User login
Synthetic HCV glycoproteins elicit narrow, but not widely effective antibodies
Immunization with two synthetic consensus constructs of hepatitis C virus (HCV) glycoproteins was found to elicit narrow, but not widely effective, virus-neutralizing antibodies in guinea pigs, according to the results of a model study published in the journal Antiviral Research.
Researchers created two novel synthetic E2 glycoprotein immunogens (NotC1 and NotC2) using consensus nucleotide sequences deduced from samples of circulating genotype 1 HCV strains, according to Alexander W. Tarr, PhD, of the Nottingham (England) University Hospitals NHS Trust, and his colleagues.
Expression of these constructs in Drosophila melanogaster cells resulted in high yields of correctly folded, monomeric E2 proteins, which were used to immunize guinea pigs. Both proteins generated antibodies capable of neutralizing the H77 strain of HCV, although NotC1 elicited antibodies that were more potent at neutralizing virus entry. The two sets of glycoprotein-induced antibodies neutralized some HCV strains representing genotype 1, but not those strains representing genotype 2 or genotype 3.
“The broader objective of eliciting antibodies that neutralize patient strains representing multiple genotypes will require further refinement of immunization protocols. A vaccine construct comprising the consensus of a minimal CD81 binding domain might be able to focus the antibody response to conserved epitopes on E2. Additionally, boosting immunized animals with glycoproteins representing different strains might be required to focus the antibody response on to conserved conformational epitopes,” the researchers concluded.
The research was funded by the Medical Research Council, the NIHR Nottingham Biomedical Research Centre, and the European Union. Disclosures were not reported.
SOURCE: Tarr AW et al. Antiviral Research 2018;160:25-37.
Immunization with two synthetic consensus constructs of hepatitis C virus (HCV) glycoproteins was found to elicit narrow, but not widely effective, virus-neutralizing antibodies in guinea pigs, according to the results of a model study published in the journal Antiviral Research.
Researchers created two novel synthetic E2 glycoprotein immunogens (NotC1 and NotC2) using consensus nucleotide sequences deduced from samples of circulating genotype 1 HCV strains, according to Alexander W. Tarr, PhD, of the Nottingham (England) University Hospitals NHS Trust, and his colleagues.
Expression of these constructs in Drosophila melanogaster cells resulted in high yields of correctly folded, monomeric E2 proteins, which were used to immunize guinea pigs. Both proteins generated antibodies capable of neutralizing the H77 strain of HCV, although NotC1 elicited antibodies that were more potent at neutralizing virus entry. The two sets of glycoprotein-induced antibodies neutralized some HCV strains representing genotype 1, but not those strains representing genotype 2 or genotype 3.
“The broader objective of eliciting antibodies that neutralize patient strains representing multiple genotypes will require further refinement of immunization protocols. A vaccine construct comprising the consensus of a minimal CD81 binding domain might be able to focus the antibody response to conserved epitopes on E2. Additionally, boosting immunized animals with glycoproteins representing different strains might be required to focus the antibody response on to conserved conformational epitopes,” the researchers concluded.
The research was funded by the Medical Research Council, the NIHR Nottingham Biomedical Research Centre, and the European Union. Disclosures were not reported.
SOURCE: Tarr AW et al. Antiviral Research 2018;160:25-37.
Immunization with two synthetic consensus constructs of hepatitis C virus (HCV) glycoproteins was found to elicit narrow, but not widely effective, virus-neutralizing antibodies in guinea pigs, according to the results of a model study published in the journal Antiviral Research.
Researchers created two novel synthetic E2 glycoprotein immunogens (NotC1 and NotC2) using consensus nucleotide sequences deduced from samples of circulating genotype 1 HCV strains, according to Alexander W. Tarr, PhD, of the Nottingham (England) University Hospitals NHS Trust, and his colleagues.
Expression of these constructs in Drosophila melanogaster cells resulted in high yields of correctly folded, monomeric E2 proteins, which were used to immunize guinea pigs. Both proteins generated antibodies capable of neutralizing the H77 strain of HCV, although NotC1 elicited antibodies that were more potent at neutralizing virus entry. The two sets of glycoprotein-induced antibodies neutralized some HCV strains representing genotype 1, but not those strains representing genotype 2 or genotype 3.
“The broader objective of eliciting antibodies that neutralize patient strains representing multiple genotypes will require further refinement of immunization protocols. A vaccine construct comprising the consensus of a minimal CD81 binding domain might be able to focus the antibody response to conserved epitopes on E2. Additionally, boosting immunized animals with glycoproteins representing different strains might be required to focus the antibody response on to conserved conformational epitopes,” the researchers concluded.
The research was funded by the Medical Research Council, the NIHR Nottingham Biomedical Research Centre, and the European Union. Disclosures were not reported.
SOURCE: Tarr AW et al. Antiviral Research 2018;160:25-37.
FROM ANTIVIRAL RESEARCH
ICYMI: Hereditary cancer screening feasible in community gynecologic practices
After a group of community obstetrics and gynecology practices underwent training in hereditary cancer screening, genetic testing rates increased by four times over the immediate preintervention rate and by eight times over the year prior to intervention, according to results of a prospective process intervention study published in Obstetrics & Gynecology (2018 Oct 5. doi: 10.1097/AOG.0000000000002916).
We covered this story before it was published in the journal. Find our conference coverage at the link below.
After a group of community obstetrics and gynecology practices underwent training in hereditary cancer screening, genetic testing rates increased by four times over the immediate preintervention rate and by eight times over the year prior to intervention, according to results of a prospective process intervention study published in Obstetrics & Gynecology (2018 Oct 5. doi: 10.1097/AOG.0000000000002916).
We covered this story before it was published in the journal. Find our conference coverage at the link below.
After a group of community obstetrics and gynecology practices underwent training in hereditary cancer screening, genetic testing rates increased by four times over the immediate preintervention rate and by eight times over the year prior to intervention, according to results of a prospective process intervention study published in Obstetrics & Gynecology (2018 Oct 5. doi: 10.1097/AOG.0000000000002916).
We covered this story before it was published in the journal. Find our conference coverage at the link below.
FROM OBSTETRICS & GYNECOLOGY
HCV adapts to HIV coinfection
HCV strains evolve differently in HIV-coinfected individuals, according to the results of a database analysis of HCV genetic sequences from patients monoinfected with HCV and those who were coinfected with HIV. The study compared results from 112 coinfected persons (CIPs) and 176 monoinfected persons (MIPs), according to the report published in the journal Infection, Genetics, and Evolution.
Genetic differences between intrahost variants of the HCV hypervariable region 1 (HVR1) were sampled from CIPs and MIPs, and the nucleotide sequences of intrahost HCV HVR1 variants (n = 28,622) obtained were represented using 148 physical-chemical (PhyChem) indexes of DNA nucleotide dimers. Changes of the intrahost HCV population were detected by measuring coevolution among the HVR1 site using new PhyChem properties extracted from the next-generation sequencing of HVR1 data. Small but statistically significant variances in seven of the PhyChem indexes, measured using these intrahost HVR1 variants, was shown to be strongly associated with CIPs and MIPs (P less than .0001).
“The computational models built using these new markers provide novel opportunities for development of cybermolecular diagnostics,” wrote James Lara, PhD, and his colleagues at the Centers for Disease Control and Prevention.
All HVR1 sequences used (n = 28,622) shared only 6,782 profiles of the selected calculated dinucleotide-based auto covariances of the seven PhyChem indexes. The vast majority (98%-99%) of these profiles were found to be specific to CIPs or MIPs, indicating that coevolution among HVR1 sites reflects HCV adaptation to HIV among coinfected individuals, according to the authors.
Because of the common occurrence of HIV-coinfection in high-risk groups, “HCV strains circulating in high-risk groups need to be carefully monitored for the identification of potentially new traits of clinical and public health relevance,” Dr. Lara and his colleagues concluded.
The authors reported having no conflicts of interest.
SOURCE: Lara J et al. Infection, Genetics and Evolution. 2018. 65:216-25.
HCV strains evolve differently in HIV-coinfected individuals, according to the results of a database analysis of HCV genetic sequences from patients monoinfected with HCV and those who were coinfected with HIV. The study compared results from 112 coinfected persons (CIPs) and 176 monoinfected persons (MIPs), according to the report published in the journal Infection, Genetics, and Evolution.
Genetic differences between intrahost variants of the HCV hypervariable region 1 (HVR1) were sampled from CIPs and MIPs, and the nucleotide sequences of intrahost HCV HVR1 variants (n = 28,622) obtained were represented using 148 physical-chemical (PhyChem) indexes of DNA nucleotide dimers. Changes of the intrahost HCV population were detected by measuring coevolution among the HVR1 site using new PhyChem properties extracted from the next-generation sequencing of HVR1 data. Small but statistically significant variances in seven of the PhyChem indexes, measured using these intrahost HVR1 variants, was shown to be strongly associated with CIPs and MIPs (P less than .0001).
“The computational models built using these new markers provide novel opportunities for development of cybermolecular diagnostics,” wrote James Lara, PhD, and his colleagues at the Centers for Disease Control and Prevention.
All HVR1 sequences used (n = 28,622) shared only 6,782 profiles of the selected calculated dinucleotide-based auto covariances of the seven PhyChem indexes. The vast majority (98%-99%) of these profiles were found to be specific to CIPs or MIPs, indicating that coevolution among HVR1 sites reflects HCV adaptation to HIV among coinfected individuals, according to the authors.
Because of the common occurrence of HIV-coinfection in high-risk groups, “HCV strains circulating in high-risk groups need to be carefully monitored for the identification of potentially new traits of clinical and public health relevance,” Dr. Lara and his colleagues concluded.
The authors reported having no conflicts of interest.
SOURCE: Lara J et al. Infection, Genetics and Evolution. 2018. 65:216-25.
HCV strains evolve differently in HIV-coinfected individuals, according to the results of a database analysis of HCV genetic sequences from patients monoinfected with HCV and those who were coinfected with HIV. The study compared results from 112 coinfected persons (CIPs) and 176 monoinfected persons (MIPs), according to the report published in the journal Infection, Genetics, and Evolution.
Genetic differences between intrahost variants of the HCV hypervariable region 1 (HVR1) were sampled from CIPs and MIPs, and the nucleotide sequences of intrahost HCV HVR1 variants (n = 28,622) obtained were represented using 148 physical-chemical (PhyChem) indexes of DNA nucleotide dimers. Changes of the intrahost HCV population were detected by measuring coevolution among the HVR1 site using new PhyChem properties extracted from the next-generation sequencing of HVR1 data. Small but statistically significant variances in seven of the PhyChem indexes, measured using these intrahost HVR1 variants, was shown to be strongly associated with CIPs and MIPs (P less than .0001).
“The computational models built using these new markers provide novel opportunities for development of cybermolecular diagnostics,” wrote James Lara, PhD, and his colleagues at the Centers for Disease Control and Prevention.
All HVR1 sequences used (n = 28,622) shared only 6,782 profiles of the selected calculated dinucleotide-based auto covariances of the seven PhyChem indexes. The vast majority (98%-99%) of these profiles were found to be specific to CIPs or MIPs, indicating that coevolution among HVR1 sites reflects HCV adaptation to HIV among coinfected individuals, according to the authors.
Because of the common occurrence of HIV-coinfection in high-risk groups, “HCV strains circulating in high-risk groups need to be carefully monitored for the identification of potentially new traits of clinical and public health relevance,” Dr. Lara and his colleagues concluded.
The authors reported having no conflicts of interest.
SOURCE: Lara J et al. Infection, Genetics and Evolution. 2018. 65:216-25.
