Mary Ann Moon

Adding the antiangiogenic agent bevacizumab to standard first-line chemotherapy improves progression-free survival in extensive small-cell lung cancer, according to a report published online Jan. 30.

In what they described as the first prospective randomized, controlled phase III trial comparing these two approaches, researchers studied 204 adults who had extensive SCLC, including brain and bone metastases, at 29 medical centers in Italy. These participants (mean age, 64 years) were randomly assigned to receive a combination of standard cisplatin, etoposide, and bevacizumab every 3 weeks or cisplatin and etoposide chemotherapy every 3 weeks. Patients who developed cisplatin contraindications or toxicity related to the drug could substitute carboplatin. In the experimental arm of the study, patients could opt to continue bevacizumab alone as maintenance therapy for a maximum of 18 cycles. Forty-one patients (42%) did so, said Marcello Tiseo, MD, PhD, of Azienda Ospedaliero Universitaria, Parma, Italy, and his associates.

After a median follow-up of 35 months, the median progression-free survival was 5.7 months with standard therapy and 6.7 months with add-on bevacizumab (hazard ratio, 0.72; 95% confidence interval, 0.54 to 0.97; P = .030). However, adding bevacizumab did not significantly improve overall survival, which was the primary endpoint of the trial. A subgroup analysis showed that bevacizumab significantly extended overall survival among men (HR, 0.55) but not among women (HR, 1.55), an association that has been reported in previous studies, Dr. Tiseo and his associates said (J Clin Oncol. 2017 Jan 30. doi:10.1200/JCO.2016.69.4844).

These findings, together with those of other investigators assessing the same class of agents, justify “further studies with novel and better antiangiogenic agents in extensive SCLC, particularly in the maintenance setting,” they added.

This trial was supported by the Agenzia Italiana del Farmaco. Dr. Tiseo reported serving as a consultant for AstraZeneca, Eli Lilly, Boehringer Ingelheim, Novartis, Bristol-Myers Squibb, Pierre Fabre, and Otsuka; his associates reported ties to numerous industry sources.

Adding the antiangiogenic agent bevacizumab to standard first-line chemotherapy improves progression-free survival in extensive small-cell lung cancer, according to a report published online Jan. 30.

In what they described as the first prospective randomized, controlled phase III trial comparing these two approaches, researchers studied 204 adults who had extensive SCLC, including brain and bone metastases, at 29 medical centers in Italy. These participants (mean age, 64 years) were randomly assigned to receive a combination of standard cisplatin, etoposide, and bevacizumab every 3 weeks or cisplatin and etoposide chemotherapy every 3 weeks. Patients who developed cisplatin contraindications or toxicity related to the drug could substitute carboplatin. In the experimental arm of the study, patients could opt to continue bevacizumab alone as maintenance therapy for a maximum of 18 cycles. Forty-one patients (42%) did so, said Marcello Tiseo, MD, PhD, of Azienda Ospedaliero Universitaria, Parma, Italy, and his associates.

After a median follow-up of 35 months, the median progression-free survival was 5.7 months with standard therapy and 6.7 months with add-on bevacizumab (hazard ratio, 0.72; 95% confidence interval, 0.54 to 0.97; P = .030). However, adding bevacizumab did not significantly improve overall survival, which was the primary endpoint of the trial. A subgroup analysis showed that bevacizumab significantly extended overall survival among men (HR, 0.55) but not among women (HR, 1.55), an association that has been reported in previous studies, Dr. Tiseo and his associates said (J Clin Oncol. 2017 Jan 30. doi:10.1200/JCO.2016.69.4844).

These findings, together with those of other investigators assessing the same class of agents, justify “further studies with novel and better antiangiogenic agents in extensive SCLC, particularly in the maintenance setting,” they added.

This trial was supported by the Agenzia Italiana del Farmaco. Dr. Tiseo reported serving as a consultant for AstraZeneca, Eli Lilly, Boehringer Ingelheim, Novartis, Bristol-Myers Squibb, Pierre Fabre, and Otsuka; his associates reported ties to numerous industry sources.

Adding the antiangiogenic agent bevacizumab to standard first-line chemotherapy improves progression-free survival in extensive small-cell lung cancer, according to a report published online Jan. 30.

In what they described as the first prospective randomized, controlled phase III trial comparing these two approaches, researchers studied 204 adults who had extensive SCLC, including brain and bone metastases, at 29 medical centers in Italy. These participants (mean age, 64 years) were randomly assigned to receive a combination of standard cisplatin, etoposide, and bevacizumab every 3 weeks or cisplatin and etoposide chemotherapy every 3 weeks. Patients who developed cisplatin contraindications or toxicity related to the drug could substitute carboplatin. In the experimental arm of the study, patients could opt to continue bevacizumab alone as maintenance therapy for a maximum of 18 cycles. Forty-one patients (42%) did so, said Marcello Tiseo, MD, PhD, of Azienda Ospedaliero Universitaria, Parma, Italy, and his associates.

After a median follow-up of 35 months, the median progression-free survival was 5.7 months with standard therapy and 6.7 months with add-on bevacizumab (hazard ratio, 0.72; 95% confidence interval, 0.54 to 0.97; P = .030). However, adding bevacizumab did not significantly improve overall survival, which was the primary endpoint of the trial. A subgroup analysis showed that bevacizumab significantly extended overall survival among men (HR, 0.55) but not among women (HR, 1.55), an association that has been reported in previous studies, Dr. Tiseo and his associates said (J Clin Oncol. 2017 Jan 30. doi:10.1200/JCO.2016.69.4844).

These findings, together with those of other investigators assessing the same class of agents, justify “further studies with novel and better antiangiogenic agents in extensive SCLC, particularly in the maintenance setting,” they added.

This trial was supported by the Agenzia Italiana del Farmaco. Dr. Tiseo reported serving as a consultant for AstraZeneca, Eli Lilly, Boehringer Ingelheim, Novartis, Bristol-Myers Squibb, Pierre Fabre, and Otsuka; his associates reported ties to numerous industry sources.

Intermittent breaks from sunitinib therapy are feasible and don’t appear to compromise the agent’s clinical efficacy against metastatic renal cell carcinoma, according to investigators.

One of the greatest challenges in treating this cancer is balancing treatment-related toxicity against efficacy “in a setting ... in which patients are largely incurable and thus subjected to chronic therapy,” said Moshe C. Ornstein, MD, and his associates at the Cleveland Clinic Taussig Cancer Institute.

They performed a single-center phase II study that they described as the first prospective trial to assess treatment interruptions whenever tumor burden was reduced by 10% or more, followed by resumption of treatment if tumors then progressed 10% or more. This approach “may result in reduced toxicities, improved quality of life, cost savings, and potentially improved clinical outcomes.”

The study involved 37 adults (median age, 63 years) who were given 50 mg sunitinib once daily for the first 28 days of a 42-day cycle, with dose adjustments allowed to minimize toxicities. Twenty patients (54%) who showed a 10% or greater reduction in tumor burden after four cycles suspended treatment until scans showed a 10% or greater progression, at which point treatment was resumed. These 20 patients were able to take up to 11 treatment breaks (median, 3 breaks per patient), with each break having a median duration of more than 8 weeks (range, 4.7-192.1 weeks).

Seven patients were able to have extended drug holidays lasting 3-43 months, and three have never had to resume sunitinib therapy after their first break. “The overall sum of all the breaks was 1,296.6 weeks, which corresponds to 216 6-week cycles with a median of 9 saved cycles per patient,” Dr. Ornstein and his associates said (J Clin Oncol. 2017 Jan 23. doi: 10.1200/JCO.2016.71.1184).

Given that the average wholesale price of sunitinib is $17,811.83 per 28-day cycle, “the 9 cycles saved per patient translates into a median cost saving of $160,302 per patient and $3.85 million overall, not including the cost of toxicity management that may have been incurred without breaks,” they noted.

The median progression-free survival was 22.4 months for the entire study cohort and 37.6 months for the 20 patients who had intermittent therapy.

Patients who showed tumor progression during a treatment break were transitioned back to standard dosing without showing any adverse clinical effects. This suggests that “with close clinical and radiographic monitoring, patients can safely take a therapy break for extended periods of time,” the investigators said.

Intermittent breaks from sunitinib therapy are feasible and don’t appear to compromise the agent’s clinical efficacy against metastatic renal cell carcinoma, according to investigators.

