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OSA home testing less expensive than polysomnography
Home respiratory polygraphy had similar efficacy with substantially lower per-patient cost, compared with traditional polysomnography for diagnosing obstructive sleep apnea, a study showed.
Obstructive sleep apnea (OSA) is a common chronic disease associated with higher risk of cardiovascular disease and traffic accidents and a lower quality of life. Although expensive and time intensive, the polysomnography (PSG) has been the preferred test for diagnosing OSA. Home respiratory polygraphy (HRP) uses portable devices that are less complex than polysomnography and has been shown to have similar effectiveness in diagnosing OSA, compared with PSG, in patients with a high clinical suspicion of OSA. However, there is limited evidence for the cost effectiveness of HRP, compared with PSG (Am J Respir Crit Care Med. 2017 Nov 1;196[9]:1181-90).
The investigators conducted a multicenter, randomized controlled, noninferiority trial and cost-effectiveness analysis comparing PSG with HRP. Inclusion criteria included snoring or observed sleep apnea, Epworth Sleepiness Scale (ESS)of 10 or higher, and no suspicion of alternative causes for daytime sleepiness. Patients with a suspicion for OSA were randomized to polysomnography or respiratory polygraphy protocols. Both arms received counseling on proper sleep hygiene; counseling on weight loss, if overweight; and auto-CPAP titration if continuous positive airway pressure (CPAP) was clinically indicated.
Assessment of CPAP compliance or dietary and sleep hygiene compliance was assessed at months 1 and 3. ESS, quality of life measures, well-being measures, 24-hour blood pressure monitoring, auto accidents, and cardiovascular events were assessed at baseline and at month 6.
CPAP treatment was indicated in 68% of the PSG arm, compared with 53% of the HRP arm. After intention-to-treat analysis, there was no statistically significant difference between the two groups for ESS improvement (HRP mean, –4.2, vs. PSG mean, –4.9; P = .14). The groups demonstrated similar results for quality of life, blood pressure, polysomnographic assessment at 6 months, CPAP compliance, and rates of cardiovascular events and accidents at follow-up.
The cost-effective analysis demonstrated respiratory polygraphy was less expensive, saving more than 400 euros/patient. “Because the effectiveness (ESS and QALYs [quality-adjusted life-years]) was similar between arms, the HRP protocol is preferable due to its lower cost,” the authors wrote.
In all, 430 patients were randomized to HRP or PSG and consisted mostly of men (70.5%) with a mean body mass index of 30.7 kg/m2. The groups had similar rates of alcohol consumption and hypertension.
Limitations of the study included unblinded randomization to the participants and researchers and the possibility of variability in therapeutic decisions. However, the authors noted that intraobserver variability was minimized by using the Spanish Sleep Network guidelines and centralized assessment.
“[The] HRP management protocol is not inferior to PSG and presents substantially lower costs. Therefore, PSG is not necessary for most patients with suspicion of OSA. This finding could change established clinical practice, with a clear economic benefit,” the authors concluded.
Home respiratory polygraphy continues to impress
This study adds strong evidence to support the use of home respiratory polygraphy for the diagnosis of obstructive sleep apnea in patients without major comorbidities such as severe chronic restrictive or obstructive lung disease, heart failure or unstable cardiovascular disease, major psychiatric diagnoses, and neuromuscular conditions, noted Ching Li Chai-Coetzer, MBBS, PhD, and R.
Doug McEvoy, MBBS, MD, in an accompanying editorial (Am J Respir Crit Care Med. 2017 Nov 1;196[9]:1096-8). However, lower-cost methods to diagnose OSA would still not address unmet needs such as the cost of continuous positive airway pressure and scarcity of sleep physicians to assess patients with OSA, and still may be too expensive for underresourced populations, they said.
Dr. Chai-Coetzer and Dr. McEvoy are affiliated with the Adelaide Institute for Sleep Health at Flinders University and the Sleep Health Service, Southern Adelaide Local Health Network, both in South Australia.
The study was supported by Sociedad Española de Neumología, Air Liquide (Spain), Asociacion de Neumologos del Sur, and Sociedad Extremeña de Neumología. The investigators report no disclosures.
Dr. Chai-Coetzer reported grants from National Health and Medical Research Council of Australia and nonfinancial support from Biotech Pharmaceuticals. Dr. McEvoy reported grants and nonfinancial support from Philips Respironics, nonfinancial support from ResMed, and grants from Fisher & Paykel.
Home respiratory polygraphy had similar efficacy with substantially lower per-patient cost, compared with traditional polysomnography for diagnosing obstructive sleep apnea, a study showed.
Obstructive sleep apnea (OSA) is a common chronic disease associated with higher risk of cardiovascular disease and traffic accidents and a lower quality of life. Although expensive and time intensive, the polysomnography (PSG) has been the preferred test for diagnosing OSA. Home respiratory polygraphy (HRP) uses portable devices that are less complex than polysomnography and has been shown to have similar effectiveness in diagnosing OSA, compared with PSG, in patients with a high clinical suspicion of OSA. However, there is limited evidence for the cost effectiveness of HRP, compared with PSG (Am J Respir Crit Care Med. 2017 Nov 1;196[9]:1181-90).
The investigators conducted a multicenter, randomized controlled, noninferiority trial and cost-effectiveness analysis comparing PSG with HRP. Inclusion criteria included snoring or observed sleep apnea, Epworth Sleepiness Scale (ESS)of 10 or higher, and no suspicion of alternative causes for daytime sleepiness. Patients with a suspicion for OSA were randomized to polysomnography or respiratory polygraphy protocols. Both arms received counseling on proper sleep hygiene; counseling on weight loss, if overweight; and auto-CPAP titration if continuous positive airway pressure (CPAP) was clinically indicated.
Assessment of CPAP compliance or dietary and sleep hygiene compliance was assessed at months 1 and 3. ESS, quality of life measures, well-being measures, 24-hour blood pressure monitoring, auto accidents, and cardiovascular events were assessed at baseline and at month 6.
CPAP treatment was indicated in 68% of the PSG arm, compared with 53% of the HRP arm. After intention-to-treat analysis, there was no statistically significant difference between the two groups for ESS improvement (HRP mean, –4.2, vs. PSG mean, –4.9; P = .14). The groups demonstrated similar results for quality of life, blood pressure, polysomnographic assessment at 6 months, CPAP compliance, and rates of cardiovascular events and accidents at follow-up.
The cost-effective analysis demonstrated respiratory polygraphy was less expensive, saving more than 400 euros/patient. “Because the effectiveness (ESS and QALYs [quality-adjusted life-years]) was similar between arms, the HRP protocol is preferable due to its lower cost,” the authors wrote.
In all, 430 patients were randomized to HRP or PSG and consisted mostly of men (70.5%) with a mean body mass index of 30.7 kg/m2. The groups had similar rates of alcohol consumption and hypertension.
Limitations of the study included unblinded randomization to the participants and researchers and the possibility of variability in therapeutic decisions. However, the authors noted that intraobserver variability was minimized by using the Spanish Sleep Network guidelines and centralized assessment.
“[The] HRP management protocol is not inferior to PSG and presents substantially lower costs. Therefore, PSG is not necessary for most patients with suspicion of OSA. This finding could change established clinical practice, with a clear economic benefit,” the authors concluded.
Home respiratory polygraphy continues to impress
This study adds strong evidence to support the use of home respiratory polygraphy for the diagnosis of obstructive sleep apnea in patients without major comorbidities such as severe chronic restrictive or obstructive lung disease, heart failure or unstable cardiovascular disease, major psychiatric diagnoses, and neuromuscular conditions, noted Ching Li Chai-Coetzer, MBBS, PhD, and R.
Doug McEvoy, MBBS, MD, in an accompanying editorial (Am J Respir Crit Care Med. 2017 Nov 1;196[9]:1096-8). However, lower-cost methods to diagnose OSA would still not address unmet needs such as the cost of continuous positive airway pressure and scarcity of sleep physicians to assess patients with OSA, and still may be too expensive for underresourced populations, they said.
Dr. Chai-Coetzer and Dr. McEvoy are affiliated with the Adelaide Institute for Sleep Health at Flinders University and the Sleep Health Service, Southern Adelaide Local Health Network, both in South Australia.
The study was supported by Sociedad Española de Neumología, Air Liquide (Spain), Asociacion de Neumologos del Sur, and Sociedad Extremeña de Neumología. The investigators report no disclosures.
Dr. Chai-Coetzer reported grants from National Health and Medical Research Council of Australia and nonfinancial support from Biotech Pharmaceuticals. Dr. McEvoy reported grants and nonfinancial support from Philips Respironics, nonfinancial support from ResMed, and grants from Fisher & Paykel.
Home respiratory polygraphy had similar efficacy with substantially lower per-patient cost, compared with traditional polysomnography for diagnosing obstructive sleep apnea, a study showed.
Obstructive sleep apnea (OSA) is a common chronic disease associated with higher risk of cardiovascular disease and traffic accidents and a lower quality of life. Although expensive and time intensive, the polysomnography (PSG) has been the preferred test for diagnosing OSA. Home respiratory polygraphy (HRP) uses portable devices that are less complex than polysomnography and has been shown to have similar effectiveness in diagnosing OSA, compared with PSG, in patients with a high clinical suspicion of OSA. However, there is limited evidence for the cost effectiveness of HRP, compared with PSG (Am J Respir Crit Care Med. 2017 Nov 1;196[9]:1181-90).
The investigators conducted a multicenter, randomized controlled, noninferiority trial and cost-effectiveness analysis comparing PSG with HRP. Inclusion criteria included snoring or observed sleep apnea, Epworth Sleepiness Scale (ESS)of 10 or higher, and no suspicion of alternative causes for daytime sleepiness. Patients with a suspicion for OSA were randomized to polysomnography or respiratory polygraphy protocols. Both arms received counseling on proper sleep hygiene; counseling on weight loss, if overweight; and auto-CPAP titration if continuous positive airway pressure (CPAP) was clinically indicated.
Assessment of CPAP compliance or dietary and sleep hygiene compliance was assessed at months 1 and 3. ESS, quality of life measures, well-being measures, 24-hour blood pressure monitoring, auto accidents, and cardiovascular events were assessed at baseline and at month 6.
CPAP treatment was indicated in 68% of the PSG arm, compared with 53% of the HRP arm. After intention-to-treat analysis, there was no statistically significant difference between the two groups for ESS improvement (HRP mean, –4.2, vs. PSG mean, –4.9; P = .14). The groups demonstrated similar results for quality of life, blood pressure, polysomnographic assessment at 6 months, CPAP compliance, and rates of cardiovascular events and accidents at follow-up.
