Sharon Worcester

Nearly one-quarter of Medicare patients hospitalized for heart failure are subsequently discharged to a skilled nursing facility, and those patients are significantly more likely to be rehospitalized or die within 1 year than are similar patients discharged to home, according to the findings of a large observational study of more than 15,400 patients from 149 hospitals.

Absolute rehospitalization rates in those discharged to a skilled nursing facility vs. home were 27% vs. 23.5%, respectively, at 30 days, and 76.1% vs. 72.2%, respectively, at 1 year. All-cause mortality rates were 14.4% vs. 4.1% at 30 days and 53.5% vs. 29.1% at 1 year, Dr. Larry A. Allen and his colleagues reported online March 29 in Circulation: Heart Failure.

After adjustment for numerous demographic and health-related factors, discharge to a skilled nursing facility in these patients remained significantly associated with an increased risk of death (hazard ratio 1.76), said Dr. Allen of the Colorado Cardiovascular Outcomes Research Consortium, University of Colorado Denver, Aurora, Colo. (Circulation: Heart Failure 2011 March 29 [doi:10.1161/CIRCHEARTFAILURE.110.959171]).

Patients included in the analysis were 15,459 adults aged 65 years or older (median age 80 years) who were discharged to a skilled nursing facility (24.1%), to home with home health service (22.3%), or to home with self-care (53.6%). The patients had been hospitalized for heart failure for at least 3 days (median 5 days) during 2005-2006.

The patients were part of the Get With The Guidelines – Heart Failure Program registry, an ongoing, voluntary quality-improvement initiative of the American Heart Association, the investigators said.

Factors found to be significantly associated with discharge to a skilled nursing facility included longer hospital stay (odds ratio 1.12 per day); advanced age (OR 1.98 per 10-year increase); female sex (OR 1.53); systolic blood pressure (OR 0.94 per 10 mm Hg increase); left ventricular ejection fraction less than 40% (OR 0.91); sodium level (OR 1.05 per 10 mEq/L increase); and history of hyperlipidemia (OR 0.74), anemia (OR 1.31), diabetes (OR 1.19), valvular heart disease (OR 0.72), myocardial infarction (OR 0.86), bypass surgery or percutaneous coronary intervention (OR 0.80), implantable defibrillator (OR 0.76), depression (OR 2.11), stroke (OR 1.55), peripheral vascular disease (OR 1.13), or chronic obstructive pulmonary disease or asthma (OR 1.11).

Across the country, the rate of discharges to skilled nursing facilities was highest in the Northeast (30%) and lowest in the West (23.6%). Hospitals that treated more racial minorities and younger patients were among those with the lowest rates of discharge to skilled nursing facilities.

In this study, hospitalized heart failure patients who were discharged to a skilled nursing facility were 79% more likely to die than those discharged to home – even after adjusting for a wide range of patient factors known to be associated with adverse outcomes, the investigators said.

"However, discharge to [a skilled nursing facility] is by its very nature determined by criteria such as poor mobility, cognitive impairment, frailty, and poor in-home support, which are also important determinants of outcome," they wrote, noting that those determinants of outcome were not captured in this analysis. Therefore, the researchers said, conclusions about whether discharge to a skilled nursing facility directly impacts patient outcomes cannot be drawn.

Still, the findings have potential implications for communicating prognoses to patients and families, medical decision-making, and assessing care provided at skilled nursing facilities, they said.

The high absolute rates of death following discharge to skilled nursing facilities, in particular, have potential implications for communication, discharge planning, and goals of care, they said.

"Additionally, we must consider whether a different set of quality measures [is] needed for this unique group of patients," the investigators concluded.

This study was funded by the American Heart Association, GlaxoSmithKline, and Medtronic through their support of the Get With The Guidelines – Heart Failure Program, and the Agency for Healthcare Research and Quality. Dr. Allen had no conflicts of interest to disclose. Other authors on the study reported numerous relationships with various pharmaceutical companies and other organizations.

Nearly one-quarter of Medicare patients hospitalized for heart failure are subsequently discharged to a skilled nursing facility, and those patients are significantly more likely to be rehospitalized or die within 1 year than are similar patients discharged to home, according to the findings of a large observational study of more than 15,400 patients from 149 hospitals.

Absolute rehospitalization rates in those discharged to a skilled nursing facility vs. home were 27% vs. 23.5%, respectively, at 30 days, and 76.1% vs. 72.2%, respectively, at 1 year. All-cause mortality rates were 14.4% vs. 4.1% at 30 days and 53.5% vs. 29.1% at 1 year, Dr. Larry A. Allen and his colleagues reported online March 29 in Circulation: Heart Failure.

After adjustment for numerous demographic and health-related factors, discharge to a skilled nursing facility in these patients remained significantly associated with an increased risk of death (hazard ratio 1.76), said Dr. Allen of the Colorado Cardiovascular Outcomes Research Consortium, University of Colorado Denver, Aurora, Colo. (Circulation: Heart Failure 2011 March 29 [doi:10.1161/CIRCHEARTFAILURE.110.959171]).

Patients included in the analysis were 15,459 adults aged 65 years or older (median age 80 years) who were discharged to a skilled nursing facility (24.1%), to home with home health service (22.3%), or to home with self-care (53.6%). The patients had been hospitalized for heart failure for at least 3 days (median 5 days) during 2005-2006.

The patients were part of the Get With The Guidelines – Heart Failure Program registry, an ongoing, voluntary quality-improvement initiative of the American Heart Association, the investigators said.

Factors found to be significantly associated with discharge to a skilled nursing facility included longer hospital stay (odds ratio 1.12 per day); advanced age (OR 1.98 per 10-year increase); female sex (OR 1.53); systolic blood pressure (OR 0.94 per 10 mm Hg increase); left ventricular ejection fraction less than 40% (OR 0.91); sodium level (OR 1.05 per 10 mEq/L increase); and history of hyperlipidemia (OR 0.74), anemia (OR 1.31), diabetes (OR 1.19), valvular heart disease (OR 0.72), myocardial infarction (OR 0.86), bypass surgery or percutaneous coronary intervention (OR 0.80), implantable defibrillator (OR 0.76), depression (OR 2.11), stroke (OR 1.55), peripheral vascular disease (OR 1.13), or chronic obstructive pulmonary disease or asthma (OR 1.11).

Across the country, the rate of discharges to skilled nursing facilities was highest in the Northeast (30%) and lowest in the West (23.6%). Hospitals that treated more racial minorities and younger patients were among those with the lowest rates of discharge to skilled nursing facilities.

In this study, hospitalized heart failure patients who were discharged to a skilled nursing facility were 79% more likely to die than those discharged to home – even after adjusting for a wide range of patient factors known to be associated with adverse outcomes, the investigators said.

"However, discharge to [a skilled nursing facility] is by its very nature determined by criteria such as poor mobility, cognitive impairment, frailty, and poor in-home support, which are also important determinants of outcome," they wrote, noting that those determinants of outcome were not captured in this analysis. Therefore, the researchers said, conclusions about whether discharge to a skilled nursing facility directly impacts patient outcomes cannot be drawn.

Still, the findings have potential implications for communicating prognoses to patients and families, medical decision-making, and assessing care provided at skilled nursing facilities, they said.

The high absolute rates of death following discharge to skilled nursing facilities, in particular, have potential implications for communication, discharge planning, and goals of care, they said.

"Additionally, we must consider whether a different set of quality measures [is] needed for this unique group of patients," the investigators concluded.

This study was funded by the American Heart Association, GlaxoSmithKline, and Medtronic through their support of the Get With The Guidelines – Heart Failure Program, and the Agency for Healthcare Research and Quality. Dr. Allen had no conflicts of interest to disclose. Other authors on the study reported numerous relationships with various pharmaceutical companies and other organizations.

Nearly one-quarter of Medicare patients hospitalized for heart failure are subsequently discharged to a skilled nursing facility, and those patients are significantly more likely to be rehospitalized or die within 1 year than are similar patients discharged to home, according to the findings of a large observational study of more than 15,400 patients from 149 hospitals.

Absolute rehospitalization rates in those discharged to a skilled nursing facility vs. home were 27% vs. 23.5%, respectively, at 30 days, and 76.1% vs. 72.2%, respectively, at 1 year. All-cause mortality rates were 14.4% vs. 4.1% at 30 days and 53.5% vs. 29.1% at 1 year, Dr. Larry A. Allen and his colleagues reported online March 29 in Circulation: Heart Failure.

After adjustment for numerous demographic and health-related factors, discharge to a skilled nursing facility in these patients remained significantly associated with an increased risk of death (hazard ratio 1.76), said Dr. Allen of the Colorado Cardiovascular Outcomes Research Consortium, University of Colorado Denver, Aurora, Colo. (Circulation: Heart Failure 2011 March 29 [doi:10.1161/CIRCHEARTFAILURE.110.959171]).

Patients included in the analysis were 15,459 adults aged 65 years or older (median age 80 years) who were discharged to a skilled nursing facility (24.1%), to home with home health service (22.3%), or to home with self-care (53.6%). The patients had been hospitalized for heart failure for at least 3 days (median 5 days) during 2005-2006.

The patients were part of the Get With The Guidelines – Heart Failure Program registry, an ongoing, voluntary quality-improvement initiative of the American Heart Association, the investigators said.

Factors found to be significantly associated with discharge to a skilled nursing facility included longer hospital stay (odds ratio 1.12 per day); advanced age (OR 1.98 per 10-year increase); female sex (OR 1.53); systolic blood pressure (OR 0.94 per 10 mm Hg increase); left ventricular ejection fraction less than 40% (OR 0.91); sodium level (OR 1.05 per 10 mEq/L increase); and history of hyperlipidemia (OR 0.74), anemia (OR 1.31), diabetes (OR 1.19), valvular heart disease (OR 0.72), myocardial infarction (OR 0.86), bypass surgery or percutaneous coronary intervention (OR 0.80), implantable defibrillator (OR 0.76), depression (OR 2.11), stroke (OR 1.55), peripheral vascular disease (OR 1.13), or chronic obstructive pulmonary disease or asthma (OR 1.11).

Across the country, the rate of discharges to skilled nursing facilities was highest in the Northeast (30%) and lowest in the West (23.6%). Hospitals that treated more racial minorities and younger patients were among those with the lowest rates of discharge to skilled nursing facilities.

In this study, hospitalized heart failure patients who were discharged to a skilled nursing facility were 79% more likely to die than those discharged to home – even after adjusting for a wide range of patient factors known to be associated with adverse outcomes, the investigators said.

"However, discharge to [a skilled nursing facility] is by its very nature determined by criteria such as poor mobility, cognitive impairment, frailty, and poor in-home support, which are also important determinants of outcome," they wrote, noting that those determinants of outcome were not captured in this analysis. Therefore, the researchers said, conclusions about whether discharge to a skilled nursing facility directly impacts patient outcomes cannot be drawn.

Still, the findings have potential implications for communicating prognoses to patients and families, medical decision-making, and assessing care provided at skilled nursing facilities, they said.

The high absolute rates of death following discharge to skilled nursing facilities, in particular, have potential implications for communication, discharge planning, and goals of care, they said.

"Additionally, we must consider whether a different set of quality measures [is] needed for this unique group of patients," the investigators concluded.