One of the greatest challenges in treating this cancer is balancing treatment-related toxicity against efficacy “in a setting ... in which patients are largely incurable and thus subjected to chronic therapy,” said Moshe C. Ornstein, MD, and his associates at the Cleveland Clinic Taussig Cancer Institute.

They performed a single-center phase II study that they described as the first prospective trial to assess treatment interruptions whenever tumor burden was reduced by 10% or more, followed by resumption of treatment if tumors then progressed 10% or more. This approach “may result in reduced toxicities, improved quality of life, cost savings, and potentially improved clinical outcomes.”

The study involved 37 adults (median age, 63 years) who were given 50 mg sunitinib once daily for the first 28 days of a 42-day cycle, with dose adjustments allowed to minimize toxicities. Twenty patients (54%) who showed a 10% or greater reduction in tumor burden after four cycles suspended treatment until scans showed a 10% or greater progression, at which point treatment was resumed. These 20 patients were able to take up to 11 treatment breaks (median, 3 breaks per patient), with each break having a median duration of more than 8 weeks (range, 4.7-192.1 weeks).

Seven patients were able to have extended drug holidays lasting 3-43 months, and three have never had to resume sunitinib therapy after their first break. “The overall sum of all the breaks was 1,296.6 weeks, which corresponds to 216 6-week cycles with a median of 9 saved cycles per patient,” Dr. Ornstein and his associates said (J Clin Oncol. 2017 Jan 23. doi: 10.1200/JCO.2016.71.1184).

Given that the average wholesale price of sunitinib is $17,811.83 per 28-day cycle, “the 9 cycles saved per patient translates into a median cost saving of $160,302 per patient and $3.85 million overall, not including the cost of toxicity management that may have been incurred without breaks,” they noted.

The median progression-free survival was 22.4 months for the entire study cohort and 37.6 months for the 20 patients who had intermittent therapy.

Patients who showed tumor progression during a treatment break were transitioned back to standard dosing without showing any adverse clinical effects. This suggests that “with close clinical and radiographic monitoring, patients can safely take a therapy break for extended periods of time,” the investigators said.

Intermittent breaks from sunitinib therapy are feasible and don’t appear to compromise the agent’s clinical efficacy against metastatic renal cell carcinoma, according to investigators.

One of the greatest challenges in treating this cancer is balancing treatment-related toxicity against efficacy “in a setting ... in which patients are largely incurable and thus subjected to chronic therapy,” said Moshe C. Ornstein, MD, and his associates at the Cleveland Clinic Taussig Cancer Institute.

They performed a single-center phase II study that they described as the first prospective trial to assess treatment interruptions whenever tumor burden was reduced by 10% or more, followed by resumption of treatment if tumors then progressed 10% or more. This approach “may result in reduced toxicities, improved quality of life, cost savings, and potentially improved clinical outcomes.”

The study involved 37 adults (median age, 63 years) who were given 50 mg sunitinib once daily for the first 28 days of a 42-day cycle, with dose adjustments allowed to minimize toxicities. Twenty patients (54%) who showed a 10% or greater reduction in tumor burden after four cycles suspended treatment until scans showed a 10% or greater progression, at which point treatment was resumed. These 20 patients were able to take up to 11 treatment breaks (median, 3 breaks per patient), with each break having a median duration of more than 8 weeks (range, 4.7-192.1 weeks).

Seven patients were able to have extended drug holidays lasting 3-43 months, and three have never had to resume sunitinib therapy after their first break. “The overall sum of all the breaks was 1,296.6 weeks, which corresponds to 216 6-week cycles with a median of 9 saved cycles per patient,” Dr. Ornstein and his associates said (J Clin Oncol. 2017 Jan 23. doi: 10.1200/JCO.2016.71.1184).

Given that the average wholesale price of sunitinib is $17,811.83 per 28-day cycle, “the 9 cycles saved per patient translates into a median cost saving of $160,302 per patient and $3.85 million overall, not including the cost of toxicity management that may have been incurred without breaks,” they noted.

The median progression-free survival was 22.4 months for the entire study cohort and 37.6 months for the 20 patients who had intermittent therapy.

Patients who showed tumor progression during a treatment break were transitioned back to standard dosing without showing any adverse clinical effects. This suggests that “with close clinical and radiographic monitoring, patients can safely take a therapy break for extended periods of time,” the investigators said.

Highly active antiretroviral therapy taken by HIV-positive men who have sex with men may be contributing to the profound escalation in syphilis infections recently observed worldwide, a recent report suggests.

After noting reports of a substantial and rapid rise in syphilis infections around the globe, which have been largely confined to HIV-positive men taking HAART, researchers constructed mathematical models to test the possibility that HAART may inadvertently alter immune responses in ways that enhance the patient’s vulnerability to Treponema pallidum.

jarun011/Thinkstock

Highly active antiretroviral therapy taken by HIV-positive men who have sex with men may be contributing to the profound escalation in syphilis infections recently observed worldwide, a recent report suggests.

After noting reports of a substantial and rapid rise in syphilis infections around the globe, which have been largely confined to HIV-positive men taking HAART, researchers constructed mathematical models to test the possibility that HAART may inadvertently alter immune responses in ways that enhance the patient’s vulnerability to Treponema pallidum.

jarun011/Thinkstock

Highly active antiretroviral therapy taken by HIV-positive men who have sex with men may be contributing to the profound escalation in syphilis infections recently observed worldwide, a recent report suggests.

After noting reports of a substantial and rapid rise in syphilis infections around the globe, which have been largely confined to HIV-positive men taking HAART, researchers constructed mathematical models to test the possibility that HAART may inadvertently alter immune responses in ways that enhance the patient’s vulnerability to Treponema pallidum.

jarun011/Thinkstock

Asymptomatic carriage of carbapenem-resistant Enterobacteriaceae is “considerable,” according to genetic analyses of bacterial isolates obtained from patients at four large U.S. hospitals.

To better understand the “urgent threat” of carbapenem resistance – specifically, to obtain a “snapshot” of how the resistant enterobacteria evolve, diversify, and spread – the researchers performed genetic analyses on 122 carbapenem-resistant and 141 carbapenem-susceptible bacterial isolates from patients hospitalized during a 16-month period at three Boston and one California medical centers. The isolates were obtained from urine (44%), respiratory tract (16%), blood (11%), wound (11%), and other samples, said Gustavo C. Cerqueira, PhD, of the Broad Institute of MIT and Harvard University in Cambridge, Mass., and his associates.

They found 8 species of bacteria that exhibited carbapenem resistance, chiefly Klebsiella pneumoniae. There also was a significant degree of diversity among resistant Enterobacteria. Most importantly, the investigators found evidence of substantial asymptomatic carriage of resistant bacteria and discovered several previously unrecognized mechanisms that produced resistance. Taken together, the findings indicate “continued innovation by these organisms to thwart the action of this important class of antibiotics,” reported Dr. Cerqueira, also affiliated with Massachusetts General Hospital in Boston, and his associates (Proc Nat Acad Sci USA. 2017 Jan 16 [doi:10.1073/pnas.1616248114]).

The study findings underscore the need for “an aggressive approach to surveillance and isolation” to control this continuing threat, they added.

This work was supported by the National Institute of Allergy and Infectious Diseases. Dr. Cerqueira and his associates reported having no relevant financial disclosures.
 

Asymptomatic carriage of carbapenem-resistant Enterobacteriaceae is “considerable,” according to genetic analyses of bacterial isolates obtained from patients at four large U.S. hospitals.

To better understand the “urgent threat” of carbapenem resistance – specifically, to obtain a “snapshot” of how the resistant enterobacteria evolve, diversify, and spread – the researchers performed genetic analyses on 122 carbapenem-resistant and 141 carbapenem-susceptible bacterial isolates from patients hospitalized during a 16-month period at three Boston and one California medical centers. The isolates were obtained from urine (44%), respiratory tract (16%), blood (11%), wound (11%), and other samples, said Gustavo C. Cerqueira, PhD, of the Broad Institute of MIT and Harvard University in Cambridge, Mass., and his associates.