The cost-effective analysis demonstrated respiratory polygraphy was less expensive, saving more than 400 euros/patient. “Because the effectiveness (ESS and QALYs [quality-adjusted life-years]) was similar between arms, the HRP protocol is preferable due to its lower cost,” the authors wrote.
In all, 430 patients were randomized to HRP or PSG and consisted mostly of men (70.5%) with a mean body mass index of 30.7 kg/m2. The groups had similar rates of alcohol consumption and hypertension.
Limitations of the study included unblinded randomization to the participants and researchers and the possibility of variability in therapeutic decisions. However, the authors noted that intraobserver variability was minimized by using the Spanish Sleep Network guidelines and centralized assessment.
“[The] HRP management protocol is not inferior to PSG and presents substantially lower costs. Therefore, PSG is not necessary for most patients with suspicion of OSA. This finding could change established clinical practice, with a clear economic benefit,” the authors concluded.
Home respiratory polygraphy continues to impress
This study adds strong evidence to support the use of home respiratory polygraphy for the diagnosis of obstructive sleep apnea in patients without major comorbidities such as severe chronic restrictive or obstructive lung disease, heart failure or unstable cardiovascular disease, major psychiatric diagnoses, and neuromuscular conditions, noted Ching Li Chai-Coetzer, MBBS, PhD, and R.
Doug McEvoy, MBBS, MD, in an accompanying editorial (Am J Respir Crit Care Med. 2017 Nov 1;196[9]:1096-8). However, lower-cost methods to diagnose OSA would still not address unmet needs such as the cost of continuous positive airway pressure and scarcity of sleep physicians to assess patients with OSA, and still may be too expensive for underresourced populations, they said.
Dr. Chai-Coetzer and Dr. McEvoy are affiliated with the Adelaide Institute for Sleep Health at Flinders University and the Sleep Health Service, Southern Adelaide Local Health Network, both in South Australia.
The study was supported by Sociedad Española de Neumología, Air Liquide (Spain), Asociacion de Neumologos del Sur, and Sociedad Extremeña de Neumología. The investigators report no disclosures.
Dr. Chai-Coetzer reported grants from National Health and Medical Research Council of Australia and nonfinancial support from Biotech Pharmaceuticals. Dr. McEvoy reported grants and nonfinancial support from Philips Respironics, nonfinancial support from ResMed, and grants from Fisher & Paykel.
FROM THE AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
Key clinical point: Home obstructive sleep apnea testing was less costly and noninferior to polysomnography.
Major finding: Using respiratory polygraphy instead of polysomnography results in savings of more than 400 euros/patient.
Data source: A multicenter, randomized controlled, noninferiority trial and cost-effectiveness analysis of 430 patients suspected of having OSA.
Disclosures: The study was supported by Sociedad Española de Neumología, Air Liquide (Spain), Asociacion de Neumologos del Sur, and Sociedad Extremeña de Neumología. The authors report no disclosures.
Neoantigen profiling predicts response to immunotherapy
In antitumor immunity and immunotherapy, quality and fitness count.
Specifically, the quality and fitness of neoantigens – tumor-specific mutated peptides on the surface of cancer cells – can influence a patient’s response to immune checkpoint inhibitors, and mathematical models of neoantigen fitness can serve as biomarkers for response to immunotherapy, according to investigators of two separate but related studies published in Nature.
In one study, Marta Łuksza, PhD, from the Simons Center for Systems Biology at the Institute for Advanced Study in Princeton, N.J., and colleagues propose a neoantigen fitness model that can predict tumor response to checkpoint blockade immunotherapy.
Importantly, low-fitness neoantigens identified by our method may be leveraged for developing novel immunotherapies,” they wrote (Nature. 2017 Nov 8. doi: 10.1038/nature24473).
In a related study, Vinod P. Balachandran, MD, from the David M. Rubinstein Center for Pancreatic Cancer Research at Memorial Sloan Kettering Cancer Center in New York and colleagues, including Dr. Łuksza and others, looked at T-cell antigens in long-term survivors of pancreatic cancer and identified specific neoantigens as T-cell targets.
“More broadly, we identify neoantigen quality as a biomarker for immunogenic tumors that may guide the application of immunotherapies,” Dr. Balachandran and colleagues wrote (Nature. 2017 Nov 8. doi: 10.1038/nature24462).
Proof of concept
The studies provide a proof of concept that mathematical modeling of tumor evolution and the interactions of tumors with the immune system may soon provide clinicians with valuable and actionable information about responses to immunotherapy, Benjamin Greenbaum, PhD, senior author on the study by Łuksza et al., and a coauthor on the pancreatic cancer study said in an interview.
“We’re trying to come up with measures that take into account what we think the underlying processes are and what lies behind therapy response, and that should lead to better predictive models associated with response in the future,” said Dr. Greenbaum, of the Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai Medical Center, New York.
One of the key findings of the studies is that neoantigen quality – the ability of neoantigens to spark T-cell recognition – seems to be as or more important than neoantigen quantity for influencing immune responses during tumor evolution.
“The general logic behind the idea that mutational burden can be a good predictor of response is that the more mutations you have, the more likely that you have a neoantigen, a peptide generated by a tumor mutation, that elicits productive T-cell recognition. We tried to model that process that might lead to productive T-cell recognition, to assign a kind of number to every neoantigen to provide some estimate of how likely it was to undergo a productive process,” Dr. Greenbaum explained.
Melanoma and lung cancer survivors
In the study by Łuksza et al., the investigators created a mathematical fitness model that can predict how tumors respond to immunotherapy based on how neoantigens interact with the immune system and applied the model to data on three previously reported patient cohorts, including two groups of patients with malignant melanoma treated with a cytotoxic T-lymphocyte associated protein 4 (CTLA4) immune checkpoint such as ipilimumab (Yervoy), and one group of patients with non–small cell lung cancer treated with a programmed death-1 (PD-1) inhibitor (for example, nivolumab [Opdivo]).
They found that their proposed model is more accurate than genomic biomarkers for predicting how a specific tumor may respond to immunotherapy.
“Importantly, low-fitness neoantigens identified by our method may be leveraged for developing novel immunotherapies. By using an immune fitness model to study immunotherapy, we reveal broad similarities between the evolution of tumors and rapidly evolving pathogens,” they wrote.
Pancreatic cancer survivors
Fewer than 7% of patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) survive more than 5 years, despite the best surgical and medical therapy. But a few lucky patients are long-term survivors, and Dr. Balachandran and associates sought to examine what aspects of T-cell immunity contributed to their longevity.
Rather than relying on genomic analysis of tumor samples, however, they used a combination of genetic, immunohistochemical, and transcriptional immunoprofiling, as well as computational biophysics and function to identify T-cell antigens in the long-term survivors.
When they compared surgically resected patients matched by tumor stage, they found that tumors from those with a median overall survival (OS) of 6 years had a 3-fold greater density of CD8-positive T cells and a 12-fold greater density of cytolytic CD8-positive cells, as well as more mature dendritic cells, regulatory T cells, and macrophages, but decreased numbers of CD4-positive T cells, compared with patients with a more typical course of survival (median OS, 0.8 years). There were no differences between long- and short-term survivors in either B cells or major histocompatibility complex (MHC) class I–positive cells.
They then performed whole-exome sequencing on tumor samples to determine the frequency of neoantigens and found a median of 38 predicted neoantigens per tumor.
“Notably, patients with both the highest predicted neoantigen number and either the greatest CD3+, CD8+, or polyclonal T-cell repertoire, but neither alone, exhibited the longest survival,” they wrote.
When they looked for qualities of neoantigens responsible for promoting T-cell activation in the long-term survivors, they found that the tumors from the survivors, compared with others, were enriched in neoantigen qualities that could be described by a mathematical fitness model.
“Our results provide insight into the heterogeneous immunobiology of PDAC, a presumed poorly immunogenic and checkpoint blockade–refractory tumor, demonstrating that neoantigens may be T-cell targets in [long-term survivors]”, they wrote.
The investigators propose that immunity to neoantigens that are generated during the outgrowth of a primary tumor could at least partially explain the lower incidence of relapse and prolonged survival of a small minority of patients with pancreatic cancer.
“Our findings support the development of strategies to harness neoantigen-specific immunity to treat checkpoint blockade–refractory cancers, and the identification of immunogenic hot spots for directed neoantigen targeting,” they concluded.
The studies were supported by grants from Stand Up to Cancer, American Cancer Society, National Science Foundation, Lustgarten Foundation, Janssen Research & Development, the STARR Cancer Consortium, the Pershing Square Sohn Cancer Research Alliance, the National Institutes of Health, the V Foundation, Swim Across America, Ludwig Institute for Cancer Research, the Parker Institute for Cancer Immunotherapy, a National Cancer Institute Career Development Award, and a Memorial Sloan Kettering Cancer Center core grant. Dr. Łuksza and Dr. Greenbaum disclosed consulting for Merck. Dr. Balachandran disclosed research funding from Bristol-Myers Squibb.
In antitumor immunity and immunotherapy, quality and fitness count.
Specifically, the quality and fitness of neoantigens – tumor-specific mutated peptides on the surface of cancer cells – can influence a patient’s response to immune checkpoint inhibitors, and mathematical models of neoantigen fitness can serve as biomarkers for response to immunotherapy, according to investigators of two separate but related studies published in Nature.
In one study, Marta Łuksza, PhD, from the Simons Center for Systems Biology at the Institute for Advanced Study in Princeton, N.J., and colleagues propose a neoantigen fitness model that can predict tumor response to checkpoint blockade immunotherapy.
Importantly, low-fitness neoantigens identified by our method may be leveraged for developing novel immunotherapies,” they wrote (Nature. 2017 Nov 8. doi: 10.1038/nature24473).
In a related study, Vinod P. Balachandran, MD, from the David M. Rubinstein Center for Pancreatic Cancer Research at Memorial Sloan Kettering Cancer Center in New York and colleagues, including Dr. Łuksza and others, looked at T-cell antigens in long-term survivors of pancreatic cancer and identified specific neoantigens as T-cell targets.
“More broadly, we identify neoantigen quality as a biomarker for immunogenic tumors that may guide the application of immunotherapies,” Dr. Balachandran and colleagues wrote (Nature. 2017 Nov 8. doi: 10.1038/nature24462).
Proof of concept
The studies provide a proof of concept that mathematical modeling of tumor evolution and the interactions of tumors with the immune system may soon provide clinicians with valuable and actionable information about responses to immunotherapy, Benjamin Greenbaum, PhD, senior author on the study by Łuksza et al., and a coauthor on the pancreatic cancer study said in an interview.
