieved statistical significance, he added.

Dr. Bondy cautioned against making too much of the apparent distinction between lipophilic and hydrophilic statin in terms of protection against breast cancer recurrence, given the inherent limitations of a meta-analysis.

“There’s always a lot of missing information, as well as a failure to adjust for comorbidities. And follow-up times in these 12 studies ranged from 2.5 to 11.5 years,” she noted.

The ongoing BIG 1-98 trial is sponsored by the International Breast Cancer Study Group. Dr. Borgquist, Dr. Bondy, and Dr. Manthravadi reported having no financial conflicts of interest.

[email protected]

SAN ANTONIO – A definitive phase III randomized controlled trial of statin therapy during adjuvant endocrine therapy for breast cancer is warranted in light of recent encouraging evidence pointing to a protective effect against disease recurrence, Melissa L. Bondy, Ph.D., said at the San Antonio Breast Cancer Symposium.

“The next phase of research in this area is to learn whether we can improve survival in breast cancer patients by having them take cholesterol-lowering medication. We really need to have a phase III trial in the adjuvant setting that includes these cholesterol-lowering drugs,” said Dr. Bondy, professor of cancer prevention and population sciences at Baylor Medical College, Houston.

Her call for a formal, randomized trial came while serving as discussant for two positive reports of an apparent beneficial effect of statins on breast cancer recurrence-free survival: one from the BIG 1-98 trial of adjuvant endocrine therapy for early-stage breast cancer, the other a meta-analysis of 12 published studies totaling 72,774 breast cancer patients.

Dr. Bondy found particularly compelling the Breast International Group (BIG) 1-98 study results presented by Dr. Signe Borgquist, an oncologist at Lund (Sweden) University. This secondary analysis of the impact of cholesterol-lowering medication included 7,963 postmenopausal women with early-stage, estrogen receptor–positive invasive breast cancer who were randomized to 5 years of tamoxifen, the aromatase inhibitor letrozole (Femara), or the two drugs in sequence. Serum total cholesterol levels and the use of cholesterol-lowering medications – a decision left up to individual physicians and patients – were assessed at baseline and again every 6 months for 5.5 years.

With a median 8 years of prospective follow-up, during which 1,432 patients experienced breast cancer recurrence, the disease-free survival rate was 18% higher in the 637 patients already on cholesterol-lowering medication – mainly statins – at enrollment, compared with those who were not. The distant recurrence-free interval was 19% better as well, with both analyses adjusted for their form of endocrine therapy, tumor size and grade, nodal status, local therapy, peritumoral vascular invasion, and other potential confounders.

Another 697 BIG 1-98 participants initiated cholesterol-lowering medication during their adjuvant endocrine therapy. In multivariate adjusted analyses, their disease-free survival rate was 21% greater and distant recurrence-free interval was 26% better than in participants not on a statin or other cholesterol-lowering medication during the trial.

As a possible mechanism by which statins might exert anticancer effects, Dr. Borgquist proposed that lowering cholesterol levels may deprive tumor cells of the ability to satisfy their increased demand for cholesterol uptake. This is a result of attenuated signaling through the estrogen receptor by the cholesterol metabolite 27-hydroxycholesterol, levels of which correlate with systemic total cholesterol.

Dr. Bondy offered another possible explanation for the reduced risk of breast cancer recurrence seen in women on cholesterol-lowering medication in BIG 1-98: “Many groups have shown that LDL affects the immune system by binding and inactivating all kinds of microorganisms and their toxic products. In other words, statins appear to affect the microbiome.”

She commented that, although the use of statins was nonrandomized in BIG 1-98, she was favorably impressed by the 8-year follow-up and careful monitoring of total cholesterol levels at 6-month intervals throughout the 5 years of adjuvant endocrine therapy.

Dr. Bondy noted that other studies – again, nonrandomized – suggest statins also interrupt the growth of colorectal cancer and other malignancies.

Dr. Sashidhar Manthravadi presented a meta-analysis of the 12 published studies that have reported data on the association of statins with recurrence-free and/or overall survival in breast cancer patients. Statin use was associated with a significant 34% improvement in recurrence-free survival.

Moreover, this benefit was confined to breast cancer patients on the lipophilic statins atorvastatin and simvastatin; the use of hydrophilic statins was not associated with a significant improvement in recurrence-free survival, according to Dr. Manthravadi, an internal medicine resident at the University of Missouri, Kansas City.

The use of statins also was associated with a 27% improvement in breast cancer–specific survival and a 33% improvement in overall survival, compared with statin nonusers; however, neither of these results achieved statistical significance, he added.

Dr. Bondy cautioned against making too much of the apparent distinction between lipophilic and hydrophilic statin in terms of protection against breast cancer recurrence, given the inherent limitations of a meta-analysis.

“There’s always a lot of missing information, as well as a failure to adjust for comorbidities. And follow-up times in these 12 studies ranged from 2.5 to 11.5 years,” she noted.

The ongoing BIG 1-98 trial is sponsored by the International Breast Cancer Study Group. Dr. Borgquist, Dr. Bondy, and Dr. Manthravadi reported having no financial conflicts of interest.

[email protected]

LAKE BUENA VISTA, FLA. – Weekly infusions of paclitaxel delayed progression in some patients with the very aggressive anaplastic thyroid cancer, a small prospective study determined.

The drug was most effective as adjuvant therapy for patients who had already undergone chemotherapy plus resection of the primary tumor, Dr. Naoyoshi Onoda reported in a poster session at the International Thyroid Conference. They survived for a median of 1 year (112-788 days) – an impressive feat considering that most patients with anaplastic thyroid cancer die within 6 months of diagnosis.

This finding suggests a place for paclitaxel as a standardized therapy for such patients, said Dr. Onoda of Osaka (Japan) City University. “We have objective data supporting standardized chemotherapy for the first time in the world.”

Anaplastic thyroid cancer is a very rare – but very aggressive – disease; there is no standardized treatment option. Dr. Onoda and his colleagues conducted a national prospective open-label study of weekly paclitaxel infusions in 56 patients with the malignancy.

The cohort was a median of 71 years old. All had stage IV disease: 10 were grade A, 18 grade B, 24 grade C, and four grade X. They received 80 mg/m² infusions once a week. The median number of cycles was 2, although it ranged from 0-23 cycles.

Almost everyone (98%) experienced adverse events; the most common was anemia (77%). About a quarter (28%) experienced adverse events of at least grade 3, but there were no serious events and no deaths related to the study drug.

The objective response rate and the clinical benefit rate were 23% and 79%. The agent was not curative; at the last follow-up, no patient had achieved a complete response, and 43 of 56 in the study had died of their disease. “Overall, the median time to progression was only 47 days, and median overall survival just 227 days. That is so very short. But it’s a little bit longer than we had been seeing rates from reported cases,” he said at the meeting held by the American Thyroid Association, Asia-Oceania Thyroid Association, European Thyroid Association, and Latin American Thyroid Society.

The study was sponsored by the Prospective Clinical Study Committee of the Anaplastic Thyroid Carcinoma Research Consortium of Japan (ATCCJ). Dr. Onoda had no financial disclosures.

[email protected]

LAKE BUENA VISTA, FLA. – Weekly infusions of paclitaxel delayed progression in some patients with the very aggressive anaplastic thyroid cancer, a small prospective study determined.