FROM INFECTION, GENETICS, AND EVOLUTION
First-line olaparib doubles PFS in BRCA-mutated advanced ovarian cancer
MUNICH – Olaparib maintenance therapy significantly reduces risk of disease progression or death in women with BRCA-mutated advanced ovarian cancer who respond to chemotherapy, according to results from the SOLO-1 trial.
The benefit from olaparib was compelling; compared with placebo, more than twice the number of women were alive and without disease progression after 3 years.
Current guidelines recommend olaparib for relapsed ovarian cancer, but the SOLO-1 results support first-line application, said lead author, Kathleen N. Moore, MD at the European Society for Medical Oncology Congress.
“We believe that the SOLO-1 data really prompts a change in the standard of care for women with advanced ovarian cancer who harbor a BRCA mutation,” said Dr. Moore of the Stephenson Cancer Center at the University of Oklahoma in Oklahoma City.
Olaparib (Lynparza) currently is approved for relapsed ovarian cancer regardless of mutation status, but poor outcomes suggest that this intervention is given too late – many patients relapse, and when they do, most do not survive.
“Although the majority of ... patients have no evidence of disease after [chemotherapy], approximately 70% have a relapse within the subsequent 3 years,” the investigators wrote in an article simultaneously published in the New England Journal of Medicine. “Recurrent ovarian cancer is typically incurable, with most patients receiving multiple additional lines of treatment before ultimately dying from the disease.”
Poly (ADP-ribose) polymerase (PARP) inhibitors, such as olaparib, are well matched for BRCA-mutated tumors; they interfere with DNA repair, thereby exploiting repair deficits conferred by BRCA mutations. One in six women with advanced ovarian cancer exhibits a BRCA mutation, so eligible patients are relatively common.
The phase 3, placebo-controlled SOLO-1 trial involved 391 patients with advanced ovarian cancer who had a complete or partial response to platinum-based chemotherapy. Patients exhibited mutations in BRCA1, BRCA2, or both (BRCA1/BRCA2). After chemotherapy, patients were randomized to receive either olaparib 300 mg twice daily or placebo (in a 2:1 ratio).
The primary endpoint was progression-free survival (PFS) determined by imaging; MRI or CT was performed at baseline and every 3 months for up to 3 years, with 6-month intervals thereafter. Patients who had no disease progression at 2 years halted therapy, whereas patients with disease progression were allowed to continue olaparib if desired.
The 3-year follow-up period (median, 40.7 months) revealed a dramatic benefit from olaparib; the PFS rate was 60% for olaparib, compared with 27% for placebo (P less than .001). This represents a 70% reduction in risk of disease progression or death. Because of the magnitude of prolonged survival, median PFS could not be determined; however, estimates suggest that olaparib adds 3 years without disease progression.
Dr. Moore noted that these benefits were consistent regardless of stage or level of response to chemotherapy (partial vs. complete). “Everyone benefits,” she said. “It really looks like an all subgroup-beneficial regimen.”
Still, questions of long-term benefit remain unanswered. “It’s too early to know what [the extended PFS] means long term,” Dr. Moore said. “We hope that it means we’ve converted a larger fraction of patients to cure, and that’s what you’re seeing with the flattening of the survival curve, but it took us 3 years just to get to this point, so how long will it take us to comment on overall survival? It’s a good problem to have, but it’s going to remain to be seen.”
As therapy was discontinued at 2 years, and yet patients remained progression free after 3 years, researchers also are left wondering about mechanisms of action. “Has olaparib eradicated all the disease?” asked Jonathan A. Ledermann, MD, member of the ESMO faculty and professor of medical oncology at University College London. “Or is something else happening, such as an immune response that’s taking over when you stop the drug? We don’t know the answer to that, but it’s an intriguing question and one that we need to follow up on.”
Safety data from SOLO-1 were comparable with previous olaparib trials. Overall, olaparib was well tolerated, with 21% of patients experiencing serious adverse events. The most common serious adverse event was neutropenia (7%).
SOLO-1 was sponsored by AstraZeneca and Merck. The authors reported financial affiliations with Clovis, Tesaro, Mateon, Merck, and others.
SOURCE: Moore et al. N Eng J Med. 2018 Oct 21. doi: 10.1056/NEJMoa1810858.
MUNICH – Olaparib maintenance therapy significantly reduces risk of disease progression or death in women with BRCA-mutated advanced ovarian cancer who respond to chemotherapy, according to results from the SOLO-1 trial.
The benefit from olaparib was compelling; compared with placebo, more than twice the number of women were alive and without disease progression after 3 years.
Current guidelines recommend olaparib for relapsed ovarian cancer, but the SOLO-1 results support first-line application, said lead author, Kathleen N. Moore, MD at the European Society for Medical Oncology Congress.
“We believe that the SOLO-1 data really prompts a change in the standard of care for women with advanced ovarian cancer who harbor a BRCA mutation,” said Dr. Moore of the Stephenson Cancer Center at the University of Oklahoma in Oklahoma City.
Olaparib (Lynparza) currently is approved for relapsed ovarian cancer regardless of mutation status, but poor outcomes suggest that this intervention is given too late – many patients relapse, and when they do, most do not survive.
“Although the majority of ... patients have no evidence of disease after [chemotherapy], approximately 70% have a relapse within the subsequent 3 years,” the investigators wrote in an article simultaneously published in the New England Journal of Medicine. “Recurrent ovarian cancer is typically incurable, with most patients receiving multiple additional lines of treatment before ultimately dying from the disease.”
Poly (ADP-ribose) polymerase (PARP) inhibitors, such as olaparib, are well matched for BRCA-mutated tumors; they interfere with DNA repair, thereby exploiting repair deficits conferred by BRCA mutations. One in six women with advanced ovarian cancer exhibits a BRCA mutation, so eligible patients are relatively common.
The phase 3, placebo-controlled SOLO-1 trial involved 391 patients with advanced ovarian cancer who had a complete or partial response to platinum-based chemotherapy. Patients exhibited mutations in BRCA1, BRCA2, or both (BRCA1/BRCA2). After chemotherapy, patients were randomized to receive either olaparib 300 mg twice daily or placebo (in a 2:1 ratio).
The primary endpoint was progression-free survival (PFS) determined by imaging; MRI or CT was performed at baseline and every 3 months for up to 3 years, with 6-month intervals thereafter. Patients who had no disease progression at 2 years halted therapy, whereas patients with disease progression were allowed to continue olaparib if desired.
The 3-year follow-up period (median, 40.7 months) revealed a dramatic benefit from olaparib; the PFS rate was 60% for olaparib, compared with 27% for placebo (P less than .001). This represents a 70% reduction in risk of disease progression or death. Because of the magnitude of prolonged survival, median PFS could not be determined; however, estimates suggest that olaparib adds 3 years without disease progression.
Dr. Moore noted that these benefits were consistent regardless of stage or level of response to chemotherapy (partial vs. complete). “Everyone benefits,” she said. “It really looks like an all subgroup-beneficial regimen.”
Still, questions of long-term benefit remain unanswered. “It’s too early to know what [the extended PFS] means long term,” Dr. Moore said. “We hope that it means we’ve converted a larger fraction of patients to cure, and that’s what you’re seeing with the flattening of the survival curve, but it took us 3 years just to get to this point, so how long will it take us to comment on overall survival? It’s a good problem to have, but it’s going to remain to be seen.”
As therapy was discontinued at 2 years, and yet patients remained progression free after 3 years, researchers also are left wondering about mechanisms of action. “Has olaparib eradicated all the disease?” asked Jonathan A. Ledermann, MD, member of the ESMO faculty and professor of medical oncology at University College London. “Or is something else happening, such as an immune response that’s taking over when you stop the drug? We don’t know the answer to that, but it’s an intriguing question and one that we need to follow up on.”
Safety data from SOLO-1 were comparable with previous olaparib trials. Overall, olaparib was well tolerated, with 21% of patients experiencing serious adverse events. The most common serious adverse event was neutropenia (7%).
SOLO-1 was sponsored by AstraZeneca and Merck. The authors reported financial affiliations with Clovis, Tesaro, Mateon, Merck, and others.
SOURCE: Moore et al. N Eng J Med. 2018 Oct 21. doi: 10.1056/NEJMoa1810858.
MUNICH – Olaparib maintenance therapy significantly reduces risk of disease progression or death in women with BRCA-mutated advanced ovarian cancer who respond to chemotherapy, according to results from the SOLO-1 trial.
The benefit from olaparib was compelling; compared with placebo, more than twice the number of women were alive and without disease progression after 3 years.
Current guidelines recommend olaparib for relapsed ovarian cancer, but the SOLO-1 results support first-line application, said lead author, Kathleen N. Moore, MD at the European Society for Medical Oncology Congress.
“We believe that the SOLO-1 data really prompts a change in the standard of care for women with advanced ovarian cancer who harbor a BRCA mutation,” said Dr. Moore of the Stephenson Cancer Center at the University of Oklahoma in Oklahoma City.
Olaparib (Lynparza) currently is approved for relapsed ovarian cancer regardless of mutation status, but poor outcomes suggest that this intervention is given too late – many patients relapse, and when they do, most do not survive.
“Although the majority of ... patients have no evidence of disease after [chemotherapy], approximately 70% have a relapse within the subsequent 3 years,” the investigators wrote in an article simultaneously published in the New England Journal of Medicine. “Recurrent ovarian cancer is typically incurable, with most patients receiving multiple additional lines of treatment before ultimately dying from the disease.”
Poly (ADP-ribose) polymerase (PARP) inhibitors, such as olaparib, are well matched for BRCA-mutated tumors; they interfere with DNA repair, thereby exploiting repair deficits conferred by BRCA mutations. One in six women with advanced ovarian cancer exhibits a BRCA mutation, so eligible patients are relatively common.
The phase 3, placebo-controlled SOLO-1 trial involved 391 patients with advanced ovarian cancer who had a complete or partial response to platinum-based chemotherapy. Patients exhibited mutations in BRCA1, BRCA2, or both (BRCA1/BRCA2). After chemotherapy, patients were randomized to receive either olaparib 300 mg twice daily or placebo (in a 2:1 ratio).
The primary endpoint was progression-free survival (PFS) determined by imaging; MRI or CT was performed at baseline and every 3 months for up to 3 years, with 6-month intervals thereafter. Patients who had no disease progression at 2 years halted therapy, whereas patients with disease progression were allowed to continue olaparib if desired.
The 3-year follow-up period (median, 40.7 months) revealed a dramatic benefit from olaparib; the PFS rate was 60% for olaparib, compared with 27% for placebo (P less than .001). This represents a 70% reduction in risk of disease progression or death. Because of the magnitude of prolonged survival, median PFS could not be determined; however, estimates suggest that olaparib adds 3 years without disease progression.
Dr. Moore noted that these benefits were consistent regardless of stage or level of response to chemotherapy (partial vs. complete). “Everyone benefits,” she said. “It really looks like an all subgroup-beneficial regimen.”
Still, questions of long-term benefit remain unanswered. “It’s too early to know what [the extended PFS] means long term,” Dr. Moore said. “We hope that it means we’ve converted a larger fraction of patients to cure, and that’s what you’re seeing with the flattening of the survival curve, but it took us 3 years just to get to this point, so how long will it take us to comment on overall survival? It’s a good problem to have, but it’s going to remain to be seen.”
As therapy was discontinued at 2 years, and yet patients remained progression free after 3 years, researchers also are left wondering about mechanisms of action. “Has olaparib eradicated all the disease?” asked Jonathan A. Ledermann, MD, member of the ESMO faculty and professor of medical oncology at University College London. “Or is something else happening, such as an immune response that’s taking over when you stop the drug? We don’t know the answer to that, but it’s an intriguing question and one that we need to follow up on.”