“We’re trying to come up with measures that take into account what we think the underlying processes are and what lies behind therapy response, and that should lead to better predictive models associated with response in the future,” said Dr. Greenbaum, of the Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai Medical Center, New York.
One of the key findings of the studies is that neoantigen quality – the ability of neoantigens to spark T-cell recognition – seems to be as or more important than neoantigen quantity for influencing immune responses during tumor evolution.
“The general logic behind the idea that mutational burden can be a good predictor of response is that the more mutations you have, the more likely that you have a neoantigen, a peptide generated by a tumor mutation, that elicits productive T-cell recognition. We tried to model that process that might lead to productive T-cell recognition, to assign a kind of number to every neoantigen to provide some estimate of how likely it was to undergo a productive process,” Dr. Greenbaum explained.
Melanoma and lung cancer survivors
In the study by Łuksza et al., the investigators created a mathematical fitness model that can predict how tumors respond to immunotherapy based on how neoantigens interact with the immune system and applied the model to data on three previously reported patient cohorts, including two groups of patients with malignant melanoma treated with a cytotoxic T-lymphocyte associated protein 4 (CTLA4) immune checkpoint such as ipilimumab (Yervoy), and one group of patients with non–small cell lung cancer treated with a programmed death-1 (PD-1) inhibitor (for example, nivolumab [Opdivo]).
They found that their proposed model is more accurate than genomic biomarkers for predicting how a specific tumor may respond to immunotherapy.
“Importantly, low-fitness neoantigens identified by our method may be leveraged for developing novel immunotherapies. By using an immune fitness model to study immunotherapy, we reveal broad similarities between the evolution of tumors and rapidly evolving pathogens,” they wrote.
Pancreatic cancer survivors
Fewer than 7% of patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) survive more than 5 years, despite the best surgical and medical therapy. But a few lucky patients are long-term survivors, and Dr. Balachandran and associates sought to examine what aspects of T-cell immunity contributed to their longevity.
Rather than relying on genomic analysis of tumor samples, however, they used a combination of genetic, immunohistochemical, and transcriptional immunoprofiling, as well as computational biophysics and function to identify T-cell antigens in the long-term survivors.
When they compared surgically resected patients matched by tumor stage, they found that tumors from those with a median overall survival (OS) of 6 years had a 3-fold greater density of CD8-positive T cells and a 12-fold greater density of cytolytic CD8-positive cells, as well as more mature dendritic cells, regulatory T cells, and macrophages, but decreased numbers of CD4-positive T cells, compared with patients with a more typical course of survival (median OS, 0.8 years). There were no differences between long- and short-term survivors in either B cells or major histocompatibility complex (MHC) class I–positive cells.
They then performed whole-exome sequencing on tumor samples to determine the frequency of neoantigens and found a median of 38 predicted neoantigens per tumor.
“Notably, patients with both the highest predicted neoantigen number and either the greatest CD3+, CD8+, or polyclonal T-cell repertoire, but neither alone, exhibited the longest survival,” they wrote.
When they looked for qualities of neoantigens responsible for promoting T-cell activation in the long-term survivors, they found that the tumors from the survivors, compared with others, were enriched in neoantigen qualities that could be described by a mathematical fitness model.
“Our results provide insight into the heterogeneous immunobiology of PDAC, a presumed poorly immunogenic and checkpoint blockade–refractory tumor, demonstrating that neoantigens may be T-cell targets in [long-term survivors]”, they wrote.
The investigators propose that immunity to neoantigens that are generated during the outgrowth of a primary tumor could at least partially explain the lower incidence of relapse and prolonged survival of a small minority of patients with pancreatic cancer.
“Our findings support the development of strategies to harness neoantigen-specific immunity to treat checkpoint blockade–refractory cancers, and the identification of immunogenic hot spots for directed neoantigen targeting,” they concluded.
The studies were supported by grants from Stand Up to Cancer, American Cancer Society, National Science Foundation, Lustgarten Foundation, Janssen Research & Development, the STARR Cancer Consortium, the Pershing Square Sohn Cancer Research Alliance, the National Institutes of Health, the V Foundation, Swim Across America, Ludwig Institute for Cancer Research, the Parker Institute for Cancer Immunotherapy, a National Cancer Institute Career Development Award, and a Memorial Sloan Kettering Cancer Center core grant. Dr. Łuksza and Dr. Greenbaum disclosed consulting for Merck. Dr. Balachandran disclosed research funding from Bristol-Myers Squibb.
In antitumor immunity and immunotherapy, quality and fitness count.
Specifically, the quality and fitness of neoantigens – tumor-specific mutated peptides on the surface of cancer cells – can influence a patient’s response to immune checkpoint inhibitors, and mathematical models of neoantigen fitness can serve as biomarkers for response to immunotherapy, according to investigators of two separate but related studies published in Nature.
In one study, Marta Łuksza, PhD, from the Simons Center for Systems Biology at the Institute for Advanced Study in Princeton, N.J., and colleagues propose a neoantigen fitness model that can predict tumor response to checkpoint blockade immunotherapy.
Importantly, low-fitness neoantigens identified by our method may be leveraged for developing novel immunotherapies,” they wrote (Nature. 2017 Nov 8. doi: 10.1038/nature24473).
In a related study, Vinod P. Balachandran, MD, from the David M. Rubinstein Center for Pancreatic Cancer Research at Memorial Sloan Kettering Cancer Center in New York and colleagues, including Dr. Łuksza and others, looked at T-cell antigens in long-term survivors of pancreatic cancer and identified specific neoantigens as T-cell targets.
“More broadly, we identify neoantigen quality as a biomarker for immunogenic tumors that may guide the application of immunotherapies,” Dr. Balachandran and colleagues wrote (Nature. 2017 Nov 8. doi: 10.1038/nature24462).
Proof of concept
The studies provide a proof of concept that mathematical modeling of tumor evolution and the interactions of tumors with the immune system may soon provide clinicians with valuable and actionable information about responses to immunotherapy, Benjamin Greenbaum, PhD, senior author on the study by Łuksza et al., and a coauthor on the pancreatic cancer study said in an interview.
“We’re trying to come up with measures that take into account what we think the underlying processes are and what lies behind therapy response, and that should lead to better predictive models associated with response in the future,” said Dr. Greenbaum, of the Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai Medical Center, New York.
One of the key findings of the studies is that neoantigen quality – the ability of neoantigens to spark T-cell recognition – seems to be as or more important than neoantigen quantity for influencing immune responses during tumor evolution.
“The general logic behind the idea that mutational burden can be a good predictor of response is that the more mutations you have, the more likely that you have a neoantigen, a peptide generated by a tumor mutation, that elicits productive T-cell recognition. We tried to model that process that might lead to productive T-cell recognition, to assign a kind of number to every neoantigen to provide some estimate of how likely it was to undergo a productive process,” Dr. Greenbaum explained.
Melanoma and lung cancer survivors
In the study by Łuksza et al., the investigators created a mathematical fitness model that can predict how tumors respond to immunotherapy based on how neoantigens interact with the immune system and applied the model to data on three previously reported patient cohorts, including two groups of patients with malignant melanoma treated with a cytotoxic T-lymphocyte associated protein 4 (CTLA4) immune checkpoint such as ipilimumab (Yervoy), and one group of patients with non–small cell lung cancer treated with a programmed death-1 (PD-1) inhibitor (for example, nivolumab [Opdivo]).
They found that their proposed model is more accurate than genomic biomarkers for predicting how a specific tumor may respond to immunotherapy.
“Importantly, low-fitness neoantigens identified by our method may be leveraged for developing novel immunotherapies. By using an immune fitness model to study immunotherapy, we reveal broad similarities between the evolution of tumors and rapidly evolving pathogens,” they wrote.
Pancreatic cancer survivors
Fewer than 7% of patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) survive more than 5 years, despite the best surgical and medical therapy. But a few lucky patients are long-term survivors, and Dr. Balachandran and associates sought to examine what aspects of T-cell immunity contributed to their longevity.
Rather than relying on genomic analysis of tumor samples, however, they used a combination of genetic, immunohistochemical, and transcriptional immunoprofiling, as well as computational biophysics and function to identify T-cell antigens in the long-term survivors.
When they compared surgically resected patients matched by tumor stage, they found that tumors from those with a median overall survival (OS) of 6 years had a 3-fold greater density of CD8-positive T cells and a 12-fold greater density of cytolytic CD8-positive cells, as well as more mature dendritic cells, regulatory T cells, and macrophages, but decreased numbers of CD4-positive T cells, compared with patients with a more typical course of survival (median OS, 0.8 years). There were no differences between long- and short-term survivors in either B cells or major histocompatibility complex (MHC) class I–positive cells.
They then performed whole-exome sequencing on tumor samples to determine the frequency of neoantigens and found a median of 38 predicted neoantigens per tumor.
“Notably, patients with both the highest predicted neoantigen number and either the greatest CD3+, CD8+, or polyclonal T-cell repertoire, but neither alone, exhibited the longest survival,” they wrote.
When they looked for qualities of neoantigens responsible for promoting T-cell activation in the long-term survivors, they found that the tumors from the survivors, compared with others, were enriched in neoantigen qualities that could be described by a mathematical fitness model.
“Our results provide insight into the heterogeneous immunobiology of PDAC, a presumed poorly immunogenic and checkpoint blockade–refractory tumor, demonstrating that neoantigens may be T-cell targets in [long-term survivors]”, they wrote.
The investigators propose that immunity to neoantigens that are generated during the outgrowth of a primary tumor could at least partially explain the lower incidence of relapse and prolonged survival of a small minority of patients with pancreatic cancer.
“Our findings support the development of strategies to harness neoantigen-specific immunity to treat checkpoint blockade–refractory cancers, and the identification of immunogenic hot spots for directed neoantigen targeting,” they concluded.
The studies were supported by grants from Stand Up to Cancer, American Cancer Society, National Science Foundation, Lustgarten Foundation, Janssen Research & Development, the STARR Cancer Consortium, the Pershing Square Sohn Cancer Research Alliance, the National Institutes of Health, the V Foundation, Swim Across America, Ludwig Institute for Cancer Research, the Parker Institute for Cancer Immunotherapy, a National Cancer Institute Career Development Award, and a Memorial Sloan Kettering Cancer Center core grant. Dr. Łuksza and Dr. Greenbaum disclosed consulting for Merck. Dr. Balachandran disclosed research funding from Bristol-Myers Squibb.
FROM NATURE
Key clinical point: Proof-of-concept studies show that mathematical modeling of neoantigens can be used to predict tumor responses to immune checkpoint inhibitors.
Major finding: Neoantigen quality may be a better biomarker for guiding immunotherapy than tumor genomic profiling.
