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Ocular MALT lymphoma: Radiation reduces relapse
“Our study represents the largest institutional cohort analysis on the course of patients with stage I POAML,” said first author Linrui Gao, MD, of the department of radiation oncology at the National Clinical Research Center for Cancer, Chinese Academy of Medical Sciences and Peking Union Medical College, in Beijing.
Dr. Gao presented these findings at ESMO 2023, held in Madrid.
“We confirm the indolent nature of this stage I disease, with mortality that is similar to the general population and a low rate of lymphoma-attributed mortality,” she said, adding that “radiation therapy was associated with the lowest relapse or disease progression, compared with [other treatments].”
POAML, which can involve lesions in areas including the eyelid, conjunctiva, orbit, and lacrimal gland, makes up about 7% of mucosa-associated lymphoid tissue (MALT) lymphomas. However, the incidence is reported to be steadily increasing. With the majority of patients, 70%-85%, diagnosed as stage I, consensus on treatment approaches is lacking.
Guidelines typically recommend radiation therapy as the standard of care, and approximately 70% of POAML patients do receive the therapy, compared with only about 36% of those with early-stage MALT lymphoma, with the indolent nature of the disease likely weighing on decisions to forgo the treatment, Dr. Gao reported.
“Adoption of initial radiotherapy in early-stage POAML is relatively low worldwide, with possible reasons being [concerns] of a low survival benefit and long-term toxicities,” she said.
To evaluate the long-term outcomes based on baseline clinical features and treatments, Dr. Gao and colleagues conducted a retrospective study of 262 patients with stage I POAML (ipsilateral or bilateral disease), enrolled between January 2000 and December 2020 at two hospitals in China.
Of the patients, who had a median age of 55 and a male-female ratio of 1:3, 82 were initially treated with radiation therapy, 81 with observation, 70 with surgery, and 29 with systemic treatment.
Those receiving radiation therapy had higher rates of an Eastern Cooperative Oncology Group performance status of 1 or higher (P = .02), higher elevations of LDH (P = .03), and higher rates of chronic disease (P < .001), while other baseline characteristics between the groups, including age, T stage, symptom duration, and other factors, were similar.
With a median follow-up of 66 months, the 5-year and 10-year overall survival rates were 96.8% and 90%, respectively, which is similar to the survival rate in the general population in China.
Likewise, the 5- and 10-year rates of lymphoma-specific mortality were both extremely low, at 0.4%, and the corresponding rates of competing nonlymphoma mortality at 5 and 10 years were 2.3% and 4.2%, also consistent with the general population.
The 5- and 10-year mortality rates remained similar to the general population in stratifying patients according to the initial treatment type (P = .767 between treatments).
In terms of recurrence, the overall failure rates were relatively high, with 19.5% of patients experiencing relapse at 5 years and 24.05% at 10 years.
“The failure rates show that the risk of relapse in POAML does not decrease over time,” Dr. Gao said.
Notably, those treated with radiation therapy had a significantly decreased 5-year cumulative risk of failure (8.5%), compared with those who only received observation (29.6%), surgery (22.9%), or systemic treatment (17.2%; overall, P = .002).
The most common failure site was the ipsilateral orbit, and again, rates of those relapses were significantly lower with radiation therapy (2.4%), compared with observation (23.5%), surgery (21.4%), and systemic treatment (17.3%).
However, rates of relapses in other sites, including the contralateral orbit, extraocular site, and multiple sites, were similar among all treatment groups. One patient receiving systemic treatment had large cell transformation, associated with poorer outcomes.
Strategies after recurrence were salvage therapy for 53 patients, including 27 receiving radiation therapy, and observation for 10 patients.
Dr. Gao noted that treatment failure was not associated with higher mortality rates. “However, given the limited number of cases, we think more cases and longer follow-up are needed,” she told MDedge.
Among the most common acute toxicities were ocular dermatitis or mucositis, described as mild, among 23 patients receiving radiation therapy. Nine patients experienced postoperative complications of mild eye irritation and periorbital edema, and five patients receiving systemic treatment experienced grade 2-3 leukopenia. There were no severe adverse events.
In terms of late ocular adverse effects, overall, 3 patients in the radiation therapy group developed cataracts and 143 patients developed dry-eye disease.
“Radiation therapy was associated with the lowest rate of relapse progression, compared with observation, surgery, and systemic treatment, with similar overall and recurrent survival,” Dr. Gao said.
“Based on our study results, radiotherapy should be considered as the optimal treatment for all patients with stage I disease because of its lowest failure risk and minor toxicity,” Dr. Gao told MDedge.
“However, the radiotherapy dose and techniques should be further optimized in good clinical trials,” she noted. “There are some clinical studies undergoing to explore the modern radiotherapy strategy, including by our group.”
Commenting on the study, discussant Olivier Casasnovas, MD, PhD, of the department of hematology, University Hospital Francois Mitterrand, in Dijon, France, noted that “interestingly, radiotherapy reduced the risk of local relapse but not systemic relapse.”
Benefits linked to radiation therapy dose?
Furthermore, the study adds to evidence suggesting the role of dose in radiation therapy’s benefits in POAML, Dr. Casanovas noted. He pointed to previous research showing that, with a median radiotherapy dose of 26 Gy, stage I POAML patients had a local relapse rate of 9.5%, whereas in the current study, which reported a median radiotherapy dose of 30.6 Gy, the local relapse rate was just 2%.
“Regarding the risk of local relapse, it’s important to see that, as previous published, the risk of a local relapse depends probably on the dose of radiotherapy,” he said.
The results indicate that “radiation therapy could impact patients’ outcome. In comparison to previous research, this suggests benefits from a higher dose.”
He added that “it would be interesting to test in this series if patients receiving more or less 30 Gy had different outcomes or the risks of failure at different sites.”
Overall, the study confirms that POAML “can be safely treated with radiation therapy, which allows for a better chance of local control, compared with other options, but does not preclude relapse over time,” Dr. Casasnovas concluded, adding, “I think that a standardization of radiotherapy dose is warranted to provide guidelines to clinicians treating this infrequent population of patients.”
The authors had no disclosures to report.
“Our study represents the largest institutional cohort analysis on the course of patients with stage I POAML,” said first author Linrui Gao, MD, of the department of radiation oncology at the National Clinical Research Center for Cancer, Chinese Academy of Medical Sciences and Peking Union Medical College, in Beijing.
Dr. Gao presented these findings at ESMO 2023, held in Madrid.
“We confirm the indolent nature of this stage I disease, with mortality that is similar to the general population and a low rate of lymphoma-attributed mortality,” she said, adding that “radiation therapy was associated with the lowest relapse or disease progression, compared with [other treatments].”
POAML, which can involve lesions in areas including the eyelid, conjunctiva, orbit, and lacrimal gland, makes up about 7% of mucosa-associated lymphoid tissue (MALT) lymphomas. However, the incidence is reported to be steadily increasing. With the majority of patients, 70%-85%, diagnosed as stage I, consensus on treatment approaches is lacking.
Guidelines typically recommend radiation therapy as the standard of care, and approximately 70% of POAML patients do receive the therapy, compared with only about 36% of those with early-stage MALT lymphoma, with the indolent nature of the disease likely weighing on decisions to forgo the treatment, Dr. Gao reported.
“Adoption of initial radiotherapy in early-stage POAML is relatively low worldwide, with possible reasons being [concerns] of a low survival benefit and long-term toxicities,” she said.
To evaluate the long-term outcomes based on baseline clinical features and treatments, Dr. Gao and colleagues conducted a retrospective study of 262 patients with stage I POAML (ipsilateral or bilateral disease), enrolled between January 2000 and December 2020 at two hospitals in China.
Of the patients, who had a median age of 55 and a male-female ratio of 1:3, 82 were initially treated with radiation therapy, 81 with observation, 70 with surgery, and 29 with systemic treatment.
Those receiving radiation therapy had higher rates of an Eastern Cooperative Oncology Group performance status of 1 or higher (P = .02), higher elevations of LDH (P = .03), and higher rates of chronic disease (P < .001), while other baseline characteristics between the groups, including age, T stage, symptom duration, and other factors, were similar.
With a median follow-up of 66 months, the 5-year and 10-year overall survival rates were 96.8% and 90%, respectively, which is similar to the survival rate in the general population in China.
Likewise, the 5- and 10-year rates of lymphoma-specific mortality were both extremely low, at 0.4%, and the corresponding rates of competing nonlymphoma mortality at 5 and 10 years were 2.3% and 4.2%, also consistent with the general population.
The 5- and 10-year mortality rates remained similar to the general population in stratifying patients according to the initial treatment type (P = .767 between treatments).
In terms of recurrence, the overall failure rates were relatively high, with 19.5% of patients experiencing relapse at 5 years and 24.05% at 10 years.
“The failure rates show that the risk of relapse in POAML does not decrease over time,” Dr. Gao said.
Notably, those treated with radiation therapy had a significantly decreased 5-year cumulative risk of failure (8.5%), compared with those who only received observation (29.6%), surgery (22.9%), or systemic treatment (17.2%; overall, P = .002).
The most common failure site was the ipsilateral orbit, and again, rates of those relapses were significantly lower with radiation therapy (2.4%), compared with observation (23.5%), surgery (21.4%), and systemic treatment (17.3%).
However, rates of relapses in other sites, including the contralateral orbit, extraocular site, and multiple sites, were similar among all treatment groups. One patient receiving systemic treatment had large cell transformation, associated with poorer outcomes.
Strategies after recurrence were salvage therapy for 53 patients, including 27 receiving radiation therapy, and observation for 10 patients.
Dr. Gao noted that treatment failure was not associated with higher mortality rates. “However, given the limited number of cases, we think more cases and longer follow-up are needed,” she told MDedge.
Among the most common acute toxicities were ocular dermatitis or mucositis, described as mild, among 23 patients receiving radiation therapy. Nine patients experienced postoperative complications of mild eye irritation and periorbital edema, and five patients receiving systemic treatment experienced grade 2-3 leukopenia. There were no severe adverse events.
In terms of late ocular adverse effects, overall, 3 patients in the radiation therapy group developed cataracts and 143 patients developed dry-eye disease.
“Radiation therapy was associated with the lowest rate of relapse progression, compared with observation, surgery, and systemic treatment, with similar overall and recurrent survival,” Dr. Gao said.
“Based on our study results, radiotherapy should be considered as the optimal treatment for all patients with stage I disease because of its lowest failure risk and minor toxicity,” Dr. Gao told MDedge.
“However, the radiotherapy dose and techniques should be further optimized in good clinical trials,” she noted. “There are some clinical studies undergoing to explore the modern radiotherapy strategy, including by our group.”
Commenting on the study, discussant Olivier Casasnovas, MD, PhD, of the department of hematology, University Hospital Francois Mitterrand, in Dijon, France, noted that “interestingly, radiotherapy reduced the risk of local relapse but not systemic relapse.”
Benefits linked to radiation therapy dose?
Furthermore, the study adds to evidence suggesting the role of dose in radiation therapy’s benefits in POAML, Dr. Casanovas noted. He pointed to previous research showing that, with a median radiotherapy dose of 26 Gy, stage I POAML patients had a local relapse rate of 9.5%, whereas in the current study, which reported a median radiotherapy dose of 30.6 Gy, the local relapse rate was just 2%.
“Regarding the risk of local relapse, it’s important to see that, as previous published, the risk of a local relapse depends probably on the dose of radiotherapy,” he said.
The results indicate that “radiation therapy could impact patients’ outcome. In comparison to previous research, this suggests benefits from a higher dose.”
He added that “it would be interesting to test in this series if patients receiving more or less 30 Gy had different outcomes or the risks of failure at different sites.”
Overall, the study confirms that POAML “can be safely treated with radiation therapy, which allows for a better chance of local control, compared with other options, but does not preclude relapse over time,” Dr. Casasnovas concluded, adding, “I think that a standardization of radiotherapy dose is warranted to provide guidelines to clinicians treating this infrequent population of patients.”
The authors had no disclosures to report.
“Our study represents the largest institutional cohort analysis on the course of patients with stage I POAML,” said first author Linrui Gao, MD, of the department of radiation oncology at the National Clinical Research Center for Cancer, Chinese Academy of Medical Sciences and Peking Union Medical College, in Beijing.
Dr. Gao presented these findings at ESMO 2023, held in Madrid.
“We confirm the indolent nature of this stage I disease, with mortality that is similar to the general population and a low rate of lymphoma-attributed mortality,” she said, adding that “radiation therapy was associated with the lowest relapse or disease progression, compared with [other treatments].”
POAML, which can involve lesions in areas including the eyelid, conjunctiva, orbit, and lacrimal gland, makes up about 7% of mucosa-associated lymphoid tissue (MALT) lymphomas. However, the incidence is reported to be steadily increasing. With the majority of patients, 70%-85%, diagnosed as stage I, consensus on treatment approaches is lacking.
Guidelines typically recommend radiation therapy as the standard of care, and approximately 70% of POAML patients do receive the therapy, compared with only about 36% of those with early-stage MALT lymphoma, with the indolent nature of the disease likely weighing on decisions to forgo the treatment, Dr. Gao reported.
“Adoption of initial radiotherapy in early-stage POAML is relatively low worldwide, with possible reasons being [concerns] of a low survival benefit and long-term toxicities,” she said.
To evaluate the long-term outcomes based on baseline clinical features and treatments, Dr. Gao and colleagues conducted a retrospective study of 262 patients with stage I POAML (ipsilateral or bilateral disease), enrolled between January 2000 and December 2020 at two hospitals in China.
Of the patients, who had a median age of 55 and a male-female ratio of 1:3, 82 were initially treated with radiation therapy, 81 with observation, 70 with surgery, and 29 with systemic treatment.
Those receiving radiation therapy had higher rates of an Eastern Cooperative Oncology Group performance status of 1 or higher (P = .02), higher elevations of LDH (P = .03), and higher rates of chronic disease (P < .001), while other baseline characteristics between the groups, including age, T stage, symptom duration, and other factors, were similar.
With a median follow-up of 66 months, the 5-year and 10-year overall survival rates were 96.8% and 90%, respectively, which is similar to the survival rate in the general population in China.
Likewise, the 5- and 10-year rates of lymphoma-specific mortality were both extremely low, at 0.4%, and the corresponding rates of competing nonlymphoma mortality at 5 and 10 years were 2.3% and 4.2%, also consistent with the general population.
The 5- and 10-year mortality rates remained similar to the general population in stratifying patients according to the initial treatment type (P = .767 between treatments).
In terms of recurrence, the overall failure rates were relatively high, with 19.5% of patients experiencing relapse at 5 years and 24.05% at 10 years.
“The failure rates show that the risk of relapse in POAML does not decrease over time,” Dr. Gao said.
Notably, those treated with radiation therapy had a significantly decreased 5-year cumulative risk of failure (8.5%), compared with those who only received observation (29.6%), surgery (22.9%), or systemic treatment (17.2%; overall, P = .002).
The most common failure site was the ipsilateral orbit, and again, rates of those relapses were significantly lower with radiation therapy (2.4%), compared with observation (23.5%), surgery (21.4%), and systemic treatment (17.3%).
However, rates of relapses in other sites, including the contralateral orbit, extraocular site, and multiple sites, were similar among all treatment groups. One patient receiving systemic treatment had large cell transformation, associated with poorer outcomes.
Strategies after recurrence were salvage therapy for 53 patients, including 27 receiving radiation therapy, and observation for 10 patients.
Dr. Gao noted that treatment failure was not associated with higher mortality rates. “However, given the limited number of cases, we think more cases and longer follow-up are needed,” she told MDedge.
Among the most common acute toxicities were ocular dermatitis or mucositis, described as mild, among 23 patients receiving radiation therapy. Nine patients experienced postoperative complications of mild eye irritation and periorbital edema, and five patients receiving systemic treatment experienced grade 2-3 leukopenia. There were no severe adverse events.
In terms of late ocular adverse effects, overall, 3 patients in the radiation therapy group developed cataracts and 143 patients developed dry-eye disease.
“Radiation therapy was associated with the lowest rate of relapse progression, compared with observation, surgery, and systemic treatment, with similar overall and recurrent survival,” Dr. Gao said.
“Based on our study results, radiotherapy should be considered as the optimal treatment for all patients with stage I disease because of its lowest failure risk and minor toxicity,” Dr. Gao told MDedge.
“However, the radiotherapy dose and techniques should be further optimized in good clinical trials,” she noted. “There are some clinical studies undergoing to explore the modern radiotherapy strategy, including by our group.”
Commenting on the study, discussant Olivier Casasnovas, MD, PhD, of the department of hematology, University Hospital Francois Mitterrand, in Dijon, France, noted that “interestingly, radiotherapy reduced the risk of local relapse but not systemic relapse.”
Benefits linked to radiation therapy dose?
Furthermore, the study adds to evidence suggesting the role of dose in radiation therapy’s benefits in POAML, Dr. Casanovas noted. He pointed to previous research showing that, with a median radiotherapy dose of 26 Gy, stage I POAML patients had a local relapse rate of 9.5%, whereas in the current study, which reported a median radiotherapy dose of 30.6 Gy, the local relapse rate was just 2%.
“Regarding the risk of local relapse, it’s important to see that, as previous published, the risk of a local relapse depends probably on the dose of radiotherapy,” he said.
The results indicate that “radiation therapy could impact patients’ outcome. In comparison to previous research, this suggests benefits from a higher dose.”
He added that “it would be interesting to test in this series if patients receiving more or less 30 Gy had different outcomes or the risks of failure at different sites.”
Overall, the study confirms that POAML “can be safely treated with radiation therapy, which allows for a better chance of local control, compared with other options, but does not preclude relapse over time,” Dr. Casasnovas concluded, adding, “I think that a standardization of radiotherapy dose is warranted to provide guidelines to clinicians treating this infrequent population of patients.”
The authors had no disclosures to report.
FROM ESMO 2023
Nonsurgical option for more large thyroid nodule patients?
WASHINGTON – , compared with only those that were.
While more research is needed, “the risk of false negative FNA results for large nodules may not be as high as reported in previous studies if you include patients who do not have indication for surgery, such as compressive symptoms, suspicious ultrasound features, etc.,” senior author Tracy Tylee, MD, an associate professor of endocrinology at the University of Washington, Seattle, said in an interview.
The implication is that nonsurgical options such as radiofrequency ablation may be appropriate for more patients than realized, she added.
“Clinicians should consider following these patients more conservatively, either with a second FNA to confirm [the] nodule is benign or with ultrasound follow-up for 5 years with intervention only if [there are] significant changes on imaging,” she said.
The findings were presented at the annual meeting of the American Thyroid Association.
Concerns about nodules over 4 cm having high false negative rates
Management of large thyroid nodules over 4 cm that are classified as Bethesda II, indicative of being benign, is complicated by concerns of false negatives in such cases. While the false negative rate for thyroid nodules in general is approximately 3%, the rate for large nodules over 4 cm has been reported as high as 35%.
Importantly, however, most studies evaluating the issue only involve patients who have received thyroid surgery, whereas most benign nodules are not referred for surgery.
“This may overestimate the false negative FNA biopsy risk for this group,” first author Melbin Thomas, MD, also of the University of Washington, said in her talk.
To better assess the false negative rate in the broader context of large nodules that did and did not undergo surgery, Dr. Thomas and her colleagues conducted a retrospective chart review of all patients undergoing FNA biopsy at her center between 2008 and 2014 for thyroid nodules larger than 4 cm and initially classified as Bethesda II, or benign.
With a follow-up of up to 10 years, nodules were considered accurately benign if they showed benign pathology on surgical resection, if they remained benign based on repeat FNA biopsy with Bethesda II results, or if there were no changes on imaging characteristics on ultrasound after at least 2 years.
Overall, 47 nodules over 4 cm and Bethesda II cytology were included, with an average follow-up of 5 years (range 2.2-9.7 years).
Of the nodules, 23 were treated with surgery, two of which were determined to have been malignant (8.7%) and, hence, false negatives. Nine of the nodules had repeat FNA, with none found to be malignant, and 15 received repeat ultrasound, also with no malignancies.
Overall, the false negative rate including all patients was 4.3%.
“False negative FNA biopsy results were not markedly elevated if nodules greater than 4 cm are evaluated, but rates were considerably higher if limited to surgical patients,” Dr. Thomas said.
Clinicians may be compelled to perform more aggressive surgery on large but benign thyroid nodules for a number of reasons, Dr. Tylee noted.
“A concern is that we may discontinue follow-up on these larger nodules and fail to diagnose a cancer early on, before there has been extrathyroidal extension or lymph node metastases,” she said.
In such cases, patients could wind up presenting at a higher stage of disease and require more intensive therapy.
However, with a low false negative rate overall, “all of this can increase the long-term health care costs and anxiety for patients, so having a better understanding of the true benign rate for large nodules is important,” she concluded.
Commenting on the research, Rodis D. Paparodis, MD, chief of Endocrinology, Diabetes, and Metabolism Clinics, in Patras, Greece, said the findings underscore that, as a surgical procedure, “thyroidectomy should be used cautiously, only when the benefit outweighs the risk.”
In his own previous multicenter study, Dr. Paparodis conducted a review of nearly 2,500 thyroidectomies that were performed based on size or longterm slow growth despite preoperative benign FNA findings. The results showed that only 1.9% of patients had any form of thyroid cancer in the nodule that had led to surgery; however, multiple other significant cancers were often present in other locations in the gland.
“Therefore, we suggest that careful sonographic evaluation of all thyroid nodules is warranted prior to deciding and planning the extent of surgical management for multinodular goiter,” he told this news organization.
“In addition, FNA of all suspicious nodules is required as well, to avoid unnecessary surprises in surgical pathology.”
Dr. Tylee, Dr. Thomas, and Dr. Paparodis report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
WASHINGTON – , compared with only those that were.
While more research is needed, “the risk of false negative FNA results for large nodules may not be as high as reported in previous studies if you include patients who do not have indication for surgery, such as compressive symptoms, suspicious ultrasound features, etc.,” senior author Tracy Tylee, MD, an associate professor of endocrinology at the University of Washington, Seattle, said in an interview.
