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Eight-week TB treatment strategy shows potential
A strategy for the
“We found that if we use the strategy of a bedaquiline-linezolid five-drug regimen for 8 weeks and then followed patients for 96 weeks, [the regimen] was noninferior, clinically, to the standard regimen in terms of the number of people alive, free of TB disease, and not on treatment,” said lead author Nicholas Paton, MD, of the National University of Singapore, in a press conference held during the Conference on Retroviruses & Opportunistic Infections.
“The total time on treatment was reduced by half – instead of 160 days, it was 85 days for the total duration.”
Commenting on the study, which was published concurrently in the New England Journal of Medicine, Richard E. Chaisson, MD, noted that, although more needs to be understood, the high number of responses is nevertheless encouraging.
“Clinicians will not feel comfortable with the short regimens at this point, but it is remarkable that so many patients did well with shorter treatments,” Dr. Chaisson, who is a professor of medicine, epidemiology, and international health and director of the Johns Hopkins University Center for Tuberculosis Research, Baltimore, said in an interview.
Importantly, the study should help push forward “future studies [that] will stratify patients according to their likelihood of responding to shorter treatments,” he said.
The current global standard for TB treatment, practiced for 4 decades, has been a 6-month rifampin-based regimen. Although the regimen performs well, curing more than 95% of cases in clinical trials, in real-world practice, the prolonged duration can be problematic, with issues of nonadherence and loss of patients to follow-up.
Previous research has shown that shorter regimens have potential, with some studies showing as many as 85% of patients cured with 3- and 4-month regimens, and some promising 2-month regimens showing efficacy specifically for those with smear-negative TB.
These efforts suggest that “the current 6-month regimen may lead to overtreatment in the majority of persons in order to prevent relapse in a minority of persons,” the authors asserted.
TRUNCATE-TB
To investigate a suitable shorter-term alternative, the authors conducted the phase 2-3, prospective, open-label TRUNCATE-TB trial, in which 674 patients with rifampin-susceptible pulmonary TB were enrolled at 18 sites in Asia and Africa.
The patients were randomly assigned to receive either the standard treatment regimen (rifampin and isoniazid for 24 weeks with pyrazinamide and ethambutol for the first 8 weeks; n = 181), or one of four novel five-drug regimens to be administered over 8 weeks, along with extended treatment for persistent clinical disease of up to 12 weeks, if needed, and a plan for retreatment in the case of relapse (n = 493).
Two of the regimens were dropped because of logistic criteria; the two remaining shorter-course groups included in the study involved either high-dose rifampin plus linezolid or bedaquiline plus linezolid, each combined with isoniazid, pyrazinamide, and ethambutol.
Of the patients, 62% were male, and four withdrew or were lost to follow-up by the end of the study at a final follow-up at week 96.
Among patients assigned to the 8-week regimens, 80% stopped at exactly 8 weeks, while 9% wound up having extended treatment to 10 weeks and 3% were extended to 12 weeks.
For the primary endpoint, a composite of death, ongoing treatment, or active disease at week 96, the rate was lowest in the standard 24-week therapy group, occurring in 7 of 181 patients (3.9%), compared with 21 of 184 patients (11.4%) in the rifampin plus linezolid group (adjusted difference, 7.4 percentage points, which did not meet noninferiority criterion), and 11 of 189 (5.8%) in the group in the bedaquiline plus linezolid group (adjusted difference, 0.8 percentage points, meeting noninferiority criterion).
The mean total duration of treatment through week 96 in the standard treatment group was 180 days versus 106 days in the rifampin–linezolid group, and 85 days in the bedaquiline-linezolid group.
The results were consistent across multiple subgroups defined according to baseline characteristics, including some that could be linked to severe disease and a high risk for relapse.
In terms of safety, there were no significant differences between the groups in terms of grade 3 or 4 adverse events.
Of note, only two patients (1.1%) in the bedaquiline plus linezolid group acquired a resistance, which Dr. Paton said was “encouraging,” because of concerns about resistance to that drug.
‘Unfavorable’ composite also evaluated
In an updated analysis of the study that Dr. Paton presented at the meeting, the authors looked at a revised “unfavorable” primary outcome – a composite including treatment failure, relapse, death, or nonattendance at week 96 without evidence of prior disease clearance.
The rate remained lowest in the standard 24-week therapy group (3.9%) versus 25% in the rifampin plus linezolid group, and 13.8% in the bedaquiline plus linezolid group.
Though the lower rate with the standard treatment was expected, Dr. Paton said the results nevertheless hold promise, at least for some patients, for successful treatment with the 8-week bedaquiline plus linezolid strategy.
“What the trial has told us is that even with that 13.8% relapse rate, we can manage patients within this strategy and people can do fine at the end, because with some simple clinical biomarkers, we can pick the people who may have a high chance of achieving a cure.”
Dr. Chaisson expressed concern over the higher unfavorable rates, but said the results help pave the way for refining a workable-shorter term strategy.
“TRUNCATE-TB did find that most patients could be successfully treated in 2 months with the novel regimen of bedaquiline plus linezolid, but the failure rate was still unacceptably high,” he said.
“This regimen will not be widely adapted at this point, but additional analyses may identify subsets of patients who will do well with shorter regimens, and future studies will stratify patients according to their likelihood of responding to shorter treatments.”
The authors of an accompanying editorial further commented that the benefits of a shorter treatment strategy could very well outweigh possible shortcomings.
“Treatment algorithms such as that used in the TRUNCATE-TB trial are fundamental to tuberculosis control,” wrote Véronique Dartois, PhD, Center for Discovery and Innovation, Nutley, N.J., and Eric J. Rubin, MD, PhD, the editor-in-chief of NEJM. “Although implementing them could be a challenge, any added burden might be offset by reduced costs, better adherence, and increased patient satisfaction. Thus, for tuberculosis, a strategy might be more than just a regimen.”
The good news, as summed up by CROI vice-chair Landon Myer, MD, PhD, in the press conference, is that “we’re moving closer and closer to the holy grail of a short, efficacious regimen for TB treatment. We’re getting there slowly, but we’re getting there.”
The study received grant funding from the Singapore National Medical Research Council; a grant from the Department of Health and Social Care; the Foreign, Commonwealth, and Development Office; the Medical Research Council; and Wellcome Trust; as well as a grant from the UK Research and Innovation Medical Research Council. Dr. Dartois reported no relevant financial relationships. Dr. Chaisson had no disclosures to report.
A version of this article originally appeared on Medscape.com.
A strategy for the
“We found that if we use the strategy of a bedaquiline-linezolid five-drug regimen for 8 weeks and then followed patients for 96 weeks, [the regimen] was noninferior, clinically, to the standard regimen in terms of the number of people alive, free of TB disease, and not on treatment,” said lead author Nicholas Paton, MD, of the National University of Singapore, in a press conference held during the Conference on Retroviruses & Opportunistic Infections.
“The total time on treatment was reduced by half – instead of 160 days, it was 85 days for the total duration.”
Commenting on the study, which was published concurrently in the New England Journal of Medicine, Richard E. Chaisson, MD, noted that, although more needs to be understood, the high number of responses is nevertheless encouraging.
“Clinicians will not feel comfortable with the short regimens at this point, but it is remarkable that so many patients did well with shorter treatments,” Dr. Chaisson, who is a professor of medicine, epidemiology, and international health and director of the Johns Hopkins University Center for Tuberculosis Research, Baltimore, said in an interview.
Importantly, the study should help push forward “future studies [that] will stratify patients according to their likelihood of responding to shorter treatments,” he said.
The current global standard for TB treatment, practiced for 4 decades, has been a 6-month rifampin-based regimen. Although the regimen performs well, curing more than 95% of cases in clinical trials, in real-world practice, the prolonged duration can be problematic, with issues of nonadherence and loss of patients to follow-up.
Previous research has shown that shorter regimens have potential, with some studies showing as many as 85% of patients cured with 3- and 4-month regimens, and some promising 2-month regimens showing efficacy specifically for those with smear-negative TB.
These efforts suggest that “the current 6-month regimen may lead to overtreatment in the majority of persons in order to prevent relapse in a minority of persons,” the authors asserted.
TRUNCATE-TB
To investigate a suitable shorter-term alternative, the authors conducted the phase 2-3, prospective, open-label TRUNCATE-TB trial, in which 674 patients with rifampin-susceptible pulmonary TB were enrolled at 18 sites in Asia and Africa.
The patients were randomly assigned to receive either the standard treatment regimen (rifampin and isoniazid for 24 weeks with pyrazinamide and ethambutol for the first 8 weeks; n = 181), or one of four novel five-drug regimens to be administered over 8 weeks, along with extended treatment for persistent clinical disease of up to 12 weeks, if needed, and a plan for retreatment in the case of relapse (n = 493).
Two of the regimens were dropped because of logistic criteria; the two remaining shorter-course groups included in the study involved either high-dose rifampin plus linezolid or bedaquiline plus linezolid, each combined with isoniazid, pyrazinamide, and ethambutol.
Of the patients, 62% were male, and four withdrew or were lost to follow-up by the end of the study at a final follow-up at week 96.
Among patients assigned to the 8-week regimens, 80% stopped at exactly 8 weeks, while 9% wound up having extended treatment to 10 weeks and 3% were extended to 12 weeks.
For the primary endpoint, a composite of death, ongoing treatment, or active disease at week 96, the rate was lowest in the standard 24-week therapy group, occurring in 7 of 181 patients (3.9%), compared with 21 of 184 patients (11.4%) in the rifampin plus linezolid group (adjusted difference, 7.4 percentage points, which did not meet noninferiority criterion), and 11 of 189 (5.8%) in the group in the bedaquiline plus linezolid group (adjusted difference, 0.8 percentage points, meeting noninferiority criterion).
The mean total duration of treatment through week 96 in the standard treatment group was 180 days versus 106 days in the rifampin–linezolid group, and 85 days in the bedaquiline-linezolid group.
The results were consistent across multiple subgroups defined according to baseline characteristics, including some that could be linked to severe disease and a high risk for relapse.
In terms of safety, there were no significant differences between the groups in terms of grade 3 or 4 adverse events.
Of note, only two patients (1.1%) in the bedaquiline plus linezolid group acquired a resistance, which Dr. Paton said was “encouraging,” because of concerns about resistance to that drug.
‘Unfavorable’ composite also evaluated
In an updated analysis of the study that Dr. Paton presented at the meeting, the authors looked at a revised “unfavorable” primary outcome – a composite including treatment failure, relapse, death, or nonattendance at week 96 without evidence of prior disease clearance.
The rate remained lowest in the standard 24-week therapy group (3.9%) versus 25% in the rifampin plus linezolid group, and 13.8% in the bedaquiline plus linezolid group.
Though the lower rate with the standard treatment was expected, Dr. Paton said the results nevertheless hold promise, at least for some patients, for successful treatment with the 8-week bedaquiline plus linezolid strategy.
“What the trial has told us is that even with that 13.8% relapse rate, we can manage patients within this strategy and people can do fine at the end, because with some simple clinical biomarkers, we can pick the people who may have a high chance of achieving a cure.”
Dr. Chaisson expressed concern over the higher unfavorable rates, but said the results help pave the way for refining a workable-shorter term strategy.
“TRUNCATE-TB did find that most patients could be successfully treated in 2 months with the novel regimen of bedaquiline plus linezolid, but the failure rate was still unacceptably high,” he said.
“This regimen will not be widely adapted at this point, but additional analyses may identify subsets of patients who will do well with shorter regimens, and future studies will stratify patients according to their likelihood of responding to shorter treatments.”
The authors of an accompanying editorial further commented that the benefits of a shorter treatment strategy could very well outweigh possible shortcomings.
“Treatment algorithms such as that used in the TRUNCATE-TB trial are fundamental to tuberculosis control,” wrote Véronique Dartois, PhD, Center for Discovery and Innovation, Nutley, N.J., and Eric J. Rubin, MD, PhD, the editor-in-chief of NEJM. “Although implementing them could be a challenge, any added burden might be offset by reduced costs, better adherence, and increased patient satisfaction. Thus, for tuberculosis, a strategy might be more than just a regimen.”
The good news, as summed up by CROI vice-chair Landon Myer, MD, PhD, in the press conference, is that “we’re moving closer and closer to the holy grail of a short, efficacious regimen for TB treatment. We’re getting there slowly, but we’re getting there.”
The study received grant funding from the Singapore National Medical Research Council; a grant from the Department of Health and Social Care; the Foreign, Commonwealth, and Development Office; the Medical Research Council; and Wellcome Trust; as well as a grant from the UK Research and Innovation Medical Research Council. Dr. Dartois reported no relevant financial relationships. Dr. Chaisson had no disclosures to report.
A version of this article originally appeared on Medscape.com.
A strategy for the
“We found that if we use the strategy of a bedaquiline-linezolid five-drug regimen for 8 weeks and then followed patients for 96 weeks, [the regimen] was noninferior, clinically, to the standard regimen in terms of the number of people alive, free of TB disease, and not on treatment,” said lead author Nicholas Paton, MD, of the National University of Singapore, in a press conference held during the Conference on Retroviruses & Opportunistic Infections.
“The total time on treatment was reduced by half – instead of 160 days, it was 85 days for the total duration.”
Commenting on the study, which was published concurrently in the New England Journal of Medicine, Richard E. Chaisson, MD, noted that, although more needs to be understood, the high number of responses is nevertheless encouraging.
“Clinicians will not feel comfortable with the short regimens at this point, but it is remarkable that so many patients did well with shorter treatments,” Dr. Chaisson, who is a professor of medicine, epidemiology, and international health and director of the Johns Hopkins University Center for Tuberculosis Research, Baltimore, said in an interview.
Importantly, the study should help push forward “future studies [that] will stratify patients according to their likelihood of responding to shorter treatments,” he said.
The current global standard for TB treatment, practiced for 4 decades, has been a 6-month rifampin-based regimen. Although the regimen performs well, curing more than 95% of cases in clinical trials, in real-world practice, the prolonged duration can be problematic, with issues of nonadherence and loss of patients to follow-up.
Previous research has shown that shorter regimens have potential, with some studies showing as many as 85% of patients cured with 3- and 4-month regimens, and some promising 2-month regimens showing efficacy specifically for those with smear-negative TB.
These efforts suggest that “the current 6-month regimen may lead to overtreatment in the majority of persons in order to prevent relapse in a minority of persons,” the authors asserted.
TRUNCATE-TB
To investigate a suitable shorter-term alternative, the authors conducted the phase 2-3, prospective, open-label TRUNCATE-TB trial, in which 674 patients with rifampin-susceptible pulmonary TB were enrolled at 18 sites in Asia and Africa.
The patients were randomly assigned to receive either the standard treatment regimen (rifampin and isoniazid for 24 weeks with pyrazinamide and ethambutol for the first 8 weeks; n = 181), or one of four novel five-drug regimens to be administered over 8 weeks, along with extended treatment for persistent clinical disease of up to 12 weeks, if needed, and a plan for retreatment in the case of relapse (n = 493).
Two of the regimens were dropped because of logistic criteria; the two remaining shorter-course groups included in the study involved either high-dose rifampin plus linezolid or bedaquiline plus linezolid, each combined with isoniazid, pyrazinamide, and ethambutol.
Of the patients, 62% were male, and four withdrew or were lost to follow-up by the end of the study at a final follow-up at week 96.
Among patients assigned to the 8-week regimens, 80% stopped at exactly 8 weeks, while 9% wound up having extended treatment to 10 weeks and 3% were extended to 12 weeks.
For the primary endpoint, a composite of death, ongoing treatment, or active disease at week 96, the rate was lowest in the standard 24-week therapy group, occurring in 7 of 181 patients (3.9%), compared with 21 of 184 patients (11.4%) in the rifampin plus linezolid group (adjusted difference, 7.4 percentage points, which did not meet noninferiority criterion), and 11 of 189 (5.8%) in the group in the bedaquiline plus linezolid group (adjusted difference, 0.8 percentage points, meeting noninferiority criterion).
The mean total duration of treatment through week 96 in the standard treatment group was 180 days versus 106 days in the rifampin–linezolid group, and 85 days in the bedaquiline-linezolid group.
The results were consistent across multiple subgroups defined according to baseline characteristics, including some that could be linked to severe disease and a high risk for relapse.
In terms of safety, there were no significant differences between the groups in terms of grade 3 or 4 adverse events.
Of note, only two patients (1.1%) in the bedaquiline plus linezolid group acquired a resistance, which Dr. Paton said was “encouraging,” because of concerns about resistance to that drug.
‘Unfavorable’ composite also evaluated
In an updated analysis of the study that Dr. Paton presented at the meeting, the authors looked at a revised “unfavorable” primary outcome – a composite including treatment failure, relapse, death, or nonattendance at week 96 without evidence of prior disease clearance.
The rate remained lowest in the standard 24-week therapy group (3.9%) versus 25% in the rifampin plus linezolid group, and 13.8% in the bedaquiline plus linezolid group.
Though the lower rate with the standard treatment was expected, Dr. Paton said the results nevertheless hold promise, at least for some patients, for successful treatment with the 8-week bedaquiline plus linezolid strategy.
“What the trial has told us is that even with that 13.8% relapse rate, we can manage patients within this strategy and people can do fine at the end, because with some simple clinical biomarkers, we can pick the people who may have a high chance of achieving a cure.”
Dr. Chaisson expressed concern over the higher unfavorable rates, but said the results help pave the way for refining a workable-shorter term strategy.
“TRUNCATE-TB did find that most patients could be successfully treated in 2 months with the novel regimen of bedaquiline plus linezolid, but the failure rate was still unacceptably high,” he said.
“This regimen will not be widely adapted at this point, but additional analyses may identify subsets of patients who will do well with shorter regimens, and future studies will stratify patients according to their likelihood of responding to shorter treatments.”
The authors of an accompanying editorial further commented that the benefits of a shorter treatment strategy could very well outweigh possible shortcomings.
“Treatment algorithms such as that used in the TRUNCATE-TB trial are fundamental to tuberculosis control,” wrote Véronique Dartois, PhD, Center for Discovery and Innovation, Nutley, N.J., and Eric J. Rubin, MD, PhD, the editor-in-chief of NEJM. “Although implementing them could be a challenge, any added burden might be offset by reduced costs, better adherence, and increased patient satisfaction. Thus, for tuberculosis, a strategy might be more than just a regimen.”
The good news, as summed up by CROI vice-chair Landon Myer, MD, PhD, in the press conference, is that “we’re moving closer and closer to the holy grail of a short, efficacious regimen for TB treatment. We’re getting there slowly, but we’re getting there.”
The study received grant funding from the Singapore National Medical Research Council; a grant from the Department of Health and Social Care; the Foreign, Commonwealth, and Development Office; the Medical Research Council; and Wellcome Trust; as well as a grant from the UK Research and Innovation Medical Research Council. Dr. Dartois reported no relevant financial relationships. Dr. Chaisson had no disclosures to report.