Data source: Basic science reports focusing on neoantigens and their potential influence on tumor interactions with the immune system.
Disclosures: The studies were supported by grants from Stand Up to Cancer, American Cancer Society, National Science Foundation, Lustgarten Foundation, Janssen Research & Development, the STARR Cancer Consortium, the Pershing Square Sohn Cancer Research Alliance, the National Institutes of Health, the V Foundation, Swim Across America, Ludwig Institute for Cancer Research, the Parker Institute for Cancer Immunotherapy, a National Cancer Institute Career Development Award, and a Memorial Sloan Kettering Cancer Center core grant. Dr. Łuksza and Dr. Greenbaum disclosed consulting for Merck. Dr. Balachandran disclosed research funding from Bristol-Myers Squibb.
FDA approves alectinib as frontline therapy for ALK-positive metastatic NSCLC
The Food and Drug Administration has approved frontline alectinib for the treatment of anaplastic lymphoma kinase (ALK)–positive metastatic non–small cell lung cancer (NSCLC) that has been detected by an FDA-approved test.
The drug previously received accelerated approval for treatment of patients with ALK-positive metastatic NSCLC whose disease progressed while receiving crizotinib or who were intolerant of that treatment.
There was also a lower incidence of progression to the central nervous system as first site of disease progression with alectinib: Incidence of progression to the CNS was 12% for patients receiving alectinib and 45% for patients receiving crizotinib.
The most common adverse events in patients receiving alectinib were fatigue, constipation, edema, myalgia, and anemia. Serious adverse events occurred in 28% of patients. Adverse events resulting in discontinuation occurred in 11% of patients.
“All patients in the trial were required to have evidence of ALK-rearrangement identified by the VENTANA ALK (D5F3) CDx Assay performed through central laboratory testing,” the FDA said in a press statement.
The recommended dose is 600 mg orally taken twice daily with food.
The Food and Drug Administration has approved frontline alectinib for the treatment of anaplastic lymphoma kinase (ALK)–positive metastatic non–small cell lung cancer (NSCLC) that has been detected by an FDA-approved test.
The drug previously received accelerated approval for treatment of patients with ALK-positive metastatic NSCLC whose disease progressed while receiving crizotinib or who were intolerant of that treatment.
There was also a lower incidence of progression to the central nervous system as first site of disease progression with alectinib: Incidence of progression to the CNS was 12% for patients receiving alectinib and 45% for patients receiving crizotinib.
The most common adverse events in patients receiving alectinib were fatigue, constipation, edema, myalgia, and anemia. Serious adverse events occurred in 28% of patients. Adverse events resulting in discontinuation occurred in 11% of patients.
“All patients in the trial were required to have evidence of ALK-rearrangement identified by the VENTANA ALK (D5F3) CDx Assay performed through central laboratory testing,” the FDA said in a press statement.
The recommended dose is 600 mg orally taken twice daily with food.
The Food and Drug Administration has approved frontline alectinib for the treatment of anaplastic lymphoma kinase (ALK)–positive metastatic non–small cell lung cancer (NSCLC) that has been detected by an FDA-approved test.
The drug previously received accelerated approval for treatment of patients with ALK-positive metastatic NSCLC whose disease progressed while receiving crizotinib or who were intolerant of that treatment.
There was also a lower incidence of progression to the central nervous system as first site of disease progression with alectinib: Incidence of progression to the CNS was 12% for patients receiving alectinib and 45% for patients receiving crizotinib.
The most common adverse events in patients receiving alectinib were fatigue, constipation, edema, myalgia, and anemia. Serious adverse events occurred in 28% of patients. Adverse events resulting in discontinuation occurred in 11% of patients.
“All patients in the trial were required to have evidence of ALK-rearrangement identified by the VENTANA ALK (D5F3) CDx Assay performed through central laboratory testing,” the FDA said in a press statement.
The recommended dose is 600 mg orally taken twice daily with food.
Warfarin may protect against cancer
Warfarin, the most frequently used anticoagulant worldwide, may be associated with a lower incidence of cancer incidence across a broad range of cancer types, according to results of a large, retrospective population-based cohort study.
Compared with non-users, warfarin users had a significantly lower rate of cancer overall (age- and sex-adjusted incidence rate ratio [IRR], .84; 95% CI, 0.82-0.86) and in common organ-specific cancer sites, according to the study, which included nearly 1.3 million individuals over 50 years of age in the Norwegian National Registry.
“An unintended consequence of this switch to new oral anticoagulants may be an increased incidence of cancer, which is an important consideration for public health,” Gry S. Haaland, MD, Department of Biomedicine, University of Bergen, Norway and her colleagues wrote in the report.
The study included population registry data on nearly 1.3 million Norwegians, correlated with more data from a prescription database and cancer registry in that country.
While there was no correlation between warfarin use and colon cancer, there were significantly reduced age- and sex-adjusted IRRs associated with other common organ-specific sites such as lung (.80); prostate (.69); and breast (.90), Dr. Haaland and her colleagues reported.
A subgroup analysis of the 33,313 patients (35.8%) with atrial fibrillation showed a significantly lower IRR for all cancer sites (IRR, .625) and most prevalent sites (compared with nonusers): IRR for prostate was.60; lung was.39; and the IRR for female breast cancer was .72.
The potential anticancer effects of warfarin have been suggested in various experimental cancer models. In particular, warfarin at doses not reaching anticoagulation levels has been shown to inhibits AXL receptor tyrosine kinase–dependent tumorigenesis, the authors said.
Beyond those models, there have been “conflicting conclusions” in the medical literature regarding whether warfarin protects against cancer, they added.
While some studies have shown no such association, Dr. Haaland and colleagues say they used a “stricter definition” of warfarin use that included at least 6 months of a warfarin prescription. Moreover, they only counted cancer cases that were diagnosed at least 2 years after the first prescription.
“Our data indicate that warfarin provides a possible cancer protection, a finding that may have important implications for choosing medications for patients who need anticoagulation,” the authors concluded.
However, further study is needed to better understand the mechanisms by which warfarin exerts this protective effect, they added.
Warfarin, the most frequently used anticoagulant worldwide, may be associated with a lower incidence of cancer incidence across a broad range of cancer types, according to results of a large, retrospective population-based cohort study.
Compared with non-users, warfarin users had a significantly lower rate of cancer overall (age- and sex-adjusted incidence rate ratio [IRR], .84; 95% CI, 0.82-0.86) and in common organ-specific cancer sites, according to the study, which included nearly 1.3 million individuals over 50 years of age in the Norwegian National Registry.
“An unintended consequence of this switch to new oral anticoagulants may be an increased incidence of cancer, which is an important consideration for public health,” Gry S. Haaland, MD, Department of Biomedicine, University of Bergen, Norway and her colleagues wrote in the report.
The study included population registry data on nearly 1.3 million Norwegians, correlated with more data from a prescription database and cancer registry in that country.
While there was no correlation between warfarin use and colon cancer, there were significantly reduced age- and sex-adjusted IRRs associated with other common organ-specific sites such as lung (.80); prostate (.69); and breast (.90), Dr. Haaland and her colleagues reported.
A subgroup analysis of the 33,313 patients (35.8%) with atrial fibrillation showed a significantly lower IRR for all cancer sites (IRR, .625) and most prevalent sites (compared with nonusers): IRR for prostate was.60; lung was.39; and the IRR for female breast cancer was .72.
The potential anticancer effects of warfarin have been suggested in various experimental cancer models. In particular, warfarin at doses not reaching anticoagulation levels has been shown to inhibits AXL receptor tyrosine kinase–dependent tumorigenesis, the authors said.
Beyond those models, there have been “conflicting conclusions” in the medical literature regarding whether warfarin protects against cancer, they added.
While some studies have shown no such association, Dr. Haaland and colleagues say they used a “stricter definition” of warfarin use that included at least 6 months of a warfarin prescription. Moreover, they only counted cancer cases that were diagnosed at least 2 years after the first prescription.
“Our data indicate that warfarin provides a possible cancer protection, a finding that may have important implications for choosing medications for patients who need anticoagulation,” the authors concluded.
However, further study is needed to better understand the mechanisms by which warfarin exerts this protective effect, they added.
Warfarin, the most frequently used anticoagulant worldwide, may be associated with a lower incidence of cancer incidence across a broad range of cancer types, according to results of a large, retrospective population-based cohort study.
Compared with non-users, warfarin users had a significantly lower rate of cancer overall (age- and sex-adjusted incidence rate ratio [IRR], .84; 95% CI, 0.82-0.86) and in common organ-specific cancer sites, according to the study, which included nearly 1.3 million individuals over 50 years of age in the Norwegian National Registry.
“An unintended consequence of this switch to new oral anticoagulants may be an increased incidence of cancer, which is an important consideration for public health,” Gry S. Haaland, MD, Department of Biomedicine, University of Bergen, Norway and her colleagues wrote in the report.
The study included population registry data on nearly 1.3 million Norwegians, correlated with more data from a prescription database and cancer registry in that country.
While there was no correlation between warfarin use and colon cancer, there were significantly reduced age- and sex-adjusted IRRs associated with other common organ-specific sites such as lung (.80); prostate (.69); and breast (.90), Dr. Haaland and her colleagues reported.
A subgroup analysis of the 33,313 patients (35.8%) with atrial fibrillation showed a significantly lower IRR for all cancer sites (IRR, .625) and most prevalent sites (compared with nonusers): IRR for prostate was.60; lung was.39; and the IRR for female breast cancer was .72.
The potential anticancer effects of warfarin have been suggested in various experimental cancer models. In particular, warfarin at doses not reaching anticoagulation levels has been shown to inhibits AXL receptor tyrosine kinase–dependent tumorigenesis, the authors said.
Beyond those models, there have been “conflicting conclusions” in the medical literature regarding whether warfarin protects against cancer, they added.
While some studies have shown no such association, Dr. Haaland and colleagues say they used a “stricter definition” of warfarin use that included at least 6 months of a warfarin prescription. Moreover, they only counted cancer cases that were diagnosed at least 2 years after the first prescription.
“Our data indicate that warfarin provides a possible cancer protection, a finding that may have important implications for choosing medications for patients who need anticoagulation,” the authors concluded.
However, further study is needed to better understand the mechanisms by which warfarin exerts this protective effect, they added.
FROM JAMA INTERNAL MEDICINE
Key clinical point: Warfarin may have broad anticancer effects, a finding which could have implications for choice of anticoagulant.
Major finding: Compared with warfarin non-users, warfarin users had a significantly lower rate of cancer overall (age- and sex-adjusted incidence rate ratio [IRR], 0.84) and in common organ-specific cancer sites.
