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Jennifer Smith is the editor of Oncology Practice, part of MDedge Hematology/Oncology. She was previously the editor of Hematology Times, an editor at Principal Investigators Association, and a reporter at The Oneida Daily Dispatch. She has a BS in journalism.
Several factors may drive recent improvements in allo-HCT outcomes
A cancer center has seen improved outcomes of allogeneic transplant in recent years, despite increases in patient age and comorbidities.
Researchers compared patients who received allogeneic hematopoietic cell transplants (allo-HCTs) during two periods, 2003-2007 and 2013-2017.
Patients treated in the 2013-2017 period were older and had more HCT-specific comorbidities at baseline, but they had lower rates of mortality, relapse, and graft-versus-host disease (GVHD) post transplant. George B. McDonald, MD, an emeritus member at Fred Hutchinson Cancer Research Center in Seattle, and coauthors described these findings in Annals of Internal Medicine.
“The primary question being addressed by this study was whether the striking improvement in survival … from the 1990s to the early 2000s, that we and other transplant centers have reported, had reached a plateau or whether further improvements in survival were being seen,” Dr. McDonald said in an interview.
“We knew that older and sicker patients were now coming for transplant, compared to 10 years ago. Our transplant protocols have backed away from the highest doses of chemotherapy and irradiation used to prepare patients for transplant, toward less toxic therapies, including reduced-intensity conditioning,” he added. “Our investigators have sought to prevent and more effectively treat the myriad of complications of allogeneic transplant, based on research done at the Fred Hutchinson Cancer Research Center and at transplant centers throughout the world.”
Baseline characteristics and treatment
Dr. McDonald and his colleagues analyzed data on patients who received allo-HCTs at Seattle Cancer Care Alliance. There were 1,148 patients treated in the 2003-2007 period and 1,131 patients treated in the 2013-2017 period.
Indications for allo-HCT were similar between the time periods. Patients were diagnosed with aplastic anemia, acute and chronic leukemias, Hodgkin and non-Hodgkin lymphomas, myelodysplastic syndromes, and multiple myeloma.
Patients in the 2013-2017 group were older and had more HCT-specific comorbidities than did the patients in the 2003-2007 group. The median age was 50.0 years (range, 0.1-80.9 years) and 47.2 years (range, 0.4-78.9 years), respectively. The median score on the augmented HCT-specific comorbidity index was 4.0 and 3.0, respectively.
The 2013-2017 group was more likely to have intermediate-risk disease (73% vs. 54%) but less likely to have high-risk disease (14% vs. 31%). The 2013-2017 group was less likely to receive high-dose myeloablative conditioning (15% vs. 67%) but more likely to have an unrelated donor (70% vs. 59%) or receive a cord blood transplant (13% vs. 4%).
GVHD prophylaxis differed between the time periods, with patients in the 2013-2017 group being more likely to receive sirolimus, posttransplant cyclophosphamide, and abatacept.
Outcomes
Overall, outcomes were superior in the 2013-2017 group. The rate of nonrelapse mortality at day 200 was higher in the 2003-2007 group than in the 2013-2017 group – 16% and 11%, respectively (adjusted hazard ratio, 0.66; P = .008).
Relapse or progression was more common in the 2003-2007 group – 348 patients vs. 244 patients (aHR, 0.76; P = .011). More patients died from relapse in the 2003-2007 group – 307 patients vs. 186 patients (aHR, 0.69; P = .002). More patients died from any cause in the 2003-2007 group – 653 patients vs. 418 patients (aHR, 0.66; P less than .001). The rate of grade 2-4 acute GVHD was higher in the 2003-2007 group – 71% vs. 69% (aHR, 0.80) – and so was the rate of chronic GVHD – 44% vs. 29% (aHR, 0.40). The risk of developing gram-negative bacteremia was lower in the 2013-2017 group (aHR, 0.42), as was the risk of invasive mold infection (aHR, 0.55).
Patients in the 2013-2017 group had a higher risk of cytomegalovirus (CMV) infection (aHR = 1.15), but they were less likely to have high levels of CMV viremia (aHR, 0.78 for greater than 250 IU/mL; aHR, 0.46 for greater than 1,000 IU/mL). Having higher levels of CMV viremia was associated with an increased risk of non-relapse mortality.
Potential drivers of outcome
Dr. McDonald said this study’s design makes it difficult to determine the causes of improved outcomes in the 2013-2017 period. However, the researchers do have theories about which practice changes may have contributed to better allo-HCT outcomes.
Dr. McDonald said the decrease in GVHD over time was “likely owing to the introduction of newer preventive strategies and immune-suppressive drugs.”
The decrease in nonrelapse mortality may have been driven, in part, by a reduction in fatal infections. Dr. McDonald said these infections were less frequent in the 2013-2017 period because of “molecular methods of diagnosis (especially for herpesviruses) and newer treatments (especially for fungal infections).”
“Another reason for a lower frequency of serious infection was a change in practice for treating graft-versus-host disease,” Dr. McDonald added. “Based on a randomized trial comparing lower- versus higher-dose prednisone for less-severe GVHD … both initial doses of prednisone and total prednisone exposure were reduced.”
Another factor that may have improved allo-HCT outcomes is the center’s change in approach to conditioning therapy over time.
“The gradual shift from very-high-dose conditioning therapy to less-intense myeloablative therapy and to reduced-intensity conditioning was likely responsible for a reduction in damage to the liver, lungs, and kidneys over the last 10 years,” Dr. McDonald said. “We were able to identify patients who were at especially high risk for mortality during a screening process before transplant ... thus allowing patients at highest risk to receive less intense conditioning therapy.”
Dr. McDonald added that this study’s results are encouraging, particularly the reduction in nonrelapse mortality. However, there is still room for improvement when it comes to relapse and progression.
This research was funded by the National Institutes of Health, the American Cancer Society, and the Patient-Centered Outcomes Research Institute. Dr. McDonald reported relationships with Sangamo Therapeutics, Soligenix Therapeutics, and Lucent Medical Systems. His coauthors disclosed relationships with a range of companies.
SOURCE: McDonald GB et al. Ann Intern Med. 2020 Jan 20. doi: 10.7326/M19-2936.
A cancer center has seen improved outcomes of allogeneic transplant in recent years, despite increases in patient age and comorbidities.
Researchers compared patients who received allogeneic hematopoietic cell transplants (allo-HCTs) during two periods, 2003-2007 and 2013-2017.
Patients treated in the 2013-2017 period were older and had more HCT-specific comorbidities at baseline, but they had lower rates of mortality, relapse, and graft-versus-host disease (GVHD) post transplant. George B. McDonald, MD, an emeritus member at Fred Hutchinson Cancer Research Center in Seattle, and coauthors described these findings in Annals of Internal Medicine.
“The primary question being addressed by this study was whether the striking improvement in survival … from the 1990s to the early 2000s, that we and other transplant centers have reported, had reached a plateau or whether further improvements in survival were being seen,” Dr. McDonald said in an interview.
“We knew that older and sicker patients were now coming for transplant, compared to 10 years ago. Our transplant protocols have backed away from the highest doses of chemotherapy and irradiation used to prepare patients for transplant, toward less toxic therapies, including reduced-intensity conditioning,” he added. “Our investigators have sought to prevent and more effectively treat the myriad of complications of allogeneic transplant, based on research done at the Fred Hutchinson Cancer Research Center and at transplant centers throughout the world.”
Baseline characteristics and treatment
Dr. McDonald and his colleagues analyzed data on patients who received allo-HCTs at Seattle Cancer Care Alliance. There were 1,148 patients treated in the 2003-2007 period and 1,131 patients treated in the 2013-2017 period.
Indications for allo-HCT were similar between the time periods. Patients were diagnosed with aplastic anemia, acute and chronic leukemias, Hodgkin and non-Hodgkin lymphomas, myelodysplastic syndromes, and multiple myeloma.
Patients in the 2013-2017 group were older and had more HCT-specific comorbidities than did the patients in the 2003-2007 group. The median age was 50.0 years (range, 0.1-80.9 years) and 47.2 years (range, 0.4-78.9 years), respectively. The median score on the augmented HCT-specific comorbidity index was 4.0 and 3.0, respectively.
The 2013-2017 group was more likely to have intermediate-risk disease (73% vs. 54%) but less likely to have high-risk disease (14% vs. 31%). The 2013-2017 group was less likely to receive high-dose myeloablative conditioning (15% vs. 67%) but more likely to have an unrelated donor (70% vs. 59%) or receive a cord blood transplant (13% vs. 4%).
GVHD prophylaxis differed between the time periods, with patients in the 2013-2017 group being more likely to receive sirolimus, posttransplant cyclophosphamide, and abatacept.
Outcomes
Overall, outcomes were superior in the 2013-2017 group. The rate of nonrelapse mortality at day 200 was higher in the 2003-2007 group than in the 2013-2017 group – 16% and 11%, respectively (adjusted hazard ratio, 0.66; P = .008).
Relapse or progression was more common in the 2003-2007 group – 348 patients vs. 244 patients (aHR, 0.76; P = .011). More patients died from relapse in the 2003-2007 group – 307 patients vs. 186 patients (aHR, 0.69; P = .002). More patients died from any cause in the 2003-2007 group – 653 patients vs. 418 patients (aHR, 0.66; P less than .001). The rate of grade 2-4 acute GVHD was higher in the 2003-2007 group – 71% vs. 69% (aHR, 0.80) – and so was the rate of chronic GVHD – 44% vs. 29% (aHR, 0.40). The risk of developing gram-negative bacteremia was lower in the 2013-2017 group (aHR, 0.42), as was the risk of invasive mold infection (aHR, 0.55).
Patients in the 2013-2017 group had a higher risk of cytomegalovirus (CMV) infection (aHR = 1.15), but they were less likely to have high levels of CMV viremia (aHR, 0.78 for greater than 250 IU/mL; aHR, 0.46 for greater than 1,000 IU/mL). Having higher levels of CMV viremia was associated with an increased risk of non-relapse mortality.
Potential drivers of outcome
Dr. McDonald said this study’s design makes it difficult to determine the causes of improved outcomes in the 2013-2017 period. However, the researchers do have theories about which practice changes may have contributed to better allo-HCT outcomes.
Dr. McDonald said the decrease in GVHD over time was “likely owing to the introduction of newer preventive strategies and immune-suppressive drugs.”
The decrease in nonrelapse mortality may have been driven, in part, by a reduction in fatal infections. Dr. McDonald said these infections were less frequent in the 2013-2017 period because of “molecular methods of diagnosis (especially for herpesviruses) and newer treatments (especially for fungal infections).”
“Another reason for a lower frequency of serious infection was a change in practice for treating graft-versus-host disease,” Dr. McDonald added. “Based on a randomized trial comparing lower- versus higher-dose prednisone for less-severe GVHD … both initial doses of prednisone and total prednisone exposure were reduced.”
Another factor that may have improved allo-HCT outcomes is the center’s change in approach to conditioning therapy over time.
“The gradual shift from very-high-dose conditioning therapy to less-intense myeloablative therapy and to reduced-intensity conditioning was likely responsible for a reduction in damage to the liver, lungs, and kidneys over the last 10 years,” Dr. McDonald said. “We were able to identify patients who were at especially high risk for mortality during a screening process before transplant ... thus allowing patients at highest risk to receive less intense conditioning therapy.”
Dr. McDonald added that this study’s results are encouraging, particularly the reduction in nonrelapse mortality. However, there is still room for improvement when it comes to relapse and progression.
This research was funded by the National Institutes of Health, the American Cancer Society, and the Patient-Centered Outcomes Research Institute. Dr. McDonald reported relationships with Sangamo Therapeutics, Soligenix Therapeutics, and Lucent Medical Systems. His coauthors disclosed relationships with a range of companies.
SOURCE: McDonald GB et al. Ann Intern Med. 2020 Jan 20. doi: 10.7326/M19-2936.
A cancer center has seen improved outcomes of allogeneic transplant in recent years, despite increases in patient age and comorbidities.
Researchers compared patients who received allogeneic hematopoietic cell transplants (allo-HCTs) during two periods, 2003-2007 and 2013-2017.
Patients treated in the 2013-2017 period were older and had more HCT-specific comorbidities at baseline, but they had lower rates of mortality, relapse, and graft-versus-host disease (GVHD) post transplant. George B. McDonald, MD, an emeritus member at Fred Hutchinson Cancer Research Center in Seattle, and coauthors described these findings in Annals of Internal Medicine.
“The primary question being addressed by this study was whether the striking improvement in survival … from the 1990s to the early 2000s, that we and other transplant centers have reported, had reached a plateau or whether further improvements in survival were being seen,” Dr. McDonald said in an interview.
“We knew that older and sicker patients were now coming for transplant, compared to 10 years ago. Our transplant protocols have backed away from the highest doses of chemotherapy and irradiation used to prepare patients for transplant, toward less toxic therapies, including reduced-intensity conditioning,” he added. “Our investigators have sought to prevent and more effectively treat the myriad of complications of allogeneic transplant, based on research done at the Fred Hutchinson Cancer Research Center and at transplant centers throughout the world.”