Safety data from SOLO-1 were comparable with previous olaparib trials. Overall, olaparib was well tolerated, with 21% of patients experiencing serious adverse events. The most common serious adverse event was neutropenia (7%).
SOLO-1 was sponsored by AstraZeneca and Merck. The authors reported financial affiliations with Clovis, Tesaro, Mateon, Merck, and others.
SOURCE: Moore et al. N Eng J Med. 2018 Oct 21. doi: 10.1056/NEJMoa1810858.
REPORTING FROM ESMO 2018
Key clinical point: Olaparib maintenance therapy significantly reduced risk of disease progression or death in women with advanced ovarian cancer who had a complete or partial response to chemotherapy,
Major finding: Olaparib reduced risk of disease progression or death by 70%, compared with placebo.
Study details: SOLO-1 was a phase 3, randomized, double-blind, placebo-controlled trial of 391 patients with advanced ovarian cancer who had a complete or partial response to platinum-based chemotherapy.
Disclosures: The study was sponsored by AstraZeneca and Merck. The authors reported financial affiliations with Clovis, Tesaro, Mateon, Merck, and others.
Source: Moore KN et al. N Engl J Med. 2018 Oct 21. doi: 10.1056/NEJMoa1810858.
Reducing alarm fatigue
Monitoring from a centralized location
Hospitalists hearing the constant noise from cardiac telemetry monitoring systems can experience alarm fatigue – a nationwide phenomenon that can lead to an increase in patient deaths.
The American Heart Association reports that fewer than one in four adults survived an in-hospital cardiac arrest in 2013; other studies showed that up to 44% of inpatient cardiac arrests were not detected appropriately, according to the Cleveland Clinic.
Clinicians at the Cleveland Clinic have tried centralized monitoring to address the problem. They’ve established a “mission control” center, where off-site personnel monitor sensors and high-definition cameras and vital signs such as blood pressure, heart rate, and respiration. On-site action is requested when appropriate; unimportant alarms are dismissed.
In August 2016, results from the first 13 months of the Cleveland Clinic program were published in JAMA. They revealed that the monitoring system could help reduce rates of unimportant alarms with no increase in cardiopulmonary arrest events. The centralized unit monitored 99,048 patient orders, and ultimately detected serious problems and accurately notified on-site staff for 79% of 3,243 events, which included a rhythm and/or rate change within 1 hour or less of the event. Accurate notification to on-site hospital staff was more than 84%.
Since then, improvements to the system have continued, according to Cleveland Clinic, and include doubling the number of monitored patients per technician and improved clinical outcomes.
Reference
Cleveland Clinic: Consult QD – An update on the centralized cardiac telemetry monitoring unit
Monitoring from a centralized location
Monitoring from a centralized location
Hospitalists hearing the constant noise from cardiac telemetry monitoring systems can experience alarm fatigue – a nationwide phenomenon that can lead to an increase in patient deaths.
The American Heart Association reports that fewer than one in four adults survived an in-hospital cardiac arrest in 2013; other studies showed that up to 44% of inpatient cardiac arrests were not detected appropriately, according to the Cleveland Clinic.
Clinicians at the Cleveland Clinic have tried centralized monitoring to address the problem. They’ve established a “mission control” center, where off-site personnel monitor sensors and high-definition cameras and vital signs such as blood pressure, heart rate, and respiration. On-site action is requested when appropriate; unimportant alarms are dismissed.
In August 2016, results from the first 13 months of the Cleveland Clinic program were published in JAMA. They revealed that the monitoring system could help reduce rates of unimportant alarms with no increase in cardiopulmonary arrest events. The centralized unit monitored 99,048 patient orders, and ultimately detected serious problems and accurately notified on-site staff for 79% of 3,243 events, which included a rhythm and/or rate change within 1 hour or less of the event. Accurate notification to on-site hospital staff was more than 84%.
Since then, improvements to the system have continued, according to Cleveland Clinic, and include doubling the number of monitored patients per technician and improved clinical outcomes.
Reference
Cleveland Clinic: Consult QD – An update on the centralized cardiac telemetry monitoring unit
Hospitalists hearing the constant noise from cardiac telemetry monitoring systems can experience alarm fatigue – a nationwide phenomenon that can lead to an increase in patient deaths.
The American Heart Association reports that fewer than one in four adults survived an in-hospital cardiac arrest in 2013; other studies showed that up to 44% of inpatient cardiac arrests were not detected appropriately, according to the Cleveland Clinic.
Clinicians at the Cleveland Clinic have tried centralized monitoring to address the problem. They’ve established a “mission control” center, where off-site personnel monitor sensors and high-definition cameras and vital signs such as blood pressure, heart rate, and respiration. On-site action is requested when appropriate; unimportant alarms are dismissed.
In August 2016, results from the first 13 months of the Cleveland Clinic program were published in JAMA. They revealed that the monitoring system could help reduce rates of unimportant alarms with no increase in cardiopulmonary arrest events. The centralized unit monitored 99,048 patient orders, and ultimately detected serious problems and accurately notified on-site staff for 79% of 3,243 events, which included a rhythm and/or rate change within 1 hour or less of the event. Accurate notification to on-site hospital staff was more than 84%.
Since then, improvements to the system have continued, according to Cleveland Clinic, and include doubling the number of monitored patients per technician and improved clinical outcomes.
Reference
Cleveland Clinic: Consult QD – An update on the centralized cardiac telemetry monitoring unit
Low and high BMI tied to higher postpartum depression risk
Women with high and low body mass index in the first trimester of their first pregnancies are at an increased risk of developing postpartum depression, a population-based study of more than 600,000 new mothers shows.
“Our findings show a U-shaped association between BMI extremes and clinically significant depression after childbirth,” Michael E. Silverman, PhD, and his associates reported in the Journal of Affective Disorders. “Specifically, women in the lowest and highest groups were at a significantly increased risk for developing [postpartum depression].”
Dr. Silverman and his associates used the Swedish Medical Birth Register to identify women who delivered first live singleton infants from 1997 to 2008. They then calculated the risk of postpartum depression in relation to each woman’s BMI and history of depression. Postpartum depression was defined as a clinical depression diagnosis within 1 year after delivery, Dr. Silverman and his associates wrote.
The investigators found that women with low BMI (less than 18.5 kg/m2) were at an increased postpartum depression risk (relative risk [RR], 1.52; 95% confidence interval, 1.30-1.78), as were those with high BMI (greater than 35 kg/m2) (RR, 1.23; 95% CI, 1.04-1.45).
In addition, an important difference was found between women with low and high BMI.
“Women in the highest BMI group were only at an increased risk for [postpartum depression] if they had no history of depression, showing for the first time how [postpartum depression] risk factors associated with BMI are modified by maternal depression history,” said Dr. Silverman of the department of psychiatry at the Icahn School of Medicine at Mount Sinai, New York, and his associates.
The investigators cited several limitations. For example, only first births were analyzed, which suggests that the incidence of postpartum depression might have been underestimated. Another limitation is that the registry might not have captured women with mild depression. Nevertheless, they said, the study has important implications.
“ Because pregnant women represent a medically captured population,” they wrote, the findings support implementing preventive strategies for postpartum depression and health literacy for high-risk women.
Dr. Silverman and his associates reported having no conflicts of interest. The study was supported by a grant from the National Institutes of Health.
SOURCE: Silverman ME et al. J Affect Disord. 2018 Nov;240:193-8.
Women with high and low body mass index in the first trimester of their first pregnancies are at an increased risk of developing postpartum depression, a population-based study of more than 600,000 new mothers shows.
“Our findings show a U-shaped association between BMI extremes and clinically significant depression after childbirth,” Michael E. Silverman, PhD, and his associates reported in the Journal of Affective Disorders. “Specifically, women in the lowest and highest groups were at a significantly increased risk for developing [postpartum depression].”
Dr. Silverman and his associates used the Swedish Medical Birth Register to identify women who delivered first live singleton infants from 1997 to 2008. They then calculated the risk of postpartum depression in relation to each woman’s BMI and history of depression. Postpartum depression was defined as a clinical depression diagnosis within 1 year after delivery, Dr. Silverman and his associates wrote.
The investigators found that women with low BMI (less than 18.5 kg/m2) were at an increased postpartum depression risk (relative risk [RR], 1.52; 95% confidence interval, 1.30-1.78), as were those with high BMI (greater than 35 kg/m2) (RR, 1.23; 95% CI, 1.04-1.45).
In addition, an important difference was found between women with low and high BMI.
“Women in the highest BMI group were only at an increased risk for [postpartum depression] if they had no history of depression, showing for the first time how [postpartum depression] risk factors associated with BMI are modified by maternal depression history,” said Dr. Silverman of the department of psychiatry at the Icahn School of Medicine at Mount Sinai, New York, and his associates.
The investigators cited several limitations. For example, only first births were analyzed, which suggests that the incidence of postpartum depression might have been underestimated. Another limitation is that the registry might not have captured women with mild depression. Nevertheless, they said, the study has important implications.
“ Because pregnant women represent a medically captured population,” they wrote, the findings support implementing preventive strategies for postpartum depression and health literacy for high-risk women.
Dr. Silverman and his associates reported having no conflicts of interest. The study was supported by a grant from the National Institutes of Health.
SOURCE: Silverman ME et al. J Affect Disord. 2018 Nov;240:193-8.
Women with high and low body mass index in the first trimester of their first pregnancies are at an increased risk of developing postpartum depression, a population-based study of more than 600,000 new mothers shows.
“Our findings show a U-shaped association between BMI extremes and clinically significant depression after childbirth,” Michael E. Silverman, PhD, and his associates reported in the Journal of Affective Disorders. “Specifically, women in the lowest and highest groups were at a significantly increased risk for developing [postpartum depression].”
Dr. Silverman and his associates used the Swedish Medical Birth Register to identify women who delivered first live singleton infants from 1997 to 2008. They then calculated the risk of postpartum depression in relation to each woman’s BMI and history of depression. Postpartum depression was defined as a clinical depression diagnosis within 1 year after delivery, Dr. Silverman and his associates wrote.
The investigators found that women with low BMI (less than 18.5 kg/m2) were at an increased postpartum depression risk (relative risk [RR], 1.52; 95% confidence interval, 1.30-1.78), as were those with high BMI (greater than 35 kg/m2) (RR, 1.23; 95% CI, 1.04-1.45).
In addition, an important difference was found between women with low and high BMI.
“Women in the highest BMI group were only at an increased risk for [postpartum depression] if they had no history of depression, showing for the first time how [postpartum depression] risk factors associated with BMI are modified by maternal depression history,” said Dr. Silverman of the department of psychiatry at the Icahn School of Medicine at Mount Sinai, New York, and his associates.
The investigators cited several limitations. For example, only first births were analyzed, which suggests that the incidence of postpartum depression might have been underestimated. Another limitation is that the registry might not have captured women with mild depression. Nevertheless, they said, the study has important implications.
“ Because pregnant women represent a medically captured population,” they wrote, the findings support implementing preventive strategies for postpartum depression and health literacy for high-risk women.
Dr. Silverman and his associates reported having no conflicts of interest. The study was supported by a grant from the National Institutes of Health.
SOURCE: Silverman ME et al. J Affect Disord. 2018 Nov;240:193-8.
FROM THE JOURNAL OF AFFECTIVE DISORDERS
Cannabis crimps teen cognitive development
BARCELONA – What would you predict has a greater detrimental effect on adolescent cognitive development: alcohol or cannabis use?