This study was funded by the American Heart Association, GlaxoSmithKline, and Medtronic through their support of the Get With The Guidelines – Heart Failure Program, and the Agency for Healthcare Research and Quality. Dr. Allen had no conflicts of interest to disclose. Other authors on the study reported numerous relationships with various pharmaceutical companies and other organizations.

Nearly one-quarter of Medicare patients hospitalized for heart failure are subsequently discharged to a skilled nursing facility, and those patients are significantly more likely to be rehospitalized or die within 1 year than are similar patients discharged to home, according to the findings of a large observational study of more than 15,400 patients from 149 hospitals.

Absolute rehospitalization rates in those discharged to a skilled nursing facility vs. home were 27% vs. 23.5%, respectively, at 30 days, and 76.1% vs. 72.2%, respectively, at 1 year. All-cause mortality rates were 14.4% vs. 4.1% at 30 days and 53.5% vs. 29.1% at 1 year, Dr. Larry A. Allen and his colleagues reported online March 29 in Circulation: Heart Failure.

After adjustment for numerous demographic and health-related factors, discharge to a skilled nursing facility in these patients remained significantly associated with an increased risk of death (hazard ratio 1.76), said Dr. Allen of the Colorado Cardiovascular Outcomes Research Consortium, University of Colorado Denver, Aurora, Colo. (Circulation: Heart Failure 2011 March 29 [doi:10.1161/CIRCHEARTFAILURE.110.959171]).

Patients included in the analysis were 15,459 adults aged 65 years or older (median age 80 years) who were discharged to a skilled nursing facility (24.1%), to home with home health service (22.3%), or to home with self-care (53.6%). The patients had been hospitalized for heart failure for at least 3 days (median 5 days) during 2005-2006.

The patients were part of the Get With The Guidelines – Heart Failure Program registry, an ongoing, voluntary quality-improvement initiative of the American Heart Association, the investigators said.

Factors found to be significantly associated with discharge to a skilled nursing facility included longer hospital stay (odds ratio 1.12 per day); advanced age (OR 1.98 per 10-year increase); female sex (OR 1.53); systolic blood pressure (OR 0.94 per 10 mm Hg increase); left ventricular ejection fraction less than 40% (OR 0.91); sodium level (OR 1.05 per 10 mEq/L increase); and history of hyperlipidemia (OR 0.74), anemia (OR 1.31), diabetes (OR 1.19), valvular heart disease (OR 0.72), myocardial infarction (OR 0.86), bypass surgery or percutaneous coronary intervention (OR 0.80), implantable defibrillator (OR 0.76), depression (OR 2.11), stroke (OR 1.55), peripheral vascular disease (OR 1.13), or chronic obstructive pulmonary disease or asthma (OR 1.11).

Across the country, the rate of discharges to skilled nursing facilities was highest in the Northeast (30%) and lowest in the West (23.6%). Hospitals that treated more racial minorities and younger patients were among those with the lowest rates of discharge to skilled nursing facilities.

In this study, hospitalized heart failure patients who were discharged to a skilled nursing facility were 79% more likely to die than those discharged to home – even after adjusting for a wide range of patient factors known to be associated with adverse outcomes, the investigators said.

"However, discharge to [a skilled nursing facility] is by its very nature determined by criteria such as poor mobility, cognitive impairment, frailty, and poor in-home support, which are also important determinants of outcome," they wrote, noting that those determinants of outcome were not captured in this analysis. Therefore, the researchers said, conclusions about whether discharge to a skilled nursing facility directly impacts patient outcomes cannot be drawn.

Still, the findings have potential implications for communicating prognoses to patients and families, medical decision-making, and assessing care provided at skilled nursing facilities, they said.

The high absolute rates of death following discharge to skilled nursing facilities, in particular, have potential implications for communication, discharge planning, and goals of care, they said.

"Additionally, we must consider whether a different set of quality measures [is] needed for this unique group of patients," the investigators concluded.

This study was funded by the American Heart Association, GlaxoSmithKline, and Medtronic through their support of the Get With The Guidelines – Heart Failure Program, and the Agency for Healthcare Research and Quality. Dr. Allen had no conflicts of interest to disclose. Other authors on the study reported numerous relationships with various pharmaceutical companies and other organizations.

Nearly one-quarter of Medicare patients hospitalized for heart failure are subsequently discharged to a skilled nursing facility, and those patients are significantly more likely to be rehospitalized or die within 1 year than are similar patients discharged to home, according to the findings of a large observational study of more than 15,400 patients from 149 hospitals.

Absolute rehospitalization rates in those discharged to a skilled nursing facility vs. home were 27% vs. 23.5%, respectively, at 30 days, and 76.1% vs. 72.2%, respectively, at 1 year. All-cause mortality rates were 14.4% vs. 4.1% at 30 days and 53.5% vs. 29.1% at 1 year, Dr. Larry A. Allen and his colleagues reported online March 29 in Circulation: Heart Failure.

After adjustment for numerous demographic and health-related factors, discharge to a skilled nursing facility in these patients remained significantly associated with an increased risk of death (hazard ratio 1.76), said Dr. Allen of the Colorado Cardiovascular Outcomes Research Consortium, University of Colorado Denver, Aurora, Colo. (Circulation: Heart Failure 2011 March 29 [doi:10.1161/CIRCHEARTFAILURE.110.959171]).

Patients included in the analysis were 15,459 adults aged 65 years or older (median age 80 years) who were discharged to a skilled nursing facility (24.1%), to home with home health service (22.3%), or to home with self-care (53.6%). The patients had been hospitalized for heart failure for at least 3 days (median 5 days) during 2005-2006.

The patients were part of the Get With The Guidelines – Heart Failure Program registry, an ongoing, voluntary quality-improvement initiative of the American Heart Association, the investigators said.

Factors found to be significantly associated with discharge to a skilled nursing facility included longer hospital stay (odds ratio 1.12 per day); advanced age (OR 1.98 per 10-year increase); female sex (OR 1.53); systolic blood pressure (OR 0.94 per 10 mm Hg increase); left ventricular ejection fraction less than 40% (OR 0.91); sodium level (OR 1.05 per 10 mEq/L increase); and history of hyperlipidemia (OR 0.74), anemia (OR 1.31), diabetes (OR 1.19), valvular heart disease (OR 0.72), myocardial infarction (OR 0.86), bypass surgery or percutaneous coronary intervention (OR 0.80), implantable defibrillator (OR 0.76), depression (OR 2.11), stroke (OR 1.55), peripheral vascular disease (OR 1.13), or chronic obstructive pulmonary disease or asthma (OR 1.11).

Across the country, the rate of discharges to skilled nursing facilities was highest in the Northeast (30%) and lowest in the West (23.6%). Hospitals that treated more racial minorities and younger patients were among those with the lowest rates of discharge to skilled nursing facilities.

In this study, hospitalized heart failure patients who were discharged to a skilled nursing facility were 79% more likely to die than those discharged to home – even after adjusting for a wide range of patient factors known to be associated with adverse outcomes, the investigators said.

"However, discharge to [a skilled nursing facility] is by its very nature determined by criteria such as poor mobility, cognitive impairment, frailty, and poor in-home support, which are also important determinants of outcome," they wrote, noting that those determinants of outcome were not captured in this analysis. Therefore, the researchers said, conclusions about whether discharge to a skilled nursing facility directly impacts patient outcomes cannot be drawn.

Still, the findings have potential implications for communicating prognoses to patients and families, medical decision-making, and assessing care provided at skilled nursing facilities, they said.

The high absolute rates of death following discharge to skilled nursing facilities, in particular, have potential implications for communication, discharge planning, and goals of care, they said.

"Additionally, we must consider whether a different set of quality measures [is] needed for this unique group of patients," the investigators concluded.

This study was funded by the American Heart Association, GlaxoSmithKline, and Medtronic through their support of the Get With The Guidelines – Heart Failure Program, and the Agency for Healthcare Research and Quality. Dr. Allen had no conflicts of interest to disclose. Other authors on the study reported numerous relationships with various pharmaceutical companies and other organizations.

Nearly one-quarter of Medicare patients hospitalized for heart failure are subsequently discharged to a skilled nursing facility, and those patients are significantly more likely to be rehospitalized or die within 1 year than are similar patients discharged to home, according to the findings of a large observational study of more than 15,400 patients from 149 hospitals.

Absolute rehospitalization rates in those discharged to a skilled nursing facility vs. home were 27% vs. 23.5%, respectively, at 30 days, and 76.1% vs. 72.2%, respectively, at 1 year. All-cause mortality rates were 14.4% vs. 4.1% at 30 days and 53.5% vs. 29.1% at 1 year, Dr. Larry A. Allen and his colleagues reported online March 29 in Circulation: Heart Failure.

After adjustment for numerous demographic and health-related factors, discharge to a skilled nursing facility in these patients remained significantly associated with an increased risk of death (hazard ratio 1.76), said Dr. Allen of the Colorado Cardiovascular Outcomes Research Consortium, University of Colorado Denver, Aurora, Colo. (Circulation: Heart Failure 2011 March 29 [doi:10.1161/CIRCHEARTFAILURE.110.959171]).

Patients included in the analysis were 15,459 adults aged 65 years or older (median age 80 years) who were discharged to a skilled nursing facility (24.1%), to home with home health service (22.3%), or to home with self-care (53.6%). The patients had been hospitalized for heart failure for at least 3 days (median 5 days) during 2005-2006.

The patients were part of the Get With The Guidelines – Heart Failure Program registry, an ongoing, voluntary quality-improvement initiative of the American Heart Association, the investigators said.

Factors found to be significantly associated with discharge to a skilled nursing facility included longer hospital stay (odds ratio 1.12 per day); advanced age (OR 1.98 per 10-year increase); female sex (OR 1.53); systolic blood pressure (OR 0.94 per 10 mm Hg increase); left ventricular ejection fraction less than 40% (OR 0.91); sodium level (OR 1.05 per 10 mEq/L increase); and history of hyperlipidemia (OR 0.74), anemia (OR 1.31), diabetes (OR 1.19), valvular heart disease (OR 0.72), myocardial infarction (OR 0.86), bypass surgery or percutaneous coronary intervention (OR 0.80), implantable defibrillator (OR 0.76), depression (OR 2.11), stroke (OR 1.55), peripheral vascular disease (OR 1.13), or chronic obstructive pulmonary disease or asthma (OR 1.11).

Across the country, the rate of discharges to skilled nursing facilities was highest in the Northeast (30%) and lowest in the West (23.6%). Hospitals that treated more racial minorities and younger patients were among those with the lowest rates of discharge to skilled nursing facilities.

In this study, hospitalized heart failure patients who were discharged to a skilled nursing facility were 79% more likely to die than those discharged to home – even after adjusting for a wide range of patient factors known to be associated with adverse outcomes, the investigators said.

"However, discharge to [a skilled nursing facility] is by its very nature determined by criteria such as poor mobility, cognitive impairment, frailty, and poor in-home support, which are also important determinants of outcome," they wrote, noting that those determinants of outcome were not captured in this analysis. Therefore, the researchers said, conclusions about whether discharge to a skilled nursing facility directly impacts patient outcomes cannot be drawn.

Still, the findings have potential implications for communicating prognoses to patients and families, medical decision-making, and assessing care provided at skilled nursing facilities, they said.