The implication is that nonsurgical options such as radiofrequency ablation may be appropriate for more patients than realized, she added.
“Clinicians should consider following these patients more conservatively, either with a second FNA to confirm [the] nodule is benign or with ultrasound follow-up for 5 years with intervention only if [there are] significant changes on imaging,” she said.
The findings were presented at the annual meeting of the American Thyroid Association.
Concerns about nodules over 4 cm having high false negative rates
Management of large thyroid nodules over 4 cm that are classified as Bethesda II, indicative of being benign, is complicated by concerns of false negatives in such cases. While the false negative rate for thyroid nodules in general is approximately 3%, the rate for large nodules over 4 cm has been reported as high as 35%.
Importantly, however, most studies evaluating the issue only involve patients who have received thyroid surgery, whereas most benign nodules are not referred for surgery.
“This may overestimate the false negative FNA biopsy risk for this group,” first author Melbin Thomas, MD, also of the University of Washington, said in her talk.
To better assess the false negative rate in the broader context of large nodules that did and did not undergo surgery, Dr. Thomas and her colleagues conducted a retrospective chart review of all patients undergoing FNA biopsy at her center between 2008 and 2014 for thyroid nodules larger than 4 cm and initially classified as Bethesda II, or benign.
With a follow-up of up to 10 years, nodules were considered accurately benign if they showed benign pathology on surgical resection, if they remained benign based on repeat FNA biopsy with Bethesda II results, or if there were no changes on imaging characteristics on ultrasound after at least 2 years.
Overall, 47 nodules over 4 cm and Bethesda II cytology were included, with an average follow-up of 5 years (range 2.2-9.7 years).
Of the nodules, 23 were treated with surgery, two of which were determined to have been malignant (8.7%) and, hence, false negatives. Nine of the nodules had repeat FNA, with none found to be malignant, and 15 received repeat ultrasound, also with no malignancies.
Overall, the false negative rate including all patients was 4.3%.
“False negative FNA biopsy results were not markedly elevated if nodules greater than 4 cm are evaluated, but rates were considerably higher if limited to surgical patients,” Dr. Thomas said.
Clinicians may be compelled to perform more aggressive surgery on large but benign thyroid nodules for a number of reasons, Dr. Tylee noted.
“A concern is that we may discontinue follow-up on these larger nodules and fail to diagnose a cancer early on, before there has been extrathyroidal extension or lymph node metastases,” she said.
In such cases, patients could wind up presenting at a higher stage of disease and require more intensive therapy.
However, with a low false negative rate overall, “all of this can increase the long-term health care costs and anxiety for patients, so having a better understanding of the true benign rate for large nodules is important,” she concluded.
Commenting on the research, Rodis D. Paparodis, MD, chief of Endocrinology, Diabetes, and Metabolism Clinics, in Patras, Greece, said the findings underscore that, as a surgical procedure, “thyroidectomy should be used cautiously, only when the benefit outweighs the risk.”
In his own previous multicenter study, Dr. Paparodis conducted a review of nearly 2,500 thyroidectomies that were performed based on size or longterm slow growth despite preoperative benign FNA findings. The results showed that only 1.9% of patients had any form of thyroid cancer in the nodule that had led to surgery; however, multiple other significant cancers were often present in other locations in the gland.
“Therefore, we suggest that careful sonographic evaluation of all thyroid nodules is warranted prior to deciding and planning the extent of surgical management for multinodular goiter,” he told this news organization.
“In addition, FNA of all suspicious nodules is required as well, to avoid unnecessary surprises in surgical pathology.”
Dr. Tylee, Dr. Thomas, and Dr. Paparodis report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
WASHINGTON – , compared with only those that were.
While more research is needed, “the risk of false negative FNA results for large nodules may not be as high as reported in previous studies if you include patients who do not have indication for surgery, such as compressive symptoms, suspicious ultrasound features, etc.,” senior author Tracy Tylee, MD, an associate professor of endocrinology at the University of Washington, Seattle, said in an interview.
The implication is that nonsurgical options such as radiofrequency ablation may be appropriate for more patients than realized, she added.
“Clinicians should consider following these patients more conservatively, either with a second FNA to confirm [the] nodule is benign or with ultrasound follow-up for 5 years with intervention only if [there are] significant changes on imaging,” she said.
The findings were presented at the annual meeting of the American Thyroid Association.
Concerns about nodules over 4 cm having high false negative rates
Management of large thyroid nodules over 4 cm that are classified as Bethesda II, indicative of being benign, is complicated by concerns of false negatives in such cases. While the false negative rate for thyroid nodules in general is approximately 3%, the rate for large nodules over 4 cm has been reported as high as 35%.
Importantly, however, most studies evaluating the issue only involve patients who have received thyroid surgery, whereas most benign nodules are not referred for surgery.
“This may overestimate the false negative FNA biopsy risk for this group,” first author Melbin Thomas, MD, also of the University of Washington, said in her talk.
To better assess the false negative rate in the broader context of large nodules that did and did not undergo surgery, Dr. Thomas and her colleagues conducted a retrospective chart review of all patients undergoing FNA biopsy at her center between 2008 and 2014 for thyroid nodules larger than 4 cm and initially classified as Bethesda II, or benign.
With a follow-up of up to 10 years, nodules were considered accurately benign if they showed benign pathology on surgical resection, if they remained benign based on repeat FNA biopsy with Bethesda II results, or if there were no changes on imaging characteristics on ultrasound after at least 2 years.
Overall, 47 nodules over 4 cm and Bethesda II cytology were included, with an average follow-up of 5 years (range 2.2-9.7 years).
Of the nodules, 23 were treated with surgery, two of which were determined to have been malignant (8.7%) and, hence, false negatives. Nine of the nodules had repeat FNA, with none found to be malignant, and 15 received repeat ultrasound, also with no malignancies.
Overall, the false negative rate including all patients was 4.3%.
“False negative FNA biopsy results were not markedly elevated if nodules greater than 4 cm are evaluated, but rates were considerably higher if limited to surgical patients,” Dr. Thomas said.
Clinicians may be compelled to perform more aggressive surgery on large but benign thyroid nodules for a number of reasons, Dr. Tylee noted.
“A concern is that we may discontinue follow-up on these larger nodules and fail to diagnose a cancer early on, before there has been extrathyroidal extension or lymph node metastases,” she said.
In such cases, patients could wind up presenting at a higher stage of disease and require more intensive therapy.
However, with a low false negative rate overall, “all of this can increase the long-term health care costs and anxiety for patients, so having a better understanding of the true benign rate for large nodules is important,” she concluded.
Commenting on the research, Rodis D. Paparodis, MD, chief of Endocrinology, Diabetes, and Metabolism Clinics, in Patras, Greece, said the findings underscore that, as a surgical procedure, “thyroidectomy should be used cautiously, only when the benefit outweighs the risk.”
In his own previous multicenter study, Dr. Paparodis conducted a review of nearly 2,500 thyroidectomies that were performed based on size or longterm slow growth despite preoperative benign FNA findings. The results showed that only 1.9% of patients had any form of thyroid cancer in the nodule that had led to surgery; however, multiple other significant cancers were often present in other locations in the gland.
“Therefore, we suggest that careful sonographic evaluation of all thyroid nodules is warranted prior to deciding and planning the extent of surgical management for multinodular goiter,” he told this news organization.
“In addition, FNA of all suspicious nodules is required as well, to avoid unnecessary surprises in surgical pathology.”
Dr. Tylee, Dr. Thomas, and Dr. Paparodis report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ATA 2023
Thyroid cancer increase observed in transgender female veterans
WASHINGTON – Experts urge a cautious interpretation of these recent study results.
“In our clinic of about 50 transgender women, we noticed that we had two diagnosed cases of thyroid cancer in a year,” first author John Christensen, MD, of UC Davis Health, division of endocrinology, diabetes & metabolism, Sacramento, said in an interivew. He presented their findings at the annual meeting of the American Thyroid Association.
Comparatively, the thyroid cancer prevalence among cisgender male veterans is estimated at about 0.19%; the rate among all those assigned male at birth in the general population is 0.13%, whereas the rate among those assigned female at birth, which has historically been higher for all thyroid cancer subtypes, is 0.44%, according to U.S. cancer statistics for 2020 from the National Cancer Institute.
“About one-third of our [veteran] patients had been receiving estrogen for an average of over 3 years before diagnosis, which could suggest estrogen gender‐affirming hormone therapy [GAHT] may be a potentially important risk factor,” Dr. Christensen said.
Sustained use of external estrogen, especially in cisgender women undergoing fertility treatments, has been linked to an increased risk for thyroid cancer. This is because it can lead to an increase in estrogen receptors in cancerous cells. But experts caution that many other factors also come into play.
“There is definitely an implication that if you give extra estrogen to someone assigned female at birth, you may have an increased risk of thyroid cancer,” Dr. Christensen said. “So, it would stand to reason that even in those who are not assigned female at birth, there may be a risk from exogenous estrogen that may lead to an increased risk of thyroid cancer down the line.”
To investigate the issue in a larger population, Dr. Christensen and colleagues evaluated data from the comprehensive, nationwide Veterans Affairs Informatics and Computing Infrastructure database, including approximately 9 million veterans who had outpatient visits between December 2017 and January 2022.
Of the veterans, 9,988 were determined to likely be transgender women, based on either having an ICD-10 diagnosis code for gender dysphoria or being assigned male at birth and having received an estrogen or estradiol prescription.
Of those patients, 76 had an ICD-10 code indicating thyroid cancer and 34 had verification of the thyroid cancer on chart review, representing a prevalence of 0.34% among transgender female veterans.
The average age at thyroid cancer diagnosis among the veterans was 53.8 years, and 29.4% (10 of 34) of those patients had extrathyroidal disease at the time of their thyroid cancer diagnosis. The median body mass index, available for 26 patients, was 32, which is indicative of obesity.
In terms of the patients’ thyroid cancer subtypes, 22 were papillary cancer, 5 were a follicular variant of papillary cancer, 5 were both papillary and follicular cancer, 4 were follicular cancer, 3 were a Hürthle cell variant of follicular cancer, and one was unknown.
Among 11 (32.3%) of the 34 veterans receiving estrogen GAHT at diagnosis, treatment began an average of 3.38 years prior to diagnosis at variable doses and using various routes of administration.
About half of the patients had a history of smoking; however, Dr. Christensen noted that the role of smoking as being a risk factor in estrogenic cancers has been debated. Though most patients were obese, obesity is both very common and not well established in terms of its quantitative impact on the risk for cancer development.
With the small size of the thyroid cancer cohort and omissions in the medical record among the study’s important limitations, Dr. Christensen urged a cautious interpretation of the findings.
“We are certainly suspicious that GAHT may be associated with an increased risk of thyroid cancer, but I would characterize the trends in our data as being potentially suggestive or hypothesis generating – not conclusive,” he added. “I would hate for any transgender women reading this to stop taking GAHT without talking to their doctors first.”
Commenting on the issue, Maurice Garcia, MD, a clinical associate professor of urology and director of the transgender surgery and health program at Cedars-Sinai Medical Center, Los Angeles, said that any definitive evidence of an increase in cancer risk among transgender people is lacking.
“With an estimated 1.5 [million] to 1.6 million people in the U.S. who are transgender, with many of them receiving GAHT, we haven’t observed a bump or high incidence of any kind of cancer among these people so far,” he said.
“There’s certainly a high potential that hormone therapy, whether it’s feminizing or masculinizing hormone therapy, can affect an individual’s cancer risk,” he added. “But we don’t know of any [definitive evidence] yet of an increase, and, there’s also even the question of whether there could be an opposite effect.”
Regarding the thyroid cancer data, Dr. Garcia agreed that the preliminary nature of the study is a key limitation. “It’s hard to tell if these were comparable groups, or whether those in the transgender group came in with higher risk factors for thyroid cancer.
“Until more statistical analysis is done, I think all that can be said is that it’s speculative.”
Dr. Garcia, who coauthored a review on cancer screening for transgender individuals, underscored that, despite a lack of data suggesting that transgender patients need cancer screening any more than their matched cisgender counterparts, “the point is that we cannot forget to screen them at all.”
Dr. Christensen and Dr. Garcia had no disclosures to report.
A version of this article first appeared on Medscape.com.
WASHINGTON – Experts urge a cautious interpretation of these recent study results.
“In our clinic of about 50 transgender women, we noticed that we had two diagnosed cases of thyroid cancer in a year,” first author John Christensen, MD, of UC Davis Health, division of endocrinology, diabetes & metabolism, Sacramento, said in an interivew. He presented their findings at the annual meeting of the American Thyroid Association.
Comparatively, the thyroid cancer prevalence among cisgender male veterans is estimated at about 0.19%; the rate among all those assigned male at birth in the general population is 0.13%, whereas the rate among those assigned female at birth, which has historically been higher for all thyroid cancer subtypes, is 0.44%, according to U.S. cancer statistics for 2020 from the National Cancer Institute.
“About one-third of our [veteran] patients had been receiving estrogen for an average of over 3 years before diagnosis, which could suggest estrogen gender‐affirming hormone therapy [GAHT] may be a potentially important risk factor,” Dr. Christensen said.
Sustained use of external estrogen, especially in cisgender women undergoing fertility treatments, has been linked to an increased risk for thyroid cancer. This is because it can lead to an increase in estrogen receptors in cancerous cells. But experts caution that many other factors also come into play.
“There is definitely an implication that if you give extra estrogen to someone assigned female at birth, you may have an increased risk of thyroid cancer,” Dr. Christensen said. “So, it would stand to reason that even in those who are not assigned female at birth, there may be a risk from exogenous estrogen that may lead to an increased risk of thyroid cancer down the line.”
To investigate the issue in a larger population, Dr. Christensen and colleagues evaluated data from the comprehensive, nationwide Veterans Affairs Informatics and Computing Infrastructure database, including approximately 9 million veterans who had outpatient visits between December 2017 and January 2022.
Of the veterans, 9,988 were determined to likely be transgender women, based on either having an ICD-10 diagnosis code for gender dysphoria or being assigned male at birth and having received an estrogen or estradiol prescription.
Of those patients, 76 had an ICD-10 code indicating thyroid cancer and 34 had verification of the thyroid cancer on chart review, representing a prevalence of 0.34% among transgender female veterans.
The average age at thyroid cancer diagnosis among the veterans was 53.8 years, and 29.4% (10 of 34) of those patients had extrathyroidal disease at the time of their thyroid cancer diagnosis. The median body mass index, available for 26 patients, was 32, which is indicative of obesity.
In terms of the patients’ thyroid cancer subtypes, 22 were papillary cancer, 5 were a follicular variant of papillary cancer, 5 were both papillary and follicular cancer, 4 were follicular cancer, 3 were a Hürthle cell variant of follicular cancer, and one was unknown.
Among 11 (32.3%) of the 34 veterans receiving estrogen GAHT at diagnosis, treatment began an average of 3.38 years prior to diagnosis at variable doses and using various routes of administration.
About half of the patients had a history of smoking; however, Dr. Christensen noted that the role of smoking as being a risk factor in estrogenic cancers has been debated. Though most patients were obese, obesity is both very common and not well established in terms of its quantitative impact on the risk for cancer development.
With the small size of the thyroid cancer cohort and omissions in the medical record among the study’s important limitations, Dr. Christensen urged a cautious interpretation of the findings.
“We are certainly suspicious that GAHT may be associated with an increased risk of thyroid cancer, but I would characterize the trends in our data as being potentially suggestive or hypothesis generating – not conclusive,” he added. “I would hate for any transgender women reading this to stop taking GAHT without talking to their doctors first.”
Commenting on the issue, Maurice Garcia, MD, a clinical associate professor of urology and director of the transgender surgery and health program at Cedars-Sinai Medical Center, Los Angeles, said that any definitive evidence of an increase in cancer risk among transgender people is lacking.
“With an estimated 1.5 [million] to 1.6 million people in the U.S. who are transgender, with many of them receiving GAHT, we haven’t observed a bump or high incidence of any kind of cancer among these people so far,” he said.
“There’s certainly a high potential that hormone therapy, whether it’s feminizing or masculinizing hormone therapy, can affect an individual’s cancer risk,” he added. “But we don’t know of any [definitive evidence] yet of an increase, and, there’s also even the question of whether there could be an opposite effect.”
Regarding the thyroid cancer data, Dr. Garcia agreed that the preliminary nature of the study is a key limitation. “It’s hard to tell if these were comparable groups, or whether those in the transgender group came in with higher risk factors for thyroid cancer.
“Until more statistical analysis is done, I think all that can be said is that it’s speculative.”
Dr. Garcia, who coauthored a review on cancer screening for transgender individuals, underscored that, despite a lack of data suggesting that transgender patients need cancer screening any more than their matched cisgender counterparts, “the point is that we cannot forget to screen them at all.”
Dr. Christensen and Dr. Garcia had no disclosures to report.
A version of this article first appeared on Medscape.com.
WASHINGTON – Experts urge a cautious interpretation of these recent study results.
“In our clinic of about 50 transgender women, we noticed that we had two diagnosed cases of thyroid cancer in a year,” first author John Christensen, MD, of UC Davis Health, division of endocrinology, diabetes & metabolism, Sacramento, said in an interivew. He presented their findings at the annual meeting of the American Thyroid Association.
Comparatively, the thyroid cancer prevalence among cisgender male veterans is estimated at about 0.19%; the rate among all those assigned male at birth in the general population is 0.13%, whereas the rate among those assigned female at birth, which has historically been higher for all thyroid cancer subtypes, is 0.44%, according to U.S. cancer statistics for 2020 from the National Cancer Institute.
“About one-third of our [veteran] patients had been receiving estrogen for an average of over 3 years before diagnosis, which could suggest estrogen gender‐affirming hormone therapy [GAHT] may be a potentially important risk factor,” Dr. Christensen said.
Sustained use of external estrogen, especially in cisgender women undergoing fertility treatments, has been linked to an increased risk for thyroid cancer. This is because it can lead to an increase in estrogen receptors in cancerous cells. But experts caution that many other factors also come into play.
“There is definitely an implication that if you give extra estrogen to someone assigned female at birth, you may have an increased risk of thyroid cancer,” Dr. Christensen said. “So, it would stand to reason that even in those who are not assigned female at birth, there may be a risk from exogenous estrogen that may lead to an increased risk of thyroid cancer down the line.”
To investigate the issue in a larger population, Dr. Christensen and colleagues evaluated data from the comprehensive, nationwide Veterans Affairs Informatics and Computing Infrastructure database, including approximately 9 million veterans who had outpatient visits between December 2017 and January 2022.
Of the veterans, 9,988 were determined to likely be transgender women, based on either having an ICD-10 diagnosis code for gender dysphoria or being assigned male at birth and having received an estrogen or estradiol prescription.
Of those patients, 76 had an ICD-10 code indicating thyroid cancer and 34 had verification of the thyroid cancer on chart review, representing a prevalence of 0.34% among transgender female veterans.
The average age at thyroid cancer diagnosis among the veterans was 53.8 years, and 29.4% (10 of 34) of those patients had extrathyroidal disease at the time of their thyroid cancer diagnosis. The median body mass index, available for 26 patients, was 32, which is indicative of obesity.
In terms of the patients’ thyroid cancer subtypes, 22 were papillary cancer, 5 were a follicular variant of papillary cancer, 5 were both papillary and follicular cancer, 4 were follicular cancer, 3 were a Hürthle cell variant of follicular cancer, and one was unknown.
Among 11 (32.3%) of the 34 veterans receiving estrogen GAHT at diagnosis, treatment began an average of 3.38 years prior to diagnosis at variable doses and using various routes of administration.
About half of the patients had a history of smoking; however, Dr. Christensen noted that the role of smoking as being a risk factor in estrogenic cancers has been debated. Though most patients were obese, obesity is both very common and not well established in terms of its quantitative impact on the risk for cancer development.
With the small size of the thyroid cancer cohort and omissions in the medical record among the study’s important limitations, Dr. Christensen urged a cautious interpretation of the findings.
“We are certainly suspicious that GAHT may be associated with an increased risk of thyroid cancer, but I would characterize the trends in our data as being potentially suggestive or hypothesis generating – not conclusive,” he added. “I would hate for any transgender women reading this to stop taking GAHT without talking to their doctors first.”
Commenting on the issue, Maurice Garcia, MD, a clinical associate professor of urology and director of the transgender surgery and health program at Cedars-Sinai Medical Center, Los Angeles, said that any definitive evidence of an increase in cancer risk among transgender people is lacking.
“With an estimated 1.5 [million] to 1.6 million people in the U.S. who are transgender, with many of them receiving GAHT, we haven’t observed a bump or high incidence of any kind of cancer among these people so far,” he said.
“There’s certainly a high potential that hormone therapy, whether it’s feminizing or masculinizing hormone therapy, can affect an individual’s cancer risk,” he added. “But we don’t know of any [definitive evidence] yet of an increase, and, there’s also even the question of whether there could be an opposite effect.”
Regarding the thyroid cancer data, Dr. Garcia agreed that the preliminary nature of the study is a key limitation. “It’s hard to tell if these were comparable groups, or whether those in the transgender group came in with higher risk factors for thyroid cancer.
“Until more statistical analysis is done, I think all that can be said is that it’s speculative.”
Dr. Garcia, who coauthored a review on cancer screening for transgender individuals, underscored that, despite a lack of data suggesting that transgender patients need cancer screening any more than their matched cisgender counterparts, “the point is that we cannot forget to screen them at all.”
Dr. Christensen and Dr. Garcia had no disclosures to report.
A version of this article first appeared on Medscape.com.
AT ATA 2023
Hold blood thinners during thyroid nodule biopsy?
WASHINGTON – The routine practice of holding use of blood-thinning medications at the time of an ultrasound-guided thyroid nodule fine needle aspiration (FNA) biopsy shows no significant safety benefit in preventing the risk of complications such as hematomas or nondiagnostic results; however, experts suggest using individualized decision-making with the practice.
first author Michelle Lundholm, MD, of the Cleveland Clinic said in an interview.
“[The practice] impacts neither the safety of the FNA procedure nor the adequacy of the sample,” she said.
The late-breaking research was presented at the annual meeting of the American Thyroid Association.