A version of this article originally appeared on Medscape.com.
FROM CROI 2023
Transplant vs. chemo: Similar AML survival rates
Notably, all patients who relapsed after consolidation chemotherapy were able to receive allogeneic HCT, suggesting that transplantation may be safely delayed in some patients until their first relapse.
“The results of this randomized clinical trial indicate that the probability of survival after [allogeneic] HCT is not superior to that of conventional consolidation chemotherapy” among patients 60 years or younger with intermediate-risk AML, the authors concluded.
However, two experts highlighted several caveats to the study, which suggest the results may not translate to current clinical practice.
The study was published online in JAMA Oncology.
Approximately 50%-70% of patients with AML who receive intensive induction chemotherapy for AML and achieve a first complete remission are referred for post-remission therapy.
While consolidation chemotherapy with high-dose cytarabine has shown a benefit for those with a favorable risk profile, patients considered high-risk with adequate performance status may be candidates for allogeneic HCT.
However, determining the optimal post-remission treatment option for patients who fall into the intermediate-risk category can be more challenging.
To compare outcomes among intermediate-risk patients, researchers from Germany conducted a multicenter trial, enrolling 143 adults aged 60 or younger with intermediate-risk AML who had achieved first complete remission or complete remission with incomplete blood cell count recovery following conventional induction therapy.
The patients, who had a mean age of 48.2 years, were randomly assigned to consolidation treatment with allogeneic HCT (n = 76) or chemotherapy with high-dose cytarabine (n = 67), with the option for salvage HCT in the case of relapse. Overall, 12 patients in the HCT group received one consolidation course of high-dose cytarabine after achieving complete remission to bridge until allogeneic HCT, while all other patients in this group received allogeneic HCT directly after induction therapy.
Overall, disease-free survival at 2 years was significantly higher in the allogeneic HCT group (69%), compared with the consolidation therapy group (40%; P = .001). And the cumulative incidence of relapse at 2 years in the allogeneic HCT group was also lower, at 20%, compared with 58% in the consolidation therapy group (P < .001).
The overall survival data, however, painted a slightly more complex picture. In the intention-to-treat analysis, the probability of survival at 2 years was similar between the allogeneic HCT group (74%, or 56 of 76 patients), compared with consolidation chemotherapy (84%, or 56 of 67 patients; P = .22).
In addition, the rates of nonrelapse mortality at 2 years were higher in the allogeneic HCT group (9%) versus chemotherapy (2%; P = .005).
Although the rate of nonrelapse mortality was higher with allogeneic HCT, the relatively low rate with each treatment strategies was “an important and rewarding finding,” the authors noted. “This achievement is clearly due to the availability of less toxic but still effective conditioning therapies and modern antiviral and antifungal prophylaxis.”
In addition, among the 41 patients who relapsed after consolidation chemotherapy, all received allogeneic HCT, and the authors observed no significant differences between the groups in terms of health-related quality of life measures.
Results ‘may not translate to real-life clinical practice’
An important caveat is that the findings do not reflect some key updated strategies currently used in clinical practice, said Diego Adrianzen Herrera, MD, from the University of Vermont’s Larner College of Medicine, Burlington, who was not involved in the study.
“A charitable interpretation of the results is that a clear, large survival benefit of transplant in first complete remission is not apparent, which in turn can inform decision-making in certain circumstances for patients meeting the trial criteria, [including] younger patients with a readily available donor,” he told this news organization.
“However, risk stratification strategies currently used were not followed,” he said.
For instance, molecular risk stratification was not universally used, which may have led the researchers to overrepresent the number of patients considered to have favorable risk disease and “could have skewed the results in favor of the chemotherapy arm,” he explained.
In addition, minimal residual disease surveillance by flow cytometry was not used. Plus, Dr. Herrera added, in practice, not all patients can be salvaged and taken to HCT when in their second complete remission, or even achieve complete remission again.
“Unfortunately, these issues make the clinical significance of these results limited,” he concluded.
Margaret Kasner, MD, who was not associated with the research, agreed that aspects of the study design may not translate to real-life clinical practice, particularly in terms of quality-of-life outcomes.
“Although the [study] showed no difference in quality of life in the patient groups, this is likely due to the patient selection,” Dr. Kasner, of the Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, said in an interview. “Most patients do not allow themselves to be randomized between these two very different strategies, so those who are willing to be randomized may be a different population in terms how their quality of life is affected by relapse.”
The authors acknowledged some of these limitations, adding that the routine use of minimal residual disease monitoring in some patients was only established once the trial was underway, and the number of patients with complete minimal residual disease was therefore limited.
In addition, Dr. Herrera explained that because HCT involves significant disruptions to daily life and extensive follow-up and monitoring, decisions to use the strategy are not taken lightly by clinicians or patients.
“This is a major issue,” he said. “HCT remains a therapeutic option which causes significant apprehension to patients.”
Nevertheless, “in my experience most patients would prefer an upfront strategy if there is a definitive need for transplant,” he added. “I think the main question patients have is whether they absolutely need an HCT and how can we better identify up front who will be in the relapse-free group at 2 years.”
The study received grant funding from the Deutsche Forschungsgemeinschaft. The authors’ disclosures are detailed in the original article. Dr. Herrera and Dr. Kasner report no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Notably, all patients who relapsed after consolidation chemotherapy were able to receive allogeneic HCT, suggesting that transplantation may be safely delayed in some patients until their first relapse.
“The results of this randomized clinical trial indicate that the probability of survival after [allogeneic] HCT is not superior to that of conventional consolidation chemotherapy” among patients 60 years or younger with intermediate-risk AML, the authors concluded.
However, two experts highlighted several caveats to the study, which suggest the results may not translate to current clinical practice.
The study was published online in JAMA Oncology.
Approximately 50%-70% of patients with AML who receive intensive induction chemotherapy for AML and achieve a first complete remission are referred for post-remission therapy.
While consolidation chemotherapy with high-dose cytarabine has shown a benefit for those with a favorable risk profile, patients considered high-risk with adequate performance status may be candidates for allogeneic HCT.
However, determining the optimal post-remission treatment option for patients who fall into the intermediate-risk category can be more challenging.
To compare outcomes among intermediate-risk patients, researchers from Germany conducted a multicenter trial, enrolling 143 adults aged 60 or younger with intermediate-risk AML who had achieved first complete remission or complete remission with incomplete blood cell count recovery following conventional induction therapy.
The patients, who had a mean age of 48.2 years, were randomly assigned to consolidation treatment with allogeneic HCT (n = 76) or chemotherapy with high-dose cytarabine (n = 67), with the option for salvage HCT in the case of relapse. Overall, 12 patients in the HCT group received one consolidation course of high-dose cytarabine after achieving complete remission to bridge until allogeneic HCT, while all other patients in this group received allogeneic HCT directly after induction therapy.
Overall, disease-free survival at 2 years was significantly higher in the allogeneic HCT group (69%), compared with the consolidation therapy group (40%; P = .001). And the cumulative incidence of relapse at 2 years in the allogeneic HCT group was also lower, at 20%, compared with 58% in the consolidation therapy group (P < .001).
The overall survival data, however, painted a slightly more complex picture. In the intention-to-treat analysis, the probability of survival at 2 years was similar between the allogeneic HCT group (74%, or 56 of 76 patients), compared with consolidation chemotherapy (84%, or 56 of 67 patients; P = .22).
In addition, the rates of nonrelapse mortality at 2 years were higher in the allogeneic HCT group (9%) versus chemotherapy (2%; P = .005).
Although the rate of nonrelapse mortality was higher with allogeneic HCT, the relatively low rate with each treatment strategies was “an important and rewarding finding,” the authors noted. “This achievement is clearly due to the availability of less toxic but still effective conditioning therapies and modern antiviral and antifungal prophylaxis.”
In addition, among the 41 patients who relapsed after consolidation chemotherapy, all received allogeneic HCT, and the authors observed no significant differences between the groups in terms of health-related quality of life measures.
Results ‘may not translate to real-life clinical practice’
An important caveat is that the findings do not reflect some key updated strategies currently used in clinical practice, said Diego Adrianzen Herrera, MD, from the University of Vermont’s Larner College of Medicine, Burlington, who was not involved in the study.
“A charitable interpretation of the results is that a clear, large survival benefit of transplant in first complete remission is not apparent, which in turn can inform decision-making in certain circumstances for patients meeting the trial criteria, [including] younger patients with a readily available donor,” he told this news organization.
“However, risk stratification strategies currently used were not followed,” he said.
For instance, molecular risk stratification was not universally used, which may have led the researchers to overrepresent the number of patients considered to have favorable risk disease and “could have skewed the results in favor of the chemotherapy arm,” he explained.
In addition, minimal residual disease surveillance by flow cytometry was not used. Plus, Dr. Herrera added, in practice, not all patients can be salvaged and taken to HCT when in their second complete remission, or even achieve complete remission again.
“Unfortunately, these issues make the clinical significance of these results limited,” he concluded.
Margaret Kasner, MD, who was not associated with the research, agreed that aspects of the study design may not translate to real-life clinical practice, particularly in terms of quality-of-life outcomes.
“Although the [study] showed no difference in quality of life in the patient groups, this is likely due to the patient selection,” Dr. Kasner, of the Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, said in an interview. “Most patients do not allow themselves to be randomized between these two very different strategies, so those who are willing to be randomized may be a different population in terms how their quality of life is affected by relapse.”
The authors acknowledged some of these limitations, adding that the routine use of minimal residual disease monitoring in some patients was only established once the trial was underway, and the number of patients with complete minimal residual disease was therefore limited.
In addition, Dr. Herrera explained that because HCT involves significant disruptions to daily life and extensive follow-up and monitoring, decisions to use the strategy are not taken lightly by clinicians or patients.
“This is a major issue,” he said. “HCT remains a therapeutic option which causes significant apprehension to patients.”
Nevertheless, “in my experience most patients would prefer an upfront strategy if there is a definitive need for transplant,” he added. “I think the main question patients have is whether they absolutely need an HCT and how can we better identify up front who will be in the relapse-free group at 2 years.”
The study received grant funding from the Deutsche Forschungsgemeinschaft. The authors’ disclosures are detailed in the original article. Dr. Herrera and Dr. Kasner report no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Notably, all patients who relapsed after consolidation chemotherapy were able to receive allogeneic HCT, suggesting that transplantation may be safely delayed in some patients until their first relapse.
“The results of this randomized clinical trial indicate that the probability of survival after [allogeneic] HCT is not superior to that of conventional consolidation chemotherapy” among patients 60 years or younger with intermediate-risk AML, the authors concluded.
However, two experts highlighted several caveats to the study, which suggest the results may not translate to current clinical practice.
The study was published online in JAMA Oncology.
Approximately 50%-70% of patients with AML who receive intensive induction chemotherapy for AML and achieve a first complete remission are referred for post-remission therapy.
While consolidation chemotherapy with high-dose cytarabine has shown a benefit for those with a favorable risk profile, patients considered high-risk with adequate performance status may be candidates for allogeneic HCT.
However, determining the optimal post-remission treatment option for patients who fall into the intermediate-risk category can be more challenging.
To compare outcomes among intermediate-risk patients, researchers from Germany conducted a multicenter trial, enrolling 143 adults aged 60 or younger with intermediate-risk AML who had achieved first complete remission or complete remission with incomplete blood cell count recovery following conventional induction therapy.
The patients, who had a mean age of 48.2 years, were randomly assigned to consolidation treatment with allogeneic HCT (n = 76) or chemotherapy with high-dose cytarabine (n = 67), with the option for salvage HCT in the case of relapse. Overall, 12 patients in the HCT group received one consolidation course of high-dose cytarabine after achieving complete remission to bridge until allogeneic HCT, while all other patients in this group received allogeneic HCT directly after induction therapy.
Overall, disease-free survival at 2 years was significantly higher in the allogeneic HCT group (69%), compared with the consolidation therapy group (40%; P = .001). And the cumulative incidence of relapse at 2 years in the allogeneic HCT group was also lower, at 20%, compared with 58% in the consolidation therapy group (P < .001).
The overall survival data, however, painted a slightly more complex picture. In the intention-to-treat analysis, the probability of survival at 2 years was similar between the allogeneic HCT group (74%, or 56 of 76 patients), compared with consolidation chemotherapy (84%, or 56 of 67 patients; P = .22).
In addition, the rates of nonrelapse mortality at 2 years were higher in the allogeneic HCT group (9%) versus chemotherapy (2%; P = .005).
Although the rate of nonrelapse mortality was higher with allogeneic HCT, the relatively low rate with each treatment strategies was “an important and rewarding finding,” the authors noted. “This achievement is clearly due to the availability of less toxic but still effective conditioning therapies and modern antiviral and antifungal prophylaxis.”
In addition, among the 41 patients who relapsed after consolidation chemotherapy, all received allogeneic HCT, and the authors observed no significant differences between the groups in terms of health-related quality of life measures.
Results ‘may not translate to real-life clinical practice’
An important caveat is that the findings do not reflect some key updated strategies currently used in clinical practice, said Diego Adrianzen Herrera, MD, from the University of Vermont’s Larner College of Medicine, Burlington, who was not involved in the study.
“A charitable interpretation of the results is that a clear, large survival benefit of transplant in first complete remission is not apparent, which in turn can inform decision-making in certain circumstances for patients meeting the trial criteria, [including] younger patients with a readily available donor,” he told this news organization.
“However, risk stratification strategies currently used were not followed,” he said.
For instance, molecular risk stratification was not universally used, which may have led the researchers to overrepresent the number of patients considered to have favorable risk disease and “could have skewed the results in favor of the chemotherapy arm,” he explained.
In addition, minimal residual disease surveillance by flow cytometry was not used. Plus, Dr. Herrera added, in practice, not all patients can be salvaged and taken to HCT when in their second complete remission, or even achieve complete remission again.
“Unfortunately, these issues make the clinical significance of these results limited,” he concluded.
Margaret Kasner, MD, who was not associated with the research, agreed that aspects of the study design may not translate to real-life clinical practice, particularly in terms of quality-of-life outcomes.
“Although the [study] showed no difference in quality of life in the patient groups, this is likely due to the patient selection,” Dr. Kasner, of the Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, said in an interview. “Most patients do not allow themselves to be randomized between these two very different strategies, so those who are willing to be randomized may be a different population in terms how their quality of life is affected by relapse.”
The authors acknowledged some of these limitations, adding that the routine use of minimal residual disease monitoring in some patients was only established once the trial was underway, and the number of patients with complete minimal residual disease was therefore limited.
In addition, Dr. Herrera explained that because HCT involves significant disruptions to daily life and extensive follow-up and monitoring, decisions to use the strategy are not taken lightly by clinicians or patients.
“This is a major issue,” he said. “HCT remains a therapeutic option which causes significant apprehension to patients.”
Nevertheless, “in my experience most patients would prefer an upfront strategy if there is a definitive need for transplant,” he added. “I think the main question patients have is whether they absolutely need an HCT and how can we better identify up front who will be in the relapse-free group at 2 years.”
The study received grant funding from the Deutsche Forschungsgemeinschaft. The authors’ disclosures are detailed in the original article. Dr. Herrera and Dr. Kasner report no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Genomic clues to poor outcomes in young breast cancer patients
and offer clues about molecular targets for future trials.
Compared with older women with early stage HR-positive breast cancer, women under 40 years of age had significantly higher frequencies of certain mutations, such as GATA3, as well as genomic features associated with a poor prognosis. Notably, the researchers found that women with such poor prognostic features vs. those with none had a significantly worse 8-year distant recurrence-free interval and overall survival.
“We have demonstrated age-related differences in genomic profiles with enrichment of genomic features associated with poor prognosis in these younger premenopausal women compared with older premenopausal and postmenopausal women,” the authors wrote in the study, published in the Annals of Oncology. Importantly, the genomic features highlight “the potential for age-focused treatment strategies.”
Charis Eng, MD, PhD, of the Cleveland Clinic Genomic Medicine Institute, Ohio, noted that the findings are promising but need further validation.
“With time and the appropriate clinical trials in place, I envision that these findings will enable the personalized genomics-driven management of these cancers – not only treatment, but also toward prevention,” said Dr. Eng, who was not involved in the study.
Young premenopausal women, particularly those with HR-positive, luminal breast cancer, are known to have significantly higher recurrence rates and worse survival, compared with older women, but the reasons have remained unclear.
Although previous studies have identified key gene expression signatures linked to worse outcomes in younger patients with breast cancer, there are limited data on this younger patient population, especially by breast cancer subtype. Given that breast cancer treatment strategies are often similar across age groups, such evidence gaps could represent missed opportunities for developing more targeted treatment strategies for this high-risk population of young women.
To further investigate the cancer-specific genetic profiles in younger women, Sherene Loi, MD, PhD, of the Peter MacCallum Cancer Centre, University of Melbourne, and colleagues turned to data from the pivotal, multicenter Suppression of Ovarian Function Trial (SOFT).
Using next-generation sequencing, Dr. Loi and colleagues evaluated HR-positive, HER2-negative tumors among a subset of 1,276 premenopausal women who were diagnosed with early stage breast cancer. The study employed deep-targeted sequencing for most patients (n = 1,258) as well as whole-exome sequencing in a matched case-control subsample of young women with a median age of 38 years (n = 82).
Compared with women aged 40 and older, those under 40 years of age (n = 359) had significantly higher frequencies of mutations in GATA3 (19% vs. 16%) and copy number-amplifications (47% vs. 26%).
Younger women also had significantly higher features suggestive of homologous recombination deficiency (27% vs. 21% in older women), and a higher proportion of PIK3CA mutations with concurrent copy number-amplifications (23% vs. 11%, respectively), all considered to be poor prognostic features.
In addition, younger women had significantly lower frequencies of certain mutations, including PIK3CA (32% vs. 47%), CDH1 (3% vs. 9%), and MAP3K1 (7% vs. 12%), compared with older women.
Overall, 46% of women had poor prognostic features. These poor prognostic features were observed in 72% of patients under age 35, compared with 54% aged 35-39, and 40% of those 40 and over.
Compared with women without those features, women with poor prognostic features had a lower 8-year distant recurrence-free interval of 84% vs. 94% (hazard ratio, 1.85), and worse 8-year overall survival of 88% vs. 96%, respectively (HR, 2.20). Notably, younger women under age 40 had the poorest outcomes, with an 8-year distant recurrence-free interval rate of 74% vs. 85% in older women, and an 8-year overall survival of 80% vs. 93%, respectively.
How might these results inform potential therapeutics?
Drugs targeting the homologous recombination deficiency pathway are well established, and up to 36% of very young patients in the study showed genomic features of homologous recombination deficiency, the authors noted.
In addition, Dr. Eng explained, there are other Food and Drug Administration–approved treatments that can target the copy number amplified, PIK3CA-mutated tumors, including therapies that target PIK3CA itself, or proteins downstream of it. However, use of such therapies would need “to be tested experimentally, especially since pathway inhibition sometimes may result in rebound signaling to promote tumor growth,” Dr. Eng said.