The drug was most effective as adjuvant therapy for patients who had already undergone chemotherapy plus resection of the primary tumor, Dr. Naoyoshi Onoda reported in a poster session at the International Thyroid Conference. They survived for a median of 1 year (112-788 days) – an impressive feat considering that most patients with anaplastic thyroid cancer die within 6 months of diagnosis.

This finding suggests a place for paclitaxel as a standardized therapy for such patients, said Dr. Onoda of Osaka (Japan) City University. “We have objective data supporting standardized chemotherapy for the first time in the world.”

Anaplastic thyroid cancer is a very rare – but very aggressive – disease; there is no standardized treatment option. Dr. Onoda and his colleagues conducted a national prospective open-label study of weekly paclitaxel infusions in 56 patients with the malignancy.

The cohort was a median of 71 years old. All had stage IV disease: 10 were grade A, 18 grade B, 24 grade C, and four grade X. They received 80 mg/m² infusions once a week. The median number of cycles was 2, although it ranged from 0-23 cycles.

Almost everyone (98%) experienced adverse events; the most common was anemia (77%). About a quarter (28%) experienced adverse events of at least grade 3, but there were no serious events and no deaths related to the study drug.

The objective response rate and the clinical benefit rate were 23% and 79%. The agent was not curative; at the last follow-up, no patient had achieved a complete response, and 43 of 56 in the study had died of their disease. “Overall, the median time to progression was only 47 days, and median overall survival just 227 days. That is so very short. But it’s a little bit longer than we had been seeing rates from reported cases,” he said at the meeting held by the American Thyroid Association, Asia-Oceania Thyroid Association, European Thyroid Association, and Latin American Thyroid Society.

The study was sponsored by the Prospective Clinical Study Committee of the Anaplastic Thyroid Carcinoma Research Consortium of Japan (ATCCJ). Dr. Onoda had no financial disclosures.

[email protected]

LAKE BUENA VISTA, FLA. – Weekly infusions of paclitaxel delayed progression in some patients with the very aggressive anaplastic thyroid cancer, a small prospective study determined.

The drug was most effective as adjuvant therapy for patients who had already undergone chemotherapy plus resection of the primary tumor, Dr. Naoyoshi Onoda reported in a poster session at the International Thyroid Conference. They survived for a median of 1 year (112-788 days) – an impressive feat considering that most patients with anaplastic thyroid cancer die within 6 months of diagnosis.

This finding suggests a place for paclitaxel as a standardized therapy for such patients, said Dr. Onoda of Osaka (Japan) City University. “We have objective data supporting standardized chemotherapy for the first time in the world.”

Anaplastic thyroid cancer is a very rare – but very aggressive – disease; there is no standardized treatment option. Dr. Onoda and his colleagues conducted a national prospective open-label study of weekly paclitaxel infusions in 56 patients with the malignancy.

The cohort was a median of 71 years old. All had stage IV disease: 10 were grade A, 18 grade B, 24 grade C, and four grade X. They received 80 mg/m² infusions once a week. The median number of cycles was 2, although it ranged from 0-23 cycles.

Almost everyone (98%) experienced adverse events; the most common was anemia (77%). About a quarter (28%) experienced adverse events of at least grade 3, but there were no serious events and no deaths related to the study drug.

The objective response rate and the clinical benefit rate were 23% and 79%. The agent was not curative; at the last follow-up, no patient had achieved a complete response, and 43 of 56 in the study had died of their disease. “Overall, the median time to progression was only 47 days, and median overall survival just 227 days. That is so very short. But it’s a little bit longer than we had been seeing rates from reported cases,” he said at the meeting held by the American Thyroid Association, Asia-Oceania Thyroid Association, European Thyroid Association, and Latin American Thyroid Society.

The study was sponsored by the Prospective Clinical Study Committee of the Anaplastic Thyroid Carcinoma Research Consortium of Japan (ATCCJ). Dr. Onoda had no financial disclosures.

[email protected]

LAKE BUENA VISTA, FLA. – More cases of thyroid cancer are being seen in Japanese youth after the Fukushima Daiichi nuclear power plant accident, but the increased incidence may be an artifact of heightened surveillance.

“The thyroid cancers appear to have already occurred prior to radiation exposure,” said Dr. Shinichi Suzuki of the department of thyroid and endocrinology at Fukushima (Japan) Medical University. Radiation-induced thyroid cancers take about 5 years to become detectable, so physicians should just now be seeing the earliest cases of thyroid cancer related to Fukushima radiation exposure, according to Dr. Suzuki. He presented interim results of Japan’s universal screening protocol for children potentially affected by the Fukushima incident at the International Thyroid Conference.

The protocol, designed to screen everyone residing in the Fukushima prefecture and aged 19 years or younger at the time of the 2011 incident, has been highly successful, with over 80% of those eligible receiving a baseline screening that included a thyroid ultrasound exam.

Screening consisted of an initial thyroid ultrasound exam performed with a portable ultrasound device. If no cyst or nodule was found, then the patient would be seen at the next scheduled thyroid ultrasound exam, 2 years later. Patients with cysts 20 mm or less in greatest diameter or nodules 5 mm or smaller also were deferred to the next scheduled examination. Patients with cysts larger than 20 mm or nodules larger than 5 mm received confirmatory examination by detailed ultrasound examination, blood work, and fine-needle aspiration.

Of the 300,476 patients who received the preliminary baseline survey, 2,294 (0.8%) had an abnormality that warranted confirmatory examination and 91.9% of patients went on to have the confirmatory exams. Of these, 113 were assessed as malignant or suspicious for malignancy. Ninety-nine patients had surgery, with findings of 98 cases of thyroid cancer and one benign tumor.

Patients examined after April 2014 were part of an expanded protocol. Under this protocol, 169,455 patients (44.7% participation) were examined and 1,223 patients (0.8%) had suspicious findings on thyroid ultrasound exam. Participation rate for confirmatory testing for this group was 62.7%, with 25 patients’ thyroids having malignant or potentially malignant findings. Six of these patients had surgery, and thyroid cancer was found in all six cases.

Pooling data from the 138 malignant or suspicious cases from the two groups, 105 patients in total have had surgery, 13 patients with small, noninvasive masses are being watched, and a further 20 are awaiting surgery, Dr. Suzuki said at the meeting held by the American Thyroid Association, Asia-Oceania Thyroid Association, European Thyroid Association, and Latin American Thyroid Society.

Of the 97 patients with thyroid cancer who were treated at Fukushima University, 61 were female. The mean patient age at the time of the disaster was 14.8 ± 2.7 years (range, 6-18 years), while the mean age at diagnosis was 17.4 ± 2.8 years (range, 9-22 years). All patients were asymptomatic.

Tumors were unilateral in all but two patients. Mean tumor size was 15.1 ± 0.8 mm (range, 5-53 mm). Nearly all of the tumors (94/97) were papillary thyroid carcinoma, with 86 of those being classical-type papillary thyroid carcinoma. Three patients had poorly differentiated thyroid carcinoma. Fifty-eight patients (60%) had some intraglandular spread, while 71 (73%) had calcifications.

Dr. Suzuki and his collaborators compared these 97 cases with 37 cases of pediatric thyroid cancer in an historical Japanese cohort and to the 26 cases seen in a cohort from Belarus following the Chernobyl disaster. The Fukushima patients were significantly older than either comparison group, with mean age of 11.9 years for the historical Japanese cohort and 10.6 years for the children from Belarus. Tumor size was smaller than the historical Japanese cohort’s mean of 4.1 cm but about the same as that seen in Belarus (1.4 cm). Pulmonary metastases were more common in the historical Japanese cohort (19% vs. 4% in Belarus and 2% in Fukushima).