The high absolute rates of death following discharge to skilled nursing facilities, in particular, have potential implications for communication, discharge planning, and goals of care, they said.

"Additionally, we must consider whether a different set of quality measures [is] needed for this unique group of patients," the investigators concluded.

This study was funded by the American Heart Association, GlaxoSmithKline, and Medtronic through their support of the Get With The Guidelines – Heart Failure Program, and the Agency for Healthcare Research and Quality. Dr. Allen had no conflicts of interest to disclose. Other authors on the study reported numerous relationships with various pharmaceutical companies and other organizations.

Nearly one-quarter of Medicare patients hospitalized for heart failure are subsequently discharged to a skilled nursing facility, and those patients are significantly more likely to be rehospitalized or die within 1 year than are similar patients discharged to home, according to the findings of a large observational study of more than 15,400 patients from 149 hospitals.

Absolute rehospitalization rates in those discharged to a skilled nursing facility vs. home were 27% vs. 23.5%, respectively, at 30 days, and 76.1% vs. 72.2%, respectively, at 1 year. All-cause mortality rates were 14.4% vs. 4.1% at 30 days and 53.5% vs. 29.1% at 1 year, Dr. Larry A. Allen and his colleagues reported online March 29 in Circulation: Heart Failure.

After adjustment for numerous demographic and health-related factors, discharge to a skilled nursing facility in these patients remained significantly associated with an increased risk of death (hazard ratio 1.76), said Dr. Allen of the Colorado Cardiovascular Outcomes Research Consortium, University of Colorado Denver, Aurora, Colo. (Circulation: Heart Failure 2011 March 29 [doi:10.1161/CIRCHEARTFAILURE.110.959171]).

Patients included in the analysis were 15,459 adults aged 65 years or older (median age 80 years) who were discharged to a skilled nursing facility (24.1%), to home with home health service (22.3%), or to home with self-care (53.6%). The patients had been hospitalized for heart failure for at least 3 days (median 5 days) during 2005-2006.

The patients were part of the Get With The Guidelines – Heart Failure Program registry, an ongoing, voluntary quality-improvement initiative of the American Heart Association, the investigators said.

Factors found to be significantly associated with discharge to a skilled nursing facility included longer hospital stay (odds ratio 1.12 per day); advanced age (OR 1.98 per 10-year increase); female sex (OR 1.53); systolic blood pressure (OR 0.94 per 10 mm Hg increase); left ventricular ejection fraction less than 40% (OR 0.91); sodium level (OR 1.05 per 10 mEq/L increase); and history of hyperlipidemia (OR 0.74), anemia (OR 1.31), diabetes (OR 1.19), valvular heart disease (OR 0.72), myocardial infarction (OR 0.86), bypass surgery or percutaneous coronary intervention (OR 0.80), implantable defibrillator (OR 0.76), depression (OR 2.11), stroke (OR 1.55), peripheral vascular disease (OR 1.13), or chronic obstructive pulmonary disease or asthma (OR 1.11).

Across the country, the rate of discharges to skilled nursing facilities was highest in the Northeast (30%) and lowest in the West (23.6%). Hospitals that treated more racial minorities and younger patients were among those with the lowest rates of discharge to skilled nursing facilities.

In this study, hospitalized heart failure patients who were discharged to a skilled nursing facility were 79% more likely to die than those discharged to home – even after adjusting for a wide range of patient factors known to be associated with adverse outcomes, the investigators said.

"However, discharge to [a skilled nursing facility] is by its very nature determined by criteria such as poor mobility, cognitive impairment, frailty, and poor in-home support, which are also important determinants of outcome," they wrote, noting that those determinants of outcome were not captured in this analysis. Therefore, the researchers said, conclusions about whether discharge to a skilled nursing facility directly impacts patient outcomes cannot be drawn.

Still, the findings have potential implications for communicating prognoses to patients and families, medical decision-making, and assessing care provided at skilled nursing facilities, they said.

The high absolute rates of death following discharge to skilled nursing facilities, in particular, have potential implications for communication, discharge planning, and goals of care, they said.

"Additionally, we must consider whether a different set of quality measures [is] needed for this unique group of patients," the investigators concluded.

This study was funded by the American Heart Association, GlaxoSmithKline, and Medtronic through their support of the Get With The Guidelines – Heart Failure Program, and the Agency for Healthcare Research and Quality. Dr. Allen had no conflicts of interest to disclose. Other authors on the study reported numerous relationships with various pharmaceutical companies and other organizations.

Nearly one-quarter of Medicare patients hospitalized for heart failure are subsequently discharged to a skilled nursing facility, and those patients are significantly more likely to be rehospitalized or die within 1 year than are similar patients discharged to home, according to the findings of a large observational study of more than 15,400 patients from 149 hospitals.

Absolute rehospitalization rates in those discharged to a skilled nursing facility vs. home were 27% vs. 23.5%, respectively, at 30 days, and 76.1% vs. 72.2%, respectively, at 1 year. All-cause mortality rates were 14.4% vs. 4.1% at 30 days and 53.5% vs. 29.1% at 1 year, Dr. Larry A. Allen and his colleagues reported online March 29 in Circulation: Heart Failure.

After adjustment for numerous demographic and health-related factors, discharge to a skilled nursing facility in these patients remained significantly associated with an increased risk of death (hazard ratio 1.76), said Dr. Allen of the Colorado Cardiovascular Outcomes Research Consortium, University of Colorado Denver, Aurora, Colo. (Circulation: Heart Failure 2011 March 29 [doi:10.1161/CIRCHEARTFAILURE.110.959171]).

Patients included in the analysis were 15,459 adults aged 65 years or older (median age 80 years) who were discharged to a skilled nursing facility (24.1%), to home with home health service (22.3%), or to home with self-care (53.6%). The patients had been hospitalized for heart failure for at least 3 days (median 5 days) during 2005-2006.

The patients were part of the Get With The Guidelines – Heart Failure Program registry, an ongoing, voluntary quality-improvement initiative of the American Heart Association, the investigators said.

Factors found to be significantly associated with discharge to a skilled nursing facility included longer hospital stay (odds ratio 1.12 per day); advanced age (OR 1.98 per 10-year increase); female sex (OR 1.53); systolic blood pressure (OR 0.94 per 10 mm Hg increase); left ventricular ejection fraction less than 40% (OR 0.91); sodium level (OR 1.05 per 10 mEq/L increase); and history of hyperlipidemia (OR 0.74), anemia (OR 1.31), diabetes (OR 1.19), valvular heart disease (OR 0.72), myocardial infarction (OR 0.86), bypass surgery or percutaneous coronary intervention (OR 0.80), implantable defibrillator (OR 0.76), depression (OR 2.11), stroke (OR 1.55), peripheral vascular disease (OR 1.13), or chronic obstructive pulmonary disease or asthma (OR 1.11).

Across the country, the rate of discharges to skilled nursing facilities was highest in the Northeast (30%) and lowest in the West (23.6%). Hospitals that treated more racial minorities and younger patients were among those with the lowest rates of discharge to skilled nursing facilities.

In this study, hospitalized heart failure patients who were discharged to a skilled nursing facility were 79% more likely to die than those discharged to home – even after adjusting for a wide range of patient factors known to be associated with adverse outcomes, the investigators said.

"However, discharge to [a skilled nursing facility] is by its very nature determined by criteria such as poor mobility, cognitive impairment, frailty, and poor in-home support, which are also important determinants of outcome," they wrote, noting that those determinants of outcome were not captured in this analysis. Therefore, the researchers said, conclusions about whether discharge to a skilled nursing facility directly impacts patient outcomes cannot be drawn.

Still, the findings have potential implications for communicating prognoses to patients and families, medical decision-making, and assessing care provided at skilled nursing facilities, they said.

The high absolute rates of death following discharge to skilled nursing facilities, in particular, have potential implications for communication, discharge planning, and goals of care, they said.

"Additionally, we must consider whether a different set of quality measures [is] needed for this unique group of patients," the investigators concluded.

This study was funded by the American Heart Association, GlaxoSmithKline, and Medtronic through their support of the Get With The Guidelines – Heart Failure Program, and the Agency for Healthcare Research and Quality. Dr. Allen had no conflicts of interest to disclose. Other authors on the study reported numerous relationships with various pharmaceutical companies and other organizations.

Nearly one-quarter of Medicare patients hospitalized for heart failure are subsequently discharged to a skilled nursing facility, and those patients are significantly more likely to be rehospitalized or die within 1 year than are similar patients discharged to home, according to the findings of a large observational study of more than 15,400 patients from 149 hospitals.

Absolute rehospitalization rates in those discharged to a skilled nursing facility vs. home were 27% vs. 23.5%, respectively, at 30 days, and 76.1% vs. 72.2%, respectively, at 1 year. All-cause mortality rates were 14.4% vs. 4.1% at 30 days and 53.5% vs. 29.1% at 1 year, Dr. Larry A. Allen and his colleagues reported online March 29 in Circulation: Heart Failure.

After adjustment for numerous demographic and health-related factors, discharge to a skilled nursing facility in these patients remained significantly associated with an increased risk of death (hazard ratio 1.76), said Dr. Allen of the Colorado Cardiovascular Outcomes Research Consortium, University of Colorado Denver, Aurora, Colo. (Circulation: Heart Failure 2011 March 29 [doi:10.1161/CIRCHEARTFAILURE.110.959171]).

Patients included in the analysis were 15,459 adults aged 65 years or older (median age 80 years) who were discharged to a skilled nursing facility (24.1%), to home with home health service (22.3%), or to home with self-care (53.6%). The patients had been hospitalized for heart failure for at least 3 days (median 5 days) during 2005-2006.

The patients were part of the Get With The Guidelines – Heart Failure Program registry, an ongoing, voluntary quality-improvement initiative of the American Heart Association, the investigators said.

Factors found to be significantly associated with discharge to a skilled nursing facility included longer hospital stay (odds ratio 1.12 per day); advanced age (OR 1.98 per 10-year increase); female sex (OR 1.53); systolic blood pressure (OR 0.94 per 10 mm Hg increase); left ventricular ejection fraction less than 40% (OR 0.91); sodium level (OR 1.05 per 10 mEq/L increase); and history of hyperlipidemia (OR 0.74), anemia (OR 1.31), diabetes (OR 1.19), valvular heart disease (OR 0.72), myocardial infarction (OR 0.86), bypass surgery or percutaneous coronary intervention (OR 0.80), implantable defibrillator (OR 0.76), depression (OR 2.11), stroke (OR 1.55), peripheral vascular disease (OR 1.13), or chronic obstructive pulmonary disease or asthma (OR 1.11).

Across the country, the rate of discharges to skilled nursing facilities was highest in the Northeast (30%) and lowest in the West (23.6%). Hospitals that treated more racial minorities and younger patients were among those with the lowest rates of discharge to skilled nursing facilities.

In this study, hospitalized heart failure patients who were discharged to a skilled nursing facility were 79% more likely to die than those discharged to home – even after adjusting for a wide range of patient factors known to be associated with adverse outcomes, the investigators said.