An important caveat is that patients with germline BRCA1 or BRCA2 mutations may be underrepresented in the SOFT clinical trial, as the trial excluded patients who already had bilateral oophorectomy or planned to within 5 years, the authors noted.
Nevertheless, Dr. Loi said that the study is important because “there are no other datasets as large or with this long follow-up for very young women with breast cancer.”
Furthermore, “the SOFT clinical trial was practice-changing, so using the tumor samples associated with this study is more impactful than smaller cohorts with no outcome data or institutional retrospective cohorts,” she said.
Dr. Eng agreed that the study’s size is an important attribute, allowing the authors to “identify differences that would have been missed in a smaller and more heterogeneous series.”
She added that future research should also include ancestry and racial diversity.
“While young women have higher occurrences of aggressive breast cancers, mortality is twice as likely in young Black women, compared to young White women,” Dr. Eng said.
The study received funding from a Susan G. Komen for the Cure Promise Grant, the National Health and Research Council of Australia, the Breast Cancer Research Foundation, and the National Breast Cancer Foundation of Australia, and support from the family of Judy Eisman in Australia. Dr. Loi and Dr. Eng report no relevant financial disclosures.
A version of this article originally appeared on Medscape.com.
and offer clues about molecular targets for future trials.
Compared with older women with early stage HR-positive breast cancer, women under 40 years of age had significantly higher frequencies of certain mutations, such as GATA3, as well as genomic features associated with a poor prognosis. Notably, the researchers found that women with such poor prognostic features vs. those with none had a significantly worse 8-year distant recurrence-free interval and overall survival.
“We have demonstrated age-related differences in genomic profiles with enrichment of genomic features associated with poor prognosis in these younger premenopausal women compared with older premenopausal and postmenopausal women,” the authors wrote in the study, published in the Annals of Oncology. Importantly, the genomic features highlight “the potential for age-focused treatment strategies.”
Charis Eng, MD, PhD, of the Cleveland Clinic Genomic Medicine Institute, Ohio, noted that the findings are promising but need further validation.
“With time and the appropriate clinical trials in place, I envision that these findings will enable the personalized genomics-driven management of these cancers – not only treatment, but also toward prevention,” said Dr. Eng, who was not involved in the study.
Young premenopausal women, particularly those with HR-positive, luminal breast cancer, are known to have significantly higher recurrence rates and worse survival, compared with older women, but the reasons have remained unclear.
Although previous studies have identified key gene expression signatures linked to worse outcomes in younger patients with breast cancer, there are limited data on this younger patient population, especially by breast cancer subtype. Given that breast cancer treatment strategies are often similar across age groups, such evidence gaps could represent missed opportunities for developing more targeted treatment strategies for this high-risk population of young women.
To further investigate the cancer-specific genetic profiles in younger women, Sherene Loi, MD, PhD, of the Peter MacCallum Cancer Centre, University of Melbourne, and colleagues turned to data from the pivotal, multicenter Suppression of Ovarian Function Trial (SOFT).
Using next-generation sequencing, Dr. Loi and colleagues evaluated HR-positive, HER2-negative tumors among a subset of 1,276 premenopausal women who were diagnosed with early stage breast cancer. The study employed deep-targeted sequencing for most patients (n = 1,258) as well as whole-exome sequencing in a matched case-control subsample of young women with a median age of 38 years (n = 82).
Compared with women aged 40 and older, those under 40 years of age (n = 359) had significantly higher frequencies of mutations in GATA3 (19% vs. 16%) and copy number-amplifications (47% vs. 26%).
Younger women also had significantly higher features suggestive of homologous recombination deficiency (27% vs. 21% in older women), and a higher proportion of PIK3CA mutations with concurrent copy number-amplifications (23% vs. 11%, respectively), all considered to be poor prognostic features.
In addition, younger women had significantly lower frequencies of certain mutations, including PIK3CA (32% vs. 47%), CDH1 (3% vs. 9%), and MAP3K1 (7% vs. 12%), compared with older women.
Overall, 46% of women had poor prognostic features. These poor prognostic features were observed in 72% of patients under age 35, compared with 54% aged 35-39, and 40% of those 40 and over.
Compared with women without those features, women with poor prognostic features had a lower 8-year distant recurrence-free interval of 84% vs. 94% (hazard ratio, 1.85), and worse 8-year overall survival of 88% vs. 96%, respectively (HR, 2.20). Notably, younger women under age 40 had the poorest outcomes, with an 8-year distant recurrence-free interval rate of 74% vs. 85% in older women, and an 8-year overall survival of 80% vs. 93%, respectively.
How might these results inform potential therapeutics?
Drugs targeting the homologous recombination deficiency pathway are well established, and up to 36% of very young patients in the study showed genomic features of homologous recombination deficiency, the authors noted.
In addition, Dr. Eng explained, there are other Food and Drug Administration–approved treatments that can target the copy number amplified, PIK3CA-mutated tumors, including therapies that target PIK3CA itself, or proteins downstream of it. However, use of such therapies would need “to be tested experimentally, especially since pathway inhibition sometimes may result in rebound signaling to promote tumor growth,” Dr. Eng said.
An important caveat is that patients with germline BRCA1 or BRCA2 mutations may be underrepresented in the SOFT clinical trial, as the trial excluded patients who already had bilateral oophorectomy or planned to within 5 years, the authors noted.
Nevertheless, Dr. Loi said that the study is important because “there are no other datasets as large or with this long follow-up for very young women with breast cancer.”
Furthermore, “the SOFT clinical trial was practice-changing, so using the tumor samples associated with this study is more impactful than smaller cohorts with no outcome data or institutional retrospective cohorts,” she said.
Dr. Eng agreed that the study’s size is an important attribute, allowing the authors to “identify differences that would have been missed in a smaller and more heterogeneous series.”
She added that future research should also include ancestry and racial diversity.
“While young women have higher occurrences of aggressive breast cancers, mortality is twice as likely in young Black women, compared to young White women,” Dr. Eng said.
The study received funding from a Susan G. Komen for the Cure Promise Grant, the National Health and Research Council of Australia, the Breast Cancer Research Foundation, and the National Breast Cancer Foundation of Australia, and support from the family of Judy Eisman in Australia. Dr. Loi and Dr. Eng report no relevant financial disclosures.
A version of this article originally appeared on Medscape.com.
and offer clues about molecular targets for future trials.
Compared with older women with early stage HR-positive breast cancer, women under 40 years of age had significantly higher frequencies of certain mutations, such as GATA3, as well as genomic features associated with a poor prognosis. Notably, the researchers found that women with such poor prognostic features vs. those with none had a significantly worse 8-year distant recurrence-free interval and overall survival.
“We have demonstrated age-related differences in genomic profiles with enrichment of genomic features associated with poor prognosis in these younger premenopausal women compared with older premenopausal and postmenopausal women,” the authors wrote in the study, published in the Annals of Oncology. Importantly, the genomic features highlight “the potential for age-focused treatment strategies.”
Charis Eng, MD, PhD, of the Cleveland Clinic Genomic Medicine Institute, Ohio, noted that the findings are promising but need further validation.
“With time and the appropriate clinical trials in place, I envision that these findings will enable the personalized genomics-driven management of these cancers – not only treatment, but also toward prevention,” said Dr. Eng, who was not involved in the study.
Young premenopausal women, particularly those with HR-positive, luminal breast cancer, are known to have significantly higher recurrence rates and worse survival, compared with older women, but the reasons have remained unclear.
Although previous studies have identified key gene expression signatures linked to worse outcomes in younger patients with breast cancer, there are limited data on this younger patient population, especially by breast cancer subtype. Given that breast cancer treatment strategies are often similar across age groups, such evidence gaps could represent missed opportunities for developing more targeted treatment strategies for this high-risk population of young women.
To further investigate the cancer-specific genetic profiles in younger women, Sherene Loi, MD, PhD, of the Peter MacCallum Cancer Centre, University of Melbourne, and colleagues turned to data from the pivotal, multicenter Suppression of Ovarian Function Trial (SOFT).
Using next-generation sequencing, Dr. Loi and colleagues evaluated HR-positive, HER2-negative tumors among a subset of 1,276 premenopausal women who were diagnosed with early stage breast cancer. The study employed deep-targeted sequencing for most patients (n = 1,258) as well as whole-exome sequencing in a matched case-control subsample of young women with a median age of 38 years (n = 82).
Compared with women aged 40 and older, those under 40 years of age (n = 359) had significantly higher frequencies of mutations in GATA3 (19% vs. 16%) and copy number-amplifications (47% vs. 26%).
Younger women also had significantly higher features suggestive of homologous recombination deficiency (27% vs. 21% in older women), and a higher proportion of PIK3CA mutations with concurrent copy number-amplifications (23% vs. 11%, respectively), all considered to be poor prognostic features.
In addition, younger women had significantly lower frequencies of certain mutations, including PIK3CA (32% vs. 47%), CDH1 (3% vs. 9%), and MAP3K1 (7% vs. 12%), compared with older women.
Overall, 46% of women had poor prognostic features. These poor prognostic features were observed in 72% of patients under age 35, compared with 54% aged 35-39, and 40% of those 40 and over.
Compared with women without those features, women with poor prognostic features had a lower 8-year distant recurrence-free interval of 84% vs. 94% (hazard ratio, 1.85), and worse 8-year overall survival of 88% vs. 96%, respectively (HR, 2.20). Notably, younger women under age 40 had the poorest outcomes, with an 8-year distant recurrence-free interval rate of 74% vs. 85% in older women, and an 8-year overall survival of 80% vs. 93%, respectively.
How might these results inform potential therapeutics?
Drugs targeting the homologous recombination deficiency pathway are well established, and up to 36% of very young patients in the study showed genomic features of homologous recombination deficiency, the authors noted.
In addition, Dr. Eng explained, there are other Food and Drug Administration–approved treatments that can target the copy number amplified, PIK3CA-mutated tumors, including therapies that target PIK3CA itself, or proteins downstream of it. However, use of such therapies would need “to be tested experimentally, especially since pathway inhibition sometimes may result in rebound signaling to promote tumor growth,” Dr. Eng said.
An important caveat is that patients with germline BRCA1 or BRCA2 mutations may be underrepresented in the SOFT clinical trial, as the trial excluded patients who already had bilateral oophorectomy or planned to within 5 years, the authors noted.
Nevertheless, Dr. Loi said that the study is important because “there are no other datasets as large or with this long follow-up for very young women with breast cancer.”
Furthermore, “the SOFT clinical trial was practice-changing, so using the tumor samples associated with this study is more impactful than smaller cohorts with no outcome data or institutional retrospective cohorts,” she said.
Dr. Eng agreed that the study’s size is an important attribute, allowing the authors to “identify differences that would have been missed in a smaller and more heterogeneous series.”
She added that future research should also include ancestry and racial diversity.
“While young women have higher occurrences of aggressive breast cancers, mortality is twice as likely in young Black women, compared to young White women,” Dr. Eng said.
The study received funding from a Susan G. Komen for the Cure Promise Grant, the National Health and Research Council of Australia, the Breast Cancer Research Foundation, and the National Breast Cancer Foundation of Australia, and support from the family of Judy Eisman in Australia. Dr. Loi and Dr. Eng report no relevant financial disclosures.
A version of this article originally appeared on Medscape.com.
FROM ANNALS OF ONCOLOGY
Disparities in breast cancer deaths, MRI screening persist
Despite improvements in access to health coverage under the Affordable Care Act (ACA), racial disparities in breast cancer mortality rates persist and the underuse of advanced breast imaging may be one culprit, experts say.
In a recent position statement, researchers highlighted the disproportionally high breast cancer mortality rates among Black women in Louisiana – a state that has one of the highest breast cancer mortality rates in the nation. In 2019, the breast cancer mortality rate among Black women in Louisiana was 29.3 per 100,000 women compared with the national rate of 19.4 per 100,000.
Although Louisiana has made strides in improving access to breast cancer screening in recent years, the use of advanced imaging – specifically breast MRI – remains underused in this high-risk population. A major barrier to wider use of breast MRI has been cost, and ACA expansion led to higher, not lower, out-of-pocket costs for this screening modality.
“Breast MRI is a powerful imaging tool for early detection and for screening women at high risk for breast cancer,” wrote the researchers, led by Brooke L. Morrell, MD, of Louisiana State University Health and Sciences Center, New Orleans.
However, greater access to health care has not necessarily translated to increased breast MRI screening or improved survival among Black women. Even years after the adoption of the ACA, “Black women in Louisiana continue to die of breast cancer at rates significantly greater than the national average,” the authors wrote.
The position statement was published in Cancer.
Breast MRI is known to provide the highest rate of breast cancer detection among commonly used imaging options, with a sensitivity ranging from 81% to 100%. That’s about twice as high as the sensitivity range for mammography after factoring in breast density.
“This is of particular importance when we consider the risk‐based screening of younger populations, in which dense breasts are more prevalent,” the authors explained.
For Black women in particular, studies show nearly a quarter (23%) who develop breast cancer are diagnosed under the age of 50, compared with 16% of White women. Black women are also more likely to develop more aggressive, premenopausal breast cancers, including triple-negative breast cancer, that are more easily detected on MRI.
“Adding supplemental screening breast MRI to annual mammography in higher risk women has been shown to detect up to 18 additional cancers out of 1,000 patients,” Dr. Morrell said. And “many of these cancers are detected much earlier than with mammography alone.”
Still, with ACA expansion, out-of-pocket costs for breast MRI actually increased. This increase likely occurred, in part, because the financial protections outlined in the ACA’s Women’s Preventive Services Guidelines covered mammograms but not breast MRI.
More specifically, under the ACA, Medicaid and most private health insurance plans are required to provide coverage for mammograms at no cost to the patient. The percentage of health plans providing zero cost sharing for mammograms increased under the ACA from 81.9% to 96.8%, but the corresponding rates of zero cost sharing for breast MRI screening went in the opposite direction – from 43.1% in 2009 to only 26.2% in 2017, a 2022 study found.
This study also highlighted geographic variations in zero cost sharing and out-of-pocket costs for screening breast MRI, with a higher financial burden observed for women living in the South. In addition, studies have demonstrated that race and socioeconomic factors, including education and income, play a role in the underuse of screening, including breast MRI.
These factors all likely contribute to screening breast MRI remaining inaccessible to many women, Dr. Morrell and colleagues said.
The authors also outlined three key action items that could help address barriers to MRI breast screening, which include reducing the high cost of breast MRI, lobbying to include breast MRI in ACA protections, and addressing knowledge gaps among patients and clinicians to better identify women who might benefit from breast MRI.
On the financial front, the team explained that a central driver for high costs is the scan time for breast MRI, which could be substantially reduced from 30 to 5 minutes, using an abbreviated protocol.
“Widespread use of low‐cost breast abbreviated MRI screening could remove the cost barrier of adding breast MRI screening to ACA coverage,” without compromising diagnostic accuracy, the authors noted.
Further efforts should focus on overcoming cultural barriers, including fear and mistrust of the health care system among Black women. Outreach efforts could include public campaigns or town hall and church gatherings that enlist patient navigators, advocates, or community members.
“Our visibility in the community builds trust and affords us the opportunity to share knowledge that may empower women to be their own health advocates,” the authors wrote.
In terms of the feasibility of revising ACA policies to improve breast MRI access and affordability, Dr. Morrell pointed to improvements made in colon cancer screening.
“Studies have demonstrated that after ACA policy changes lowering out-of-pocket cost for colonoscopies, screening colonoscopy rates significantly increased among men, predominantly in socioeconomically disadvantaged population,” she noted. “Similarly, we should investigate how to this can be applied to screening breast MRI.”
A version of this article first appeared on Medscape.com.
Despite improvements in access to health coverage under the Affordable Care Act (ACA), racial disparities in breast cancer mortality rates persist and the underuse of advanced breast imaging may be one culprit, experts say.
In a recent position statement, researchers highlighted the disproportionally high breast cancer mortality rates among Black women in Louisiana – a state that has one of the highest breast cancer mortality rates in the nation. In 2019, the breast cancer mortality rate among Black women in Louisiana was 29.3 per 100,000 women compared with the national rate of 19.4 per 100,000.
Although Louisiana has made strides in improving access to breast cancer screening in recent years, the use of advanced imaging – specifically breast MRI – remains underused in this high-risk population. A major barrier to wider use of breast MRI has been cost, and ACA expansion led to higher, not lower, out-of-pocket costs for this screening modality.
“Breast MRI is a powerful imaging tool for early detection and for screening women at high risk for breast cancer,” wrote the researchers, led by Brooke L. Morrell, MD, of Louisiana State University Health and Sciences Center, New Orleans.
However, greater access to health care has not necessarily translated to increased breast MRI screening or improved survival among Black women. Even years after the adoption of the ACA, “Black women in Louisiana continue to die of breast cancer at rates significantly greater than the national average,” the authors wrote.
The position statement was published in Cancer.
Breast MRI is known to provide the highest rate of breast cancer detection among commonly used imaging options, with a sensitivity ranging from 81% to 100%. That’s about twice as high as the sensitivity range for mammography after factoring in breast density.
“This is of particular importance when we consider the risk‐based screening of younger populations, in which dense breasts are more prevalent,” the authors explained.
For Black women in particular, studies show nearly a quarter (23%) who develop breast cancer are diagnosed under the age of 50, compared with 16% of White women. Black women are also more likely to develop more aggressive, premenopausal breast cancers, including triple-negative breast cancer, that are more easily detected on MRI.
“Adding supplemental screening breast MRI to annual mammography in higher risk women has been shown to detect up to 18 additional cancers out of 1,000 patients,” Dr. Morrell said. And “many of these cancers are detected much earlier than with mammography alone.”
Still, with ACA expansion, out-of-pocket costs for breast MRI actually increased. This increase likely occurred, in part, because the financial protections outlined in the ACA’s Women’s Preventive Services Guidelines covered mammograms but not breast MRI.
More specifically, under the ACA, Medicaid and most private health insurance plans are required to provide coverage for mammograms at no cost to the patient. The percentage of health plans providing zero cost sharing for mammograms increased under the ACA from 81.9% to 96.8%, but the corresponding rates of zero cost sharing for breast MRI screening went in the opposite direction – from 43.1% in 2009 to only 26.2% in 2017, a 2022 study found.
This study also highlighted geographic variations in zero cost sharing and out-of-pocket costs for screening breast MRI, with a higher financial burden observed for women living in the South. In addition, studies have demonstrated that race and socioeconomic factors, including education and income, play a role in the underuse of screening, including breast MRI.
These factors all likely contribute to screening breast MRI remaining inaccessible to many women, Dr. Morrell and colleagues said.
The authors also outlined three key action items that could help address barriers to MRI breast screening, which include reducing the high cost of breast MRI, lobbying to include breast MRI in ACA protections, and addressing knowledge gaps among patients and clinicians to better identify women who might benefit from breast MRI.