To have reference data that use similar techniques on a similar population, Japanese researchers are conducting thyroid ultrasound examsaccording to the Fukushima protocol concurrently in three other Japanese prefectures. This is especially important, Dr. Suzuki said, because rapid technological advances in ultrasound imaging mean that screening is much more likely to detect small abnormalities in the thyroid than would have been the case even a few years ago. For this reason, and also because much more radiation was released at the site of the Chernobyl nuclear disaster, only limited comparisons can be made between pediatric thyroid cancer rates from the two nuclear accidents.

Thyroid ultrasound exam “has the ability to detect a lot of thyroid cancers,” he said, so care must be taken to avoid overdiagnosis and overtreatment in this group of young people. Information to date from the Fukushima surveillance project does not yet “give us the clear view about the influence of radiation exposure after the accident on thyroid cancer occurrence,” he said.

Dr. Suzuki reported no relevant disclosures.

[email protected]

On Twitter @karioakes

LAKE BUENA VISTA, FLA. – More cases of thyroid cancer are being seen in Japanese youth after the Fukushima Daiichi nuclear power plant accident, but the increased incidence may be an artifact of heightened surveillance.

“The thyroid cancers appear to have already occurred prior to radiation exposure,” said Dr. Shinichi Suzuki of the department of thyroid and endocrinology at Fukushima (Japan) Medical University. Radiation-induced thyroid cancers take about 5 years to become detectable, so physicians should just now be seeing the earliest cases of thyroid cancer related to Fukushima radiation exposure, according to Dr. Suzuki. He presented interim results of Japan’s universal screening protocol for children potentially affected by the Fukushima incident at the International Thyroid Conference.

The protocol, designed to screen everyone residing in the Fukushima prefecture and aged 19 years or younger at the time of the 2011 incident, has been highly successful, with over 80% of those eligible receiving a baseline screening that included a thyroid ultrasound exam.

Screening consisted of an initial thyroid ultrasound exam performed with a portable ultrasound device. If no cyst or nodule was found, then the patient would be seen at the next scheduled thyroid ultrasound exam, 2 years later. Patients with cysts 20 mm or less in greatest diameter or nodules 5 mm or smaller also were deferred to the next scheduled examination. Patients with cysts larger than 20 mm or nodules larger than 5 mm received confirmatory examination by detailed ultrasound examination, blood work, and fine-needle aspiration.

Of the 300,476 patients who received the preliminary baseline survey, 2,294 (0.8%) had an abnormality that warranted confirmatory examination and 91.9% of patients went on to have the confirmatory exams. Of these, 113 were assessed as malignant or suspicious for malignancy. Ninety-nine patients had surgery, with findings of 98 cases of thyroid cancer and one benign tumor.

Patients examined after April 2014 were part of an expanded protocol. Under this protocol, 169,455 patients (44.7% participation) were examined and 1,223 patients (0.8%) had suspicious findings on thyroid ultrasound exam. Participation rate for confirmatory testing for this group was 62.7%, with 25 patients’ thyroids having malignant or potentially malignant findings. Six of these patients had surgery, and thyroid cancer was found in all six cases.

Pooling data from the 138 malignant or suspicious cases from the two groups, 105 patients in total have had surgery, 13 patients with small, noninvasive masses are being watched, and a further 20 are awaiting surgery, Dr. Suzuki said at the meeting held by the American Thyroid Association, Asia-Oceania Thyroid Association, European Thyroid Association, and Latin American Thyroid Society.

Of the 97 patients with thyroid cancer who were treated at Fukushima University, 61 were female. The mean patient age at the time of the disaster was 14.8 ± 2.7 years (range, 6-18 years), while the mean age at diagnosis was 17.4 ± 2.8 years (range, 9-22 years). All patients were asymptomatic.

Tumors were unilateral in all but two patients. Mean tumor size was 15.1 ± 0.8 mm (range, 5-53 mm). Nearly all of the tumors (94/97) were papillary thyroid carcinoma, with 86 of those being classical-type papillary thyroid carcinoma. Three patients had poorly differentiated thyroid carcinoma. Fifty-eight patients (60%) had some intraglandular spread, while 71 (73%) had calcifications.

Dr. Suzuki and his collaborators compared these 97 cases with 37 cases of pediatric thyroid cancer in an historical Japanese cohort and to the 26 cases seen in a cohort from Belarus following the Chernobyl disaster. The Fukushima patients were significantly older than either comparison group, with mean age of 11.9 years for the historical Japanese cohort and 10.6 years for the children from Belarus. Tumor size was smaller than the historical Japanese cohort’s mean of 4.1 cm but about the same as that seen in Belarus (1.4 cm). Pulmonary metastases were more common in the historical Japanese cohort (19% vs. 4% in Belarus and 2% in Fukushima).

To have reference data that use similar techniques on a similar population, Japanese researchers are conducting thyroid ultrasound examsaccording to the Fukushima protocol concurrently in three other Japanese prefectures. This is especially important, Dr. Suzuki said, because rapid technological advances in ultrasound imaging mean that screening is much more likely to detect small abnormalities in the thyroid than would have been the case even a few years ago. For this reason, and also because much more radiation was released at the site of the Chernobyl nuclear disaster, only limited comparisons can be made between pediatric thyroid cancer rates from the two nuclear accidents.

Thyroid ultrasound exam “has the ability to detect a lot of thyroid cancers,” he said, so care must be taken to avoid overdiagnosis and overtreatment in this group of young people. Information to date from the Fukushima surveillance project does not yet “give us the clear view about the influence of radiation exposure after the accident on thyroid cancer occurrence,” he said.

Dr. Suzuki reported no relevant disclosures.

[email protected]

On Twitter @karioakes

LAKE BUENA VISTA, FLA. – More cases of thyroid cancer are being seen in Japanese youth after the Fukushima Daiichi nuclear power plant accident, but the increased incidence may be an artifact of heightened surveillance.

“The thyroid cancers appear to have already occurred prior to radiation exposure,” said Dr. Shinichi Suzuki of the department of thyroid and endocrinology at Fukushima (Japan) Medical University. Radiation-induced thyroid cancers take about 5 years to become detectable, so physicians should just now be seeing the earliest cases of thyroid cancer related to Fukushima radiation exposure, according to Dr. Suzuki. He presented interim results of Japan’s universal screening protocol for children potentially affected by the Fukushima incident at the International Thyroid Conference.

The protocol, designed to screen everyone residing in the Fukushima prefecture and aged 19 years or younger at the time of the 2011 incident, has been highly successful, with over 80% of those eligible receiving a baseline screening that included a thyroid ultrasound exam.

Screening consisted of an initial thyroid ultrasound exam performed with a portable ultrasound device. If no cyst or nodule was found, then the patient would be seen at the next scheduled thyroid ultrasound exam, 2 years later. Patients with cysts 20 mm or less in greatest diameter or nodules 5 mm or smaller also were deferred to the next scheduled examination. Patients with cysts larger than 20 mm or nodules larger than 5 mm received confirmatory examination by detailed ultrasound examination, blood work, and fine-needle aspiration.