Baseline characteristics and treatment
Dr. McDonald and his colleagues analyzed data on patients who received allo-HCTs at Seattle Cancer Care Alliance. There were 1,148 patients treated in the 2003-2007 period and 1,131 patients treated in the 2013-2017 period.
Indications for allo-HCT were similar between the time periods. Patients were diagnosed with aplastic anemia, acute and chronic leukemias, Hodgkin and non-Hodgkin lymphomas, myelodysplastic syndromes, and multiple myeloma.
Patients in the 2013-2017 group were older and had more HCT-specific comorbidities than did the patients in the 2003-2007 group. The median age was 50.0 years (range, 0.1-80.9 years) and 47.2 years (range, 0.4-78.9 years), respectively. The median score on the augmented HCT-specific comorbidity index was 4.0 and 3.0, respectively.
The 2013-2017 group was more likely to have intermediate-risk disease (73% vs. 54%) but less likely to have high-risk disease (14% vs. 31%). The 2013-2017 group was less likely to receive high-dose myeloablative conditioning (15% vs. 67%) but more likely to have an unrelated donor (70% vs. 59%) or receive a cord blood transplant (13% vs. 4%).
GVHD prophylaxis differed between the time periods, with patients in the 2013-2017 group being more likely to receive sirolimus, posttransplant cyclophosphamide, and abatacept.
Outcomes
Overall, outcomes were superior in the 2013-2017 group. The rate of nonrelapse mortality at day 200 was higher in the 2003-2007 group than in the 2013-2017 group – 16% and 11%, respectively (adjusted hazard ratio, 0.66; P = .008).
Relapse or progression was more common in the 2003-2007 group – 348 patients vs. 244 patients (aHR, 0.76; P = .011). More patients died from relapse in the 2003-2007 group – 307 patients vs. 186 patients (aHR, 0.69; P = .002). More patients died from any cause in the 2003-2007 group – 653 patients vs. 418 patients (aHR, 0.66; P less than .001). The rate of grade 2-4 acute GVHD was higher in the 2003-2007 group – 71% vs. 69% (aHR, 0.80) – and so was the rate of chronic GVHD – 44% vs. 29% (aHR, 0.40). The risk of developing gram-negative bacteremia was lower in the 2013-2017 group (aHR, 0.42), as was the risk of invasive mold infection (aHR, 0.55).
Patients in the 2013-2017 group had a higher risk of cytomegalovirus (CMV) infection (aHR = 1.15), but they were less likely to have high levels of CMV viremia (aHR, 0.78 for greater than 250 IU/mL; aHR, 0.46 for greater than 1,000 IU/mL). Having higher levels of CMV viremia was associated with an increased risk of non-relapse mortality.
Potential drivers of outcome
Dr. McDonald said this study’s design makes it difficult to determine the causes of improved outcomes in the 2013-2017 period. However, the researchers do have theories about which practice changes may have contributed to better allo-HCT outcomes.
Dr. McDonald said the decrease in GVHD over time was “likely owing to the introduction of newer preventive strategies and immune-suppressive drugs.”
The decrease in nonrelapse mortality may have been driven, in part, by a reduction in fatal infections. Dr. McDonald said these infections were less frequent in the 2013-2017 period because of “molecular methods of diagnosis (especially for herpesviruses) and newer treatments (especially for fungal infections).”
“Another reason for a lower frequency of serious infection was a change in practice for treating graft-versus-host disease,” Dr. McDonald added. “Based on a randomized trial comparing lower- versus higher-dose prednisone for less-severe GVHD … both initial doses of prednisone and total prednisone exposure were reduced.”
Another factor that may have improved allo-HCT outcomes is the center’s change in approach to conditioning therapy over time.
“The gradual shift from very-high-dose conditioning therapy to less-intense myeloablative therapy and to reduced-intensity conditioning was likely responsible for a reduction in damage to the liver, lungs, and kidneys over the last 10 years,” Dr. McDonald said. “We were able to identify patients who were at especially high risk for mortality during a screening process before transplant ... thus allowing patients at highest risk to receive less intense conditioning therapy.”
Dr. McDonald added that this study’s results are encouraging, particularly the reduction in nonrelapse mortality. However, there is still room for improvement when it comes to relapse and progression.
This research was funded by the National Institutes of Health, the American Cancer Society, and the Patient-Centered Outcomes Research Institute. Dr. McDonald reported relationships with Sangamo Therapeutics, Soligenix Therapeutics, and Lucent Medical Systems. His coauthors disclosed relationships with a range of companies.
SOURCE: McDonald GB et al. Ann Intern Med. 2020 Jan 20. doi: 10.7326/M19-2936.
FROM ANNALS OF INTERNAL MEDICINE
Key clinical point: At a single center, outcomes of allogeneic hematopoietic cell transplant improved for patients treated in 2013-2017, compared with patients treated in 2003-2007.
Major finding: Rates of nonrelapse mortality at day 200 were higher in the 2003-2007 group than in the 2013-2017 group – 16% and 11%, respectively (adjusted hazard ratio, 0.66; P = .008).
Study details: A single-center study of 1,148 patients treated in the 2003-2007 period and 1,131 patients treated in the 2013-2017 period.
Disclosures: The research was funded by the National Institutes of Health, the American Cancer Society, and the Patient-Centered Outcomes Research Institute. Dr. McDonald reported relationships with Sangamo Therapeutics, Soligenix Therapeutics, and Lucent Medical Systems. His coauthors disclosed relationships with a range of companies.
Source: McDonald GB et al. Ann Intern Med. 2020 Jan 20. doi: 10.7326/M19-2936.
Cardiovascular risks associated with cannabis use
Researchers are recommending routine screening of marijuana use in cardiovascular care settings.
A review of current evidence suggests an association between marijuana use and adverse cardiovascular effects, as well as interactions between marijuana and cardiovascular medications.
Although more research is needed, the review authors suggested patients may benefit from marijuana screening and testing as well as discussions about the potential risks of marijuana use in the setting of cardiovascular disease.
Ersilia M. DeFilippis, MD, of Columbia University Irving Medical Center in New York and colleagues conducted this review, which was published in the Journal of the American College of Cardiology.
The authors noted that research on marijuana use and cardiovascular disease is limited. The different forms of cannabis and various routes of administration have made it difficult to draw concrete conclusions about marijuana products. Additionally, there have been no randomized, controlled trials of marijuana products in the United States because such trials are illegal; however, there are observational studies linking marijuana use and adverse cardiovascular effects.
Snapshot of available evidence
One study showed that smoking marijuana produces many of the same cardiotoxic chemicals produced by smoking tobacco (BMJ. 2003 May 3;326[7396]:942-3). Another study suggested marijuana smokers may have greater exposure to harmful chemicals (J Psychoactive Drugs. 1988 Jan-Mar;20[1]:43-6).
More specifically, a meta-analysis suggested that smoking marijuana was one of the top three triggers of myocardial infarction (Lancet. 2011 Feb 26;377[9767]:732-40). And in a systematic analysis, 28 of 33 studies linked marijuana use to an increased risk of acute coronary syndromes (Clin Toxicol [Phila]. 2019 Oct;57[10]:831-41).
Furthermore, a study of 2.5 million marijuana users showed that 3% experienced arrhythmias (Int J Cardiol. 2018 Aug 1;264:91-2). A population survey showed that people who smoked marijuana in the past year experienced a 3.3-fold higher rate of cerebrovascular events (Aust N Z J Public Health. 2016 Jun;40[3]:226-30).
Studies have also indicated that cannabinoids can affect cardiovascular medications, including antiarrhythmics, calcium-channel blockers, isosorbide dinitrate/mononitrate, statins, beta-blockers, warfarin, theophylline, and nonsteroidal anti-inflammatory drugs (Medicines [Basel]. 2018 Dec 23;6[1] pii: E3; Curr Top Behav Neurosci. 2017;32:249-62; Pharmacogenet Genomics. 2009 Jul;19[7]:559-62; Ann Pharmacother. 2009 Jul;43[7]:1347-53; Pharmacol Ther. 2019 Sep;201:25-38).
Reviewer recommendations
Cardiovascular specialists should be informed about regulations governing marijuana products, as well as “potential health consequences of marijuana and its derivatives,” according to Dr. DeFilippis and colleagues.
The authors recommend routinely screening patients for marijuana use, perhaps using the Daily Sessions, Frequency, Age of Onset, and Quantity of Cannabis Use Inventory (PLoS One. 2017 May 26;12[5]:e0178194) or the Cannabis Abuse Screening Test (Int J Methods Psychiatr Res. 2018 Jun;27[2]:e1597).
The authors say urine toxicology “may be reasonable” for patients with myocardial infarction or new-onset heart failure. Such testing is required for patients undergoing a heart transplant because marijuana use may affect their candidacy.
Dr. DeFilippis and colleagues say cardiovascular specialists should inform patients about the risks associated with marijuana use. The authors recommend shared decision making for patients who use marijuana for symptom management or palliative purposes.
Three review authors disclosed relationships with many different pharmaceutical companies. One author disclosed relationships with Medscape Cardiology and WebMD, which are owned by the same parent company as MDedge.
SOURCE: J Am Coll Cardiol. 2020 Jan 20. doi: 10.1016/j.jacc.2019.11.025.
Researchers are recommending routine screening of marijuana use in cardiovascular care settings.
A review of current evidence suggests an association between marijuana use and adverse cardiovascular effects, as well as interactions between marijuana and cardiovascular medications.
Although more research is needed, the review authors suggested patients may benefit from marijuana screening and testing as well as discussions about the potential risks of marijuana use in the setting of cardiovascular disease.
Ersilia M. DeFilippis, MD, of Columbia University Irving Medical Center in New York and colleagues conducted this review, which was published in the Journal of the American College of Cardiology.
The authors noted that research on marijuana use and cardiovascular disease is limited. The different forms of cannabis and various routes of administration have made it difficult to draw concrete conclusions about marijuana products. Additionally, there have been no randomized, controlled trials of marijuana products in the United States because such trials are illegal; however, there are observational studies linking marijuana use and adverse cardiovascular effects.
Snapshot of available evidence
One study showed that smoking marijuana produces many of the same cardiotoxic chemicals produced by smoking tobacco (BMJ. 2003 May 3;326[7396]:942-3). Another study suggested marijuana smokers may have greater exposure to harmful chemicals (J Psychoactive Drugs. 1988 Jan-Mar;20[1]:43-6).
More specifically, a meta-analysis suggested that smoking marijuana was one of the top three triggers of myocardial infarction (Lancet. 2011 Feb 26;377[9767]:732-40). And in a systematic analysis, 28 of 33 studies linked marijuana use to an increased risk of acute coronary syndromes (Clin Toxicol [Phila]. 2019 Oct;57[10]:831-41).
Furthermore, a study of 2.5 million marijuana users showed that 3% experienced arrhythmias (Int J Cardiol. 2018 Aug 1;264:91-2). A population survey showed that people who smoked marijuana in the past year experienced a 3.3-fold higher rate of cerebrovascular events (Aust N Z J Public Health. 2016 Jun;40[3]:226-30).
Studies have also indicated that cannabinoids can affect cardiovascular medications, including antiarrhythmics, calcium-channel blockers, isosorbide dinitrate/mononitrate, statins, beta-blockers, warfarin, theophylline, and nonsteroidal anti-inflammatory drugs (Medicines [Basel]. 2018 Dec 23;6[1] pii: E3; Curr Top Behav Neurosci. 2017;32:249-62; Pharmacogenet Genomics. 2009 Jul;19[7]:559-62; Ann Pharmacother. 2009 Jul;43[7]:1347-53; Pharmacol Ther. 2019 Sep;201:25-38).
Reviewer recommendations
Cardiovascular specialists should be informed about regulations governing marijuana products, as well as “potential health consequences of marijuana and its derivatives,” according to Dr. DeFilippis and colleagues.
The authors recommend routinely screening patients for marijuana use, perhaps using the Daily Sessions, Frequency, Age of Onset, and Quantity of Cannabis Use Inventory (PLoS One. 2017 May 26;12[5]:e0178194) or the Cannabis Abuse Screening Test (Int J Methods Psychiatr Res. 2018 Jun;27[2]:e1597).
The authors say urine toxicology “may be reasonable” for patients with myocardial infarction or new-onset heart failure. Such testing is required for patients undergoing a heart transplant because marijuana use may affect their candidacy.
Dr. DeFilippis and colleagues say cardiovascular specialists should inform patients about the risks associated with marijuana use. The authors recommend shared decision making for patients who use marijuana for symptom management or palliative purposes.
Three review authors disclosed relationships with many different pharmaceutical companies. One author disclosed relationships with Medscape Cardiology and WebMD, which are owned by the same parent company as MDedge.
SOURCE: J Am Coll Cardiol. 2020 Jan 20. doi: 10.1016/j.jacc.2019.11.025.
Researchers are recommending routine screening of marijuana use in cardiovascular care settings.
A review of current evidence suggests an association between marijuana use and adverse cardiovascular effects, as well as interactions between marijuana and cardiovascular medications.
Although more research is needed, the review authors suggested patients may benefit from marijuana screening and testing as well as discussions about the potential risks of marijuana use in the setting of cardiovascular disease.