Data source: A retrospective population-based cohort study of nearly 1.3 million individuals over 50 years of age in the Norwegian National Registry.
Disclosures: James B. Lorens, PhD, reported ownership interest in BerGenBio ASA.
VIDEO: Rapid influenza test obviates empiric antivirals
TORONTO – A test that only requires a maximum 2-hour wait for results was highly accurate at detecting influenza and respiratory syncytial virus infection in lung transplant patients, according to research presented at the CHEST annual meeting on Oct. 30.
This rapid and highly accurate test for detecting three common respiratory viruses has dramatically cut the need for empiric treatments and the risk for causing nosocomial infections in lung transplant patients who develop severe upper respiratory infections, Macé M. Schuurmans, MD, noted during the presentation.
This study involved 100 consecutive lung transplant patients who presented at Zurich University Hospital with signs of severe upper respiratory infection. The researchers ran the rapid and standard diagnostic tests for each patient and found that, relative to the standard test, the rapid test had positive and negative predictive values of 95%.
The number of empiric treatments with oseltamivir (Tamiflu) and ribavirin to treat a suspected influenza or respiratory syncytial virus infection (RSV) has “strongly diminished” by about two-thirds, noted Dr. Schuurmans, who is a pulmonologist at the hospital.
Until the rapid test became available, Dr. Shuurmans and his associates used a standard polymerase chain reaction test that takes 36-48 hours to yield a result. Using this test made treating patients empirically with oseltamivir and oral antibiotics for a couple of days a necessity, he said in a video interview. The older test also required isolating patients to avoid the potential spread of influenza or RSV in the hospital.
The rapid test, which became available for U.S. use in early 2017, covers influenza A and B and RSV in a single test with a single mouth-swab specimen.
“We now routinely use the rapid test and don’t prescribe empiric antivirals or antibiotics as often,” Dr. Schuurmans said. “There is much less drug cost and fewer potential adverse effects from empiric treatment.” Specimens still also undergo conventional testing, however, because that can identify eight additional viruses that the rapid test doesn’t cover.
Dr. Schuurmans acknowledged that further study needs to assess the cost-benefit of the rapid test to confirm that its added expense is offset by reduced expenses for empiric treatment and hospital isolation.
He had no disclosures. The study received no commercial support.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @mitchelzoler
TORONTO – A test that only requires a maximum 2-hour wait for results was highly accurate at detecting influenza and respiratory syncytial virus infection in lung transplant patients, according to research presented at the CHEST annual meeting on Oct. 30.
This rapid and highly accurate test for detecting three common respiratory viruses has dramatically cut the need for empiric treatments and the risk for causing nosocomial infections in lung transplant patients who develop severe upper respiratory infections, Macé M. Schuurmans, MD, noted during the presentation.
This study involved 100 consecutive lung transplant patients who presented at Zurich University Hospital with signs of severe upper respiratory infection. The researchers ran the rapid and standard diagnostic tests for each patient and found that, relative to the standard test, the rapid test had positive and negative predictive values of 95%.
The number of empiric treatments with oseltamivir (Tamiflu) and ribavirin to treat a suspected influenza or respiratory syncytial virus infection (RSV) has “strongly diminished” by about two-thirds, noted Dr. Schuurmans, who is a pulmonologist at the hospital.
Until the rapid test became available, Dr. Shuurmans and his associates used a standard polymerase chain reaction test that takes 36-48 hours to yield a result. Using this test made treating patients empirically with oseltamivir and oral antibiotics for a couple of days a necessity, he said in a video interview. The older test also required isolating patients to avoid the potential spread of influenza or RSV in the hospital.
The rapid test, which became available for U.S. use in early 2017, covers influenza A and B and RSV in a single test with a single mouth-swab specimen.
“We now routinely use the rapid test and don’t prescribe empiric antivirals or antibiotics as often,” Dr. Schuurmans said. “There is much less drug cost and fewer potential adverse effects from empiric treatment.” Specimens still also undergo conventional testing, however, because that can identify eight additional viruses that the rapid test doesn’t cover.
Dr. Schuurmans acknowledged that further study needs to assess the cost-benefit of the rapid test to confirm that its added expense is offset by reduced expenses for empiric treatment and hospital isolation.
He had no disclosures. The study received no commercial support.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @mitchelzoler
TORONTO – A test that only requires a maximum 2-hour wait for results was highly accurate at detecting influenza and respiratory syncytial virus infection in lung transplant patients, according to research presented at the CHEST annual meeting on Oct. 30.
This rapid and highly accurate test for detecting three common respiratory viruses has dramatically cut the need for empiric treatments and the risk for causing nosocomial infections in lung transplant patients who develop severe upper respiratory infections, Macé M. Schuurmans, MD, noted during the presentation.
This study involved 100 consecutive lung transplant patients who presented at Zurich University Hospital with signs of severe upper respiratory infection. The researchers ran the rapid and standard diagnostic tests for each patient and found that, relative to the standard test, the rapid test had positive and negative predictive values of 95%.
The number of empiric treatments with oseltamivir (Tamiflu) and ribavirin to treat a suspected influenza or respiratory syncytial virus infection (RSV) has “strongly diminished” by about two-thirds, noted Dr. Schuurmans, who is a pulmonologist at the hospital.
Until the rapid test became available, Dr. Shuurmans and his associates used a standard polymerase chain reaction test that takes 36-48 hours to yield a result. Using this test made treating patients empirically with oseltamivir and oral antibiotics for a couple of days a necessity, he said in a video interview. The older test also required isolating patients to avoid the potential spread of influenza or RSV in the hospital.
The rapid test, which became available for U.S. use in early 2017, covers influenza A and B and RSV in a single test with a single mouth-swab specimen.
“We now routinely use the rapid test and don’t prescribe empiric antivirals or antibiotics as often,” Dr. Schuurmans said. “There is much less drug cost and fewer potential adverse effects from empiric treatment.” Specimens still also undergo conventional testing, however, because that can identify eight additional viruses that the rapid test doesn’t cover.
Dr. Schuurmans acknowledged that further study needs to assess the cost-benefit of the rapid test to confirm that its added expense is offset by reduced expenses for empiric treatment and hospital isolation.
He had no disclosures. The study received no commercial support.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @mitchelzoler
AT CHEST 2017
Key clinical point:
Major finding: The rapid test had positive and negative predictive values of 95%.
Data source: A single-center observational study of 100 consecutive lung transplant recipients who presented with severe, acute respiratory infection.
Disclosures: Dr. Schuurmans had no disclosures. The study received no commercial support.
Cold stored platelets control bleeding after complex cardiac surgery
SAN DIEGO – Cold stored leukoreduced apheresis platelets in platelet additive solution were effective for controlling bleeding in a small study of patients undergoing complex cardiothoracic surgery, according to findings presented at the annual meeting of the American Association of Blood Banks.
The volume of postoperative bleeding was significantly lower among patients who received cold stored platelets compared with those who received standard room temperature storage platelets. Thromboembolic events did not differ between the two groups, nor did measures of coagulation at varying time points. Platelet counts and blood usage were also similar in the two groups. The study was small, however, and further studies are needed to confirm the findings.
“These patients are undergoing major surgery and are at high risk in every aspect,” said Torunn Oveland Apelseth, MD, PhD, of the Laboratory of Clinical Biochemistry, Haukeland (Norway) University Hospital. “They are at high risk for bleeding, at high risk for thromboembolic events and high blood usage, and there is a need for optimized blood components.”
There has been debate over the use of cold stored platelets, she noted. While storage at 4° C shortens platelet circulation time, some research shows that cold stored platelets have better hemostatic function.
In this study, one patient cohort was transfused with leukoreduced apheresis platelets stored at 4° C in platelet additive solution for up to 7 days under constant agitation, while the other group received platelets stored at standard room temperature. The study endpoints were comparisons between the two groups of postoperative bleeding, total blood usage, and laboratory measures of coagulation and blood cell counts within the first postoperative day. Thromboembolic events in the 28 days after surgery were also evaluated.
The study evaluated 17 patients who received cold stored platelets and 22 who received room temperature storage platelets. Patient demographics for the two groups were similar – as were their international normalized ratios, activated partial thromboplastin times, and fibrinogen levels – before surgery, immediately after heparin reversal, and the morning following the procedure.
Platelet counts and hemoglobin levels also did not significantly differ between groups.
As measured by chest drain output after chest closure, patients who received cold stored platelets had a significantly lower median amount of bleeding in the postoperative period compared with patients given room temperature storage platelets: 576 mL vs. 838 mL. Average chest drain output after chest closure was 594 mL in those who did not receive any transfusions.
Thromboembolic events occurred in 3 patients (18%) who received cold stored platelets and 7 (31%) of those given room temperature storage platelets. The difference was not statistically significant. In addition, blood usage – platelets, red blood cells, and solvent/detergent-treated pooled plasma – was similar for the two cohorts.
“There were also no differences in the number of thromboembolic episodes or length of stay in ICU,” said Dr. Apelseth, who recommended larger studies to explore the use of use of cold stored platelet transfusion in the critical care setting.
SAN DIEGO – Cold stored leukoreduced apheresis platelets in platelet additive solution were effective for controlling bleeding in a small study of patients undergoing complex cardiothoracic surgery, according to findings presented at the annual meeting of the American Association of Blood Banks.
The volume of postoperative bleeding was significantly lower among patients who received cold stored platelets compared with those who received standard room temperature storage platelets. Thromboembolic events did not differ between the two groups, nor did measures of coagulation at varying time points. Platelet counts and blood usage were also similar in the two groups. The study was small, however, and further studies are needed to confirm the findings.
“These patients are undergoing major surgery and are at high risk in every aspect,” said Torunn Oveland Apelseth, MD, PhD, of the Laboratory of Clinical Biochemistry, Haukeland (Norway) University Hospital. “They are at high risk for bleeding, at high risk for thromboembolic events and high blood usage, and there is a need for optimized blood components.”
There has been debate over the use of cold stored platelets, she noted. While storage at 4° C shortens platelet circulation time, some research shows that cold stored platelets have better hemostatic function.
In this study, one patient cohort was transfused with leukoreduced apheresis platelets stored at 4° C in platelet additive solution for up to 7 days under constant agitation, while the other group received platelets stored at standard room temperature. The study endpoints were comparisons between the two groups of postoperative bleeding, total blood usage, and laboratory measures of coagulation and blood cell counts within the first postoperative day. Thromboembolic events in the 28 days after surgery were also evaluated.