The evidence-based answer may come as a surprise. It certainly did for Patricia Conrod, PhD, who led the large population-based study that addressed the question.
“Generally, we found no effect of alcohol on cognitive development, which was a huge surprise to us. It might be related to the fact that the quantity of alcohol consumption in this young sample just wasn’t high enough to produce significant effects on cognitive development. But, to our surprise, we found rather significant effects of cannabis use on cognitive development,” she said at the annual congress of the European College of Neuropsychopharmacology.
Indeed, cannabis use proved to have detrimental effects on all four cognitive domains assessed in the study: working memory, perceptual reasoning, delayed recall, and inhibitory control, reported Dr. Conrod, professor of psychiatry at the University of Montreal.
Her recently study, published in the American Journal of Psychiatry, included 3,826 seventh-grade students at 31 Montreal-area schools. They constituted 5% of all students entering that grade in the greater Montreal area. Participants were prospectively assessed annually for 4 years regarding their use or nonuse of alcohol or cannabis and also underwent neurocognitive testing on the four domains of interest. The assessments were done on school computers with preservation of student confidentiality. Investigators used a Big Data approach to model the relationship between the extent of substance use and neurocognitive function variables over time.
Abstinent students were the best performers on the neurocognitive testing. Cannabis use, but not alcohol, in a given year was associated with concurrent adverse effects on all four cognitive domains. In addition, cannabis use showed evidence of having a neurotoxic lag effect on inhibitory control and working memory. This took the form of a lasting effect: A student who reported using cannabis 1 year but not the next showed impairment of inhibitory control and working memory during both years. And a student who used cannabis both years was even more impaired in those domains.
Dr. Conrod found the evidence of a neurotoxic effect of cannabis use on inhibitory control to be of particular concern because in earlier studies she established that impaired inhibitory control is a strong independent risk factor for subsequent substance use disorders.
”So what we’re seeing is indeed that early onset substance use is interfering with cognitive development, which now sets us up to be able to answer the question of whether evidence-based prevention protects cognitive development by delaying early onset of substance use. And over the longer term, does that protect young people against addiction?”
Dr. Conrod and her coworkers are now in the process of obtaining answers to those questions in the large ongoing Canadian Institutes of Health Research-funded Co-Venture Trial. This randomized trial involving thousands of adolescent students used the investigators’ Preventure Program, a school-based, personality-targeted intervention for prevention of substance use and abuse.
The Preventure Program involves two 90-minute group sessions of manual-based cognitive-behavioral therapy. Students are invited to participate if they score at least one standard deviation above the school mean on one of four personality traits that have been shown to increase the risk of substance misuse and psychiatric disorders. The four personality traits are sensation seeking, impulsivity, anxiety sensitivity, and hopelessness. Typically, about 45% of students met that threshold, and 85% of those invited to participate in the program volunteered to do so. Students of similar personality type are grouped together for the targeted therapy sessions.
This brief coping skills intervention has been shown in multiple randomized trials around the world to reduce the likelihood of substance use in at-risk adolescents. For example, in an early trial involving 732 high school students in London, participation in the Preventure Program was associated with a 30% reduction in the likelihood of taking up the use of cannabis within the next 2 years, an 80% reduction in the likelihood of taking up cocaine, and a 50% reduction in the use of other drugs (Arch Gen Psychiatry. 2010 Jan;67[1]:85-93).
[email protected]
SOURCE: Conrod P. Am J Psychiatry. 2018 Oct 3. doi: 10.1176/appi.ajp.2018.18020202.
BARCELONA – What would you predict has a greater detrimental effect on adolescent cognitive development: alcohol or cannabis use?
The evidence-based answer may come as a surprise. It certainly did for Patricia Conrod, PhD, who led the large population-based study that addressed the question.
“Generally, we found no effect of alcohol on cognitive development, which was a huge surprise to us. It might be related to the fact that the quantity of alcohol consumption in this young sample just wasn’t high enough to produce significant effects on cognitive development. But, to our surprise, we found rather significant effects of cannabis use on cognitive development,” she said at the annual congress of the European College of Neuropsychopharmacology.
Indeed, cannabis use proved to have detrimental effects on all four cognitive domains assessed in the study: working memory, perceptual reasoning, delayed recall, and inhibitory control, reported Dr. Conrod, professor of psychiatry at the University of Montreal.
Her recently study, published in the American Journal of Psychiatry, included 3,826 seventh-grade students at 31 Montreal-area schools. They constituted 5% of all students entering that grade in the greater Montreal area. Participants were prospectively assessed annually for 4 years regarding their use or nonuse of alcohol or cannabis and also underwent neurocognitive testing on the four domains of interest. The assessments were done on school computers with preservation of student confidentiality. Investigators used a Big Data approach to model the relationship between the extent of substance use and neurocognitive function variables over time.
Abstinent students were the best performers on the neurocognitive testing. Cannabis use, but not alcohol, in a given year was associated with concurrent adverse effects on all four cognitive domains. In addition, cannabis use showed evidence of having a neurotoxic lag effect on inhibitory control and working memory. This took the form of a lasting effect: A student who reported using cannabis 1 year but not the next showed impairment of inhibitory control and working memory during both years. And a student who used cannabis both years was even more impaired in those domains.
Dr. Conrod found the evidence of a neurotoxic effect of cannabis use on inhibitory control to be of particular concern because in earlier studies she established that impaired inhibitory control is a strong independent risk factor for subsequent substance use disorders.
”So what we’re seeing is indeed that early onset substance use is interfering with cognitive development, which now sets us up to be able to answer the question of whether evidence-based prevention protects cognitive development by delaying early onset of substance use. And over the longer term, does that protect young people against addiction?”
Dr. Conrod and her coworkers are now in the process of obtaining answers to those questions in the large ongoing Canadian Institutes of Health Research-funded Co-Venture Trial. This randomized trial involving thousands of adolescent students used the investigators’ Preventure Program, a school-based, personality-targeted intervention for prevention of substance use and abuse.
The Preventure Program involves two 90-minute group sessions of manual-based cognitive-behavioral therapy. Students are invited to participate if they score at least one standard deviation above the school mean on one of four personality traits that have been shown to increase the risk of substance misuse and psychiatric disorders. The four personality traits are sensation seeking, impulsivity, anxiety sensitivity, and hopelessness. Typically, about 45% of students met that threshold, and 85% of those invited to participate in the program volunteered to do so. Students of similar personality type are grouped together for the targeted therapy sessions.
This brief coping skills intervention has been shown in multiple randomized trials around the world to reduce the likelihood of substance use in at-risk adolescents. For example, in an early trial involving 732 high school students in London, participation in the Preventure Program was associated with a 30% reduction in the likelihood of taking up the use of cannabis within the next 2 years, an 80% reduction in the likelihood of taking up cocaine, and a 50% reduction in the use of other drugs (Arch Gen Psychiatry. 2010 Jan;67[1]:85-93).
[email protected]
SOURCE: Conrod P. Am J Psychiatry. 2018 Oct 3. doi: 10.1176/appi.ajp.2018.18020202.
BARCELONA – What would you predict has a greater detrimental effect on adolescent cognitive development: alcohol or cannabis use?
The evidence-based answer may come as a surprise. It certainly did for Patricia Conrod, PhD, who led the large population-based study that addressed the question.
“Generally, we found no effect of alcohol on cognitive development, which was a huge surprise to us. It might be related to the fact that the quantity of alcohol consumption in this young sample just wasn’t high enough to produce significant effects on cognitive development. But, to our surprise, we found rather significant effects of cannabis use on cognitive development,” she said at the annual congress of the European College of Neuropsychopharmacology.
Indeed, cannabis use proved to have detrimental effects on all four cognitive domains assessed in the study: working memory, perceptual reasoning, delayed recall, and inhibitory control, reported Dr. Conrod, professor of psychiatry at the University of Montreal.
Her recently study, published in the American Journal of Psychiatry, included 3,826 seventh-grade students at 31 Montreal-area schools. They constituted 5% of all students entering that grade in the greater Montreal area. Participants were prospectively assessed annually for 4 years regarding their use or nonuse of alcohol or cannabis and also underwent neurocognitive testing on the four domains of interest. The assessments were done on school computers with preservation of student confidentiality. Investigators used a Big Data approach to model the relationship between the extent of substance use and neurocognitive function variables over time.
Abstinent students were the best performers on the neurocognitive testing. Cannabis use, but not alcohol, in a given year was associated with concurrent adverse effects on all four cognitive domains. In addition, cannabis use showed evidence of having a neurotoxic lag effect on inhibitory control and working memory. This took the form of a lasting effect: A student who reported using cannabis 1 year but not the next showed impairment of inhibitory control and working memory during both years. And a student who used cannabis both years was even more impaired in those domains.
Dr. Conrod found the evidence of a neurotoxic effect of cannabis use on inhibitory control to be of particular concern because in earlier studies she established that impaired inhibitory control is a strong independent risk factor for subsequent substance use disorders.
”So what we’re seeing is indeed that early onset substance use is interfering with cognitive development, which now sets us up to be able to answer the question of whether evidence-based prevention protects cognitive development by delaying early onset of substance use. And over the longer term, does that protect young people against addiction?”
Dr. Conrod and her coworkers are now in the process of obtaining answers to those questions in the large ongoing Canadian Institutes of Health Research-funded Co-Venture Trial. This randomized trial involving thousands of adolescent students used the investigators’ Preventure Program, a school-based, personality-targeted intervention for prevention of substance use and abuse.
The Preventure Program involves two 90-minute group sessions of manual-based cognitive-behavioral therapy. Students are invited to participate if they score at least one standard deviation above the school mean on one of four personality traits that have been shown to increase the risk of substance misuse and psychiatric disorders. The four personality traits are sensation seeking, impulsivity, anxiety sensitivity, and hopelessness. Typically, about 45% of students met that threshold, and 85% of those invited to participate in the program volunteered to do so. Students of similar personality type are grouped together for the targeted therapy sessions.
This brief coping skills intervention has been shown in multiple randomized trials around the world to reduce the likelihood of substance use in at-risk adolescents. For example, in an early trial involving 732 high school students in London, participation in the Preventure Program was associated with a 30% reduction in the likelihood of taking up the use of cannabis within the next 2 years, an 80% reduction in the likelihood of taking up cocaine, and a 50% reduction in the use of other drugs (Arch Gen Psychiatry. 2010 Jan;67[1]:85-93).
[email protected]
SOURCE: Conrod P. Am J Psychiatry. 2018 Oct 3. doi: 10.1176/appi.ajp.2018.18020202.
REPORTING FROM THE ECNP CONGRESS
Key clinical point:
Major finding: The observed neurotoxic effect on impulse control may spell future trouble.
Study details: This population-based study included 3,826 Montreal-area seventh graders who were prospectively assessed annually for 4 years regarding their cannabis and alcohol use and also underwent neurocognitive testing.
Disclosures: The study was funded by the Canadian Institutes of Health Research.
Source: Conrod P. Am J Psychiatry. 2018 Oct 3. doi: 10.1176/appi.ajp.2018.18020202.
Aspirin cuts risk of liver and ovarian cancer
Regular long-term aspirin use may lower the risk of hepatocellular carcinoma (HCC) and ovarian cancer, adding to the growing evidence that aspirin may play a role as a chemopreventive agent, according to two new studies published in JAMA Oncology.
In the first study, led by Tracey G. Simon, MD, of Massachusetts General Hospital, Boston, the authors evaluated the associations between aspirin dose and duration of use and the risk of developing HCC. They conducted a population-based study, with a pooled analysis of two large prospective U.S. cohort studies: the Nurses’ Health Study and the Health Professionals Follow-up Study. The cohort included a total of 133,371 health care professionals who reported long-term data on aspirin use, frequency, dosage, and duration of use.