Key concerns in the use of anticoagulants and/or antiplatelet medications during thyroid nodule FNA biopsy include the increased risk of postprocedural hematoma or nondiagnostic results, with, for instance, one study showing higher rates of nondiagnostic results among patients remaining on aspirin therapy during the FNA biopsy.
However, holding the medically indicated therapies can have risks of its own, including concerns of thrombotic events such as deep vein thrombosis or stroke. However, evidence comparing the risks with each strategy in thyroid nodule FNA is lacking.
To investigate, Dr. Lundholm and colleagues conducted a review of data on 2,945 patients who had undergone a total of 4,741 thyroid nodule FNAs in the Cleveland Clinic’s diverse network of centers between 2010 and 2023. The patients had a mean age of 66.2; 69.6% were female and 75.7% were White.
All patients had an active prescription for an anticoagulant or antiplatelet medication up to 10 days prior to their thyroid nodule FNA biopsy. Specifically, 73.7% were on 81 mg aspirin, 8.5% were on 325 mg aspirin, 7.4% were taking other antiplatelet medication such as clopidogrel or ticagrelor; 7.0% were on warfarin, 8.2% were on a direct oral anticoagulant (DOAC); 6.3% were on heparin products; and 10.3% of patients were on two or more blood-thinning medications.
The results show that, overall, 13.0% (n = 614) of the thyroid nodule FNA biopsies had nondiagnostic results, which is within the average rates in the literature ranging from 6% to 36%, Dr. Lundholm noted.
Blood-thinning medications were held in 20.8% of the FNA biopsies, however, there were no differences in nondiagnostic results between those who had drugs held (12.2%) or who continued on the medications (13.2%; P = .41).
After multivariate adjustment for age and sex, the lack of significant differences in receiving nondiagnostic results among those who did or did not continue blood thinners was consistent overall (odds ratio, 1.10; P = .38), and in the specific groups of 81 mg aspirin (OR, 1.00; P = .99); 325 mg aspirin or clopidogrel/ticagrelor (OR, 1.50; P = .15); or warfarin, DOAC, or heparin/enoxaparin (OR, 1.27; P = .27).
In terms of hematoma risk, ED records within 48 hours of the FNA showed that such events were rare, with only one hematoma occurring overall, involving a patient who was on 81 mg of aspirin for secondary stroke prevention that was not interrupted for FNA biopsy. The patient was discharged and did not require medical intervention.
Four other hematomas occurred among patients who were not being treated with blood thinners, with none requiring intervention.
The findings indicate that “hematoma can happen in any patient, but rarely requires intervention,” Dr. Lundholm said.
However, while thrombotic events were also rare, serious events occurred in three patients within 48 hours of the thyroid nodule FNA biopsy when a blood thinner was withheld, including ischemic strokes among two patients who were on a DOAC and 81 mg of aspirin that were withheld, and one MI occurring in a patient on a DOAC that was held for the FNA.
Unlike hematomas, the thrombotic events each had significant long‐term sequelae, Dr. Lundholm noted.
“Having these ischemic strokes and heart attack really led to a change in these patients’ lives,” she said. “While we can never assume that [the events occurred] because the blood-thinner therapy was held, the timing within 48 hours is certainly very suspicious.”
There were no deep vein thrombosis or pulmonary embolism events.
Withholding practices vary
In a previous survey of 60 clinicians conducted by Dr. Lundholm and colleagues, wide variation was reported in the rates of withholding antiplatelet or anticoagulant medications prior to thyroid nodule FNA biopsy.
The survey of endocrinologists, interventional radiologists, and ear, nose, and throat providers showed rates of withholding 81 mg of aspirin prior to FNA biopsy of just 13.3%, withholding 325 mg of aspirin, 15%, other antiplatelets, 41.7%, warfarin, 73.3%, DOACs, 43.3%, and heparin, 43.3%.
“We found heterogeneity in withholding patterns even within the same department,” she said. “This is reflective of the fact that evidence is mixed.”
Guidelines on the issue from the Society of Interventional Radiology and the International Society on Thrombosis and Hemostasis recommend that providers consider the balance of the procedure and patient bleeding risk versus the clotting risk, Dr. Lundholm noted.
However, a caveat is that those recommendations are based on pooled data from similar minimal risk procedures, she explained.
“There is a lack of data on bleeding risks for individual interventions like thyroid biopsy, and, as such, there is no specific procedure-related risk determination.”
Meanwhile, Dr. Lundholm said that notable limitations regarding the current research include that the study may not have caught all patient cases that presented with complications to an outside ED.
Furthermore, the study results pertain to the safety of blood thinners in routine use, with key aspects that can influence complication rates, such as provider experience, needle size, and nodule features unavailable for analysis.
At MD Anderson, case-by-case
Commenting on the research, Anastasios Maniakas, MD, PhD, of the department of head and neck surgery, division of surgery, University of Texas MD Anderson Cancer Center, Houston, said the study is important, noting that, at his institution, the approach regarding holding blood-thinning medications is generally determined on an individual basis.
“I think this was a good study, but I don’t think it’s practice changing because these decisions may differ on a case-by-case basis,” Dr. Maniakas, who comoderated the session, said in an interview.
“At MD Anderson, we probably have one of the highest volumes in the country for thyroid nodule FNAs, and we do hold blood thinners because we often have to do more significant biopsies, with multiple passages and larger needles to be used,” Dr. Maniakas said.
“If you’re going to use perhaps the smallest possible gauge needle, then I think it is reasonable to not hold blood thinners, but if you’re going to be doing multiple passages and you need to do a core biopsy and use a large needle, then it is wiser to try to hold the medications for a day or 2.
“We haven’t had any complications, but I think there’s still a lot of apprehension to not hold blood thinners,” Dr. Maniakas said. “So, overall, I think the message is that it has to be on a case-by-case basis.”
Dr. Lundholm and Dr. Maniakas reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
WASHINGTON – The routine practice of holding use of blood-thinning medications at the time of an ultrasound-guided thyroid nodule fine needle aspiration (FNA) biopsy shows no significant safety benefit in preventing the risk of complications such as hematomas or nondiagnostic results; however, experts suggest using individualized decision-making with the practice.
first author Michelle Lundholm, MD, of the Cleveland Clinic said in an interview.
“[The practice] impacts neither the safety of the FNA procedure nor the adequacy of the sample,” she said.
The late-breaking research was presented at the annual meeting of the American Thyroid Association.
Key concerns in the use of anticoagulants and/or antiplatelet medications during thyroid nodule FNA biopsy include the increased risk of postprocedural hematoma or nondiagnostic results, with, for instance, one study showing higher rates of nondiagnostic results among patients remaining on aspirin therapy during the FNA biopsy.
However, holding the medically indicated therapies can have risks of its own, including concerns of thrombotic events such as deep vein thrombosis or stroke. However, evidence comparing the risks with each strategy in thyroid nodule FNA is lacking.
To investigate, Dr. Lundholm and colleagues conducted a review of data on 2,945 patients who had undergone a total of 4,741 thyroid nodule FNAs in the Cleveland Clinic’s diverse network of centers between 2010 and 2023. The patients had a mean age of 66.2; 69.6% were female and 75.7% were White.
All patients had an active prescription for an anticoagulant or antiplatelet medication up to 10 days prior to their thyroid nodule FNA biopsy. Specifically, 73.7% were on 81 mg aspirin, 8.5% were on 325 mg aspirin, 7.4% were taking other antiplatelet medication such as clopidogrel or ticagrelor; 7.0% were on warfarin, 8.2% were on a direct oral anticoagulant (DOAC); 6.3% were on heparin products; and 10.3% of patients were on two or more blood-thinning medications.
The results show that, overall, 13.0% (n = 614) of the thyroid nodule FNA biopsies had nondiagnostic results, which is within the average rates in the literature ranging from 6% to 36%, Dr. Lundholm noted.
Blood-thinning medications were held in 20.8% of the FNA biopsies, however, there were no differences in nondiagnostic results between those who had drugs held (12.2%) or who continued on the medications (13.2%; P = .41).
After multivariate adjustment for age and sex, the lack of significant differences in receiving nondiagnostic results among those who did or did not continue blood thinners was consistent overall (odds ratio, 1.10; P = .38), and in the specific groups of 81 mg aspirin (OR, 1.00; P = .99); 325 mg aspirin or clopidogrel/ticagrelor (OR, 1.50; P = .15); or warfarin, DOAC, or heparin/enoxaparin (OR, 1.27; P = .27).
In terms of hematoma risk, ED records within 48 hours of the FNA showed that such events were rare, with only one hematoma occurring overall, involving a patient who was on 81 mg of aspirin for secondary stroke prevention that was not interrupted for FNA biopsy. The patient was discharged and did not require medical intervention.
Four other hematomas occurred among patients who were not being treated with blood thinners, with none requiring intervention.
The findings indicate that “hematoma can happen in any patient, but rarely requires intervention,” Dr. Lundholm said.
However, while thrombotic events were also rare, serious events occurred in three patients within 48 hours of the thyroid nodule FNA biopsy when a blood thinner was withheld, including ischemic strokes among two patients who were on a DOAC and 81 mg of aspirin that were withheld, and one MI occurring in a patient on a DOAC that was held for the FNA.
Unlike hematomas, the thrombotic events each had significant long‐term sequelae, Dr. Lundholm noted.
“Having these ischemic strokes and heart attack really led to a change in these patients’ lives,” she said. “While we can never assume that [the events occurred] because the blood-thinner therapy was held, the timing within 48 hours is certainly very suspicious.”
There were no deep vein thrombosis or pulmonary embolism events.
Withholding practices vary
In a previous survey of 60 clinicians conducted by Dr. Lundholm and colleagues, wide variation was reported in the rates of withholding antiplatelet or anticoagulant medications prior to thyroid nodule FNA biopsy.
The survey of endocrinologists, interventional radiologists, and ear, nose, and throat providers showed rates of withholding 81 mg of aspirin prior to FNA biopsy of just 13.3%, withholding 325 mg of aspirin, 15%, other antiplatelets, 41.7%, warfarin, 73.3%, DOACs, 43.3%, and heparin, 43.3%.
“We found heterogeneity in withholding patterns even within the same department,” she said. “This is reflective of the fact that evidence is mixed.”
Guidelines on the issue from the Society of Interventional Radiology and the International Society on Thrombosis and Hemostasis recommend that providers consider the balance of the procedure and patient bleeding risk versus the clotting risk, Dr. Lundholm noted.
However, a caveat is that those recommendations are based on pooled data from similar minimal risk procedures, she explained.
“There is a lack of data on bleeding risks for individual interventions like thyroid biopsy, and, as such, there is no specific procedure-related risk determination.”
Meanwhile, Dr. Lundholm said that notable limitations regarding the current research include that the study may not have caught all patient cases that presented with complications to an outside ED.
Furthermore, the study results pertain to the safety of blood thinners in routine use, with key aspects that can influence complication rates, such as provider experience, needle size, and nodule features unavailable for analysis.
At MD Anderson, case-by-case
Commenting on the research, Anastasios Maniakas, MD, PhD, of the department of head and neck surgery, division of surgery, University of Texas MD Anderson Cancer Center, Houston, said the study is important, noting that, at his institution, the approach regarding holding blood-thinning medications is generally determined on an individual basis.
“I think this was a good study, but I don’t think it’s practice changing because these decisions may differ on a case-by-case basis,” Dr. Maniakas, who comoderated the session, said in an interview.
“At MD Anderson, we probably have one of the highest volumes in the country for thyroid nodule FNAs, and we do hold blood thinners because we often have to do more significant biopsies, with multiple passages and larger needles to be used,” Dr. Maniakas said.
“If you’re going to use perhaps the smallest possible gauge needle, then I think it is reasonable to not hold blood thinners, but if you’re going to be doing multiple passages and you need to do a core biopsy and use a large needle, then it is wiser to try to hold the medications for a day or 2.
“We haven’t had any complications, but I think there’s still a lot of apprehension to not hold blood thinners,” Dr. Maniakas said. “So, overall, I think the message is that it has to be on a case-by-case basis.”
Dr. Lundholm and Dr. Maniakas reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
WASHINGTON – The routine practice of holding use of blood-thinning medications at the time of an ultrasound-guided thyroid nodule fine needle aspiration (FNA) biopsy shows no significant safety benefit in preventing the risk of complications such as hematomas or nondiagnostic results; however, experts suggest using individualized decision-making with the practice.
first author Michelle Lundholm, MD, of the Cleveland Clinic said in an interview.
“[The practice] impacts neither the safety of the FNA procedure nor the adequacy of the sample,” she said.
The late-breaking research was presented at the annual meeting of the American Thyroid Association.
Key concerns in the use of anticoagulants and/or antiplatelet medications during thyroid nodule FNA biopsy include the increased risk of postprocedural hematoma or nondiagnostic results, with, for instance, one study showing higher rates of nondiagnostic results among patients remaining on aspirin therapy during the FNA biopsy.
However, holding the medically indicated therapies can have risks of its own, including concerns of thrombotic events such as deep vein thrombosis or stroke. However, evidence comparing the risks with each strategy in thyroid nodule FNA is lacking.
To investigate, Dr. Lundholm and colleagues conducted a review of data on 2,945 patients who had undergone a total of 4,741 thyroid nodule FNAs in the Cleveland Clinic’s diverse network of centers between 2010 and 2023. The patients had a mean age of 66.2; 69.6% were female and 75.7% were White.
All patients had an active prescription for an anticoagulant or antiplatelet medication up to 10 days prior to their thyroid nodule FNA biopsy. Specifically, 73.7% were on 81 mg aspirin, 8.5% were on 325 mg aspirin, 7.4% were taking other antiplatelet medication such as clopidogrel or ticagrelor; 7.0% were on warfarin, 8.2% were on a direct oral anticoagulant (DOAC); 6.3% were on heparin products; and 10.3% of patients were on two or more blood-thinning medications.
The results show that, overall, 13.0% (n = 614) of the thyroid nodule FNA biopsies had nondiagnostic results, which is within the average rates in the literature ranging from 6% to 36%, Dr. Lundholm noted.
Blood-thinning medications were held in 20.8% of the FNA biopsies, however, there were no differences in nondiagnostic results between those who had drugs held (12.2%) or who continued on the medications (13.2%; P = .41).
After multivariate adjustment for age and sex, the lack of significant differences in receiving nondiagnostic results among those who did or did not continue blood thinners was consistent overall (odds ratio, 1.10; P = .38), and in the specific groups of 81 mg aspirin (OR, 1.00; P = .99); 325 mg aspirin or clopidogrel/ticagrelor (OR, 1.50; P = .15); or warfarin, DOAC, or heparin/enoxaparin (OR, 1.27; P = .27).
In terms of hematoma risk, ED records within 48 hours of the FNA showed that such events were rare, with only one hematoma occurring overall, involving a patient who was on 81 mg of aspirin for secondary stroke prevention that was not interrupted for FNA biopsy. The patient was discharged and did not require medical intervention.
Four other hematomas occurred among patients who were not being treated with blood thinners, with none requiring intervention.
The findings indicate that “hematoma can happen in any patient, but rarely requires intervention,” Dr. Lundholm said.
However, while thrombotic events were also rare, serious events occurred in three patients within 48 hours of the thyroid nodule FNA biopsy when a blood thinner was withheld, including ischemic strokes among two patients who were on a DOAC and 81 mg of aspirin that were withheld, and one MI occurring in a patient on a DOAC that was held for the FNA.
Unlike hematomas, the thrombotic events each had significant long‐term sequelae, Dr. Lundholm noted.
“Having these ischemic strokes and heart attack really led to a change in these patients’ lives,” she said. “While we can never assume that [the events occurred] because the blood-thinner therapy was held, the timing within 48 hours is certainly very suspicious.”
There were no deep vein thrombosis or pulmonary embolism events.
Withholding practices vary
In a previous survey of 60 clinicians conducted by Dr. Lundholm and colleagues, wide variation was reported in the rates of withholding antiplatelet or anticoagulant medications prior to thyroid nodule FNA biopsy.
The survey of endocrinologists, interventional radiologists, and ear, nose, and throat providers showed rates of withholding 81 mg of aspirin prior to FNA biopsy of just 13.3%, withholding 325 mg of aspirin, 15%, other antiplatelets, 41.7%, warfarin, 73.3%, DOACs, 43.3%, and heparin, 43.3%.
“We found heterogeneity in withholding patterns even within the same department,” she said. “This is reflective of the fact that evidence is mixed.”
Guidelines on the issue from the Society of Interventional Radiology and the International Society on Thrombosis and Hemostasis recommend that providers consider the balance of the procedure and patient bleeding risk versus the clotting risk, Dr. Lundholm noted.
However, a caveat is that those recommendations are based on pooled data from similar minimal risk procedures, she explained.
“There is a lack of data on bleeding risks for individual interventions like thyroid biopsy, and, as such, there is no specific procedure-related risk determination.”
Meanwhile, Dr. Lundholm said that notable limitations regarding the current research include that the study may not have caught all patient cases that presented with complications to an outside ED.
Furthermore, the study results pertain to the safety of blood thinners in routine use, with key aspects that can influence complication rates, such as provider experience, needle size, and nodule features unavailable for analysis.
At MD Anderson, case-by-case
Commenting on the research, Anastasios Maniakas, MD, PhD, of the department of head and neck surgery, division of surgery, University of Texas MD Anderson Cancer Center, Houston, said the study is important, noting that, at his institution, the approach regarding holding blood-thinning medications is generally determined on an individual basis.
“I think this was a good study, but I don’t think it’s practice changing because these decisions may differ on a case-by-case basis,” Dr. Maniakas, who comoderated the session, said in an interview.
“At MD Anderson, we probably have one of the highest volumes in the country for thyroid nodule FNAs, and we do hold blood thinners because we often have to do more significant biopsies, with multiple passages and larger needles to be used,” Dr. Maniakas said.
“If you’re going to use perhaps the smallest possible gauge needle, then I think it is reasonable to not hold blood thinners, but if you’re going to be doing multiple passages and you need to do a core biopsy and use a large needle, then it is wiser to try to hold the medications for a day or 2.
“We haven’t had any complications, but I think there’s still a lot of apprehension to not hold blood thinners,” Dr. Maniakas said. “So, overall, I think the message is that it has to be on a case-by-case basis.”
Dr. Lundholm and Dr. Maniakas reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT ATA 2023
Triple therapy boosts anaplastic thyroid cancer survival
WASHINGTON – - particularly when administered in a neoadjuvant fashion, prior to surgery. Overall survival rates in the study exceeded 5 years.
“The very long median overall survival in the study’s neoadjuvant group is quite remarkable for a group of patients who used to have a very poor prognosis,” senior author Maria E. Cabanillas, MD, associate professor in the department of endocrine neoplasia and hormonal disorders at the University of Texas MD Anderson Cancer Center in Houston, said in an interview.
“This median overall survival definitely exceeds any other treatments thus far in BRAF-mutated anaplastic thyroid cancer.”
The research was presented at the annual meeting of the American Thyroid Association.
Anaplastic thyroid cancer, though rare, is the most aggressive form of thyroid cancer. It accounts for just 1% of the cancers but causes about 50% of thyroid cancer mortality.
The historical median overall survival is 5-6 months.
With research in recent years showing that as many as 40% of anaplastic thyroid cancers harbor BRAF V600E mutations, the door has opened for potential benefits with the combination of the BRAF inhibitor dabrafenib with the MEK-inhibitor drug trametinib.
The treatment combination was shown in research that included the phase 2 ROAR trial to yield important responses. It was approved by the Food and Drug Administration in 2018 for locally advanced or metastatic BRAF V600E-mutant anaplastic thyroid cancer, as well as other cancers.
However, a key caveat of DT is that patients eventually develop resistance mutations, leading to disease progression.
To overcome the problem, Dr. Cabanillas and her team found two key strategies that show promise – the addition of immunotherapy, such as pembrolizumab to DT, and the use of a neoadjuvant approach, with surgery performed after an initial response to the triplet therapy.
Triple therapy showed highly favorable results
In a study presented at the 2022 ATA annual meeting, researchers reported on the triple therapy of BRAF/MEK inhibitors vemurafenib and cobimetinib plus immunotherapy with atezolizumab. Results were highly favorable, with an overall response rate of 72% and an impressive 2-year survival of 67%.
However, a major limitation was that the study lacked a control arm. In the current study, the addition of pembrolizumab to DT was compared with DT alone. The investigators also sought to determine the survival benefits of a neoadjuvant strategy.
For the study, first author Sarah Hamidi, MD, also of the MD Anderson Cancer Center, and her colleagues identified 94 patients with BRAF-mutated anaplastic thyroid cancer who were treated either with first‐line DT or DT plus pembrolizumab between 2014 and 2023, either outside of a trial or in a reported clinical trial.
The study compared three treatment regimens – DT alone (n = 23), DT with pembrolizumab added before or after disease progression (n = 48), and DT with neoadjuvant pembrolizumab added prior to or after surgery (n = 23).
There were no significant differences in baseline characteristics between the groups. Metastatic disease was present at the start of treatment among 87.0% of the DT group, 79.2% of the pembrolizumab group prior to or after disease progression, and 65.2% of the neoadjuvant pembrolizumab group.
The median follow-up of the three groups was 102 months, 28 months, and 42 months, respectively. The median overall survival was 9 months with DT alone, vs. 17 months with DT plus pembrolizumab before or after progression and 63 months with neoadjuvant pembrolizumab plus DT (P < .001).
The 12- and 24-month survival rates with DT alone were 33.7% and 28.9%, respectively; for DT plus pembrolizumab before or after progression, the rates were 60.2% and 36.5%; and for neoadjuvant pembrolizumab plus DT, the rates were 80.7% and 74.5%.
In an analysis that did not include the neoadjuvant group, median progression-free survival was significantly longer with DT plus pembrolizumab as an initial treatment (11.0 months) compared with DT alone (4.0 months; P = .049).
A subanalysis that evaluated the timing of the addition of pembrolizumab to DT before or after disease progression showed no significant differences between the two in median overall survival (17 months vs. 16 months; P = .554).