On the financial front, the team explained that a central driver for high costs is the scan time for breast MRI, which could be substantially reduced from 30 to 5 minutes, using an abbreviated protocol.
“Widespread use of low‐cost breast abbreviated MRI screening could remove the cost barrier of adding breast MRI screening to ACA coverage,” without compromising diagnostic accuracy, the authors noted.
Further efforts should focus on overcoming cultural barriers, including fear and mistrust of the health care system among Black women. Outreach efforts could include public campaigns or town hall and church gatherings that enlist patient navigators, advocates, or community members.
“Our visibility in the community builds trust and affords us the opportunity to share knowledge that may empower women to be their own health advocates,” the authors wrote.
In terms of the feasibility of revising ACA policies to improve breast MRI access and affordability, Dr. Morrell pointed to improvements made in colon cancer screening.
“Studies have demonstrated that after ACA policy changes lowering out-of-pocket cost for colonoscopies, screening colonoscopy rates significantly increased among men, predominantly in socioeconomically disadvantaged population,” she noted. “Similarly, we should investigate how to this can be applied to screening breast MRI.”
A version of this article first appeared on Medscape.com.
Despite improvements in access to health coverage under the Affordable Care Act (ACA), racial disparities in breast cancer mortality rates persist and the underuse of advanced breast imaging may be one culprit, experts say.
In a recent position statement, researchers highlighted the disproportionally high breast cancer mortality rates among Black women in Louisiana – a state that has one of the highest breast cancer mortality rates in the nation. In 2019, the breast cancer mortality rate among Black women in Louisiana was 29.3 per 100,000 women compared with the national rate of 19.4 per 100,000.
Although Louisiana has made strides in improving access to breast cancer screening in recent years, the use of advanced imaging – specifically breast MRI – remains underused in this high-risk population. A major barrier to wider use of breast MRI has been cost, and ACA expansion led to higher, not lower, out-of-pocket costs for this screening modality.
“Breast MRI is a powerful imaging tool for early detection and for screening women at high risk for breast cancer,” wrote the researchers, led by Brooke L. Morrell, MD, of Louisiana State University Health and Sciences Center, New Orleans.
However, greater access to health care has not necessarily translated to increased breast MRI screening or improved survival among Black women. Even years after the adoption of the ACA, “Black women in Louisiana continue to die of breast cancer at rates significantly greater than the national average,” the authors wrote.
The position statement was published in Cancer.
Breast MRI is known to provide the highest rate of breast cancer detection among commonly used imaging options, with a sensitivity ranging from 81% to 100%. That’s about twice as high as the sensitivity range for mammography after factoring in breast density.
“This is of particular importance when we consider the risk‐based screening of younger populations, in which dense breasts are more prevalent,” the authors explained.
For Black women in particular, studies show nearly a quarter (23%) who develop breast cancer are diagnosed under the age of 50, compared with 16% of White women. Black women are also more likely to develop more aggressive, premenopausal breast cancers, including triple-negative breast cancer, that are more easily detected on MRI.
“Adding supplemental screening breast MRI to annual mammography in higher risk women has been shown to detect up to 18 additional cancers out of 1,000 patients,” Dr. Morrell said. And “many of these cancers are detected much earlier than with mammography alone.”
Still, with ACA expansion, out-of-pocket costs for breast MRI actually increased. This increase likely occurred, in part, because the financial protections outlined in the ACA’s Women’s Preventive Services Guidelines covered mammograms but not breast MRI.
More specifically, under the ACA, Medicaid and most private health insurance plans are required to provide coverage for mammograms at no cost to the patient. The percentage of health plans providing zero cost sharing for mammograms increased under the ACA from 81.9% to 96.8%, but the corresponding rates of zero cost sharing for breast MRI screening went in the opposite direction – from 43.1% in 2009 to only 26.2% in 2017, a 2022 study found.
This study also highlighted geographic variations in zero cost sharing and out-of-pocket costs for screening breast MRI, with a higher financial burden observed for women living in the South. In addition, studies have demonstrated that race and socioeconomic factors, including education and income, play a role in the underuse of screening, including breast MRI.
These factors all likely contribute to screening breast MRI remaining inaccessible to many women, Dr. Morrell and colleagues said.
The authors also outlined three key action items that could help address barriers to MRI breast screening, which include reducing the high cost of breast MRI, lobbying to include breast MRI in ACA protections, and addressing knowledge gaps among patients and clinicians to better identify women who might benefit from breast MRI.
On the financial front, the team explained that a central driver for high costs is the scan time for breast MRI, which could be substantially reduced from 30 to 5 minutes, using an abbreviated protocol.
“Widespread use of low‐cost breast abbreviated MRI screening could remove the cost barrier of adding breast MRI screening to ACA coverage,” without compromising diagnostic accuracy, the authors noted.
Further efforts should focus on overcoming cultural barriers, including fear and mistrust of the health care system among Black women. Outreach efforts could include public campaigns or town hall and church gatherings that enlist patient navigators, advocates, or community members.
“Our visibility in the community builds trust and affords us the opportunity to share knowledge that may empower women to be their own health advocates,” the authors wrote.
In terms of the feasibility of revising ACA policies to improve breast MRI access and affordability, Dr. Morrell pointed to improvements made in colon cancer screening.
“Studies have demonstrated that after ACA policy changes lowering out-of-pocket cost for colonoscopies, screening colonoscopy rates significantly increased among men, predominantly in socioeconomically disadvantaged population,” she noted. “Similarly, we should investigate how to this can be applied to screening breast MRI.”
A version of this article first appeared on Medscape.com.
FROM CANCER
Does obesity blunt effects of vitamin D supplementation?
compared with normal-weight individuals in a new analysis of a randomized trial.
“There seems to be something different happening with vitamin D metabolism at higher body weights, and this study may help explain diminished outcomes of supplementation for individuals with an elevated body mass index (BMI),” said first author Deirdre K. Tobias, ScD, an associate epidemiologist at Brigham and Women’s Hospital’s division of preventive medicine in Boston. She made the comments in a press statement issued with the study, published online in JAMA Network Open.
The findings are from a post hoc analysis of the large-scale Vitamin D and Omega-3 Trial (VITAL), which overall, showed no benefits among those randomized to 5 years of vitamin D supplementation (2,000 IU/day) versus placebo in terms of the primary endpoints of cancer or major cardiovascular disease outcomes.
However, prespecified secondary analyses according to body weight showed that those of normal weight (body mass index < 25.0 kg/m2) did have significant benefits from supplementation versus placebo in terms of cancer incidence (24% lower), cancer mortality (42% lower), and autoimmune disease (22% lower), while no corresponding benefits were observed among those who were overweight or had obesity.
The new analysis adds important context to the trial’s overall findings, noted Katherine N. Bachmann, MD, in an accompanying editorial.
“Thanks to its very large sample size and detailed biomarker analyses, the current study is able to provide novel evidence that responses to vitamin D supplementation may be attenuated in individuals with overweight and obesity, and that this may contribute to the differential outcomes by BMI noted in the original VITAL,” she wrote.
“Further studies are warranted to determine the optimal dose or circulating vitamin D level for individuals with obesity for nonskeletal health-related outcomes,” added Dr. Bachmann, division of diabetes, endocrinology, and metabolism at Vanderbilt University Medical Center, Nashville, Tenn.
New analysis examined vitamin D and biomarkers at baseline and 2 years
To take a closer look at the specific changes in vitamin D serum and biomarker levels between the different body-weight groups, Dr. Tobias and colleagues evaluated data from 16,515 participants in the trial (of the 25,000 originally included in VITAL) and looked at changes in key vitamin D serum levels and biomarkers at baseline and follow-up.
Consistent with common observations of lower vitamin D levels with obesity, participants in the higher BMI categories had incrementally lower mean levels of serum total 25-hydroxyvitamin D (25-OHD) prior to randomization, with levels ranging from 32.3 ng/mL for normal weight individuals to 28.0 ng/mL for those with obesity class II (P < .001 for a linear trend).
Baseline levels of other vitamin D biomarkers were also lower with higher BMI, including total 25-OHD 3, free vitamin D (FVD), and bioavailable vitamin D (BioD).
Among 2,742 participants with repeated blood collections at year 2, significant mean increases were observed overall at the end of the study period in serum 25-OHD levels (11.9 ng/mL) among those randomized to vitamin D supplementation, compared with little change in the placebo group (–0.7 ng/mL).
There were also significant increases, overall, in mean total 25-OHD, 25-OHD3, FVD, and BioD levels at 2 years among those receiving supplementation, with little or no change in the placebo group.
When stratified by BMI level, however, the magnitude of increase was lower among those with higher baseline BMI (all treatment effect interactions P < .001). For instance, the mean increases in total 25-OHD level at 2 years for supplementation versus placebo were 13.5 ng/mL for those with a BMI less than 25.0 versus only 10.0 ng/mL for those with a BMI of at least 35.0.
Importantly, even after controlling for baseline vitamin D status of sufficiency or insufficiency, BMI was still significantly associated with changes seen with supplementation.
“It was surprising that, even in the context of low vitamin D levels, those with higher BMI still had a blunted response to supplementation, suggesting the interaction between supplementation and BMI with health outcomes is not simply due to higher prevalence of deficiency,” Dr. Tobias said in an interview. “It really does seem that, even with insufficient or low levels at baseline, those with higher BMI are not able to catch up to sufficient levels as well as those with normal BMI.”
Mechanisms?
Among leading theories as to why higher BMI would be associated with lower serum vitamin D levels and a lower response to supplementation is that because vitamin D is a fat-soluble vitamin, the increased adiposity and fat storage capacity with higher BMI results in greater removal of the vitamin from circulation.
“Our results are largely consistent with this hypothesis,” the authors noted.
They added that weight-loss studies, including those involving bariatric surgery, have further shown greater increases in serum 25-OHD or circulating vitamin D levels after weight loss compared with baseline.
Other theories suggest that obesity-induced hepatic dysfunction can contribute to impaired vitamin D metabolism.
Without a clear understanding of the exact mechanisms, the potential for addressing the lower vitamin D levels with, for instance, higher doses of supplementation among those with obesity, also remains unclear, Dr. Tobias noted.
“I think once there’s more clarity on what the mechanism is, then it would make sense to consider what doses could be necessary to achieve the internal levels desired,” she said.
The VITAL study received funding from a grant from the National Center for Complementary and Integrative Health and other sources.
A version of this article first appeared on Medscape.com.
compared with normal-weight individuals in a new analysis of a randomized trial.
“There seems to be something different happening with vitamin D metabolism at higher body weights, and this study may help explain diminished outcomes of supplementation for individuals with an elevated body mass index (BMI),” said first author Deirdre K. Tobias, ScD, an associate epidemiologist at Brigham and Women’s Hospital’s division of preventive medicine in Boston. She made the comments in a press statement issued with the study, published online in JAMA Network Open.
The findings are from a post hoc analysis of the large-scale Vitamin D and Omega-3 Trial (VITAL), which overall, showed no benefits among those randomized to 5 years of vitamin D supplementation (2,000 IU/day) versus placebo in terms of the primary endpoints of cancer or major cardiovascular disease outcomes.
However, prespecified secondary analyses according to body weight showed that those of normal weight (body mass index < 25.0 kg/m2) did have significant benefits from supplementation versus placebo in terms of cancer incidence (24% lower), cancer mortality (42% lower), and autoimmune disease (22% lower), while no corresponding benefits were observed among those who were overweight or had obesity.
The new analysis adds important context to the trial’s overall findings, noted Katherine N. Bachmann, MD, in an accompanying editorial.
“Thanks to its very large sample size and detailed biomarker analyses, the current study is able to provide novel evidence that responses to vitamin D supplementation may be attenuated in individuals with overweight and obesity, and that this may contribute to the differential outcomes by BMI noted in the original VITAL,” she wrote.
“Further studies are warranted to determine the optimal dose or circulating vitamin D level for individuals with obesity for nonskeletal health-related outcomes,” added Dr. Bachmann, division of diabetes, endocrinology, and metabolism at Vanderbilt University Medical Center, Nashville, Tenn.
New analysis examined vitamin D and biomarkers at baseline and 2 years
To take a closer look at the specific changes in vitamin D serum and biomarker levels between the different body-weight groups, Dr. Tobias and colleagues evaluated data from 16,515 participants in the trial (of the 25,000 originally included in VITAL) and looked at changes in key vitamin D serum levels and biomarkers at baseline and follow-up.
Consistent with common observations of lower vitamin D levels with obesity, participants in the higher BMI categories had incrementally lower mean levels of serum total 25-hydroxyvitamin D (25-OHD) prior to randomization, with levels ranging from 32.3 ng/mL for normal weight individuals to 28.0 ng/mL for those with obesity class II (P < .001 for a linear trend).
Baseline levels of other vitamin D biomarkers were also lower with higher BMI, including total 25-OHD 3, free vitamin D (FVD), and bioavailable vitamin D (BioD).
Among 2,742 participants with repeated blood collections at year 2, significant mean increases were observed overall at the end of the study period in serum 25-OHD levels (11.9 ng/mL) among those randomized to vitamin D supplementation, compared with little change in the placebo group (–0.7 ng/mL).
There were also significant increases, overall, in mean total 25-OHD, 25-OHD3, FVD, and BioD levels at 2 years among those receiving supplementation, with little or no change in the placebo group.
When stratified by BMI level, however, the magnitude of increase was lower among those with higher baseline BMI (all treatment effect interactions P < .001). For instance, the mean increases in total 25-OHD level at 2 years for supplementation versus placebo were 13.5 ng/mL for those with a BMI less than 25.0 versus only 10.0 ng/mL for those with a BMI of at least 35.0.
Importantly, even after controlling for baseline vitamin D status of sufficiency or insufficiency, BMI was still significantly associated with changes seen with supplementation.
“It was surprising that, even in the context of low vitamin D levels, those with higher BMI still had a blunted response to supplementation, suggesting the interaction between supplementation and BMI with health outcomes is not simply due to higher prevalence of deficiency,” Dr. Tobias said in an interview. “It really does seem that, even with insufficient or low levels at baseline, those with higher BMI are not able to catch up to sufficient levels as well as those with normal BMI.”
Mechanisms?
Among leading theories as to why higher BMI would be associated with lower serum vitamin D levels and a lower response to supplementation is that because vitamin D is a fat-soluble vitamin, the increased adiposity and fat storage capacity with higher BMI results in greater removal of the vitamin from circulation.
“Our results are largely consistent with this hypothesis,” the authors noted.
They added that weight-loss studies, including those involving bariatric surgery, have further shown greater increases in serum 25-OHD or circulating vitamin D levels after weight loss compared with baseline.
Other theories suggest that obesity-induced hepatic dysfunction can contribute to impaired vitamin D metabolism.
Without a clear understanding of the exact mechanisms, the potential for addressing the lower vitamin D levels with, for instance, higher doses of supplementation among those with obesity, also remains unclear, Dr. Tobias noted.
“I think once there’s more clarity on what the mechanism is, then it would make sense to consider what doses could be necessary to achieve the internal levels desired,” she said.
The VITAL study received funding from a grant from the National Center for Complementary and Integrative Health and other sources.
A version of this article first appeared on Medscape.com.
compared with normal-weight individuals in a new analysis of a randomized trial.
“There seems to be something different happening with vitamin D metabolism at higher body weights, and this study may help explain diminished outcomes of supplementation for individuals with an elevated body mass index (BMI),” said first author Deirdre K. Tobias, ScD, an associate epidemiologist at Brigham and Women’s Hospital’s division of preventive medicine in Boston. She made the comments in a press statement issued with the study, published online in JAMA Network Open.
The findings are from a post hoc analysis of the large-scale Vitamin D and Omega-3 Trial (VITAL), which overall, showed no benefits among those randomized to 5 years of vitamin D supplementation (2,000 IU/day) versus placebo in terms of the primary endpoints of cancer or major cardiovascular disease outcomes.
However, prespecified secondary analyses according to body weight showed that those of normal weight (body mass index < 25.0 kg/m2) did have significant benefits from supplementation versus placebo in terms of cancer incidence (24% lower), cancer mortality (42% lower), and autoimmune disease (22% lower), while no corresponding benefits were observed among those who were overweight or had obesity.
The new analysis adds important context to the trial’s overall findings, noted Katherine N. Bachmann, MD, in an accompanying editorial.
“Thanks to its very large sample size and detailed biomarker analyses, the current study is able to provide novel evidence that responses to vitamin D supplementation may be attenuated in individuals with overweight and obesity, and that this may contribute to the differential outcomes by BMI noted in the original VITAL,” she wrote.
“Further studies are warranted to determine the optimal dose or circulating vitamin D level for individuals with obesity for nonskeletal health-related outcomes,” added Dr. Bachmann, division of diabetes, endocrinology, and metabolism at Vanderbilt University Medical Center, Nashville, Tenn.
New analysis examined vitamin D and biomarkers at baseline and 2 years
To take a closer look at the specific changes in vitamin D serum and biomarker levels between the different body-weight groups, Dr. Tobias and colleagues evaluated data from 16,515 participants in the trial (of the 25,000 originally included in VITAL) and looked at changes in key vitamin D serum levels and biomarkers at baseline and follow-up.
Consistent with common observations of lower vitamin D levels with obesity, participants in the higher BMI categories had incrementally lower mean levels of serum total 25-hydroxyvitamin D (25-OHD) prior to randomization, with levels ranging from 32.3 ng/mL for normal weight individuals to 28.0 ng/mL for those with obesity class II (P < .001 for a linear trend).
Baseline levels of other vitamin D biomarkers were also lower with higher BMI, including total 25-OHD 3, free vitamin D (FVD), and bioavailable vitamin D (BioD).
Among 2,742 participants with repeated blood collections at year 2, significant mean increases were observed overall at the end of the study period in serum 25-OHD levels (11.9 ng/mL) among those randomized to vitamin D supplementation, compared with little change in the placebo group (–0.7 ng/mL).
There were also significant increases, overall, in mean total 25-OHD, 25-OHD3, FVD, and BioD levels at 2 years among those receiving supplementation, with little or no change in the placebo group.
When stratified by BMI level, however, the magnitude of increase was lower among those with higher baseline BMI (all treatment effect interactions P < .001). For instance, the mean increases in total 25-OHD level at 2 years for supplementation versus placebo were 13.5 ng/mL for those with a BMI less than 25.0 versus only 10.0 ng/mL for those with a BMI of at least 35.0.
Importantly, even after controlling for baseline vitamin D status of sufficiency or insufficiency, BMI was still significantly associated with changes seen with supplementation.
“It was surprising that, even in the context of low vitamin D levels, those with higher BMI still had a blunted response to supplementation, suggesting the interaction between supplementation and BMI with health outcomes is not simply due to higher prevalence of deficiency,” Dr. Tobias said in an interview. “It really does seem that, even with insufficient or low levels at baseline, those with higher BMI are not able to catch up to sufficient levels as well as those with normal BMI.”
Mechanisms?