"However, discharge to [a skilled nursing facility] is by its very nature determined by criteria such as poor mobility, cognitive impairment, frailty, and poor in-home support, which are also important determinants of outcome," they wrote, noting that those determinants of outcome were not captured in this analysis. Therefore, the researchers said, conclusions about whether discharge to a skilled nursing facility directly impacts patient outcomes cannot be drawn.

Still, the findings have potential implications for communicating prognoses to patients and families, medical decision-making, and assessing care provided at skilled nursing facilities, they said.

The high absolute rates of death following discharge to skilled nursing facilities, in particular, have potential implications for communication, discharge planning, and goals of care, they said.

"Additionally, we must consider whether a different set of quality measures [is] needed for this unique group of patients," the investigators concluded.

This study was funded by the American Heart Association, GlaxoSmithKline, and Medtronic through their support of the Get With The Guidelines – Heart Failure Program, and the Agency for Healthcare Research and Quality. Dr. Allen had no conflicts of interest to disclose. Other authors on the study reported numerous relationships with various pharmaceutical companies and other organizations.

ORLANDO – Endobronchial dysplasia appears useful as a biomarker for measuring the success of lung cancer chemoprevention, investigators reported at the annual meeting of the American Association for Cancer Research.

Bronchoscopies, along with biopsies of standard endobronchial sites and any other abnormal appearing areas, were performed at baseline and at 6 months after randomization to treatment with iloprost (Ventavis) or placebo in a phase II chemoprevention trial involving 152 former or current smokers with at least a 20 pack-year history.

Former smokers who received iloprost, an oral prostacyclin analog approved for the treatment of primary pulmonary hypertension, had significant improvements on several measures of endobronchial dysplasia, while current smokers had no improvement, Dr. Paul Bunn reported.

The findings demonstrate that iloprost, which has been shown to prevent the development of lung cancer in various murine models involving cigarette-smoke exposure, also might have the same effect in humans and thus deserves further study for this purpose, Dr. Bunn and his coauthors concluded.

The results also demonstrate that endobronchial dysplasia could serve as a biomarker for effectiveness of chemopreventive treatment– much as cholesterol does in patients being treated with statins to prevent cardiovascular disease, according to Dr. Bunn, executive director of the International Association for the Study of Lung Cancer. He is also the James Dudley endowed professor of lung cancer research at the cancer center at the University of Colorado, Aurora.

In the current study, baseline histology was significantly worse in current smokers than in former smokers (average biopsy scores of 3.0 vs. 2.1, respectively, with a score of 4 indicating mild dysplasia). Former smokers experienced a 0.41-point improvement in average biopsy score (P = .010), a 1.10-point improvement in their worst baseline biopsy score (P = .002), and a 12.5% improvement in dysplasia index (P = .006), which was the percentage of biopsies with a score of at least 4, said Dr. Bunn.

"The histologic improvement in the treated patients who were former smokers was larger than the magnitude of the difference between current and former smokers," he said.

For example, the baseline dysplasia index in current and former smokers was 46% and 31%, respectively, but the pre- and post-treatment dysplasia index in former smokers was 43% and 19.6%, respectively.

Study participants had an average 30 pack-year history of smoking, and at least mild cytologic atypia on sputum cytology, but no previous history of cancer. Iloprost was given in escalating doses across the 6-month treatment period and was well tolerated. The treatment and placebo groups were well-matched for age, tobacco exposure and baseline histology, and there was no difference in dropout rate or serious adverse events between the treatment and placebo groups, Dr. Bunn noted.

Although antismoking campaigns are working – and about half of all smokers have quit, those who quit remain at greater risk for developing lung cancer than are nonsmokers; about half of all cases of lung cancer are in former smokers, and it is important to find effective chemopreventive measures for these individuals, he said.

Dr. Bunn discussed off-label use of iloprost for chemoprevention of lung cancer. He had no other disclosures.

ORLANDO – Endobronchial dysplasia appears useful as a biomarker for measuring the success of lung cancer chemoprevention, investigators reported at the annual meeting of the American Association for Cancer Research.

Bronchoscopies, along with biopsies of standard endobronchial sites and any other abnormal appearing areas, were performed at baseline and at 6 months after randomization to treatment with iloprost (Ventavis) or placebo in a phase II chemoprevention trial involving 152 former or current smokers with at least a 20 pack-year history.

Former smokers who received iloprost, an oral prostacyclin analog approved for the treatment of primary pulmonary hypertension, had significant improvements on several measures of endobronchial dysplasia, while current smokers had no improvement, Dr. Paul Bunn reported.

The findings demonstrate that iloprost, which has been shown to prevent the development of lung cancer in various murine models involving cigarette-smoke exposure, also might have the same effect in humans and thus deserves further study for this purpose, Dr. Bunn and his coauthors concluded.

The results also demonstrate that endobronchial dysplasia could serve as a biomarker for effectiveness of chemopreventive treatment– much as cholesterol does in patients being treated with statins to prevent cardiovascular disease, according to Dr. Bunn, executive director of the International Association for the Study of Lung Cancer. He is also the James Dudley endowed professor of lung cancer research at the cancer center at the University of Colorado, Aurora.

In the current study, baseline histology was significantly worse in current smokers than in former smokers (average biopsy scores of 3.0 vs. 2.1, respectively, with a score of 4 indicating mild dysplasia). Former smokers experienced a 0.41-point improvement in average biopsy score (P = .010), a 1.10-point improvement in their worst baseline biopsy score (P = .002), and a 12.5% improvement in dysplasia index (P = .006), which was the percentage of biopsies with a score of at least 4, said Dr. Bunn.

"The histologic improvement in the treated patients who were former smokers was larger than the magnitude of the difference between current and former smokers," he said.

For example, the baseline dysplasia index in current and former smokers was 46% and 31%, respectively, but the pre- and post-treatment dysplasia index in former smokers was 43% and 19.6%, respectively.

Study participants had an average 30 pack-year history of smoking, and at least mild cytologic atypia on sputum cytology, but no previous history of cancer. Iloprost was given in escalating doses across the 6-month treatment period and was well tolerated. The treatment and placebo groups were well-matched for age, tobacco exposure and baseline histology, and there was no difference in dropout rate or serious adverse events between the treatment and placebo groups, Dr. Bunn noted.

Although antismoking campaigns are working – and about half of all smokers have quit, those who quit remain at greater risk for developing lung cancer than are nonsmokers; about half of all cases of lung cancer are in former smokers, and it is important to find effective chemopreventive measures for these individuals, he said.

Dr. Bunn discussed off-label use of iloprost for chemoprevention of lung cancer. He had no other disclosures.

ORLANDO – Endobronchial dysplasia appears useful as a biomarker for measuring the success of lung cancer chemoprevention, investigators reported at the annual meeting of the American Association for Cancer Research.

Bronchoscopies, along with biopsies of standard endobronchial sites and any other abnormal appearing areas, were performed at baseline and at 6 months after randomization to treatment with iloprost (Ventavis) or placebo in a phase II chemoprevention trial involving 152 former or current smokers with at least a 20 pack-year history.

Former smokers who received iloprost, an oral prostacyclin analog approved for the treatment of primary pulmonary hypertension, had significant improvements on several measures of endobronchial dysplasia, while current smokers had no improvement, Dr. Paul Bunn reported.

The findings demonstrate that iloprost, which has been shown to prevent the development of lung cancer in various murine models involving cigarette-smoke exposure, also might have the same effect in humans and thus deserves further study for this purpose, Dr. Bunn and his coauthors concluded.

The results also demonstrate that endobronchial dysplasia could serve as a biomarker for effectiveness of chemopreventive treatment– much as cholesterol does in patients being treated with statins to prevent cardiovascular disease, according to Dr. Bunn, executive director of the International Association for the Study of Lung Cancer. He is also the James Dudley endowed professor of lung cancer research at the cancer center at the University of Colorado, Aurora.

In the current study, baseline histology was significantly worse in current smokers than in former smokers (average biopsy scores of 3.0 vs. 2.1, respectively, with a score of 4 indicating mild dysplasia). Former smokers experienced a 0.41-point improvement in average biopsy score (P = .010), a 1.10-point improvement in their worst baseline biopsy score (P = .002), and a 12.5% improvement in dysplasia index (P = .006), which was the percentage of biopsies with a score of at least 4, said Dr. Bunn.

"The histologic improvement in the treated patients who were former smokers was larger than the magnitude of the difference between current and former smokers," he said.

For example, the baseline dysplasia index in current and former smokers was 46% and 31%, respectively, but the pre- and post-treatment dysplasia index in former smokers was 43% and 19.6%, respectively.

Study participants had an average 30 pack-year history of smoking, and at least mild cytologic atypia on sputum cytology, but no previous history of cancer. Iloprost was given in escalating doses across the 6-month treatment period and was well tolerated. The treatment and placebo groups were well-matched for age, tobacco exposure and baseline histology, and there was no difference in dropout rate or serious adverse events between the treatment and placebo groups, Dr. Bunn noted.

Although antismoking campaigns are working – and about half of all smokers have quit, those who quit remain at greater risk for developing lung cancer than are nonsmokers; about half of all cases of lung cancer are in former smokers, and it is important to find effective chemopreventive measures for these individuals, he said.

Dr. Bunn discussed off-label use of iloprost for chemoprevention of lung cancer. He had no other disclosures.

ORLANDO – Endobronchial dysplasia appears useful as a biomarker for measuring the success of lung cancer chemoprevention, investigators reported at the annual meeting of the American Association for Cancer Research.

Bronchoscopies, along with biopsies of standard endobronchial sites and any other abnormal appearing areas, were performed at baseline and at 6 months after randomization to treatment with iloprost (Ventavis) or placebo in a phase II chemoprevention trial involving 152 former or current smokers with at least a 20 pack-year history.

Former smokers who received iloprost, an oral prostacyclin analog approved for the treatment of primary pulmonary hypertension, had significant improvements on several measures of endobronchial dysplasia, while current smokers had no improvement, Dr. Paul Bunn reported.

The findings demonstrate that iloprost, which has been shown to prevent the development of lung cancer in various murine models involving cigarette-smoke exposure, also might have the same effect in humans and thus deserves further study for this purpose, Dr. Bunn and his coauthors concluded.

The results also demonstrate that endobronchial dysplasia could serve as a biomarker for effectiveness of chemopreventive treatment– much as cholesterol does in patients being treated with statins to prevent cardiovascular disease, according to Dr. Bunn, executive director of the International Association for the Study of Lung Cancer. He is also the James Dudley endowed professor of lung cancer research at the cancer center at the University of Colorado, Aurora.

In the current study, baseline histology was significantly worse in current smokers than in former smokers (average biopsy scores of 3.0 vs. 2.1, respectively, with a score of 4 indicating mild dysplasia). Former smokers experienced a 0.41-point improvement in average biopsy score (P = .010), a 1.10-point improvement in their worst baseline biopsy score (P = .002), and a 12.5% improvement in dysplasia index (P = .006), which was the percentage of biopsies with a score of at least 4, said Dr. Bunn.

"The histologic improvement in the treated patients who were former smokers was larger than the magnitude of the difference between current and former smokers," he said.

For example, the baseline dysplasia index in current and former smokers was 46% and 31%, respectively, but the pre- and post-treatment dysplasia index in former smokers was 43% and 19.6%, respectively.