“This is valuable information, especially for centers where pembrolizumab cannot be easily obtained as a first-line therapy for anaplastic thyroid cancer,” Dr. Hamidi said in presenting the findings.
She noted, however, that the results should be interpreted with caution, given the small number of patients who received pembrolizumab before progression (n = 34) and especially after progression (n = 14).
In terms of safety, there were no grade 5 adverse events (AEs); 32.4% of patients experienced immune‐related AEs, most frequently, colitis and hepatitis.
Therapies “improve survival”
Overall, the results are important, Dr. Cabanillas said.
The results are “very exciting when you think about the fact that 10 years ago, patients with anaplastic thyroid cancer had a median overall survival measured in months, and now we see that those with a BRAF mutation have a real chance at survival when managed appropriately from the start,” she told this news organization.
She noted that a key caveat is the study’s retrospective nature. Other important considerations are that pembrolizumab adds toxicity as well as cost, and it is largely used off label in anaplastic thyroid cancer.
Nevertheless, “it does feel like there needs to be a call to action in the guidelines for this disease so that it includes neoadjuvant DT or DT plus pembrolizumab as the primary treatment of patients with BRAF-mutated anaplastic thyroid cancer because the initial treatment is critical here,” Dr. Cabanillas said.
She added that a phase 2 trial with neoadjuvant DT plus pembrolizumab is ongoing. Enrollment is expected to be completed soon.
Commenting on the findings, Sarimar Agosto Salgado, MD, of the department of head and neck – endocrine oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Fla., who was a comoderator of the session, said the results are encouraging.
“These findings are promising because they open the landscape of options of therapies that we can provide these patients,” she said in an interview.
“Anaplastic thyroid cancer has been a disease with a very short survival despite aggressive therapies, but we are seeing that not only have these therapies been able to improve survival but also patients’ quality of life.”
Particularly encouraging is how quickly the therapies can work, Dr. Salgado added.
“Many times when patients present to the clinic, the rapid response to these systemic therapies can even [allow them to avoid] having a tracheostomy, and we’re also seeing that some of these patients are able to go from unresectable disease to resectable disease, and then by having the main tumor out, their survival improves.
“So, this is definitely a big ray of hope for these patients.”
Dr. Cabanillas has received research funding from Merck. Dr. Hamidi has disclosed no relevant financial relationships. Dr. Salgado has relationships with Lilly and Exelixis.
A version of this article appeared on Medscape.com.
WASHINGTON – - particularly when administered in a neoadjuvant fashion, prior to surgery. Overall survival rates in the study exceeded 5 years.
“The very long median overall survival in the study’s neoadjuvant group is quite remarkable for a group of patients who used to have a very poor prognosis,” senior author Maria E. Cabanillas, MD, associate professor in the department of endocrine neoplasia and hormonal disorders at the University of Texas MD Anderson Cancer Center in Houston, said in an interview.
“This median overall survival definitely exceeds any other treatments thus far in BRAF-mutated anaplastic thyroid cancer.”
The research was presented at the annual meeting of the American Thyroid Association.
Anaplastic thyroid cancer, though rare, is the most aggressive form of thyroid cancer. It accounts for just 1% of the cancers but causes about 50% of thyroid cancer mortality.
The historical median overall survival is 5-6 months.
With research in recent years showing that as many as 40% of anaplastic thyroid cancers harbor BRAF V600E mutations, the door has opened for potential benefits with the combination of the BRAF inhibitor dabrafenib with the MEK-inhibitor drug trametinib.
The treatment combination was shown in research that included the phase 2 ROAR trial to yield important responses. It was approved by the Food and Drug Administration in 2018 for locally advanced or metastatic BRAF V600E-mutant anaplastic thyroid cancer, as well as other cancers.
However, a key caveat of DT is that patients eventually develop resistance mutations, leading to disease progression.
To overcome the problem, Dr. Cabanillas and her team found two key strategies that show promise – the addition of immunotherapy, such as pembrolizumab to DT, and the use of a neoadjuvant approach, with surgery performed after an initial response to the triplet therapy.
Triple therapy showed highly favorable results
In a study presented at the 2022 ATA annual meeting, researchers reported on the triple therapy of BRAF/MEK inhibitors vemurafenib and cobimetinib plus immunotherapy with atezolizumab. Results were highly favorable, with an overall response rate of 72% and an impressive 2-year survival of 67%.
However, a major limitation was that the study lacked a control arm. In the current study, the addition of pembrolizumab to DT was compared with DT alone. The investigators also sought to determine the survival benefits of a neoadjuvant strategy.
For the study, first author Sarah Hamidi, MD, also of the MD Anderson Cancer Center, and her colleagues identified 94 patients with BRAF-mutated anaplastic thyroid cancer who were treated either with first‐line DT or DT plus pembrolizumab between 2014 and 2023, either outside of a trial or in a reported clinical trial.
The study compared three treatment regimens – DT alone (n = 23), DT with pembrolizumab added before or after disease progression (n = 48), and DT with neoadjuvant pembrolizumab added prior to or after surgery (n = 23).
There were no significant differences in baseline characteristics between the groups. Metastatic disease was present at the start of treatment among 87.0% of the DT group, 79.2% of the pembrolizumab group prior to or after disease progression, and 65.2% of the neoadjuvant pembrolizumab group.
The median follow-up of the three groups was 102 months, 28 months, and 42 months, respectively. The median overall survival was 9 months with DT alone, vs. 17 months with DT plus pembrolizumab before or after progression and 63 months with neoadjuvant pembrolizumab plus DT (P < .001).
The 12- and 24-month survival rates with DT alone were 33.7% and 28.9%, respectively; for DT plus pembrolizumab before or after progression, the rates were 60.2% and 36.5%; and for neoadjuvant pembrolizumab plus DT, the rates were 80.7% and 74.5%.
In an analysis that did not include the neoadjuvant group, median progression-free survival was significantly longer with DT plus pembrolizumab as an initial treatment (11.0 months) compared with DT alone (4.0 months; P = .049).
A subanalysis that evaluated the timing of the addition of pembrolizumab to DT before or after disease progression showed no significant differences between the two in median overall survival (17 months vs. 16 months; P = .554).
“This is valuable information, especially for centers where pembrolizumab cannot be easily obtained as a first-line therapy for anaplastic thyroid cancer,” Dr. Hamidi said in presenting the findings.
She noted, however, that the results should be interpreted with caution, given the small number of patients who received pembrolizumab before progression (n = 34) and especially after progression (n = 14).
In terms of safety, there were no grade 5 adverse events (AEs); 32.4% of patients experienced immune‐related AEs, most frequently, colitis and hepatitis.
Therapies “improve survival”
Overall, the results are important, Dr. Cabanillas said.
The results are “very exciting when you think about the fact that 10 years ago, patients with anaplastic thyroid cancer had a median overall survival measured in months, and now we see that those with a BRAF mutation have a real chance at survival when managed appropriately from the start,” she told this news organization.
She noted that a key caveat is the study’s retrospective nature. Other important considerations are that pembrolizumab adds toxicity as well as cost, and it is largely used off label in anaplastic thyroid cancer.
Nevertheless, “it does feel like there needs to be a call to action in the guidelines for this disease so that it includes neoadjuvant DT or DT plus pembrolizumab as the primary treatment of patients with BRAF-mutated anaplastic thyroid cancer because the initial treatment is critical here,” Dr. Cabanillas said.
She added that a phase 2 trial with neoadjuvant DT plus pembrolizumab is ongoing. Enrollment is expected to be completed soon.
Commenting on the findings, Sarimar Agosto Salgado, MD, of the department of head and neck – endocrine oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Fla., who was a comoderator of the session, said the results are encouraging.
“These findings are promising because they open the landscape of options of therapies that we can provide these patients,” she said in an interview.
“Anaplastic thyroid cancer has been a disease with a very short survival despite aggressive therapies, but we are seeing that not only have these therapies been able to improve survival but also patients’ quality of life.”
Particularly encouraging is how quickly the therapies can work, Dr. Salgado added.
“Many times when patients present to the clinic, the rapid response to these systemic therapies can even [allow them to avoid] having a tracheostomy, and we’re also seeing that some of these patients are able to go from unresectable disease to resectable disease, and then by having the main tumor out, their survival improves.
“So, this is definitely a big ray of hope for these patients.”
Dr. Cabanillas has received research funding from Merck. Dr. Hamidi has disclosed no relevant financial relationships. Dr. Salgado has relationships with Lilly and Exelixis.
A version of this article appeared on Medscape.com.
WASHINGTON – - particularly when administered in a neoadjuvant fashion, prior to surgery. Overall survival rates in the study exceeded 5 years.
“The very long median overall survival in the study’s neoadjuvant group is quite remarkable for a group of patients who used to have a very poor prognosis,” senior author Maria E. Cabanillas, MD, associate professor in the department of endocrine neoplasia and hormonal disorders at the University of Texas MD Anderson Cancer Center in Houston, said in an interview.
“This median overall survival definitely exceeds any other treatments thus far in BRAF-mutated anaplastic thyroid cancer.”
The research was presented at the annual meeting of the American Thyroid Association.
Anaplastic thyroid cancer, though rare, is the most aggressive form of thyroid cancer. It accounts for just 1% of the cancers but causes about 50% of thyroid cancer mortality.
The historical median overall survival is 5-6 months.
With research in recent years showing that as many as 40% of anaplastic thyroid cancers harbor BRAF V600E mutations, the door has opened for potential benefits with the combination of the BRAF inhibitor dabrafenib with the MEK-inhibitor drug trametinib.
The treatment combination was shown in research that included the phase 2 ROAR trial to yield important responses. It was approved by the Food and Drug Administration in 2018 for locally advanced or metastatic BRAF V600E-mutant anaplastic thyroid cancer, as well as other cancers.
However, a key caveat of DT is that patients eventually develop resistance mutations, leading to disease progression.
To overcome the problem, Dr. Cabanillas and her team found two key strategies that show promise – the addition of immunotherapy, such as pembrolizumab to DT, and the use of a neoadjuvant approach, with surgery performed after an initial response to the triplet therapy.
Triple therapy showed highly favorable results
In a study presented at the 2022 ATA annual meeting, researchers reported on the triple therapy of BRAF/MEK inhibitors vemurafenib and cobimetinib plus immunotherapy with atezolizumab. Results were highly favorable, with an overall response rate of 72% and an impressive 2-year survival of 67%.
However, a major limitation was that the study lacked a control arm. In the current study, the addition of pembrolizumab to DT was compared with DT alone. The investigators also sought to determine the survival benefits of a neoadjuvant strategy.
For the study, first author Sarah Hamidi, MD, also of the MD Anderson Cancer Center, and her colleagues identified 94 patients with BRAF-mutated anaplastic thyroid cancer who were treated either with first‐line DT or DT plus pembrolizumab between 2014 and 2023, either outside of a trial or in a reported clinical trial.
The study compared three treatment regimens – DT alone (n = 23), DT with pembrolizumab added before or after disease progression (n = 48), and DT with neoadjuvant pembrolizumab added prior to or after surgery (n = 23).
There were no significant differences in baseline characteristics between the groups. Metastatic disease was present at the start of treatment among 87.0% of the DT group, 79.2% of the pembrolizumab group prior to or after disease progression, and 65.2% of the neoadjuvant pembrolizumab group.
The median follow-up of the three groups was 102 months, 28 months, and 42 months, respectively. The median overall survival was 9 months with DT alone, vs. 17 months with DT plus pembrolizumab before or after progression and 63 months with neoadjuvant pembrolizumab plus DT (P < .001).
The 12- and 24-month survival rates with DT alone were 33.7% and 28.9%, respectively; for DT plus pembrolizumab before or after progression, the rates were 60.2% and 36.5%; and for neoadjuvant pembrolizumab plus DT, the rates were 80.7% and 74.5%.
In an analysis that did not include the neoadjuvant group, median progression-free survival was significantly longer with DT plus pembrolizumab as an initial treatment (11.0 months) compared with DT alone (4.0 months; P = .049).
A subanalysis that evaluated the timing of the addition of pembrolizumab to DT before or after disease progression showed no significant differences between the two in median overall survival (17 months vs. 16 months; P = .554).
“This is valuable information, especially for centers where pembrolizumab cannot be easily obtained as a first-line therapy for anaplastic thyroid cancer,” Dr. Hamidi said in presenting the findings.
She noted, however, that the results should be interpreted with caution, given the small number of patients who received pembrolizumab before progression (n = 34) and especially after progression (n = 14).
In terms of safety, there were no grade 5 adverse events (AEs); 32.4% of patients experienced immune‐related AEs, most frequently, colitis and hepatitis.
Therapies “improve survival”
Overall, the results are important, Dr. Cabanillas said.
The results are “very exciting when you think about the fact that 10 years ago, patients with anaplastic thyroid cancer had a median overall survival measured in months, and now we see that those with a BRAF mutation have a real chance at survival when managed appropriately from the start,” she told this news organization.
She noted that a key caveat is the study’s retrospective nature. Other important considerations are that pembrolizumab adds toxicity as well as cost, and it is largely used off label in anaplastic thyroid cancer.
Nevertheless, “it does feel like there needs to be a call to action in the guidelines for this disease so that it includes neoadjuvant DT or DT plus pembrolizumab as the primary treatment of patients with BRAF-mutated anaplastic thyroid cancer because the initial treatment is critical here,” Dr. Cabanillas said.
She added that a phase 2 trial with neoadjuvant DT plus pembrolizumab is ongoing. Enrollment is expected to be completed soon.
Commenting on the findings, Sarimar Agosto Salgado, MD, of the department of head and neck – endocrine oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Fla., who was a comoderator of the session, said the results are encouraging.
“These findings are promising because they open the landscape of options of therapies that we can provide these patients,” she said in an interview.
“Anaplastic thyroid cancer has been a disease with a very short survival despite aggressive therapies, but we are seeing that not only have these therapies been able to improve survival but also patients’ quality of life.”
Particularly encouraging is how quickly the therapies can work, Dr. Salgado added.
“Many times when patients present to the clinic, the rapid response to these systemic therapies can even [allow them to avoid] having a tracheostomy, and we’re also seeing that some of these patients are able to go from unresectable disease to resectable disease, and then by having the main tumor out, their survival improves.
“So, this is definitely a big ray of hope for these patients.”
Dr. Cabanillas has received research funding from Merck. Dr. Hamidi has disclosed no relevant financial relationships. Dr. Salgado has relationships with Lilly and Exelixis.
A version of this article appeared on Medscape.com.
AT ATA 2023
What potential does AI offer for endocrinology?
However, hurdles encountered with the latest AI iterations of chatbots underscore the need to proceed with caution.
“In contrast to other medical fields, endocrinology is not connected to a single organ structure; rather, it is a complicated biological system of hormones and metabolites, [intertwined with] various receptors, signaling pathways and intricate feedback mechanisms,” explained the authors of a recent article on the issue in Nature Reviews Endocrinology.
With interconnections that are “often beyond the comprehension and reasoning capabilities of the human brain, AI [is anticipated] to be exceptionally well-suited to tackle this remarkable heterogeneity and complexity,” they wrote.
Since the first regulatory approvals for AI-based technology were granted back in 2015, endocrinology has already been revolutionized by AI-based tools, most notably with AI biosensors for continuous glucose monitoring systems alerting patients of glucose levels, and automated insulin-delivery systems.
AI-based machine learning has also ushered in improved detection and analysis of thyroid nodules and potential malignancies, with algorithms in the analysis of radiological test images enabling detection through a deeper analysis than can be applied with individual specialists.
Likewise, the benefits of AI in imaging extend to osteoporosis.
“Imaging certainly is one of the most promising fields, including (but not limited to) conventional radiography, computed tomography, and magnetic resonance tomography,” explained Hans Peter Dimai, MD, a professor of medicine and endocrinology at the Medical University of Graz (Austria), and the past president of the Austrian Bone and Mineral Society.
“A typical indication is fracture detection, not in terms of replacing expert radiologists or orthopedists but rather in terms of supporting those who are in specialist training,” he said in an interview.
“Particularly the underdiagnosis of vertebral fractures has been an issue in past decades, with dramatic implications for the individual, since the first vertebral fracture would multiply the risk for any future fracture, and therefore requires immediate action from a physician’s side.”
The areas expected to further benefit from AI continue to grow as systems evolve, with advances being reported across a variety of endocrinologic conditions.
Papillary thyroid cancer (PTC): Central lymph node metastasis of papillary thyroid cancer is predictive of tumor recurrence and overall survival in PTC. However, few tests are able to diagnose the metastasis in the cancer with high accuracy. Using a convolutional neural network prediction model built with a deep-learning algorithm, researchers described high diagnostic sensitivity and specificity of a model, as reported in a study published in Feburary. The prediction model, developed using genetic mutations and clinicopathologic factors, showed high prediction efficacy, with validation in subclinical as well as clinical metastasis groups, suggesting broad applicability.
Adrenal tumors: Adrenal incidentalomas, or masses that are incidentally discovered when performing abdominal imaging for other reasons, can be a perplexing clinical challenge. Discovery of these is increasing as imaging technology advances. However, an AI-based machine learning approach utilizing CT is being developed to differentiate between subclinical pheochromocytoma and lipid-poor adenomas. As reported in a 2022 study, the prediction model scoring system used traditional radiological features on CT images to provide for a noninvasive method in assisting in the diagnosis and providing personalized care for people with adrenal tumors.
Osteoporosis – bone mineral density (BMD): In the diagnosis of osteoporosis, the measurement of BMD using dual-energy x-ray absorptiometry (DXA) is the gold standard. However, the availability of DXA devices in many countries is inadequate, leaving an unmet need for alternative approaches. But one AI-based algorithm shows promising diagnostic accuracy, compared with DXA, potentially providing a low-cost screening alternative for the early diagnosis of osteoporosis.
Osteoporosis – Fracture Risk Assessment Tool (FRAX): In fracture risk and prevention, the free FRAX tool, available online, is the gold standard and recommended in nearly all osteoporosis guidelines. However, several studies on AI-based tools show some benefit over FRAX, including one approach using longitudinal data with conventional spine radiographs, showing predictive accuracy that exceeds FRAX.
Osteoporosis – treatment: And for the often challenging process of treatment decision-making in osteoporosis, AI-based software, developed from more than 15,000 osteoporosis patients followed over 10 years, shows high accuracy in the prediction of response to treatment in terms of BMD increase, as described in another study. “Our results show that it is feasible to use a combination of electronic medical records–derived information to develop a machine-learning algorithm to predict a BMD response following osteoporosis treatment,” the authors reported. “This alternative approach can aid physicians to select an optimal therapeutic regimen in order to maximize a patient-specific treatment outcome.”
Chatbot wrinkles
The prospects of large language models (LLMs) and ChatGPT unleash the potential to understand and generate text in a similar capacity as humans. Although controversial, they could likewise be compelling.
However, such systems can be vastly more complex than earlier AI-based tools, and some studies are illustrating the kinds of stumbling blocks that need to be overcome.
For instance, in a study published in May, researchers explored the potential of ChatGPT 4.0 to synthesize clinical guidelines for diabetic ketoacidosis from three different sources to reflect the latest evidence and local context.
Such efforts are important but can be very resource-intensive when conducted without the use of AI assistance.
The study’s results showed that, although ChatGPT was able to generate a comprehensive table comparing the guidelines, there were multiple recurrent errors in misreporting and nonreporting, as well as inconsistencies, “rendering the results unreliable,” the authors wrote.
“Although ChatGPT demonstrates the potential for the synthesis of clinical guidelines, the presence of multiple recurrent errors and inconsistencies underscores the need for expert human intervention and validation,” the authors concluded.
Likewise, other research using ChatGPT for use in vitreoretinal diseases, including diabetic retinopathy, further demonstrated disappointing results, with the technology showing the chatbot provided completely accurate responses to only 8 (15.4%) of 52 questions, with some responses containing inappropriate or potentially harmful medical advice.
“For example, in response to ‘How do you get rid of epiretinal membrane?’, the platform described vitrectomy but also included incorrect options of injection therapy and laser therapy,” the authors wrote.
“The study highlights the limitations of using ChatGPT for the adaptation of clinical guidelines without expert human intervention,” they concluded.
And in research published in August that looked at the ability of ChatGPT to interpret guidelines – in this case 26 diagnosis descriptions from the National Comprehensive Cancer Network – results showed that as many as one-third of treatments recommended by the chatbot were at least partially not concordant with information stated in the NCCN guidelines, with recommendations varying based on how the question about treatment was presented.
“Clinicians should advise patients that LLM chatbots are not a reliable source of treatment information,” the authors wrote.
Diversity concerns
Among the most prominent concerns about chatbot inaccuracy has been the known lack of racial and ethnic diversity in large databases utilized in developing AI systems, potentially resulting in critical flaws in the information the systems produce.
In an editorial published with the NCCN guideline study, Atul Butte, MD, PhD, from the University of California, San Francisco, noted that the shortcomings should be weighed with the potential benefits.
“There is no doubt that AI and LLMs are not yet perfect, and they carry biases that will need to be addressed,” Dr. Butte wrote. “These algorithms will need to be carefully monitored as they are brought into health systems, [but] this does not alter the potential of how they can improve care for both the haves and have-nots of health care.”
In a comment, Dr. Butte elaborated that, once the system flaws are refined, a key benefit will be the broader application of top standards of care to more patients who may have limited resources.
“It is a privilege to get the very best level of care from the very best centers, but that privilege is not distributable to all right now,” Dr. Butte said.
“The real potential of LLMs and AI will be their ability to be trained from the patient, clinical, and outcomes data from the very best centers, and then used to deliver the best care through digital tools to all patients, especially to those without access to the best care or [those with] limited resources,” he said.
Further commenting on the issue of potential bias with chatbots, Matthew Li, MD, from the University of Alberta, Edmonton, said that awareness of the nature of the problem and need for diversity in data for training and testing AI-systems issues appears to be improving.
“Thanks to much research on this topic in recent years, I think most AI researchers in medicine are at least aware of these challenges now, which was not the case only a few years ago,” he said in an interview.
Across specialties, “the careful deployment of AI tools accounting for issues regarding AI model generalization, biases, and performance drift will be critical for ensuring safe and fair patient care,” Dr. Li noted.