The study evaluated 17 patients who received cold stored platelets and 22 who received room temperature storage platelets. Patient demographics for the two groups were similar – as were their international normalized ratios, activated partial thromboplastin times, and fibrinogen levels – before surgery, immediately after heparin reversal, and the morning following the procedure.
Platelet counts and hemoglobin levels also did not significantly differ between groups.
As measured by chest drain output after chest closure, patients who received cold stored platelets had a significantly lower median amount of bleeding in the postoperative period compared with patients given room temperature storage platelets: 576 mL vs. 838 mL. Average chest drain output after chest closure was 594 mL in those who did not receive any transfusions.
Thromboembolic events occurred in 3 patients (18%) who received cold stored platelets and 7 (31%) of those given room temperature storage platelets. The difference was not statistically significant. In addition, blood usage – platelets, red blood cells, and solvent/detergent-treated pooled plasma – was similar for the two cohorts.
“There were also no differences in the number of thromboembolic episodes or length of stay in ICU,” said Dr. Apelseth, who recommended larger studies to explore the use of use of cold stored platelet transfusion in the critical care setting.
SAN DIEGO – Cold stored leukoreduced apheresis platelets in platelet additive solution were effective for controlling bleeding in a small study of patients undergoing complex cardiothoracic surgery, according to findings presented at the annual meeting of the American Association of Blood Banks.
The volume of postoperative bleeding was significantly lower among patients who received cold stored platelets compared with those who received standard room temperature storage platelets. Thromboembolic events did not differ between the two groups, nor did measures of coagulation at varying time points. Platelet counts and blood usage were also similar in the two groups. The study was small, however, and further studies are needed to confirm the findings.
“These patients are undergoing major surgery and are at high risk in every aspect,” said Torunn Oveland Apelseth, MD, PhD, of the Laboratory of Clinical Biochemistry, Haukeland (Norway) University Hospital. “They are at high risk for bleeding, at high risk for thromboembolic events and high blood usage, and there is a need for optimized blood components.”
There has been debate over the use of cold stored platelets, she noted. While storage at 4° C shortens platelet circulation time, some research shows that cold stored platelets have better hemostatic function.
In this study, one patient cohort was transfused with leukoreduced apheresis platelets stored at 4° C in platelet additive solution for up to 7 days under constant agitation, while the other group received platelets stored at standard room temperature. The study endpoints were comparisons between the two groups of postoperative bleeding, total blood usage, and laboratory measures of coagulation and blood cell counts within the first postoperative day. Thromboembolic events in the 28 days after surgery were also evaluated.
The study evaluated 17 patients who received cold stored platelets and 22 who received room temperature storage platelets. Patient demographics for the two groups were similar – as were their international normalized ratios, activated partial thromboplastin times, and fibrinogen levels – before surgery, immediately after heparin reversal, and the morning following the procedure.
Platelet counts and hemoglobin levels also did not significantly differ between groups.
As measured by chest drain output after chest closure, patients who received cold stored platelets had a significantly lower median amount of bleeding in the postoperative period compared with patients given room temperature storage platelets: 576 mL vs. 838 mL. Average chest drain output after chest closure was 594 mL in those who did not receive any transfusions.
Thromboembolic events occurred in 3 patients (18%) who received cold stored platelets and 7 (31%) of those given room temperature storage platelets. The difference was not statistically significant. In addition, blood usage – platelets, red blood cells, and solvent/detergent-treated pooled plasma – was similar for the two cohorts.
“There were also no differences in the number of thromboembolic episodes or length of stay in ICU,” said Dr. Apelseth, who recommended larger studies to explore the use of use of cold stored platelet transfusion in the critical care setting.
AT AABB17
Key clinical point: Cold stored leukoreduced apheresis platelets in platelet additive solution are effective for treating bleeding in patients undergoing complex cardiothoracic surgery.
Major finding: Patients who underwent procedures requiring cardiopulmonary bypass circulation had a significantly lower median amount of bleeding in the postoperative period with cold stored platelets compared with standard room temperature platelets: 576 mL vs. 838 mL.
Data source: Randomized two-arm pilot trial of cardiothoracic surgery patients.
Disclosures: The authors have no relevant financial disclosures.
Yoga benefits lung cancer patients and caregivers alike
Yoga provides physical and mental benefits for both lung cancer patients and their caregivers, according to results of a randomized study presented at the Palliative and Supportive Care in Oncology Symposium.
“Overall, we are encouraged by the findings,” said lead study author, Kathrin Milbury, PhD, of University of Texas MD Anderson Cancer Center, Houston.
This study provides preliminary evidence that a yoga program can provide a “buffer” and improve physical function for patients, as well as self-reported improved quality of life for both patients and their caregivers, she added.
All patients in the study had non–small cell lung cancer and were undergoing thoracic radiation therapy, which can cause respiratory toxicities that negatively affect quality of life and physical activity, according to Dr. Milbury and her coinvestigators.
A total of 32 patient-caregiver dyads were randomized to participate in 15 yoga sessions or to be in a “wait-list” control group, and 26 dyads completed all assessments.
Patients who practiced yoga had significantly better scores on a 6-minute walking test (478 vs. 402 for wait-list enrollees; P less than .05), plus better stamina and mental health. Caregivers had improved fatigue and better stamina at work.
Almost all patients (96%) rated the program as “very useful,” investigators reported at the symposium, which was cosponsored by AAHPM, ASCO, ASTRO, and MASCC.
This study provides additional evidence that yoga and other nonpharmacologic supportive therapies “can be integrated into not only the care of cancer patients, but also the family caregivers who support them,” according to Andrew S. Epstein, MD, of Memorial Sloan Kettering Cancer Center, New York.
Next, the researchers plan to conduct a larger, randomized, controlled trial with a more stringent comparison group, according to Dr. Milbury.
This is an interesting study further supporting the benefits of yoga and meditation when dealing with a chronic illness such as lung cancer. The benefits included reducing stress and improving quality of life, not only for the patient but also the caregiver.
This is an interesting study further supporting the benefits of yoga and meditation when dealing with a chronic illness such as lung cancer. The benefits included reducing stress and improving quality of life, not only for the patient but also the caregiver.
This is an interesting study further supporting the benefits of yoga and meditation when dealing with a chronic illness such as lung cancer. The benefits included reducing stress and improving quality of life, not only for the patient but also the caregiver.
Yoga provides physical and mental benefits for both lung cancer patients and their caregivers, according to results of a randomized study presented at the Palliative and Supportive Care in Oncology Symposium.
“Overall, we are encouraged by the findings,” said lead study author, Kathrin Milbury, PhD, of University of Texas MD Anderson Cancer Center, Houston.
This study provides preliminary evidence that a yoga program can provide a “buffer” and improve physical function for patients, as well as self-reported improved quality of life for both patients and their caregivers, she added.
All patients in the study had non–small cell lung cancer and were undergoing thoracic radiation therapy, which can cause respiratory toxicities that negatively affect quality of life and physical activity, according to Dr. Milbury and her coinvestigators.
A total of 32 patient-caregiver dyads were randomized to participate in 15 yoga sessions or to be in a “wait-list” control group, and 26 dyads completed all assessments.
Patients who practiced yoga had significantly better scores on a 6-minute walking test (478 vs. 402 for wait-list enrollees; P less than .05), plus better stamina and mental health. Caregivers had improved fatigue and better stamina at work.
Almost all patients (96%) rated the program as “very useful,” investigators reported at the symposium, which was cosponsored by AAHPM, ASCO, ASTRO, and MASCC.
This study provides additional evidence that yoga and other nonpharmacologic supportive therapies “can be integrated into not only the care of cancer patients, but also the family caregivers who support them,” according to Andrew S. Epstein, MD, of Memorial Sloan Kettering Cancer Center, New York.
Next, the researchers plan to conduct a larger, randomized, controlled trial with a more stringent comparison group, according to Dr. Milbury.
Yoga provides physical and mental benefits for both lung cancer patients and their caregivers, according to results of a randomized study presented at the Palliative and Supportive Care in Oncology Symposium.
“Overall, we are encouraged by the findings,” said lead study author, Kathrin Milbury, PhD, of University of Texas MD Anderson Cancer Center, Houston.
This study provides preliminary evidence that a yoga program can provide a “buffer” and improve physical function for patients, as well as self-reported improved quality of life for both patients and their caregivers, she added.
All patients in the study had non–small cell lung cancer and were undergoing thoracic radiation therapy, which can cause respiratory toxicities that negatively affect quality of life and physical activity, according to Dr. Milbury and her coinvestigators.
A total of 32 patient-caregiver dyads were randomized to participate in 15 yoga sessions or to be in a “wait-list” control group, and 26 dyads completed all assessments.
Patients who practiced yoga had significantly better scores on a 6-minute walking test (478 vs. 402 for wait-list enrollees; P less than .05), plus better stamina and mental health. Caregivers had improved fatigue and better stamina at work.
Almost all patients (96%) rated the program as “very useful,” investigators reported at the symposium, which was cosponsored by AAHPM, ASCO, ASTRO, and MASCC.
This study provides additional evidence that yoga and other nonpharmacologic supportive therapies “can be integrated into not only the care of cancer patients, but also the family caregivers who support them,” according to Andrew S. Epstein, MD, of Memorial Sloan Kettering Cancer Center, New York.
Next, the researchers plan to conduct a larger, randomized, controlled trial with a more stringent comparison group, according to Dr. Milbury.
FROM PALLONC 2017
Key clinical point: Yoga provides both physical and mental benefits for lung cancer patients undergoing radiotherapy and their caregivers.
Major finding: Patients who practiced yoga had significantly better scores on a 6-minute walking test (478 vs. 402 for wait-list enrollees; P less than .05), plus better stamina and mental health. Caregivers had improved fatigue and better stamina at work.
Data source: Randomized study including 47 patient-caregiver dyads, of which 32 consented and 26 completed all assessments.
Disclosures: Funding for this study came from the National Institutes of Health. Lead author Kathrin Milbury, PhD, reported no potential conflicts of interest.
Robotic-assisted pulmonary lobectomy effective for large tumors
Robotic-assisted pulmonary lobectomy is a safe and effective way to remove large tumors in patients with non–small cell lung cancer (NSCLC), according to the abstract of a study scheduled to be presented at the CHEST annual meeting.
The study covers a retrospective analysis of 345 NSCLC patients with tumors who underwent robotic-assisted pulmonary lobectomy performed by one surgeon from September 2010 through August 2016. The participants were grouped into the following three cohorts: patients with tumors less than 5 cm in diameter, patients with tumors from 5 to 7 cm, and patients with tumors larger than 7 cm. The researchers excluded patients with pulmonary metastases or benign lesions from the study.