Among leading theories as to why higher BMI would be associated with lower serum vitamin D levels and a lower response to supplementation is that because vitamin D is a fat-soluble vitamin, the increased adiposity and fat storage capacity with higher BMI results in greater removal of the vitamin from circulation.
“Our results are largely consistent with this hypothesis,” the authors noted.
They added that weight-loss studies, including those involving bariatric surgery, have further shown greater increases in serum 25-OHD or circulating vitamin D levels after weight loss compared with baseline.
Other theories suggest that obesity-induced hepatic dysfunction can contribute to impaired vitamin D metabolism.
Without a clear understanding of the exact mechanisms, the potential for addressing the lower vitamin D levels with, for instance, higher doses of supplementation among those with obesity, also remains unclear, Dr. Tobias noted.
“I think once there’s more clarity on what the mechanism is, then it would make sense to consider what doses could be necessary to achieve the internal levels desired,” she said.
The VITAL study received funding from a grant from the National Center for Complementary and Integrative Health and other sources.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN
New consensus on thyroid eye disease prompts some debate
A new consensus statement from the American Thyroid Association (ATA) and European Thyroid Association (ETA) offers recommendations for endocrinologists on the management of thyroid eye disease (TED), addressing key questions, including about important novel treatments, that transcend international borders.
The consensus statement is important as new therapies transform the treatment of TED that, notably, have even played a key role in simplifying the name of the disease, which has had numerous other, often confusing names over the years, ranging from thyrotropic exophthalmos to Graves ophthalmopathy, Terry F. Davies, MD, of the thyroid research unit, department of medicine, Icahn School of Medicine at Mount Sinai, New York, said in an editorial published along with the statement in Thyroid.
“The emergence of novel therapies has changed the entire discussion concerning TED and not just its name,” he wrote. “These are early and exciting days in the treatment of TED, which is likely to be a much more manageable disease in the years to come.”
However, Dr. Davies stressed to this news organization that there are still a lot of unanswered questions, particularly when it comes to newer therapies. For example, teprotumumab can cost up to $300,000 for one course of treatment for one patient, the consensus statement notes.
When to consult an ophthalmologist
Graves disease is the most common cause of hyperthyroidism and affects > 1% of the U.S. population. TED is the most common complication of Graves disease that occurs outside of the thyroid gland. TED causes a variety of eye-related signs and symptoms, which can be disfiguring and negatively affect quality of life, and in rare cases, threaten vision.
Key issues covered in the consensus statement include timely diagnosis of TED, assessment of disease activity and severity, initial care and referral for specialty care, and treatment recommendations for moderate to severe TED.
In terms of disease assessment, for instance, the statement authors noted the important distinction in TED “between the two interdependent components of inflammatory activity, manifested by pain, redness, and edema, and disease severity, including proptosis, lid malposition, exposure keratopathy, impaired ocular motility, and optic neuropathy.”
“The presence of multiple features of inflammation usually signifies active disease,” they explained.
For initial care, input from endocrinologists as well as ophthalmologists with experience in TED management is urged, and “an ophthalmologist should be consulted when the diagnosis of TED is uncertain, in cases of moderate to severe TED, and when surgical intervention needs to be considered.”
Furthermore, “urgent referral is required when sight-threatening TED is suspected or confirmed,” the authors noted.
Debate over some treatment recommendations
In terms of therapy, for initial care, “a single course of selenium selenite 100 mcg twice daily for 6 months may be considered for patients with mild, active TED, particularly in regions of selenium insufficiency,” the consensus statement recommends.
Intravenous glucocorticoid (IVGC) therapy is meanwhile recommended as a preferred treatment for active moderate to severe TED specifically when disease activity is the prominent feature in the absence of significant proptosis or diplopia.
For patients with active moderate to severe TED who are glucocorticoid-resistant, the authors noted that rituximab and tocilizumab may be considered and that teprotumumab has not been evaluated in this setting.
Teprotumumab, if available, is a preferred therapy for patients with active moderate to severe TED who have significant proptosis.
There is, however, some debate over the issue, editorial author Dr. Davies told this news organization.
“It is still argued over how bad the eyes need to be before recommending this new treatment,” he said. “I think the answer is in the proptosis – the amount of bulging present rather than just inflammation,” Dr. Davies said.
“There is also a real clinical problem in that we have no specific biomarker for the disease, however, high levels of TSH receptor antibody are often a good indicator of eye disease.”
The authors cautioned, however, that clinical trials with medical therapies have been limited by inclusion criteria and other factors, and biologics have meanwhile increased the cost of treatment “many-fold” compared with conventional agents.
Therefore, “clinicians should balance the demonstrated efficacy of recently introduced therapies [such as teprotumumab] against the absence of experience on sustained long-term efficacy, safety, and cost-effectiveness,” they noted.
Importantly, “one course consisting of eight infusions of teprotumumab has a retail cost of approximately $300,000, depending on patient weight, [which is] approximately 2,000 times that of IVGC,” they noted.
“The process involved in selecting therapy with these drugs and other drugs includes a consideration of both short- and long-term efficacy, adverse effects that are both known and unknown, the likelihood of disease aggravation or relapse after a previously beneficial response, and the relative cost and availability,” said Henry B. Burch, MD, who is at the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, in Bethesda, Md., and is on the consensus statement task force.
To help with those decisions, the consensus statement provides comprehensive tables that compare drug efficacy for key outcomes including inflammation, proptosis, diplopia, and quality of life, and importantly, comparisons also of drug costs and potential adverse effects for each of the current TED therapies.
Consensus statement not a guideline
The groups noted that the consensus statement is not meant to be a clinical practice guideline and was not written to “establish a standard of care, replace sound clinical judgment, or capture all nuances likely to be present in any particular patient,” and “specific outcomes are not guaranteed.”
What the statement is intended for is to “provide a concise and timely appraisal of a rapidly changing therapeutic arena” for practicing endocrinologists, they explained.
Overall, the authors recommend an individualized management approach, based on factors ranging from disease severity, duration, its impact on daily living, patient age, comorbidities, and importantly, the costs of therapies.
Ultimately, patient satisfaction is essential in TED management, Dr. Burch added.
“Consideration of the impact of TED on patient’s satisfaction with their appearance and visual functioning is a key component in management decisions concerning TED.”A version of this article first appeared on Medscape.com.
A new consensus statement from the American Thyroid Association (ATA) and European Thyroid Association (ETA) offers recommendations for endocrinologists on the management of thyroid eye disease (TED), addressing key questions, including about important novel treatments, that transcend international borders.
The consensus statement is important as new therapies transform the treatment of TED that, notably, have even played a key role in simplifying the name of the disease, which has had numerous other, often confusing names over the years, ranging from thyrotropic exophthalmos to Graves ophthalmopathy, Terry F. Davies, MD, of the thyroid research unit, department of medicine, Icahn School of Medicine at Mount Sinai, New York, said in an editorial published along with the statement in Thyroid.
“The emergence of novel therapies has changed the entire discussion concerning TED and not just its name,” he wrote. “These are early and exciting days in the treatment of TED, which is likely to be a much more manageable disease in the years to come.”
However, Dr. Davies stressed to this news organization that there are still a lot of unanswered questions, particularly when it comes to newer therapies. For example, teprotumumab can cost up to $300,000 for one course of treatment for one patient, the consensus statement notes.
When to consult an ophthalmologist
Graves disease is the most common cause of hyperthyroidism and affects > 1% of the U.S. population. TED is the most common complication of Graves disease that occurs outside of the thyroid gland. TED causes a variety of eye-related signs and symptoms, which can be disfiguring and negatively affect quality of life, and in rare cases, threaten vision.
Key issues covered in the consensus statement include timely diagnosis of TED, assessment of disease activity and severity, initial care and referral for specialty care, and treatment recommendations for moderate to severe TED.
In terms of disease assessment, for instance, the statement authors noted the important distinction in TED “between the two interdependent components of inflammatory activity, manifested by pain, redness, and edema, and disease severity, including proptosis, lid malposition, exposure keratopathy, impaired ocular motility, and optic neuropathy.”
“The presence of multiple features of inflammation usually signifies active disease,” they explained.
For initial care, input from endocrinologists as well as ophthalmologists with experience in TED management is urged, and “an ophthalmologist should be consulted when the diagnosis of TED is uncertain, in cases of moderate to severe TED, and when surgical intervention needs to be considered.”
Furthermore, “urgent referral is required when sight-threatening TED is suspected or confirmed,” the authors noted.
Debate over some treatment recommendations
In terms of therapy, for initial care, “a single course of selenium selenite 100 mcg twice daily for 6 months may be considered for patients with mild, active TED, particularly in regions of selenium insufficiency,” the consensus statement recommends.
Intravenous glucocorticoid (IVGC) therapy is meanwhile recommended as a preferred treatment for active moderate to severe TED specifically when disease activity is the prominent feature in the absence of significant proptosis or diplopia.
For patients with active moderate to severe TED who are glucocorticoid-resistant, the authors noted that rituximab and tocilizumab may be considered and that teprotumumab has not been evaluated in this setting.
Teprotumumab, if available, is a preferred therapy for patients with active moderate to severe TED who have significant proptosis.
There is, however, some debate over the issue, editorial author Dr. Davies told this news organization.
“It is still argued over how bad the eyes need to be before recommending this new treatment,” he said. “I think the answer is in the proptosis – the amount of bulging present rather than just inflammation,” Dr. Davies said.
“There is also a real clinical problem in that we have no specific biomarker for the disease, however, high levels of TSH receptor antibody are often a good indicator of eye disease.”
The authors cautioned, however, that clinical trials with medical therapies have been limited by inclusion criteria and other factors, and biologics have meanwhile increased the cost of treatment “many-fold” compared with conventional agents.
Therefore, “clinicians should balance the demonstrated efficacy of recently introduced therapies [such as teprotumumab] against the absence of experience on sustained long-term efficacy, safety, and cost-effectiveness,” they noted.
Importantly, “one course consisting of eight infusions of teprotumumab has a retail cost of approximately $300,000, depending on patient weight, [which is] approximately 2,000 times that of IVGC,” they noted.
“The process involved in selecting therapy with these drugs and other drugs includes a consideration of both short- and long-term efficacy, adverse effects that are both known and unknown, the likelihood of disease aggravation or relapse after a previously beneficial response, and the relative cost and availability,” said Henry B. Burch, MD, who is at the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, in Bethesda, Md., and is on the consensus statement task force.
To help with those decisions, the consensus statement provides comprehensive tables that compare drug efficacy for key outcomes including inflammation, proptosis, diplopia, and quality of life, and importantly, comparisons also of drug costs and potential adverse effects for each of the current TED therapies.
Consensus statement not a guideline
The groups noted that the consensus statement is not meant to be a clinical practice guideline and was not written to “establish a standard of care, replace sound clinical judgment, or capture all nuances likely to be present in any particular patient,” and “specific outcomes are not guaranteed.”
What the statement is intended for is to “provide a concise and timely appraisal of a rapidly changing therapeutic arena” for practicing endocrinologists, they explained.
Overall, the authors recommend an individualized management approach, based on factors ranging from disease severity, duration, its impact on daily living, patient age, comorbidities, and importantly, the costs of therapies.
Ultimately, patient satisfaction is essential in TED management, Dr. Burch added.
“Consideration of the impact of TED on patient’s satisfaction with their appearance and visual functioning is a key component in management decisions concerning TED.”A version of this article first appeared on Medscape.com.
A new consensus statement from the American Thyroid Association (ATA) and European Thyroid Association (ETA) offers recommendations for endocrinologists on the management of thyroid eye disease (TED), addressing key questions, including about important novel treatments, that transcend international borders.
The consensus statement is important as new therapies transform the treatment of TED that, notably, have even played a key role in simplifying the name of the disease, which has had numerous other, often confusing names over the years, ranging from thyrotropic exophthalmos to Graves ophthalmopathy, Terry F. Davies, MD, of the thyroid research unit, department of medicine, Icahn School of Medicine at Mount Sinai, New York, said in an editorial published along with the statement in Thyroid.
“The emergence of novel therapies has changed the entire discussion concerning TED and not just its name,” he wrote. “These are early and exciting days in the treatment of TED, which is likely to be a much more manageable disease in the years to come.”
However, Dr. Davies stressed to this news organization that there are still a lot of unanswered questions, particularly when it comes to newer therapies. For example, teprotumumab can cost up to $300,000 for one course of treatment for one patient, the consensus statement notes.
When to consult an ophthalmologist
Graves disease is the most common cause of hyperthyroidism and affects > 1% of the U.S. population. TED is the most common complication of Graves disease that occurs outside of the thyroid gland. TED causes a variety of eye-related signs and symptoms, which can be disfiguring and negatively affect quality of life, and in rare cases, threaten vision.
Key issues covered in the consensus statement include timely diagnosis of TED, assessment of disease activity and severity, initial care and referral for specialty care, and treatment recommendations for moderate to severe TED.
In terms of disease assessment, for instance, the statement authors noted the important distinction in TED “between the two interdependent components of inflammatory activity, manifested by pain, redness, and edema, and disease severity, including proptosis, lid malposition, exposure keratopathy, impaired ocular motility, and optic neuropathy.”
“The presence of multiple features of inflammation usually signifies active disease,” they explained.
For initial care, input from endocrinologists as well as ophthalmologists with experience in TED management is urged, and “an ophthalmologist should be consulted when the diagnosis of TED is uncertain, in cases of moderate to severe TED, and when surgical intervention needs to be considered.”
Furthermore, “urgent referral is required when sight-threatening TED is suspected or confirmed,” the authors noted.
Debate over some treatment recommendations
In terms of therapy, for initial care, “a single course of selenium selenite 100 mcg twice daily for 6 months may be considered for patients with mild, active TED, particularly in regions of selenium insufficiency,” the consensus statement recommends.
Intravenous glucocorticoid (IVGC) therapy is meanwhile recommended as a preferred treatment for active moderate to severe TED specifically when disease activity is the prominent feature in the absence of significant proptosis or diplopia.
For patients with active moderate to severe TED who are glucocorticoid-resistant, the authors noted that rituximab and tocilizumab may be considered and that teprotumumab has not been evaluated in this setting.
Teprotumumab, if available, is a preferred therapy for patients with active moderate to severe TED who have significant proptosis.
There is, however, some debate over the issue, editorial author Dr. Davies told this news organization.
“It is still argued over how bad the eyes need to be before recommending this new treatment,” he said. “I think the answer is in the proptosis – the amount of bulging present rather than just inflammation,” Dr. Davies said.
“There is also a real clinical problem in that we have no specific biomarker for the disease, however, high levels of TSH receptor antibody are often a good indicator of eye disease.”
The authors cautioned, however, that clinical trials with medical therapies have been limited by inclusion criteria and other factors, and biologics have meanwhile increased the cost of treatment “many-fold” compared with conventional agents.
Therefore, “clinicians should balance the demonstrated efficacy of recently introduced therapies [such as teprotumumab] against the absence of experience on sustained long-term efficacy, safety, and cost-effectiveness,” they noted.
Importantly, “one course consisting of eight infusions of teprotumumab has a retail cost of approximately $300,000, depending on patient weight, [which is] approximately 2,000 times that of IVGC,” they noted.
“The process involved in selecting therapy with these drugs and other drugs includes a consideration of both short- and long-term efficacy, adverse effects that are both known and unknown, the likelihood of disease aggravation or relapse after a previously beneficial response, and the relative cost and availability,” said Henry B. Burch, MD, who is at the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, in Bethesda, Md., and is on the consensus statement task force.
To help with those decisions, the consensus statement provides comprehensive tables that compare drug efficacy for key outcomes including inflammation, proptosis, diplopia, and quality of life, and importantly, comparisons also of drug costs and potential adverse effects for each of the current TED therapies.
Consensus statement not a guideline
The groups noted that the consensus statement is not meant to be a clinical practice guideline and was not written to “establish a standard of care, replace sound clinical judgment, or capture all nuances likely to be present in any particular patient,” and “specific outcomes are not guaranteed.”
What the statement is intended for is to “provide a concise and timely appraisal of a rapidly changing therapeutic arena” for practicing endocrinologists, they explained.
Overall, the authors recommend an individualized management approach, based on factors ranging from disease severity, duration, its impact on daily living, patient age, comorbidities, and importantly, the costs of therapies.
Ultimately, patient satisfaction is essential in TED management, Dr. Burch added.
“Consideration of the impact of TED on patient’s satisfaction with their appearance and visual functioning is a key component in management decisions concerning TED.”A version of this article first appeared on Medscape.com.
Adverse events linked to better survival with ICIs in melanoma
Among Survival is further improved if the immunotherapy is continued after the adverse event develops, a new study confirms.
“In the largest clinical cohort to date, our data support a positive association with overall survival for patients who develop clinically significant immune-related adverse events while receiving combination immune checkpoint blockade, in keeping with other reported series,” the authors wrote.
The study was published online in JAMA Network Open.
Immune-related adverse events are common with these drugs. Severe events of grade 3 or higher occur in 59% of trial patients who receive combination ICI therapy.
The adverse events have increasingly been positively associated with survival. However, the effects for patients with metastatic melanoma, in particular, are less clear. There is little research on the effects in relation to combination therapy with ipilimumab and nivolumab, which is the standard of care for many patients with metastatic melanoma.
To investigate, Alexander S. Watson, MD, and colleagues evaluated data on 492 patients with metastatic melanoma who had been treated with one or more doses of an anti–programmed death 1 agent as single or combination immune checkpoint blockade in the multicenter Alberta Immunotherapy Database from August 2013 to May 2020.
Of these 492 patients, 198 patients (40%) developed immune-related adverse events. The mean age of the patients who developed adverse events was 61.8 years; of those who did not develop adverse events, the mean age was 65.5 years. Men made up 69.2% and 62.2%, respectively.
A total of 288 patients received pembrolizumab as their first ICI therapy, 80 received nivolumab, and 124 received combination blockade with ipilimumab-nivolumab.
Overall, with a median follow-up of 36.6 months, among patients who experienced clinically significant immune-related adverse events, defined as requiring systemic corticosteroids and/or a treatment delay, median overall survival was significantly improved, at 56.3 months, compared with 18.5 months among those who did not experience immune-related adverse events (P < .001).
In addition, among those who received combination ICI treatment, the median overall survival was 56.2 months for those who experienced adverse events versus 19.0 months for those who did not (P < .001).
There were no significant differences in overall survival between those who were and those who were not hospitalized for their immune-related adverse events (P = .53).
For patients who resumed their ICI therapy following the adverse events, overall survival was longer, compared with those who did not resume the therapy (median, 56.3 months vs. 31.5 months; P = .009).
The improvements in overall survival seen with immune-related adverse events remained consistent after adjustment in a multivariable analysis (hazard ratio for death, 0.382; P < .001).
There were no significant differences in the median number of cycles of ICIs between those with and those without the adverse events.