On a broader level is the ongoing general concern of the potential for over-reliance on the technology by clinicians. For example, a recent study showing radiologists across all experience levels reading mammograms were prone to automation bias when being supported by an AI-based system.
“Concerns regarding over-reliance on AI remain,” said Dr. Li, who coauthored a study published in June on the issue.
“Ongoing research into and monitoring of the impact of AI systems as they are developed and deployed will be important to ensure safe patient care moving forward,” he said.
Ultimately, the clinical benefit of AI systems to patients should be the bottom line, Dr. Dimai added.
“In my opinion, the clinical relevance, i.e., the benefit for patients and/or physicians of a to-be-developed AI tool, must be clearly proven before its development starts and first clinical studies are carried out,” he said.
“This is not always the case,” Dr. Dimai said. “In other words, innovation per se should not be the only rationale and driving force for the development of such tools.”
Dr. Li, an associate editor for the journal Radiology: Artificial Intelligence, reports no relevant financial relationships. Dr. Dimai is a member of the key medical advisor team of Image Biopsy Lab.
A version of this article first appeared on Medscape.com.
However, hurdles encountered with the latest AI iterations of chatbots underscore the need to proceed with caution.
“In contrast to other medical fields, endocrinology is not connected to a single organ structure; rather, it is a complicated biological system of hormones and metabolites, [intertwined with] various receptors, signaling pathways and intricate feedback mechanisms,” explained the authors of a recent article on the issue in Nature Reviews Endocrinology.
With interconnections that are “often beyond the comprehension and reasoning capabilities of the human brain, AI [is anticipated] to be exceptionally well-suited to tackle this remarkable heterogeneity and complexity,” they wrote.
Since the first regulatory approvals for AI-based technology were granted back in 2015, endocrinology has already been revolutionized by AI-based tools, most notably with AI biosensors for continuous glucose monitoring systems alerting patients of glucose levels, and automated insulin-delivery systems.
AI-based machine learning has also ushered in improved detection and analysis of thyroid nodules and potential malignancies, with algorithms in the analysis of radiological test images enabling detection through a deeper analysis than can be applied with individual specialists.
Likewise, the benefits of AI in imaging extend to osteoporosis.
“Imaging certainly is one of the most promising fields, including (but not limited to) conventional radiography, computed tomography, and magnetic resonance tomography,” explained Hans Peter Dimai, MD, a professor of medicine and endocrinology at the Medical University of Graz (Austria), and the past president of the Austrian Bone and Mineral Society.
“A typical indication is fracture detection, not in terms of replacing expert radiologists or orthopedists but rather in terms of supporting those who are in specialist training,” he said in an interview.
“Particularly the underdiagnosis of vertebral fractures has been an issue in past decades, with dramatic implications for the individual, since the first vertebral fracture would multiply the risk for any future fracture, and therefore requires immediate action from a physician’s side.”
The areas expected to further benefit from AI continue to grow as systems evolve, with advances being reported across a variety of endocrinologic conditions.
Papillary thyroid cancer (PTC): Central lymph node metastasis of papillary thyroid cancer is predictive of tumor recurrence and overall survival in PTC. However, few tests are able to diagnose the metastasis in the cancer with high accuracy. Using a convolutional neural network prediction model built with a deep-learning algorithm, researchers described high diagnostic sensitivity and specificity of a model, as reported in a study published in Feburary. The prediction model, developed using genetic mutations and clinicopathologic factors, showed high prediction efficacy, with validation in subclinical as well as clinical metastasis groups, suggesting broad applicability.
Adrenal tumors: Adrenal incidentalomas, or masses that are incidentally discovered when performing abdominal imaging for other reasons, can be a perplexing clinical challenge. Discovery of these is increasing as imaging technology advances. However, an AI-based machine learning approach utilizing CT is being developed to differentiate between subclinical pheochromocytoma and lipid-poor adenomas. As reported in a 2022 study, the prediction model scoring system used traditional radiological features on CT images to provide for a noninvasive method in assisting in the diagnosis and providing personalized care for people with adrenal tumors.
Osteoporosis – bone mineral density (BMD): In the diagnosis of osteoporosis, the measurement of BMD using dual-energy x-ray absorptiometry (DXA) is the gold standard. However, the availability of DXA devices in many countries is inadequate, leaving an unmet need for alternative approaches. But one AI-based algorithm shows promising diagnostic accuracy, compared with DXA, potentially providing a low-cost screening alternative for the early diagnosis of osteoporosis.
Osteoporosis – Fracture Risk Assessment Tool (FRAX): In fracture risk and prevention, the free FRAX tool, available online, is the gold standard and recommended in nearly all osteoporosis guidelines. However, several studies on AI-based tools show some benefit over FRAX, including one approach using longitudinal data with conventional spine radiographs, showing predictive accuracy that exceeds FRAX.
Osteoporosis – treatment: And for the often challenging process of treatment decision-making in osteoporosis, AI-based software, developed from more than 15,000 osteoporosis patients followed over 10 years, shows high accuracy in the prediction of response to treatment in terms of BMD increase, as described in another study. “Our results show that it is feasible to use a combination of electronic medical records–derived information to develop a machine-learning algorithm to predict a BMD response following osteoporosis treatment,” the authors reported. “This alternative approach can aid physicians to select an optimal therapeutic regimen in order to maximize a patient-specific treatment outcome.”
Chatbot wrinkles
The prospects of large language models (LLMs) and ChatGPT unleash the potential to understand and generate text in a similar capacity as humans. Although controversial, they could likewise be compelling.
However, such systems can be vastly more complex than earlier AI-based tools, and some studies are illustrating the kinds of stumbling blocks that need to be overcome.
For instance, in a study published in May, researchers explored the potential of ChatGPT 4.0 to synthesize clinical guidelines for diabetic ketoacidosis from three different sources to reflect the latest evidence and local context.
Such efforts are important but can be very resource-intensive when conducted without the use of AI assistance.
The study’s results showed that, although ChatGPT was able to generate a comprehensive table comparing the guidelines, there were multiple recurrent errors in misreporting and nonreporting, as well as inconsistencies, “rendering the results unreliable,” the authors wrote.
“Although ChatGPT demonstrates the potential for the synthesis of clinical guidelines, the presence of multiple recurrent errors and inconsistencies underscores the need for expert human intervention and validation,” the authors concluded.
Likewise, other research using ChatGPT for use in vitreoretinal diseases, including diabetic retinopathy, further demonstrated disappointing results, with the technology showing the chatbot provided completely accurate responses to only 8 (15.4%) of 52 questions, with some responses containing inappropriate or potentially harmful medical advice.
“For example, in response to ‘How do you get rid of epiretinal membrane?’, the platform described vitrectomy but also included incorrect options of injection therapy and laser therapy,” the authors wrote.
“The study highlights the limitations of using ChatGPT for the adaptation of clinical guidelines without expert human intervention,” they concluded.
And in research published in August that looked at the ability of ChatGPT to interpret guidelines – in this case 26 diagnosis descriptions from the National Comprehensive Cancer Network – results showed that as many as one-third of treatments recommended by the chatbot were at least partially not concordant with information stated in the NCCN guidelines, with recommendations varying based on how the question about treatment was presented.
“Clinicians should advise patients that LLM chatbots are not a reliable source of treatment information,” the authors wrote.
Diversity concerns
Among the most prominent concerns about chatbot inaccuracy has been the known lack of racial and ethnic diversity in large databases utilized in developing AI systems, potentially resulting in critical flaws in the information the systems produce.
In an editorial published with the NCCN guideline study, Atul Butte, MD, PhD, from the University of California, San Francisco, noted that the shortcomings should be weighed with the potential benefits.
“There is no doubt that AI and LLMs are not yet perfect, and they carry biases that will need to be addressed,” Dr. Butte wrote. “These algorithms will need to be carefully monitored as they are brought into health systems, [but] this does not alter the potential of how they can improve care for both the haves and have-nots of health care.”
In a comment, Dr. Butte elaborated that, once the system flaws are refined, a key benefit will be the broader application of top standards of care to more patients who may have limited resources.
“It is a privilege to get the very best level of care from the very best centers, but that privilege is not distributable to all right now,” Dr. Butte said.
“The real potential of LLMs and AI will be their ability to be trained from the patient, clinical, and outcomes data from the very best centers, and then used to deliver the best care through digital tools to all patients, especially to those without access to the best care or [those with] limited resources,” he said.
Further commenting on the issue of potential bias with chatbots, Matthew Li, MD, from the University of Alberta, Edmonton, said that awareness of the nature of the problem and need for diversity in data for training and testing AI-systems issues appears to be improving.
“Thanks to much research on this topic in recent years, I think most AI researchers in medicine are at least aware of these challenges now, which was not the case only a few years ago,” he said in an interview.
Across specialties, “the careful deployment of AI tools accounting for issues regarding AI model generalization, biases, and performance drift will be critical for ensuring safe and fair patient care,” Dr. Li noted.
On a broader level is the ongoing general concern of the potential for over-reliance on the technology by clinicians. For example, a recent study showing radiologists across all experience levels reading mammograms were prone to automation bias when being supported by an AI-based system.
“Concerns regarding over-reliance on AI remain,” said Dr. Li, who coauthored a study published in June on the issue.
“Ongoing research into and monitoring of the impact of AI systems as they are developed and deployed will be important to ensure safe patient care moving forward,” he said.
Ultimately, the clinical benefit of AI systems to patients should be the bottom line, Dr. Dimai added.
“In my opinion, the clinical relevance, i.e., the benefit for patients and/or physicians of a to-be-developed AI tool, must be clearly proven before its development starts and first clinical studies are carried out,” he said.
“This is not always the case,” Dr. Dimai said. “In other words, innovation per se should not be the only rationale and driving force for the development of such tools.”
Dr. Li, an associate editor for the journal Radiology: Artificial Intelligence, reports no relevant financial relationships. Dr. Dimai is a member of the key medical advisor team of Image Biopsy Lab.
A version of this article first appeared on Medscape.com.
However, hurdles encountered with the latest AI iterations of chatbots underscore the need to proceed with caution.
“In contrast to other medical fields, endocrinology is not connected to a single organ structure; rather, it is a complicated biological system of hormones and metabolites, [intertwined with] various receptors, signaling pathways and intricate feedback mechanisms,” explained the authors of a recent article on the issue in Nature Reviews Endocrinology.
With interconnections that are “often beyond the comprehension and reasoning capabilities of the human brain, AI [is anticipated] to be exceptionally well-suited to tackle this remarkable heterogeneity and complexity,” they wrote.
Since the first regulatory approvals for AI-based technology were granted back in 2015, endocrinology has already been revolutionized by AI-based tools, most notably with AI biosensors for continuous glucose monitoring systems alerting patients of glucose levels, and automated insulin-delivery systems.
AI-based machine learning has also ushered in improved detection and analysis of thyroid nodules and potential malignancies, with algorithms in the analysis of radiological test images enabling detection through a deeper analysis than can be applied with individual specialists.
Likewise, the benefits of AI in imaging extend to osteoporosis.
“Imaging certainly is one of the most promising fields, including (but not limited to) conventional radiography, computed tomography, and magnetic resonance tomography,” explained Hans Peter Dimai, MD, a professor of medicine and endocrinology at the Medical University of Graz (Austria), and the past president of the Austrian Bone and Mineral Society.
“A typical indication is fracture detection, not in terms of replacing expert radiologists or orthopedists but rather in terms of supporting those who are in specialist training,” he said in an interview.
“Particularly the underdiagnosis of vertebral fractures has been an issue in past decades, with dramatic implications for the individual, since the first vertebral fracture would multiply the risk for any future fracture, and therefore requires immediate action from a physician’s side.”
The areas expected to further benefit from AI continue to grow as systems evolve, with advances being reported across a variety of endocrinologic conditions.
Papillary thyroid cancer (PTC): Central lymph node metastasis of papillary thyroid cancer is predictive of tumor recurrence and overall survival in PTC. However, few tests are able to diagnose the metastasis in the cancer with high accuracy. Using a convolutional neural network prediction model built with a deep-learning algorithm, researchers described high diagnostic sensitivity and specificity of a model, as reported in a study published in Feburary. The prediction model, developed using genetic mutations and clinicopathologic factors, showed high prediction efficacy, with validation in subclinical as well as clinical metastasis groups, suggesting broad applicability.
Adrenal tumors: Adrenal incidentalomas, or masses that are incidentally discovered when performing abdominal imaging for other reasons, can be a perplexing clinical challenge. Discovery of these is increasing as imaging technology advances. However, an AI-based machine learning approach utilizing CT is being developed to differentiate between subclinical pheochromocytoma and lipid-poor adenomas. As reported in a 2022 study, the prediction model scoring system used traditional radiological features on CT images to provide for a noninvasive method in assisting in the diagnosis and providing personalized care for people with adrenal tumors.
Osteoporosis – bone mineral density (BMD): In the diagnosis of osteoporosis, the measurement of BMD using dual-energy x-ray absorptiometry (DXA) is the gold standard. However, the availability of DXA devices in many countries is inadequate, leaving an unmet need for alternative approaches. But one AI-based algorithm shows promising diagnostic accuracy, compared with DXA, potentially providing a low-cost screening alternative for the early diagnosis of osteoporosis.
Osteoporosis – Fracture Risk Assessment Tool (FRAX): In fracture risk and prevention, the free FRAX tool, available online, is the gold standard and recommended in nearly all osteoporosis guidelines. However, several studies on AI-based tools show some benefit over FRAX, including one approach using longitudinal data with conventional spine radiographs, showing predictive accuracy that exceeds FRAX.
Osteoporosis – treatment: And for the often challenging process of treatment decision-making in osteoporosis, AI-based software, developed from more than 15,000 osteoporosis patients followed over 10 years, shows high accuracy in the prediction of response to treatment in terms of BMD increase, as described in another study. “Our results show that it is feasible to use a combination of electronic medical records–derived information to develop a machine-learning algorithm to predict a BMD response following osteoporosis treatment,” the authors reported. “This alternative approach can aid physicians to select an optimal therapeutic regimen in order to maximize a patient-specific treatment outcome.”
Chatbot wrinkles
The prospects of large language models (LLMs) and ChatGPT unleash the potential to understand and generate text in a similar capacity as humans. Although controversial, they could likewise be compelling.
However, such systems can be vastly more complex than earlier AI-based tools, and some studies are illustrating the kinds of stumbling blocks that need to be overcome.
For instance, in a study published in May, researchers explored the potential of ChatGPT 4.0 to synthesize clinical guidelines for diabetic ketoacidosis from three different sources to reflect the latest evidence and local context.
Such efforts are important but can be very resource-intensive when conducted without the use of AI assistance.
The study’s results showed that, although ChatGPT was able to generate a comprehensive table comparing the guidelines, there were multiple recurrent errors in misreporting and nonreporting, as well as inconsistencies, “rendering the results unreliable,” the authors wrote.
“Although ChatGPT demonstrates the potential for the synthesis of clinical guidelines, the presence of multiple recurrent errors and inconsistencies underscores the need for expert human intervention and validation,” the authors concluded.
Likewise, other research using ChatGPT for use in vitreoretinal diseases, including diabetic retinopathy, further demonstrated disappointing results, with the technology showing the chatbot provided completely accurate responses to only 8 (15.4%) of 52 questions, with some responses containing inappropriate or potentially harmful medical advice.
“For example, in response to ‘How do you get rid of epiretinal membrane?’, the platform described vitrectomy but also included incorrect options of injection therapy and laser therapy,” the authors wrote.
“The study highlights the limitations of using ChatGPT for the adaptation of clinical guidelines without expert human intervention,” they concluded.
And in research published in August that looked at the ability of ChatGPT to interpret guidelines – in this case 26 diagnosis descriptions from the National Comprehensive Cancer Network – results showed that as many as one-third of treatments recommended by the chatbot were at least partially not concordant with information stated in the NCCN guidelines, with recommendations varying based on how the question about treatment was presented.
“Clinicians should advise patients that LLM chatbots are not a reliable source of treatment information,” the authors wrote.
Diversity concerns
Among the most prominent concerns about chatbot inaccuracy has been the known lack of racial and ethnic diversity in large databases utilized in developing AI systems, potentially resulting in critical flaws in the information the systems produce.
In an editorial published with the NCCN guideline study, Atul Butte, MD, PhD, from the University of California, San Francisco, noted that the shortcomings should be weighed with the potential benefits.
“There is no doubt that AI and LLMs are not yet perfect, and they carry biases that will need to be addressed,” Dr. Butte wrote. “These algorithms will need to be carefully monitored as they are brought into health systems, [but] this does not alter the potential of how they can improve care for both the haves and have-nots of health care.”
In a comment, Dr. Butte elaborated that, once the system flaws are refined, a key benefit will be the broader application of top standards of care to more patients who may have limited resources.
“It is a privilege to get the very best level of care from the very best centers, but that privilege is not distributable to all right now,” Dr. Butte said.
“The real potential of LLMs and AI will be their ability to be trained from the patient, clinical, and outcomes data from the very best centers, and then used to deliver the best care through digital tools to all patients, especially to those without access to the best care or [those with] limited resources,” he said.
Further commenting on the issue of potential bias with chatbots, Matthew Li, MD, from the University of Alberta, Edmonton, said that awareness of the nature of the problem and need for diversity in data for training and testing AI-systems issues appears to be improving.
“Thanks to much research on this topic in recent years, I think most AI researchers in medicine are at least aware of these challenges now, which was not the case only a few years ago,” he said in an interview.
Across specialties, “the careful deployment of AI tools accounting for issues regarding AI model generalization, biases, and performance drift will be critical for ensuring safe and fair patient care,” Dr. Li noted.
On a broader level is the ongoing general concern of the potential for over-reliance on the technology by clinicians. For example, a recent study showing radiologists across all experience levels reading mammograms were prone to automation bias when being supported by an AI-based system.
“Concerns regarding over-reliance on AI remain,” said Dr. Li, who coauthored a study published in June on the issue.
“Ongoing research into and monitoring of the impact of AI systems as they are developed and deployed will be important to ensure safe patient care moving forward,” he said.
Ultimately, the clinical benefit of AI systems to patients should be the bottom line, Dr. Dimai added.
“In my opinion, the clinical relevance, i.e., the benefit for patients and/or physicians of a to-be-developed AI tool, must be clearly proven before its development starts and first clinical studies are carried out,” he said.
“This is not always the case,” Dr. Dimai said. “In other words, innovation per se should not be the only rationale and driving force for the development of such tools.”
Dr. Li, an associate editor for the journal Radiology: Artificial Intelligence, reports no relevant financial relationships. Dr. Dimai is a member of the key medical advisor team of Image Biopsy Lab.
A version of this article first appeared on Medscape.com.
Dispelling clinicians’ misconceptions about sickle cell disease
Affecting more than 20 million people globally and 100,000 people nationwide, SCD is the most common inherited blood disorder in the United States. It occurs largely but not exclusively among people of African descent.
Patients with SCD develop crescent-shaped or “sickled” red blood cells that, unlike normally round cells, can potentially block blood flow and thus cause a host of problems ranging from a risk of stroke or infections to sometimes severe pain crises, called vaso-occlusive episodes.
To help ward off such complications, some key preventative measures and an array of therapies have become available in recent years: Newborn screening and prophylaxis, including the introduction of pneumococcal vaccines, have substantially reduced rates of invasive pneumococcal infection, which previously accounted for 32% of all causes of death in patients with SCD under the age of 20.
And while hydroxyurea was the only medication from 1998 to 2017 to alleviate acute pain episodes in SCD, newer options have become available in recent years, with l-glutamine, voxelotor, and crizanlizumab gaining FDA approval to further help prevent the episodes.
However, studies show that many if not most patients fail to receive adequate treatment, with one recent report indicating that, between 2016 and 2020, hydroxyurea was prescribed to fewer than 25% of patients with SCD, and fewer than 4% of people with the disease who experience chronic pain episodes had prescriptions for the newer FDA-approved drugs.
Myths and truths
To help clarify some common misconceptions that contribute to the problems, Lewis Hsu, MD, PhD, chief medical officer of the Sickle Cell Disease Association of America, detailed some of the most prevalent and persistent myths among clinicians about SCD:
Pain level
Myths: Firstly, that sickle cell pain is not that bad, and patients therefore don’t really need opioid pain treatment, and secondly, that sickle cell pain is measurable by lab tests, such as the number of sickled red blood cells on a blood smear, reticulocytes, or hemoglobin level.
Truths: “Sickle cell vaso-occlusive pain can be very severe – a 10 on a scale of 10 – but the pain is usually only known by subjective report,” said Dr. Hsu, a pediatric hematologist who serves as director of the Sickle Cell Center and professor of pediatrics for the University of Illinois at Chicago.
“No lab test can be used to measure pain,” he said. “Other lab tests can be abnormal, and some have statistical correlation with lifetime severity of disease course, but the lab tests are not for determination of acute level of pain or absence of pain.”
Blacks only
Myth: SCD only affects Black people.
Truth: People who have sickle cell disease from many ethnic backgrounds and skin colors.
“Around the Mediterranean, there are sickle cell patients from Greece, Turkey, Italy, and Spain. Some are blond and blue-eyed. People in India and Pakistan have sickle cell disease,” Dr. Hsu explained.
In addition, “people from the Arabian Peninsula have sickle cell disease; some Malaysians have sickle cell disease; one child who is about third generation in Hong Kong has sickle cell disease.”
Parental link
Myth: Sickle cell disease only occurs in individuals both of whose parents have the sickle gene.
Truth: “There are types of sickle cell disease [involving] a sickle cell gene from one parent and a gene for hemoglobin C from the other parent,” Dr. Hsu noted. “Others inherited one sickle gene [from one parent] and inherited from the other parent a gene for beta thalassemia. Others involve an inherited sickle gene and hemoglobin E; others have inherited one sickle gene and inherited a gene for hemoglobin D-Punjab, while others have sickle and hemoglobin O-Arab.”
Effects beyond pain
Myth: A person who is not having sickle cell pain is otherwise not significantly affected by their disease.