Of the 300,476 patients who received the preliminary baseline survey, 2,294 (0.8%) had an abnormality that warranted confirmatory examination and 91.9% of patients went on to have the confirmatory exams. Of these, 113 were assessed as malignant or suspicious for malignancy. Ninety-nine patients had surgery, with findings of 98 cases of thyroid cancer and one benign tumor.

Patients examined after April 2014 were part of an expanded protocol. Under this protocol, 169,455 patients (44.7% participation) were examined and 1,223 patients (0.8%) had suspicious findings on thyroid ultrasound exam. Participation rate for confirmatory testing for this group was 62.7%, with 25 patients’ thyroids having malignant or potentially malignant findings. Six of these patients had surgery, and thyroid cancer was found in all six cases.

Pooling data from the 138 malignant or suspicious cases from the two groups, 105 patients in total have had surgery, 13 patients with small, noninvasive masses are being watched, and a further 20 are awaiting surgery, Dr. Suzuki said at the meeting held by the American Thyroid Association, Asia-Oceania Thyroid Association, European Thyroid Association, and Latin American Thyroid Society.

Of the 97 patients with thyroid cancer who were treated at Fukushima University, 61 were female. The mean patient age at the time of the disaster was 14.8 ± 2.7 years (range, 6-18 years), while the mean age at diagnosis was 17.4 ± 2.8 years (range, 9-22 years). All patients were asymptomatic.

Tumors were unilateral in all but two patients. Mean tumor size was 15.1 ± 0.8 mm (range, 5-53 mm). Nearly all of the tumors (94/97) were papillary thyroid carcinoma, with 86 of those being classical-type papillary thyroid carcinoma. Three patients had poorly differentiated thyroid carcinoma. Fifty-eight patients (60%) had some intraglandular spread, while 71 (73%) had calcifications.

Dr. Suzuki and his collaborators compared these 97 cases with 37 cases of pediatric thyroid cancer in an historical Japanese cohort and to the 26 cases seen in a cohort from Belarus following the Chernobyl disaster. The Fukushima patients were significantly older than either comparison group, with mean age of 11.9 years for the historical Japanese cohort and 10.6 years for the children from Belarus. Tumor size was smaller than the historical Japanese cohort’s mean of 4.1 cm but about the same as that seen in Belarus (1.4 cm). Pulmonary metastases were more common in the historical Japanese cohort (19% vs. 4% in Belarus and 2% in Fukushima).

To have reference data that use similar techniques on a similar population, Japanese researchers are conducting thyroid ultrasound examsaccording to the Fukushima protocol concurrently in three other Japanese prefectures. This is especially important, Dr. Suzuki said, because rapid technological advances in ultrasound imaging mean that screening is much more likely to detect small abnormalities in the thyroid than would have been the case even a few years ago. For this reason, and also because much more radiation was released at the site of the Chernobyl nuclear disaster, only limited comparisons can be made between pediatric thyroid cancer rates from the two nuclear accidents.

Thyroid ultrasound exam “has the ability to detect a lot of thyroid cancers,” he said, so care must be taken to avoid overdiagnosis and overtreatment in this group of young people. Information to date from the Fukushima surveillance project does not yet “give us the clear view about the influence of radiation exposure after the accident on thyroid cancer occurrence,” he said.

Dr. Suzuki reported no relevant disclosures.

[email protected]

On Twitter @karioakes

LAKE BUENA VISTA, FLA. – Ethanol ablation is just as effective as radiofrequency ablation for cystic thyroid nodules, resulting in similar volume reduction and similarly improving symptomatic and cosmetic outcomes at 6 months.

Radiofrequnecy ablation (RFA) did have a slight edge over ethanol injection (EA) in therapeutic response, Dr. Hye Sun Park said at the International Thyroid Conference. But because ethanol ablation is easier and less expensive, she recommended that it be considered as first-line therapy for these lesions.

Dr. Park of the University of Ulsan, Asan Medical Center in Seoul, South Korea, reported a trial of 46 patients, mean age 50 years old, with benign cystic thyroid nodules who were randomized to the two treatments. Patients randomized to ethanol, however, had significantly larger-volume lesions (14.7 vs. 8.6 mL), and symptom scores. Cosmetic scores and nodule vascularity were similar.

RFA was performed with an 18-gauge monopolar, internally cooled electrode with a 1-cm active tip, using the moving shot technique. Patients undergoing EA first had fluid removed from the nodules using a 16-gauge needle. Ablation consisted of an injection of 99% ethanol into the cystic space, which was removed after 2 minutes.

The primary outcome was nodule volume at 6 months. Secondary outcomes were postprocedural pain and complications, Dr. Park said at the meeting held by the American Thyroid Association, Asia-Oceania Thyroid Association , European Thyroid Association, and Latin American Thyroid Society.

At follow-up, the volume reductions were similar in RFA and EA (87.5 vs. 82.4 ml). The therapeutic success rate was 100% for patients who had RFA and 92% for those who had EA. Two patients in the EA group had major bleeding from the nodule, which interrupted the procedure; they later had a successful RFA. There were no complications in the RFA group.

There was only one major complication during follow-up: One patient who received EA complained of voice change, which resolved spontaneously by 2 months after ablation.

Dr. Park had no financial disclosures.

[email protected]

LAKE BUENA VISTA, FLA. – Ethanol ablation is just as effective as radiofrequency ablation for cystic thyroid nodules, resulting in similar volume reduction and similarly improving symptomatic and cosmetic outcomes at 6 months.

Radiofrequnecy ablation (RFA) did have a slight edge over ethanol injection (EA) in therapeutic response, Dr. Hye Sun Park said at the International Thyroid Conference. But because ethanol ablation is easier and less expensive, she recommended that it be considered as first-line therapy for these lesions.

Dr. Park of the University of Ulsan, Asan Medical Center in Seoul, South Korea, reported a trial of 46 patients, mean age 50 years old, with benign cystic thyroid nodules who were randomized to the two treatments. Patients randomized to ethanol, however, had significantly larger-volume lesions (14.7 vs. 8.6 mL), and symptom scores. Cosmetic scores and nodule vascularity were similar.

RFA was performed with an 18-gauge monopolar, internally cooled electrode with a 1-cm active tip, using the moving shot technique. Patients undergoing EA first had fluid removed from the nodules using a 16-gauge needle. Ablation consisted of an injection of 99% ethanol into the cystic space, which was removed after 2 minutes.

The primary outcome was nodule volume at 6 months. Secondary outcomes were postprocedural pain and complications, Dr. Park said at the meeting held by the American Thyroid Association, Asia-Oceania Thyroid Association , European Thyroid Association, and Latin American Thyroid Society.

At follow-up, the volume reductions were similar in RFA and EA (87.5 vs. 82.4 ml). The therapeutic success rate was 100% for patients who had RFA and 92% for those who had EA. Two patients in the EA group had major bleeding from the nodule, which interrupted the procedure; they later had a successful RFA. There were no complications in the RFA group.

There was only one major complication during follow-up: One patient who received EA complained of voice change, which resolved spontaneously by 2 months after ablation.

Dr. Park had no financial disclosures.

[email protected]

LAKE BUENA VISTA, FLA. – Ethanol ablation is just as effective as radiofrequency ablation for cystic thyroid nodules, resulting in similar volume reduction and similarly improving symptomatic and cosmetic outcomes at 6 months.

Radiofrequnecy ablation (RFA) did have a slight edge over ethanol injection (EA) in therapeutic response, Dr. Hye Sun Park said at the International Thyroid Conference. But because ethanol ablation is easier and less expensive, she recommended that it be considered as first-line therapy for these lesions.