Ersilia M. DeFilippis, MD, of Columbia University Irving Medical Center in New York and colleagues conducted this review, which was published in the Journal of the American College of Cardiology.
The authors noted that research on marijuana use and cardiovascular disease is limited. The different forms of cannabis and various routes of administration have made it difficult to draw concrete conclusions about marijuana products. Additionally, there have been no randomized, controlled trials of marijuana products in the United States because such trials are illegal; however, there are observational studies linking marijuana use and adverse cardiovascular effects.
Snapshot of available evidence
One study showed that smoking marijuana produces many of the same cardiotoxic chemicals produced by smoking tobacco (BMJ. 2003 May 3;326[7396]:942-3). Another study suggested marijuana smokers may have greater exposure to harmful chemicals (J Psychoactive Drugs. 1988 Jan-Mar;20[1]:43-6).
More specifically, a meta-analysis suggested that smoking marijuana was one of the top three triggers of myocardial infarction (Lancet. 2011 Feb 26;377[9767]:732-40). And in a systematic analysis, 28 of 33 studies linked marijuana use to an increased risk of acute coronary syndromes (Clin Toxicol [Phila]. 2019 Oct;57[10]:831-41).
Furthermore, a study of 2.5 million marijuana users showed that 3% experienced arrhythmias (Int J Cardiol. 2018 Aug 1;264:91-2). A population survey showed that people who smoked marijuana in the past year experienced a 3.3-fold higher rate of cerebrovascular events (Aust N Z J Public Health. 2016 Jun;40[3]:226-30).
Studies have also indicated that cannabinoids can affect cardiovascular medications, including antiarrhythmics, calcium-channel blockers, isosorbide dinitrate/mononitrate, statins, beta-blockers, warfarin, theophylline, and nonsteroidal anti-inflammatory drugs (Medicines [Basel]. 2018 Dec 23;6[1] pii: E3; Curr Top Behav Neurosci. 2017;32:249-62; Pharmacogenet Genomics. 2009 Jul;19[7]:559-62; Ann Pharmacother. 2009 Jul;43[7]:1347-53; Pharmacol Ther. 2019 Sep;201:25-38).
Reviewer recommendations
Cardiovascular specialists should be informed about regulations governing marijuana products, as well as “potential health consequences of marijuana and its derivatives,” according to Dr. DeFilippis and colleagues.
The authors recommend routinely screening patients for marijuana use, perhaps using the Daily Sessions, Frequency, Age of Onset, and Quantity of Cannabis Use Inventory (PLoS One. 2017 May 26;12[5]:e0178194) or the Cannabis Abuse Screening Test (Int J Methods Psychiatr Res. 2018 Jun;27[2]:e1597).
The authors say urine toxicology “may be reasonable” for patients with myocardial infarction or new-onset heart failure. Such testing is required for patients undergoing a heart transplant because marijuana use may affect their candidacy.
Dr. DeFilippis and colleagues say cardiovascular specialists should inform patients about the risks associated with marijuana use. The authors recommend shared decision making for patients who use marijuana for symptom management or palliative purposes.
Three review authors disclosed relationships with many different pharmaceutical companies. One author disclosed relationships with Medscape Cardiology and WebMD, which are owned by the same parent company as MDedge.
SOURCE: J Am Coll Cardiol. 2020 Jan 20. doi: 10.1016/j.jacc.2019.11.025.
FROM JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Travelers to three U.S. airports to be screened for novel coronavirus
according to an announcement from the Centers for Disease Control and Prevention.
Starting today, Jan. 17, 2020, people traveling from Wuhan to New York (JFK), San Francisco (SFO), and Los Angeles (LAX) airports will be screened for symptoms associated with 2019-nCoV, which include fever, cough, and difficulty breathing.
“Based on the information that CDC has today, we believe the current risk for this virus to the general public is low,” Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases, said during a CDC telebriefing.
To date, 45 cases of 2019-nCoV have been reported in Wuhan, according to the CDC. The Wuhan Municipal Health Commission said 15 patients have been cured and discharged, 5 severe cases are still being treated, and 2 patients have died. Both deaths occurred in older patients, one of whom was aged 69 years and one aged 61 years. One of the patients was known to have underlying health conditions.
Three cases of 2019-nCoV have been confirmed outside of Wuhan, one in Japan and two in Thailand. All three were travelers from Wuhan.
The virus is believed to have originated at Wuhan South China Seafood City, a market that sold seafood, chickens, bats, cats, marmots, and other wild animals. (The market has since been closed and disinfected.) The origin suggests animal-to-human transmission of 2019-nCoV, but it appears that human-to-human transmission can occur as well.
“While most of these infections seem to be happening from animals to people, there is some indication that limited person-to-person spread is happening,” Dr. Messonnier said.
Because of this potential risk, the CDC is working with the Department of Homeland Security’s Customs and Border Protection to screen travelers from Wuhan to the United States. The CDC is deploying about 100 additional staff to JFK, SFO, and LAX, where direct flights (JFK and SFO) or connecting flights (LAX) from Wuhan land.
The CDC could not confirm if exit screening is planned for people traveling abroad from Wuhan.
At the U.S. airports, travelers from Wuhan will be given a questionnaire asking about symptoms of 2019-nCoV (fever, cough, and difficulty breathing). People who exhibit symptoms will be assessed and questioned further. If they are believed to have 2019-nCoV, they will be sent to designated hospitals, where they will be examined, and samples will be collected.
Samples from patients with suspected 2019-nCoV will be sent to the CDC for analysis. Chinese health authorities made the full genome of 2019-nCoV publicly available, which will allow the CDC to confirm any cases that may arise in the United States. The CDC is currently working on a test to detect 2019-nCoV, which can be distributed to state health departments.
Earlier this month, the CDC issued a Level 1 Travel Health Notice for travelers to Wuhan and a Health Alert on 2019-nCoV. The latest information on 2019-nCoV can be found on the CDC’s Novel Coronavirus 2019 webpage.
according to an announcement from the Centers for Disease Control and Prevention.
Starting today, Jan. 17, 2020, people traveling from Wuhan to New York (JFK), San Francisco (SFO), and Los Angeles (LAX) airports will be screened for symptoms associated with 2019-nCoV, which include fever, cough, and difficulty breathing.
“Based on the information that CDC has today, we believe the current risk for this virus to the general public is low,” Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases, said during a CDC telebriefing.
To date, 45 cases of 2019-nCoV have been reported in Wuhan, according to the CDC. The Wuhan Municipal Health Commission said 15 patients have been cured and discharged, 5 severe cases are still being treated, and 2 patients have died. Both deaths occurred in older patients, one of whom was aged 69 years and one aged 61 years. One of the patients was known to have underlying health conditions.
Three cases of 2019-nCoV have been confirmed outside of Wuhan, one in Japan and two in Thailand. All three were travelers from Wuhan.
The virus is believed to have originated at Wuhan South China Seafood City, a market that sold seafood, chickens, bats, cats, marmots, and other wild animals. (The market has since been closed and disinfected.) The origin suggests animal-to-human transmission of 2019-nCoV, but it appears that human-to-human transmission can occur as well.
“While most of these infections seem to be happening from animals to people, there is some indication that limited person-to-person spread is happening,” Dr. Messonnier said.
Because of this potential risk, the CDC is working with the Department of Homeland Security’s Customs and Border Protection to screen travelers from Wuhan to the United States. The CDC is deploying about 100 additional staff to JFK, SFO, and LAX, where direct flights (JFK and SFO) or connecting flights (LAX) from Wuhan land.
The CDC could not confirm if exit screening is planned for people traveling abroad from Wuhan.
At the U.S. airports, travelers from Wuhan will be given a questionnaire asking about symptoms of 2019-nCoV (fever, cough, and difficulty breathing). People who exhibit symptoms will be assessed and questioned further. If they are believed to have 2019-nCoV, they will be sent to designated hospitals, where they will be examined, and samples will be collected.
Samples from patients with suspected 2019-nCoV will be sent to the CDC for analysis. Chinese health authorities made the full genome of 2019-nCoV publicly available, which will allow the CDC to confirm any cases that may arise in the United States. The CDC is currently working on a test to detect 2019-nCoV, which can be distributed to state health departments.
Earlier this month, the CDC issued a Level 1 Travel Health Notice for travelers to Wuhan and a Health Alert on 2019-nCoV. The latest information on 2019-nCoV can be found on the CDC’s Novel Coronavirus 2019 webpage.
according to an announcement from the Centers for Disease Control and Prevention.
Starting today, Jan. 17, 2020, people traveling from Wuhan to New York (JFK), San Francisco (SFO), and Los Angeles (LAX) airports will be screened for symptoms associated with 2019-nCoV, which include fever, cough, and difficulty breathing.
“Based on the information that CDC has today, we believe the current risk for this virus to the general public is low,” Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases, said during a CDC telebriefing.
To date, 45 cases of 2019-nCoV have been reported in Wuhan, according to the CDC. The Wuhan Municipal Health Commission said 15 patients have been cured and discharged, 5 severe cases are still being treated, and 2 patients have died. Both deaths occurred in older patients, one of whom was aged 69 years and one aged 61 years. One of the patients was known to have underlying health conditions.
Three cases of 2019-nCoV have been confirmed outside of Wuhan, one in Japan and two in Thailand. All three were travelers from Wuhan.
The virus is believed to have originated at Wuhan South China Seafood City, a market that sold seafood, chickens, bats, cats, marmots, and other wild animals. (The market has since been closed and disinfected.) The origin suggests animal-to-human transmission of 2019-nCoV, but it appears that human-to-human transmission can occur as well.
“While most of these infections seem to be happening from animals to people, there is some indication that limited person-to-person spread is happening,” Dr. Messonnier said.
Because of this potential risk, the CDC is working with the Department of Homeland Security’s Customs and Border Protection to screen travelers from Wuhan to the United States. The CDC is deploying about 100 additional staff to JFK, SFO, and LAX, where direct flights (JFK and SFO) or connecting flights (LAX) from Wuhan land.
The CDC could not confirm if exit screening is planned for people traveling abroad from Wuhan.
At the U.S. airports, travelers from Wuhan will be given a questionnaire asking about symptoms of 2019-nCoV (fever, cough, and difficulty breathing). People who exhibit symptoms will be assessed and questioned further. If they are believed to have 2019-nCoV, they will be sent to designated hospitals, where they will be examined, and samples will be collected.
Samples from patients with suspected 2019-nCoV will be sent to the CDC for analysis. Chinese health authorities made the full genome of 2019-nCoV publicly available, which will allow the CDC to confirm any cases that may arise in the United States. The CDC is currently working on a test to detect 2019-nCoV, which can be distributed to state health departments.
Earlier this month, the CDC issued a Level 1 Travel Health Notice for travelers to Wuhan and a Health Alert on 2019-nCoV. The latest information on 2019-nCoV can be found on the CDC’s Novel Coronavirus 2019 webpage.
Are providers asking about menstrual bleeding before/during anticoagulant therapy?
ORLANDO – A small study suggests health care providers may fail to ask patients about heavy menstrual bleeding before or during treatment with oral anticoagulants.
Researchers performed a chart review at a single center, which indicated that 60% of women were not asked about heavy menstrual bleeding before they were prescribed an oral anticoagulant.
Six months after the women started anticoagulant therapy, 29% required treatment for heavy menstrual bleeding. Charts for the remaining 71% of women contained no information about heavy menstrual bleeding.
“We were unable to distinguish between true absence of heavy menstrual bleeding and absence of reporting,” said Bethany T. Samuelson Bannow, MD, of Oregon Health & Science University, Portland.
Dr. Samuelson Bannow presented these findings at the annual meeting of the American Society of Hematology.
She explained that heavy menstrual bleeding is defined as more than 80 mL of blood loss per cycle. It affects 10%-15% of women in their lifetime, and anticoagulants increase the risk of heavy menstrual bleeding.
Studies have shown that heavy menstrual bleeding occurs in 22%-65% of women treated with vitamin K agonists and 20%-27% of women treated with rivaroxaban (Blood. 2017;130[24]:2603-9). However, many anticoagulant studies don’t include heavy menstrual bleeding as an outcome.
To gain more insight, Dr. Samuelson Bannow and colleagues conducted a chart review. Their study included 236 women of reproductive age treated at Oregon Health & Science University between Jan. 1, 2012, and Dec. 31, 2018.
The patients’ median age was 37 years (range, 18-50 years). Most patients (67%) were receiving an oral anticoagulant for venous thromboembolism. The rest were on anticoagulant therapy for arterial thrombosis (6%), atrial fibrillation (6%), a mechanical valve (1%), or “other” reasons (20%).
Dr. Samuelson Bannow said the other group was “almost exclusively women who were receiving prophylaxis” postoperatively or for travel. Most women in this group were receiving rivaroxaban.
Rivaroxaban was the most commonly prescribed anticoagulant in the entire cohort (41%), followed by warfarin (34%) and apixaban (25%).
At the time of anticoagulant prescription, 12% of women reported a history of heavy menstrual bleeding, and 28% did not. For most patients – 60% – there was no discussion of menstrual history documented.
Six months after starting oral anticoagulant therapy, 29% of patients required treatment for heavy menstrual bleeding. For 71% of patients, there was no documentation on the treatment of heavy menstrual bleeding.