Truth: “Organs can be damaged silently every day,” Dr. Hsu said. “Kidney failure, retina damage, and pulmonary hypertension are the most notable of organ systems that can suffer damage for a long time without symptoms, then develop symptoms when it is too late to intervene.”
“For this reason, individuals with sickle cell disease should have regular expert care for health maintenance that is disease specific,” Dr. Hsu added.
Consult guidelines
One final concern is a basic failure to utilize critical information sources and guidelines, especially by primary care providers and/or other nonspecialists from whom patients with SCD may often seek treatment. “Awareness of these guidelines is low,” Dr. Hsu said.
Key resources that can be helpful include evidence-based guidelines developed by an expert panel of the National Heart, Lung, and Blood Institute, and the American Society of Hematology has a Pocket Guide app on management of sickle cell disease.
Another key resource being highlighted in September, which is National Sickle Cell Disease Awareness Month, is the NHLBI’s comprehensive website, providing information ranging from fact sheets on the disease and treatments to social media resources and inspiring stories of people with SCD.
“We are trying to bring more sickle cell information and case studies into medical school curricula, nursing curricula, social workers and community health workers awareness, [and] apps and online guidelines are proliferating,” Dr. Hsu says.
He goes on to say, “We need more recognition and resources from insurance providers that quality care for sickle cell disease is measured and rewarded.”
Dr. Hsu coauthored “Hope and Destiny: The Patient and Parent’s Guide to Sickle Cell Disease and Sickle Cell Trait.” He reported relationships with Novartis, Emmaus, Forma Therapeutic, Dupont/Nemours Children’s Hospital, Hilton Publishing, Asklepion, Bayer, CRISPR/Vertex, Cyclerion, Pfizer, and Aruvant.
Affecting more than 20 million people globally and 100,000 people nationwide, SCD is the most common inherited blood disorder in the United States. It occurs largely but not exclusively among people of African descent.
Patients with SCD develop crescent-shaped or “sickled” red blood cells that, unlike normally round cells, can potentially block blood flow and thus cause a host of problems ranging from a risk of stroke or infections to sometimes severe pain crises, called vaso-occlusive episodes.
To help ward off such complications, some key preventative measures and an array of therapies have become available in recent years: Newborn screening and prophylaxis, including the introduction of pneumococcal vaccines, have substantially reduced rates of invasive pneumococcal infection, which previously accounted for 32% of all causes of death in patients with SCD under the age of 20.
And while hydroxyurea was the only medication from 1998 to 2017 to alleviate acute pain episodes in SCD, newer options have become available in recent years, with l-glutamine, voxelotor, and crizanlizumab gaining FDA approval to further help prevent the episodes.
However, studies show that many if not most patients fail to receive adequate treatment, with one recent report indicating that, between 2016 and 2020, hydroxyurea was prescribed to fewer than 25% of patients with SCD, and fewer than 4% of people with the disease who experience chronic pain episodes had prescriptions for the newer FDA-approved drugs.
Myths and truths
To help clarify some common misconceptions that contribute to the problems, Lewis Hsu, MD, PhD, chief medical officer of the Sickle Cell Disease Association of America, detailed some of the most prevalent and persistent myths among clinicians about SCD:
Pain level
Myths: Firstly, that sickle cell pain is not that bad, and patients therefore don’t really need opioid pain treatment, and secondly, that sickle cell pain is measurable by lab tests, such as the number of sickled red blood cells on a blood smear, reticulocytes, or hemoglobin level.
Truths: “Sickle cell vaso-occlusive pain can be very severe – a 10 on a scale of 10 – but the pain is usually only known by subjective report,” said Dr. Hsu, a pediatric hematologist who serves as director of the Sickle Cell Center and professor of pediatrics for the University of Illinois at Chicago.
“No lab test can be used to measure pain,” he said. “Other lab tests can be abnormal, and some have statistical correlation with lifetime severity of disease course, but the lab tests are not for determination of acute level of pain or absence of pain.”
Blacks only
Myth: SCD only affects Black people.
Truth: People who have sickle cell disease from many ethnic backgrounds and skin colors.
“Around the Mediterranean, there are sickle cell patients from Greece, Turkey, Italy, and Spain. Some are blond and blue-eyed. People in India and Pakistan have sickle cell disease,” Dr. Hsu explained.
In addition, “people from the Arabian Peninsula have sickle cell disease; some Malaysians have sickle cell disease; one child who is about third generation in Hong Kong has sickle cell disease.”
Parental link
Myth: Sickle cell disease only occurs in individuals both of whose parents have the sickle gene.
Truth: “There are types of sickle cell disease [involving] a sickle cell gene from one parent and a gene for hemoglobin C from the other parent,” Dr. Hsu noted. “Others inherited one sickle gene [from one parent] and inherited from the other parent a gene for beta thalassemia. Others involve an inherited sickle gene and hemoglobin E; others have inherited one sickle gene and inherited a gene for hemoglobin D-Punjab, while others have sickle and hemoglobin O-Arab.”
Effects beyond pain
Myth: A person who is not having sickle cell pain is otherwise not significantly affected by their disease.
Truth: “Organs can be damaged silently every day,” Dr. Hsu said. “Kidney failure, retina damage, and pulmonary hypertension are the most notable of organ systems that can suffer damage for a long time without symptoms, then develop symptoms when it is too late to intervene.”
“For this reason, individuals with sickle cell disease should have regular expert care for health maintenance that is disease specific,” Dr. Hsu added.
Consult guidelines
One final concern is a basic failure to utilize critical information sources and guidelines, especially by primary care providers and/or other nonspecialists from whom patients with SCD may often seek treatment. “Awareness of these guidelines is low,” Dr. Hsu said.
Key resources that can be helpful include evidence-based guidelines developed by an expert panel of the National Heart, Lung, and Blood Institute, and the American Society of Hematology has a Pocket Guide app on management of sickle cell disease.
Another key resource being highlighted in September, which is National Sickle Cell Disease Awareness Month, is the NHLBI’s comprehensive website, providing information ranging from fact sheets on the disease and treatments to social media resources and inspiring stories of people with SCD.
“We are trying to bring more sickle cell information and case studies into medical school curricula, nursing curricula, social workers and community health workers awareness, [and] apps and online guidelines are proliferating,” Dr. Hsu says.
He goes on to say, “We need more recognition and resources from insurance providers that quality care for sickle cell disease is measured and rewarded.”
Dr. Hsu coauthored “Hope and Destiny: The Patient and Parent’s Guide to Sickle Cell Disease and Sickle Cell Trait.” He reported relationships with Novartis, Emmaus, Forma Therapeutic, Dupont/Nemours Children’s Hospital, Hilton Publishing, Asklepion, Bayer, CRISPR/Vertex, Cyclerion, Pfizer, and Aruvant.
Affecting more than 20 million people globally and 100,000 people nationwide, SCD is the most common inherited blood disorder in the United States. It occurs largely but not exclusively among people of African descent.
Patients with SCD develop crescent-shaped or “sickled” red blood cells that, unlike normally round cells, can potentially block blood flow and thus cause a host of problems ranging from a risk of stroke or infections to sometimes severe pain crises, called vaso-occlusive episodes.
To help ward off such complications, some key preventative measures and an array of therapies have become available in recent years: Newborn screening and prophylaxis, including the introduction of pneumococcal vaccines, have substantially reduced rates of invasive pneumococcal infection, which previously accounted for 32% of all causes of death in patients with SCD under the age of 20.
And while hydroxyurea was the only medication from 1998 to 2017 to alleviate acute pain episodes in SCD, newer options have become available in recent years, with l-glutamine, voxelotor, and crizanlizumab gaining FDA approval to further help prevent the episodes.
However, studies show that many if not most patients fail to receive adequate treatment, with one recent report indicating that, between 2016 and 2020, hydroxyurea was prescribed to fewer than 25% of patients with SCD, and fewer than 4% of people with the disease who experience chronic pain episodes had prescriptions for the newer FDA-approved drugs.
Myths and truths
To help clarify some common misconceptions that contribute to the problems, Lewis Hsu, MD, PhD, chief medical officer of the Sickle Cell Disease Association of America, detailed some of the most prevalent and persistent myths among clinicians about SCD:
Pain level
Myths: Firstly, that sickle cell pain is not that bad, and patients therefore don’t really need opioid pain treatment, and secondly, that sickle cell pain is measurable by lab tests, such as the number of sickled red blood cells on a blood smear, reticulocytes, or hemoglobin level.
Truths: “Sickle cell vaso-occlusive pain can be very severe – a 10 on a scale of 10 – but the pain is usually only known by subjective report,” said Dr. Hsu, a pediatric hematologist who serves as director of the Sickle Cell Center and professor of pediatrics for the University of Illinois at Chicago.
“No lab test can be used to measure pain,” he said. “Other lab tests can be abnormal, and some have statistical correlation with lifetime severity of disease course, but the lab tests are not for determination of acute level of pain or absence of pain.”
Blacks only
Myth: SCD only affects Black people.
Truth: People who have sickle cell disease from many ethnic backgrounds and skin colors.
“Around the Mediterranean, there are sickle cell patients from Greece, Turkey, Italy, and Spain. Some are blond and blue-eyed. People in India and Pakistan have sickle cell disease,” Dr. Hsu explained.
In addition, “people from the Arabian Peninsula have sickle cell disease; some Malaysians have sickle cell disease; one child who is about third generation in Hong Kong has sickle cell disease.”
Parental link
Myth: Sickle cell disease only occurs in individuals both of whose parents have the sickle gene.
Truth: “There are types of sickle cell disease [involving] a sickle cell gene from one parent and a gene for hemoglobin C from the other parent,” Dr. Hsu noted. “Others inherited one sickle gene [from one parent] and inherited from the other parent a gene for beta thalassemia. Others involve an inherited sickle gene and hemoglobin E; others have inherited one sickle gene and inherited a gene for hemoglobin D-Punjab, while others have sickle and hemoglobin O-Arab.”
Effects beyond pain
Myth: A person who is not having sickle cell pain is otherwise not significantly affected by their disease.
Truth: “Organs can be damaged silently every day,” Dr. Hsu said. “Kidney failure, retina damage, and pulmonary hypertension are the most notable of organ systems that can suffer damage for a long time without symptoms, then develop symptoms when it is too late to intervene.”
“For this reason, individuals with sickle cell disease should have regular expert care for health maintenance that is disease specific,” Dr. Hsu added.
Consult guidelines
One final concern is a basic failure to utilize critical information sources and guidelines, especially by primary care providers and/or other nonspecialists from whom patients with SCD may often seek treatment. “Awareness of these guidelines is low,” Dr. Hsu said.
Key resources that can be helpful include evidence-based guidelines developed by an expert panel of the National Heart, Lung, and Blood Institute, and the American Society of Hematology has a Pocket Guide app on management of sickle cell disease.
Another key resource being highlighted in September, which is National Sickle Cell Disease Awareness Month, is the NHLBI’s comprehensive website, providing information ranging from fact sheets on the disease and treatments to social media resources and inspiring stories of people with SCD.
“We are trying to bring more sickle cell information and case studies into medical school curricula, nursing curricula, social workers and community health workers awareness, [and] apps and online guidelines are proliferating,” Dr. Hsu says.
He goes on to say, “We need more recognition and resources from insurance providers that quality care for sickle cell disease is measured and rewarded.”
Dr. Hsu coauthored “Hope and Destiny: The Patient and Parent’s Guide to Sickle Cell Disease and Sickle Cell Trait.” He reported relationships with Novartis, Emmaus, Forma Therapeutic, Dupont/Nemours Children’s Hospital, Hilton Publishing, Asklepion, Bayer, CRISPR/Vertex, Cyclerion, Pfizer, and Aruvant.
Pediatrician with SCD gives her young patients hope
These days, thanks to transformative advances in treating SCD that have substantially improved survival, Dr. Fasipe’s mission for a new generation of patients and their families is to replace their pain and fear with relief and hope.
“If you grow up thinking that you’re going to die when you’re 18, it changes your world and your viewpoints, and it impacts your mental health,” she told this news organization.
“We are trying to make sure our children and their families know that there is a new story for sickle cell disease, and you don’t have to use any age as your prediction marker for your lifespan,” Dr. Fasipe said.
SCD, which affects about 100,000 people nationwide, is an inherited blood disorder, with the majority of patients – but not all – being of African descent. This condition is characterized by pain crises, or vaso-occlusive episodes, triggered when cells that are sickled get stuck and impede blood flow. These crises can come on suddenly and range from mild to severe.
Dr. Fasipe was born in Nigeria, where rates of SCD are among the world’s highest. She attended elementary school in the United States, where her father was studying theology, before returning to Nigeria with her family at age 11.
Back in those days, in both nations only about 50% of children with SCD lived beyond their 18th birthday. The survival rates in Nigeria and sub-Saharan Africa countries continue to be poor. In some more developed regions elsewhere, advances such as universal newborn screening, penicillin prophylaxis, pneumococcal vaccination, stroke screening, and hydroxyurea therapy have yielded substantial improvements, with 95% or more patients with SCD reaching their 18th birthday.
“With measures such as newborn screening, we can immediately start prevention measures in sickle cell disease, such as prevention of infection, which was the number one reason why children were dying,” Dr. Fasipe explained. “With global initiatives, we want that story to be the same in sub-Saharan Africa as well.”
Cousin’s early death inspires medical studies
In an essay published by Texas Medical Center that describes her childhood experiences, Dr. Fasipe recounts a pivotal event in her life: The heartbreaking death of her beloved cousin at the age of just 17, from a complication of SCD. This bereavement fueled Dr. Fasipe’s determination to pursue a medical career, to do all that she could to prevent such losses.
“Having sickle cell disease myself wasn’t the trigger that made me become a doctor. But when Femi [her cousin] died, I thought: ‘This shouldn’t happen,’ ” Dr. Fasipe wrote.
When she applied to medical school back in the United States, she declared in her application essay: “I want to cure sickle cell.”
By the time Dr. Fasipe was ready to undertake residency and fellowship applications, her essay had shifted to focus on pediatrics “specifically because I want to reach sickle cell patients before they’ve defined how their lives are going to be,” she said. “I want to give them hope.”
Hope for a cure
Fast-forwarding to this point in Dr. Fasipe’s career, she noted that her dream of a cure for SCD is no longer a distant aspiration, thanks to the advent of stem cell transplantation and more recently, gene therapy. These advancements have elevated her hope for a cure to an entirely new level.
Each new treatment comes with caveats. Stem cell transplantation requires a matching donor, leaving the majority of patients ineligible. And while gene therapy eliminates the need for a donor, treatment can reportedly cost nearly $3 million. Nevertheless, Dr. Fasipe emphasized the promise that these new advancements represent.
“The scientists that work in these spaces do appreciate these [accessibility barriers], and the expectation is these therapies will be more accessible with time and effort,” she said. “We’ve got to start somewhere, and it’s exciting that they’re making these early successes.”
Advice for clinicians
With firsthand knowledge of how it feels to be the patient, as well as on the clinician side of SCD treatment, Dr. Fasipe advises colleagues on some ways that they can improve care while boosting their patients’ hope:
Speak with empathy
Acknowledge the ‘elephant in the room’; the pain that patients with SCD can experience is real.
“When I’m managing any patient with pain, I first acknowledge the suffering because while we may not understand what that person is going through, acknowledgment is part of showing empathy,” she explains.
Seek out resources
Patients with SCD may typically seek treatment in primary care, where expertise in the disease may be lacking, and general practitioners may feel frustrated that there are limited treatment options.
“If you do find yourself treating a sickle cell disease patient, you may not have all of the answers, but there are good resources, whether it’s a nearby sickle cell disease centers or national guidelines,” Dr. Fasipe said.
Access to treatment
With research, including a recent study, showing that only about 25% of patients with SCD are prescribed hydroxyurea and even fewer – only about 5% – receive more recently approved SCD treatments, clinicians should be proactive by making sure that patients receive needed treatments.
“Clearly medicines like hydroxyurea are not as optimized in this community space as they should be, and then there are newer therapies that families, patients, and even providers may not be aware of, so it is important to be informed of the guidelines and provide all patients with comprehensive, high-quality care,” Dr. Fasipe said.
In the ED, patients with SCD are ‘care-seeking,’ not drug-seeking
Due to the sometimes rapid onset of severe pain symptoms, patients with SCD commonly wind up in the emergency department. In this time of an opioid epidemic, patients too often are suspected of merely seeking drugs.
“Sickle cell disease tends to get lumped into a category of a disease of pain, but pain is subjective and it is difficult to quantify, so unfortunately, patients can be labeled as potentially drug-seeking,” Dr. Fasipe explained, citing an article that detailed this problem.
Consequently, patients may have particularly negative experiences in the emergency department, but the use of resources such as a sickle cell disease point-of-care tool developed by the American College of Emergency Physicians and the American Society of Hematology can help improve care for those patients.
“One of the [point-of-care recommendations] before even managing the pain is that physicians show compassion by acknowledging the patient’s pain and that they understand why pain with sickle cell disease might look different than other types of pain,” Dr. Fasipe said.
Building trust
Encounters such as negative emergency department experiences can perpetuate a deeper issue of distrust between those with SCD and the medical community, which originated in long-held, well-documented racial disparities in health care.
“We know historically and even today that there are difficulties facing our families who are impacted by sickle cell disease, and they are related to structural racism and socioeconomic barriers,” Dr. Fasipe explained.
With these issues in mind, she said, “I refer to sickle cell disease as the medical representation of the Black experience in America.” However, she added, the good news is “we are now doing our best now to improve that.”
Among key efforts in building trust is the inclusion of patients with SCD and their families in as many aspects of research and clinical care as possible.
“In the global health care community, it is imperative to invite people with sickle cell disease and from the community to the decision-making table,” she noted.
“Now, when we’re talking about research for therapies, their expectation is that research trials and other initiatives for sickle cell disease must have input from the community; there are no initiatives for sickle cell disease that do not have input from the community.
“The patients and community members may not be experts on the science of sickle cell, but they’re experts on the lived experience and that’s very important when you’re thinking about new bringing in a new therapy.”
Forward momentum
Meanwhile, Dr. Fasipe observed, with the collective, advocacy-driven, forward momentum of the SCD community as a whole, things should only continue to improve.
“Because of the various barriers, some progress may not be immediately around the corner, but I do have confidence that this current generation of children with sickle cell will have improved health equity by the time they reach adulthood,” she said.
“I believe in this future, so I’m doing the work now, and it’s a promise I tell parents: I want your future adult child to live their best life, and we’re working hard to ensure that that becomes their future reality.”
Sickle cell disease awareness
September is National Sickle Cell Disease Awareness Month, and the National Heart, Lung, and Blood Institute offers a comprehensive website that clinicians can pass along to their patients, with information ranging from fact sheets on the disease and treatments to social media resources and inspiring stories of people with the disease.
In a comment, Lewis Hsu, MD, PhD, chief medical officer of the Sickle Cell Disease Association of America, underscored the uniquely important contributions of people like Dr. Fasipe, in providing inspiration to patients and clinicians alike.
“I have worked with several physicians, nurses, psychologists, and public health specialists who have sickle cell disease,” said Dr. Hsu, who is a pediatric hematologist who also serves as director of the Sickle Cell Center and professor of pediatrics for the University of Illinois at Chicago.
“They are ambassadors who have the trust of both patients and healthcare providers,” Dr. Hsu said.
In addition to providing inspiration of resilience, such care providers can serve as “communication bridges,” he explained.
“When they are conference speakers, everybody wants to hear them; when they sit on advisory committees or focus groups, they can help find the compromise or set the priorities.”
“Their impact on the whole sickle cell community is very large,” Dr. Hsu said.
These days, thanks to transformative advances in treating SCD that have substantially improved survival, Dr. Fasipe’s mission for a new generation of patients and their families is to replace their pain and fear with relief and hope.
“If you grow up thinking that you’re going to die when you’re 18, it changes your world and your viewpoints, and it impacts your mental health,” she told this news organization.
“We are trying to make sure our children and their families know that there is a new story for sickle cell disease, and you don’t have to use any age as your prediction marker for your lifespan,” Dr. Fasipe said.
SCD, which affects about 100,000 people nationwide, is an inherited blood disorder, with the majority of patients – but not all – being of African descent. This condition is characterized by pain crises, or vaso-occlusive episodes, triggered when cells that are sickled get stuck and impede blood flow. These crises can come on suddenly and range from mild to severe.
Dr. Fasipe was born in Nigeria, where rates of SCD are among the world’s highest. She attended elementary school in the United States, where her father was studying theology, before returning to Nigeria with her family at age 11.
Back in those days, in both nations only about 50% of children with SCD lived beyond their 18th birthday. The survival rates in Nigeria and sub-Saharan Africa countries continue to be poor. In some more developed regions elsewhere, advances such as universal newborn screening, penicillin prophylaxis, pneumococcal vaccination, stroke screening, and hydroxyurea therapy have yielded substantial improvements, with 95% or more patients with SCD reaching their 18th birthday.
“With measures such as newborn screening, we can immediately start prevention measures in sickle cell disease, such as prevention of infection, which was the number one reason why children were dying,” Dr. Fasipe explained. “With global initiatives, we want that story to be the same in sub-Saharan Africa as well.”
Cousin’s early death inspires medical studies
In an essay published by Texas Medical Center that describes her childhood experiences, Dr. Fasipe recounts a pivotal event in her life: The heartbreaking death of her beloved cousin at the age of just 17, from a complication of SCD. This bereavement fueled Dr. Fasipe’s determination to pursue a medical career, to do all that she could to prevent such losses.
“Having sickle cell disease myself wasn’t the trigger that made me become a doctor. But when Femi [her cousin] died, I thought: ‘This shouldn’t happen,’ ” Dr. Fasipe wrote.
When she applied to medical school back in the United States, she declared in her application essay: “I want to cure sickle cell.”
By the time Dr. Fasipe was ready to undertake residency and fellowship applications, her essay had shifted to focus on pediatrics “specifically because I want to reach sickle cell patients before they’ve defined how their lives are going to be,” she said. “I want to give them hope.”