They found 8 species of bacteria that exhibited carbapenem resistance, chiefly Klebsiella pneumoniae. There also was a significant degree of diversity among resistant Enterobacteria. Most importantly, the investigators found evidence of substantial asymptomatic carriage of resistant bacteria and discovered several previously unrecognized mechanisms that produced resistance. Taken together, the findings indicate “continued innovation by these organisms to thwart the action of this important class of antibiotics,” reported Dr. Cerqueira, also affiliated with Massachusetts General Hospital in Boston, and his associates (Proc Nat Acad Sci USA. 2017 Jan 16 [doi:10.1073/pnas.1616248114]).

The study findings underscore the need for “an aggressive approach to surveillance and isolation” to control this continuing threat, they added.

This work was supported by the National Institute of Allergy and Infectious Diseases. Dr. Cerqueira and his associates reported having no relevant financial disclosures.
 

Asymptomatic carriage of carbapenem-resistant Enterobacteriaceae is “considerable,” according to genetic analyses of bacterial isolates obtained from patients at four large U.S. hospitals.

To better understand the “urgent threat” of carbapenem resistance – specifically, to obtain a “snapshot” of how the resistant enterobacteria evolve, diversify, and spread – the researchers performed genetic analyses on 122 carbapenem-resistant and 141 carbapenem-susceptible bacterial isolates from patients hospitalized during a 16-month period at three Boston and one California medical centers. The isolates were obtained from urine (44%), respiratory tract (16%), blood (11%), wound (11%), and other samples, said Gustavo C. Cerqueira, PhD, of the Broad Institute of MIT and Harvard University in Cambridge, Mass., and his associates.

They found 8 species of bacteria that exhibited carbapenem resistance, chiefly Klebsiella pneumoniae. There also was a significant degree of diversity among resistant Enterobacteria. Most importantly, the investigators found evidence of substantial asymptomatic carriage of resistant bacteria and discovered several previously unrecognized mechanisms that produced resistance. Taken together, the findings indicate “continued innovation by these organisms to thwart the action of this important class of antibiotics,” reported Dr. Cerqueira, also affiliated with Massachusetts General Hospital in Boston, and his associates (Proc Nat Acad Sci USA. 2017 Jan 16 [doi:10.1073/pnas.1616248114]).

The study findings underscore the need for “an aggressive approach to surveillance and isolation” to control this continuing threat, they added.

This work was supported by the National Institute of Allergy and Infectious Diseases. Dr. Cerqueira and his associates reported having no relevant financial disclosures.
 

Adding bezlotoxumab to standard antibiotic treatment of primary or recurrent Clostridium difficile infection reduces recurrences by 38% (10 percentage points), according to a report published in the New England Journal of Medicine.

As many as 35% of patients who complete initial antibiotic treatment have at least one recurrence of C. difficile infection, and the rate of repeat recurrence rate jumps to 60% after the initial recurrence. Researchers performed two parallel international phase III trials to assess the efficacy and safety of bezlotoxumab, alone or in combination with actoxumab, for preventing such recurrences. Both monoclonal antibodies work by binding to and neutralizing C. difficile toxins; bezlotoxumab targets toxin B and actoxumab targets toxin A, said Mark H. Wilcox, MD, of the division of microbiology, Leeds (England) General Infirmary, and his associates.

cjc2nd/Wikimedia Commons/CC ASA-3.0

Adding bezlotoxumab to standard antibiotic treatment of primary or recurrent Clostridium difficile infection reduces recurrences by 38% (10 percentage points), according to a report published in the New England Journal of Medicine.

As many as 35% of patients who complete initial antibiotic treatment have at least one recurrence of C. difficile infection, and the rate of repeat recurrence rate jumps to 60% after the initial recurrence. Researchers performed two parallel international phase III trials to assess the efficacy and safety of bezlotoxumab, alone or in combination with actoxumab, for preventing such recurrences. Both monoclonal antibodies work by binding to and neutralizing C. difficile toxins; bezlotoxumab targets toxin B and actoxumab targets toxin A, said Mark H. Wilcox, MD, of the division of microbiology, Leeds (England) General Infirmary, and his associates.

cjc2nd/Wikimedia Commons/CC ASA-3.0

Adding bezlotoxumab to standard antibiotic treatment of primary or recurrent Clostridium difficile infection reduces recurrences by 38% (10 percentage points), according to a report published in the New England Journal of Medicine.

As many as 35% of patients who complete initial antibiotic treatment have at least one recurrence of C. difficile infection, and the rate of repeat recurrence rate jumps to 60% after the initial recurrence. Researchers performed two parallel international phase III trials to assess the efficacy and safety of bezlotoxumab, alone or in combination with actoxumab, for preventing such recurrences. Both monoclonal antibodies work by binding to and neutralizing C. difficile toxins; bezlotoxumab targets toxin B and actoxumab targets toxin A, said Mark H. Wilcox, MD, of the division of microbiology, Leeds (England) General Infirmary, and his associates.

cjc2nd/Wikimedia Commons/CC ASA-3.0

A 6-month course of continuous glucose monitoring modestly cut hemoglobin A_1c levels in patients with type 1 diabetes who used multiple daily insulin injections, according to two separate randomized trials reported online Jan. 24 in JAMA.

Compared with usual care, continuous glucose monitoring decreased mean HbA_1c levels by 0.6% in a multicenter open-label U.S. study involving 158 participants and by 0.4% in a multicenter open-label crossover trial in Sweden. Both research groups noted that lengthier trials are needed to assess longer-term effectiveness of continuous glucose monitoring in this patient population, the possible adverse effects of long-term use, and whether the reduction in HbA_1c levels translates into improved clinical outcomes.

The first trial, which was conducted at 24 U.S. endocrinology practices, involved patients aged 25 and older (mean age, 48 years) who had had type 1 diabetes for a median of 19 years and whose baseline HbA₁c levels ranged from 7.5% to 10%. A total of 105 of these participants were randomly assigned to use continuous glucose monitoring (CGM group) and 53 to receive usual care (control group) for 24 weeks, said Roy W. Beck, MD, PhD, of the Jaeb Center for Health Research, Tampa, and his associates.

The CGM group was instructed to wear the device on at least 85% of days and to calibrate it at least twice per day, and they were to verify their glucose level by doing blood glucose meter testing at least three times daily before injecting insulin. The control group was instructed to do blood glucose meter testing at least four times per day.

The primary outcome, reduction in HbA_1c level, was 1.1% at 12 weeks and 1% at 24 weeks with CGM, compared with 0.5% at 12 weeks and 0.4% at 24 weeks with usual care. At the end of the treatment period, the mean difference between the two study groups in HbA_1c reduction was 0.6%.

Secondary outcomes also favored CGM, including the time spent with glucose levels within the target range of 70-180 mg/dL, duration of hypoglycemia, duration of hyperglycemia, and glycemic variability. In addition, patients reported a high level of satisfaction with CGM, Dr. Beck and his associates said (JAMA. 2017 Jan 24. doi: 10.1001/jama.2016.19975).

The second trial was conducted at 15 medical centers in Sweden and involved 161 adults aged 18 and older (mean age, 44 years) whose baseline HbA_1c levels were 7.5% or higher. The participants served as their own controls, randomly assigned to use either CGM or usual care for 26 weeks and then to crossover to the other group for 26 weeks, said Marcus Lind, MD, PhD, of the diabetes outpatient clinic, Uddevalla (Sweden) Hospital, and his associates.

The primary outcome, reduction in HbA_1c level, was lower by 0.4% with CGM than with usual care. In addition, secondary outcomes also favored CGM, including treatment satisfaction, patient concern about having a hypoglycemic episode, overall well-being, and mean glucose levels. However, in this study, patients measured their blood glucose levels less often with CGM (2.7 measurements per day) than with usual care (3.7 measurements per day).

One patient developed an allergic reaction to the device’s internal sensor and had it removed, according to Dr. Lind and his associates (JAMA. 2017 Jan 24. doi: 10.1001/jama.2016.19976).

Dr. Beck’s study was sponsored by Dexcom, maker of the CGM device, which also participated in designing the study, writing the protocol, reviewing and approving the manuscripts, and interpreting the data. Dr. Beck reported financial relationships with Dexcom and Abbott Diabetes Care, and his associates reported ties to numerous industry sources. Dr. Lind’s study was sponsored by the NU Hospital Group and Dexcom. Dr. Lind reported financial relationships with AstraZeneca, Dexcom, Eli Lilly, Medtronic, Novo Nordisk, and Rubin Medical, and his associates reported ties to numerous industry sources.