For the 87,507 female participants, reporting began in 1980, and for the 45,864 men, reporting began in 1986. The mean age for women was 62 years and was 64 years for men at the midpoint of follow-up (1996). Compared with nonaspirin users, those who used aspirin regularly tended to be older, former smokers, and regularly used statins and multivitamins. During the follow-up period, which was more than 26 years, there were 108 incident cases of HCC (65 women, 43 men; 47 with noncirrhotic HCC).
The investigators found that regular aspirin use was associated with a significantly lower HCC risk versus nonregular use (multivariable hazard ratio, 0.51; 95% confidence interval, 0.34-0.77), and estimates were similar for both sexes. Adjustments for regular NSAID use (for example, at least two tablets per week) did not change the data, and results were similar after further adjustment for coffee consumption and adherence to a healthy diet. The benefit also appeared to be dose related, as compared with nonuse, the multivariable-adjusted HR for HCC was 0.87 (95% CI, 0.51-1.48) for up to 1.5 tablets of standard-dose aspirin per week and 0.51 (95% CI, 0.30-0.86) for 1.5-5 tablets per week. The most benefit was for at least five tablets per week (HR, 0.49; 95% CI, 0.28-0.96; P = .006).
“Our findings add to the growing literature suggesting that the chemopreventive effects of aspirin may extend beyond colorectal cancer,” they wrote.
In the second study, Mollie E. Barnard, ScD, of the Harvard School of Public Health, Boston, and her colleagues looked at whether regular aspirin or NSAID use, as well as the patterns of use, were associated with a lower risk of ovarian cancer.
The data used were obtained from 93,664 women in the Nurses’ Health Study (NHS), who were followed up from 1980 to 2014, and 111,834 people in the Nurses’ Health Study II (NHSII), who were followed up from 1989 to 2015. For each type of agent, including aspirin, low-dose aspirin, nonaspirin NSAIDs, and acetaminophen, they evaluated the timing, duration, frequency, and number of tablets that were used. The mean age of participants in the NHS at baseline was 45.9 years and 34.2 years in the NHSII.
There were 1,054 incident cases of epithelial ovarian cancer identified during the study period. The authors did not detect any significant associations between aspirin and ovarian cancer risk when current users and nonusers were compared, regardless of dose (HR, 0.99; 95% CI, 0.83-1.19). But when low-dose (less than or equal to 100 mg) and standard-dose (325 mg) aspirin were analyzed separately, an inverse association for low-dose aspirin (HR, 0.77; 95% CI, 0.61-0.96) was observed. However, there was no association for standard-dose aspirin (HR, 1.17; 95% CI, 0.92-1.49).
In contrast, use of nonaspirin NSAIDs was positively associated with a higher risk of ovarian cancer when compared with nonuse (HR, 1.19; 95% CI, 1.00-1.41), and there were significant positive trends for duration of use (P = .02) and cumulative average tablets per week (P = .03). No clear associations were identified for acetaminophen use.
“Our results also suggest an increased risk of ovarian cancer among long-term, high-quantity users of nonaspirin analgesics, although this finding may reflect unmeasured confounding,” wrote Dr. Barnard and her coauthors. “Further exploration is warranted to evaluate the mechanisms by which heavy use of aspirin, nonaspirin NSAIDs, and acetaminophen may contribute to the development of ovarian cancer and to replicate our findings.”
The ovarian cancer study was supported by awards from the National Institutes of Health. Dr. Barnard was supported by awards from the National Cancer Institute, and her coauthors had no disclosures to report. The HCC study was funded by an infrastructure grant from the Nurses’ Health Study, an infrastructure grant from the Health Professionals Follow-up Study, and NIH grants to several of the authors. Dr. Chan has previously served as a consultant for Bayer on work unrelated to this article. No other disclosures were reported.
SOURCES: Barnard ME et al. JAMA Oncol. 2018 Oct 4. doi: 10.1001/jamaoncol.2018.4149; Simon TG et al. JAMA Oncol. 2018 Oct 4. doi: 10.1001/jamaoncol.2018.4154.
In an accompanying editorial published in JAMA Oncology, Victoria L. Seewaldt, MD, of the City of Hope Comprehensive Cancer Center in Duarte, Calif., asked if we “have arrived,” as these two studies are a critical step in realizing the potential of aspirin for cancer chemoprevention beyond colorectal cancer.
Aspirin use is very common in the United States, with almost half of adults aged between 45 and 75 years taking it regularly. Many regular users also believe that aspirin has potential to protect against cancer, and in a 2015 study – which was conducted prior to any formal cancer prevention guidelines – 18% of those taking aspirin on a regular basis reported doing so to prevent cancer.
Based on the strength of the association between aspirin use and colorectal cancer risk reduction, the U.S. Preventive Services Task Force recommended in 2015 that, among individuals aged between 50 and 69 years who have specific cardiovascular risk profiles, colorectal cancer prevention be included as part of the rationale for regular aspirin prophylaxis, Dr. Seewaldt noted. Aspirin became the first drug to be included in USPSTF recommendations for cancer chemoprevention in a “population not characterized as having a high risk of developing cancer.”
But it now appears aspirin may be able to go beyond colorectal cancer for chemoprevention. Ovarian cancer and hepatocellular carcinoma are in need of new prevention strategies and these findings provide important information that can help guide chemoprevention with aspirin.
These two studies “have the power to start to change clinical practice,” Dr. Seewaldt wrote, but more research is needed to better understand the underlying mechanism behind the appropriate dose and duration of use. Importantly, the authors of both studies cautioned that the potential benefits of aspirin must be weighed against the risk of bleeding, which is particularly important in patients with chronic liver disease.
“To reach the full promise of aspirin’s ability to prevent cancer, there needs to be better understanding of dose, duration, and mechanism,” she emphasized.
Dr. Seewaldt reported receiving grants from the National Institutes of Health/National Cancer Institute and is supported by the Prevent Cancer Foundation.
In an accompanying editorial published in JAMA Oncology, Victoria L. Seewaldt, MD, of the City of Hope Comprehensive Cancer Center in Duarte, Calif., asked if we “have arrived,” as these two studies are a critical step in realizing the potential of aspirin for cancer chemoprevention beyond colorectal cancer.
Aspirin use is very common in the United States, with almost half of adults aged between 45 and 75 years taking it regularly. Many regular users also believe that aspirin has potential to protect against cancer, and in a 2015 study – which was conducted prior to any formal cancer prevention guidelines – 18% of those taking aspirin on a regular basis reported doing so to prevent cancer.
Based on the strength of the association between aspirin use and colorectal cancer risk reduction, the U.S. Preventive Services Task Force recommended in 2015 that, among individuals aged between 50 and 69 years who have specific cardiovascular risk profiles, colorectal cancer prevention be included as part of the rationale for regular aspirin prophylaxis, Dr. Seewaldt noted. Aspirin became the first drug to be included in USPSTF recommendations for cancer chemoprevention in a “population not characterized as having a high risk of developing cancer.”
But it now appears aspirin may be able to go beyond colorectal cancer for chemoprevention. Ovarian cancer and hepatocellular carcinoma are in need of new prevention strategies and these findings provide important information that can help guide chemoprevention with aspirin.
These two studies “have the power to start to change clinical practice,” Dr. Seewaldt wrote, but more research is needed to better understand the underlying mechanism behind the appropriate dose and duration of use. Importantly, the authors of both studies cautioned that the potential benefits of aspirin must be weighed against the risk of bleeding, which is particularly important in patients with chronic liver disease.
“To reach the full promise of aspirin’s ability to prevent cancer, there needs to be better understanding of dose, duration, and mechanism,” she emphasized.
Dr. Seewaldt reported receiving grants from the National Institutes of Health/National Cancer Institute and is supported by the Prevent Cancer Foundation.
In an accompanying editorial published in JAMA Oncology, Victoria L. Seewaldt, MD, of the City of Hope Comprehensive Cancer Center in Duarte, Calif., asked if we “have arrived,” as these two studies are a critical step in realizing the potential of aspirin for cancer chemoprevention beyond colorectal cancer.
Aspirin use is very common in the United States, with almost half of adults aged between 45 and 75 years taking it regularly. Many regular users also believe that aspirin has potential to protect against cancer, and in a 2015 study – which was conducted prior to any formal cancer prevention guidelines – 18% of those taking aspirin on a regular basis reported doing so to prevent cancer.
Based on the strength of the association between aspirin use and colorectal cancer risk reduction, the U.S. Preventive Services Task Force recommended in 2015 that, among individuals aged between 50 and 69 years who have specific cardiovascular risk profiles, colorectal cancer prevention be included as part of the rationale for regular aspirin prophylaxis, Dr. Seewaldt noted. Aspirin became the first drug to be included in USPSTF recommendations for cancer chemoprevention in a “population not characterized as having a high risk of developing cancer.”
But it now appears aspirin may be able to go beyond colorectal cancer for chemoprevention. Ovarian cancer and hepatocellular carcinoma are in need of new prevention strategies and these findings provide important information that can help guide chemoprevention with aspirin.
These two studies “have the power to start to change clinical practice,” Dr. Seewaldt wrote, but more research is needed to better understand the underlying mechanism behind the appropriate dose and duration of use. Importantly, the authors of both studies cautioned that the potential benefits of aspirin must be weighed against the risk of bleeding, which is particularly important in patients with chronic liver disease.
“To reach the full promise of aspirin’s ability to prevent cancer, there needs to be better understanding of dose, duration, and mechanism,” she emphasized.
Dr. Seewaldt reported receiving grants from the National Institutes of Health/National Cancer Institute and is supported by the Prevent Cancer Foundation.
Regular long-term aspirin use may lower the risk of hepatocellular carcinoma (HCC) and ovarian cancer, adding to the growing evidence that aspirin may play a role as a chemopreventive agent, according to two new studies published in JAMA Oncology.
In the first study, led by Tracey G. Simon, MD, of Massachusetts General Hospital, Boston, the authors evaluated the associations between aspirin dose and duration of use and the risk of developing HCC. They conducted a population-based study, with a pooled analysis of two large prospective U.S. cohort studies: the Nurses’ Health Study and the Health Professionals Follow-up Study. The cohort included a total of 133,371 health care professionals who reported long-term data on aspirin use, frequency, dosage, and duration of use.
For the 87,507 female participants, reporting began in 1980, and for the 45,864 men, reporting began in 1986. The mean age for women was 62 years and was 64 years for men at the midpoint of follow-up (1996). Compared with nonaspirin users, those who used aspirin regularly tended to be older, former smokers, and regularly used statins and multivitamins. During the follow-up period, which was more than 26 years, there were 108 incident cases of HCC (65 women, 43 men; 47 with noncirrhotic HCC).
The investigators found that regular aspirin use was associated with a significantly lower HCC risk versus nonregular use (multivariable hazard ratio, 0.51; 95% confidence interval, 0.34-0.77), and estimates were similar for both sexes. Adjustments for regular NSAID use (for example, at least two tablets per week) did not change the data, and results were similar after further adjustment for coffee consumption and adherence to a healthy diet. The benefit also appeared to be dose related, as compared with nonuse, the multivariable-adjusted HR for HCC was 0.87 (95% CI, 0.51-1.48) for up to 1.5 tablets of standard-dose aspirin per week and 0.51 (95% CI, 0.30-0.86) for 1.5-5 tablets per week. The most benefit was for at least five tablets per week (HR, 0.49; 95% CI, 0.28-0.96; P = .006).