Hope for a cure
Fast-forwarding to this point in Dr. Fasipe’s career, she noted that her dream of a cure for SCD is no longer a distant aspiration, thanks to the advent of stem cell transplantation and more recently, gene therapy. These advancements have elevated her hope for a cure to an entirely new level.
Each new treatment comes with caveats. Stem cell transplantation requires a matching donor, leaving the majority of patients ineligible. And while gene therapy eliminates the need for a donor, treatment can reportedly cost nearly $3 million. Nevertheless, Dr. Fasipe emphasized the promise that these new advancements represent.
“The scientists that work in these spaces do appreciate these [accessibility barriers], and the expectation is these therapies will be more accessible with time and effort,” she said. “We’ve got to start somewhere, and it’s exciting that they’re making these early successes.”
Advice for clinicians
With firsthand knowledge of how it feels to be the patient, as well as on the clinician side of SCD treatment, Dr. Fasipe advises colleagues on some ways that they can improve care while boosting their patients’ hope:
Speak with empathy
Acknowledge the ‘elephant in the room’; the pain that patients with SCD can experience is real.
“When I’m managing any patient with pain, I first acknowledge the suffering because while we may not understand what that person is going through, acknowledgment is part of showing empathy,” she explains.
Seek out resources
Patients with SCD may typically seek treatment in primary care, where expertise in the disease may be lacking, and general practitioners may feel frustrated that there are limited treatment options.
“If you do find yourself treating a sickle cell disease patient, you may not have all of the answers, but there are good resources, whether it’s a nearby sickle cell disease centers or national guidelines,” Dr. Fasipe said.
Access to treatment
With research, including a recent study, showing that only about 25% of patients with SCD are prescribed hydroxyurea and even fewer – only about 5% – receive more recently approved SCD treatments, clinicians should be proactive by making sure that patients receive needed treatments.
“Clearly medicines like hydroxyurea are not as optimized in this community space as they should be, and then there are newer therapies that families, patients, and even providers may not be aware of, so it is important to be informed of the guidelines and provide all patients with comprehensive, high-quality care,” Dr. Fasipe said.
In the ED, patients with SCD are ‘care-seeking,’ not drug-seeking
Due to the sometimes rapid onset of severe pain symptoms, patients with SCD commonly wind up in the emergency department. In this time of an opioid epidemic, patients too often are suspected of merely seeking drugs.
“Sickle cell disease tends to get lumped into a category of a disease of pain, but pain is subjective and it is difficult to quantify, so unfortunately, patients can be labeled as potentially drug-seeking,” Dr. Fasipe explained, citing an article that detailed this problem.
Consequently, patients may have particularly negative experiences in the emergency department, but the use of resources such as a sickle cell disease point-of-care tool developed by the American College of Emergency Physicians and the American Society of Hematology can help improve care for those patients.
“One of the [point-of-care recommendations] before even managing the pain is that physicians show compassion by acknowledging the patient’s pain and that they understand why pain with sickle cell disease might look different than other types of pain,” Dr. Fasipe said.
Building trust
Encounters such as negative emergency department experiences can perpetuate a deeper issue of distrust between those with SCD and the medical community, which originated in long-held, well-documented racial disparities in health care.
“We know historically and even today that there are difficulties facing our families who are impacted by sickle cell disease, and they are related to structural racism and socioeconomic barriers,” Dr. Fasipe explained.
With these issues in mind, she said, “I refer to sickle cell disease as the medical representation of the Black experience in America.” However, she added, the good news is “we are now doing our best now to improve that.”
Among key efforts in building trust is the inclusion of patients with SCD and their families in as many aspects of research and clinical care as possible.
“In the global health care community, it is imperative to invite people with sickle cell disease and from the community to the decision-making table,” she noted.
“Now, when we’re talking about research for therapies, their expectation is that research trials and other initiatives for sickle cell disease must have input from the community; there are no initiatives for sickle cell disease that do not have input from the community.
“The patients and community members may not be experts on the science of sickle cell, but they’re experts on the lived experience and that’s very important when you’re thinking about new bringing in a new therapy.”
Forward momentum
Meanwhile, Dr. Fasipe observed, with the collective, advocacy-driven, forward momentum of the SCD community as a whole, things should only continue to improve.
“Because of the various barriers, some progress may not be immediately around the corner, but I do have confidence that this current generation of children with sickle cell will have improved health equity by the time they reach adulthood,” she said.
“I believe in this future, so I’m doing the work now, and it’s a promise I tell parents: I want your future adult child to live their best life, and we’re working hard to ensure that that becomes their future reality.”
Sickle cell disease awareness
September is National Sickle Cell Disease Awareness Month, and the National Heart, Lung, and Blood Institute offers a comprehensive website that clinicians can pass along to their patients, with information ranging from fact sheets on the disease and treatments to social media resources and inspiring stories of people with the disease.
In a comment, Lewis Hsu, MD, PhD, chief medical officer of the Sickle Cell Disease Association of America, underscored the uniquely important contributions of people like Dr. Fasipe, in providing inspiration to patients and clinicians alike.
“I have worked with several physicians, nurses, psychologists, and public health specialists who have sickle cell disease,” said Dr. Hsu, who is a pediatric hematologist who also serves as director of the Sickle Cell Center and professor of pediatrics for the University of Illinois at Chicago.
“They are ambassadors who have the trust of both patients and healthcare providers,” Dr. Hsu said.
In addition to providing inspiration of resilience, such care providers can serve as “communication bridges,” he explained.
“When they are conference speakers, everybody wants to hear them; when they sit on advisory committees or focus groups, they can help find the compromise or set the priorities.”
“Their impact on the whole sickle cell community is very large,” Dr. Hsu said.
These days, thanks to transformative advances in treating SCD that have substantially improved survival, Dr. Fasipe’s mission for a new generation of patients and their families is to replace their pain and fear with relief and hope.
“If you grow up thinking that you’re going to die when you’re 18, it changes your world and your viewpoints, and it impacts your mental health,” she told this news organization.
“We are trying to make sure our children and their families know that there is a new story for sickle cell disease, and you don’t have to use any age as your prediction marker for your lifespan,” Dr. Fasipe said.
SCD, which affects about 100,000 people nationwide, is an inherited blood disorder, with the majority of patients – but not all – being of African descent. This condition is characterized by pain crises, or vaso-occlusive episodes, triggered when cells that are sickled get stuck and impede blood flow. These crises can come on suddenly and range from mild to severe.
Dr. Fasipe was born in Nigeria, where rates of SCD are among the world’s highest. She attended elementary school in the United States, where her father was studying theology, before returning to Nigeria with her family at age 11.
Back in those days, in both nations only about 50% of children with SCD lived beyond their 18th birthday. The survival rates in Nigeria and sub-Saharan Africa countries continue to be poor. In some more developed regions elsewhere, advances such as universal newborn screening, penicillin prophylaxis, pneumococcal vaccination, stroke screening, and hydroxyurea therapy have yielded substantial improvements, with 95% or more patients with SCD reaching their 18th birthday.
“With measures such as newborn screening, we can immediately start prevention measures in sickle cell disease, such as prevention of infection, which was the number one reason why children were dying,” Dr. Fasipe explained. “With global initiatives, we want that story to be the same in sub-Saharan Africa as well.”
Cousin’s early death inspires medical studies
In an essay published by Texas Medical Center that describes her childhood experiences, Dr. Fasipe recounts a pivotal event in her life: The heartbreaking death of her beloved cousin at the age of just 17, from a complication of SCD. This bereavement fueled Dr. Fasipe’s determination to pursue a medical career, to do all that she could to prevent such losses.
“Having sickle cell disease myself wasn’t the trigger that made me become a doctor. But when Femi [her cousin] died, I thought: ‘This shouldn’t happen,’ ” Dr. Fasipe wrote.
When she applied to medical school back in the United States, she declared in her application essay: “I want to cure sickle cell.”
By the time Dr. Fasipe was ready to undertake residency and fellowship applications, her essay had shifted to focus on pediatrics “specifically because I want to reach sickle cell patients before they’ve defined how their lives are going to be,” she said. “I want to give them hope.”
Hope for a cure
Fast-forwarding to this point in Dr. Fasipe’s career, she noted that her dream of a cure for SCD is no longer a distant aspiration, thanks to the advent of stem cell transplantation and more recently, gene therapy. These advancements have elevated her hope for a cure to an entirely new level.
Each new treatment comes with caveats. Stem cell transplantation requires a matching donor, leaving the majority of patients ineligible. And while gene therapy eliminates the need for a donor, treatment can reportedly cost nearly $3 million. Nevertheless, Dr. Fasipe emphasized the promise that these new advancements represent.
“The scientists that work in these spaces do appreciate these [accessibility barriers], and the expectation is these therapies will be more accessible with time and effort,” she said. “We’ve got to start somewhere, and it’s exciting that they’re making these early successes.”
Advice for clinicians
With firsthand knowledge of how it feels to be the patient, as well as on the clinician side of SCD treatment, Dr. Fasipe advises colleagues on some ways that they can improve care while boosting their patients’ hope:
Speak with empathy
Acknowledge the ‘elephant in the room’; the pain that patients with SCD can experience is real.
“When I’m managing any patient with pain, I first acknowledge the suffering because while we may not understand what that person is going through, acknowledgment is part of showing empathy,” she explains.
Seek out resources
Patients with SCD may typically seek treatment in primary care, where expertise in the disease may be lacking, and general practitioners may feel frustrated that there are limited treatment options.
“If you do find yourself treating a sickle cell disease patient, you may not have all of the answers, but there are good resources, whether it’s a nearby sickle cell disease centers or national guidelines,” Dr. Fasipe said.
Access to treatment
With research, including a recent study, showing that only about 25% of patients with SCD are prescribed hydroxyurea and even fewer – only about 5% – receive more recently approved SCD treatments, clinicians should be proactive by making sure that patients receive needed treatments.
“Clearly medicines like hydroxyurea are not as optimized in this community space as they should be, and then there are newer therapies that families, patients, and even providers may not be aware of, so it is important to be informed of the guidelines and provide all patients with comprehensive, high-quality care,” Dr. Fasipe said.
In the ED, patients with SCD are ‘care-seeking,’ not drug-seeking
Due to the sometimes rapid onset of severe pain symptoms, patients with SCD commonly wind up in the emergency department. In this time of an opioid epidemic, patients too often are suspected of merely seeking drugs.
“Sickle cell disease tends to get lumped into a category of a disease of pain, but pain is subjective and it is difficult to quantify, so unfortunately, patients can be labeled as potentially drug-seeking,” Dr. Fasipe explained, citing an article that detailed this problem.
Consequently, patients may have particularly negative experiences in the emergency department, but the use of resources such as a sickle cell disease point-of-care tool developed by the American College of Emergency Physicians and the American Society of Hematology can help improve care for those patients.
“One of the [point-of-care recommendations] before even managing the pain is that physicians show compassion by acknowledging the patient’s pain and that they understand why pain with sickle cell disease might look different than other types of pain,” Dr. Fasipe said.
Building trust
Encounters such as negative emergency department experiences can perpetuate a deeper issue of distrust between those with SCD and the medical community, which originated in long-held, well-documented racial disparities in health care.
“We know historically and even today that there are difficulties facing our families who are impacted by sickle cell disease, and they are related to structural racism and socioeconomic barriers,” Dr. Fasipe explained.
With these issues in mind, she said, “I refer to sickle cell disease as the medical representation of the Black experience in America.” However, she added, the good news is “we are now doing our best now to improve that.”
Among key efforts in building trust is the inclusion of patients with SCD and their families in as many aspects of research and clinical care as possible.
“In the global health care community, it is imperative to invite people with sickle cell disease and from the community to the decision-making table,” she noted.
“Now, when we’re talking about research for therapies, their expectation is that research trials and other initiatives for sickle cell disease must have input from the community; there are no initiatives for sickle cell disease that do not have input from the community.
“The patients and community members may not be experts on the science of sickle cell, but they’re experts on the lived experience and that’s very important when you’re thinking about new bringing in a new therapy.”
Forward momentum
Meanwhile, Dr. Fasipe observed, with the collective, advocacy-driven, forward momentum of the SCD community as a whole, things should only continue to improve.
“Because of the various barriers, some progress may not be immediately around the corner, but I do have confidence that this current generation of children with sickle cell will have improved health equity by the time they reach adulthood,” she said.
“I believe in this future, so I’m doing the work now, and it’s a promise I tell parents: I want your future adult child to live their best life, and we’re working hard to ensure that that becomes their future reality.”
Sickle cell disease awareness
September is National Sickle Cell Disease Awareness Month, and the National Heart, Lung, and Blood Institute offers a comprehensive website that clinicians can pass along to their patients, with information ranging from fact sheets on the disease and treatments to social media resources and inspiring stories of people with the disease.
In a comment, Lewis Hsu, MD, PhD, chief medical officer of the Sickle Cell Disease Association of America, underscored the uniquely important contributions of people like Dr. Fasipe, in providing inspiration to patients and clinicians alike.
“I have worked with several physicians, nurses, psychologists, and public health specialists who have sickle cell disease,” said Dr. Hsu, who is a pediatric hematologist who also serves as director of the Sickle Cell Center and professor of pediatrics for the University of Illinois at Chicago.
“They are ambassadors who have the trust of both patients and healthcare providers,” Dr. Hsu said.
In addition to providing inspiration of resilience, such care providers can serve as “communication bridges,” he explained.
“When they are conference speakers, everybody wants to hear them; when they sit on advisory committees or focus groups, they can help find the compromise or set the priorities.”
“Their impact on the whole sickle cell community is very large,” Dr. Hsu said.
Adhering to endocrine therapy is hard. What can be done?
Patients with breast cancer often stay on endocrine therapy for 5-10 years.
For many, however, long-term use is a challenge.
Stopping adjuvant endocrine therapy prematurely can have major consequences. These patients are more likely to experience cancer recurrence and to die earlier, research shows.
“Given that suboptimal adjuvant endocrine therapy adherence is common and is associated with breast cancer recurrence and mortality, there is a vital need for effective interventions to promote adherence,” Joanna J. Arch, PhD, from the University of Colorado Boulder, and colleagues write in a recent meta-analysis.
Experts discuss why it’s so challenging for patients to adhere to adjuvant endocrine therapy as well as which strategies may help boost long-term use and which likely will not.
The adherence problem
To improve adherence to adjuvant endocrine therapy, clinicians first need to understand the barriers patients face.
Studies indicate that a host of issues play into long-term adherence. Medication side effects, such as insomnia, fatigue, anxiety, depression, joint pain, and hot flashes, can deter patients from continuing endocrine therapy.
Tamoxifen, in particular, is known for its severe adverse events. Research suggests it may even increase patients’ risk for endometrial cancer and other uterine diseases.
Recent approvals of aromatase inhibitors – such as anastrozole, exemestane, and letrozole – have provided patients a tamoxifen alterative, but these agents come with their own issues, which include bone loss and vaginal dryness.
Common and severe side effects that affect adherence “should absolutely be addressed sooner, more frequently, and by any provider, not just the medical oncologist,” said Anna Weiss, MD, a breast cancer surgeon with the Wilmot Cancer Center, University of Rochester Medical Center, N.Y.
Other barriers to long-term use include the burden of managing comorbidities and drug costs as well as patients’ uncertainty about the value of long-term cancer therapy.
The issues that take center stage for individual patients may also vary by age. For older patients, comorbidities, cognitive function, and lack of social support may be key barriers to adherence, while for younger patients, fertility and sexual health issues are more pressing.
Clinicians should especially not underestimate the effects of hormonal suppression on adherence, explained Dr. Weiss, who recently published practice pearls on managing side effects of adjunctive endocrine therapy. “I do believe that we have been ignoring the sexual wellness aspect of breast cancer survivorship care for too long,” she said.
An array of fixes needed
Given the array of potential obstacles to endocrine therapy adherence, improving long-term use may be equally complex.
In a recent meta-analysis, Dr. Arch and colleagues combed the literature for studies exploring a host of strategies to improve endocrine therapy adherence. The team focused on 25 studies involving 367,873 women with breast cancer who were prescribed tamoxifen or an aromatase inhibitor.
The studies assessed a variety of interventions – disease management and exercise programs to lower side effects, medication reminders via phone or letter to limit missed doses, online educational materials to highlight the importance of adherence, as well as medication changes to reduce drug costs.
Overall, these interventions were of modest benefit in improving adherence. The findings indicate that “a variety of approaches” can be effective, Dr. Arch said.
But, she noted, aside from cost-cutting strategies, “no single approach stood out as more effective than others,” and some studies found minimal or inconsistent benefits to specific interventions.
One analysis, for instance, explored a text message intervention that involved sending patients several texts per week reminding them to take their medication, exercise more, or monitor their side effects. Overall, participants who received text messages missed fewer endocrine therapy doses, compared with those who didn’t – 7.1% versus 17.0% – and for about two-thirds of participants, the text messages motivated lifestyle changes.
Another study included in the meta-analysis, however, found that “twice-weekly text reminders did not improve adherence to aromatase inhibitors.”
Studies in which patients received educational materials about the importance of adherence or how to manage side effects found that effectiveness varied as well. Other analyses indicated that integrating relaxation techniques or other cognitive-behavioral approaches into patient care may have small beneficial effects on adherence.
Dr. Arch’s meta-analysis did, however, find a consistent benefit for cost-cutting interventions. Three large studies reported that medication adherence improved following policy changes that were focused on reducing costs of adjuvant endocrine therapy, either through legislation limiting out-of-pocket costs for oral drugs or by switching to generic formulations.
Xuanzi Qin, PhD, first author on one of the studies, explained that after generic aromatase inhibitor options became available, patients who switched to these options had lower out-of-pocket costs and higher rates of drug adherence.
The take-home message of the study is that “clinicians should know the out-of-pocket costs of the drugs and discuss the costs with patients,” Dr. Qin, of the University of Maryland School of Public Health, College Park, told this news organization.
Dr. Arch pointed out that although the meta-analysis found a consistent benefit to cost-cutting strategies, that does not necessarily translate to a strong benefit.
And overall, the body of research indicates that “we need to develop and test new strategies and hone existing ones,” Dr. Arch said, “so that we can boost adherence even more and help more women benefit fully from these life-extending medications.”
However, Dr. Weiss explained, seemingly small measures may still make important clinical differences for individual patients, even if studies don’t show a statistically significant impact overall on endocrine therapy adherence.
For Dr. Weiss, “even getting one patient to continue their endocrine therapy is a win in my book.”
Dr. Arch reported a consulting or advisory role with AbbVie/Genentech and Bristol-Meyers Squibb and research funding from NCCN/Astrazeneca. Dr. Weiss reports being on the advisory board for Merck and Myriad. Dr. Qin has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Patients with breast cancer often stay on endocrine therapy for 5-10 years.
For many, however, long-term use is a challenge.
Stopping adjuvant endocrine therapy prematurely can have major consequences. These patients are more likely to experience cancer recurrence and to die earlier, research shows.
“Given that suboptimal adjuvant endocrine therapy adherence is common and is associated with breast cancer recurrence and mortality, there is a vital need for effective interventions to promote adherence,” Joanna J. Arch, PhD, from the University of Colorado Boulder, and colleagues write in a recent meta-analysis.
Experts discuss why it’s so challenging for patients to adhere to adjuvant endocrine therapy as well as which strategies may help boost long-term use and which likely will not.
The adherence problem
To improve adherence to adjuvant endocrine therapy, clinicians first need to understand the barriers patients face.
Studies indicate that a host of issues play into long-term adherence. Medication side effects, such as insomnia, fatigue, anxiety, depression, joint pain, and hot flashes, can deter patients from continuing endocrine therapy.
Tamoxifen, in particular, is known for its severe adverse events. Research suggests it may even increase patients’ risk for endometrial cancer and other uterine diseases.
Recent approvals of aromatase inhibitors – such as anastrozole, exemestane, and letrozole – have provided patients a tamoxifen alterative, but these agents come with their own issues, which include bone loss and vaginal dryness.
Common and severe side effects that affect adherence “should absolutely be addressed sooner, more frequently, and by any provider, not just the medical oncologist,” said Anna Weiss, MD, a breast cancer surgeon with the Wilmot Cancer Center, University of Rochester Medical Center, N.Y.
Other barriers to long-term use include the burden of managing comorbidities and drug costs as well as patients’ uncertainty about the value of long-term cancer therapy.
The issues that take center stage for individual patients may also vary by age. For older patients, comorbidities, cognitive function, and lack of social support may be key barriers to adherence, while for younger patients, fertility and sexual health issues are more pressing.
Clinicians should especially not underestimate the effects of hormonal suppression on adherence, explained Dr. Weiss, who recently published practice pearls on managing side effects of adjunctive endocrine therapy. “I do believe that we have been ignoring the sexual wellness aspect of breast cancer survivorship care for too long,” she said.
An array of fixes needed
Given the array of potential obstacles to endocrine therapy adherence, improving long-term use may be equally complex.
In a recent meta-analysis, Dr. Arch and colleagues combed the literature for studies exploring a host of strategies to improve endocrine therapy adherence. The team focused on 25 studies involving 367,873 women with breast cancer who were prescribed tamoxifen or an aromatase inhibitor.
The studies assessed a variety of interventions – disease management and exercise programs to lower side effects, medication reminders via phone or letter to limit missed doses, online educational materials to highlight the importance of adherence, as well as medication changes to reduce drug costs.
Overall, these interventions were of modest benefit in improving adherence. The findings indicate that “a variety of approaches” can be effective, Dr. Arch said.
But, she noted, aside from cost-cutting strategies, “no single approach stood out as more effective than others,” and some studies found minimal or inconsistent benefits to specific interventions.
One analysis, for instance, explored a text message intervention that involved sending patients several texts per week reminding them to take their medication, exercise more, or monitor their side effects. Overall, participants who received text messages missed fewer endocrine therapy doses, compared with those who didn’t – 7.1% versus 17.0% – and for about two-thirds of participants, the text messages motivated lifestyle changes.
Another study included in the meta-analysis, however, found that “twice-weekly text reminders did not improve adherence to aromatase inhibitors.”
Studies in which patients received educational materials about the importance of adherence or how to manage side effects found that effectiveness varied as well. Other analyses indicated that integrating relaxation techniques or other cognitive-behavioral approaches into patient care may have small beneficial effects on adherence.