A 6-month course of continuous glucose monitoring modestly cut hemoglobin A_1c levels in patients with type 1 diabetes who used multiple daily insulin injections, according to two separate randomized trials reported online Jan. 24 in JAMA.

Compared with usual care, continuous glucose monitoring decreased mean HbA_1c levels by 0.6% in a multicenter open-label U.S. study involving 158 participants and by 0.4% in a multicenter open-label crossover trial in Sweden. Both research groups noted that lengthier trials are needed to assess longer-term effectiveness of continuous glucose monitoring in this patient population, the possible adverse effects of long-term use, and whether the reduction in HbA_1c levels translates into improved clinical outcomes.

The first trial, which was conducted at 24 U.S. endocrinology practices, involved patients aged 25 and older (mean age, 48 years) who had had type 1 diabetes for a median of 19 years and whose baseline HbA₁c levels ranged from 7.5% to 10%. A total of 105 of these participants were randomly assigned to use continuous glucose monitoring (CGM group) and 53 to receive usual care (control group) for 24 weeks, said Roy W. Beck, MD, PhD, of the Jaeb Center for Health Research, Tampa, and his associates.

The CGM group was instructed to wear the device on at least 85% of days and to calibrate it at least twice per day, and they were to verify their glucose level by doing blood glucose meter testing at least three times daily before injecting insulin. The control group was instructed to do blood glucose meter testing at least four times per day.

The primary outcome, reduction in HbA_1c level, was 1.1% at 12 weeks and 1% at 24 weeks with CGM, compared with 0.5% at 12 weeks and 0.4% at 24 weeks with usual care. At the end of the treatment period, the mean difference between the two study groups in HbA_1c reduction was 0.6%.

Secondary outcomes also favored CGM, including the time spent with glucose levels within the target range of 70-180 mg/dL, duration of hypoglycemia, duration of hyperglycemia, and glycemic variability. In addition, patients reported a high level of satisfaction with CGM, Dr. Beck and his associates said (JAMA. 2017 Jan 24. doi: 10.1001/jama.2016.19975).

The second trial was conducted at 15 medical centers in Sweden and involved 161 adults aged 18 and older (mean age, 44 years) whose baseline HbA_1c levels were 7.5% or higher. The participants served as their own controls, randomly assigned to use either CGM or usual care for 26 weeks and then to crossover to the other group for 26 weeks, said Marcus Lind, MD, PhD, of the diabetes outpatient clinic, Uddevalla (Sweden) Hospital, and his associates.

The primary outcome, reduction in HbA_1c level, was lower by 0.4% with CGM than with usual care. In addition, secondary outcomes also favored CGM, including treatment satisfaction, patient concern about having a hypoglycemic episode, overall well-being, and mean glucose levels. However, in this study, patients measured their blood glucose levels less often with CGM (2.7 measurements per day) than with usual care (3.7 measurements per day).

One patient developed an allergic reaction to the device’s internal sensor and had it removed, according to Dr. Lind and his associates (JAMA. 2017 Jan 24. doi: 10.1001/jama.2016.19976).

Dr. Beck’s study was sponsored by Dexcom, maker of the CGM device, which also participated in designing the study, writing the protocol, reviewing and approving the manuscripts, and interpreting the data. Dr. Beck reported financial relationships with Dexcom and Abbott Diabetes Care, and his associates reported ties to numerous industry sources. Dr. Lind’s study was sponsored by the NU Hospital Group and Dexcom. Dr. Lind reported financial relationships with AstraZeneca, Dexcom, Eli Lilly, Medtronic, Novo Nordisk, and Rubin Medical, and his associates reported ties to numerous industry sources.

A 6-month course of continuous glucose monitoring modestly cut hemoglobin A_1c levels in patients with type 1 diabetes who used multiple daily insulin injections, according to two separate randomized trials reported online Jan. 24 in JAMA.

Compared with usual care, continuous glucose monitoring decreased mean HbA_1c levels by 0.6% in a multicenter open-label U.S. study involving 158 participants and by 0.4% in a multicenter open-label crossover trial in Sweden. Both research groups noted that lengthier trials are needed to assess longer-term effectiveness of continuous glucose monitoring in this patient population, the possible adverse effects of long-term use, and whether the reduction in HbA_1c levels translates into improved clinical outcomes.

The first trial, which was conducted at 24 U.S. endocrinology practices, involved patients aged 25 and older (mean age, 48 years) who had had type 1 diabetes for a median of 19 years and whose baseline HbA₁c levels ranged from 7.5% to 10%. A total of 105 of these participants were randomly assigned to use continuous glucose monitoring (CGM group) and 53 to receive usual care (control group) for 24 weeks, said Roy W. Beck, MD, PhD, of the Jaeb Center for Health Research, Tampa, and his associates.

The CGM group was instructed to wear the device on at least 85% of days and to calibrate it at least twice per day, and they were to verify their glucose level by doing blood glucose meter testing at least three times daily before injecting insulin. The control group was instructed to do blood glucose meter testing at least four times per day.

The primary outcome, reduction in HbA_1c level, was 1.1% at 12 weeks and 1% at 24 weeks with CGM, compared with 0.5% at 12 weeks and 0.4% at 24 weeks with usual care. At the end of the treatment period, the mean difference between the two study groups in HbA_1c reduction was 0.6%.

Secondary outcomes also favored CGM, including the time spent with glucose levels within the target range of 70-180 mg/dL, duration of hypoglycemia, duration of hyperglycemia, and glycemic variability. In addition, patients reported a high level of satisfaction with CGM, Dr. Beck and his associates said (JAMA. 2017 Jan 24. doi: 10.1001/jama.2016.19975).

The second trial was conducted at 15 medical centers in Sweden and involved 161 adults aged 18 and older (mean age, 44 years) whose baseline HbA_1c levels were 7.5% or higher. The participants served as their own controls, randomly assigned to use either CGM or usual care for 26 weeks and then to crossover to the other group for 26 weeks, said Marcus Lind, MD, PhD, of the diabetes outpatient clinic, Uddevalla (Sweden) Hospital, and his associates.

The primary outcome, reduction in HbA_1c level, was lower by 0.4% with CGM than with usual care. In addition, secondary outcomes also favored CGM, including treatment satisfaction, patient concern about having a hypoglycemic episode, overall well-being, and mean glucose levels. However, in this study, patients measured their blood glucose levels less often with CGM (2.7 measurements per day) than with usual care (3.7 measurements per day).

One patient developed an allergic reaction to the device’s internal sensor and had it removed, according to Dr. Lind and his associates (JAMA. 2017 Jan 24. doi: 10.1001/jama.2016.19976).

Dr. Beck’s study was sponsored by Dexcom, maker of the CGM device, which also participated in designing the study, writing the protocol, reviewing and approving the manuscripts, and interpreting the data. Dr. Beck reported financial relationships with Dexcom and Abbott Diabetes Care, and his associates reported ties to numerous industry sources. Dr. Lind’s study was sponsored by the NU Hospital Group and Dexcom. Dr. Lind reported financial relationships with AstraZeneca, Dexcom, Eli Lilly, Medtronic, Novo Nordisk, and Rubin Medical, and his associates reported ties to numerous industry sources.

The U.S. Preventive Services Task Force neither supports nor rejects screening asymptomatic adults for obstructive sleep apnea in the primary-care setting, because the current evidence is inadequate to assess the benefits and harms of doing so, according to a Recommendation Statement published online Jan. 23 in JAMA.

The USPSTF makes recommendations about the effectiveness of specific health care services for patients who don’t have related signs or symptoms. In this case, the Recommendation Statement addresses adults who don’t snore excessively; gasp or choke while sleeping; or report the daytime sleepiness, impaired cognition, or mood changes typically associated with obstructive sleep apnea, said Kirsten Bobbins-Domingo, PhD, MD, chair of the organization and lead author of the Recommendation Statement, and her associates (JAMA 2017 Jan 23. doi: 10.1001/jama.2016.20325).

The USPSTF commissioned a comprehensive review of the literature to examine whether screening such patients by primary caregivers would effectively identify those who have obstructive sleep apnea and lead to treatment that would prevent the elevated rates of death, cognitive impairment, motor vehicle crashes, cardiovascular events, and cerebrovascular events related to the disorder. Daniel E. Jonas, MD, of the University of North Carolina at Chapel Hill and his associates reviewed 110 relevant studies involving 46,188 participants.