“Our findings add to the growing literature suggesting that the chemopreventive effects of aspirin may extend beyond colorectal cancer,” they wrote.
In the second study, Mollie E. Barnard, ScD, of the Harvard School of Public Health, Boston, and her colleagues looked at whether regular aspirin or NSAID use, as well as the patterns of use, were associated with a lower risk of ovarian cancer.
The data used were obtained from 93,664 women in the Nurses’ Health Study (NHS), who were followed up from 1980 to 2014, and 111,834 people in the Nurses’ Health Study II (NHSII), who were followed up from 1989 to 2015. For each type of agent, including aspirin, low-dose aspirin, nonaspirin NSAIDs, and acetaminophen, they evaluated the timing, duration, frequency, and number of tablets that were used. The mean age of participants in the NHS at baseline was 45.9 years and 34.2 years in the NHSII.
There were 1,054 incident cases of epithelial ovarian cancer identified during the study period. The authors did not detect any significant associations between aspirin and ovarian cancer risk when current users and nonusers were compared, regardless of dose (HR, 0.99; 95% CI, 0.83-1.19). But when low-dose (less than or equal to 100 mg) and standard-dose (325 mg) aspirin were analyzed separately, an inverse association for low-dose aspirin (HR, 0.77; 95% CI, 0.61-0.96) was observed. However, there was no association for standard-dose aspirin (HR, 1.17; 95% CI, 0.92-1.49).
In contrast, use of nonaspirin NSAIDs was positively associated with a higher risk of ovarian cancer when compared with nonuse (HR, 1.19; 95% CI, 1.00-1.41), and there were significant positive trends for duration of use (P = .02) and cumulative average tablets per week (P = .03). No clear associations were identified for acetaminophen use.
“Our results also suggest an increased risk of ovarian cancer among long-term, high-quantity users of nonaspirin analgesics, although this finding may reflect unmeasured confounding,” wrote Dr. Barnard and her coauthors. “Further exploration is warranted to evaluate the mechanisms by which heavy use of aspirin, nonaspirin NSAIDs, and acetaminophen may contribute to the development of ovarian cancer and to replicate our findings.”
The ovarian cancer study was supported by awards from the National Institutes of Health. Dr. Barnard was supported by awards from the National Cancer Institute, and her coauthors had no disclosures to report. The HCC study was funded by an infrastructure grant from the Nurses’ Health Study, an infrastructure grant from the Health Professionals Follow-up Study, and NIH grants to several of the authors. Dr. Chan has previously served as a consultant for Bayer on work unrelated to this article. No other disclosures were reported.
SOURCES: Barnard ME et al. JAMA Oncol. 2018 Oct 4. doi: 10.1001/jamaoncol.2018.4149; Simon TG et al. JAMA Oncol. 2018 Oct 4. doi: 10.1001/jamaoncol.2018.4154.
Regular long-term aspirin use may lower the risk of hepatocellular carcinoma (HCC) and ovarian cancer, adding to the growing evidence that aspirin may play a role as a chemopreventive agent, according to two new studies published in JAMA Oncology.
In the first study, led by Tracey G. Simon, MD, of Massachusetts General Hospital, Boston, the authors evaluated the associations between aspirin dose and duration of use and the risk of developing HCC. They conducted a population-based study, with a pooled analysis of two large prospective U.S. cohort studies: the Nurses’ Health Study and the Health Professionals Follow-up Study. The cohort included a total of 133,371 health care professionals who reported long-term data on aspirin use, frequency, dosage, and duration of use.
For the 87,507 female participants, reporting began in 1980, and for the 45,864 men, reporting began in 1986. The mean age for women was 62 years and was 64 years for men at the midpoint of follow-up (1996). Compared with nonaspirin users, those who used aspirin regularly tended to be older, former smokers, and regularly used statins and multivitamins. During the follow-up period, which was more than 26 years, there were 108 incident cases of HCC (65 women, 43 men; 47 with noncirrhotic HCC).
The investigators found that regular aspirin use was associated with a significantly lower HCC risk versus nonregular use (multivariable hazard ratio, 0.51; 95% confidence interval, 0.34-0.77), and estimates were similar for both sexes. Adjustments for regular NSAID use (for example, at least two tablets per week) did not change the data, and results were similar after further adjustment for coffee consumption and adherence to a healthy diet. The benefit also appeared to be dose related, as compared with nonuse, the multivariable-adjusted HR for HCC was 0.87 (95% CI, 0.51-1.48) for up to 1.5 tablets of standard-dose aspirin per week and 0.51 (95% CI, 0.30-0.86) for 1.5-5 tablets per week. The most benefit was for at least five tablets per week (HR, 0.49; 95% CI, 0.28-0.96; P = .006).
“Our findings add to the growing literature suggesting that the chemopreventive effects of aspirin may extend beyond colorectal cancer,” they wrote.
In the second study, Mollie E. Barnard, ScD, of the Harvard School of Public Health, Boston, and her colleagues looked at whether regular aspirin or NSAID use, as well as the patterns of use, were associated with a lower risk of ovarian cancer.
The data used were obtained from 93,664 women in the Nurses’ Health Study (NHS), who were followed up from 1980 to 2014, and 111,834 people in the Nurses’ Health Study II (NHSII), who were followed up from 1989 to 2015. For each type of agent, including aspirin, low-dose aspirin, nonaspirin NSAIDs, and acetaminophen, they evaluated the timing, duration, frequency, and number of tablets that were used. The mean age of participants in the NHS at baseline was 45.9 years and 34.2 years in the NHSII.
There were 1,054 incident cases of epithelial ovarian cancer identified during the study period. The authors did not detect any significant associations between aspirin and ovarian cancer risk when current users and nonusers were compared, regardless of dose (HR, 0.99; 95% CI, 0.83-1.19). But when low-dose (less than or equal to 100 mg) and standard-dose (325 mg) aspirin were analyzed separately, an inverse association for low-dose aspirin (HR, 0.77; 95% CI, 0.61-0.96) was observed. However, there was no association for standard-dose aspirin (HR, 1.17; 95% CI, 0.92-1.49).
In contrast, use of nonaspirin NSAIDs was positively associated with a higher risk of ovarian cancer when compared with nonuse (HR, 1.19; 95% CI, 1.00-1.41), and there were significant positive trends for duration of use (P = .02) and cumulative average tablets per week (P = .03). No clear associations were identified for acetaminophen use.
“Our results also suggest an increased risk of ovarian cancer among long-term, high-quantity users of nonaspirin analgesics, although this finding may reflect unmeasured confounding,” wrote Dr. Barnard and her coauthors. “Further exploration is warranted to evaluate the mechanisms by which heavy use of aspirin, nonaspirin NSAIDs, and acetaminophen may contribute to the development of ovarian cancer and to replicate our findings.”
The ovarian cancer study was supported by awards from the National Institutes of Health. Dr. Barnard was supported by awards from the National Cancer Institute, and her coauthors had no disclosures to report. The HCC study was funded by an infrastructure grant from the Nurses’ Health Study, an infrastructure grant from the Health Professionals Follow-up Study, and NIH grants to several of the authors. Dr. Chan has previously served as a consultant for Bayer on work unrelated to this article. No other disclosures were reported.
SOURCES: Barnard ME et al. JAMA Oncol. 2018 Oct 4. doi: 10.1001/jamaoncol.2018.4149; Simon TG et al. JAMA Oncol. 2018 Oct 4. doi: 10.1001/jamaoncol.2018.4154.
FROM JAMA ONCOLOGY
Key clinical point: Regular aspirin use was associated with a decreased risk of ovarian cancer and hepatocellular carcinoma.
Major finding: Low-dose aspirin was associated with a 23% lower risk of ovarian cancer and a 49% reduced risk of developing hepatocellular carcinoma.
Study details: The hepatocellular carcinoma study was a population-based study of two nationwide, prospective cohorts of 87,507 men and 45,864 women; the ovarian cancer study was a cohort study using data from two prospective cohorts, with 93,664 people in one and 111,834 in the other.
Disclosures: The ovarian cancer study was supported by awards from the National Institutes of Health. Dr. Barnard was supported by awards from the National Cancer Institute, and her coauthors had no disclosures to report. The hepatocellular carcinoma study was funded by an infrastructure grant from the Nurses’ Health Study, an infrastructure grant from the Health Professionals Follow-up Study, and NIH grants to several of the authors. Dr. Chan has previously served as a consultant for Bayer on work unrelated to this article. No other disclosures were reported.
Sources: Barnard ME et al. JAMA Oncol. 2018 Oct 4. doi: 10.1001/jamaoncol.2018.4149; Simon TG et al. JAMA Oncol. 2018 Oct 4. doi: 10.1001/jamaoncol.2018.4154.
STAMPEDE: Radiation to prostate boosts survival of metastatic cancer
MUNICH – Radiotherapy of the primary tumor can improve overall survival in men with untreated metastatic adenocarcinoma of the prostate, a finding that suggests a possible life-extending role of radiotherapy in other metastatic tumor types, investigators in the STAMPEDE trial reported.
Among 2,061 men from the United Kingdom and Switzerland with previously untreated metastatic prostate cancer, there was no survival advantage to adding local radiation to standard drug therapy in the overall study population. But among men with low disease burden (local invasion of bone or lymphatics) radiation to the prostate plus standard of care was associated with a 32% improvement in overall survival compared with standard therapy alone, said Chris Parker, MD, from the Royal Marsden NHS Foundation Trust.
“Prostate radiotherapy is a simple treatment, it’s very well tolerated, and it’s widely available in any cancer center throughout the world,” Dr. Parker said in a briefing prior to his presentation in a presidential symposium at the European Society for Medical Oncology Congress.
The study was published online in the Lancet Oncology to coincide with the presentation.
Men who first present with metastatic prostate cancer account for about 10% of prostate cancer patients in the Western world, but may comprise as much as 60% of the prostate cancer population in some parts of Asia, noted briefing moderator and discussant Ignacio Duran, MD, from the Hospital Universitario Marques de Valdecilla, in Santander, Spain.
Prior to STAMPEDE, “we had never considered treating the local tumor in the context of wider-spread disease, and this is what the group of STAMPEDE really answered today with this study,” he said. “I think there is a substantial group of prostate cancer patients who might benefit from that. This opens the door to apply a new treatment that may have an impact in the life of these patients.”
The overarching goal of the STAMPEDE (Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy) study is to assess novel approaches for men with hormone-naive prostate cancer.
For this aspect of the randomized, phase 3 trial, 2,061 men with newly diagnosed M1 prostate cancer were enrolled and randomly assigned to either androgen deprivation with or without docetaxel or to the same standard of care plus radiotherapy. Radiation was delivered in one of two schedules: 55 Gy delivered in 20 fractions over 4 weeks or 36 Gy in 6 fractions delivered over 6 weeks, started within 8 weeks of randomization or the start of docetaxel.
As noted before, death from any cause, the primary endpoint, was not significantly different between the study arms. But in a subgroup analysis by metastatic burden, the rate of 3-year overall survival in patients with low burden was 81% in the radiotherapy group, compared with 73% in the standard-of-care arm. The hazard ratio was 0.68 (P = .007) favoring radiation.
In contrast, the 3-year overall survival rate in the high metastatic burden arm (patients with four or more metastases to bone with at least one outside the axial skeleton and/or visceral metastases) was 53% with radiation, versus 54% without.
In all, 5% of patients in the radiotherapy arm had grade 3 or 4 adverse events during therapy, and 4% had postradiation adverse events.
Radiation was associated with small increases in the risk for bladder and bowel events, but these were generally “modest” in nature and were outweighed by the survival benefit, Dr. Parker said.