Study participants had an average 30 pack-year history of smoking, and at least mild cytologic atypia on sputum cytology, but no previous history of cancer. Iloprost was given in escalating doses across the 6-month treatment period and was well tolerated. The treatment and placebo groups were well-matched for age, tobacco exposure and baseline histology, and there was no difference in dropout rate or serious adverse events between the treatment and placebo groups, Dr. Bunn noted.

Although antismoking campaigns are working – and about half of all smokers have quit, those who quit remain at greater risk for developing lung cancer than are nonsmokers; about half of all cases of lung cancer are in former smokers, and it is important to find effective chemopreventive measures for these individuals, he said.

Dr. Bunn discussed off-label use of iloprost for chemoprevention of lung cancer. He had no other disclosures.

ORLANDO – Endobronchial dysplasia appears useful as a biomarker for measuring the success of lung cancer chemoprevention, investigators reported at the annual meeting of the American Association for Cancer Research.

Bronchoscopies, along with biopsies of standard endobronchial sites and any other abnormal appearing areas, were performed at baseline and at 6 months after randomization to treatment with iloprost (Ventavis) or placebo in a phase II chemoprevention trial involving 152 former or current smokers with at least a 20 pack-year history.

Former smokers who received iloprost, an oral prostacyclin analog approved for the treatment of primary pulmonary hypertension, had significant improvements on several measures of endobronchial dysplasia, while current smokers had no improvement, Dr. Paul Bunn reported.

The findings demonstrate that iloprost, which has been shown to prevent the development of lung cancer in various murine models involving cigarette-smoke exposure, also might have the same effect in humans and thus deserves further study for this purpose, Dr. Bunn and his coauthors concluded.

The results also demonstrate that endobronchial dysplasia could serve as a biomarker for effectiveness of chemopreventive treatment– much as cholesterol does in patients being treated with statins to prevent cardiovascular disease, according to Dr. Bunn, executive director of the International Association for the Study of Lung Cancer. He is also the James Dudley endowed professor of lung cancer research at the cancer center at the University of Colorado, Aurora.

In the current study, baseline histology was significantly worse in current smokers than in former smokers (average biopsy scores of 3.0 vs. 2.1, respectively, with a score of 4 indicating mild dysplasia). Former smokers experienced a 0.41-point improvement in average biopsy score (P = .010), a 1.10-point improvement in their worst baseline biopsy score (P = .002), and a 12.5% improvement in dysplasia index (P = .006), which was the percentage of biopsies with a score of at least 4, said Dr. Bunn.

"The histologic improvement in the treated patients who were former smokers was larger than the magnitude of the difference between current and former smokers," he said.

For example, the baseline dysplasia index in current and former smokers was 46% and 31%, respectively, but the pre- and post-treatment dysplasia index in former smokers was 43% and 19.6%, respectively.

Study participants had an average 30 pack-year history of smoking, and at least mild cytologic atypia on sputum cytology, but no previous history of cancer. Iloprost was given in escalating doses across the 6-month treatment period and was well tolerated. The treatment and placebo groups were well-matched for age, tobacco exposure and baseline histology, and there was no difference in dropout rate or serious adverse events between the treatment and placebo groups, Dr. Bunn noted.

Although antismoking campaigns are working – and about half of all smokers have quit, those who quit remain at greater risk for developing lung cancer than are nonsmokers; about half of all cases of lung cancer are in former smokers, and it is important to find effective chemopreventive measures for these individuals, he said.

Dr. Bunn discussed off-label use of iloprost for chemoprevention of lung cancer. He had no other disclosures.

ORLANDO – Endobronchial dysplasia appears useful as a biomarker for measuring the success of lung cancer chemoprevention, investigators reported at the annual meeting of the American Association for Cancer Research.

Bronchoscopies, along with biopsies of standard endobronchial sites and any other abnormal appearing areas, were performed at baseline and at 6 months after randomization to treatment with iloprost (Ventavis) or placebo in a phase II chemoprevention trial involving 152 former or current smokers with at least a 20 pack-year history.

Former smokers who received iloprost, an oral prostacyclin analog approved for the treatment of primary pulmonary hypertension, had significant improvements on several measures of endobronchial dysplasia, while current smokers had no improvement, Dr. Paul Bunn reported.

The findings demonstrate that iloprost, which has been shown to prevent the development of lung cancer in various murine models involving cigarette-smoke exposure, also might have the same effect in humans and thus deserves further study for this purpose, Dr. Bunn and his coauthors concluded.

The results also demonstrate that endobronchial dysplasia could serve as a biomarker for effectiveness of chemopreventive treatment– much as cholesterol does in patients being treated with statins to prevent cardiovascular disease, according to Dr. Bunn, executive director of the International Association for the Study of Lung Cancer. He is also the James Dudley endowed professor of lung cancer research at the cancer center at the University of Colorado, Aurora.

In the current study, baseline histology was significantly worse in current smokers than in former smokers (average biopsy scores of 3.0 vs. 2.1, respectively, with a score of 4 indicating mild dysplasia). Former smokers experienced a 0.41-point improvement in average biopsy score (P = .010), a 1.10-point improvement in their worst baseline biopsy score (P = .002), and a 12.5% improvement in dysplasia index (P = .006), which was the percentage of biopsies with a score of at least 4, said Dr. Bunn.

"The histologic improvement in the treated patients who were former smokers was larger than the magnitude of the difference between current and former smokers," he said.

For example, the baseline dysplasia index in current and former smokers was 46% and 31%, respectively, but the pre- and post-treatment dysplasia index in former smokers was 43% and 19.6%, respectively.

Study participants had an average 30 pack-year history of smoking, and at least mild cytologic atypia on sputum cytology, but no previous history of cancer. Iloprost was given in escalating doses across the 6-month treatment period and was well tolerated. The treatment and placebo groups were well-matched for age, tobacco exposure and baseline histology, and there was no difference in dropout rate or serious adverse events between the treatment and placebo groups, Dr. Bunn noted.

Although antismoking campaigns are working – and about half of all smokers have quit, those who quit remain at greater risk for developing lung cancer than are nonsmokers; about half of all cases of lung cancer are in former smokers, and it is important to find effective chemopreventive measures for these individuals, he said.

Dr. Bunn discussed off-label use of iloprost for chemoprevention of lung cancer. He had no other disclosures.

ORLANDO – A novel hedgehog pathway inhibitor significantly and rapidly reduced the development of new basal cell carcinomas – as well as the size and severity of existing ones – in a randomized, controlled phase II study of 41 patients with basal cell nevus syndrome.

The number of new surgically eligible basal cell carcinomas (BCCs) that developed was 0.07/month in patients receiving active treatment with vismodegib (GDC-0449), compared with 1.74/month in those who received placebo (P less than .0001).

The change from baseline in the aggregate size of existing BCCs was –24 cm in the vismodegib group, compared with –3 cm in the placebo group (P = .006), Dr. Ervin H. Epstein Jr. reported at the annual meeting of the American Association for Cancer Research.

The investigator-initiated study was stopped at an interim analysis because of the highly statistically significant differences between the treatment and placebo groups.

"We have a drug, developed by Genentech, based on the fundamental knowledge that hedgehog signaling is pivotal to all BCCs – including in these patients who carry a defective copy of the gene that inhibits hedgehog signaling," said Dr. Epstein, senior scientist at Children’s Hospital of Oakland (Calif.) Research Institute.

"It is the first drug used in man that replaces the function of the missing gene ... and it actually works," added Dr. Epstein, who helped lay the foundation for the development of vismodegib in 1996 when, along with his colleagues, he identified the site of the mutation that causes basal cell nevus syndrome (the PTCH gene, which encodes a primary inhibitor of the hedgehog signaling pathway).

Patients from three clinical centers were enrolled from September 2009 to January 2011 in the current trial and were randomized 2:1 to receive 150 mg of vismodegib orally once daily, or placebo. Molecular analysis of samples from 23 subjects showed that anti-BCC efficacy was associated with on-target reduction of the hedgehog pathway; Gli1mRNA levels were decreased 200-fold after 1 month in BCCs of patients in the active treatment group, while levels remained unchanged in BCCs of patients in the placebo group.

Dr. Epstein showed several images demonstrating the dramatic improvement in patients with severe disease – sometimes as early as 1-2 months after treatment initiation, and noted that no resistance to treatment developed. Some patients achieved near remission. He cautioned, however, that the drug is associated with toxicity that makes it an unlikely treatment for "the usual patient with one BCC."

One fifth of participants discontinued the study because of toxicity. Common grade 1/2 adverse events were taste loss (in 83% of patients on treatment vs. 8% on placebo), muscle cramps (in 67% vs. 8%), and weight loss (in 50% vs. 8%). Hair loss also was common, which is not surprising, because the targeted pathway is important in hair follicle regeneration, Dr. Epstein explained.

Two grade 3/4 events occurred in patients in the study as well. These included muscle cramps, and a suicide attempt, he said.

While BCC is the most common type of cancer, affecting more than a million people in the United States each year – particularly those of European descent, most develop only one or a small number, and these can be managed with surgery, which currently can cure 98%-99% of cases, he said.

Only a very small number of patients – estimates range from 1/50,000 to 1/250,000 – have heritable conditions such as basal cell nevus syndrome (Gorlin’s syndrome), which can be associated with the development of dozens, if not thousands, of lesions that require surgical management, and for these patients, the adverse events might be much more acceptable.

Indeed, for these patients this drug is "a breakthrough – with a capital B," said Dr. Daniel D. Von Hoff, physician-in-chief and distinguished professor at the Translational Genomics Research Institute (TGen) in Phoenix and moderator of an AACR press briefing during which Dr. Epstein discussed his findings.

Additional study is needed to assess long-term adverse events and to determine whether different dosing strategies would improve tolerance, Dr. Epstein said. Genentech has announced that is conducting an expanded patient access study while the company discusses its next steps with the U.S. Food and Drug Administration.

Dr. Epstein had no disclosures.

ORLANDO – A novel hedgehog pathway inhibitor significantly and rapidly reduced the development of new basal cell carcinomas – as well as the size and severity of existing ones – in a randomized, controlled phase II study of 41 patients with basal cell nevus syndrome.

The number of new surgically eligible basal cell carcinomas (BCCs) that developed was 0.07/month in patients receiving active treatment with vismodegib (GDC-0449), compared with 1.74/month in those who received placebo (P less than .0001).

The change from baseline in the aggregate size of existing BCCs was –24 cm in the vismodegib group, compared with –3 cm in the placebo group (P = .006), Dr. Ervin H. Epstein Jr. reported at the annual meeting of the American Association for Cancer Research.

The investigator-initiated study was stopped at an interim analysis because of the highly statistically significant differences between the treatment and placebo groups.

"We have a drug, developed by Genentech, based on the fundamental knowledge that hedgehog signaling is pivotal to all BCCs – including in these patients who carry a defective copy of the gene that inhibits hedgehog signaling," said Dr. Epstein, senior scientist at Children’s Hospital of Oakland (Calif.) Research Institute.

"It is the first drug used in man that replaces the function of the missing gene ... and it actually works," added Dr. Epstein, who helped lay the foundation for the development of vismodegib in 1996 when, along with his colleagues, he identified the site of the mutation that causes basal cell nevus syndrome (the PTCH gene, which encodes a primary inhibitor of the hedgehog signaling pathway).