They found that the accuracy and clinical utility of numerous OSA screening tools was uncertain. In particular, the Epworth Sleepiness Scale, the STOP (Snoring, Tiredness, Observed Apnea, and High Blood Pressure) questionnaire, the STOP-BANG (STOP plus BMI, Age, Neck Circumference, and Gender) questionnaire, the Berlin Questionnaire, the Wisconsin Sleep Questionnaire, and the Multivariable Apnea Prediction (MVAP) tool have not been adequately validated in primary care settings.

Moreover, no studies directly assessed whether screening had an impact on actual health outcomes. Several treatments, notably CPAP and mandibular advancement devices, did improve intermediate outcomes such as scores on the apnea-hypopnea index, scores on the Epworth Sleepiness Scale, and blood pressure levels, but the evidence did not show that this in turn improved mortality, cardiovascular events, or the other “hard” outcomes of interest, Dr. Jonas and his associates said in their Evidence Report (JAMA 2017 Jan 23. doi: 10.1001/jama.2016.19635).

Dr. Bobbins-Domingo and her associates on the task force noted that this Recommendation Statement is consistent with that of the American Academy of Family Physicians, which also concluded that the current evidence is insufficient to assess the balance of benefits and harms of screening asymptomatic adults for obstructive sleep apnea.

The American College of Physicians offers a “weak” recommendation based on low-quality evidence that patients with unexplained daytime sleepiness and patients suspected of having apnea undergo a sleep study, said Dr. Bobbins-Domingo, professor of medicine at the University of California, San Francisco, and her associates.

In contrast, the American Academy of Sleep Medicine recommends that routine health visits should include questions about OSA and evaluation of risk factors such as obesity, retrognathia, and treatment-refractory hypertension. If there are positive findings, a comprehensive sleep evaluation should follow, according to the AASM.

The USPSTF is an independent voluntary group supported by the Agency for Healthcare Research and Quality as mandated by the U.S. Congress. The authors’ conflict of interest disclosures are available at www.uspreventiveservicestaskforce.org.

The U.S. Preventive Services Task Force neither supports nor rejects screening asymptomatic adults for obstructive sleep apnea in the primary-care setting, because the current evidence is inadequate to assess the benefits and harms of doing so, according to a Recommendation Statement published online Jan. 23 in JAMA.

The USPSTF makes recommendations about the effectiveness of specific health care services for patients who don’t have related signs or symptoms. In this case, the Recommendation Statement addresses adults who don’t snore excessively; gasp or choke while sleeping; or report the daytime sleepiness, impaired cognition, or mood changes typically associated with obstructive sleep apnea, said Kirsten Bobbins-Domingo, PhD, MD, chair of the organization and lead author of the Recommendation Statement, and her associates (JAMA 2017 Jan 23. doi: 10.1001/jama.2016.20325).

The USPSTF commissioned a comprehensive review of the literature to examine whether screening such patients by primary caregivers would effectively identify those who have obstructive sleep apnea and lead to treatment that would prevent the elevated rates of death, cognitive impairment, motor vehicle crashes, cardiovascular events, and cerebrovascular events related to the disorder. Daniel E. Jonas, MD, of the University of North Carolina at Chapel Hill and his associates reviewed 110 relevant studies involving 46,188 participants.

They found that the accuracy and clinical utility of numerous OSA screening tools was uncertain. In particular, the Epworth Sleepiness Scale, the STOP (Snoring, Tiredness, Observed Apnea, and High Blood Pressure) questionnaire, the STOP-BANG (STOP plus BMI, Age, Neck Circumference, and Gender) questionnaire, the Berlin Questionnaire, the Wisconsin Sleep Questionnaire, and the Multivariable Apnea Prediction (MVAP) tool have not been adequately validated in primary care settings.

Moreover, no studies directly assessed whether screening had an impact on actual health outcomes. Several treatments, notably CPAP and mandibular advancement devices, did improve intermediate outcomes such as scores on the apnea-hypopnea index, scores on the Epworth Sleepiness Scale, and blood pressure levels, but the evidence did not show that this in turn improved mortality, cardiovascular events, or the other “hard” outcomes of interest, Dr. Jonas and his associates said in their Evidence Report (JAMA 2017 Jan 23. doi: 10.1001/jama.2016.19635).

Dr. Bobbins-Domingo and her associates on the task force noted that this Recommendation Statement is consistent with that of the American Academy of Family Physicians, which also concluded that the current evidence is insufficient to assess the balance of benefits and harms of screening asymptomatic adults for obstructive sleep apnea.

The American College of Physicians offers a “weak” recommendation based on low-quality evidence that patients with unexplained daytime sleepiness and patients suspected of having apnea undergo a sleep study, said Dr. Bobbins-Domingo, professor of medicine at the University of California, San Francisco, and her associates.

In contrast, the American Academy of Sleep Medicine recommends that routine health visits should include questions about OSA and evaluation of risk factors such as obesity, retrognathia, and treatment-refractory hypertension. If there are positive findings, a comprehensive sleep evaluation should follow, according to the AASM.

The USPSTF is an independent voluntary group supported by the Agency for Healthcare Research and Quality as mandated by the U.S. Congress. The authors’ conflict of interest disclosures are available at www.uspreventiveservicestaskforce.org.

The U.S. Preventive Services Task Force neither supports nor rejects screening asymptomatic adults for obstructive sleep apnea in the primary-care setting, because the current evidence is inadequate to assess the benefits and harms of doing so, according to a Recommendation Statement published online Jan. 23 in JAMA.

The USPSTF makes recommendations about the effectiveness of specific health care services for patients who don’t have related signs or symptoms. In this case, the Recommendation Statement addresses adults who don’t snore excessively; gasp or choke while sleeping; or report the daytime sleepiness, impaired cognition, or mood changes typically associated with obstructive sleep apnea, said Kirsten Bobbins-Domingo, PhD, MD, chair of the organization and lead author of the Recommendation Statement, and her associates (JAMA 2017 Jan 23. doi: 10.1001/jama.2016.20325).

The USPSTF commissioned a comprehensive review of the literature to examine whether screening such patients by primary caregivers would effectively identify those who have obstructive sleep apnea and lead to treatment that would prevent the elevated rates of death, cognitive impairment, motor vehicle crashes, cardiovascular events, and cerebrovascular events related to the disorder. Daniel E. Jonas, MD, of the University of North Carolina at Chapel Hill and his associates reviewed 110 relevant studies involving 46,188 participants.

They found that the accuracy and clinical utility of numerous OSA screening tools was uncertain. In particular, the Epworth Sleepiness Scale, the STOP (Snoring, Tiredness, Observed Apnea, and High Blood Pressure) questionnaire, the STOP-BANG (STOP plus BMI, Age, Neck Circumference, and Gender) questionnaire, the Berlin Questionnaire, the Wisconsin Sleep Questionnaire, and the Multivariable Apnea Prediction (MVAP) tool have not been adequately validated in primary care settings.

Moreover, no studies directly assessed whether screening had an impact on actual health outcomes. Several treatments, notably CPAP and mandibular advancement devices, did improve intermediate outcomes such as scores on the apnea-hypopnea index, scores on the Epworth Sleepiness Scale, and blood pressure levels, but the evidence did not show that this in turn improved mortality, cardiovascular events, or the other “hard” outcomes of interest, Dr. Jonas and his associates said in their Evidence Report (JAMA 2017 Jan 23. doi: 10.1001/jama.2016.19635).

Dr. Bobbins-Domingo and her associates on the task force noted that this Recommendation Statement is consistent with that of the American Academy of Family Physicians, which also concluded that the current evidence is insufficient to assess the balance of benefits and harms of screening asymptomatic adults for obstructive sleep apnea.

The American College of Physicians offers a “weak” recommendation based on low-quality evidence that patients with unexplained daytime sleepiness and patients suspected of having apnea undergo a sleep study, said Dr. Bobbins-Domingo, professor of medicine at the University of California, San Francisco, and her associates.

In contrast, the American Academy of Sleep Medicine recommends that routine health visits should include questions about OSA and evaluation of risk factors such as obesity, retrognathia, and treatment-refractory hypertension. If there are positive findings, a comprehensive sleep evaluation should follow, according to the AASM.