The risk of recurrence of immune-related adverse events following the reintroduction of therapy after initial events was a concern, so the improved overall survival among those patients is encouraging, although further investigation is needed, commented lead author Dr. Watson, from the department of oncology, University of Calgary (Alta.).
“It may be, for certain patients with immune-related adverse events, that continued immune-priming is safe and optimizes anticancer response,” he told this news organization. “However, in a retrospective analysis such as ours, selection bias can have an impact.”
“Confirming this finding and better identifying patients who may benefit from resumption will be an area for future investigation,” he said.
Patients who developed immune-related adverse events were more likely to be younger than 50 years (21.8% vs. 13.9%), have normal albumin levels (86.4% vs. 74.8%), and have a more robust Eastern Cooperative Oncology Group status, which is consistent with other studies that have shown survival benefits among those who experience adverse events.
“We, and others, speculate this could be due to such groups having immune systems more ready to respond strongly to immunotherapy,” Dr. Watson explained.
After controlling for age and performance status in the multivariable analysis, however, “immune-related adverse events remained strongly associated with survival, potentially [indicating] that robust responses to immunotherapy lead to both cancer control and immune-related adverse events,” he said.
Overall, “we feel these findings will help clinicians in discussions with patients and in clinical decision-making after adverse events develop,” Dr. Watson said.
Dr. Watson has received personal fees from Apobiologix Canada.
A version of this article first appeared on Medscape.com.
Among Survival is further improved if the immunotherapy is continued after the adverse event develops, a new study confirms.
“In the largest clinical cohort to date, our data support a positive association with overall survival for patients who develop clinically significant immune-related adverse events while receiving combination immune checkpoint blockade, in keeping with other reported series,” the authors wrote.
The study was published online in JAMA Network Open.
Immune-related adverse events are common with these drugs. Severe events of grade 3 or higher occur in 59% of trial patients who receive combination ICI therapy.
The adverse events have increasingly been positively associated with survival. However, the effects for patients with metastatic melanoma, in particular, are less clear. There is little research on the effects in relation to combination therapy with ipilimumab and nivolumab, which is the standard of care for many patients with metastatic melanoma.
To investigate, Alexander S. Watson, MD, and colleagues evaluated data on 492 patients with metastatic melanoma who had been treated with one or more doses of an anti–programmed death 1 agent as single or combination immune checkpoint blockade in the multicenter Alberta Immunotherapy Database from August 2013 to May 2020.
Of these 492 patients, 198 patients (40%) developed immune-related adverse events. The mean age of the patients who developed adverse events was 61.8 years; of those who did not develop adverse events, the mean age was 65.5 years. Men made up 69.2% and 62.2%, respectively.
A total of 288 patients received pembrolizumab as their first ICI therapy, 80 received nivolumab, and 124 received combination blockade with ipilimumab-nivolumab.
Overall, with a median follow-up of 36.6 months, among patients who experienced clinically significant immune-related adverse events, defined as requiring systemic corticosteroids and/or a treatment delay, median overall survival was significantly improved, at 56.3 months, compared with 18.5 months among those who did not experience immune-related adverse events (P < .001).
In addition, among those who received combination ICI treatment, the median overall survival was 56.2 months for those who experienced adverse events versus 19.0 months for those who did not (P < .001).
There were no significant differences in overall survival between those who were and those who were not hospitalized for their immune-related adverse events (P = .53).
For patients who resumed their ICI therapy following the adverse events, overall survival was longer, compared with those who did not resume the therapy (median, 56.3 months vs. 31.5 months; P = .009).
The improvements in overall survival seen with immune-related adverse events remained consistent after adjustment in a multivariable analysis (hazard ratio for death, 0.382; P < .001).
There were no significant differences in the median number of cycles of ICIs between those with and those without the adverse events.
The risk of recurrence of immune-related adverse events following the reintroduction of therapy after initial events was a concern, so the improved overall survival among those patients is encouraging, although further investigation is needed, commented lead author Dr. Watson, from the department of oncology, University of Calgary (Alta.).
“It may be, for certain patients with immune-related adverse events, that continued immune-priming is safe and optimizes anticancer response,” he told this news organization. “However, in a retrospective analysis such as ours, selection bias can have an impact.”
“Confirming this finding and better identifying patients who may benefit from resumption will be an area for future investigation,” he said.
Patients who developed immune-related adverse events were more likely to be younger than 50 years (21.8% vs. 13.9%), have normal albumin levels (86.4% vs. 74.8%), and have a more robust Eastern Cooperative Oncology Group status, which is consistent with other studies that have shown survival benefits among those who experience adverse events.
“We, and others, speculate this could be due to such groups having immune systems more ready to respond strongly to immunotherapy,” Dr. Watson explained.
After controlling for age and performance status in the multivariable analysis, however, “immune-related adverse events remained strongly associated with survival, potentially [indicating] that robust responses to immunotherapy lead to both cancer control and immune-related adverse events,” he said.
Overall, “we feel these findings will help clinicians in discussions with patients and in clinical decision-making after adverse events develop,” Dr. Watson said.
Dr. Watson has received personal fees from Apobiologix Canada.
A version of this article first appeared on Medscape.com.
Among Survival is further improved if the immunotherapy is continued after the adverse event develops, a new study confirms.
“In the largest clinical cohort to date, our data support a positive association with overall survival for patients who develop clinically significant immune-related adverse events while receiving combination immune checkpoint blockade, in keeping with other reported series,” the authors wrote.
The study was published online in JAMA Network Open.
Immune-related adverse events are common with these drugs. Severe events of grade 3 or higher occur in 59% of trial patients who receive combination ICI therapy.
The adverse events have increasingly been positively associated with survival. However, the effects for patients with metastatic melanoma, in particular, are less clear. There is little research on the effects in relation to combination therapy with ipilimumab and nivolumab, which is the standard of care for many patients with metastatic melanoma.
To investigate, Alexander S. Watson, MD, and colleagues evaluated data on 492 patients with metastatic melanoma who had been treated with one or more doses of an anti–programmed death 1 agent as single or combination immune checkpoint blockade in the multicenter Alberta Immunotherapy Database from August 2013 to May 2020.
Of these 492 patients, 198 patients (40%) developed immune-related adverse events. The mean age of the patients who developed adverse events was 61.8 years; of those who did not develop adverse events, the mean age was 65.5 years. Men made up 69.2% and 62.2%, respectively.
A total of 288 patients received pembrolizumab as their first ICI therapy, 80 received nivolumab, and 124 received combination blockade with ipilimumab-nivolumab.
Overall, with a median follow-up of 36.6 months, among patients who experienced clinically significant immune-related adverse events, defined as requiring systemic corticosteroids and/or a treatment delay, median overall survival was significantly improved, at 56.3 months, compared with 18.5 months among those who did not experience immune-related adverse events (P < .001).
In addition, among those who received combination ICI treatment, the median overall survival was 56.2 months for those who experienced adverse events versus 19.0 months for those who did not (P < .001).
There were no significant differences in overall survival between those who were and those who were not hospitalized for their immune-related adverse events (P = .53).
For patients who resumed their ICI therapy following the adverse events, overall survival was longer, compared with those who did not resume the therapy (median, 56.3 months vs. 31.5 months; P = .009).
The improvements in overall survival seen with immune-related adverse events remained consistent after adjustment in a multivariable analysis (hazard ratio for death, 0.382; P < .001).
There were no significant differences in the median number of cycles of ICIs between those with and those without the adverse events.
The risk of recurrence of immune-related adverse events following the reintroduction of therapy after initial events was a concern, so the improved overall survival among those patients is encouraging, although further investigation is needed, commented lead author Dr. Watson, from the department of oncology, University of Calgary (Alta.).
“It may be, for certain patients with immune-related adverse events, that continued immune-priming is safe and optimizes anticancer response,” he told this news organization. “However, in a retrospective analysis such as ours, selection bias can have an impact.”
“Confirming this finding and better identifying patients who may benefit from resumption will be an area for future investigation,” he said.
Patients who developed immune-related adverse events were more likely to be younger than 50 years (21.8% vs. 13.9%), have normal albumin levels (86.4% vs. 74.8%), and have a more robust Eastern Cooperative Oncology Group status, which is consistent with other studies that have shown survival benefits among those who experience adverse events.
“We, and others, speculate this could be due to such groups having immune systems more ready to respond strongly to immunotherapy,” Dr. Watson explained.
After controlling for age and performance status in the multivariable analysis, however, “immune-related adverse events remained strongly associated with survival, potentially [indicating] that robust responses to immunotherapy lead to both cancer control and immune-related adverse events,” he said.
Overall, “we feel these findings will help clinicians in discussions with patients and in clinical decision-making after adverse events develop,” Dr. Watson said.
Dr. Watson has received personal fees from Apobiologix Canada.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN
Depression: Think outside of the box for diagnosis, treatment
In the treatment of depression, clinicians are commonly dealing with a mix of comorbidities that are more complex than just depression, and as such, effective treatment options may likewise require thinking outside of the box – and beyond the definitions of the DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision).
“The DSM-5 isn’t handed to us on tablets from Mount Sinai,” said Charles B. Nemeroff, MD, PhD, professor and chair in the department of psychiatry and behavioral sciences at the Mulva Clinic for the Neurosciences at the University of Texas at Austin. He spoke at the 21st Annual Psychopharmacology Update presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.
“Our patients don’t fall into these very convenient buckets,” Dr. Nemeroff said. “The problem with depression is patients have very high rates of morbidity and comorbidity.”
The array of potential psychiatric comorbidities that are common in depression is somewhat staggering: As many as 70% of patients also have social anxiety disorder; 67% of patients have obsessive-compulsive disorder (OCD); up to 65% of patients have panic disorder; 48% of patients have posttraumatic stress disorder (PTSD); and 42% have generalized anxiety disorder, Dr. Nemeroff said.
And while the DSM-5 may have all those bases covered, in real world clinical practice, cracking the code of each patient’s unique and often more complicated psychiatric profile – and how to best manage it – can be a challenge. But Dr. Nemeroff said important clues can guide the clinician’s path.
A key starting point is making sure to gauge the severity of the patient’s core depression with one of the validated depression scales – whether it’s the self-reported Beck Depression Inventory, the clinician-rated Hamilton Rating Scale for Depression, the clinician-rated Montgomery Asberg Depression Rating Scale, or the Inventory of Depressive Symptoms, clinicians should pick one and track the score with each visit, Dr. Nemeroff advised.
“It doesn’t matter which tool you prefer – most tend to like the Beck Depression Scale, but the bottom line is that you have to get a measure of severity at every visit,” he said.
Among the most important comorbidities to identify as soon as possible is bipolar disorder, due to the potential worsening of the condition that can occur among those patients if treated with antidepressants, Dr. Nemeroff said.
“The question of whether the patient is bipolar should always be in the back of your mind,” he cautioned. “And if patients have been started on antidepressants, the clues may become evident very quickly.”
The most important indicator that the patient has bipolar disorder “is if they tell you that they were prescribed an antidepressant and it resulted in an increase in what we know to be hypomania – they may describe it as agitation or an inability to sleep,” Dr. Nemeroff said.
Of note, the effect is much more common with SNRIs [serotonin norepinephrine reuptake inhibitors] than SSRIs [selective serotonin reuptake inhibitors], he said.
“The effect is particularly notable with venlafaxine,” he said. “But SNRIs all have the propensity to switch people with depression into hypomania, but only patients who have bipolar disorder.”
“If you give a patient 150 mg of venlafaxine and they switch to developing hypomania, you now have the diagnosis of bipolar disorder, and you can treat them appropriately.”
Other important clues of bipolarity in depressed patients include:
- Family history: Most cases are genetically driven.
- Earlier age of onset (younger than age 25): “If the patient tells you they were depressed prepuberty, you should be thinking about the possibility of bipolar disorder, as it often presents as depression in childhood.”
- Psychotic features: As many as 80% of patients with psychotic depression end up being bipolar, Dr. Nemeroff said.
- Atypical depression: For example, depression with hypersomnia, or having an increased appetite instead of decreased, or a high amount of anxiety.
Remission should be the goal of treatment, and Dr. Nemeroff said that in efforts to accomplish that with the help of medications, psychiatrists may need to think “outside of the box” – or beyond the label.
“Many practitioners become slaves to the PDR [Physicians’ Desk Reference],” he said. “It is only a guide to what the clinical trials show, and not a mandate in terms of dosing.”
“There’s often strong data in the literature that supports going to a higher dose, if necessary, and I have [plenty] of patients, for instance, on 450 or 600 mg of venlafaxine who had not responded to 150 or even 300 mg.”
Treatment resistance
When patients continue to fail to respond, regardless of dosing or medication adjustments, Dr. Nemeroff suggested that clinicians should consider the potential important reasons. For instance, in addition to comorbid psychiatric conditions, practitioners should determine if there are medical conditions that they are not aware of.
“Does the patient have an underlying medical condition, such as thyroid dysfunction, early Parkinson’s disease, or even something like cancer?” he said.
There is also the inevitable question of whether the patient is indeed taking the medication. “We know that 30% of our patients do not follow their prescriptions, so of course that’s an important question to ask,” Dr. Nemeroff said.
Finally, while some pharmacogenomic tests are emerging with the suggestion of identifying which patients may or may not respond to certain drugs, Dr. Nemeroff says he’s seen little convincing evidence of their benefits.
“We have a problem in this field in that we don’t have the kinds of markers that they do in oncology, so we’re left with having to generally play trial and error,” he said.
“But when it comes to these pharmacogenomic tests, there’s just no ‘there there’,” he asserted. “From what I’ve seen so far, it’s frankly neuro-mythology.”
Dr. Nemeroff disclosed that he receives grant/research support from the National Institutes of Health and serves as a consultant for and/or on the advisory boards of multiple pharmaceutical companies.
The Psychopharmacology Update was sponsored by Medscape Live. Medscape Live and this news organization are owned by the same parent company.
In the treatment of depression, clinicians are commonly dealing with a mix of comorbidities that are more complex than just depression, and as such, effective treatment options may likewise require thinking outside of the box – and beyond the definitions of the DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision).
“The DSM-5 isn’t handed to us on tablets from Mount Sinai,” said Charles B. Nemeroff, MD, PhD, professor and chair in the department of psychiatry and behavioral sciences at the Mulva Clinic for the Neurosciences at the University of Texas at Austin. He spoke at the 21st Annual Psychopharmacology Update presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.
“Our patients don’t fall into these very convenient buckets,” Dr. Nemeroff said. “The problem with depression is patients have very high rates of morbidity and comorbidity.”
The array of potential psychiatric comorbidities that are common in depression is somewhat staggering: As many as 70% of patients also have social anxiety disorder; 67% of patients have obsessive-compulsive disorder (OCD); up to 65% of patients have panic disorder; 48% of patients have posttraumatic stress disorder (PTSD); and 42% have generalized anxiety disorder, Dr. Nemeroff said.
And while the DSM-5 may have all those bases covered, in real world clinical practice, cracking the code of each patient’s unique and often more complicated psychiatric profile – and how to best manage it – can be a challenge. But Dr. Nemeroff said important clues can guide the clinician’s path.
A key starting point is making sure to gauge the severity of the patient’s core depression with one of the validated depression scales – whether it’s the self-reported Beck Depression Inventory, the clinician-rated Hamilton Rating Scale for Depression, the clinician-rated Montgomery Asberg Depression Rating Scale, or the Inventory of Depressive Symptoms, clinicians should pick one and track the score with each visit, Dr. Nemeroff advised.
“It doesn’t matter which tool you prefer – most tend to like the Beck Depression Scale, but the bottom line is that you have to get a measure of severity at every visit,” he said.
Among the most important comorbidities to identify as soon as possible is bipolar disorder, due to the potential worsening of the condition that can occur among those patients if treated with antidepressants, Dr. Nemeroff said.
“The question of whether the patient is bipolar should always be in the back of your mind,” he cautioned. “And if patients have been started on antidepressants, the clues may become evident very quickly.”
The most important indicator that the patient has bipolar disorder “is if they tell you that they were prescribed an antidepressant and it resulted in an increase in what we know to be hypomania – they may describe it as agitation or an inability to sleep,” Dr. Nemeroff said.
Of note, the effect is much more common with SNRIs [serotonin norepinephrine reuptake inhibitors] than SSRIs [selective serotonin reuptake inhibitors], he said.
“The effect is particularly notable with venlafaxine,” he said. “But SNRIs all have the propensity to switch people with depression into hypomania, but only patients who have bipolar disorder.”
“If you give a patient 150 mg of venlafaxine and they switch to developing hypomania, you now have the diagnosis of bipolar disorder, and you can treat them appropriately.”
Other important clues of bipolarity in depressed patients include:
- Family history: Most cases are genetically driven.
- Earlier age of onset (younger than age 25): “If the patient tells you they were depressed prepuberty, you should be thinking about the possibility of bipolar disorder, as it often presents as depression in childhood.”
- Psychotic features: As many as 80% of patients with psychotic depression end up being bipolar, Dr. Nemeroff said.
- Atypical depression: For example, depression with hypersomnia, or having an increased appetite instead of decreased, or a high amount of anxiety.
Remission should be the goal of treatment, and Dr. Nemeroff said that in efforts to accomplish that with the help of medications, psychiatrists may need to think “outside of the box” – or beyond the label.
“Many practitioners become slaves to the PDR [Physicians’ Desk Reference],” he said. “It is only a guide to what the clinical trials show, and not a mandate in terms of dosing.”
“There’s often strong data in the literature that supports going to a higher dose, if necessary, and I have [plenty] of patients, for instance, on 450 or 600 mg of venlafaxine who had not responded to 150 or even 300 mg.”
Treatment resistance
When patients continue to fail to respond, regardless of dosing or medication adjustments, Dr. Nemeroff suggested that clinicians should consider the potential important reasons. For instance, in addition to comorbid psychiatric conditions, practitioners should determine if there are medical conditions that they are not aware of.
“Does the patient have an underlying medical condition, such as thyroid dysfunction, early Parkinson’s disease, or even something like cancer?” he said.
There is also the inevitable question of whether the patient is indeed taking the medication. “We know that 30% of our patients do not follow their prescriptions, so of course that’s an important question to ask,” Dr. Nemeroff said.
Finally, while some pharmacogenomic tests are emerging with the suggestion of identifying which patients may or may not respond to certain drugs, Dr. Nemeroff says he’s seen little convincing evidence of their benefits.
“We have a problem in this field in that we don’t have the kinds of markers that they do in oncology, so we’re left with having to generally play trial and error,” he said.
“But when it comes to these pharmacogenomic tests, there’s just no ‘there there’,” he asserted. “From what I’ve seen so far, it’s frankly neuro-mythology.”
Dr. Nemeroff disclosed that he receives grant/research support from the National Institutes of Health and serves as a consultant for and/or on the advisory boards of multiple pharmaceutical companies.
The Psychopharmacology Update was sponsored by Medscape Live. Medscape Live and this news organization are owned by the same parent company.