Patients from three clinical centers were enrolled from September 2009 to January 2011 in the current trial and were randomized 2:1 to receive 150 mg of vismodegib orally once daily, or placebo. Molecular analysis of samples from 23 subjects showed that anti-BCC efficacy was associated with on-target reduction of the hedgehog pathway; Gli1mRNA levels were decreased 200-fold after 1 month in BCCs of patients in the active treatment group, while levels remained unchanged in BCCs of patients in the placebo group.

Dr. Epstein showed several images demonstrating the dramatic improvement in patients with severe disease – sometimes as early as 1-2 months after treatment initiation, and noted that no resistance to treatment developed. Some patients achieved near remission. He cautioned, however, that the drug is associated with toxicity that makes it an unlikely treatment for "the usual patient with one BCC."

One fifth of participants discontinued the study because of toxicity. Common grade 1/2 adverse events were taste loss (in 83% of patients on treatment vs. 8% on placebo), muscle cramps (in 67% vs. 8%), and weight loss (in 50% vs. 8%). Hair loss also was common, which is not surprising, because the targeted pathway is important in hair follicle regeneration, Dr. Epstein explained.

Two grade 3/4 events occurred in patients in the study as well. These included muscle cramps, and a suicide attempt, he said.

While BCC is the most common type of cancer, affecting more than a million people in the United States each year – particularly those of European descent, most develop only one or a small number, and these can be managed with surgery, which currently can cure 98%-99% of cases, he said.

Only a very small number of patients – estimates range from 1/50,000 to 1/250,000 – have heritable conditions such as basal cell nevus syndrome (Gorlin’s syndrome), which can be associated with the development of dozens, if not thousands, of lesions that require surgical management, and for these patients, the adverse events might be much more acceptable.

Indeed, for these patients this drug is "a breakthrough – with a capital B," said Dr. Daniel D. Von Hoff, physician-in-chief and distinguished professor at the Translational Genomics Research Institute (TGen) in Phoenix and moderator of an AACR press briefing during which Dr. Epstein discussed his findings.

Additional study is needed to assess long-term adverse events and to determine whether different dosing strategies would improve tolerance, Dr. Epstein said. Genentech has announced that is conducting an expanded patient access study while the company discusses its next steps with the U.S. Food and Drug Administration.

Dr. Epstein had no disclosures.

ORLANDO – A novel hedgehog pathway inhibitor significantly and rapidly reduced the development of new basal cell carcinomas – as well as the size and severity of existing ones – in a randomized, controlled phase II study of 41 patients with basal cell nevus syndrome.

The number of new surgically eligible basal cell carcinomas (BCCs) that developed was 0.07/month in patients receiving active treatment with vismodegib (GDC-0449), compared with 1.74/month in those who received placebo (P less than .0001).

The change from baseline in the aggregate size of existing BCCs was –24 cm in the vismodegib group, compared with –3 cm in the placebo group (P = .006), Dr. Ervin H. Epstein Jr. reported at the annual meeting of the American Association for Cancer Research.

The investigator-initiated study was stopped at an interim analysis because of the highly statistically significant differences between the treatment and placebo groups.

"We have a drug, developed by Genentech, based on the fundamental knowledge that hedgehog signaling is pivotal to all BCCs – including in these patients who carry a defective copy of the gene that inhibits hedgehog signaling," said Dr. Epstein, senior scientist at Children’s Hospital of Oakland (Calif.) Research Institute.

"It is the first drug used in man that replaces the function of the missing gene ... and it actually works," added Dr. Epstein, who helped lay the foundation for the development of vismodegib in 1996 when, along with his colleagues, he identified the site of the mutation that causes basal cell nevus syndrome (the PTCH gene, which encodes a primary inhibitor of the hedgehog signaling pathway).

Patients from three clinical centers were enrolled from September 2009 to January 2011 in the current trial and were randomized 2:1 to receive 150 mg of vismodegib orally once daily, or placebo. Molecular analysis of samples from 23 subjects showed that anti-BCC efficacy was associated with on-target reduction of the hedgehog pathway; Gli1mRNA levels were decreased 200-fold after 1 month in BCCs of patients in the active treatment group, while levels remained unchanged in BCCs of patients in the placebo group.

Dr. Epstein showed several images demonstrating the dramatic improvement in patients with severe disease – sometimes as early as 1-2 months after treatment initiation, and noted that no resistance to treatment developed. Some patients achieved near remission. He cautioned, however, that the drug is associated with toxicity that makes it an unlikely treatment for "the usual patient with one BCC."

One fifth of participants discontinued the study because of toxicity. Common grade 1/2 adverse events were taste loss (in 83% of patients on treatment vs. 8% on placebo), muscle cramps (in 67% vs. 8%), and weight loss (in 50% vs. 8%). Hair loss also was common, which is not surprising, because the targeted pathway is important in hair follicle regeneration, Dr. Epstein explained.

Two grade 3/4 events occurred in patients in the study as well. These included muscle cramps, and a suicide attempt, he said.

While BCC is the most common type of cancer, affecting more than a million people in the United States each year – particularly those of European descent, most develop only one or a small number, and these can be managed with surgery, which currently can cure 98%-99% of cases, he said.

Only a very small number of patients – estimates range from 1/50,000 to 1/250,000 – have heritable conditions such as basal cell nevus syndrome (Gorlin’s syndrome), which can be associated with the development of dozens, if not thousands, of lesions that require surgical management, and for these patients, the adverse events might be much more acceptable.

Indeed, for these patients this drug is "a breakthrough – with a capital B," said Dr. Daniel D. Von Hoff, physician-in-chief and distinguished professor at the Translational Genomics Research Institute (TGen) in Phoenix and moderator of an AACR press briefing during which Dr. Epstein discussed his findings.

Additional study is needed to assess long-term adverse events and to determine whether different dosing strategies would improve tolerance, Dr. Epstein said. Genentech has announced that is conducting an expanded patient access study while the company discusses its next steps with the U.S. Food and Drug Administration.

Dr. Epstein had no disclosures.

ORLANDO – A novel hedgehog pathway inhibitor significantly and rapidly reduced the development of new basal cell carcinomas – as well as the size and severity of existing ones – in a randomized, controlled phase II study of 41 patients with basal cell nevus syndrome.

The number of new surgically eligible basal cell carcinomas (BCCs) that developed was 0.07/month in patients receiving active treatment with vismodegib (GDC-0449), compared with 1.74/month in those who received placebo (P less than .0001).

The change from baseline in the aggregate size of existing BCCs was –24 cm in the vismodegib group, compared with –3 cm in the placebo group (P = .006), Dr. Ervin H. Epstein Jr. reported at the annual meeting of the American Association for Cancer Research.

The investigator-initiated study was stopped at an interim analysis because of the highly statistically significant differences between the treatment and placebo groups.

"We have a drug, developed by Genentech, based on the fundamental knowledge that hedgehog signaling is pivotal to all BCCs – including in these patients who carry a defective copy of the gene that inhibits hedgehog signaling," said Dr. Epstein, senior scientist at Children’s Hospital of Oakland (Calif.) Research Institute.

"It is the first drug used in man that replaces the function of the missing gene ... and it actually works," added Dr. Epstein, who helped lay the foundation for the development of vismodegib in 1996 when, along with his colleagues, he identified the site of the mutation that causes basal cell nevus syndrome (the PTCH gene, which encodes a primary inhibitor of the hedgehog signaling pathway).

Patients from three clinical centers were enrolled from September 2009 to January 2011 in the current trial and were randomized 2:1 to receive 150 mg of vismodegib orally once daily, or placebo. Molecular analysis of samples from 23 subjects showed that anti-BCC efficacy was associated with on-target reduction of the hedgehog pathway; Gli1mRNA levels were decreased 200-fold after 1 month in BCCs of patients in the active treatment group, while levels remained unchanged in BCCs of patients in the placebo group.

Dr. Epstein showed several images demonstrating the dramatic improvement in patients with severe disease – sometimes as early as 1-2 months after treatment initiation, and noted that no resistance to treatment developed. Some patients achieved near remission. He cautioned, however, that the drug is associated with toxicity that makes it an unlikely treatment for "the usual patient with one BCC."

One fifth of participants discontinued the study because of toxicity. Common grade 1/2 adverse events were taste loss (in 83% of patients on treatment vs. 8% on placebo), muscle cramps (in 67% vs. 8%), and weight loss (in 50% vs. 8%). Hair loss also was common, which is not surprising, because the targeted pathway is important in hair follicle regeneration, Dr. Epstein explained.

Two grade 3/4 events occurred in patients in the study as well. These included muscle cramps, and a suicide attempt, he said.

While BCC is the most common type of cancer, affecting more than a million people in the United States each year – particularly those of European descent, most develop only one or a small number, and these can be managed with surgery, which currently can cure 98%-99% of cases, he said.

Only a very small number of patients – estimates range from 1/50,000 to 1/250,000 – have heritable conditions such as basal cell nevus syndrome (Gorlin’s syndrome), which can be associated with the development of dozens, if not thousands, of lesions that require surgical management, and for these patients, the adverse events might be much more acceptable.

Indeed, for these patients this drug is "a breakthrough – with a capital B," said Dr. Daniel D. Von Hoff, physician-in-chief and distinguished professor at the Translational Genomics Research Institute (TGen) in Phoenix and moderator of an AACR press briefing during which Dr. Epstein discussed his findings.

Additional study is needed to assess long-term adverse events and to determine whether different dosing strategies would improve tolerance, Dr. Epstein said. Genentech has announced that is conducting an expanded patient access study while the company discusses its next steps with the U.S. Food and Drug Administration.

Dr. Epstein had no disclosures.

ORLANDO – A novel hedgehog pathway inhibitor significantly and rapidly reduced the development of new basal cell carcinomas – as well as the size and severity of existing ones – in a randomized, controlled phase II study of 41 patients with basal cell nevus syndrome.

The number of new surgically eligible basal cell carcinomas (BCCs) that developed was 0.07/month in patients receiving active treatment with vismodegib (GDC-0449), compared with 1.74/month in those who received placebo (P less than .0001).

The change from baseline in the aggregate size of existing BCCs was –24 cm in the vismodegib group, compared with –3 cm in the placebo group (P = .006), Dr. Ervin H. Epstein Jr. reported at the annual meeting of the American Association for Cancer Research.

The investigator-initiated study was stopped at an interim analysis because of the highly statistically significant differences between the treatment and placebo groups.

"We have a drug, developed by Genentech, based on the fundamental knowledge that hedgehog signaling is pivotal to all BCCs – including in these patients who carry a defective copy of the gene that inhibits hedgehog signaling," said Dr. Epstein, senior scientist at Children’s Hospital of Oakland (Calif.) Research Institute.

"It is the first drug used in man that replaces the function of the missing gene ... and it actually works," added Dr. Epstein, who helped lay the foundation for the development of vismodegib in 1996 when, along with his colleagues, he identified the site of the mutation that causes basal cell nevus syndrome (the PTCH gene, which encodes a primary inhibitor of the hedgehog signaling pathway).