Patients with smaller tumors were more likely to have simple lobectomy or lobectomy plus wedge, while patients with larger tumors were more likely to require lobectomy with chest wall resection. Increased tumor size was also associated with increased intraoperative estimated blood loss, skin-to-skin operative time, hospital length of stay, and overall conversion to open lobectomy.
There was no association found between tumor size and increased overall intraoperative or postoperative complications, or in-hospital mortality.
Nirav Patel, MD, FCCP, of the Tampa Bay Sleep Center is scheduled to present his abstract on Sunday Oct. 29th, between 2:15 and 2:30 p.m. in Convention Center – 606. Dr. Patel’s research is part of the Cardiothoracic Surgery session, running from 1:30 p.m. to 3:00 p.m. at the CHEST annual meeting.
Robotic-assisted pulmonary lobectomy is a safe and effective way to remove large tumors in patients with non–small cell lung cancer (NSCLC), according to the abstract of a study scheduled to be presented at the CHEST annual meeting.
The study covers a retrospective analysis of 345 NSCLC patients with tumors who underwent robotic-assisted pulmonary lobectomy performed by one surgeon from September 2010 through August 2016. The participants were grouped into the following three cohorts: patients with tumors less than 5 cm in diameter, patients with tumors from 5 to 7 cm, and patients with tumors larger than 7 cm. The researchers excluded patients with pulmonary metastases or benign lesions from the study.
Patients with smaller tumors were more likely to have simple lobectomy or lobectomy plus wedge, while patients with larger tumors were more likely to require lobectomy with chest wall resection. Increased tumor size was also associated with increased intraoperative estimated blood loss, skin-to-skin operative time, hospital length of stay, and overall conversion to open lobectomy.
There was no association found between tumor size and increased overall intraoperative or postoperative complications, or in-hospital mortality.
Nirav Patel, MD, FCCP, of the Tampa Bay Sleep Center is scheduled to present his abstract on Sunday Oct. 29th, between 2:15 and 2:30 p.m. in Convention Center – 606. Dr. Patel’s research is part of the Cardiothoracic Surgery session, running from 1:30 p.m. to 3:00 p.m. at the CHEST annual meeting.
Robotic-assisted pulmonary lobectomy is a safe and effective way to remove large tumors in patients with non–small cell lung cancer (NSCLC), according to the abstract of a study scheduled to be presented at the CHEST annual meeting.
The study covers a retrospective analysis of 345 NSCLC patients with tumors who underwent robotic-assisted pulmonary lobectomy performed by one surgeon from September 2010 through August 2016. The participants were grouped into the following three cohorts: patients with tumors less than 5 cm in diameter, patients with tumors from 5 to 7 cm, and patients with tumors larger than 7 cm. The researchers excluded patients with pulmonary metastases or benign lesions from the study.
Patients with smaller tumors were more likely to have simple lobectomy or lobectomy plus wedge, while patients with larger tumors were more likely to require lobectomy with chest wall resection. Increased tumor size was also associated with increased intraoperative estimated blood loss, skin-to-skin operative time, hospital length of stay, and overall conversion to open lobectomy.
There was no association found between tumor size and increased overall intraoperative or postoperative complications, or in-hospital mortality.
Nirav Patel, MD, FCCP, of the Tampa Bay Sleep Center is scheduled to present his abstract on Sunday Oct. 29th, between 2:15 and 2:30 p.m. in Convention Center – 606. Dr. Patel’s research is part of the Cardiothoracic Surgery session, running from 1:30 p.m. to 3:00 p.m. at the CHEST annual meeting.
FROM CHEST 2017
Ideal intubation position still unknown
In critically ill adults undergoing endotracheal intubation, the ramped position does not significantly improve oxygenation compared with the sniffing position, according to results of a multicenter, randomized trial of 260 patients treated in an intensive care unit.
Moreover, “[ramped] position appeared to worsen glottic view and increase the number of attempts required for successful intubation,” wrote Matthew W. Semler, MD, of Vanderbilt University Medical Center, Nashville, Tenn., and his coauthors (Chest. 2017 Oct. doi: 10.1016/j.chest.2017.03.061).
The ramped and sniffing positions are the two most common patient positions used during emergent intubation, according to investigators. The sniffing position is characterized by supine torso, neck flexed forward, and head extended, while ramped position involves elevating the torso and head.
Some believe the ramped position may offer superior anatomic alignment of the upper airway; however, only a few observational studies suggest it is associated with fewer complications than the sniffing position, the authors wrote.
Accordingly, they conducted a multicenter randomized trial with a primary endpoint of lowest arterial oxygen saturation, hypothesizing that the endpoint would be higher for the ramped position: “Our primary outcome of lowest arterial oxygen saturation is an established endpoint in ICU intubation trials, and is linked to periprocedural cardiac arrest and death,” they wrote.
The investigators instead found that median lowest arterial oxygen saturation was not statistically different between groups, at 93% for the ramped position, and 92% for the sniffing position (P = 0.27), published data show.
Further results showed that the ramped position appeared to be associated with poor glottic view and more difficult intubation. The incidence of grade III (only epiglottis) or grade IV (no visible glottis structures) views were 25.4% for ramped vs. 11.5% for sniffing (P = .01), while the rate of first-attempt intubation was 76.2% for ramped vs 85.4% for sniffing (P = .02).
While the findings are compelling, the authors were forthcoming about the potential limitations of the study and differences compared with earlier investigations. Notably, they said, all prior controlled trials of patient positioning during endotracheal intubation were conducted in the operating room, rather than in the ICU.
Also, the operators’ skill levels may further explain differences in this study’s outcomes from those of similar studies, the researchers noted. Earlier studies included patients intubated by one or two senior anesthesiologists from one center, while this trial involved 30 operators across multiple centers, with the average operator having performed 60 previous intubations. “Thus, our findings may generalize to settings in which airway management is performed by trainees, but whether results would be similar among expert operators remains unknown,” the investigators noted.
The authors reported no potential conflicts of interest. One coauthor reported serving on an advisory board for Avisa Pharma.
Editorialists praised the multicenter, randomized design of this study, and its total recruitment of 260 patients. They also noted several limitations of the study that “could shed some light” on the group’s conclusions (Chest. 2017 Oct. doi: 10.1016/j.chest.2017.06.002).
“The results diverge from [operating room] literature of the past 15 years that suggest that the ramped position is the preferred intubation position for obese patients or those with an anticipated difficult airway.” This may have been caused by shortcomings of this study’s design and differences between it and other research exploring the topic of patient positioning during endotracheal intubation, they wrote.
The study lacked a prespecified algorithm for preoxygenation and the operators had relatively low amounts of experience with intubations. Finally, the beds used in this study could contribute to the divergences between this intensive care unit experience and the operating room literature. The operating room table is narrower, firmer, and more stable, while by contrast, the ICU bed is wider and softer, they noted. This “may make initial positioning, maintenance of positioning, and accessing the patient’s head more difficult.”
Nevertheless, “[this] important study provides ideas for further study of optimal positioning in the ICU and adds valuable data to the sparse literature on the subject in the ICU setting,” they concluded.
James Aaron Scott, DO, Jens Matthias Walz, MD, FCCP, and Stephen O. Heard, MD, FCCP, are in the department of anesthesiology and perioperative medicine, UMass Memorial Medical Center, Worcester, Mass. The authors reported no conflicts of interest. These comments are based on their editorial.
Editorialists praised the multicenter, randomized design of this study, and its total recruitment of 260 patients. They also noted several limitations of the study that “could shed some light” on the group’s conclusions (Chest. 2017 Oct. doi: 10.1016/j.chest.2017.06.002).
“The results diverge from [operating room] literature of the past 15 years that suggest that the ramped position is the preferred intubation position for obese patients or those with an anticipated difficult airway.” This may have been caused by shortcomings of this study’s design and differences between it and other research exploring the topic of patient positioning during endotracheal intubation, they wrote.
The study lacked a prespecified algorithm for preoxygenation and the operators had relatively low amounts of experience with intubations. Finally, the beds used in this study could contribute to the divergences between this intensive care unit experience and the operating room literature. The operating room table is narrower, firmer, and more stable, while by contrast, the ICU bed is wider and softer, they noted. This “may make initial positioning, maintenance of positioning, and accessing the patient’s head more difficult.”
Nevertheless, “[this] important study provides ideas for further study of optimal positioning in the ICU and adds valuable data to the sparse literature on the subject in the ICU setting,” they concluded.
James Aaron Scott, DO, Jens Matthias Walz, MD, FCCP, and Stephen O. Heard, MD, FCCP, are in the department of anesthesiology and perioperative medicine, UMass Memorial Medical Center, Worcester, Mass. The authors reported no conflicts of interest. These comments are based on their editorial.
Editorialists praised the multicenter, randomized design of this study, and its total recruitment of 260 patients. They also noted several limitations of the study that “could shed some light” on the group’s conclusions (Chest. 2017 Oct. doi: 10.1016/j.chest.2017.06.002).
“The results diverge from [operating room] literature of the past 15 years that suggest that the ramped position is the preferred intubation position for obese patients or those with an anticipated difficult airway.” This may have been caused by shortcomings of this study’s design and differences between it and other research exploring the topic of patient positioning during endotracheal intubation, they wrote.
The study lacked a prespecified algorithm for preoxygenation and the operators had relatively low amounts of experience with intubations. Finally, the beds used in this study could contribute to the divergences between this intensive care unit experience and the operating room literature. The operating room table is narrower, firmer, and more stable, while by contrast, the ICU bed is wider and softer, they noted. This “may make initial positioning, maintenance of positioning, and accessing the patient’s head more difficult.”
Nevertheless, “[this] important study provides ideas for further study of optimal positioning in the ICU and adds valuable data to the sparse literature on the subject in the ICU setting,” they concluded.
James Aaron Scott, DO, Jens Matthias Walz, MD, FCCP, and Stephen O. Heard, MD, FCCP, are in the department of anesthesiology and perioperative medicine, UMass Memorial Medical Center, Worcester, Mass. The authors reported no conflicts of interest. These comments are based on their editorial.
In critically ill adults undergoing endotracheal intubation, the ramped position does not significantly improve oxygenation compared with the sniffing position, according to results of a multicenter, randomized trial of 260 patients treated in an intensive care unit.
Moreover, “[ramped] position appeared to worsen glottic view and increase the number of attempts required for successful intubation,” wrote Matthew W. Semler, MD, of Vanderbilt University Medical Center, Nashville, Tenn., and his coauthors (Chest. 2017 Oct. doi: 10.1016/j.chest.2017.03.061).
The ramped and sniffing positions are the two most common patient positions used during emergent intubation, according to investigators. The sniffing position is characterized by supine torso, neck flexed forward, and head extended, while ramped position involves elevating the torso and head.