The USPSTF is an independent voluntary group supported by the Agency for Healthcare Research and Quality as mandated by the U.S. Congress. The authors’ conflict of interest disclosures are available at www.uspreventiveservicestaskforce.org.

Deferring radiotherapy to administer epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) first doesn’t prolong overall survival, it shortens survival in patients who have brain metastases of EGFR-mutated non–small-cell lung cancer (NSCLC), according to a report in the Journal of Clinical Oncology.

Upfront therapy using EGFR TKIs such as erlotinib has been proposed as a way to avoid radiotherapy altogether in this patient population, or to at least defer it and any related toxicities until intracranial disease progresses, said William J. Magnuson, MD, of Yale University, New Haven, Conn., and his associates.

To assess the advantages and disadvantages of upfront EGFR TKIs vs. initial radiotherapy, the researchers pooled survival data for 351 patients treated at six academic medical centers during 2008-2015. A total of 131 (37%) received upfront EGFR TKIs followed by stereotactic radiosurgery or whole-brain radiotherapy when the brain metastases progressed, 120 (34%) received whole-brain radiotherapy followed by EGFR TKIs, and 100 (29%) received stereotactic radiosurgery followed by EGFR TKIs. These patients were followed for a median of 22 months.

Median overall survival was 25 months for upfront EGFR TKIs, compared with 30 months for initial whole-brain radiotherapy and 46 months for initial stereotactic radiosurgery. At 2 years, overall survival rates for the three study groups were 51%, 62%, and 78%, respectively. Both forms of initial radiotherapy were associated with improved overall survival relative to EGFR TKIs, with a hazard ratio of 0.39 for stereotactic radiosurgery and a hazard ratio of 0.70 for whole-brain irradiation.

This survival advantage was even more pronounced in the subgroup of patients who had more favorable prognostic features at baseline. These patients had a median overall survival of 64 months if they received radiotherapy followed by EGFR TKIs, compared with only 32 months if EGFR TKIs were taken before radiotherapy, the investigators said (J Clin Oncol. 2017 Jan 23. doi: 10.1200/JCO.2016.69.7144).

These findings have the potential to change clinical practice, but prospective randomized data to confirm the results are urgently needed. “Until such a study is conducted and published, the standard-of-care treatment of newly diagnosed brain metastases should remain stereotactic radiosurgery followed by systemic therapy,” Dr. Magnuson and his associates said.

No funding source was cited for this study. Dr. Magnuson reported having no relevant financial disclosures; his associates reported having ties to numerous industry sources.

Deferring radiotherapy to administer epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) first doesn’t prolong overall survival, it shortens survival in patients who have brain metastases of EGFR-mutated non–small-cell lung cancer (NSCLC), according to a report in the Journal of Clinical Oncology.

Upfront therapy using EGFR TKIs such as erlotinib has been proposed as a way to avoid radiotherapy altogether in this patient population, or to at least defer it and any related toxicities until intracranial disease progresses, said William J. Magnuson, MD, of Yale University, New Haven, Conn., and his associates.

To assess the advantages and disadvantages of upfront EGFR TKIs vs. initial radiotherapy, the researchers pooled survival data for 351 patients treated at six academic medical centers during 2008-2015. A total of 131 (37%) received upfront EGFR TKIs followed by stereotactic radiosurgery or whole-brain radiotherapy when the brain metastases progressed, 120 (34%) received whole-brain radiotherapy followed by EGFR TKIs, and 100 (29%) received stereotactic radiosurgery followed by EGFR TKIs. These patients were followed for a median of 22 months.

Median overall survival was 25 months for upfront EGFR TKIs, compared with 30 months for initial whole-brain radiotherapy and 46 months for initial stereotactic radiosurgery. At 2 years, overall survival rates for the three study groups were 51%, 62%, and 78%, respectively. Both forms of initial radiotherapy were associated with improved overall survival relative to EGFR TKIs, with a hazard ratio of 0.39 for stereotactic radiosurgery and a hazard ratio of 0.70 for whole-brain irradiation.

This survival advantage was even more pronounced in the subgroup of patients who had more favorable prognostic features at baseline. These patients had a median overall survival of 64 months if they received radiotherapy followed by EGFR TKIs, compared with only 32 months if EGFR TKIs were taken before radiotherapy, the investigators said (J Clin Oncol. 2017 Jan 23. doi: 10.1200/JCO.2016.69.7144).

These findings have the potential to change clinical practice, but prospective randomized data to confirm the results are urgently needed. “Until such a study is conducted and published, the standard-of-care treatment of newly diagnosed brain metastases should remain stereotactic radiosurgery followed by systemic therapy,” Dr. Magnuson and his associates said.

No funding source was cited for this study. Dr. Magnuson reported having no relevant financial disclosures; his associates reported having ties to numerous industry sources.

Deferring radiotherapy to administer epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) first doesn’t prolong overall survival, it shortens survival in patients who have brain metastases of EGFR-mutated non–small-cell lung cancer (NSCLC), according to a report in the Journal of Clinical Oncology.

Upfront therapy using EGFR TKIs such as erlotinib has been proposed as a way to avoid radiotherapy altogether in this patient population, or to at least defer it and any related toxicities until intracranial disease progresses, said William J. Magnuson, MD, of Yale University, New Haven, Conn., and his associates.

To assess the advantages and disadvantages of upfront EGFR TKIs vs. initial radiotherapy, the researchers pooled survival data for 351 patients treated at six academic medical centers during 2008-2015. A total of 131 (37%) received upfront EGFR TKIs followed by stereotactic radiosurgery or whole-brain radiotherapy when the brain metastases progressed, 120 (34%) received whole-brain radiotherapy followed by EGFR TKIs, and 100 (29%) received stereotactic radiosurgery followed by EGFR TKIs. These patients were followed for a median of 22 months.

Median overall survival was 25 months for upfront EGFR TKIs, compared with 30 months for initial whole-brain radiotherapy and 46 months for initial stereotactic radiosurgery. At 2 years, overall survival rates for the three study groups were 51%, 62%, and 78%, respectively. Both forms of initial radiotherapy were associated with improved overall survival relative to EGFR TKIs, with a hazard ratio of 0.39 for stereotactic radiosurgery and a hazard ratio of 0.70 for whole-brain irradiation.

This survival advantage was even more pronounced in the subgroup of patients who had more favorable prognostic features at baseline. These patients had a median overall survival of 64 months if they received radiotherapy followed by EGFR TKIs, compared with only 32 months if EGFR TKIs were taken before radiotherapy, the investigators said (J Clin Oncol. 2017 Jan 23. doi: 10.1200/JCO.2016.69.7144).

These findings have the potential to change clinical practice, but prospective randomized data to confirm the results are urgently needed. “Until such a study is conducted and published, the standard-of-care treatment of newly diagnosed brain metastases should remain stereotactic radiosurgery followed by systemic therapy,” Dr. Magnuson and his associates said.

No funding source was cited for this study. Dr. Magnuson reported having no relevant financial disclosures; his associates reported having ties to numerous industry sources.

Cardiac events are “relatively common,” affecting 23% of patients, and occur earlier than previously thought following radiotherapy for non–small-cell lung cancer (NSCLC), according to a report in the Journal of Clinical Oncology.

Radiation-associated cardiac toxicity has long been recognized in patients treated for other thoracic cancers, but the conventional wisdom has been that it isn’t a consideration in patients with stage III NSCLC because “there are few long-term survivors to experience toxicity, given the typically long latency of radiotherapy-associated heart injury and the poor prognosis” of this cancer. However, the findings “challenge the perception that minimizing heart dose is not important in the treatment of patients with stage III NSCLC,” said Kyle Wang, MD, of University of North Carolina Hospitals, Chapel Hill, and his associates.

“Our data support minimization of heart radiation exposure whenever possible to doses lower than commonly recommended in patients with stage III NSCLC, to reduce risks of [cardiac] toxicity,” they noted.

Dr. Wang and his associates performed a retrospective post hoc analysis of data pooled from six prospective phase I and II trials that the University of North Carolina was involved in between 1996 and 2009. The studies assessed both dose-escalated radiotherapy and various chemotherapeutic regimens in 112 patients who were followed for a median of 8.8 years (range, 2.3-17.3 years). All the patients received induction chemotherapy, 90% received concurrent chemotherapy, and 25% received consolidation chemotherapy.