Dr. Park of the University of Ulsan, Asan Medical Center in Seoul, South Korea, reported a trial of 46 patients, mean age 50 years old, with benign cystic thyroid nodules who were randomized to the two treatments. Patients randomized to ethanol, however, had significantly larger-volume lesions (14.7 vs. 8.6 mL), and symptom scores. Cosmetic scores and nodule vascularity were similar.

RFA was performed with an 18-gauge monopolar, internally cooled electrode with a 1-cm active tip, using the moving shot technique. Patients undergoing EA first had fluid removed from the nodules using a 16-gauge needle. Ablation consisted of an injection of 99% ethanol into the cystic space, which was removed after 2 minutes.

The primary outcome was nodule volume at 6 months. Secondary outcomes were postprocedural pain and complications, Dr. Park said at the meeting held by the American Thyroid Association, Asia-Oceania Thyroid Association , European Thyroid Association, and Latin American Thyroid Society.

At follow-up, the volume reductions were similar in RFA and EA (87.5 vs. 82.4 ml). The therapeutic success rate was 100% for patients who had RFA and 92% for those who had EA. Two patients in the EA group had major bleeding from the nodule, which interrupted the procedure; they later had a successful RFA. There were no complications in the RFA group.

There was only one major complication during follow-up: One patient who received EA complained of voice change, which resolved spontaneously by 2 months after ablation.

Dr. Park had no financial disclosures.

[email protected]

Moderate thyroid hormone suppression therapy (THST) is associated with the best outcomes for patients with all stages of thyroid cancer, according to a prospective analysis of a multi-institutional registry published in the Journal of Clinical Endocrinology & Metabolism.

The researchers examined the outcomes of initial treatment for 4,941 patients with differentiated thyroid cancer (DTC), according to registry data from the National Thyroid Cancer Treatment Cooperative Study Group. The treatments included total/near total thyroidectomy (T/NTT), postoperative radioactive iodine-131 (¹³¹I), and THST. The median duration between treatment and follow-up for a patient was 6 years, with follow-up information available for all but 94 (1.9%) of the patients in the cohort.

Overall improvement was noted in stage III patients who received ¹³¹I (risk ratio, 0.66; P = .04) and stage IV patients who received both T/NTT and ¹³¹I (RR, 0.66; P = .049). In all stages, moderate THST was associated with significantly improved overall survival (RR stages I-IV: 0.13, 0.09, 0.13, and 0.33, respectively) and disease-free survival (DFS) (RR stages I-III: 0.52, 0.40, and 0.18, respectively); no additional survival benefit was achieved with more aggressive THST, even when distant metastatic disease was diagnosed during follow-up.

Lower initial stage and moderate THST were independent predictors of improved overall survival during follow-up years 1-3.

Consistent with previous research, this study also showed that T/NTT followed by ¹³¹I is associated with benefit in high-risk, but not low-risk patients.

“We report for the first time, in multivariate analysis of primary treatments for DTC, across all stages, only THST was associated with both improved stage-adjusted OS and DFS,” noted Dr. Aubrey A. Carhill and his colleagues.

“This analysis of the larger, more mature registry database extends and refines earlier observations regarding the impact of initial therapies on patient outcomes and further justifies the need for prospective, long-term, controlled studies,” the researchers noted.

Read the full study in the Journal of Clinical Endocrinology & Metabolism (doi:10.1210/JC.2015-1346).

[email protected]

Moderate thyroid hormone suppression therapy (THST) is associated with the best outcomes for patients with all stages of thyroid cancer, according to a prospective analysis of a multi-institutional registry published in the Journal of Clinical Endocrinology & Metabolism.

The researchers examined the outcomes of initial treatment for 4,941 patients with differentiated thyroid cancer (DTC), according to registry data from the National Thyroid Cancer Treatment Cooperative Study Group. The treatments included total/near total thyroidectomy (T/NTT), postoperative radioactive iodine-131 (¹³¹I), and THST. The median duration between treatment and follow-up for a patient was 6 years, with follow-up information available for all but 94 (1.9%) of the patients in the cohort.

Overall improvement was noted in stage III patients who received ¹³¹I (risk ratio, 0.66; P = .04) and stage IV patients who received both T/NTT and ¹³¹I (RR, 0.66; P = .049). In all stages, moderate THST was associated with significantly improved overall survival (RR stages I-IV: 0.13, 0.09, 0.13, and 0.33, respectively) and disease-free survival (DFS) (RR stages I-III: 0.52, 0.40, and 0.18, respectively); no additional survival benefit was achieved with more aggressive THST, even when distant metastatic disease was diagnosed during follow-up.

Lower initial stage and moderate THST were independent predictors of improved overall survival during follow-up years 1-3.

Consistent with previous research, this study also showed that T/NTT followed by ¹³¹I is associated with benefit in high-risk, but not low-risk patients.

“We report for the first time, in multivariate analysis of primary treatments for DTC, across all stages, only THST was associated with both improved stage-adjusted OS and DFS,” noted Dr. Aubrey A. Carhill and his colleagues.

“This analysis of the larger, more mature registry database extends and refines earlier observations regarding the impact of initial therapies on patient outcomes and further justifies the need for prospective, long-term, controlled studies,” the researchers noted.

Read the full study in the Journal of Clinical Endocrinology & Metabolism (doi:10.1210/JC.2015-1346).

[email protected]

Moderate thyroid hormone suppression therapy (THST) is associated with the best outcomes for patients with all stages of thyroid cancer, according to a prospective analysis of a multi-institutional registry published in the Journal of Clinical Endocrinology & Metabolism.

The researchers examined the outcomes of initial treatment for 4,941 patients with differentiated thyroid cancer (DTC), according to registry data from the National Thyroid Cancer Treatment Cooperative Study Group. The treatments included total/near total thyroidectomy (T/NTT), postoperative radioactive iodine-131 (¹³¹I), and THST. The median duration between treatment and follow-up for a patient was 6 years, with follow-up information available for all but 94 (1.9%) of the patients in the cohort.

Overall improvement was noted in stage III patients who received ¹³¹I (risk ratio, 0.66; P = .04) and stage IV patients who received both T/NTT and ¹³¹I (RR, 0.66; P = .049). In all stages, moderate THST was associated with significantly improved overall survival (RR stages I-IV: 0.13, 0.09, 0.13, and 0.33, respectively) and disease-free survival (DFS) (RR stages I-III: 0.52, 0.40, and 0.18, respectively); no additional survival benefit was achieved with more aggressive THST, even when distant metastatic disease was diagnosed during follow-up.

Lower initial stage and moderate THST were independent predictors of improved overall survival during follow-up years 1-3.

Consistent with previous research, this study also showed that T/NTT followed by ¹³¹I is associated with benefit in high-risk, but not low-risk patients.

“We report for the first time, in multivariate analysis of primary treatments for DTC, across all stages, only THST was associated with both improved stage-adjusted OS and DFS,” noted Dr. Aubrey A. Carhill and his colleagues.

“This analysis of the larger, more mature registry database extends and refines earlier observations regarding the impact of initial therapies on patient outcomes and further justifies the need for prospective, long-term, controlled studies,” the researchers noted.

Read the full study in the Journal of Clinical Endocrinology & Metabolism (doi:10.1210/JC.2015-1346).