Patients from three clinical centers were enrolled from September 2009 to January 2011 in the current trial and were randomized 2:1 to receive 150 mg of vismodegib orally once daily, or placebo. Molecular analysis of samples from 23 subjects showed that anti-BCC efficacy was associated with on-target reduction of the hedgehog pathway; Gli1mRNA levels were decreased 200-fold after 1 month in BCCs of patients in the active treatment group, while levels remained unchanged in BCCs of patients in the placebo group.

Dr. Epstein showed several images demonstrating the dramatic improvement in patients with severe disease – sometimes as early as 1-2 months after treatment initiation, and noted that no resistance to treatment developed. Some patients achieved near remission. He cautioned, however, that the drug is associated with toxicity that makes it an unlikely treatment for "the usual patient with one BCC."

One fifth of participants discontinued the study because of toxicity. Common grade 1/2 adverse events were taste loss (in 83% of patients on treatment vs. 8% on placebo), muscle cramps (in 67% vs. 8%), and weight loss (in 50% vs. 8%). Hair loss also was common, which is not surprising, because the targeted pathway is important in hair follicle regeneration, Dr. Epstein explained.

Two grade 3/4 events occurred in patients in the study as well. These included muscle cramps, and a suicide attempt, he said.

While BCC is the most common type of cancer, affecting more than a million people in the United States each year – particularly those of European descent, most develop only one or a small number, and these can be managed with surgery, which currently can cure 98%-99% of cases, he said.

Only a very small number of patients – estimates range from 1/50,000 to 1/250,000 – have heritable conditions such as basal cell nevus syndrome (Gorlin’s syndrome), which can be associated with the development of dozens, if not thousands, of lesions that require surgical management, and for these patients, the adverse events might be much more acceptable.

Indeed, for these patients this drug is "a breakthrough – with a capital B," said Dr. Daniel D. Von Hoff, physician-in-chief and distinguished professor at the Translational Genomics Research Institute (TGen) in Phoenix and moderator of an AACR press briefing during which Dr. Epstein discussed his findings.

Additional study is needed to assess long-term adverse events and to determine whether different dosing strategies would improve tolerance, Dr. Epstein said. Genentech has announced that is conducting an expanded patient access study while the company discusses its next steps with the U.S. Food and Drug Administration.

Dr. Epstein had no disclosures.

ORLANDO – A novel hedgehog pathway inhibitor significantly and rapidly reduced the development of new basal cell carcinomas – as well as the size and severity of existing ones – in a randomized, controlled phase II study of 41 patients with basal cell nevus syndrome.

The number of new surgically eligible basal cell carcinomas (BCCs) that developed was 0.07/month in patients receiving active treatment with vismodegib (GDC-0449), compared with 1.74/month in those who received placebo (P less than .0001).

The change from baseline in the aggregate size of existing BCCs was –24 cm in the vismodegib group, compared with –3 cm in the placebo group (P = .006), Dr. Ervin H. Epstein Jr. reported at the annual meeting of the American Association for Cancer Research.

The investigator-initiated study was stopped at an interim analysis because of the highly statistically significant differences between the treatment and placebo groups.

"We have a drug, developed by Genentech, based on the fundamental knowledge that hedgehog signaling is pivotal to all BCCs – including in these patients who carry a defective copy of the gene that inhibits hedgehog signaling," said Dr. Epstein, senior scientist at Children’s Hospital of Oakland (Calif.) Research Institute.

"It is the first drug used in man that replaces the function of the missing gene ... and it actually works," added Dr. Epstein, who helped lay the foundation for the development of vismodegib in 1996 when, along with his colleagues, he identified the site of the mutation that causes basal cell nevus syndrome (the PTCH gene, which encodes a primary inhibitor of the hedgehog signaling pathway).

Patients from three clinical centers were enrolled from September 2009 to January 2011 in the current trial and were randomized 2:1 to receive 150 mg of vismodegib orally once daily, or placebo. Molecular analysis of samples from 23 subjects showed that anti-BCC efficacy was associated with on-target reduction of the hedgehog pathway; Gli1mRNA levels were decreased 200-fold after 1 month in BCCs of patients in the active treatment group, while levels remained unchanged in BCCs of patients in the placebo group.

Dr. Epstein showed several images demonstrating the dramatic improvement in patients with severe disease – sometimes as early as 1-2 months after treatment initiation, and noted that no resistance to treatment developed. Some patients achieved near remission. He cautioned, however, that the drug is associated with toxicity that makes it an unlikely treatment for "the usual patient with one BCC."

One fifth of participants discontinued the study because of toxicity. Common grade 1/2 adverse events were taste loss (in 83% of patients on treatment vs. 8% on placebo), muscle cramps (in 67% vs. 8%), and weight loss (in 50% vs. 8%). Hair loss also was common, which is not surprising, because the targeted pathway is important in hair follicle regeneration, Dr. Epstein explained.

Two grade 3/4 events occurred in patients in the study as well. These included muscle cramps, and a suicide attempt, he said.

While BCC is the most common type of cancer, affecting more than a million people in the United States each year – particularly those of European descent, most develop only one or a small number, and these can be managed with surgery, which currently can cure 98%-99% of cases, he said.

Only a very small number of patients – estimates range from 1/50,000 to 1/250,000 – have heritable conditions such as basal cell nevus syndrome (Gorlin’s syndrome), which can be associated with the development of dozens, if not thousands, of lesions that require surgical management, and for these patients, the adverse events might be much more acceptable.

Indeed, for these patients this drug is "a breakthrough – with a capital B," said Dr. Daniel D. Von Hoff, physician-in-chief and distinguished professor at the Translational Genomics Research Institute (TGen) in Phoenix and moderator of an AACR press briefing during which Dr. Epstein discussed his findings.

Additional study is needed to assess long-term adverse events and to determine whether different dosing strategies would improve tolerance, Dr. Epstein said. Genentech has announced that is conducting an expanded patient access study while the company discusses its next steps with the U.S. Food and Drug Administration.

Dr. Epstein had no disclosures.

ORLANDO – A novel hedgehog pathway inhibitor significantly and rapidly reduced the development of new basal cell carcinomas – as well as the size and severity of existing ones – in a randomized, controlled phase II study of 41 patients with basal cell nevus syndrome.

The number of new surgically eligible basal cell carcinomas (BCCs) that developed was 0.07/month in patients receiving active treatment with vismodegib (GDC-0449), compared with 1.74/month in those who received placebo (P less than .0001).

The change from baseline in the aggregate size of existing BCCs was –24 cm in the vismodegib group, compared with –3 cm in the placebo group (P = .006), Dr. Ervin H. Epstein Jr. reported at the annual meeting of the American Association for Cancer Research.

The investigator-initiated study was stopped at an interim analysis because of the highly statistically significant differences between the treatment and placebo groups.

"We have a drug, developed by Genentech, based on the fundamental knowledge that hedgehog signaling is pivotal to all BCCs – including in these patients who carry a defective copy of the gene that inhibits hedgehog signaling," said Dr. Epstein, senior scientist at Children’s Hospital of Oakland (Calif.) Research Institute.

"It is the first drug used in man that replaces the function of the missing gene ... and it actually works," added Dr. Epstein, who helped lay the foundation for the development of vismodegib in 1996 when, along with his colleagues, he identified the site of the mutation that causes basal cell nevus syndrome (the PTCH gene, which encodes a primary inhibitor of the hedgehog signaling pathway).

Patients from three clinical centers were enrolled from September 2009 to January 2011 in the current trial and were randomized 2:1 to receive 150 mg of vismodegib orally once daily, or placebo. Molecular analysis of samples from 23 subjects showed that anti-BCC efficacy was associated with on-target reduction of the hedgehog pathway; Gli1mRNA levels were decreased 200-fold after 1 month in BCCs of patients in the active treatment group, while levels remained unchanged in BCCs of patients in the placebo group.

Dr. Epstein showed several images demonstrating the dramatic improvement in patients with severe disease – sometimes as early as 1-2 months after treatment initiation, and noted that no resistance to treatment developed. Some patients achieved near remission. He cautioned, however, that the drug is associated with toxicity that makes it an unlikely treatment for "the usual patient with one BCC."

One fifth of participants discontinued the study because of toxicity. Common grade 1/2 adverse events were taste loss (in 83% of patients on treatment vs. 8% on placebo), muscle cramps (in 67% vs. 8%), and weight loss (in 50% vs. 8%). Hair loss also was common, which is not surprising, because the targeted pathway is important in hair follicle regeneration, Dr. Epstein explained.

Two grade 3/4 events occurred in patients in the study as well. These included muscle cramps, and a suicide attempt, he said.

While BCC is the most common type of cancer, affecting more than a million people in the United States each year – particularly those of European descent, most develop only one or a small number, and these can be managed with surgery, which currently can cure 98%-99% of cases, he said.

Only a very small number of patients – estimates range from 1/50,000 to 1/250,000 – have heritable conditions such as basal cell nevus syndrome (Gorlin's syndrome), which can be associated with the development of dozens, if not thousands, of lesions that require surgical management, and for these patients, the adverse events might be much more acceptable.

Indeed, for these patients this drug is "a breakthrough – with a capital B," said Dr. Daniel D. Von Hoff, physician-in-chief and distinguished professor at the Translational Genomics Research Institute (TGen) in Phoenix and moderator of an AACR press briefing during which Dr. Epstein discussed his findings.

Additional study is needed to assess long-term adverse events and to determine whether different dosing strategies would improve tolerance, Dr. Epstein said. Genentech has announced that is conducting an expanded patient access study while the company discusses its next steps with the U.S. Food and Drug Administration.

Dr. Epstein had no disclosures.

ORLANDO – A novel hedgehog pathway inhibitor significantly and rapidly reduced the development of new basal cell carcinomas – as well as the size and severity of existing ones – in a randomized, controlled phase II study of 41 patients with basal cell nevus syndrome.

The number of new surgically eligible basal cell carcinomas (BCCs) that developed was 0.07/month in patients receiving active treatment with vismodegib (GDC-0449), compared with 1.74/month in those who received placebo (P less than .0001).

The change from baseline in the aggregate size of existing BCCs was –24 cm in the vismodegib group, compared with –3 cm in the placebo group (P = .006), Dr. Ervin H. Epstein Jr. reported at the annual meeting of the American Association for Cancer Research.

The investigator-initiated study was stopped at an interim analysis because of the highly statistically significant differences between the treatment and placebo groups.

"We have a drug, developed by Genentech, based on the fundamental knowledge that hedgehog signaling is pivotal to all BCCs – including in these patients who carry a defective copy of the gene that inhibits hedgehog signaling," said Dr. Epstein, senior scientist at Children’s Hospital of Oakland (Calif.) Research Institute.

"It is the first drug used in man that replaces the function of the missing gene ... and it actually works," added Dr. Epstein, who helped lay the foundation for the development of vismodegib in 1996 when, along with his colleagues, he identified the site of the mutation that causes basal cell nevus syndrome (the PTCH gene, which encodes a primary inhibitor of the hedgehog signaling pathway).

Patients from three clinical centers were enrolled from September 2009 to January 2011 in the current trial and were randomized 2:1 to receive 150 mg of vismodegib orally once daily, or placebo. Molecular analysis of samples from 23 subjects showed that anti-BCC efficacy was associated with on-target reduction of the hedgehog pathway; Gli1mRNA levels were decreased 200-fold after 1 month in BCCs of patients in the active treatment group, while levels remained unchanged in BCCs of patients in the placebo group.