A total of 26 patients (23%) had at least one symptomatic cardiac event following radiotherapy: pericardial effusion (7 patients), MI (5 patients), unstable angina (3 patients), pericarditis (2 patients), significant arrhythmia (12 patients), and heart failure (1 patient). After the data were adjusted to account for competing risks of death, the 2-year rate of symptomatic cardiac toxicity was 10% and the 4-year rate was 18%. The first adverse cardiac event occurred at a median of 26 months (range, 1-84 months).

The risk of cardiac toxicities rose with increasing radiation exposure: At 2 years, the rate of cardiac events was 4% for those exposed to less than 10 Gy, 7% for those exposed to 10-20 Gy, and 21% for those exposed to greater than 20 Gy. At 4 years, those rates were 4%, 13%, and 41%, respectively. Patients whose hearts were exposed to greater than 20 Gy had a significantly higher rate of cardiac events than did those exposed to less than 10 Gy (HR, 5.47) or to 10-20 Gy (HR, 2.76).

Even though the prognosis may be poor in patients with stage III NSCLC, “they generally receive higher heart doses and may also have more comorbidities and smoking history, thus increasing risk and perhaps shortening the latency between radiotherapy and resultant heart disease,” Dr. Wang and his associates said (J Clin Oncol. 2017 Jan 23 [doi: 10.1200/JCO.2016.70.0229]).

“In our opinion, tumor coverage should rarely be compromised to meet a heart dose constraint. However, it would be reasonable to try to limit heart mean dose to less than 20 Gy (lower if possible) on the basis of the high event rate we observed in patients exceeding this dose (21% at 2 years and 41% at 4 years). Sophisticated radiation treatment planning techniques (e.g., [intensity-modulated radiation therapy]) and charged-particle therapy with protons or carbon ions may provide increased flexibility to generate more conformal treatment plans and reduce heart dose, which could potentially improve the clinical outcomes in patients with stage III NSCLC,” they added.

Cardiac events are “relatively common,” affecting 23% of patients, and occur earlier than previously thought following radiotherapy for non–small-cell lung cancer (NSCLC), according to a report in the Journal of Clinical Oncology.

Radiation-associated cardiac toxicity has long been recognized in patients treated for other thoracic cancers, but the conventional wisdom has been that it isn’t a consideration in patients with stage III NSCLC because “there are few long-term survivors to experience toxicity, given the typically long latency of radiotherapy-associated heart injury and the poor prognosis” of this cancer. However, the findings “challenge the perception that minimizing heart dose is not important in the treatment of patients with stage III NSCLC,” said Kyle Wang, MD, of University of North Carolina Hospitals, Chapel Hill, and his associates.

“Our data support minimization of heart radiation exposure whenever possible to doses lower than commonly recommended in patients with stage III NSCLC, to reduce risks of [cardiac] toxicity,” they noted.

Dr. Wang and his associates performed a retrospective post hoc analysis of data pooled from six prospective phase I and II trials that the University of North Carolina was involved in between 1996 and 2009. The studies assessed both dose-escalated radiotherapy and various chemotherapeutic regimens in 112 patients who were followed for a median of 8.8 years (range, 2.3-17.3 years). All the patients received induction chemotherapy, 90% received concurrent chemotherapy, and 25% received consolidation chemotherapy.

A total of 26 patients (23%) had at least one symptomatic cardiac event following radiotherapy: pericardial effusion (7 patients), MI (5 patients), unstable angina (3 patients), pericarditis (2 patients), significant arrhythmia (12 patients), and heart failure (1 patient). After the data were adjusted to account for competing risks of death, the 2-year rate of symptomatic cardiac toxicity was 10% and the 4-year rate was 18%. The first adverse cardiac event occurred at a median of 26 months (range, 1-84 months).

The risk of cardiac toxicities rose with increasing radiation exposure: At 2 years, the rate of cardiac events was 4% for those exposed to less than 10 Gy, 7% for those exposed to 10-20 Gy, and 21% for those exposed to greater than 20 Gy. At 4 years, those rates were 4%, 13%, and 41%, respectively. Patients whose hearts were exposed to greater than 20 Gy had a significantly higher rate of cardiac events than did those exposed to less than 10 Gy (HR, 5.47) or to 10-20 Gy (HR, 2.76).

Even though the prognosis may be poor in patients with stage III NSCLC, “they generally receive higher heart doses and may also have more comorbidities and smoking history, thus increasing risk and perhaps shortening the latency between radiotherapy and resultant heart disease,” Dr. Wang and his associates said (J Clin Oncol. 2017 Jan 23 [doi: 10.1200/JCO.2016.70.0229]).

“In our opinion, tumor coverage should rarely be compromised to meet a heart dose constraint. However, it would be reasonable to try to limit heart mean dose to less than 20 Gy (lower if possible) on the basis of the high event rate we observed in patients exceeding this dose (21% at 2 years and 41% at 4 years). Sophisticated radiation treatment planning techniques (e.g., [intensity-modulated radiation therapy]) and charged-particle therapy with protons or carbon ions may provide increased flexibility to generate more conformal treatment plans and reduce heart dose, which could potentially improve the clinical outcomes in patients with stage III NSCLC,” they added.

Cardiac events are “relatively common,” affecting 23% of patients, and occur earlier than previously thought following radiotherapy for non–small-cell lung cancer (NSCLC), according to a report in the Journal of Clinical Oncology.

Radiation-associated cardiac toxicity has long been recognized in patients treated for other thoracic cancers, but the conventional wisdom has been that it isn’t a consideration in patients with stage III NSCLC because “there are few long-term survivors to experience toxicity, given the typically long latency of radiotherapy-associated heart injury and the poor prognosis” of this cancer. However, the findings “challenge the perception that minimizing heart dose is not important in the treatment of patients with stage III NSCLC,” said Kyle Wang, MD, of University of North Carolina Hospitals, Chapel Hill, and his associates.

“Our data support minimization of heart radiation exposure whenever possible to doses lower than commonly recommended in patients with stage III NSCLC, to reduce risks of [cardiac] toxicity,” they noted.

Dr. Wang and his associates performed a retrospective post hoc analysis of data pooled from six prospective phase I and II trials that the University of North Carolina was involved in between 1996 and 2009. The studies assessed both dose-escalated radiotherapy and various chemotherapeutic regimens in 112 patients who were followed for a median of 8.8 years (range, 2.3-17.3 years). All the patients received induction chemotherapy, 90% received concurrent chemotherapy, and 25% received consolidation chemotherapy.

A total of 26 patients (23%) had at least one symptomatic cardiac event following radiotherapy: pericardial effusion (7 patients), MI (5 patients), unstable angina (3 patients), pericarditis (2 patients), significant arrhythmia (12 patients), and heart failure (1 patient). After the data were adjusted to account for competing risks of death, the 2-year rate of symptomatic cardiac toxicity was 10% and the 4-year rate was 18%. The first adverse cardiac event occurred at a median of 26 months (range, 1-84 months).

The risk of cardiac toxicities rose with increasing radiation exposure: At 2 years, the rate of cardiac events was 4% for those exposed to less than 10 Gy, 7% for those exposed to 10-20 Gy, and 21% for those exposed to greater than 20 Gy. At 4 years, those rates were 4%, 13%, and 41%, respectively. Patients whose hearts were exposed to greater than 20 Gy had a significantly higher rate of cardiac events than did those exposed to less than 10 Gy (HR, 5.47) or to 10-20 Gy (HR, 2.76).

Even though the prognosis may be poor in patients with stage III NSCLC, “they generally receive higher heart doses and may also have more comorbidities and smoking history, thus increasing risk and perhaps shortening the latency between radiotherapy and resultant heart disease,” Dr. Wang and his associates said (J Clin Oncol. 2017 Jan 23 [doi: 10.1200/JCO.2016.70.0229]).

“In our opinion, tumor coverage should rarely be compromised to meet a heart dose constraint. However, it would be reasonable to try to limit heart mean dose to less than 20 Gy (lower if possible) on the basis of the high event rate we observed in patients exceeding this dose (21% at 2 years and 41% at 4 years). Sophisticated radiation treatment planning techniques (e.g., [intensity-modulated radiation therapy]) and charged-particle therapy with protons or carbon ions may provide increased flexibility to generate more conformal treatment plans and reduce heart dose, which could potentially improve the clinical outcomes in patients with stage III NSCLC,” they added.