[email protected]

NASHVILLE, TENN. – Patients with stage I or II differentiated thyroid cancers do not need radioactive iodine treatment if their nonsuppressed thyroglobulin level is less than 2 ng/mL 2 weeks after surgery, according to Dr. Kathleen Hands.

When that’s the case, “I know the patient had an excellent surgery and will have an excellent prognosis with an extremely low likelihood of recurrence over the next 10 years without radioactive iodine. These patients can be managed safely and effectively without radioactive iodine in a community setting,” said Dr. Hands, a thyroidologist who practices in San Antonio.

It’s common for patients in the United States to receive iodine-131 (I-131) after surgery for low-risk thyroid cancers “despite the abundance of evidence” showing that it does them no good and may cause harm and despite guidelines calling for conservative use of I-131, she said (World. J. Surg. 2002;26:879-85).

“It’s a habit,” a holdover from decades ago “when we didn’t actually have good surgical technique. We need to [heed recent data] and step away from what we did in the 60s, 70s, and 80s and get into the 21st century. We should stop using radioactive iodine in these low-risk patients,” Dr. Hands said at the American Association of Clinical Endocrinologists annual meeting.

Among radioactive iodine’s drawbacks are its expense and sometimes salivary and lacrimal problems associated with its use. Earlier in her career, “I personally had two of my cases” – 19 and 22 years old – “develop acute myelogenous leukemia [shortly] after I-131, one of whom succumbed. I took that very seriously. I’ve become very conservative in the use of this drug. Ablation should be restricted to patients with incomplete surgical excision or poor prognostic factors for recurrence or death,” she said.

This advice is backed up by findings from her review of 378 patients who underwent surgery for differentiated thyroid cancer, with MACIS (metastasis, age, completeness of resection, invasion, and size) scores below 7, meaning low-intermediate-risk disease. Patients ranged from 18 to 79 years old. The majority were women, and about a third had multifocal disease. Tumor sizes ranged from 0.8 mm to 4.0 cm. Twenty-one patients under 45 years old had lymph node metastases of less than 5 mm.

The patients had nonsuppressed thyroglobulin levels below 2 ng/mL 2 weeks after surgery. They opted against I-131, and were started on levothyroxine. There’s been no recurrence of disease in the group after 8 years’ follow-up; thyroglobulin was undetectable in 72% by 2 years. Those in whom thyroglobulin remained detectable had thyroglobulin velocities below 10% over a period of 5 years.

“Nonsuppressed thyroglobulin” means that the patients were not put on thyroxine right after surgery, so that Dr. Hands could get an idea if any tumor was left 2 weeks later. They also weren’t put on low-iodine diets in the interim, she said, because she had no intention of giving them I-131.

To get the most out of the approach, patients need excellent and complete surgeries. That means that endocrinologists should learn to perform preoperative neck ultrasounds – or refer to someone who can – to give surgeons a heads-up about tumor location, size, shape, and invasiveness, as well as lymph node involvement, calcifications, and other issues. “This is the kind of information your surgeon needs” to do a good job, Dr. Hands said.

She said she doesn’t worry about hypothyroidism when patients don’t get thyroxine right after surgery. Manipulation of the thyroid during surgery releases hormone into the system, and “I think that tides them over; It’s a long-acting hormone. Patients tolerate not having replacement immediately [after surgery],” Dr. Hands said.

There was no funding for the project, and Dr. Hands said she had no relevant financial disclosures.

[email protected]

NASHVILLE, TENN. – Patients with stage I or II differentiated thyroid cancers do not need radioactive iodine treatment if their nonsuppressed thyroglobulin level is less than 2 ng/mL 2 weeks after surgery, according to Dr. Kathleen Hands.

When that’s the case, “I know the patient had an excellent surgery and will have an excellent prognosis with an extremely low likelihood of recurrence over the next 10 years without radioactive iodine. These patients can be managed safely and effectively without radioactive iodine in a community setting,” said Dr. Hands, a thyroidologist who practices in San Antonio.

It’s common for patients in the United States to receive iodine-131 (I-131) after surgery for low-risk thyroid cancers “despite the abundance of evidence” showing that it does them no good and may cause harm and despite guidelines calling for conservative use of I-131, she said (World. J. Surg. 2002;26:879-85).

“It’s a habit,” a holdover from decades ago “when we didn’t actually have good surgical technique. We need to [heed recent data] and step away from what we did in the 60s, 70s, and 80s and get into the 21st century. We should stop using radioactive iodine in these low-risk patients,” Dr. Hands said at the American Association of Clinical Endocrinologists annual meeting.

Among radioactive iodine’s drawbacks are its expense and sometimes salivary and lacrimal problems associated with its use. Earlier in her career, “I personally had two of my cases” – 19 and 22 years old – “develop acute myelogenous leukemia [shortly] after I-131, one of whom succumbed. I took that very seriously. I’ve become very conservative in the use of this drug. Ablation should be restricted to patients with incomplete surgical excision or poor prognostic factors for recurrence or death,” she said.

This advice is backed up by findings from her review of 378 patients who underwent surgery for differentiated thyroid cancer, with MACIS (metastasis, age, completeness of resection, invasion, and size) scores below 7, meaning low-intermediate-risk disease. Patients ranged from 18 to 79 years old. The majority were women, and about a third had multifocal disease. Tumor sizes ranged from 0.8 mm to 4.0 cm. Twenty-one patients under 45 years old had lymph node metastases of less than 5 mm.

The patients had nonsuppressed thyroglobulin levels below 2 ng/mL 2 weeks after surgery. They opted against I-131, and were started on levothyroxine. There’s been no recurrence of disease in the group after 8 years’ follow-up; thyroglobulin was undetectable in 72% by 2 years. Those in whom thyroglobulin remained detectable had thyroglobulin velocities below 10% over a period of 5 years.

“Nonsuppressed thyroglobulin” means that the patients were not put on thyroxine right after surgery, so that Dr. Hands could get an idea if any tumor was left 2 weeks later. They also weren’t put on low-iodine diets in the interim, she said, because she had no intention of giving them I-131.

To get the most out of the approach, patients need excellent and complete surgeries. That means that endocrinologists should learn to perform preoperative neck ultrasounds – or refer to someone who can – to give surgeons a heads-up about tumor location, size, shape, and invasiveness, as well as lymph node involvement, calcifications, and other issues. “This is the kind of information your surgeon needs” to do a good job, Dr. Hands said.

She said she doesn’t worry about hypothyroidism when patients don’t get thyroxine right after surgery. Manipulation of the thyroid during surgery releases hormone into the system, and “I think that tides them over; It’s a long-acting hormone. Patients tolerate not having replacement immediately [after surgery],” Dr. Hands said.

There was no funding for the project, and Dr. Hands said she had no relevant financial disclosures.

[email protected]

NASHVILLE, TENN. – Patients with stage I or II differentiated thyroid cancers do not need radioactive iodine treatment if their nonsuppressed thyroglobulin level is less than 2 ng/mL 2 weeks after surgery, according to Dr. Kathleen Hands.

When that’s the case, “I know the patient had an excellent surgery and will have an excellent prognosis with an extremely low likelihood of recurrence over the next 10 years without radioactive iodine. These patients can be managed safely and effectively without radioactive iodine in a community setting,” said Dr. Hands, a thyroidologist who practices in San Antonio.