Treatment for heavy menstrual bleeding was required in 33% of patients on rivaroxaban, 24% of those on apixaban, and 29% of those on warfarin, a significant difference (P less than .001).
“Rates of heavy menstrual bleeding … are higher in rivaroxaban users,” Dr. Samuelson Bannow said. “This is not the first study to demonstrate this. However, [the rate of heavy menstrual bleeding in this study] is still a lot lower than we would expect based on past levels with warfarin. This tells us we’re probably missing a lot of heavy menstrual bleeding. That’s not too surprising considering how few providers are actually asking about the menses.”
Dr. Samuelson Bannow and colleagues disclosed no conflicts of interest.
SOURCE: Samuelson Bannow BT et al. ASH 2019, Abstract 60.
ORLANDO – A small study suggests health care providers may fail to ask patients about heavy menstrual bleeding before or during treatment with oral anticoagulants.
Researchers performed a chart review at a single center, which indicated that 60% of women were not asked about heavy menstrual bleeding before they were prescribed an oral anticoagulant.
Six months after the women started anticoagulant therapy, 29% required treatment for heavy menstrual bleeding. Charts for the remaining 71% of women contained no information about heavy menstrual bleeding.
“We were unable to distinguish between true absence of heavy menstrual bleeding and absence of reporting,” said Bethany T. Samuelson Bannow, MD, of Oregon Health & Science University, Portland.
Dr. Samuelson Bannow presented these findings at the annual meeting of the American Society of Hematology.
She explained that heavy menstrual bleeding is defined as more than 80 mL of blood loss per cycle. It affects 10%-15% of women in their lifetime, and anticoagulants increase the risk of heavy menstrual bleeding.
Studies have shown that heavy menstrual bleeding occurs in 22%-65% of women treated with vitamin K agonists and 20%-27% of women treated with rivaroxaban (Blood. 2017;130[24]:2603-9). However, many anticoagulant studies don’t include heavy menstrual bleeding as an outcome.
To gain more insight, Dr. Samuelson Bannow and colleagues conducted a chart review. Their study included 236 women of reproductive age treated at Oregon Health & Science University between Jan. 1, 2012, and Dec. 31, 2018.
The patients’ median age was 37 years (range, 18-50 years). Most patients (67%) were receiving an oral anticoagulant for venous thromboembolism. The rest were on anticoagulant therapy for arterial thrombosis (6%), atrial fibrillation (6%), a mechanical valve (1%), or “other” reasons (20%).
Dr. Samuelson Bannow said the other group was “almost exclusively women who were receiving prophylaxis” postoperatively or for travel. Most women in this group were receiving rivaroxaban.
Rivaroxaban was the most commonly prescribed anticoagulant in the entire cohort (41%), followed by warfarin (34%) and apixaban (25%).
At the time of anticoagulant prescription, 12% of women reported a history of heavy menstrual bleeding, and 28% did not. For most patients – 60% – there was no discussion of menstrual history documented.
Six months after starting oral anticoagulant therapy, 29% of patients required treatment for heavy menstrual bleeding. For 71% of patients, there was no documentation on the treatment of heavy menstrual bleeding.
Treatment for heavy menstrual bleeding was required in 33% of patients on rivaroxaban, 24% of those on apixaban, and 29% of those on warfarin, a significant difference (P less than .001).
“Rates of heavy menstrual bleeding … are higher in rivaroxaban users,” Dr. Samuelson Bannow said. “This is not the first study to demonstrate this. However, [the rate of heavy menstrual bleeding in this study] is still a lot lower than we would expect based on past levels with warfarin. This tells us we’re probably missing a lot of heavy menstrual bleeding. That’s not too surprising considering how few providers are actually asking about the menses.”
Dr. Samuelson Bannow and colleagues disclosed no conflicts of interest.
SOURCE: Samuelson Bannow BT et al. ASH 2019, Abstract 60.
ORLANDO – A small study suggests health care providers may fail to ask patients about heavy menstrual bleeding before or during treatment with oral anticoagulants.
Researchers performed a chart review at a single center, which indicated that 60% of women were not asked about heavy menstrual bleeding before they were prescribed an oral anticoagulant.
Six months after the women started anticoagulant therapy, 29% required treatment for heavy menstrual bleeding. Charts for the remaining 71% of women contained no information about heavy menstrual bleeding.
“We were unable to distinguish between true absence of heavy menstrual bleeding and absence of reporting,” said Bethany T. Samuelson Bannow, MD, of Oregon Health & Science University, Portland.
Dr. Samuelson Bannow presented these findings at the annual meeting of the American Society of Hematology.
She explained that heavy menstrual bleeding is defined as more than 80 mL of blood loss per cycle. It affects 10%-15% of women in their lifetime, and anticoagulants increase the risk of heavy menstrual bleeding.
Studies have shown that heavy menstrual bleeding occurs in 22%-65% of women treated with vitamin K agonists and 20%-27% of women treated with rivaroxaban (Blood. 2017;130[24]:2603-9). However, many anticoagulant studies don’t include heavy menstrual bleeding as an outcome.
To gain more insight, Dr. Samuelson Bannow and colleagues conducted a chart review. Their study included 236 women of reproductive age treated at Oregon Health & Science University between Jan. 1, 2012, and Dec. 31, 2018.
The patients’ median age was 37 years (range, 18-50 years). Most patients (67%) were receiving an oral anticoagulant for venous thromboembolism. The rest were on anticoagulant therapy for arterial thrombosis (6%), atrial fibrillation (6%), a mechanical valve (1%), or “other” reasons (20%).
Dr. Samuelson Bannow said the other group was “almost exclusively women who were receiving prophylaxis” postoperatively or for travel. Most women in this group were receiving rivaroxaban.
Rivaroxaban was the most commonly prescribed anticoagulant in the entire cohort (41%), followed by warfarin (34%) and apixaban (25%).
At the time of anticoagulant prescription, 12% of women reported a history of heavy menstrual bleeding, and 28% did not. For most patients – 60% – there was no discussion of menstrual history documented.
Six months after starting oral anticoagulant therapy, 29% of patients required treatment for heavy menstrual bleeding. For 71% of patients, there was no documentation on the treatment of heavy menstrual bleeding.
Treatment for heavy menstrual bleeding was required in 33% of patients on rivaroxaban, 24% of those on apixaban, and 29% of those on warfarin, a significant difference (P less than .001).
“Rates of heavy menstrual bleeding … are higher in rivaroxaban users,” Dr. Samuelson Bannow said. “This is not the first study to demonstrate this. However, [the rate of heavy menstrual bleeding in this study] is still a lot lower than we would expect based on past levels with warfarin. This tells us we’re probably missing a lot of heavy menstrual bleeding. That’s not too surprising considering how few providers are actually asking about the menses.”
Dr. Samuelson Bannow and colleagues disclosed no conflicts of interest.
SOURCE: Samuelson Bannow BT et al. ASH 2019, Abstract 60.
REPORTING FROM ASH 2019
BET inhibitor exhibits activity in myelofibrosis
ORLANDO – The BET inhibitor CPI-0610, given alone or in combination with ruxolitinib, has demonstrated activity in a phase 2 trial of patients with relapsed/refractory myelofibrosis (MF).
Responses were best among transfusion-dependent patients who received CPI-0610 and ruxolitinib. All but one of these patients experienced symptom improvement.
In the monotherapy group, results were best among transfusion-independent patients. All of these patients had an improvement in Patient Global Impression of Change (PGIC) score, and most had a 50% or greater improvement in total symptom score (TSS).
John Mascarenhas, MD, of the Icahn School of Medicine at Mount Sinai, New York, presented these results from the phase 2 MANIFEST trial (NCT02158858) at the annual meeting of the American Society of Hematology.
Dr. Mascarenhas presented data on 90 patients – 59 with primary MF, 16 with post–polycythemia vera MF, 13 with post–essential thrombocythemia MF, and 2 whose type of MF was unknown. At baseline, the patients’ median age was 69 years and 76.7% of patients had received at least 6 months of ruxolitinib treatment.
Of the 36 patients who received CPI-0610 monotherapy, 34 were still receiving the treatment as of Oct. 17, 2019. Of the 54 patients treated with CPI-0610 and ruxolitinib, 41 were still receiving the combination at that time. The median duration of treatment was 11.3 weeks in the monotherapy arm and 25.9 weeks in the combination arm. Responses were assessed at 24 weeks.
“CPI-0610 monotherapy or added on to ruxolitinib in a relapsed/refractory MF population demonstrated antitumor activity, as evidenced by spleen and symptom improvement,” Dr. Mascarenhas said. “Symptom responses were observed in a majority of patients. We treated these patients, and they felt much better. It was impressive.”
Efficacy of monotherapy
There were two evaluable patients who had been transfusion dependent at baseline and received CPI-0610 monotherapy for at least 24 weeks. Neither patient achieved transfusion independence, and neither had a spleen volume reduction of at least 35% (SVR35). One patient had a 50% or greater improvement in TSS, and one had an improvement in PGIC score.
There were seven evaluable patients who were transfusion independent at baseline and received CPI-0610 for at least 24 weeks. None of these patients had an SVR35 response, three of five evaluable patients had a 50% or greater improvement in TSS, and all seven had an improvement in PGIC score.
Efficacy of the combination
There were 14 patients who had been transfusion dependent at baseline and received CPI-0610 and ruxolitinib for at least 24 weeks. Six of these patients had become transfusion independent at week 24.
Among the patients who were transfusion dependent at baseline, 25% (3/12) had an SVR35 response at week 24, 54% (7/13) had a 50% or greater improvement in TSS, and 75% (9/12) had an improvement in PGIC score.
There were 13 evaluable patients who were transfusion independent at baseline and received CPI-0610 and ruxolitinib for at least 24 weeks. None of these patients had an SVR35 response, 38% had a 50% or greater improvement in TSS, and 69% had an improvement in PGIC score.
Safety
“CPI-0610 monotherapy or as an add-on to [ruxolitinib] was generally well tolerated,” Dr. Mascarenhas said. “Thrombocytopenia was asymptomatic, generally reversible, and manageable. There were no other unanticipated safety concerns.”
All 90 patients were evaluable for safety. Hematologic adverse events included thrombocytopenia (23.3%) and anemia (8.9%).
The most common nonhematologic adverse events were diarrhea (32.2%), nausea (22.2%), cough (16.7%), fatigue (14.4%), vomiting (14.4%), and upper respiratory tract infection (14.4%).
Eight patients (8.9%) experienced grade 4 adverse events, but all events resolved. Four events occurred in the monotherapy arm, and one (rash) required dose interruption. Of the four events in the combination arm, one (anemia) was considered treatment related.
There were three fatal adverse events – acute kidney injury, traumatic subdural hematoma, and brain stem hemorrhage. None of these events were considered related to CPI-0610.
Based on these preliminary results, the cohort of transfusion-dependent patients receiving CPI-0610 and ruxolitinib has been expanded. A cohort of ruxolitinib-naive patients receiving CPI-0610 and ruxolitinib has been expanded as well.
The MANIFEST trial is funded by Constellation Pharmaceuticals in collaboration with the Leukemia & Lymphoma Society. Dr. Mascarenhas reported relationships with Incyte, Janssen, CTI Biopharma, Novartis, Roche, Merck, Celgene, Promedior, Merus, and PharmaEssentia.
SOURCE: Mascarenhas J et al. ASH 2019, Abstract 670.
ORLANDO – The BET inhibitor CPI-0610, given alone or in combination with ruxolitinib, has demonstrated activity in a phase 2 trial of patients with relapsed/refractory myelofibrosis (MF).
Responses were best among transfusion-dependent patients who received CPI-0610 and ruxolitinib. All but one of these patients experienced symptom improvement.
In the monotherapy group, results were best among transfusion-independent patients. All of these patients had an improvement in Patient Global Impression of Change (PGIC) score, and most had a 50% or greater improvement in total symptom score (TSS).
John Mascarenhas, MD, of the Icahn School of Medicine at Mount Sinai, New York, presented these results from the phase 2 MANIFEST trial (NCT02158858) at the annual meeting of the American Society of Hematology.
Dr. Mascarenhas presented data on 90 patients – 59 with primary MF, 16 with post–polycythemia vera MF, 13 with post–essential thrombocythemia MF, and 2 whose type of MF was unknown. At baseline, the patients’ median age was 69 years and 76.7% of patients had received at least 6 months of ruxolitinib treatment.
Of the 36 patients who received CPI-0610 monotherapy, 34 were still receiving the treatment as of Oct. 17, 2019. Of the 54 patients treated with CPI-0610 and ruxolitinib, 41 were still receiving the combination at that time. The median duration of treatment was 11.3 weeks in the monotherapy arm and 25.9 weeks in the combination arm. Responses were assessed at 24 weeks.
“CPI-0610 monotherapy or added on to ruxolitinib in a relapsed/refractory MF population demonstrated antitumor activity, as evidenced by spleen and symptom improvement,” Dr. Mascarenhas said. “Symptom responses were observed in a majority of patients. We treated these patients, and they felt much better. It was impressive.”