He noted that men with regional nodal invasion but not metastases were not included in the trial. “However, if prostate radiotherapy improves survival for men with distant metastases, we can be very confident that it would improve survival for men with regional nodal disease. There aren’t any trials addressing that question, and currently many of these men receive drug treatment alone. So going forward, prostate radiotherapy should be the standard treatment for these men as well.”
The concept of primary tumor irradiation may work for patients with other malignancies who have low burden (oligometastatic) disease, he added.
“Based on the findings of STAMPEDE, radiotherapy could be considered for patients with newly diagnosed oligometastatic prostate cancer, but further studies are needed to delineate the clinical implementation of such treatment,” commented R. Jeffrey Karnes, MD, from the Mayo Clinic in Rochester, Minnesota, and his colleagues, in an editorial accompanying the article in the Lancet Oncology.
The study is sponsored by the Medical Research Council of the United Kingdom. Dr. Parker disclosed research funding and personal fees from Bayer and personal fees from Advanced Accelerator Applications and Janssen Pharmaceuticals. Dr. Duran disclosed participation in compensated advisory boards for Roche and Bristol-Myers Squibb and speaker honoraria from Roche, Bristol-Myers Squibb, and Merck.
SOURCE: Parker C et al. ESMO 2018, Abstract LBA5_PR.
MUNICH – Radiotherapy of the primary tumor can improve overall survival in men with untreated metastatic adenocarcinoma of the prostate, a finding that suggests a possible life-extending role of radiotherapy in other metastatic tumor types, investigators in the STAMPEDE trial reported.
Among 2,061 men from the United Kingdom and Switzerland with previously untreated metastatic prostate cancer, there was no survival advantage to adding local radiation to standard drug therapy in the overall study population. But among men with low disease burden (local invasion of bone or lymphatics) radiation to the prostate plus standard of care was associated with a 32% improvement in overall survival compared with standard therapy alone, said Chris Parker, MD, from the Royal Marsden NHS Foundation Trust.
“Prostate radiotherapy is a simple treatment, it’s very well tolerated, and it’s widely available in any cancer center throughout the world,” Dr. Parker said in a briefing prior to his presentation in a presidential symposium at the European Society for Medical Oncology Congress.
The study was published online in the Lancet Oncology to coincide with the presentation.
Men who first present with metastatic prostate cancer account for about 10% of prostate cancer patients in the Western world, but may comprise as much as 60% of the prostate cancer population in some parts of Asia, noted briefing moderator and discussant Ignacio Duran, MD, from the Hospital Universitario Marques de Valdecilla, in Santander, Spain.
Prior to STAMPEDE, “we had never considered treating the local tumor in the context of wider-spread disease, and this is what the group of STAMPEDE really answered today with this study,” he said. “I think there is a substantial group of prostate cancer patients who might benefit from that. This opens the door to apply a new treatment that may have an impact in the life of these patients.”
The overarching goal of the STAMPEDE (Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy) study is to assess novel approaches for men with hormone-naive prostate cancer.
For this aspect of the randomized, phase 3 trial, 2,061 men with newly diagnosed M1 prostate cancer were enrolled and randomly assigned to either androgen deprivation with or without docetaxel or to the same standard of care plus radiotherapy. Radiation was delivered in one of two schedules: 55 Gy delivered in 20 fractions over 4 weeks or 36 Gy in 6 fractions delivered over 6 weeks, started within 8 weeks of randomization or the start of docetaxel.
As noted before, death from any cause, the primary endpoint, was not significantly different between the study arms. But in a subgroup analysis by metastatic burden, the rate of 3-year overall survival in patients with low burden was 81% in the radiotherapy group, compared with 73% in the standard-of-care arm. The hazard ratio was 0.68 (P = .007) favoring radiation.
In contrast, the 3-year overall survival rate in the high metastatic burden arm (patients with four or more metastases to bone with at least one outside the axial skeleton and/or visceral metastases) was 53% with radiation, versus 54% without.
In all, 5% of patients in the radiotherapy arm had grade 3 or 4 adverse events during therapy, and 4% had postradiation adverse events.
Radiation was associated with small increases in the risk for bladder and bowel events, but these were generally “modest” in nature and were outweighed by the survival benefit, Dr. Parker said.
He noted that men with regional nodal invasion but not metastases were not included in the trial. “However, if prostate radiotherapy improves survival for men with distant metastases, we can be very confident that it would improve survival for men with regional nodal disease. There aren’t any trials addressing that question, and currently many of these men receive drug treatment alone. So going forward, prostate radiotherapy should be the standard treatment for these men as well.”
The concept of primary tumor irradiation may work for patients with other malignancies who have low burden (oligometastatic) disease, he added.
“Based on the findings of STAMPEDE, radiotherapy could be considered for patients with newly diagnosed oligometastatic prostate cancer, but further studies are needed to delineate the clinical implementation of such treatment,” commented R. Jeffrey Karnes, MD, from the Mayo Clinic in Rochester, Minnesota, and his colleagues, in an editorial accompanying the article in the Lancet Oncology.
The study is sponsored by the Medical Research Council of the United Kingdom. Dr. Parker disclosed research funding and personal fees from Bayer and personal fees from Advanced Accelerator Applications and Janssen Pharmaceuticals. Dr. Duran disclosed participation in compensated advisory boards for Roche and Bristol-Myers Squibb and speaker honoraria from Roche, Bristol-Myers Squibb, and Merck.
SOURCE: Parker C et al. ESMO 2018, Abstract LBA5_PR.
MUNICH – Radiotherapy of the primary tumor can improve overall survival in men with untreated metastatic adenocarcinoma of the prostate, a finding that suggests a possible life-extending role of radiotherapy in other metastatic tumor types, investigators in the STAMPEDE trial reported.
Among 2,061 men from the United Kingdom and Switzerland with previously untreated metastatic prostate cancer, there was no survival advantage to adding local radiation to standard drug therapy in the overall study population. But among men with low disease burden (local invasion of bone or lymphatics) radiation to the prostate plus standard of care was associated with a 32% improvement in overall survival compared with standard therapy alone, said Chris Parker, MD, from the Royal Marsden NHS Foundation Trust.
“Prostate radiotherapy is a simple treatment, it’s very well tolerated, and it’s widely available in any cancer center throughout the world,” Dr. Parker said in a briefing prior to his presentation in a presidential symposium at the European Society for Medical Oncology Congress.
The study was published online in the Lancet Oncology to coincide with the presentation.
Men who first present with metastatic prostate cancer account for about 10% of prostate cancer patients in the Western world, but may comprise as much as 60% of the prostate cancer population in some parts of Asia, noted briefing moderator and discussant Ignacio Duran, MD, from the Hospital Universitario Marques de Valdecilla, in Santander, Spain.
Prior to STAMPEDE, “we had never considered treating the local tumor in the context of wider-spread disease, and this is what the group of STAMPEDE really answered today with this study,” he said. “I think there is a substantial group of prostate cancer patients who might benefit from that. This opens the door to apply a new treatment that may have an impact in the life of these patients.”
The overarching goal of the STAMPEDE (Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy) study is to assess novel approaches for men with hormone-naive prostate cancer.
For this aspect of the randomized, phase 3 trial, 2,061 men with newly diagnosed M1 prostate cancer were enrolled and randomly assigned to either androgen deprivation with or without docetaxel or to the same standard of care plus radiotherapy. Radiation was delivered in one of two schedules: 55 Gy delivered in 20 fractions over 4 weeks or 36 Gy in 6 fractions delivered over 6 weeks, started within 8 weeks of randomization or the start of docetaxel.
As noted before, death from any cause, the primary endpoint, was not significantly different between the study arms. But in a subgroup analysis by metastatic burden, the rate of 3-year overall survival in patients with low burden was 81% in the radiotherapy group, compared with 73% in the standard-of-care arm. The hazard ratio was 0.68 (P = .007) favoring radiation.
In contrast, the 3-year overall survival rate in the high metastatic burden arm (patients with four or more metastases to bone with at least one outside the axial skeleton and/or visceral metastases) was 53% with radiation, versus 54% without.
In all, 5% of patients in the radiotherapy arm had grade 3 or 4 adverse events during therapy, and 4% had postradiation adverse events.
Radiation was associated with small increases in the risk for bladder and bowel events, but these were generally “modest” in nature and were outweighed by the survival benefit, Dr. Parker said.
He noted that men with regional nodal invasion but not metastases were not included in the trial. “However, if prostate radiotherapy improves survival for men with distant metastases, we can be very confident that it would improve survival for men with regional nodal disease. There aren’t any trials addressing that question, and currently many of these men receive drug treatment alone. So going forward, prostate radiotherapy should be the standard treatment for these men as well.”
The concept of primary tumor irradiation may work for patients with other malignancies who have low burden (oligometastatic) disease, he added.
“Based on the findings of STAMPEDE, radiotherapy could be considered for patients with newly diagnosed oligometastatic prostate cancer, but further studies are needed to delineate the clinical implementation of such treatment,” commented R. Jeffrey Karnes, MD, from the Mayo Clinic in Rochester, Minnesota, and his colleagues, in an editorial accompanying the article in the Lancet Oncology.
The study is sponsored by the Medical Research Council of the United Kingdom. Dr. Parker disclosed research funding and personal fees from Bayer and personal fees from Advanced Accelerator Applications and Janssen Pharmaceuticals. Dr. Duran disclosed participation in compensated advisory boards for Roche and Bristol-Myers Squibb and speaker honoraria from Roche, Bristol-Myers Squibb, and Merck.
SOURCE: Parker C et al. ESMO 2018, Abstract LBA5_PR.
REPORTING FROM ESMO 2018
Key clinical point: Local radiation can improve survival of low-burden metastatic prostate cancer.
Major finding: In men with low-burden metastatic disease, the 3-year overall survival rate was 81% with radiation versus 73% without.
Study details: A prospective study of 2,061 men in a randomized, phase 3 trial exploring new therapeutic options for prostate cancer.
Disclosures: The study is sponsored by the Medical Research Council of the United Kingdom. Dr. Parker disclosed research funding and personal fees from Bayer and personal fees from Advanced Accelerator Applications and Janssen Pharmaceuticals. Dr. Duran disclosed participation in compensated advisory boards for Roche and Bristol-Myers Squibb and speaker honoraria from Roche, Bristol-Myers Squibb, and Merck.
Source: Parker C et al. ESMO 2018, Abstract LBA5_PR.
Readmission to non-index hospital following acute stroke linked to worse outcomes
ATLANTA – Following an acute stroke, optimizing stroke secondary prevention measures, medical complications, and transitions of care is essential to reducing 30-day readmissions and improving patient outcomes, a large analysis of national data showed.
“Care that is fragmented with readmissions to other hospitals results not only in more expensive care and longer length of stay but also increased mortality for our acute stroke patients,” lead study author Laura K. Stein, MD, said in an interview in advance of the annual meeting of the American Neurological Association.
In 2017, a study of the Nationwide Readmissions Database demonstrated that 12.1% of patients with acute ischemic stroke were readmitted within 30 days (Stroke 2017;48:1386-8). It cited that 89.6% were unplanned and 12.9% were preventable. “However, this study did not examine whether patients were admitted to the discharging hospital or a different hospital,” said Dr. Stein, a neurologist at the Icahn School of Medicine at Mount Sinai, New York. “Furthermore, it did not include metrics such as cost, length of stay, and mortality with 30-day readmissions. Hospitals are increasingly held accountable and penalized for metrics such as length of stay and 30-day readmissions.”