It’s common for patients in the United States to receive iodine-131 (I-131) after surgery for low-risk thyroid cancers “despite the abundance of evidence” showing that it does them no good and may cause harm and despite guidelines calling for conservative use of I-131, she said (World. J. Surg. 2002;26:879-85).

“It’s a habit,” a holdover from decades ago “when we didn’t actually have good surgical technique. We need to [heed recent data] and step away from what we did in the 60s, 70s, and 80s and get into the 21st century. We should stop using radioactive iodine in these low-risk patients,” Dr. Hands said at the American Association of Clinical Endocrinologists annual meeting.

Among radioactive iodine’s drawbacks are its expense and sometimes salivary and lacrimal problems associated with its use. Earlier in her career, “I personally had two of my cases” – 19 and 22 years old – “develop acute myelogenous leukemia [shortly] after I-131, one of whom succumbed. I took that very seriously. I’ve become very conservative in the use of this drug. Ablation should be restricted to patients with incomplete surgical excision or poor prognostic factors for recurrence or death,” she said.

This advice is backed up by findings from her review of 378 patients who underwent surgery for differentiated thyroid cancer, with MACIS (metastasis, age, completeness of resection, invasion, and size) scores below 7, meaning low-intermediate-risk disease. Patients ranged from 18 to 79 years old. The majority were women, and about a third had multifocal disease. Tumor sizes ranged from 0.8 mm to 4.0 cm. Twenty-one patients under 45 years old had lymph node metastases of less than 5 mm.

The patients had nonsuppressed thyroglobulin levels below 2 ng/mL 2 weeks after surgery. They opted against I-131, and were started on levothyroxine. There’s been no recurrence of disease in the group after 8 years’ follow-up; thyroglobulin was undetectable in 72% by 2 years. Those in whom thyroglobulin remained detectable had thyroglobulin velocities below 10% over a period of 5 years.

“Nonsuppressed thyroglobulin” means that the patients were not put on thyroxine right after surgery, so that Dr. Hands could get an idea if any tumor was left 2 weeks later. They also weren’t put on low-iodine diets in the interim, she said, because she had no intention of giving them I-131.

To get the most out of the approach, patients need excellent and complete surgeries. That means that endocrinologists should learn to perform preoperative neck ultrasounds – or refer to someone who can – to give surgeons a heads-up about tumor location, size, shape, and invasiveness, as well as lymph node involvement, calcifications, and other issues. “This is the kind of information your surgeon needs” to do a good job, Dr. Hands said.

She said she doesn’t worry about hypothyroidism when patients don’t get thyroxine right after surgery. Manipulation of the thyroid during surgery releases hormone into the system, and “I think that tides them over; It’s a long-acting hormone. Patients tolerate not having replacement immediately [after surgery],” Dr. Hands said.

There was no funding for the project, and Dr. Hands said she had no relevant financial disclosures.

[email protected]

CHICAGO – It’s getting very personal in oncology, and that’s a very good thing.

At the annual meeting of the American Society of Clinical Oncology, major cancer organizations announced new precision medicine initiatives that will attempt to match patients who have advanced cancers with the best available therapies based not on the location or histologic subtypes of their tumors, but on specific molecular abnormalities.

The National Cancer Institute’s Molecular Analysis for Therapy Choice (NCI-MATCH) trial will begin enrolling patients in July 2015. The study’s objective is “to understand the relative efficacy of the same therapy applied to oncogene-defined subsets across the entire cancer population as defined by site of origin or tumor histology,” said co–principal investigator Dr. Keith T. Flaherty of Harvard Medical School, Boston.

“This is the beginning, not the end, in terms of how we think about applying these therapies,” he said at a briefing that was held to announce the start of trial enrollment and a second initiative – the Targeted Agent and Profiling Utilization Registry (TAPUR) Study – by ASCO in cooperation with major pharmaceutical companies.

NCI-MATCH

NCI-MATCH is a phase II trial that will be operated through the National Clinical Trials Network. Oncologists at participating centers throughout the United States can enroll patients aged 18 years and older who have solid tumors or lymphomas that have relapsed or are refractory to conventional therapy, or who have a type of cancer for which no effective, consensus-based therapy is available.

Investigators plan to screen 3,000 patients initially, with the goal of enrolling 1,000 patients distributed among several substudies that will be evaluating specific drugs against specific molecular targets.

Patients will undergo biopsy at study entry, and their tumors will be subjected to genomic analysis to detect specific, targetable molecular abnormalities.

If a patient has a specific abnormality that is being explored in a current substudy, that patient will be further evaluated to determine whether he or she meets the eligibility criteria for that trial arm. Once enrolled, patients can remain on therapy until disease progression. The therapies will include both currently marketed agents and investigational therapies contributed by drug companies. Most of the trial arms will explore monotherapy with a targeted agent, but a few may investigate combinations which have accumulated enough safety and efficacy data to suggest that they might work against a specific molecular target.

The primary endpoint will be overall response rate, with a secondary endpoint of 6-month progression-free survival (PFS).

“This holds promise to bring faster cures to millions of Americans who so desperately need them,” ASCO past president Dr. Clifford A. Hudis said at the briefing.

TAPUR Trial

In cooperation with major pharmaceutical manufacturers (currently five, with more expected to sign on), ASCO has initiated a study designed to help answer the question, “I’ve got the tumor genome – now what do I do with it?”

The goal of the TAPUR trial, says ASCO Chief Medical Officer Dr. Richard Schilsky, is “to learn from the real world practice of prescribing targeted therapies to patients with advanced cancer whose tumor harbors a genomic variant known to be a drug target.”

The primary objectives are to describe the antitumor activity and toxicity profiles of targeted therapies, and to help patients get access to Food and Drug Administration–approved agents from which they may be able to benefit.

The trial will enroll patients with advanced solid tumors, B-cell non-Hodgkin’s lymphomas, and multiple myelomas for which there are no standard therapies. The patients must have adequate organ function and good performance status (0-2).

Patients will be matched by their personal physicians to specific therapies, if such a match exists; otherwise, they will be treated at the physician’s discretion.

The primary endpoint of the study will be overall response rates by Response Evaluation Criteria in Solid Tumors (RECIST). Secondary endpoints will be PFS, OS, time on treatment, grade 3 or greater adverse events, and serious adverse event. The investigators plan to begin patient enrollment in the fourth quarter of 2015.

Current industry partners include AstraZeneca, Bristol Myers Squibb, Eli Lilly, Genentech, and Pfizer.

The NCI-MATCH study is funded by the National Institutes of Health. Dr. Flaherty has received NIH research grants. Dr. Hudis disclosed ties to AstraZeneca, Sanofi-Aventis, Amgen, Bristol-Myers Squibb, Genentech, Eli Lilly, Novartis, Ortho Biotech, Pfizer, and Roche. Dr. Schilsky disclosed no relevant conflicts of interest.

CHICAGO – It’s getting very personal in oncology, and that’s a very good thing.

At the annual meeting of the American Society of Clinical Oncology, major cancer organizations announced new precision medicine initiatives that will attempt to match patients who have advanced cancers with the best available therapies based not on the location or histologic subtypes of their tumors, but on specific molecular abnormalities.

The National Cancer Institute’s Molecular Analysis for Therapy Choice (NCI-MATCH) trial will begin enrolling patients in July 2015. The study’s objective is “to understand the relative efficacy of the same therapy applied to oncogene-defined subsets across the entire cancer population as defined by site of origin or tumor histology,” said co–principal investigator Dr. Keith T. Flaherty of Harvard Medical School, Boston.