Efficacy of monotherapy
There were two evaluable patients who had been transfusion dependent at baseline and received CPI-0610 monotherapy for at least 24 weeks. Neither patient achieved transfusion independence, and neither had a spleen volume reduction of at least 35% (SVR35). One patient had a 50% or greater improvement in TSS, and one had an improvement in PGIC score.
There were seven evaluable patients who were transfusion independent at baseline and received CPI-0610 for at least 24 weeks. None of these patients had an SVR35 response, three of five evaluable patients had a 50% or greater improvement in TSS, and all seven had an improvement in PGIC score.
Efficacy of the combination
There were 14 patients who had been transfusion dependent at baseline and received CPI-0610 and ruxolitinib for at least 24 weeks. Six of these patients had become transfusion independent at week 24.
Among the patients who were transfusion dependent at baseline, 25% (3/12) had an SVR35 response at week 24, 54% (7/13) had a 50% or greater improvement in TSS, and 75% (9/12) had an improvement in PGIC score.
There were 13 evaluable patients who were transfusion independent at baseline and received CPI-0610 and ruxolitinib for at least 24 weeks. None of these patients had an SVR35 response, 38% had a 50% or greater improvement in TSS, and 69% had an improvement in PGIC score.
Safety
“CPI-0610 monotherapy or as an add-on to [ruxolitinib] was generally well tolerated,” Dr. Mascarenhas said. “Thrombocytopenia was asymptomatic, generally reversible, and manageable. There were no other unanticipated safety concerns.”
All 90 patients were evaluable for safety. Hematologic adverse events included thrombocytopenia (23.3%) and anemia (8.9%).
The most common nonhematologic adverse events were diarrhea (32.2%), nausea (22.2%), cough (16.7%), fatigue (14.4%), vomiting (14.4%), and upper respiratory tract infection (14.4%).
Eight patients (8.9%) experienced grade 4 adverse events, but all events resolved. Four events occurred in the monotherapy arm, and one (rash) required dose interruption. Of the four events in the combination arm, one (anemia) was considered treatment related.
There were three fatal adverse events – acute kidney injury, traumatic subdural hematoma, and brain stem hemorrhage. None of these events were considered related to CPI-0610.
Based on these preliminary results, the cohort of transfusion-dependent patients receiving CPI-0610 and ruxolitinib has been expanded. A cohort of ruxolitinib-naive patients receiving CPI-0610 and ruxolitinib has been expanded as well.
The MANIFEST trial is funded by Constellation Pharmaceuticals in collaboration with the Leukemia & Lymphoma Society. Dr. Mascarenhas reported relationships with Incyte, Janssen, CTI Biopharma, Novartis, Roche, Merck, Celgene, Promedior, Merus, and PharmaEssentia.
SOURCE: Mascarenhas J et al. ASH 2019, Abstract 670.
ORLANDO – The BET inhibitor CPI-0610, given alone or in combination with ruxolitinib, has demonstrated activity in a phase 2 trial of patients with relapsed/refractory myelofibrosis (MF).
Responses were best among transfusion-dependent patients who received CPI-0610 and ruxolitinib. All but one of these patients experienced symptom improvement.
In the monotherapy group, results were best among transfusion-independent patients. All of these patients had an improvement in Patient Global Impression of Change (PGIC) score, and most had a 50% or greater improvement in total symptom score (TSS).
John Mascarenhas, MD, of the Icahn School of Medicine at Mount Sinai, New York, presented these results from the phase 2 MANIFEST trial (NCT02158858) at the annual meeting of the American Society of Hematology.
Dr. Mascarenhas presented data on 90 patients – 59 with primary MF, 16 with post–polycythemia vera MF, 13 with post–essential thrombocythemia MF, and 2 whose type of MF was unknown. At baseline, the patients’ median age was 69 years and 76.7% of patients had received at least 6 months of ruxolitinib treatment.
Of the 36 patients who received CPI-0610 monotherapy, 34 were still receiving the treatment as of Oct. 17, 2019. Of the 54 patients treated with CPI-0610 and ruxolitinib, 41 were still receiving the combination at that time. The median duration of treatment was 11.3 weeks in the monotherapy arm and 25.9 weeks in the combination arm. Responses were assessed at 24 weeks.
“CPI-0610 monotherapy or added on to ruxolitinib in a relapsed/refractory MF population demonstrated antitumor activity, as evidenced by spleen and symptom improvement,” Dr. Mascarenhas said. “Symptom responses were observed in a majority of patients. We treated these patients, and they felt much better. It was impressive.”
Efficacy of monotherapy
There were two evaluable patients who had been transfusion dependent at baseline and received CPI-0610 monotherapy for at least 24 weeks. Neither patient achieved transfusion independence, and neither had a spleen volume reduction of at least 35% (SVR35). One patient had a 50% or greater improvement in TSS, and one had an improvement in PGIC score.
There were seven evaluable patients who were transfusion independent at baseline and received CPI-0610 for at least 24 weeks. None of these patients had an SVR35 response, three of five evaluable patients had a 50% or greater improvement in TSS, and all seven had an improvement in PGIC score.
Efficacy of the combination
There were 14 patients who had been transfusion dependent at baseline and received CPI-0610 and ruxolitinib for at least 24 weeks. Six of these patients had become transfusion independent at week 24.
Among the patients who were transfusion dependent at baseline, 25% (3/12) had an SVR35 response at week 24, 54% (7/13) had a 50% or greater improvement in TSS, and 75% (9/12) had an improvement in PGIC score.
There were 13 evaluable patients who were transfusion independent at baseline and received CPI-0610 and ruxolitinib for at least 24 weeks. None of these patients had an SVR35 response, 38% had a 50% or greater improvement in TSS, and 69% had an improvement in PGIC score.
Safety
“CPI-0610 monotherapy or as an add-on to [ruxolitinib] was generally well tolerated,” Dr. Mascarenhas said. “Thrombocytopenia was asymptomatic, generally reversible, and manageable. There were no other unanticipated safety concerns.”
All 90 patients were evaluable for safety. Hematologic adverse events included thrombocytopenia (23.3%) and anemia (8.9%).
The most common nonhematologic adverse events were diarrhea (32.2%), nausea (22.2%), cough (16.7%), fatigue (14.4%), vomiting (14.4%), and upper respiratory tract infection (14.4%).
Eight patients (8.9%) experienced grade 4 adverse events, but all events resolved. Four events occurred in the monotherapy arm, and one (rash) required dose interruption. Of the four events in the combination arm, one (anemia) was considered treatment related.
There were three fatal adverse events – acute kidney injury, traumatic subdural hematoma, and brain stem hemorrhage. None of these events were considered related to CPI-0610.
Based on these preliminary results, the cohort of transfusion-dependent patients receiving CPI-0610 and ruxolitinib has been expanded. A cohort of ruxolitinib-naive patients receiving CPI-0610 and ruxolitinib has been expanded as well.
The MANIFEST trial is funded by Constellation Pharmaceuticals in collaboration with the Leukemia & Lymphoma Society. Dr. Mascarenhas reported relationships with Incyte, Janssen, CTI Biopharma, Novartis, Roche, Merck, Celgene, Promedior, Merus, and PharmaEssentia.
SOURCE: Mascarenhas J et al. ASH 2019, Abstract 670.
REPORTING FROM ASH 2019
NCCN guidelines highlight ‘complicated’ treatment for pediatric lymphomas
The National Comprehensive Cancer Network (NCCN) has released its first set of guidelines for managing pediatric aggressive mature B-cell lymphomas.
The guidelines highlight the complexities of treating pediatric Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL), as recommendations include a range of multiagent regimens for different patient groups at various time points.
“The treatment of this disease is relatively complicated,” said Kimberly J. Davies, MD, a pediatric hematologist/oncologist at Dana-Farber Cancer Institute in Boston and chair of the guidelines panel. “The chemotherapy regimens have a lot of drugs, a lot of nuances to how they’re supposed to be given. These guidelines delineate that treatment and help the provider … make sure they are delivering the treatment a patient needs.”
The guidelines recommend different regimens according to a patient’s risk group, but the same treatment approach should be used for patients with BL and those with DLBCL.
“The biggest difference between pediatric and adult patients is that pediatric patients are more uniformly treated, regardless of what type of aggressive B-cell lymphoma they have,” said Matthew Barth, MD, a pediatric hematologist/oncologist at Roswell Park Comprehensive Cancer Center in Buffalo, N.Y., and vice chair of the NCCN guidelines panel.
“Adults with diffuse large B-cell lymphoma and Burkitt lymphoma are generally treated with different chemotherapy regimens, but, in pediatrics, we use the same treatment regimens for both diffuse large B-cell lymphoma and Burkitt lymphoma,” he added.
As an example, the new guidelines recommend that pediatric patients with low-risk BL/DLBCL receive the POG9219 regimen (N Engl J Med. 1997 Oct 30;337[18]:1259-66) or FAB/LMB96 regimen A (Br J Haematol. 2008 Jun;141[6]:840-7) as induction, or they should be enrolled in a clinical trial.
On the other hand, induction for high-risk pediatric BL/DLBCL patients should consist of rituximab and a chemotherapy regimen used in the COG ANHL1131 trial. The recommendation to incorporate rituximab in high-risk pediatric patients is based on results from that trial (J Clin Oncol. 2016 May 20. doi: 10.1200/JCO.2016.34.15_suppl.10507).
“Until recent clinical trial data was available, we weren’t really sure how to incorporate rituximab into the treatment of pediatric patients with mature B-cell lymphomas,” Dr. Barth said. “We now have evidence that rituximab is clearly beneficial for patients who are in higher-risk groups.”
Dr. Barth and Dr. Davies both noted that pediatric BL and DLBCL have high cure rates. Long-term survival rates range from about 80% to more than 90%, according to the American Cancer Society. However, the patients who do relapse or progress can be difficult to treat.
“We have quite good cure rates at this point in time, which is a great success, but that means that a very small population of patients don’t respond to initial therapy, and … it’s hard to know what the best treatment for those patients is,” Dr. Davies said.
She noted that studies are underway to determine if immunotherapies, including chimeric antigen receptor T-cell therapy, might improve outcomes in patients with relapsed or refractory disease.
For now, the NCCN guidelines recommend clinical trial enrollment for relapsed/refractory patients. Alternatively, these patients can receive additional chemotherapy, and responders can proceed to transplant. Patients who don’t achieve at least a partial response may go on to a clinical trial or receive best supportive care.
Dr. Davies and Dr. Barth reported having no conflicts of interest.
The National Comprehensive Cancer Network (NCCN) has released its first set of guidelines for managing pediatric aggressive mature B-cell lymphomas.
The guidelines highlight the complexities of treating pediatric Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL), as recommendations include a range of multiagent regimens for different patient groups at various time points.
“The treatment of this disease is relatively complicated,” said Kimberly J. Davies, MD, a pediatric hematologist/oncologist at Dana-Farber Cancer Institute in Boston and chair of the guidelines panel. “The chemotherapy regimens have a lot of drugs, a lot of nuances to how they’re supposed to be given. These guidelines delineate that treatment and help the provider … make sure they are delivering the treatment a patient needs.”
The guidelines recommend different regimens according to a patient’s risk group, but the same treatment approach should be used for patients with BL and those with DLBCL.
“The biggest difference between pediatric and adult patients is that pediatric patients are more uniformly treated, regardless of what type of aggressive B-cell lymphoma they have,” said Matthew Barth, MD, a pediatric hematologist/oncologist at Roswell Park Comprehensive Cancer Center in Buffalo, N.Y., and vice chair of the NCCN guidelines panel.
“Adults with diffuse large B-cell lymphoma and Burkitt lymphoma are generally treated with different chemotherapy regimens, but, in pediatrics, we use the same treatment regimens for both diffuse large B-cell lymphoma and Burkitt lymphoma,” he added.
As an example, the new guidelines recommend that pediatric patients with low-risk BL/DLBCL receive the POG9219 regimen (N Engl J Med. 1997 Oct 30;337[18]:1259-66) or FAB/LMB96 regimen A (Br J Haematol. 2008 Jun;141[6]:840-7) as induction, or they should be enrolled in a clinical trial.
On the other hand, induction for high-risk pediatric BL/DLBCL patients should consist of rituximab and a chemotherapy regimen used in the COG ANHL1131 trial. The recommendation to incorporate rituximab in high-risk pediatric patients is based on results from that trial (J Clin Oncol. 2016 May 20. doi: 10.1200/JCO.2016.34.15_suppl.10507).
“Until recent clinical trial data was available, we weren’t really sure how to incorporate rituximab into the treatment of pediatric patients with mature B-cell lymphomas,” Dr. Barth said. “We now have evidence that rituximab is clearly beneficial for patients who are in higher-risk groups.”
Dr. Barth and Dr. Davies both noted that pediatric BL and DLBCL have high cure rates. Long-term survival rates range from about 80% to more than 90%, according to the American Cancer Society. However, the patients who do relapse or progress can be difficult to treat.
“We have quite good cure rates at this point in time, which is a great success, but that means that a very small population of patients don’t respond to initial therapy, and … it’s hard to know what the best treatment for those patients is,” Dr. Davies said.