Dr. Epstein showed several images demonstrating the dramatic improvement in patients with severe disease – sometimes as early as 1-2 months after treatment initiation, and noted that no resistance to treatment developed. Some patients achieved near remission. He cautioned, however, that the drug is associated with toxicity that makes it an unlikely treatment for "the usual patient with one BCC."

One fifth of participants discontinued the study because of toxicity. Common grade 1/2 adverse events were taste loss (in 83% of patients on treatment vs. 8% on placebo), muscle cramps (in 67% vs. 8%), and weight loss (in 50% vs. 8%). Hair loss also was common, which is not surprising, because the targeted pathway is important in hair follicle regeneration, Dr. Epstein explained.

Two grade 3/4 events occurred in patients in the study as well. These included muscle cramps, and a suicide attempt, he said.

While BCC is the most common type of cancer, affecting more than a million people in the United States each year – particularly those of European descent, most develop only one or a small number, and these can be managed with surgery, which currently can cure 98%-99% of cases, he said.

Only a very small number of patients – estimates range from 1/50,000 to 1/250,000 – have heritable conditions such as basal cell nevus syndrome (Gorlin's syndrome), which can be associated with the development of dozens, if not thousands, of lesions that require surgical management, and for these patients, the adverse events might be much more acceptable.

Indeed, for these patients this drug is "a breakthrough – with a capital B," said Dr. Daniel D. Von Hoff, physician-in-chief and distinguished professor at the Translational Genomics Research Institute (TGen) in Phoenix and moderator of an AACR press briefing during which Dr. Epstein discussed his findings.

Additional study is needed to assess long-term adverse events and to determine whether different dosing strategies would improve tolerance, Dr. Epstein said. Genentech has announced that is conducting an expanded patient access study while the company discusses its next steps with the U.S. Food and Drug Administration.

Dr. Epstein had no disclosures.

ORLANDO – A novel hedgehog pathway inhibitor significantly and rapidly reduced the development of new basal cell carcinomas – as well as the size and severity of existing ones – in a randomized, controlled phase II study of 41 patients with basal cell nevus syndrome.

The number of new surgically eligible basal cell carcinomas (BCCs) that developed was 0.07/month in patients receiving active treatment with vismodegib (GDC-0449), compared with 1.74/month in those who received placebo (P less than .0001).

The change from baseline in the aggregate size of existing BCCs was –24 cm in the vismodegib group, compared with –3 cm in the placebo group (P = .006), Dr. Ervin H. Epstein Jr. reported at the annual meeting of the American Association for Cancer Research.

The investigator-initiated study was stopped at an interim analysis because of the highly statistically significant differences between the treatment and placebo groups.

"We have a drug, developed by Genentech, based on the fundamental knowledge that hedgehog signaling is pivotal to all BCCs – including in these patients who carry a defective copy of the gene that inhibits hedgehog signaling," said Dr. Epstein, senior scientist at Children’s Hospital of Oakland (Calif.) Research Institute.

"It is the first drug used in man that replaces the function of the missing gene ... and it actually works," added Dr. Epstein, who helped lay the foundation for the development of vismodegib in 1996 when, along with his colleagues, he identified the site of the mutation that causes basal cell nevus syndrome (the PTCH gene, which encodes a primary inhibitor of the hedgehog signaling pathway).

Patients from three clinical centers were enrolled from September 2009 to January 2011 in the current trial and were randomized 2:1 to receive 150 mg of vismodegib orally once daily, or placebo. Molecular analysis of samples from 23 subjects showed that anti-BCC efficacy was associated with on-target reduction of the hedgehog pathway; Gli1mRNA levels were decreased 200-fold after 1 month in BCCs of patients in the active treatment group, while levels remained unchanged in BCCs of patients in the placebo group.

Dr. Epstein showed several images demonstrating the dramatic improvement in patients with severe disease – sometimes as early as 1-2 months after treatment initiation, and noted that no resistance to treatment developed. Some patients achieved near remission. He cautioned, however, that the drug is associated with toxicity that makes it an unlikely treatment for "the usual patient with one BCC."

One fifth of participants discontinued the study because of toxicity. Common grade 1/2 adverse events were taste loss (in 83% of patients on treatment vs. 8% on placebo), muscle cramps (in 67% vs. 8%), and weight loss (in 50% vs. 8%). Hair loss also was common, which is not surprising, because the targeted pathway is important in hair follicle regeneration, Dr. Epstein explained.

Two grade 3/4 events occurred in patients in the study as well. These included muscle cramps, and a suicide attempt, he said.

While BCC is the most common type of cancer, affecting more than a million people in the United States each year – particularly those of European descent, most develop only one or a small number, and these can be managed with surgery, which currently can cure 98%-99% of cases, he said.

Only a very small number of patients – estimates range from 1/50,000 to 1/250,000 – have heritable conditions such as basal cell nevus syndrome (Gorlin's syndrome), which can be associated with the development of dozens, if not thousands, of lesions that require surgical management, and for these patients, the adverse events might be much more acceptable.

Indeed, for these patients this drug is "a breakthrough – with a capital B," said Dr. Daniel D. Von Hoff, physician-in-chief and distinguished professor at the Translational Genomics Research Institute (TGen) in Phoenix and moderator of an AACR press briefing during which Dr. Epstein discussed his findings.

Additional study is needed to assess long-term adverse events and to determine whether different dosing strategies would improve tolerance, Dr. Epstein said. Genentech has announced that is conducting an expanded patient access study while the company discusses its next steps with the U.S. Food and Drug Administration.

Dr. Epstein had no disclosures.

ORLANDO – The American Association for Cancer Research is rallying support for an outcry against proposed budget cuts by Congress that could cut funding to the National Institutes of Health by up to $1.6 billion.

The AACR is asking its membership of approximately 33,000 cancer physicians and researchers – as well as numerous other groups and the community in general – to voice their concerns on April 6 at 2 p.m. Eastern Time.

Cuts to the National Cancer Institute amounting to about $300 million would drastically affect research grant funding and would stymie the current unprecedented level of progress and innovation in cancer research, Dr. Jon Retzlaff said at a press conference during the AACR’s annual meeting. Dr. Retzlaff is managing director of the AACR’s Office of Science Policy and Government Affairs in Washington, D.C.

The organization is asking that at the designated time, "every single patient, every cancer researcher call or e-mail members of Congress ... so they hear that it is crazy to go down this path," Dr. Retzlaff said.

"We have to make our voice heard in ways we’ve never done before," he said, noting that the AACR has sent numerous alerts to members, and is working with various other groups to enlist their support in this effort.

The $1.6 billion in cuts to the NIH is part of the $61 billion in proposed cuts by the U.S. House of Representatives. The Senate has proposed $33 billion in budget cuts. As Congress grapples with the budget as well as the possibility that the government will be shut down in the coming days if a compromise is not reached, cancer researchers are left wondering if all their current research projects are in jeopardy.

"It’s all about patients – about finding cures, and improving health," Dr. Retzlaff said, adding that there is an important economic development component that must also be considered: The investments in the NIH contribute greatly to economic development and innovation, which are priorities for the country – and which are imperative for its success in the future, he said.

The proposed cuts would likely mean reduced funding for major research programs and for cancer centers across the country, as well as the discontinuation of many grant programs that scientists rely on to pursue their research.

"We completely agree there have to be some tough choices, but ... let’s not put our deficit on the backs of patients who are looking for hope and researchers who think they have wonderful opportunities to make a difference," he said.

ORLANDO – The American Association for Cancer Research is rallying support for an outcry against proposed budget cuts by Congress that could cut funding to the National Institutes of Health by up to $1.6 billion.

The AACR is asking its membership of approximately 33,000 cancer physicians and researchers – as well as numerous other groups and the community in general – to voice their concerns on April 6 at 2 p.m. Eastern Time.

Cuts to the National Cancer Institute amounting to about $300 million would drastically affect research grant funding and would stymie the current unprecedented level of progress and innovation in cancer research, Dr. Jon Retzlaff said at a press conference during the AACR’s annual meeting. Dr. Retzlaff is managing director of the AACR’s Office of Science Policy and Government Affairs in Washington, D.C.

The organization is asking that at the designated time, "every single patient, every cancer researcher call or e-mail members of Congress ... so they hear that it is crazy to go down this path," Dr. Retzlaff said.

"We have to make our voice heard in ways we’ve never done before," he said, noting that the AACR has sent numerous alerts to members, and is working with various other groups to enlist their support in this effort.

The $1.6 billion in cuts to the NIH is part of the $61 billion in proposed cuts by the U.S. House of Representatives. The Senate has proposed $33 billion in budget cuts. As Congress grapples with the budget as well as the possibility that the government will be shut down in the coming days if a compromise is not reached, cancer researchers are left wondering if all their current research projects are in jeopardy.

"It’s all about patients – about finding cures, and improving health," Dr. Retzlaff said, adding that there is an important economic development component that must also be considered: The investments in the NIH contribute greatly to economic development and innovation, which are priorities for the country – and which are imperative for its success in the future, he said.

The proposed cuts would likely mean reduced funding for major research programs and for cancer centers across the country, as well as the discontinuation of many grant programs that scientists rely on to pursue their research.

"We completely agree there have to be some tough choices, but ... let’s not put our deficit on the backs of patients who are looking for hope and researchers who think they have wonderful opportunities to make a difference," he said.

ORLANDO – The American Association for Cancer Research is rallying support for an outcry against proposed budget cuts by Congress that could cut funding to the National Institutes of Health by up to $1.6 billion.

The AACR is asking its membership of approximately 33,000 cancer physicians and researchers – as well as numerous other groups and the community in general – to voice their concerns on April 6 at 2 p.m. Eastern Time.

Cuts to the National Cancer Institute amounting to about $300 million would drastically affect research grant funding and would stymie the current unprecedented level of progress and innovation in cancer research, Dr. Jon Retzlaff said at a press conference during the AACR’s annual meeting. Dr. Retzlaff is managing director of the AACR’s Office of Science Policy and Government Affairs in Washington, D.C.

The organization is asking that at the designated time, "every single patient, every cancer researcher call or e-mail members of Congress ... so they hear that it is crazy to go down this path," Dr. Retzlaff said.

"We have to make our voice heard in ways we’ve never done before," he said, noting that the AACR has sent numerous alerts to members, and is working with various other groups to enlist their support in this effort.

The $1.6 billion in cuts to the NIH is part of the $61 billion in proposed cuts by the U.S. House of Representatives. The Senate has proposed $33 billion in budget cuts. As Congress grapples with the budget as well as the possibility that the government will be shut down in the coming days if a compromise is not reached, cancer researchers are left wondering if all their current research projects are in jeopardy.

"It’s all about patients – about finding cures, and improving health," Dr. Retzlaff said, adding that there is an important economic development component that must also be considered: The investments in the NIH contribute greatly to economic development and innovation, which are priorities for the country – and which are imperative for its success in the future, he said.

The proposed cuts would likely mean reduced funding for major research programs and for cancer centers across the country, as well as the discontinuation of many grant programs that scientists rely on to pursue their research.

"We completely agree there have to be some tough choices, but ... let’s not put our deficit on the backs of patients who are looking for hope and researchers who think they have wonderful opportunities to make a difference," he said.