Dr. Arch’s meta-analysis did, however, find a consistent benefit for cost-cutting interventions. Three large studies reported that medication adherence improved following policy changes that were focused on reducing costs of adjuvant endocrine therapy, either through legislation limiting out-of-pocket costs for oral drugs or by switching to generic formulations.
Xuanzi Qin, PhD, first author on one of the studies, explained that after generic aromatase inhibitor options became available, patients who switched to these options had lower out-of-pocket costs and higher rates of drug adherence.
The take-home message of the study is that “clinicians should know the out-of-pocket costs of the drugs and discuss the costs with patients,” Dr. Qin, of the University of Maryland School of Public Health, College Park, told this news organization.
Dr. Arch pointed out that although the meta-analysis found a consistent benefit to cost-cutting strategies, that does not necessarily translate to a strong benefit.
And overall, the body of research indicates that “we need to develop and test new strategies and hone existing ones,” Dr. Arch said, “so that we can boost adherence even more and help more women benefit fully from these life-extending medications.”
However, Dr. Weiss explained, seemingly small measures may still make important clinical differences for individual patients, even if studies don’t show a statistically significant impact overall on endocrine therapy adherence.
For Dr. Weiss, “even getting one patient to continue their endocrine therapy is a win in my book.”
Dr. Arch reported a consulting or advisory role with AbbVie/Genentech and Bristol-Meyers Squibb and research funding from NCCN/Astrazeneca. Dr. Weiss reports being on the advisory board for Merck and Myriad. Dr. Qin has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Patients with breast cancer often stay on endocrine therapy for 5-10 years.
For many, however, long-term use is a challenge.
Stopping adjuvant endocrine therapy prematurely can have major consequences. These patients are more likely to experience cancer recurrence and to die earlier, research shows.
“Given that suboptimal adjuvant endocrine therapy adherence is common and is associated with breast cancer recurrence and mortality, there is a vital need for effective interventions to promote adherence,” Joanna J. Arch, PhD, from the University of Colorado Boulder, and colleagues write in a recent meta-analysis.
Experts discuss why it’s so challenging for patients to adhere to adjuvant endocrine therapy as well as which strategies may help boost long-term use and which likely will not.
The adherence problem
To improve adherence to adjuvant endocrine therapy, clinicians first need to understand the barriers patients face.
Studies indicate that a host of issues play into long-term adherence. Medication side effects, such as insomnia, fatigue, anxiety, depression, joint pain, and hot flashes, can deter patients from continuing endocrine therapy.
Tamoxifen, in particular, is known for its severe adverse events. Research suggests it may even increase patients’ risk for endometrial cancer and other uterine diseases.
Recent approvals of aromatase inhibitors – such as anastrozole, exemestane, and letrozole – have provided patients a tamoxifen alterative, but these agents come with their own issues, which include bone loss and vaginal dryness.
Common and severe side effects that affect adherence “should absolutely be addressed sooner, more frequently, and by any provider, not just the medical oncologist,” said Anna Weiss, MD, a breast cancer surgeon with the Wilmot Cancer Center, University of Rochester Medical Center, N.Y.
Other barriers to long-term use include the burden of managing comorbidities and drug costs as well as patients’ uncertainty about the value of long-term cancer therapy.
The issues that take center stage for individual patients may also vary by age. For older patients, comorbidities, cognitive function, and lack of social support may be key barriers to adherence, while for younger patients, fertility and sexual health issues are more pressing.
Clinicians should especially not underestimate the effects of hormonal suppression on adherence, explained Dr. Weiss, who recently published practice pearls on managing side effects of adjunctive endocrine therapy. “I do believe that we have been ignoring the sexual wellness aspect of breast cancer survivorship care for too long,” she said.
An array of fixes needed
Given the array of potential obstacles to endocrine therapy adherence, improving long-term use may be equally complex.
In a recent meta-analysis, Dr. Arch and colleagues combed the literature for studies exploring a host of strategies to improve endocrine therapy adherence. The team focused on 25 studies involving 367,873 women with breast cancer who were prescribed tamoxifen or an aromatase inhibitor.
The studies assessed a variety of interventions – disease management and exercise programs to lower side effects, medication reminders via phone or letter to limit missed doses, online educational materials to highlight the importance of adherence, as well as medication changes to reduce drug costs.
Overall, these interventions were of modest benefit in improving adherence. The findings indicate that “a variety of approaches” can be effective, Dr. Arch said.
But, she noted, aside from cost-cutting strategies, “no single approach stood out as more effective than others,” and some studies found minimal or inconsistent benefits to specific interventions.
One analysis, for instance, explored a text message intervention that involved sending patients several texts per week reminding them to take their medication, exercise more, or monitor their side effects. Overall, participants who received text messages missed fewer endocrine therapy doses, compared with those who didn’t – 7.1% versus 17.0% – and for about two-thirds of participants, the text messages motivated lifestyle changes.
Another study included in the meta-analysis, however, found that “twice-weekly text reminders did not improve adherence to aromatase inhibitors.”
Studies in which patients received educational materials about the importance of adherence or how to manage side effects found that effectiveness varied as well. Other analyses indicated that integrating relaxation techniques or other cognitive-behavioral approaches into patient care may have small beneficial effects on adherence.
Dr. Arch’s meta-analysis did, however, find a consistent benefit for cost-cutting interventions. Three large studies reported that medication adherence improved following policy changes that were focused on reducing costs of adjuvant endocrine therapy, either through legislation limiting out-of-pocket costs for oral drugs or by switching to generic formulations.
Xuanzi Qin, PhD, first author on one of the studies, explained that after generic aromatase inhibitor options became available, patients who switched to these options had lower out-of-pocket costs and higher rates of drug adherence.
The take-home message of the study is that “clinicians should know the out-of-pocket costs of the drugs and discuss the costs with patients,” Dr. Qin, of the University of Maryland School of Public Health, College Park, told this news organization.
Dr. Arch pointed out that although the meta-analysis found a consistent benefit to cost-cutting strategies, that does not necessarily translate to a strong benefit.
And overall, the body of research indicates that “we need to develop and test new strategies and hone existing ones,” Dr. Arch said, “so that we can boost adherence even more and help more women benefit fully from these life-extending medications.”
However, Dr. Weiss explained, seemingly small measures may still make important clinical differences for individual patients, even if studies don’t show a statistically significant impact overall on endocrine therapy adherence.
For Dr. Weiss, “even getting one patient to continue their endocrine therapy is a win in my book.”
Dr. Arch reported a consulting or advisory role with AbbVie/Genentech and Bristol-Meyers Squibb and research funding from NCCN/Astrazeneca. Dr. Weiss reports being on the advisory board for Merck and Myriad. Dr. Qin has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Tirzepatide superior to semaglutide for A1c control, weight loss
, results from a meta-analysis of 22 randomized controlled trials show.
“The results indicate tirzepatide’s superior performance over subcutaneous semaglutide in managing blood sugar and achieving weight loss, making it a promising option in the pharmaceutical management of type 2 diabetes,” first author Thomas Karagiannis, MD, PhD, Aristotle University of Thessaloniki, Greece, said in an interview.
“In clinical context, the most potent doses of each drug revealed a clear difference regarding weight loss, with tirzepatide resulting in an average weight reduction that exceeded that of semaglutide by 5.7 kg (12.6 pounds),” he said.
The study is scheduled to be presented at the annual meeting of the European Association for the Study of Diabetes (EASD) in early October.
While a multitude of studies have been conducted for tirzepatide, a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1) receptor agonist, and semaglutide, a selective GLP-1 agonist, studies comparing the two drugs directly are lacking.
For a more comprehensive understanding of how the drugs compare, Dr. Karagiannis and colleagues conducted the meta-analysis of 22 trials, including two direct comparisons, the SURPASS-2 trial and a smaller trial, and 20 other studies comparing either semaglutide or tirzepatide with a common comparator, such as placebo, basal insulin, or other GLP-RA-1 drugs.
Overall, 18,472 participants were included in the studies.
All included studies had assessed a maintenance dose of tirzepatide of either 5, 10, or 15 mg once weekly or semaglutide at doses of 0.5, 1.0, or 2.0 mg once weekly for at least 12 weeks. All comparisons were for subcutaneous injection formulations (semaglutide can also be taken orally).
Blood glucose reduction
Tirzepatide at 15 mg was found to have the highest efficacy in the reduction of A1c compared with placebo, with a mean difference of –2.00%, followed by tirzepatide 10 mg (–1.86%) and semaglutide 2.0 mg (–1.62%).
All three of the tirzepatide doses had greater reductions in A1c compared with the respective low, medium, and high doses of semaglutide.
Dr. Karagiannis noted that the differences are significant: “An A1c reduction even by 0.5% is often deemed clinically important,” he said.
Body weight reduction comparisons
The reductions in body weight across the three drug doses were greater with tirzepatide (–10.96 kg [24.2 pounds], –8.75 kg [19.3 pounds], and –6.16 kg [13.6 pounds] for 15, 10, and 5 mg, respectively) compared with semaglutide (–5.24 kg [11.6 pounds], –4.44 kg [9.8 pounds], and –2.72 kg [6 pounds] for semaglutide 2.0, 1.0, and 0.5 mg, respectively).
In terms of drug-to-drug comparisons, tirzepatide 15 mg had a mean of 5.72 kg (12.6 pounds) greater reduction in body weight vs. semaglutide 2.0 mg; tirzepatide 10 mg had a mean of 3.52 kg (7.8 pounds) reduction vs. semaglutide 2.0 mg; and tirzepatide 5 mg had a mean of a 1.72 kg (3.8 pounds) greater reduction vs. semaglutide 1.0 mg.
Adverse events: Increased GI events with highest tirzepatide dose
Regarding the gastrointestinal adverse events associated with the drugs, tirzepatide 15 mg had the highest rate of the two drugs at their various doses, with a risk ratio (RR) of 3.57 compared with placebo for nausea, an RR of 4.35 for vomiting, and 2.04 for diarrhea.
There were no significant differences between the two drugs for the gastrointestinal events, with the exception of the highest dose of tirzepatide, 15 mg, which had a higher risk of vomiting vs. semaglutide 1.0 (RR 1.39) and semaglutide 0.5 mg (RR 1.85).
In addition, tirzepatide 15 mg had a higher risk vs. semaglutide 0.5 mg for nausea (RR 1.45).
There were no significant differences between the two drugs and placebo in the risk of serious adverse events.
Real-world applications, comparisons
Dr. Karagiannis noted that the results indicate that benefits of the efficacy of the higher tirzepatide dose need to be balanced with those potential side effects.
“Although the efficacy of the high tirzepatide dose might make it a favorable choice, its real-world application can be affected on an individual’s ability to tolerate these side effects in case they occur,” he explained.
Ultimately, “some patients may prioritize tolerability over enhanced efficacy,” he added.
Furthermore, while all three maintenance doses of tirzepatide analyzed have received marketing authorization, “to get a clearer picture of the real-world tolerance to these doses outside the context of randomized controlled trials, well-designed observational studies would be necessary,” Dr. Karagiannis said.
Among other issues of comparison with the two drugs is cost.
In a recent analysis, the cost per 1% of body weight reduction was reported to be $1,197 for high-dose tirzepatide (15 mg) vs. $1,511 for semaglutide 2.4 mg, with an overall cost of 72 weeks of therapy with tirzepatide at $17,527 compared with $22,878 for semaglutide.
Overall, patients and clinicians should consider the full range of differences and similarities between the medications, “from [their] efficacy and side effects to cost-effectiveness, long-term safety, and cardiovascular profile,” Dr. Karagiannis said.
Semaglutide is currently approved by the Food and Drug Administration for treatment of type 2 diabetes and obesity/weight loss management.
Tirzepatide has also received approval for the treatment of type 2 diabetes and its manufacturers have submitted applications for its approval for obesity/weight loss management.
Dr. Karagiannis reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, results from a meta-analysis of 22 randomized controlled trials show.
“The results indicate tirzepatide’s superior performance over subcutaneous semaglutide in managing blood sugar and achieving weight loss, making it a promising option in the pharmaceutical management of type 2 diabetes,” first author Thomas Karagiannis, MD, PhD, Aristotle University of Thessaloniki, Greece, said in an interview.
“In clinical context, the most potent doses of each drug revealed a clear difference regarding weight loss, with tirzepatide resulting in an average weight reduction that exceeded that of semaglutide by 5.7 kg (12.6 pounds),” he said.
The study is scheduled to be presented at the annual meeting of the European Association for the Study of Diabetes (EASD) in early October.
While a multitude of studies have been conducted for tirzepatide, a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1) receptor agonist, and semaglutide, a selective GLP-1 agonist, studies comparing the two drugs directly are lacking.
For a more comprehensive understanding of how the drugs compare, Dr. Karagiannis and colleagues conducted the meta-analysis of 22 trials, including two direct comparisons, the SURPASS-2 trial and a smaller trial, and 20 other studies comparing either semaglutide or tirzepatide with a common comparator, such as placebo, basal insulin, or other GLP-RA-1 drugs.
Overall, 18,472 participants were included in the studies.
All included studies had assessed a maintenance dose of tirzepatide of either 5, 10, or 15 mg once weekly or semaglutide at doses of 0.5, 1.0, or 2.0 mg once weekly for at least 12 weeks. All comparisons were for subcutaneous injection formulations (semaglutide can also be taken orally).
Blood glucose reduction
Tirzepatide at 15 mg was found to have the highest efficacy in the reduction of A1c compared with placebo, with a mean difference of –2.00%, followed by tirzepatide 10 mg (–1.86%) and semaglutide 2.0 mg (–1.62%).
All three of the tirzepatide doses had greater reductions in A1c compared with the respective low, medium, and high doses of semaglutide.
Dr. Karagiannis noted that the differences are significant: “An A1c reduction even by 0.5% is often deemed clinically important,” he said.
Body weight reduction comparisons
The reductions in body weight across the three drug doses were greater with tirzepatide (–10.96 kg [24.2 pounds], –8.75 kg [19.3 pounds], and –6.16 kg [13.6 pounds] for 15, 10, and 5 mg, respectively) compared with semaglutide (–5.24 kg [11.6 pounds], –4.44 kg [9.8 pounds], and –2.72 kg [6 pounds] for semaglutide 2.0, 1.0, and 0.5 mg, respectively).
In terms of drug-to-drug comparisons, tirzepatide 15 mg had a mean of 5.72 kg (12.6 pounds) greater reduction in body weight vs. semaglutide 2.0 mg; tirzepatide 10 mg had a mean of 3.52 kg (7.8 pounds) reduction vs. semaglutide 2.0 mg; and tirzepatide 5 mg had a mean of a 1.72 kg (3.8 pounds) greater reduction vs. semaglutide 1.0 mg.
Adverse events: Increased GI events with highest tirzepatide dose
Regarding the gastrointestinal adverse events associated with the drugs, tirzepatide 15 mg had the highest rate of the two drugs at their various doses, with a risk ratio (RR) of 3.57 compared with placebo for nausea, an RR of 4.35 for vomiting, and 2.04 for diarrhea.
There were no significant differences between the two drugs for the gastrointestinal events, with the exception of the highest dose of tirzepatide, 15 mg, which had a higher risk of vomiting vs. semaglutide 1.0 (RR 1.39) and semaglutide 0.5 mg (RR 1.85).
In addition, tirzepatide 15 mg had a higher risk vs. semaglutide 0.5 mg for nausea (RR 1.45).
There were no significant differences between the two drugs and placebo in the risk of serious adverse events.
Real-world applications, comparisons
Dr. Karagiannis noted that the results indicate that benefits of the efficacy of the higher tirzepatide dose need to be balanced with those potential side effects.
“Although the efficacy of the high tirzepatide dose might make it a favorable choice, its real-world application can be affected on an individual’s ability to tolerate these side effects in case they occur,” he explained.
Ultimately, “some patients may prioritize tolerability over enhanced efficacy,” he added.
Furthermore, while all three maintenance doses of tirzepatide analyzed have received marketing authorization, “to get a clearer picture of the real-world tolerance to these doses outside the context of randomized controlled trials, well-designed observational studies would be necessary,” Dr. Karagiannis said.
Among other issues of comparison with the two drugs is cost.
In a recent analysis, the cost per 1% of body weight reduction was reported to be $1,197 for high-dose tirzepatide (15 mg) vs. $1,511 for semaglutide 2.4 mg, with an overall cost of 72 weeks of therapy with tirzepatide at $17,527 compared with $22,878 for semaglutide.
Overall, patients and clinicians should consider the full range of differences and similarities between the medications, “from [their] efficacy and side effects to cost-effectiveness, long-term safety, and cardiovascular profile,” Dr. Karagiannis said.
Semaglutide is currently approved by the Food and Drug Administration for treatment of type 2 diabetes and obesity/weight loss management.
Tirzepatide has also received approval for the treatment of type 2 diabetes and its manufacturers have submitted applications for its approval for obesity/weight loss management.
Dr. Karagiannis reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, results from a meta-analysis of 22 randomized controlled trials show.
“The results indicate tirzepatide’s superior performance over subcutaneous semaglutide in managing blood sugar and achieving weight loss, making it a promising option in the pharmaceutical management of type 2 diabetes,” first author Thomas Karagiannis, MD, PhD, Aristotle University of Thessaloniki, Greece, said in an interview.
“In clinical context, the most potent doses of each drug revealed a clear difference regarding weight loss, with tirzepatide resulting in an average weight reduction that exceeded that of semaglutide by 5.7 kg (12.6 pounds),” he said.
The study is scheduled to be presented at the annual meeting of the European Association for the Study of Diabetes (EASD) in early October.
While a multitude of studies have been conducted for tirzepatide, a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1) receptor agonist, and semaglutide, a selective GLP-1 agonist, studies comparing the two drugs directly are lacking.
For a more comprehensive understanding of how the drugs compare, Dr. Karagiannis and colleagues conducted the meta-analysis of 22 trials, including two direct comparisons, the SURPASS-2 trial and a smaller trial, and 20 other studies comparing either semaglutide or tirzepatide with a common comparator, such as placebo, basal insulin, or other GLP-RA-1 drugs.
Overall, 18,472 participants were included in the studies.
All included studies had assessed a maintenance dose of tirzepatide of either 5, 10, or 15 mg once weekly or semaglutide at doses of 0.5, 1.0, or 2.0 mg once weekly for at least 12 weeks. All comparisons were for subcutaneous injection formulations (semaglutide can also be taken orally).
Blood glucose reduction
Tirzepatide at 15 mg was found to have the highest efficacy in the reduction of A1c compared with placebo, with a mean difference of –2.00%, followed by tirzepatide 10 mg (–1.86%) and semaglutide 2.0 mg (–1.62%).
All three of the tirzepatide doses had greater reductions in A1c compared with the respective low, medium, and high doses of semaglutide.
Dr. Karagiannis noted that the differences are significant: “An A1c reduction even by 0.5% is often deemed clinically important,” he said.
Body weight reduction comparisons
The reductions in body weight across the three drug doses were greater with tirzepatide (–10.96 kg [24.2 pounds], –8.75 kg [19.3 pounds], and –6.16 kg [13.6 pounds] for 15, 10, and 5 mg, respectively) compared with semaglutide (–5.24 kg [11.6 pounds], –4.44 kg [9.8 pounds], and –2.72 kg [6 pounds] for semaglutide 2.0, 1.0, and 0.5 mg, respectively).
In terms of drug-to-drug comparisons, tirzepatide 15 mg had a mean of 5.72 kg (12.6 pounds) greater reduction in body weight vs. semaglutide 2.0 mg; tirzepatide 10 mg had a mean of 3.52 kg (7.8 pounds) reduction vs. semaglutide 2.0 mg; and tirzepatide 5 mg had a mean of a 1.72 kg (3.8 pounds) greater reduction vs. semaglutide 1.0 mg.
Adverse events: Increased GI events with highest tirzepatide dose
Regarding the gastrointestinal adverse events associated with the drugs, tirzepatide 15 mg had the highest rate of the two drugs at their various doses, with a risk ratio (RR) of 3.57 compared with placebo for nausea, an RR of 4.35 for vomiting, and 2.04 for diarrhea.
There were no significant differences between the two drugs for the gastrointestinal events, with the exception of the highest dose of tirzepatide, 15 mg, which had a higher risk of vomiting vs. semaglutide 1.0 (RR 1.39) and semaglutide 0.5 mg (RR 1.85).
In addition, tirzepatide 15 mg had a higher risk vs. semaglutide 0.5 mg for nausea (RR 1.45).
There were no significant differences between the two drugs and placebo in the risk of serious adverse events.
Real-world applications, comparisons
Dr. Karagiannis noted that the results indicate that benefits of the efficacy of the higher tirzepatide dose need to be balanced with those potential side effects.
“Although the efficacy of the high tirzepatide dose might make it a favorable choice, its real-world application can be affected on an individual’s ability to tolerate these side effects in case they occur,” he explained.
Ultimately, “some patients may prioritize tolerability over enhanced efficacy,” he added.
Furthermore, while all three maintenance doses of tirzepatide analyzed have received marketing authorization, “to get a clearer picture of the real-world tolerance to these doses outside the context of randomized controlled trials, well-designed observational studies would be necessary,” Dr. Karagiannis said.
Among other issues of comparison with the two drugs is cost.
In a recent analysis, the cost per 1% of body weight reduction was reported to be $1,197 for high-dose tirzepatide (15 mg) vs. $1,511 for semaglutide 2.4 mg, with an overall cost of 72 weeks of therapy with tirzepatide at $17,527 compared with $22,878 for semaglutide.
Overall, patients and clinicians should consider the full range of differences and similarities between the medications, “from [their] efficacy and side effects to cost-effectiveness, long-term safety, and cardiovascular profile,” Dr. Karagiannis said.
Semaglutide is currently approved by the Food and Drug Administration for treatment of type 2 diabetes and obesity/weight loss management.
Tirzepatide has also received approval for the treatment of type 2 diabetes and its manufacturers have submitted applications for its approval for obesity/weight loss management.
Dr. Karagiannis reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM EASD 2023