In the treatment of depression, clinicians are commonly dealing with a mix of comorbidities that are more complex than just depression, and as such, effective treatment options may likewise require thinking outside of the box – and beyond the definitions of the DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision).
“The DSM-5 isn’t handed to us on tablets from Mount Sinai,” said Charles B. Nemeroff, MD, PhD, professor and chair in the department of psychiatry and behavioral sciences at the Mulva Clinic for the Neurosciences at the University of Texas at Austin. He spoke at the 21st Annual Psychopharmacology Update presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.
“Our patients don’t fall into these very convenient buckets,” Dr. Nemeroff said. “The problem with depression is patients have very high rates of morbidity and comorbidity.”
The array of potential psychiatric comorbidities that are common in depression is somewhat staggering: As many as 70% of patients also have social anxiety disorder; 67% of patients have obsessive-compulsive disorder (OCD); up to 65% of patients have panic disorder; 48% of patients have posttraumatic stress disorder (PTSD); and 42% have generalized anxiety disorder, Dr. Nemeroff said.
And while the DSM-5 may have all those bases covered, in real world clinical practice, cracking the code of each patient’s unique and often more complicated psychiatric profile – and how to best manage it – can be a challenge. But Dr. Nemeroff said important clues can guide the clinician’s path.
A key starting point is making sure to gauge the severity of the patient’s core depression with one of the validated depression scales – whether it’s the self-reported Beck Depression Inventory, the clinician-rated Hamilton Rating Scale for Depression, the clinician-rated Montgomery Asberg Depression Rating Scale, or the Inventory of Depressive Symptoms, clinicians should pick one and track the score with each visit, Dr. Nemeroff advised.
“It doesn’t matter which tool you prefer – most tend to like the Beck Depression Scale, but the bottom line is that you have to get a measure of severity at every visit,” he said.
Among the most important comorbidities to identify as soon as possible is bipolar disorder, due to the potential worsening of the condition that can occur among those patients if treated with antidepressants, Dr. Nemeroff said.
“The question of whether the patient is bipolar should always be in the back of your mind,” he cautioned. “And if patients have been started on antidepressants, the clues may become evident very quickly.”
The most important indicator that the patient has bipolar disorder “is if they tell you that they were prescribed an antidepressant and it resulted in an increase in what we know to be hypomania – they may describe it as agitation or an inability to sleep,” Dr. Nemeroff said.
Of note, the effect is much more common with SNRIs [serotonin norepinephrine reuptake inhibitors] than SSRIs [selective serotonin reuptake inhibitors], he said.
“The effect is particularly notable with venlafaxine,” he said. “But SNRIs all have the propensity to switch people with depression into hypomania, but only patients who have bipolar disorder.”
“If you give a patient 150 mg of venlafaxine and they switch to developing hypomania, you now have the diagnosis of bipolar disorder, and you can treat them appropriately.”
Other important clues of bipolarity in depressed patients include:
- Family history: Most cases are genetically driven.
- Earlier age of onset (younger than age 25): “If the patient tells you they were depressed prepuberty, you should be thinking about the possibility of bipolar disorder, as it often presents as depression in childhood.”
- Psychotic features: As many as 80% of patients with psychotic depression end up being bipolar, Dr. Nemeroff said.
- Atypical depression: For example, depression with hypersomnia, or having an increased appetite instead of decreased, or a high amount of anxiety.
Remission should be the goal of treatment, and Dr. Nemeroff said that in efforts to accomplish that with the help of medications, psychiatrists may need to think “outside of the box” – or beyond the label.
“Many practitioners become slaves to the PDR [Physicians’ Desk Reference],” he said. “It is only a guide to what the clinical trials show, and not a mandate in terms of dosing.”
“There’s often strong data in the literature that supports going to a higher dose, if necessary, and I have [plenty] of patients, for instance, on 450 or 600 mg of venlafaxine who had not responded to 150 or even 300 mg.”
Treatment resistance
When patients continue to fail to respond, regardless of dosing or medication adjustments, Dr. Nemeroff suggested that clinicians should consider the potential important reasons. For instance, in addition to comorbid psychiatric conditions, practitioners should determine if there are medical conditions that they are not aware of.
“Does the patient have an underlying medical condition, such as thyroid dysfunction, early Parkinson’s disease, or even something like cancer?” he said.
There is also the inevitable question of whether the patient is indeed taking the medication. “We know that 30% of our patients do not follow their prescriptions, so of course that’s an important question to ask,” Dr. Nemeroff said.
Finally, while some pharmacogenomic tests are emerging with the suggestion of identifying which patients may or may not respond to certain drugs, Dr. Nemeroff says he’s seen little convincing evidence of their benefits.
“We have a problem in this field in that we don’t have the kinds of markers that they do in oncology, so we’re left with having to generally play trial and error,” he said.
“But when it comes to these pharmacogenomic tests, there’s just no ‘there there’,” he asserted. “From what I’ve seen so far, it’s frankly neuro-mythology.”
Dr. Nemeroff disclosed that he receives grant/research support from the National Institutes of Health and serves as a consultant for and/or on the advisory boards of multiple pharmaceutical companies.
The Psychopharmacology Update was sponsored by Medscape Live. Medscape Live and this news organization are owned by the same parent company.
FROM PSYCHOPHARMACOLOGY UPDATE
Guideline stresses new strategies for hypoglycemia management
The Endocrine Society has issued an updated clinical practice guideline on the prevention and management of hypoglycemia in patients with diabetes who are at high risk, addressing the wide variety of treatment advances, such as insulin pumps and continuous glucose monitoring (CGM) systems, that have appeared since the publication of the society’s last guideline on hypoglycemia, in 2009.
“CGM and insulin pumps have been much more commonly used in the last decade among people with diabetes, including children, and there are new forms of glucagon available,” said Anthony L. McCall, MD, PhD, chair of the panel that wrote the guideline.
“We had to update our guideline to match these developments in the diabetes field,” noted Dr. McCall, University of Virginia, Charlottesville, in a press statement.
The new guideline, developed by a multidisciplinary panel of clinical experts and published in the Journal of Clinical Endocrinology and Metabolism, addresses 10 key clinical questions regarding current issues relevant to hypoglycemia prevention and treatment in adult or pediatric patients with either type 1 or type 2 diabetes in the outpatient or inpatient setting.
Key guideline recommendations
The recommendations are based on factors including critical outcomes, implementation feasibility, and patient preferences.
Key guideline recommendations that are considered “strong,” based on evidence, include:
- The use of CGM rather than self-monitoring of blood glucose by fingerstick for patients with type 1 diabetes receiving multiple daily injections. The panel underscored that “comprehensive patient education on how to use and troubleshoot CGM devices and interpret these data is critically important for maximum benefit and successful outcomes.”
The use of a structured program for patient education versus unstructured advice for adult and pediatric outpatients with type 1 diabetes or type 2 diabetes receiving insulin therapy.
- Structured education on how to avoid repeated hypoglycemia is critical, and this education should be performed by experienced diabetes clinicians,” the panel asserts. “Moreover, insurance coverage for education should be available for all insulin-using patients.”
- The use of glucagon preparations that do not have to be reconstituted, as opposed to those that do (that is, available as a powder and diluent) in the treatment of outpatients with severe hypoglycemia.
Guideline recommendations that received conditional recommendations include:
- Use of real-time CGM and algorithm-driven insulin pumps in people with type 1 diabetes.
- Use of CGM for outpatients with type 2 diabetes at high risk for hypoglycemia.
- Use of long-acting and rapid-acting insulin analogs for patients at high risk for hypoglycemia.
Noting that there is “moderate-certainty” evidence for severe hypoglycemia reduction as an outcome in those using long-acting analog insulins versus human neutral protamine Hagedorn (NPH) insulin, the panel cautions that “most studies of long-acting analog insulins do not assess for significant adverse effects, including cardiovascular outcomes, and that many studies were designed to demonstrate noninferiority of analog insulin, compared with human NPH insulin.”
- Initiation of and continuation of CGM for select inpatient populations at high risk for hypoglycemia.
Hypoglycemia: One of top three preventable adverse drug reactions
The updated guidelines are especially important considering the common incidence of hypoglycemia, which the U.S. Department of Health and Human Services has determined to be one of the top 3 preventable adverse drug reactions, the panel says.
They note that between January 2007 and December 2011, emergency department visits for therapy-associated hypoglycemia among Medicare beneficiaries resulted in more than $600 million in spending.
Meanwhile, many people with type 1 or 2 diabetes may not experience or recognize the symptoms of hypoglycemia, which, in severe cases, can lead to unconsciousness or seizures, in addition to affecting quality of life, social life, work productivity, and ability to drive safely.
The key to accurate diagnosis of those patients is assessment of the three levels of hypoglycemia, described in a 2018 consensus statement:
- Level 1: Glucose less than 70 mg/dL (3.9 mmol/L) and greater than or equal to 54 mg/dL (3.0 mmol/L). This level of hypoglycemia should alert patients that they may need to ingest carbohydrate to prevent progressive hypoglycemia.
- Level 2: Glucose less than 54 mg/dL (3.0 mmol/L). This level of hypoglycemia is associated with increased risk for cognitive dysfunction and mortality.
- Level 3: A severe event characterized by altered mental and/or physical status requiring assistance. This level of hypoglycemia is life-threatening and requires emergent treatment, typically with glucagon.
Ultimately, “new technology and medications will help reduce hypoglycemia, and [clinicians] can better treat patients now with new, easier glucagons,” Dr. McCall told this news organization.
“People with diabetes, their caregivers, and diabetes specialists will all benefit from our guideline with a better understanding of best practices and interventions,” the panel notes.
Disparities still exist in access to insulin pumps
Separately, new research shows that while use of insulin pumps to manage type 1 diabetes has grown over 20 years, there has been no improvement in racial, ethnic, and socioeconomic disparities in their use in the United States. The findings are reported in Diabetes Technology & Therapeutics.
Using data from the SEARCH for Diabetes Youth Study across four time periods between 2001 and 2019, the researchers show that by the end of the period studied, insulin pump use was 67% among non-Hispanic White people, 41% among Hispanic people, 29% among Black people, and 46% among other racial and ethnic groups.
In addition, 70% of people with bachelor’s degrees or higher used the pumps, compared with 56% among those with some college, 40% among holders of high school degrees, and 18% among those with no high school education. By income level, 74% of those with household incomes of $75,000 or more, 66% with $50,000-$74,999, 51% with $25,000-$49,999, and 41% with less than $25,000 used the pumps.
“Diabetes technology has numerous benefits for patients with type 1 diabetes, but the problem is that there is a huge divide in who actually has access to these technologies,” said study lead Estelle Everett, MD, assistant professor of medicine in the division of endocrinology, diabetes & metabolism at the University of California, Los Angeles.
A version of this article first appeared on Medscape.com.
The Endocrine Society has issued an updated clinical practice guideline on the prevention and management of hypoglycemia in patients with diabetes who are at high risk, addressing the wide variety of treatment advances, such as insulin pumps and continuous glucose monitoring (CGM) systems, that have appeared since the publication of the society’s last guideline on hypoglycemia, in 2009.
“CGM and insulin pumps have been much more commonly used in the last decade among people with diabetes, including children, and there are new forms of glucagon available,” said Anthony L. McCall, MD, PhD, chair of the panel that wrote the guideline.
“We had to update our guideline to match these developments in the diabetes field,” noted Dr. McCall, University of Virginia, Charlottesville, in a press statement.
The new guideline, developed by a multidisciplinary panel of clinical experts and published in the Journal of Clinical Endocrinology and Metabolism, addresses 10 key clinical questions regarding current issues relevant to hypoglycemia prevention and treatment in adult or pediatric patients with either type 1 or type 2 diabetes in the outpatient or inpatient setting.
Key guideline recommendations
The recommendations are based on factors including critical outcomes, implementation feasibility, and patient preferences.
Key guideline recommendations that are considered “strong,” based on evidence, include:
- The use of CGM rather than self-monitoring of blood glucose by fingerstick for patients with type 1 diabetes receiving multiple daily injections. The panel underscored that “comprehensive patient education on how to use and troubleshoot CGM devices and interpret these data is critically important for maximum benefit and successful outcomes.”
The use of a structured program for patient education versus unstructured advice for adult and pediatric outpatients with type 1 diabetes or type 2 diabetes receiving insulin therapy.
- Structured education on how to avoid repeated hypoglycemia is critical, and this education should be performed by experienced diabetes clinicians,” the panel asserts. “Moreover, insurance coverage for education should be available for all insulin-using patients.”
- The use of glucagon preparations that do not have to be reconstituted, as opposed to those that do (that is, available as a powder and diluent) in the treatment of outpatients with severe hypoglycemia.
Guideline recommendations that received conditional recommendations include:
- Use of real-time CGM and algorithm-driven insulin pumps in people with type 1 diabetes.
- Use of CGM for outpatients with type 2 diabetes at high risk for hypoglycemia.
- Use of long-acting and rapid-acting insulin analogs for patients at high risk for hypoglycemia.
Noting that there is “moderate-certainty” evidence for severe hypoglycemia reduction as an outcome in those using long-acting analog insulins versus human neutral protamine Hagedorn (NPH) insulin, the panel cautions that “most studies of long-acting analog insulins do not assess for significant adverse effects, including cardiovascular outcomes, and that many studies were designed to demonstrate noninferiority of analog insulin, compared with human NPH insulin.”
- Initiation of and continuation of CGM for select inpatient populations at high risk for hypoglycemia.
Hypoglycemia: One of top three preventable adverse drug reactions
The updated guidelines are especially important considering the common incidence of hypoglycemia, which the U.S. Department of Health and Human Services has determined to be one of the top 3 preventable adverse drug reactions, the panel says.
They note that between January 2007 and December 2011, emergency department visits for therapy-associated hypoglycemia among Medicare beneficiaries resulted in more than $600 million in spending.
Meanwhile, many people with type 1 or 2 diabetes may not experience or recognize the symptoms of hypoglycemia, which, in severe cases, can lead to unconsciousness or seizures, in addition to affecting quality of life, social life, work productivity, and ability to drive safely.
The key to accurate diagnosis of those patients is assessment of the three levels of hypoglycemia, described in a 2018 consensus statement:
- Level 1: Glucose less than 70 mg/dL (3.9 mmol/L) and greater than or equal to 54 mg/dL (3.0 mmol/L). This level of hypoglycemia should alert patients that they may need to ingest carbohydrate to prevent progressive hypoglycemia.
- Level 2: Glucose less than 54 mg/dL (3.0 mmol/L). This level of hypoglycemia is associated with increased risk for cognitive dysfunction and mortality.
- Level 3: A severe event characterized by altered mental and/or physical status requiring assistance. This level of hypoglycemia is life-threatening and requires emergent treatment, typically with glucagon.
Ultimately, “new technology and medications will help reduce hypoglycemia, and [clinicians] can better treat patients now with new, easier glucagons,” Dr. McCall told this news organization.
“People with diabetes, their caregivers, and diabetes specialists will all benefit from our guideline with a better understanding of best practices and interventions,” the panel notes.
Disparities still exist in access to insulin pumps
Separately, new research shows that while use of insulin pumps to manage type 1 diabetes has grown over 20 years, there has been no improvement in racial, ethnic, and socioeconomic disparities in their use in the United States. The findings are reported in Diabetes Technology & Therapeutics.
Using data from the SEARCH for Diabetes Youth Study across four time periods between 2001 and 2019, the researchers show that by the end of the period studied, insulin pump use was 67% among non-Hispanic White people, 41% among Hispanic people, 29% among Black people, and 46% among other racial and ethnic groups.
In addition, 70% of people with bachelor’s degrees or higher used the pumps, compared with 56% among those with some college, 40% among holders of high school degrees, and 18% among those with no high school education. By income level, 74% of those with household incomes of $75,000 or more, 66% with $50,000-$74,999, 51% with $25,000-$49,999, and 41% with less than $25,000 used the pumps.
“Diabetes technology has numerous benefits for patients with type 1 diabetes, but the problem is that there is a huge divide in who actually has access to these technologies,” said study lead Estelle Everett, MD, assistant professor of medicine in the division of endocrinology, diabetes & metabolism at the University of California, Los Angeles.
A version of this article first appeared on Medscape.com.
The Endocrine Society has issued an updated clinical practice guideline on the prevention and management of hypoglycemia in patients with diabetes who are at high risk, addressing the wide variety of treatment advances, such as insulin pumps and continuous glucose monitoring (CGM) systems, that have appeared since the publication of the society’s last guideline on hypoglycemia, in 2009.
“CGM and insulin pumps have been much more commonly used in the last decade among people with diabetes, including children, and there are new forms of glucagon available,” said Anthony L. McCall, MD, PhD, chair of the panel that wrote the guideline.
“We had to update our guideline to match these developments in the diabetes field,” noted Dr. McCall, University of Virginia, Charlottesville, in a press statement.
The new guideline, developed by a multidisciplinary panel of clinical experts and published in the Journal of Clinical Endocrinology and Metabolism, addresses 10 key clinical questions regarding current issues relevant to hypoglycemia prevention and treatment in adult or pediatric patients with either type 1 or type 2 diabetes in the outpatient or inpatient setting.
Key guideline recommendations
The recommendations are based on factors including critical outcomes, implementation feasibility, and patient preferences.
Key guideline recommendations that are considered “strong,” based on evidence, include:
- The use of CGM rather than self-monitoring of blood glucose by fingerstick for patients with type 1 diabetes receiving multiple daily injections. The panel underscored that “comprehensive patient education on how to use and troubleshoot CGM devices and interpret these data is critically important for maximum benefit and successful outcomes.”
The use of a structured program for patient education versus unstructured advice for adult and pediatric outpatients with type 1 diabetes or type 2 diabetes receiving insulin therapy.
- Structured education on how to avoid repeated hypoglycemia is critical, and this education should be performed by experienced diabetes clinicians,” the panel asserts. “Moreover, insurance coverage for education should be available for all insulin-using patients.”
- The use of glucagon preparations that do not have to be reconstituted, as opposed to those that do (that is, available as a powder and diluent) in the treatment of outpatients with severe hypoglycemia.
Guideline recommendations that received conditional recommendations include:
- Use of real-time CGM and algorithm-driven insulin pumps in people with type 1 diabetes.
- Use of CGM for outpatients with type 2 diabetes at high risk for hypoglycemia.
- Use of long-acting and rapid-acting insulin analogs for patients at high risk for hypoglycemia.
Noting that there is “moderate-certainty” evidence for severe hypoglycemia reduction as an outcome in those using long-acting analog insulins versus human neutral protamine Hagedorn (NPH) insulin, the panel cautions that “most studies of long-acting analog insulins do not assess for significant adverse effects, including cardiovascular outcomes, and that many studies were designed to demonstrate noninferiority of analog insulin, compared with human NPH insulin.”
- Initiation of and continuation of CGM for select inpatient populations at high risk for hypoglycemia.