Some believe the ramped position may offer superior anatomic alignment of the upper airway; however, only a few observational studies suggest it is associated with fewer complications than the sniffing position, the authors wrote.
Accordingly, they conducted a multicenter randomized trial with a primary endpoint of lowest arterial oxygen saturation, hypothesizing that the endpoint would be higher for the ramped position: “Our primary outcome of lowest arterial oxygen saturation is an established endpoint in ICU intubation trials, and is linked to periprocedural cardiac arrest and death,” they wrote.
The investigators instead found that median lowest arterial oxygen saturation was not statistically different between groups, at 93% for the ramped position, and 92% for the sniffing position (P = 0.27), published data show.
Further results showed that the ramped position appeared to be associated with poor glottic view and more difficult intubation. The incidence of grade III (only epiglottis) or grade IV (no visible glottis structures) views were 25.4% for ramped vs. 11.5% for sniffing (P = .01), while the rate of first-attempt intubation was 76.2% for ramped vs 85.4% for sniffing (P = .02).
While the findings are compelling, the authors were forthcoming about the potential limitations of the study and differences compared with earlier investigations. Notably, they said, all prior controlled trials of patient positioning during endotracheal intubation were conducted in the operating room, rather than in the ICU.
Also, the operators’ skill levels may further explain differences in this study’s outcomes from those of similar studies, the researchers noted. Earlier studies included patients intubated by one or two senior anesthesiologists from one center, while this trial involved 30 operators across multiple centers, with the average operator having performed 60 previous intubations. “Thus, our findings may generalize to settings in which airway management is performed by trainees, but whether results would be similar among expert operators remains unknown,” the investigators noted.
The authors reported no potential conflicts of interest. One coauthor reported serving on an advisory board for Avisa Pharma.
In critically ill adults undergoing endotracheal intubation, the ramped position does not significantly improve oxygenation compared with the sniffing position, according to results of a multicenter, randomized trial of 260 patients treated in an intensive care unit.
Moreover, “[ramped] position appeared to worsen glottic view and increase the number of attempts required for successful intubation,” wrote Matthew W. Semler, MD, of Vanderbilt University Medical Center, Nashville, Tenn., and his coauthors (Chest. 2017 Oct. doi: 10.1016/j.chest.2017.03.061).
The ramped and sniffing positions are the two most common patient positions used during emergent intubation, according to investigators. The sniffing position is characterized by supine torso, neck flexed forward, and head extended, while ramped position involves elevating the torso and head.
Some believe the ramped position may offer superior anatomic alignment of the upper airway; however, only a few observational studies suggest it is associated with fewer complications than the sniffing position, the authors wrote.
Accordingly, they conducted a multicenter randomized trial with a primary endpoint of lowest arterial oxygen saturation, hypothesizing that the endpoint would be higher for the ramped position: “Our primary outcome of lowest arterial oxygen saturation is an established endpoint in ICU intubation trials, and is linked to periprocedural cardiac arrest and death,” they wrote.
The investigators instead found that median lowest arterial oxygen saturation was not statistically different between groups, at 93% for the ramped position, and 92% for the sniffing position (P = 0.27), published data show.
Further results showed that the ramped position appeared to be associated with poor glottic view and more difficult intubation. The incidence of grade III (only epiglottis) or grade IV (no visible glottis structures) views were 25.4% for ramped vs. 11.5% for sniffing (P = .01), while the rate of first-attempt intubation was 76.2% for ramped vs 85.4% for sniffing (P = .02).
While the findings are compelling, the authors were forthcoming about the potential limitations of the study and differences compared with earlier investigations. Notably, they said, all prior controlled trials of patient positioning during endotracheal intubation were conducted in the operating room, rather than in the ICU.
Also, the operators’ skill levels may further explain differences in this study’s outcomes from those of similar studies, the researchers noted. Earlier studies included patients intubated by one or two senior anesthesiologists from one center, while this trial involved 30 operators across multiple centers, with the average operator having performed 60 previous intubations. “Thus, our findings may generalize to settings in which airway management is performed by trainees, but whether results would be similar among expert operators remains unknown,” the investigators noted.
The authors reported no potential conflicts of interest. One coauthor reported serving on an advisory board for Avisa Pharma.
FROM CHEST
Key clinical point: During endotracheal intubation of critically ill adults, use of the ramped position did not significantly improve oxygenation compared with the sniffing position, and it increased the number of attempts needed to achieve successful intubation.
Major finding: The median lowest arterial oxygen saturation was 93% for the ramped position and 92% for the sniffing position (P = .27).
Data source: Multicenter, randomized trial of 260 critically ill adults undergoing endotracheal intubation.
Disclosures: The authors reported no potential conflicts of interest. One coauthor reported serving on an advisory board for Avisa Pharma.
Dabrafenib/trametinib bests docetaxel for advanced NSCLC in indirect comparison
CHICAGO – Compared with docetaxel in matched external controls, combination therapy with dabrafenib and trametinib was associated with significantly prolonged progression-free and overall survival in previously treated patients with metastatic non–small cell lung cancer in a phase 2 trial.
Median progression-free survival (PFS) was 9.7 months in 57 patients in an open-label, multicenter phase 2 trial that investigated dabrafenib/trametinib treatment for metastatic BRAF V600E–mutated NSCLC, compared with 4.2 months in 290 patients treated with docetaxel in the randomized phase 3 CheckMate057 trial, which compared nivolumab and docetaxel in similar patients (hazard ratio, 0.32). Overall survival in the groups was 19.2 vs. 9.3 months, respectively (HR, 0.41), Junlong Li, MD, of Analysis Group, Boston, reported at the Chicago Multidisciplinary Symposium in Thoracic Oncology.
Patients treated with the combination of dabrafenib and trametinib also had a significantly higher overall response rate (61% vs. 12%) and disease control rate (77% vs. 55%), Dr. Li said.
Patient-level data for the combination therapy patients and summary data for the docetaxel-treated patients were used for the current analysis. Patients and controls were matched based on age, sex, race, smoking history, performance score, tumor histology, prior regimens, prior radiotherapy, and prior maintenance therapy. The two trials used for the analysis (NCT01336634 and CheckMate 057) were comparable in design and inclusion/exclusion criteria, and both used RECIST v1.1 to evaluate response to therapy.
“In the absence of head-to-head trials ... this study contributes some comparative efficacy evidence in this area,” Dr. Li concluded.
Invited discussant, Thomas Eldridge Stinchcombe, MD, of Duke University, Durham, N.C., said that the findings are unsurprising but important in that they are confirmatory.
Dr. Li is a consultant for Novartis, which sponsored the analysis.
CHICAGO – Compared with docetaxel in matched external controls, combination therapy with dabrafenib and trametinib was associated with significantly prolonged progression-free and overall survival in previously treated patients with metastatic non–small cell lung cancer in a phase 2 trial.
Median progression-free survival (PFS) was 9.7 months in 57 patients in an open-label, multicenter phase 2 trial that investigated dabrafenib/trametinib treatment for metastatic BRAF V600E–mutated NSCLC, compared with 4.2 months in 290 patients treated with docetaxel in the randomized phase 3 CheckMate057 trial, which compared nivolumab and docetaxel in similar patients (hazard ratio, 0.32). Overall survival in the groups was 19.2 vs. 9.3 months, respectively (HR, 0.41), Junlong Li, MD, of Analysis Group, Boston, reported at the Chicago Multidisciplinary Symposium in Thoracic Oncology.
Patients treated with the combination of dabrafenib and trametinib also had a significantly higher overall response rate (61% vs. 12%) and disease control rate (77% vs. 55%), Dr. Li said.
Patient-level data for the combination therapy patients and summary data for the docetaxel-treated patients were used for the current analysis. Patients and controls were matched based on age, sex, race, smoking history, performance score, tumor histology, prior regimens, prior radiotherapy, and prior maintenance therapy. The two trials used for the analysis (NCT01336634 and CheckMate 057) were comparable in design and inclusion/exclusion criteria, and both used RECIST v1.1 to evaluate response to therapy.
“In the absence of head-to-head trials ... this study contributes some comparative efficacy evidence in this area,” Dr. Li concluded.
Invited discussant, Thomas Eldridge Stinchcombe, MD, of Duke University, Durham, N.C., said that the findings are unsurprising but important in that they are confirmatory.
Dr. Li is a consultant for Novartis, which sponsored the analysis.
CHICAGO – Compared with docetaxel in matched external controls, combination therapy with dabrafenib and trametinib was associated with significantly prolonged progression-free and overall survival in previously treated patients with metastatic non–small cell lung cancer in a phase 2 trial.
Median progression-free survival (PFS) was 9.7 months in 57 patients in an open-label, multicenter phase 2 trial that investigated dabrafenib/trametinib treatment for metastatic BRAF V600E–mutated NSCLC, compared with 4.2 months in 290 patients treated with docetaxel in the randomized phase 3 CheckMate057 trial, which compared nivolumab and docetaxel in similar patients (hazard ratio, 0.32). Overall survival in the groups was 19.2 vs. 9.3 months, respectively (HR, 0.41), Junlong Li, MD, of Analysis Group, Boston, reported at the Chicago Multidisciplinary Symposium in Thoracic Oncology.
Patients treated with the combination of dabrafenib and trametinib also had a significantly higher overall response rate (61% vs. 12%) and disease control rate (77% vs. 55%), Dr. Li said.
Patient-level data for the combination therapy patients and summary data for the docetaxel-treated patients were used for the current analysis. Patients and controls were matched based on age, sex, race, smoking history, performance score, tumor histology, prior regimens, prior radiotherapy, and prior maintenance therapy. The two trials used for the analysis (NCT01336634 and CheckMate 057) were comparable in design and inclusion/exclusion criteria, and both used RECIST v1.1 to evaluate response to therapy.
“In the absence of head-to-head trials ... this study contributes some comparative efficacy evidence in this area,” Dr. Li concluded.
Invited discussant, Thomas Eldridge Stinchcombe, MD, of Duke University, Durham, N.C., said that the findings are unsurprising but important in that they are confirmatory.
Dr. Li is a consultant for Novartis, which sponsored the analysis.
AT A SYMPOSIUM IN THORACIC ONCOLOGY
Key clinical point:
Major finding: Median PFS with dabrafenib and trametinib vs. docetaxel: 9.7 vs. 4.2 months (HR, 0.32); overall survival: 19.2 vs. 9.3 months (HR, 0.41).
Data source: An adjusted indirect comparison of data from 347 patients from two separate studies.
Disclosures: Dr. Li is a consultant for Novartis, which sponsored the analysis.