She noted that studies are underway to determine if immunotherapies, including chimeric antigen receptor T-cell therapy, might improve outcomes in patients with relapsed or refractory disease.
For now, the NCCN guidelines recommend clinical trial enrollment for relapsed/refractory patients. Alternatively, these patients can receive additional chemotherapy, and responders can proceed to transplant. Patients who don’t achieve at least a partial response may go on to a clinical trial or receive best supportive care.
Dr. Davies and Dr. Barth reported having no conflicts of interest.
The National Comprehensive Cancer Network (NCCN) has released its first set of guidelines for managing pediatric aggressive mature B-cell lymphomas.
The guidelines highlight the complexities of treating pediatric Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL), as recommendations include a range of multiagent regimens for different patient groups at various time points.
“The treatment of this disease is relatively complicated,” said Kimberly J. Davies, MD, a pediatric hematologist/oncologist at Dana-Farber Cancer Institute in Boston and chair of the guidelines panel. “The chemotherapy regimens have a lot of drugs, a lot of nuances to how they’re supposed to be given. These guidelines delineate that treatment and help the provider … make sure they are delivering the treatment a patient needs.”
The guidelines recommend different regimens according to a patient’s risk group, but the same treatment approach should be used for patients with BL and those with DLBCL.
“The biggest difference between pediatric and adult patients is that pediatric patients are more uniformly treated, regardless of what type of aggressive B-cell lymphoma they have,” said Matthew Barth, MD, a pediatric hematologist/oncologist at Roswell Park Comprehensive Cancer Center in Buffalo, N.Y., and vice chair of the NCCN guidelines panel.
“Adults with diffuse large B-cell lymphoma and Burkitt lymphoma are generally treated with different chemotherapy regimens, but, in pediatrics, we use the same treatment regimens for both diffuse large B-cell lymphoma and Burkitt lymphoma,” he added.
As an example, the new guidelines recommend that pediatric patients with low-risk BL/DLBCL receive the POG9219 regimen (N Engl J Med. 1997 Oct 30;337[18]:1259-66) or FAB/LMB96 regimen A (Br J Haematol. 2008 Jun;141[6]:840-7) as induction, or they should be enrolled in a clinical trial.
On the other hand, induction for high-risk pediatric BL/DLBCL patients should consist of rituximab and a chemotherapy regimen used in the COG ANHL1131 trial. The recommendation to incorporate rituximab in high-risk pediatric patients is based on results from that trial (J Clin Oncol. 2016 May 20. doi: 10.1200/JCO.2016.34.15_suppl.10507).
“Until recent clinical trial data was available, we weren’t really sure how to incorporate rituximab into the treatment of pediatric patients with mature B-cell lymphomas,” Dr. Barth said. “We now have evidence that rituximab is clearly beneficial for patients who are in higher-risk groups.”
Dr. Barth and Dr. Davies both noted that pediatric BL and DLBCL have high cure rates. Long-term survival rates range from about 80% to more than 90%, according to the American Cancer Society. However, the patients who do relapse or progress can be difficult to treat.
“We have quite good cure rates at this point in time, which is a great success, but that means that a very small population of patients don’t respond to initial therapy, and … it’s hard to know what the best treatment for those patients is,” Dr. Davies said.
She noted that studies are underway to determine if immunotherapies, including chimeric antigen receptor T-cell therapy, might improve outcomes in patients with relapsed or refractory disease.
For now, the NCCN guidelines recommend clinical trial enrollment for relapsed/refractory patients. Alternatively, these patients can receive additional chemotherapy, and responders can proceed to transplant. Patients who don’t achieve at least a partial response may go on to a clinical trial or receive best supportive care.
Dr. Davies and Dr. Barth reported having no conflicts of interest.
9/11 responders show increased risk of leukemia, other cancers
New data suggest an increased risk of leukemia among responders who worked at the World Trade Center site after the attacks on Sept. 11, 2001.
Previous studies have shown that 9/11 responders have a higher incidence of cancers than does the general population. The current study is the first to show a higher incidence of leukemia among responders. It also shows a higher incidence of thyroid and prostate cancers as well as all cancer types combined.
These findings were published in JNCI Cancer Spectrum.
“This study showed increased incidence of several cancer types compared to previously conducted studies with shorter follow-up periods,” study author Susan L, Teitelbaum, PhD, of the Icahn School of Medicine at Mount Sinai, New York, said in a press release.
“Because of the long latency period of many types of cancer, it is possible that increased rates of other cancers, as well as World Trade Center exposure health issues, may emerge after longer periods of study.”
Dr. Teitelbaum and colleagues evaluated responders enrolled in the World Trade Center Health Program General Responder Cohort from when it was established in July 2002 through the end of follow-up, which was Dec. 31, 2013, for New York residents and Dec. 31, 2012, for residents of other states.
To be eligible for the cohort, responders must have worked on the World Trade Center rescue and recovery effort a minimum of 4 hours in the first 4 days from Sept. 11, 2001, 24 hours in September 2001, or 80 hours from September through December 2001. Responders also had to complete at least one monitoring visit.
Responders’ data were linked to data from cancer registries in New York, New Jersey, Pennsylvania, and Connecticut (where most responders lived at the time of the attacks), as well as Florida and North Carolina (where responders were known to retire). The responders were linked to the registries using probabilistic matching algorithms, which made use of information such as patient name, address, social security number, sex, race, and birth date.
The researchers noted that patients who enrolled in the General Responder Cohort had their cancer certified for federally funded treatment, and this factor might result in “sicker members disproportionately self-selecting into the program.” To reduce this potential bias, the researchers conducted a restricted analysis in which counts of cancer cases and person-years of observation began 6 months after responder enrollment.
The researchers analyzed data on 28,729 responders who primarily worked in protective services (49.0%) and construction (20.8%). Responders spent a median of 52 days on the rescue and recovery effort, and 44.4% of them had some exposure to the dust cloud caused by the collapse of the towers.
In the restricted analysis, there were 1,072 cancers observed in 999 responders. Compared with the general population, responders had a significantly higher incidence of all cancers combined, with a standardized incidence ratio (SIR) of 1.09.
Responders had a significantly higher incidence of prostate cancer (SIR,1.25), thyroid cancer (SIR, 2.19), and leukemia (SIR, 1.41). The leukemia category included acute myeloid leukemia (SIR,1.58) and chronic lymphocytic leukemia (SIR, 1.08).
“Although other studies have revealed elevated SIRs for other hematologic malignancies, this is the first reported, statistically significant, elevated SIR for leukemia,” the researchers wrote. “Leukemia is known to occur after exposure to occupational carcinogens, including benzene (burning jet fuel and other sources at the [World Trade Center] site), possibly at low levels of exposure and with a latency of several years from exposure.”
A multivariate analysis showed no association between cancer incidence and the length of time responders spent on the rescue and recovery effort or the intensity of their exposure to the dust cloud or debris pile.
The analysis did show an elevated risk of all cancers combined with each 1-year increase in responder age (hazard ratio, 1.09), among male responders (HR, 1.21), and among responders who smoked at baseline (HR, 1.29).
This research was supported by the Centers for Disease Control and Prevention/National Institute for Occupational Safety and Health. The researchers disclosed no conflicts of interest.
SOURCE: Shapiro MZ et al. JNCI Cancer Spectr. 2020 Jan 14. doi: 10.1093/jncics/pkz090.
New data suggest an increased risk of leukemia among responders who worked at the World Trade Center site after the attacks on Sept. 11, 2001.
Previous studies have shown that 9/11 responders have a higher incidence of cancers than does the general population. The current study is the first to show a higher incidence of leukemia among responders. It also shows a higher incidence of thyroid and prostate cancers as well as all cancer types combined.
These findings were published in JNCI Cancer Spectrum.
“This study showed increased incidence of several cancer types compared to previously conducted studies with shorter follow-up periods,” study author Susan L, Teitelbaum, PhD, of the Icahn School of Medicine at Mount Sinai, New York, said in a press release.
“Because of the long latency period of many types of cancer, it is possible that increased rates of other cancers, as well as World Trade Center exposure health issues, may emerge after longer periods of study.”
Dr. Teitelbaum and colleagues evaluated responders enrolled in the World Trade Center Health Program General Responder Cohort from when it was established in July 2002 through the end of follow-up, which was Dec. 31, 2013, for New York residents and Dec. 31, 2012, for residents of other states.
To be eligible for the cohort, responders must have worked on the World Trade Center rescue and recovery effort a minimum of 4 hours in the first 4 days from Sept. 11, 2001, 24 hours in September 2001, or 80 hours from September through December 2001. Responders also had to complete at least one monitoring visit.
Responders’ data were linked to data from cancer registries in New York, New Jersey, Pennsylvania, and Connecticut (where most responders lived at the time of the attacks), as well as Florida and North Carolina (where responders were known to retire). The responders were linked to the registries using probabilistic matching algorithms, which made use of information such as patient name, address, social security number, sex, race, and birth date.
The researchers noted that patients who enrolled in the General Responder Cohort had their cancer certified for federally funded treatment, and this factor might result in “sicker members disproportionately self-selecting into the program.” To reduce this potential bias, the researchers conducted a restricted analysis in which counts of cancer cases and person-years of observation began 6 months after responder enrollment.
The researchers analyzed data on 28,729 responders who primarily worked in protective services (49.0%) and construction (20.8%). Responders spent a median of 52 days on the rescue and recovery effort, and 44.4% of them had some exposure to the dust cloud caused by the collapse of the towers.
In the restricted analysis, there were 1,072 cancers observed in 999 responders. Compared with the general population, responders had a significantly higher incidence of all cancers combined, with a standardized incidence ratio (SIR) of 1.09.
Responders had a significantly higher incidence of prostate cancer (SIR,1.25), thyroid cancer (SIR, 2.19), and leukemia (SIR, 1.41). The leukemia category included acute myeloid leukemia (SIR,1.58) and chronic lymphocytic leukemia (SIR, 1.08).
“Although other studies have revealed elevated SIRs for other hematologic malignancies, this is the first reported, statistically significant, elevated SIR for leukemia,” the researchers wrote. “Leukemia is known to occur after exposure to occupational carcinogens, including benzene (burning jet fuel and other sources at the [World Trade Center] site), possibly at low levels of exposure and with a latency of several years from exposure.”
A multivariate analysis showed no association between cancer incidence and the length of time responders spent on the rescue and recovery effort or the intensity of their exposure to the dust cloud or debris pile.
The analysis did show an elevated risk of all cancers combined with each 1-year increase in responder age (hazard ratio, 1.09), among male responders (HR, 1.21), and among responders who smoked at baseline (HR, 1.29).
This research was supported by the Centers for Disease Control and Prevention/National Institute for Occupational Safety and Health. The researchers disclosed no conflicts of interest.
SOURCE: Shapiro MZ et al. JNCI Cancer Spectr. 2020 Jan 14. doi: 10.1093/jncics/pkz090.
New data suggest an increased risk of leukemia among responders who worked at the World Trade Center site after the attacks on Sept. 11, 2001.
Previous studies have shown that 9/11 responders have a higher incidence of cancers than does the general population. The current study is the first to show a higher incidence of leukemia among responders. It also shows a higher incidence of thyroid and prostate cancers as well as all cancer types combined.
These findings were published in JNCI Cancer Spectrum.
“This study showed increased incidence of several cancer types compared to previously conducted studies with shorter follow-up periods,” study author Susan L, Teitelbaum, PhD, of the Icahn School of Medicine at Mount Sinai, New York, said in a press release.
“Because of the long latency period of many types of cancer, it is possible that increased rates of other cancers, as well as World Trade Center exposure health issues, may emerge after longer periods of study.”
Dr. Teitelbaum and colleagues evaluated responders enrolled in the World Trade Center Health Program General Responder Cohort from when it was established in July 2002 through the end of follow-up, which was Dec. 31, 2013, for New York residents and Dec. 31, 2012, for residents of other states.
To be eligible for the cohort, responders must have worked on the World Trade Center rescue and recovery effort a minimum of 4 hours in the first 4 days from Sept. 11, 2001, 24 hours in September 2001, or 80 hours from September through December 2001. Responders also had to complete at least one monitoring visit.
Responders’ data were linked to data from cancer registries in New York, New Jersey, Pennsylvania, and Connecticut (where most responders lived at the time of the attacks), as well as Florida and North Carolina (where responders were known to retire). The responders were linked to the registries using probabilistic matching algorithms, which made use of information such as patient name, address, social security number, sex, race, and birth date.
The researchers noted that patients who enrolled in the General Responder Cohort had their cancer certified for federally funded treatment, and this factor might result in “sicker members disproportionately self-selecting into the program.” To reduce this potential bias, the researchers conducted a restricted analysis in which counts of cancer cases and person-years of observation began 6 months after responder enrollment.
The researchers analyzed data on 28,729 responders who primarily worked in protective services (49.0%) and construction (20.8%). Responders spent a median of 52 days on the rescue and recovery effort, and 44.4% of them had some exposure to the dust cloud caused by the collapse of the towers.
In the restricted analysis, there were 1,072 cancers observed in 999 responders. Compared with the general population, responders had a significantly higher incidence of all cancers combined, with a standardized incidence ratio (SIR) of 1.09.