Hypoglycemia: One of top three preventable adverse drug reactions
The updated guidelines are especially important considering the common incidence of hypoglycemia, which the U.S. Department of Health and Human Services has determined to be one of the top 3 preventable adverse drug reactions, the panel says.
They note that between January 2007 and December 2011, emergency department visits for therapy-associated hypoglycemia among Medicare beneficiaries resulted in more than $600 million in spending.
Meanwhile, many people with type 1 or 2 diabetes may not experience or recognize the symptoms of hypoglycemia, which, in severe cases, can lead to unconsciousness or seizures, in addition to affecting quality of life, social life, work productivity, and ability to drive safely.
The key to accurate diagnosis of those patients is assessment of the three levels of hypoglycemia, described in a 2018 consensus statement:
- Level 1: Glucose less than 70 mg/dL (3.9 mmol/L) and greater than or equal to 54 mg/dL (3.0 mmol/L). This level of hypoglycemia should alert patients that they may need to ingest carbohydrate to prevent progressive hypoglycemia.
- Level 2: Glucose less than 54 mg/dL (3.0 mmol/L). This level of hypoglycemia is associated with increased risk for cognitive dysfunction and mortality.
- Level 3: A severe event characterized by altered mental and/or physical status requiring assistance. This level of hypoglycemia is life-threatening and requires emergent treatment, typically with glucagon.
Ultimately, “new technology and medications will help reduce hypoglycemia, and [clinicians] can better treat patients now with new, easier glucagons,” Dr. McCall told this news organization.
“People with diabetes, their caregivers, and diabetes specialists will all benefit from our guideline with a better understanding of best practices and interventions,” the panel notes.
Disparities still exist in access to insulin pumps
Separately, new research shows that while use of insulin pumps to manage type 1 diabetes has grown over 20 years, there has been no improvement in racial, ethnic, and socioeconomic disparities in their use in the United States. The findings are reported in Diabetes Technology & Therapeutics.
Using data from the SEARCH for Diabetes Youth Study across four time periods between 2001 and 2019, the researchers show that by the end of the period studied, insulin pump use was 67% among non-Hispanic White people, 41% among Hispanic people, 29% among Black people, and 46% among other racial and ethnic groups.
In addition, 70% of people with bachelor’s degrees or higher used the pumps, compared with 56% among those with some college, 40% among holders of high school degrees, and 18% among those with no high school education. By income level, 74% of those with household incomes of $75,000 or more, 66% with $50,000-$74,999, 51% with $25,000-$49,999, and 41% with less than $25,000 used the pumps.
“Diabetes technology has numerous benefits for patients with type 1 diabetes, but the problem is that there is a huge divide in who actually has access to these technologies,” said study lead Estelle Everett, MD, assistant professor of medicine in the division of endocrinology, diabetes & metabolism at the University of California, Los Angeles.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM
‘Game changer’: Thyroid cancer recurrence no higher with lobectomy
Patients with intermediate-risk papillary thyroid cancer and lymph node metastasis show no significant increase in tumor recurrence when undergoing lobectomy compared with a total thyroidectomy, new research shows.
“Results of this cohort study suggest that patients with ipsilateral clinical lateral neck metastasis (cN1b) papillary thyroid cancer who underwent lobectomy exhibited recurrence-free survival rates similar to those who underwent total thyroidectomy after controlling for major prognostic factors,” the authors conclude in the study published online in JAMA Surgery.
“These findings suggest that cN1b alone should not be an absolute indication for total thyroidectomy,” they note.
The study, involving the largest cohort to date to compare patients with intermediate-risk papillary thyroid cancer treated with lobectomy versus total thyroidectomy, “challenged the current guidelines and pushed the boundary of limited surgical treatment even further,” say Michelle B. Mulder, MD, and Quan-Yang Duh, MD, of the department of surgery, University of California, San Francisco, in an accompanying editorial.
“It can be a game changer if confirmed by future prospective and multicenter studies,” they add.
Guidelines still recommend total thyroidectomy with subsequent RAI
While lower-intensity treatment options, with a lower risk of complications, have gained favor in the treatment of low-risk papillary thyroid cancer, guidelines still recommend the consideration of total thyroidectomy and subsequent radioactive iodine ablation (RAI) for intermediate-risk cancers because of the higher chance of recurrence, particularly among those with clinically positive nodes.
However, data on the superiority of a total thyroidectomy, with or without RAI, versus lobectomy is inconsistent, prompting first author Siyuan Xu, MD, of the department of head and neck surgical oncology, National Cancer Center, Beijing, and colleagues to compare the risk of recurrence with the two approaches.
For the study, patients with intermediate-risk papillary thyroid cancer treated at the Chinese Academy of Medical Sciences Cancer Hospital in Beijing between January 2000 and December 2017, who had a lobectomy or total thyroidectomy, were paired 1:1 in a propensity score matching analysis.
Other than treatment type, the 265 pairs of patients were matched based on all other potential prognostic factors, including age, sex, primary tumor size, minor extrathyroidal extension, multifocality, number of lymph node metastases, and lymph node ratio.
Participants were a mean age of 37 years and 66% were female.
With a median follow-up of 60 months in the lobectomy group and 58 months in the total thyroidectomy group, structural recurrences occurred in 7.9% (21) and 6.4% (17) of patients, respectively, which was not significantly different.
The primary endpoint, 5-year rate of recurrence-free survival, was also not significantly different between the lobectomy (92.3%) and total thyroidectomy groups (93.7%) (adjusted hazard ratio, 1.10; P = .77).
In a further stratified analysis of patients treated with total thyroidectomy along with RAI (n = 75), the lack of a significant difference in recurrence-free survival versus lobectomy remained (aHR, 0.59; P = .46).
The results were similar in unadjusted as well as adjusted analyses, and a power analysis indicated that the study had a 90% power to detect a more than 4.9% difference in recurrence-free survival.
“Given the lower complication rate of lobectomy, a maximal 4.9% recurrence-free survival difference is acceptable, which enhances the reliability of the study results,” the authors say.
They conclude that “our findings call into question whether cN1b alone [ipsilateral clinical lateral neck metastasis papillary thyroid cancer] should be an absolute determinant for deciding the optimal extent of thyroid surgery for papillary thyroid cancer.”
With total thyroidectomy, RAI can be given
An important argument in favor of total thyroidectomy is that with the complete resection of thyroid tissue, RAI ablation can then be used for postoperative detection of residual or metastatic disease, as well as for treatment, the authors note.
Indeed, a study using the Surveillance, Epidemiology, and End Results (SEER) database showed RAI ablation is associated with a 29% reduction in the risk of death in patients with intermediate-risk papillary thyroid cancer, with a hazard risk of 0.71.
However, conflicting data from Memorial Sloan-Kettering Cancer Center, New York, suggests no significant benefit with total thyroidectomy and RAI ablation.
The current study’s analysis of patients treated with RAI, though limited in size, supports the latter study’s findings, the authors note.
“When we performed further stratified analyses in patients treated with total thyroidectomy plus RAI ablation and their counterparts, no significant difference was found, which conformed with [the] result from the whole cohort.”
“Certainly, the stratified comparison did not have enough power to examine the effect of RAI ablation on tumor recurrence subject to the limitation of sample size and case selection [and] further study is needed on this topic,” they write.
Some limitations warrant cautious interpretation
In their editorial, Dr. Mulder and Dr. Duh note that while some previous studies have shown similar outcomes relating to tumor size, thyroid hormone suppression therapy, and multifocality, “few have addressed lateral neck involvement.”
They suggest cautious interpretation, however, due to limitations, acknowledged by the authors, including the single-center nature of the study.
“Appropriate propensity matching may mitigate selection bias but cannot eliminate it entirely and their findings may not be replicated in other institutions by other surgeons,” they note.
Other limitations include that changes in clinical practice and patient selection were likely over the course of the study because of significant changes in American Thyroid Association (ATA) guidelines between 2009 and 2017, and characteristics including molecular genetic testing, which could have influenced final results, were not taken into consideration.
Furthermore, for patients with intermediate-risk cancer, modifications in postoperative follow-up are necessary following lobectomy versus total thyroidectomy; “the role of radioiodine is limited and the levels of thyroglobulin more complicated to interpret,” they note.
The study and editorial authors had no disclosures to report.
A version of this article first appeared on Medscape.com.
Patients with intermediate-risk papillary thyroid cancer and lymph node metastasis show no significant increase in tumor recurrence when undergoing lobectomy compared with a total thyroidectomy, new research shows.
“Results of this cohort study suggest that patients with ipsilateral clinical lateral neck metastasis (cN1b) papillary thyroid cancer who underwent lobectomy exhibited recurrence-free survival rates similar to those who underwent total thyroidectomy after controlling for major prognostic factors,” the authors conclude in the study published online in JAMA Surgery.
“These findings suggest that cN1b alone should not be an absolute indication for total thyroidectomy,” they note.
The study, involving the largest cohort to date to compare patients with intermediate-risk papillary thyroid cancer treated with lobectomy versus total thyroidectomy, “challenged the current guidelines and pushed the boundary of limited surgical treatment even further,” say Michelle B. Mulder, MD, and Quan-Yang Duh, MD, of the department of surgery, University of California, San Francisco, in an accompanying editorial.
“It can be a game changer if confirmed by future prospective and multicenter studies,” they add.
Guidelines still recommend total thyroidectomy with subsequent RAI
While lower-intensity treatment options, with a lower risk of complications, have gained favor in the treatment of low-risk papillary thyroid cancer, guidelines still recommend the consideration of total thyroidectomy and subsequent radioactive iodine ablation (RAI) for intermediate-risk cancers because of the higher chance of recurrence, particularly among those with clinically positive nodes.
However, data on the superiority of a total thyroidectomy, with or without RAI, versus lobectomy is inconsistent, prompting first author Siyuan Xu, MD, of the department of head and neck surgical oncology, National Cancer Center, Beijing, and colleagues to compare the risk of recurrence with the two approaches.
For the study, patients with intermediate-risk papillary thyroid cancer treated at the Chinese Academy of Medical Sciences Cancer Hospital in Beijing between January 2000 and December 2017, who had a lobectomy or total thyroidectomy, were paired 1:1 in a propensity score matching analysis.
Other than treatment type, the 265 pairs of patients were matched based on all other potential prognostic factors, including age, sex, primary tumor size, minor extrathyroidal extension, multifocality, number of lymph node metastases, and lymph node ratio.
Participants were a mean age of 37 years and 66% were female.
With a median follow-up of 60 months in the lobectomy group and 58 months in the total thyroidectomy group, structural recurrences occurred in 7.9% (21) and 6.4% (17) of patients, respectively, which was not significantly different.
The primary endpoint, 5-year rate of recurrence-free survival, was also not significantly different between the lobectomy (92.3%) and total thyroidectomy groups (93.7%) (adjusted hazard ratio, 1.10; P = .77).
In a further stratified analysis of patients treated with total thyroidectomy along with RAI (n = 75), the lack of a significant difference in recurrence-free survival versus lobectomy remained (aHR, 0.59; P = .46).
The results were similar in unadjusted as well as adjusted analyses, and a power analysis indicated that the study had a 90% power to detect a more than 4.9% difference in recurrence-free survival.
“Given the lower complication rate of lobectomy, a maximal 4.9% recurrence-free survival difference is acceptable, which enhances the reliability of the study results,” the authors say.
They conclude that “our findings call into question whether cN1b alone [ipsilateral clinical lateral neck metastasis papillary thyroid cancer] should be an absolute determinant for deciding the optimal extent of thyroid surgery for papillary thyroid cancer.”
With total thyroidectomy, RAI can be given
An important argument in favor of total thyroidectomy is that with the complete resection of thyroid tissue, RAI ablation can then be used for postoperative detection of residual or metastatic disease, as well as for treatment, the authors note.
Indeed, a study using the Surveillance, Epidemiology, and End Results (SEER) database showed RAI ablation is associated with a 29% reduction in the risk of death in patients with intermediate-risk papillary thyroid cancer, with a hazard risk of 0.71.
However, conflicting data from Memorial Sloan-Kettering Cancer Center, New York, suggests no significant benefit with total thyroidectomy and RAI ablation.
The current study’s analysis of patients treated with RAI, though limited in size, supports the latter study’s findings, the authors note.
“When we performed further stratified analyses in patients treated with total thyroidectomy plus RAI ablation and their counterparts, no significant difference was found, which conformed with [the] result from the whole cohort.”
“Certainly, the stratified comparison did not have enough power to examine the effect of RAI ablation on tumor recurrence subject to the limitation of sample size and case selection [and] further study is needed on this topic,” they write.
Some limitations warrant cautious interpretation
In their editorial, Dr. Mulder and Dr. Duh note that while some previous studies have shown similar outcomes relating to tumor size, thyroid hormone suppression therapy, and multifocality, “few have addressed lateral neck involvement.”
They suggest cautious interpretation, however, due to limitations, acknowledged by the authors, including the single-center nature of the study.
“Appropriate propensity matching may mitigate selection bias but cannot eliminate it entirely and their findings may not be replicated in other institutions by other surgeons,” they note.
Other limitations include that changes in clinical practice and patient selection were likely over the course of the study because of significant changes in American Thyroid Association (ATA) guidelines between 2009 and 2017, and characteristics including molecular genetic testing, which could have influenced final results, were not taken into consideration.
Furthermore, for patients with intermediate-risk cancer, modifications in postoperative follow-up are necessary following lobectomy versus total thyroidectomy; “the role of radioiodine is limited and the levels of thyroglobulin more complicated to interpret,” they note.
The study and editorial authors had no disclosures to report.
A version of this article first appeared on Medscape.com.
Patients with intermediate-risk papillary thyroid cancer and lymph node metastasis show no significant increase in tumor recurrence when undergoing lobectomy compared with a total thyroidectomy, new research shows.
“Results of this cohort study suggest that patients with ipsilateral clinical lateral neck metastasis (cN1b) papillary thyroid cancer who underwent lobectomy exhibited recurrence-free survival rates similar to those who underwent total thyroidectomy after controlling for major prognostic factors,” the authors conclude in the study published online in JAMA Surgery.
“These findings suggest that cN1b alone should not be an absolute indication for total thyroidectomy,” they note.
The study, involving the largest cohort to date to compare patients with intermediate-risk papillary thyroid cancer treated with lobectomy versus total thyroidectomy, “challenged the current guidelines and pushed the boundary of limited surgical treatment even further,” say Michelle B. Mulder, MD, and Quan-Yang Duh, MD, of the department of surgery, University of California, San Francisco, in an accompanying editorial.
“It can be a game changer if confirmed by future prospective and multicenter studies,” they add.
Guidelines still recommend total thyroidectomy with subsequent RAI
While lower-intensity treatment options, with a lower risk of complications, have gained favor in the treatment of low-risk papillary thyroid cancer, guidelines still recommend the consideration of total thyroidectomy and subsequent radioactive iodine ablation (RAI) for intermediate-risk cancers because of the higher chance of recurrence, particularly among those with clinically positive nodes.
However, data on the superiority of a total thyroidectomy, with or without RAI, versus lobectomy is inconsistent, prompting first author Siyuan Xu, MD, of the department of head and neck surgical oncology, National Cancer Center, Beijing, and colleagues to compare the risk of recurrence with the two approaches.
For the study, patients with intermediate-risk papillary thyroid cancer treated at the Chinese Academy of Medical Sciences Cancer Hospital in Beijing between January 2000 and December 2017, who had a lobectomy or total thyroidectomy, were paired 1:1 in a propensity score matching analysis.
Other than treatment type, the 265 pairs of patients were matched based on all other potential prognostic factors, including age, sex, primary tumor size, minor extrathyroidal extension, multifocality, number of lymph node metastases, and lymph node ratio.
Participants were a mean age of 37 years and 66% were female.
With a median follow-up of 60 months in the lobectomy group and 58 months in the total thyroidectomy group, structural recurrences occurred in 7.9% (21) and 6.4% (17) of patients, respectively, which was not significantly different.
The primary endpoint, 5-year rate of recurrence-free survival, was also not significantly different between the lobectomy (92.3%) and total thyroidectomy groups (93.7%) (adjusted hazard ratio, 1.10; P = .77).
In a further stratified analysis of patients treated with total thyroidectomy along with RAI (n = 75), the lack of a significant difference in recurrence-free survival versus lobectomy remained (aHR, 0.59; P = .46).
The results were similar in unadjusted as well as adjusted analyses, and a power analysis indicated that the study had a 90% power to detect a more than 4.9% difference in recurrence-free survival.
“Given the lower complication rate of lobectomy, a maximal 4.9% recurrence-free survival difference is acceptable, which enhances the reliability of the study results,” the authors say.
They conclude that “our findings call into question whether cN1b alone [ipsilateral clinical lateral neck metastasis papillary thyroid cancer] should be an absolute determinant for deciding the optimal extent of thyroid surgery for papillary thyroid cancer.”
With total thyroidectomy, RAI can be given
An important argument in favor of total thyroidectomy is that with the complete resection of thyroid tissue, RAI ablation can then be used for postoperative detection of residual or metastatic disease, as well as for treatment, the authors note.
Indeed, a study using the Surveillance, Epidemiology, and End Results (SEER) database showed RAI ablation is associated with a 29% reduction in the risk of death in patients with intermediate-risk papillary thyroid cancer, with a hazard risk of 0.71.
However, conflicting data from Memorial Sloan-Kettering Cancer Center, New York, suggests no significant benefit with total thyroidectomy and RAI ablation.
The current study’s analysis of patients treated with RAI, though limited in size, supports the latter study’s findings, the authors note.
“When we performed further stratified analyses in patients treated with total thyroidectomy plus RAI ablation and their counterparts, no significant difference was found, which conformed with [the] result from the whole cohort.”
“Certainly, the stratified comparison did not have enough power to examine the effect of RAI ablation on tumor recurrence subject to the limitation of sample size and case selection [and] further study is needed on this topic,” they write.
Some limitations warrant cautious interpretation
In their editorial, Dr. Mulder and Dr. Duh note that while some previous studies have shown similar outcomes relating to tumor size, thyroid hormone suppression therapy, and multifocality, “few have addressed lateral neck involvement.”
They suggest cautious interpretation, however, due to limitations, acknowledged by the authors, including the single-center nature of the study.
“Appropriate propensity matching may mitigate selection bias but cannot eliminate it entirely and their findings may not be replicated in other institutions by other surgeons,” they note.
Other limitations include that changes in clinical practice and patient selection were likely over the course of the study because of significant changes in American Thyroid Association (ATA) guidelines between 2009 and 2017, and characteristics including molecular genetic testing, which could have influenced final results, were not taken into consideration.
Furthermore, for patients with intermediate-risk cancer, modifications in postoperative follow-up are necessary following lobectomy versus total thyroidectomy; “the role of radioiodine is limited and the levels of thyroglobulin more complicated to interpret,” they note.
The study and editorial authors had no disclosures to report.
A version of this article first appeared on Medscape.com.
FROM JAMA SURGERY