In 2010, the Centers for Medicare & Medicaid Services introduced the Hospital Readmissions Reduction Program in an attempt to decrease readmissions following hospitalizations for acute myocardial infarction, heart failure, and pneumonia. “In 2012, CMS started reducing Medicare payments for hospitals with excess readmissions,” said Dr. Stein, who is a fellowship-trained stroke specialist. “While readmission to the same hospital has great implications for hospital systems, any readmission has great implications for patients.”
In what is believed to be the first study of its kind, Dr. Stein and her colleagues drew from the 2013 Nationwide Readmissions Database to examine in-hospital outcomes associated with 30-day readmission to a different hospital for acute ischemic stroke. They used ICD-9 codes to identify index stroke admissions and all-cause readmissions. Outcomes of interest were length of stay, total charges, and in-hospital mortality during the 30-day readmission. The main predictor was readmission to another hospital, compared with readmission to the same hospital as the index acute stroke admission. The researchers used linear regression for the outcomes of length of stay and charges, and logistic regression for in-hospital mortality. They adjusted for several variables during the index admission, including age, sex, vascular risk factors, hospital bed size, teaching hospital status, insurance status, discharge destination, National Center for Health Statistics urban-rural location classification, length of stay, and total charges.
Of 24,545 acute stroke patients readmitted within 30 days, 7,274 (30%) were readmitted to a different hospital. The top three reasons for readmission were acute cerebrovascular disease, septicemia, and renal failure. In fully adjusted models, readmission to a different hospital was associated with an increased length of stay of 0.97 days (P less than .0001) and a mean of $7,677.28 greater total charges, compared with readmission to the same hospital (P less than .0001). The fully adjusted odds ratio for in-hospital mortality during readmission was 1.17 for readmission to another hospital vs. readmission to the same hospital (P = .0079).
“While it is conceivable that cost and length of stay could be higher with readmission to a different hospital because of a need for additional testing with a lack of familiarity with the patient, it is concerning that mortality is higher,” Dr. Stein said. “These findings emphasize the importance of optimizing secondary stroke prevention and medical complications following acute stroke before discharge. Additionally, they emphasize the importance of good transitions of care from the inpatient to outpatient setting (whether that’s to a rehabilitation facility, skilled nursing facility, or home) and accessibility of the discharging stroke team after discharge.”
She acknowledged certain limitations of the analysis, including its reliance of administrative data, which could include misclassification of diagnoses and comorbidities based on ICD-9 codes. “However, we have chosen ICD-9 codes for stroke that have been previously validated in the literature,” Dr. Stein said. “For instance, the validated codes for stroke as the primary discharge diagnosis have a sensitivity of 74%, specificity of 95%, and positive predictive value of 88%. Second, we do not know stroke subtype or severity of stroke. Third, we do not know what the transitions of care plan were when the patients left the hospital following index acute ischemic stroke admission and why these patients ended up being readmitted to a different hospital rather than the one that treated them for their acute stroke.”
The researchers reported having no financial disclosures.
SOURCE: Stein L et al. Ann Neurol. 2018;84[S22]:S149. Abstract M127.
ATLANTA – Following an acute stroke, optimizing stroke secondary prevention measures, medical complications, and transitions of care is essential to reducing 30-day readmissions and improving patient outcomes, a large analysis of national data showed.
“Care that is fragmented with readmissions to other hospitals results not only in more expensive care and longer length of stay but also increased mortality for our acute stroke patients,” lead study author Laura K. Stein, MD, said in an interview in advance of the annual meeting of the American Neurological Association.
In 2017, a study of the Nationwide Readmissions Database demonstrated that 12.1% of patients with acute ischemic stroke were readmitted within 30 days (Stroke 2017;48:1386-8). It cited that 89.6% were unplanned and 12.9% were preventable. “However, this study did not examine whether patients were admitted to the discharging hospital or a different hospital,” said Dr. Stein, a neurologist at the Icahn School of Medicine at Mount Sinai, New York. “Furthermore, it did not include metrics such as cost, length of stay, and mortality with 30-day readmissions. Hospitals are increasingly held accountable and penalized for metrics such as length of stay and 30-day readmissions.”
In 2010, the Centers for Medicare & Medicaid Services introduced the Hospital Readmissions Reduction Program in an attempt to decrease readmissions following hospitalizations for acute myocardial infarction, heart failure, and pneumonia. “In 2012, CMS started reducing Medicare payments for hospitals with excess readmissions,” said Dr. Stein, who is a fellowship-trained stroke specialist. “While readmission to the same hospital has great implications for hospital systems, any readmission has great implications for patients.”
In what is believed to be the first study of its kind, Dr. Stein and her colleagues drew from the 2013 Nationwide Readmissions Database to examine in-hospital outcomes associated with 30-day readmission to a different hospital for acute ischemic stroke. They used ICD-9 codes to identify index stroke admissions and all-cause readmissions. Outcomes of interest were length of stay, total charges, and in-hospital mortality during the 30-day readmission. The main predictor was readmission to another hospital, compared with readmission to the same hospital as the index acute stroke admission. The researchers used linear regression for the outcomes of length of stay and charges, and logistic regression for in-hospital mortality. They adjusted for several variables during the index admission, including age, sex, vascular risk factors, hospital bed size, teaching hospital status, insurance status, discharge destination, National Center for Health Statistics urban-rural location classification, length of stay, and total charges.
Of 24,545 acute stroke patients readmitted within 30 days, 7,274 (30%) were readmitted to a different hospital. The top three reasons for readmission were acute cerebrovascular disease, septicemia, and renal failure. In fully adjusted models, readmission to a different hospital was associated with an increased length of stay of 0.97 days (P less than .0001) and a mean of $7,677.28 greater total charges, compared with readmission to the same hospital (P less than .0001). The fully adjusted odds ratio for in-hospital mortality during readmission was 1.17 for readmission to another hospital vs. readmission to the same hospital (P = .0079).
“While it is conceivable that cost and length of stay could be higher with readmission to a different hospital because of a need for additional testing with a lack of familiarity with the patient, it is concerning that mortality is higher,” Dr. Stein said. “These findings emphasize the importance of optimizing secondary stroke prevention and medical complications following acute stroke before discharge. Additionally, they emphasize the importance of good transitions of care from the inpatient to outpatient setting (whether that’s to a rehabilitation facility, skilled nursing facility, or home) and accessibility of the discharging stroke team after discharge.”
She acknowledged certain limitations of the analysis, including its reliance of administrative data, which could include misclassification of diagnoses and comorbidities based on ICD-9 codes. “However, we have chosen ICD-9 codes for stroke that have been previously validated in the literature,” Dr. Stein said. “For instance, the validated codes for stroke as the primary discharge diagnosis have a sensitivity of 74%, specificity of 95%, and positive predictive value of 88%. Second, we do not know stroke subtype or severity of stroke. Third, we do not know what the transitions of care plan were when the patients left the hospital following index acute ischemic stroke admission and why these patients ended up being readmitted to a different hospital rather than the one that treated them for their acute stroke.”
The researchers reported having no financial disclosures.
SOURCE: Stein L et al. Ann Neurol. 2018;84[S22]:S149. Abstract M127.
ATLANTA – Following an acute stroke, optimizing stroke secondary prevention measures, medical complications, and transitions of care is essential to reducing 30-day readmissions and improving patient outcomes, a large analysis of national data showed.
“Care that is fragmented with readmissions to other hospitals results not only in more expensive care and longer length of stay but also increased mortality for our acute stroke patients,” lead study author Laura K. Stein, MD, said in an interview in advance of the annual meeting of the American Neurological Association.
In 2017, a study of the Nationwide Readmissions Database demonstrated that 12.1% of patients with acute ischemic stroke were readmitted within 30 days (Stroke 2017;48:1386-8). It cited that 89.6% were unplanned and 12.9% were preventable. “However, this study did not examine whether patients were admitted to the discharging hospital or a different hospital,” said Dr. Stein, a neurologist at the Icahn School of Medicine at Mount Sinai, New York. “Furthermore, it did not include metrics such as cost, length of stay, and mortality with 30-day readmissions. Hospitals are increasingly held accountable and penalized for metrics such as length of stay and 30-day readmissions.”
In 2010, the Centers for Medicare & Medicaid Services introduced the Hospital Readmissions Reduction Program in an attempt to decrease readmissions following hospitalizations for acute myocardial infarction, heart failure, and pneumonia. “In 2012, CMS started reducing Medicare payments for hospitals with excess readmissions,” said Dr. Stein, who is a fellowship-trained stroke specialist. “While readmission to the same hospital has great implications for hospital systems, any readmission has great implications for patients.”
In what is believed to be the first study of its kind, Dr. Stein and her colleagues drew from the 2013 Nationwide Readmissions Database to examine in-hospital outcomes associated with 30-day readmission to a different hospital for acute ischemic stroke. They used ICD-9 codes to identify index stroke admissions and all-cause readmissions. Outcomes of interest were length of stay, total charges, and in-hospital mortality during the 30-day readmission. The main predictor was readmission to another hospital, compared with readmission to the same hospital as the index acute stroke admission. The researchers used linear regression for the outcomes of length of stay and charges, and logistic regression for in-hospital mortality. They adjusted for several variables during the index admission, including age, sex, vascular risk factors, hospital bed size, teaching hospital status, insurance status, discharge destination, National Center for Health Statistics urban-rural location classification, length of stay, and total charges.
Of 24,545 acute stroke patients readmitted within 30 days, 7,274 (30%) were readmitted to a different hospital. The top three reasons for readmission were acute cerebrovascular disease, septicemia, and renal failure. In fully adjusted models, readmission to a different hospital was associated with an increased length of stay of 0.97 days (P less than .0001) and a mean of $7,677.28 greater total charges, compared with readmission to the same hospital (P less than .0001). The fully adjusted odds ratio for in-hospital mortality during readmission was 1.17 for readmission to another hospital vs. readmission to the same hospital (P = .0079).
“While it is conceivable that cost and length of stay could be higher with readmission to a different hospital because of a need for additional testing with a lack of familiarity with the patient, it is concerning that mortality is higher,” Dr. Stein said. “These findings emphasize the importance of optimizing secondary stroke prevention and medical complications following acute stroke before discharge. Additionally, they emphasize the importance of good transitions of care from the inpatient to outpatient setting (whether that’s to a rehabilitation facility, skilled nursing facility, or home) and accessibility of the discharging stroke team after discharge.”
She acknowledged certain limitations of the analysis, including its reliance of administrative data, which could include misclassification of diagnoses and comorbidities based on ICD-9 codes. “However, we have chosen ICD-9 codes for stroke that have been previously validated in the literature,” Dr. Stein said. “For instance, the validated codes for stroke as the primary discharge diagnosis have a sensitivity of 74%, specificity of 95%, and positive predictive value of 88%. Second, we do not know stroke subtype or severity of stroke. Third, we do not know what the transitions of care plan were when the patients left the hospital following index acute ischemic stroke admission and why these patients ended up being readmitted to a different hospital rather than the one that treated them for their acute stroke.”
The researchers reported having no financial disclosures.
SOURCE: Stein L et al. Ann Neurol. 2018;84[S22]:S149. Abstract M127.
REPORTING FROM ANA 2018
Key clinical point:
Major finding: The adjusted odds ratio for in-hospital mortality during readmission was 1.17 for readmission to another hospital vs. readmission to the same hospital (P = .0079).
Study details: A review of 24,545 acute stroke patients 2013 from the Nationwide Readmissions Database.
Disclosures: The researchers reported having no financial disclosures.
Source: Stein L et al. Ann Neurol. 2018;84[S22]:S149. Abstract M127.