Responders had a significantly higher incidence of prostate cancer (SIR,1.25), thyroid cancer (SIR, 2.19), and leukemia (SIR, 1.41). The leukemia category included acute myeloid leukemia (SIR,1.58) and chronic lymphocytic leukemia (SIR, 1.08).
“Although other studies have revealed elevated SIRs for other hematologic malignancies, this is the first reported, statistically significant, elevated SIR for leukemia,” the researchers wrote. “Leukemia is known to occur after exposure to occupational carcinogens, including benzene (burning jet fuel and other sources at the [World Trade Center] site), possibly at low levels of exposure and with a latency of several years from exposure.”
A multivariate analysis showed no association between cancer incidence and the length of time responders spent on the rescue and recovery effort or the intensity of their exposure to the dust cloud or debris pile.
The analysis did show an elevated risk of all cancers combined with each 1-year increase in responder age (hazard ratio, 1.09), among male responders (HR, 1.21), and among responders who smoked at baseline (HR, 1.29).
This research was supported by the Centers for Disease Control and Prevention/National Institute for Occupational Safety and Health. The researchers disclosed no conflicts of interest.
SOURCE: Shapiro MZ et al. JNCI Cancer Spectr. 2020 Jan 14. doi: 10.1093/jncics/pkz090.
FROM JNCI CANCER SPECTRUM
Researchers win funding for breast cancer studies
Five breast cancer researchers have won 3 years of funding from the National Comprehensive Cancer Network’s Oncology Research Program and Pfizer Global Medical Grants. The researchers will receive up to $1.4 million.
Allison Lipitz-Snyderman, PhD, and Erin Gillespie, MD, of Memorial Sloan Kettering Cancer Center in New York, have won funding for a project entitled, “Leveraging an academic-community partnership model to improve the quality of radiation treatment for metastatic breast cancer patients.”
Dr. Gillespie and Dr. Lipitz-Snyderman plan to use an existing partnership between Memorial Sloan Kettering and three community-based institutions to test a system for implementing best practices in radiation treatment. The system includes a web-based platform that disseminates expert recommendations as well as weekly conferences during which community radiation oncologists can consult with specialists on complex cases.
Aki Morikawa, MD, PhD, of the University of Michigan Rogel Cancer Center in Ann Arbor, won funding for a project entitled, “Personalized multi-care: A tailored approach to multidisciplinary care coordination delivery for metastatic breast cancer patients with central nervous system metastases.”
The goals of Dr. Morikawa’s project are to educate patients and providers on managing central nervous system metastases in the breast cancer setting, tailor care coordination and planning to patient and provider needs, and increase patient participation in studies.
Karen Lisa Smith, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore, won funding for a project entitled, “The Johns Hopkins Metastatic Breast Cancer Partners Program: Collaborating to improve metastatic breast cancer care.”
The goal of the Metastatic Breast Cancer Partners Program is for Johns Hopkins and mid-Atlantic regional practices to fight metastatic breast cancer together. To that end, Dr. Smith plans to create a multidisciplinary clinic that offers supportive care and treatment recommendations, a database for patient tracking and trial screening, educational resources, and new opportunities for provider collaboration.
Laura Spring, MD, of Massachusetts General Hospital Cancer Center in Boston, won funding for a project entitled, “Expanding precision medicine for patients with metastatic breast cancer in the community: Leveraging academic strength and community partnership.”
The goal of Dr. Spring’s project is to extend academic resources to affiliated network sites. This will involve increasing access to tissue-based and blood-based tumor genotyping for patients with metastatic breast cancer, creating a virtual molecular and precision medicine clinic that provides interpretation of genomic data and treatment recommendations, and offering clinical trial matching to metastatic breast cancer patients treated at network sites.
Five breast cancer researchers have won 3 years of funding from the National Comprehensive Cancer Network’s Oncology Research Program and Pfizer Global Medical Grants. The researchers will receive up to $1.4 million.
Allison Lipitz-Snyderman, PhD, and Erin Gillespie, MD, of Memorial Sloan Kettering Cancer Center in New York, have won funding for a project entitled, “Leveraging an academic-community partnership model to improve the quality of radiation treatment for metastatic breast cancer patients.”
Dr. Gillespie and Dr. Lipitz-Snyderman plan to use an existing partnership between Memorial Sloan Kettering and three community-based institutions to test a system for implementing best practices in radiation treatment. The system includes a web-based platform that disseminates expert recommendations as well as weekly conferences during which community radiation oncologists can consult with specialists on complex cases.
Aki Morikawa, MD, PhD, of the University of Michigan Rogel Cancer Center in Ann Arbor, won funding for a project entitled, “Personalized multi-care: A tailored approach to multidisciplinary care coordination delivery for metastatic breast cancer patients with central nervous system metastases.”
The goals of Dr. Morikawa’s project are to educate patients and providers on managing central nervous system metastases in the breast cancer setting, tailor care coordination and planning to patient and provider needs, and increase patient participation in studies.
Karen Lisa Smith, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore, won funding for a project entitled, “The Johns Hopkins Metastatic Breast Cancer Partners Program: Collaborating to improve metastatic breast cancer care.”
The goal of the Metastatic Breast Cancer Partners Program is for Johns Hopkins and mid-Atlantic regional practices to fight metastatic breast cancer together. To that end, Dr. Smith plans to create a multidisciplinary clinic that offers supportive care and treatment recommendations, a database for patient tracking and trial screening, educational resources, and new opportunities for provider collaboration.
Laura Spring, MD, of Massachusetts General Hospital Cancer Center in Boston, won funding for a project entitled, “Expanding precision medicine for patients with metastatic breast cancer in the community: Leveraging academic strength and community partnership.”
The goal of Dr. Spring’s project is to extend academic resources to affiliated network sites. This will involve increasing access to tissue-based and blood-based tumor genotyping for patients with metastatic breast cancer, creating a virtual molecular and precision medicine clinic that provides interpretation of genomic data and treatment recommendations, and offering clinical trial matching to metastatic breast cancer patients treated at network sites.
Five breast cancer researchers have won 3 years of funding from the National Comprehensive Cancer Network’s Oncology Research Program and Pfizer Global Medical Grants. The researchers will receive up to $1.4 million.
Allison Lipitz-Snyderman, PhD, and Erin Gillespie, MD, of Memorial Sloan Kettering Cancer Center in New York, have won funding for a project entitled, “Leveraging an academic-community partnership model to improve the quality of radiation treatment for metastatic breast cancer patients.”
Dr. Gillespie and Dr. Lipitz-Snyderman plan to use an existing partnership between Memorial Sloan Kettering and three community-based institutions to test a system for implementing best practices in radiation treatment. The system includes a web-based platform that disseminates expert recommendations as well as weekly conferences during which community radiation oncologists can consult with specialists on complex cases.
Aki Morikawa, MD, PhD, of the University of Michigan Rogel Cancer Center in Ann Arbor, won funding for a project entitled, “Personalized multi-care: A tailored approach to multidisciplinary care coordination delivery for metastatic breast cancer patients with central nervous system metastases.”
The goals of Dr. Morikawa’s project are to educate patients and providers on managing central nervous system metastases in the breast cancer setting, tailor care coordination and planning to patient and provider needs, and increase patient participation in studies.
Karen Lisa Smith, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore, won funding for a project entitled, “The Johns Hopkins Metastatic Breast Cancer Partners Program: Collaborating to improve metastatic breast cancer care.”
The goal of the Metastatic Breast Cancer Partners Program is for Johns Hopkins and mid-Atlantic regional practices to fight metastatic breast cancer together. To that end, Dr. Smith plans to create a multidisciplinary clinic that offers supportive care and treatment recommendations, a database for patient tracking and trial screening, educational resources, and new opportunities for provider collaboration.
Laura Spring, MD, of Massachusetts General Hospital Cancer Center in Boston, won funding for a project entitled, “Expanding precision medicine for patients with metastatic breast cancer in the community: Leveraging academic strength and community partnership.”
The goal of Dr. Spring’s project is to extend academic resources to affiliated network sites. This will involve increasing access to tissue-based and blood-based tumor genotyping for patients with metastatic breast cancer, creating a virtual molecular and precision medicine clinic that provides interpretation of genomic data and treatment recommendations, and offering clinical trial matching to metastatic breast cancer patients treated at network sites.
Score predicts locoregional recurrence of breast cancer
The 21-gene assay recurrence score can aid decisions about radiotherapy for postmenopausal patients with node-positive breast cancer, according to researchers.
The researchers analyzed patients who underwent mastectomy or breast-conserving surgery (excision and radiation) and received chemotherapy plus tamoxifen or tamoxifen alone. Results showed that patients with an intermediate or high recurrence score, according to the 21-gene assay OncotypeDX, were more likely to have locoregional recurrence (LRR).
“We believe that the recurrence score adds independent prognostic information that could be used with standard clinical factors for identifying LRR risk and making radiotherapy decisions,” Wendy A. Woodward, MD, PhD, of the University of Texas MD Anderson Cancer Center, Houston, and coauthors wrote in JAMA Oncology.
Dr. Woodward and colleagues analyzed data from a phase 3 trial (NCT00929591) of postmenopausal women with estrogen or progesterone receptor–positive, node-positive breast cancer. There were 367 patients who received tamoxifen alone (n = 148) or cyclophosphamide, doxorubicin, and fluorouracil followed by tamoxifen (n = 219).
Of the 367 patients, 316 were included in the primary analysis. This includes 252 patients who underwent mastectomy without radiotherapy and 64 patients who underwent breast-conserving surgery with radiotherapy.
The researchers defined LRR as a recurrence in the breast; chest wall; or axillary, infraclavicular, supraclavicular, or internal mammary lymph nodes.
The LRR incidence was 5.8% (7/121) among patients with a low recurrence score and 13.8% (27/195) among patients with an intermediate or high recurrence score. The estimated 10-year cumulative LRR incidence rates were 9.7% and 16.5%, respectively (P = .02).
The researchers conducted a multivariable analysis for LRR, which included the recurrence score, randomized treatment (combination regimen vs. tamoxifen alone), number of positive nodes (three or fewer vs. four or more), and type of surgery (mastectomy vs. excision and radiation).
Having intermediate or high recurrence scores was a significant predictor of LRR, with a hazard ratio of 2.36 (P = .04). Having four or more involved nodes was a significant predictor of LRR as well (hazard ratio, 3.37; P = .001). Randomized treatment and surgery were not significantly associated with LRR.
The researchers also conducted an exploratory analysis and found that a recurrence score of 18 was the optimal cutoff for the association of recurrence score and LRR.
“This study found that higher recurrence scores were associated with increased LRR after adjustment for treatment, type of surgical procedure, and number of positive nodes,” Dr. Woodward and colleagues wrote. “This finding suggests that the recurrence score may be used, along with accepted clinical variables, to assess the risk of LRR during radiotherapy decision making. We recommend considering the recurrence score, when available, as one of the factors in selecting patients for postmastectomy radiotherapy.”
This research was funded by the National Cancer Institute of Canada, Canadian Cancer Society, and Genomic Health, which markets the 21-gene assay OncotypeDX. Dr. Woodward disclosed receiving personal fees from Genomic Health outside this research as well as an advisory fee from Merck.
SOURCE: Woodward WA et al. JAMA Oncol. 2020 Jan 9. doi: 10.1001/jamaoncol.2019.5559.
The 21-gene assay recurrence score can aid decisions about radiotherapy for postmenopausal patients with node-positive breast cancer, according to researchers.
The researchers analyzed patients who underwent mastectomy or breast-conserving surgery (excision and radiation) and received chemotherapy plus tamoxifen or tamoxifen alone. Results showed that patients with an intermediate or high recurrence score, according to the 21-gene assay OncotypeDX, were more likely to have locoregional recurrence (LRR).
“We believe that the recurrence score adds independent prognostic information that could be used with standard clinical factors for identifying LRR risk and making radiotherapy decisions,” Wendy A. Woodward, MD, PhD, of the University of Texas MD Anderson Cancer Center, Houston, and coauthors wrote in JAMA Oncology.
Dr. Woodward and colleagues analyzed data from a phase 3 trial (NCT00929591) of postmenopausal women with estrogen or progesterone receptor–positive, node-positive breast cancer. There were 367 patients who received tamoxifen alone (n = 148) or cyclophosphamide, doxorubicin, and fluorouracil followed by tamoxifen (n = 219).
Of the 367 patients, 316 were included in the primary analysis. This includes 252 patients who underwent mastectomy without radiotherapy and 64 patients who underwent breast-conserving surgery with radiotherapy.
The researchers defined LRR as a recurrence in the breast; chest wall; or axillary, infraclavicular, supraclavicular, or internal mammary lymph nodes.
The LRR incidence was 5.8% (7/121) among patients with a low recurrence score and 13.8% (27/195) among patients with an intermediate or high recurrence score. The estimated 10-year cumulative LRR incidence rates were 9.7% and 16.5%, respectively (P = .02).
The researchers conducted a multivariable analysis for LRR, which included the recurrence score, randomized treatment (combination regimen vs. tamoxifen alone), number of positive nodes (three or fewer vs. four or more), and type of surgery (mastectomy vs. excision and radiation).