A risk-assessment tool that incorporates more data on patient and partner behavior is more specific than are the CDC criteria for initiating HIV preexposure prophylaxis and would allow more targeted treatment, according to a report published in the January issue of Sexually Transmitted Diseases.

To construct a risk-assessment tool that incorporated the most relevant information for predicting HIV acquisition, researchers collected data for all the men who have sex with men who underwent serial HIV testing at a single Los Angeles facility during a 4-year period. These 9,481 men were HIV negative at their baseline visit and were followed for a mean of 2 years (range, from less than 1 year to more than 4 years) for seroconversion, said Matthew R. Beymer, PhD, of the Los Angeles LGBT Center and the University of California, Los Angeles, and his associates.

A total of 370 of these men acquired HIV infection during 16,894 person-years of follow-up.

The investigators constructed a risk-assessment tool to guide the initiation of PrEP, which included seven factors that were the most predictive of HIV seroconversion: Hispanic or African-American ethnicity; a self-reported history of chlamydia, gonorrhea, and/or syphilis; not using a condom during their last occasion of receptive anal sex; having more than three sexual partners during the preceding month or more than five during the preceding 3 months; being of the same ethnicity as the last sexual partner; experiencing intimate partner violence; and using methamphetamines or inhaled nitrates during the preceding year.

“If all individuals in our population who had a risk score of greater than or equal to 5 (51%) had been given PrEP [at baseline], 75% of HIV infections would [have been] averted during follow-up, assuming adequate regimen adherence and near complete effectiveness,” Dr. Beymer and his associates said (Sex Transm Dis. 2017;44[1]:49-57).

In contrast, CDC criteria would have selected 69% of this cohort to begin PrEP. The additional behavioral data incorporated into the risk-assessment tool “allowed for more targeted PrEP. Physicians, their patients, and other interested individuals can obtain their own personalized risk score by visiting www.IsPrEPforMe.org,” the investigators said.

They recommend that men with a risk score of 5 or higher on this instrument begin PrEP, and strongly recommend that men with a risk score of 8 or higher do so. “For individuals whose risk score is less than 5 but who request PrEP, we believe the provider should consider it in light of their patient’s overall concerns.”

Using this tool instead of CDC criteria permits a more personalized recommendation, the authors wrote. Also, those at risk will be better informed about what actions and circumstances specifically lead to their increased HIV risk, which can aid in deciding “to initiate PrEP, reduce sexual risk, or make a plan that incorporates both PrEP initiation and sexual risk reduction,” Dr. Beymer and his associates said.

The Center for HIV Identification, Prevention, and Treatment; the National Institute of Mental Health; and the UCLA Center for AIDS Research supported the study. Dr. Beymer and his associates reported having no relevant disclosures.

A risk-assessment tool that incorporates more data on patient and partner behavior is more specific than are the CDC criteria for initiating HIV preexposure prophylaxis and would allow more targeted treatment, according to a report published in the January issue of Sexually Transmitted Diseases.

To construct a risk-assessment tool that incorporated the most relevant information for predicting HIV acquisition, researchers collected data for all the men who have sex with men who underwent serial HIV testing at a single Los Angeles facility during a 4-year period. These 9,481 men were HIV negative at their baseline visit and were followed for a mean of 2 years (range, from less than 1 year to more than 4 years) for seroconversion, said Matthew R. Beymer, PhD, of the Los Angeles LGBT Center and the University of California, Los Angeles, and his associates.

A total of 370 of these men acquired HIV infection during 16,894 person-years of follow-up.

The investigators constructed a risk-assessment tool to guide the initiation of PrEP, which included seven factors that were the most predictive of HIV seroconversion: Hispanic or African-American ethnicity; a self-reported history of chlamydia, gonorrhea, and/or syphilis; not using a condom during their last occasion of receptive anal sex; having more than three sexual partners during the preceding month or more than five during the preceding 3 months; being of the same ethnicity as the last sexual partner; experiencing intimate partner violence; and using methamphetamines or inhaled nitrates during the preceding year.

“If all individuals in our population who had a risk score of greater than or equal to 5 (51%) had been given PrEP [at baseline], 75% of HIV infections would [have been] averted during follow-up, assuming adequate regimen adherence and near complete effectiveness,” Dr. Beymer and his associates said (Sex Transm Dis. 2017;44[1]:49-57).

In contrast, CDC criteria would have selected 69% of this cohort to begin PrEP. The additional behavioral data incorporated into the risk-assessment tool “allowed for more targeted PrEP. Physicians, their patients, and other interested individuals can obtain their own personalized risk score by visiting www.IsPrEPforMe.org,” the investigators said.

They recommend that men with a risk score of 5 or higher on this instrument begin PrEP, and strongly recommend that men with a risk score of 8 or higher do so. “For individuals whose risk score is less than 5 but who request PrEP, we believe the provider should consider it in light of their patient’s overall concerns.”

Using this tool instead of CDC criteria permits a more personalized recommendation, the authors wrote. Also, those at risk will be better informed about what actions and circumstances specifically lead to their increased HIV risk, which can aid in deciding “to initiate PrEP, reduce sexual risk, or make a plan that incorporates both PrEP initiation and sexual risk reduction,” Dr. Beymer and his associates said.

The Center for HIV Identification, Prevention, and Treatment; the National Institute of Mental Health; and the UCLA Center for AIDS Research supported the study. Dr. Beymer and his associates reported having no relevant disclosures.

A risk-assessment tool that incorporates more data on patient and partner behavior is more specific than are the CDC criteria for initiating HIV preexposure prophylaxis and would allow more targeted treatment, according to a report published in the January issue of Sexually Transmitted Diseases.

To construct a risk-assessment tool that incorporated the most relevant information for predicting HIV acquisition, researchers collected data for all the men who have sex with men who underwent serial HIV testing at a single Los Angeles facility during a 4-year period. These 9,481 men were HIV negative at their baseline visit and were followed for a mean of 2 years (range, from less than 1 year to more than 4 years) for seroconversion, said Matthew R. Beymer, PhD, of the Los Angeles LGBT Center and the University of California, Los Angeles, and his associates.

A total of 370 of these men acquired HIV infection during 16,894 person-years of follow-up.

The investigators constructed a risk-assessment tool to guide the initiation of PrEP, which included seven factors that were the most predictive of HIV seroconversion: Hispanic or African-American ethnicity; a self-reported history of chlamydia, gonorrhea, and/or syphilis; not using a condom during their last occasion of receptive anal sex; having more than three sexual partners during the preceding month or more than five during the preceding 3 months; being of the same ethnicity as the last sexual partner; experiencing intimate partner violence; and using methamphetamines or inhaled nitrates during the preceding year.

“If all individuals in our population who had a risk score of greater than or equal to 5 (51%) had been given PrEP [at baseline], 75% of HIV infections would [have been] averted during follow-up, assuming adequate regimen adherence and near complete effectiveness,” Dr. Beymer and his associates said (Sex Transm Dis. 2017;44[1]:49-57).

In contrast, CDC criteria would have selected 69% of this cohort to begin PrEP. The additional behavioral data incorporated into the risk-assessment tool “allowed for more targeted PrEP. Physicians, their patients, and other interested individuals can obtain their own personalized risk score by visiting www.IsPrEPforMe.org,” the investigators said.

They recommend that men with a risk score of 5 or higher on this instrument begin PrEP, and strongly recommend that men with a risk score of 8 or higher do so. “For individuals whose risk score is less than 5 but who request PrEP, we believe the provider should consider it in light of their patient’s overall concerns.”

Using this tool instead of CDC criteria permits a more personalized recommendation, the authors wrote. Also, those at risk will be better informed about what actions and circumstances specifically lead to their increased HIV risk, which can aid in deciding “to initiate PrEP, reduce sexual risk, or make a plan that incorporates both PrEP initiation and sexual risk reduction,” Dr. Beymer and his associates said.

The Center for HIV Identification, Prevention, and Treatment; the National Institute of Mental Health; and the UCLA Center for AIDS Research supported the study. Dr. Beymer and his associates reported having no relevant disclosures.