“This is the beginning, not the end, in terms of how we think about applying these therapies,” he said at a briefing that was held to announce the start of trial enrollment and a second initiative – the Targeted Agent and Profiling Utilization Registry (TAPUR) Study – by ASCO in cooperation with major pharmaceutical companies.

NCI-MATCH

NCI-MATCH is a phase II trial that will be operated through the National Clinical Trials Network. Oncologists at participating centers throughout the United States can enroll patients aged 18 years and older who have solid tumors or lymphomas that have relapsed or are refractory to conventional therapy, or who have a type of cancer for which no effective, consensus-based therapy is available.

Investigators plan to screen 3,000 patients initially, with the goal of enrolling 1,000 patients distributed among several substudies that will be evaluating specific drugs against specific molecular targets.

Patients will undergo biopsy at study entry, and their tumors will be subjected to genomic analysis to detect specific, targetable molecular abnormalities.

If a patient has a specific abnormality that is being explored in a current substudy, that patient will be further evaluated to determine whether he or she meets the eligibility criteria for that trial arm. Once enrolled, patients can remain on therapy until disease progression. The therapies will include both currently marketed agents and investigational therapies contributed by drug companies. Most of the trial arms will explore monotherapy with a targeted agent, but a few may investigate combinations which have accumulated enough safety and efficacy data to suggest that they might work against a specific molecular target.

The primary endpoint will be overall response rate, with a secondary endpoint of 6-month progression-free survival (PFS).

“This holds promise to bring faster cures to millions of Americans who so desperately need them,” ASCO past president Dr. Clifford A. Hudis said at the briefing.

TAPUR Trial

In cooperation with major pharmaceutical manufacturers (currently five, with more expected to sign on), ASCO has initiated a study designed to help answer the question, “I’ve got the tumor genome – now what do I do with it?”

The goal of the TAPUR trial, says ASCO Chief Medical Officer Dr. Richard Schilsky, is “to learn from the real world practice of prescribing targeted therapies to patients with advanced cancer whose tumor harbors a genomic variant known to be a drug target.”

The primary objectives are to describe the antitumor activity and toxicity profiles of targeted therapies, and to help patients get access to Food and Drug Administration–approved agents from which they may be able to benefit.

The trial will enroll patients with advanced solid tumors, B-cell non-Hodgkin’s lymphomas, and multiple myelomas for which there are no standard therapies. The patients must have adequate organ function and good performance status (0-2).

Patients will be matched by their personal physicians to specific therapies, if such a match exists; otherwise, they will be treated at the physician’s discretion.

The primary endpoint of the study will be overall response rates by Response Evaluation Criteria in Solid Tumors (RECIST). Secondary endpoints will be PFS, OS, time on treatment, grade 3 or greater adverse events, and serious adverse event. The investigators plan to begin patient enrollment in the fourth quarter of 2015.

Current industry partners include AstraZeneca, Bristol Myers Squibb, Eli Lilly, Genentech, and Pfizer.

The NCI-MATCH study is funded by the National Institutes of Health. Dr. Flaherty has received NIH research grants. Dr. Hudis disclosed ties to AstraZeneca, Sanofi-Aventis, Amgen, Bristol-Myers Squibb, Genentech, Eli Lilly, Novartis, Ortho Biotech, Pfizer, and Roche. Dr. Schilsky disclosed no relevant conflicts of interest.

CHICAGO – It’s getting very personal in oncology, and that’s a very good thing.

At the annual meeting of the American Society of Clinical Oncology, major cancer organizations announced new precision medicine initiatives that will attempt to match patients who have advanced cancers with the best available therapies based not on the location or histologic subtypes of their tumors, but on specific molecular abnormalities.

The National Cancer Institute’s Molecular Analysis for Therapy Choice (NCI-MATCH) trial will begin enrolling patients in July 2015. The study’s objective is “to understand the relative efficacy of the same therapy applied to oncogene-defined subsets across the entire cancer population as defined by site of origin or tumor histology,” said co–principal investigator Dr. Keith T. Flaherty of Harvard Medical School, Boston.

“This is the beginning, not the end, in terms of how we think about applying these therapies,” he said at a briefing that was held to announce the start of trial enrollment and a second initiative – the Targeted Agent and Profiling Utilization Registry (TAPUR) Study – by ASCO in cooperation with major pharmaceutical companies.

NCI-MATCH

NCI-MATCH is a phase II trial that will be operated through the National Clinical Trials Network. Oncologists at participating centers throughout the United States can enroll patients aged 18 years and older who have solid tumors or lymphomas that have relapsed or are refractory to conventional therapy, or who have a type of cancer for which no effective, consensus-based therapy is available.

Investigators plan to screen 3,000 patients initially, with the goal of enrolling 1,000 patients distributed among several substudies that will be evaluating specific drugs against specific molecular targets.

Patients will undergo biopsy at study entry, and their tumors will be subjected to genomic analysis to detect specific, targetable molecular abnormalities.

If a patient has a specific abnormality that is being explored in a current substudy, that patient will be further evaluated to determine whether he or she meets the eligibility criteria for that trial arm. Once enrolled, patients can remain on therapy until disease progression. The therapies will include both currently marketed agents and investigational therapies contributed by drug companies. Most of the trial arms will explore monotherapy with a targeted agent, but a few may investigate combinations which have accumulated enough safety and efficacy data to suggest that they might work against a specific molecular target.

The primary endpoint will be overall response rate, with a secondary endpoint of 6-month progression-free survival (PFS).

“This holds promise to bring faster cures to millions of Americans who so desperately need them,” ASCO past president Dr. Clifford A. Hudis said at the briefing.

TAPUR Trial

In cooperation with major pharmaceutical manufacturers (currently five, with more expected to sign on), ASCO has initiated a study designed to help answer the question, “I’ve got the tumor genome – now what do I do with it?”

The goal of the TAPUR trial, says ASCO Chief Medical Officer Dr. Richard Schilsky, is “to learn from the real world practice of prescribing targeted therapies to patients with advanced cancer whose tumor harbors a genomic variant known to be a drug target.”

The primary objectives are to describe the antitumor activity and toxicity profiles of targeted therapies, and to help patients get access to Food and Drug Administration–approved agents from which they may be able to benefit.

The trial will enroll patients with advanced solid tumors, B-cell non-Hodgkin’s lymphomas, and multiple myelomas for which there are no standard therapies. The patients must have adequate organ function and good performance status (0-2).

Patients will be matched by their personal physicians to specific therapies, if such a match exists; otherwise, they will be treated at the physician’s discretion.

The primary endpoint of the study will be overall response rates by Response Evaluation Criteria in Solid Tumors (RECIST). Secondary endpoints will be PFS, OS, time on treatment, grade 3 or greater adverse events, and serious adverse event. The investigators plan to begin patient enrollment in the fourth quarter of 2015.

Current industry partners include AstraZeneca, Bristol Myers Squibb, Eli Lilly, Genentech, and Pfizer.

The NCI-MATCH study is funded by the National Institutes of Health. Dr. Flaherty has received NIH research grants. Dr. Hudis disclosed ties to AstraZeneca, Sanofi-Aventis, Amgen, Bristol-Myers Squibb, Genentech, Eli Lilly, Novartis, Ortho Biotech, Pfizer, and Roche. Dr. Schilsky disclosed no relevant conflicts of interest.