Having intermediate or high recurrence scores was a significant predictor of LRR, with a hazard ratio of 2.36 (P = .04). Having four or more involved nodes was a significant predictor of LRR as well (hazard ratio, 3.37; P = .001). Randomized treatment and surgery were not significantly associated with LRR.
The researchers also conducted an exploratory analysis and found that a recurrence score of 18 was the optimal cutoff for the association of recurrence score and LRR.
“This study found that higher recurrence scores were associated with increased LRR after adjustment for treatment, type of surgical procedure, and number of positive nodes,” Dr. Woodward and colleagues wrote. “This finding suggests that the recurrence score may be used, along with accepted clinical variables, to assess the risk of LRR during radiotherapy decision making. We recommend considering the recurrence score, when available, as one of the factors in selecting patients for postmastectomy radiotherapy.”
This research was funded by the National Cancer Institute of Canada, Canadian Cancer Society, and Genomic Health, which markets the 21-gene assay OncotypeDX. Dr. Woodward disclosed receiving personal fees from Genomic Health outside this research as well as an advisory fee from Merck.
SOURCE: Woodward WA et al. JAMA Oncol. 2020 Jan 9. doi: 10.1001/jamaoncol.2019.5559.
The 21-gene assay recurrence score can aid decisions about radiotherapy for postmenopausal patients with node-positive breast cancer, according to researchers.
The researchers analyzed patients who underwent mastectomy or breast-conserving surgery (excision and radiation) and received chemotherapy plus tamoxifen or tamoxifen alone. Results showed that patients with an intermediate or high recurrence score, according to the 21-gene assay OncotypeDX, were more likely to have locoregional recurrence (LRR).
“We believe that the recurrence score adds independent prognostic information that could be used with standard clinical factors for identifying LRR risk and making radiotherapy decisions,” Wendy A. Woodward, MD, PhD, of the University of Texas MD Anderson Cancer Center, Houston, and coauthors wrote in JAMA Oncology.
Dr. Woodward and colleagues analyzed data from a phase 3 trial (NCT00929591) of postmenopausal women with estrogen or progesterone receptor–positive, node-positive breast cancer. There were 367 patients who received tamoxifen alone (n = 148) or cyclophosphamide, doxorubicin, and fluorouracil followed by tamoxifen (n = 219).
Of the 367 patients, 316 were included in the primary analysis. This includes 252 patients who underwent mastectomy without radiotherapy and 64 patients who underwent breast-conserving surgery with radiotherapy.
The researchers defined LRR as a recurrence in the breast; chest wall; or axillary, infraclavicular, supraclavicular, or internal mammary lymph nodes.
The LRR incidence was 5.8% (7/121) among patients with a low recurrence score and 13.8% (27/195) among patients with an intermediate or high recurrence score. The estimated 10-year cumulative LRR incidence rates were 9.7% and 16.5%, respectively (P = .02).
The researchers conducted a multivariable analysis for LRR, which included the recurrence score, randomized treatment (combination regimen vs. tamoxifen alone), number of positive nodes (three or fewer vs. four or more), and type of surgery (mastectomy vs. excision and radiation).
Having intermediate or high recurrence scores was a significant predictor of LRR, with a hazard ratio of 2.36 (P = .04). Having four or more involved nodes was a significant predictor of LRR as well (hazard ratio, 3.37; P = .001). Randomized treatment and surgery were not significantly associated with LRR.
The researchers also conducted an exploratory analysis and found that a recurrence score of 18 was the optimal cutoff for the association of recurrence score and LRR.
“This study found that higher recurrence scores were associated with increased LRR after adjustment for treatment, type of surgical procedure, and number of positive nodes,” Dr. Woodward and colleagues wrote. “This finding suggests that the recurrence score may be used, along with accepted clinical variables, to assess the risk of LRR during radiotherapy decision making. We recommend considering the recurrence score, when available, as one of the factors in selecting patients for postmastectomy radiotherapy.”
This research was funded by the National Cancer Institute of Canada, Canadian Cancer Society, and Genomic Health, which markets the 21-gene assay OncotypeDX. Dr. Woodward disclosed receiving personal fees from Genomic Health outside this research as well as an advisory fee from Merck.
SOURCE: Woodward WA et al. JAMA Oncol. 2020 Jan 9. doi: 10.1001/jamaoncol.2019.5559.
FROM JAMA ONCOLOGY
Adenotonsillectomy doesn’t improve cognitive function in preschoolers with OSA
according to a prospective study.
The study showed no significant difference in global IQ at 12 months between children who underwent adenotonsillectomy and those who did not. However, as expected, the adenotonsillectomy group did experience improvements in sleep.
Karen A. Waters, MBBS, PhD, of the Children’s Hospital at Westmead and the University of Sydney, and her colleagues reported these results in Pediatrics. There also was a related commentary.
The study enrolled 190 children (ages 3-5 years) with mild obstructive sleep apnea. Roughly half of patients (n = 99) were randomized to early adenotonsillectomy (within 2 months), and the other half (n = 91) were randomized to no adenotonsillectomy (12-month routine wait). There were 121 patients who had global IQ assessments at 12 months, as measured by the Woodcock Johnson III Brief Intellectual Ability (BIA) test. Of these patients, 61 were in the adenotonsillectomy group, and 60 were in the control group.
Both groups had improvements in BIA scores from baseline to 12 months, and the 12-month BIA score was not significantly different between the groups.
At baseline, the mean W score (task proficiency) for BIA was 448.36 in the adenotonsillectomy group and 451.3 in the control group. At 12 months, the scores were 465.46 and 463.12, respectively (P = .29).
“Intellectual ability scores improved in both groups over time with no effect attributable to the intervention [adenotonsillectomy],” Dr. Waters and her colleagues wrote.
However, patients in the adenotonsillectomy group did have greater improvements in sleep than patients in the control group, as assessed by polysomnogram and parent reports.
In the adenotonsillectomy group, the mean total sleep time was 469.2 minutes at baseline and 481.8 minutes at 12 months. In the control group, the mean total sleep time was 463.8 minutes at baseline and 475.3 minutes at 12 months. The adjusted mean difference was –2.12 (P less than .001).
According to parent reports, children in the adenotonsillectomy group were significantly less likely than those in the control group to have trouble sleeping at night at 12 months: 8% and 74%, respectively (P less than .001).
“Children randomly assigned to adenotonsillectomy did show greater improvement in polysomnography obstructive indices and parent-reported behavior but did not demonstrate a treatment-attributable improvement in cognitive function,” David O. Francis, MD, of University of Wisconsin–Madison, and Derek J. Lam, MD, of Oregon Health & Science University in Portland, wrote in a related commentary.
The commentators noted that these results are similar to those of the CHAT study, which showed no significant differences in Developmental Neuropsychological Assessment results between children (ages 5-9 years) who underwent adenotonsillectomy and those who did not (N Engl J Med. 2013 Jun 20;368[25]:2366-76).
The current study was funded by the National Health and Medical Research Council, Sydney University, The Garnett Passe and Rodney Williams Memorial Foundation, and The Golden Casket, Brisbane. Dr. Waters, her coauthors, and the commentary authors said they have no relevant conflicts of interest. The commentators received no external funding.
SOURCE: Waters KA et al. Pediatrics. 2020;145(2):e20191450; Francis DO and Lam DJ. Pediatrics. 2020;145(2):e20192479.
according to a prospective study.
The study showed no significant difference in global IQ at 12 months between children who underwent adenotonsillectomy and those who did not. However, as expected, the adenotonsillectomy group did experience improvements in sleep.
Karen A. Waters, MBBS, PhD, of the Children’s Hospital at Westmead and the University of Sydney, and her colleagues reported these results in Pediatrics. There also was a related commentary.
The study enrolled 190 children (ages 3-5 years) with mild obstructive sleep apnea. Roughly half of patients (n = 99) were randomized to early adenotonsillectomy (within 2 months), and the other half (n = 91) were randomized to no adenotonsillectomy (12-month routine wait). There were 121 patients who had global IQ assessments at 12 months, as measured by the Woodcock Johnson III Brief Intellectual Ability (BIA) test. Of these patients, 61 were in the adenotonsillectomy group, and 60 were in the control group.
Both groups had improvements in BIA scores from baseline to 12 months, and the 12-month BIA score was not significantly different between the groups.
At baseline, the mean W score (task proficiency) for BIA was 448.36 in the adenotonsillectomy group and 451.3 in the control group. At 12 months, the scores were 465.46 and 463.12, respectively (P = .29).
“Intellectual ability scores improved in both groups over time with no effect attributable to the intervention [adenotonsillectomy],” Dr. Waters and her colleagues wrote.
However, patients in the adenotonsillectomy group did have greater improvements in sleep than patients in the control group, as assessed by polysomnogram and parent reports.
In the adenotonsillectomy group, the mean total sleep time was 469.2 minutes at baseline and 481.8 minutes at 12 months. In the control group, the mean total sleep time was 463.8 minutes at baseline and 475.3 minutes at 12 months. The adjusted mean difference was –2.12 (P less than .001).
According to parent reports, children in the adenotonsillectomy group were significantly less likely than those in the control group to have trouble sleeping at night at 12 months: 8% and 74%, respectively (P less than .001).
“Children randomly assigned to adenotonsillectomy did show greater improvement in polysomnography obstructive indices and parent-reported behavior but did not demonstrate a treatment-attributable improvement in cognitive function,” David O. Francis, MD, of University of Wisconsin–Madison, and Derek J. Lam, MD, of Oregon Health & Science University in Portland, wrote in a related commentary.
The commentators noted that these results are similar to those of the CHAT study, which showed no significant differences in Developmental Neuropsychological Assessment results between children (ages 5-9 years) who underwent adenotonsillectomy and those who did not (N Engl J Med. 2013 Jun 20;368[25]:2366-76).
The current study was funded by the National Health and Medical Research Council, Sydney University, The Garnett Passe and Rodney Williams Memorial Foundation, and The Golden Casket, Brisbane. Dr. Waters, her coauthors, and the commentary authors said they have no relevant conflicts of interest. The commentators received no external funding.
SOURCE: Waters KA et al. Pediatrics. 2020;145(2):e20191450; Francis DO and Lam DJ. Pediatrics. 2020;145(2):e20192479.
according to a prospective study.
The study showed no significant difference in global IQ at 12 months between children who underwent adenotonsillectomy and those who did not. However, as expected, the adenotonsillectomy group did experience improvements in sleep.
Karen A. Waters, MBBS, PhD, of the Children’s Hospital at Westmead and the University of Sydney, and her colleagues reported these results in Pediatrics. There also was a related commentary.
The study enrolled 190 children (ages 3-5 years) with mild obstructive sleep apnea. Roughly half of patients (n = 99) were randomized to early adenotonsillectomy (within 2 months), and the other half (n = 91) were randomized to no adenotonsillectomy (12-month routine wait). There were 121 patients who had global IQ assessments at 12 months, as measured by the Woodcock Johnson III Brief Intellectual Ability (BIA) test. Of these patients, 61 were in the adenotonsillectomy group, and 60 were in the control group.
Both groups had improvements in BIA scores from baseline to 12 months, and the 12-month BIA score was not significantly different between the groups.
At baseline, the mean W score (task proficiency) for BIA was 448.36 in the adenotonsillectomy group and 451.3 in the control group. At 12 months, the scores were 465.46 and 463.12, respectively (P = .29).
“Intellectual ability scores improved in both groups over time with no effect attributable to the intervention [adenotonsillectomy],” Dr. Waters and her colleagues wrote.
However, patients in the adenotonsillectomy group did have greater improvements in sleep than patients in the control group, as assessed by polysomnogram and parent reports.
In the adenotonsillectomy group, the mean total sleep time was 469.2 minutes at baseline and 481.8 minutes at 12 months. In the control group, the mean total sleep time was 463.8 minutes at baseline and 475.3 minutes at 12 months. The adjusted mean difference was –2.12 (P less than .001).
According to parent reports, children in the adenotonsillectomy group were significantly less likely than those in the control group to have trouble sleeping at night at 12 months: 8% and 74%, respectively (P less than .001).
“Children randomly assigned to adenotonsillectomy did show greater improvement in polysomnography obstructive indices and parent-reported behavior but did not demonstrate a treatment-attributable improvement in cognitive function,” David O. Francis, MD, of University of Wisconsin–Madison, and Derek J. Lam, MD, of Oregon Health & Science University in Portland, wrote in a related commentary.
The commentators noted that these results are similar to those of the CHAT study, which showed no significant differences in Developmental Neuropsychological Assessment results between children (ages 5-9 years) who underwent adenotonsillectomy and those who did not (N Engl J Med. 2013 Jun 20;368[25]:2366-76).
The current study was funded by the National Health and Medical Research Council, Sydney University, The Garnett Passe and Rodney Williams Memorial Foundation, and The Golden Casket, Brisbane. Dr. Waters, her coauthors, and the commentary authors said they have no relevant conflicts of interest. The commentators received no external funding.
SOURCE: Waters KA et al. Pediatrics. 2020;145(2):e20191450; Francis DO and Lam DJ. Pediatrics. 2020;145(2):e20192479.
FROM PEDIATRICS