Damian McNamara

DENVER – Although some studies show a delay in growth among boys taking stimulants for attention-deficit/hyperactivity disorder, a new study appears to clear the medications of postponing pubertal onset.

"Given that growth has been associated with pubertal onset, one might hypothesize that stimulant medication might affect the onset of puberty," Jennifer M. Steffes said at the annual meeting of the Pediatric Academic Societies. "Few data exist, however, as to the potential association."

Ms. Steffes and her colleagues studied a multiethnic cohort of 3,868 boys who were seen at 141 clinical practices in the SSCIB (Secondary Sexual Characteristics in Boys) study. In all, 277 (7%) were taking stimulant medication. Clinicians received standardized training and evaluated genital development, pubic hair growth, and testicular volume for these boys (aged 6-16 years).

There were no significant differences between medicated and nonmedicated participants. Mean onset of genital growth (Tanner stage II) in the stimulant group was 9.84 years vs. 9.85 years in the nonstimulant group. Mean onset of pubic hair (Tanner stage II) in the stimulant group was 11.49 years vs. 11.14 years, and testicular volume of 3 mL or greater was observed in the stimulant group at a median 10.11 years, compared with 9.80 years among those who were not taking stimulant medication.

"Our results suggest that there is no difference in age of pubertal onset between boys taking stimulant medication and their nonmedicated counterparts," Ms. Steffes said.

"For clinicians, our research should be used as reassurance to parents – should stimulant medication be recommended – that the use of these stimulants will not delay pubertal maturation," said Ms. Steffes, an investigator for the PROS (Pediatric Research in Office Settings) research network at the American Academy of Pediatrics.

In addition, there were no significant differences in age of pubertal onset by race or ethnicity. The study included 1,979 white, 963 black, and 926 Hispanic children. Consecutive children and adolescents who were seen for well-child visits in 2005-2010 in 41 states were recruited through practices that participated in PROS, the Academic Pediatric Association’s CORNET (Continuity Research Network), and the NMA PedsNet (National Medical Association’s Pediatric Research Network).

Participants in the stimulant cohort took the medications regularly for 3 consecutive months within the past year. Testicular volume measurements were standardized via a modified Prader orchidometer.

Rigorous clinician training, use of the orchidometer, and inclusion of a broadly-representative geographic sample of children are among the strengths of the study, Ms. Steffes said. Limitations include its cross-sectional design; she noted that a randomized sample and/or longitudinal study design might have been more rigorous. Also, stimulant use was reported from multiple sources (chart review and self- or parent-report).

A meeting attendee asked about the science behind the evidence pointing to delayed growth with stimulant medications. Ms. Steffes deferred to a study coauthor in the audience.

"There [are some] data for a number of psychoactive medications possibly altering growth hormone release," Dr. Steven A. Dowshen said. "The problem with the studies is ... there really is inconsistency in terms of effects [of stimulants] on linear growth, although those [children] who show it tend to show a slowing of linear growth. The commonly accepted end point, though, is that eventually those kids catch up.

"That brings up the possibility, certainly to an endocrinologist, that the effects on growth might be mediated by delayed puberty. So in essence, the drug might be creating a constitutional growth delay," added Dr. Dowshen, a private practice pediatric endocrinologist in Wilmington, Del. "One of the reasons we were interested in looking at the data from PROS was to [to test] that hypothesis. And that wasn’t the case."

Ms. Steffes disclosed that she received a research grant from Pfizer to fund this project.

DENVER – Although some studies show a delay in growth among boys taking stimulants for attention-deficit/hyperactivity disorder, a new study appears to clear the medications of postponing pubertal onset.

"Given that growth has been associated with pubertal onset, one might hypothesize that stimulant medication might affect the onset of puberty," Jennifer M. Steffes said at the annual meeting of the Pediatric Academic Societies. "Few data exist, however, as to the potential association."

Ms. Steffes and her colleagues studied a multiethnic cohort of 3,868 boys who were seen at 141 clinical practices in the SSCIB (Secondary Sexual Characteristics in Boys) study. In all, 277 (7%) were taking stimulant medication. Clinicians received standardized training and evaluated genital development, pubic hair growth, and testicular volume for these boys (aged 6-16 years).

There were no significant differences between medicated and nonmedicated participants. Mean onset of genital growth (Tanner stage II) in the stimulant group was 9.84 years vs. 9.85 years in the nonstimulant group. Mean onset of pubic hair (Tanner stage II) in the stimulant group was 11.49 years vs. 11.14 years, and testicular volume of 3 mL or greater was observed in the stimulant group at a median 10.11 years, compared with 9.80 years among those who were not taking stimulant medication.

"Our results suggest that there is no difference in age of pubertal onset between boys taking stimulant medication and their nonmedicated counterparts," Ms. Steffes said.

"For clinicians, our research should be used as reassurance to parents – should stimulant medication be recommended – that the use of these stimulants will not delay pubertal maturation," said Ms. Steffes, an investigator for the PROS (Pediatric Research in Office Settings) research network at the American Academy of Pediatrics.

In addition, there were no significant differences in age of pubertal onset by race or ethnicity. The study included 1,979 white, 963 black, and 926 Hispanic children. Consecutive children and adolescents who were seen for well-child visits in 2005-2010 in 41 states were recruited through practices that participated in PROS, the Academic Pediatric Association’s CORNET (Continuity Research Network), and the NMA PedsNet (National Medical Association’s Pediatric Research Network).

Participants in the stimulant cohort took the medications regularly for 3 consecutive months within the past year. Testicular volume measurements were standardized via a modified Prader orchidometer.

Rigorous clinician training, use of the orchidometer, and inclusion of a broadly-representative geographic sample of children are among the strengths of the study, Ms. Steffes said. Limitations include its cross-sectional design; she noted that a randomized sample and/or longitudinal study design might have been more rigorous. Also, stimulant use was reported from multiple sources (chart review and self- or parent-report).

A meeting attendee asked about the science behind the evidence pointing to delayed growth with stimulant medications. Ms. Steffes deferred to a study coauthor in the audience.

"There [are some] data for a number of psychoactive medications possibly altering growth hormone release," Dr. Steven A. Dowshen said. "The problem with the studies is ... there really is inconsistency in terms of effects [of stimulants] on linear growth, although those [children] who show it tend to show a slowing of linear growth. The commonly accepted end point, though, is that eventually those kids catch up.

"That brings up the possibility, certainly to an endocrinologist, that the effects on growth might be mediated by delayed puberty. So in essence, the drug might be creating a constitutional growth delay," added Dr. Dowshen, a private practice pediatric endocrinologist in Wilmington, Del. "One of the reasons we were interested in looking at the data from PROS was to [to test] that hypothesis. And that wasn’t the case."

Ms. Steffes disclosed that she received a research grant from Pfizer to fund this project.

DENVER – Although some studies show a delay in growth among boys taking stimulants for attention-deficit/hyperactivity disorder, a new study appears to clear the medications of postponing pubertal onset.

"Given that growth has been associated with pubertal onset, one might hypothesize that stimulant medication might affect the onset of puberty," Jennifer M. Steffes said at the annual meeting of the Pediatric Academic Societies. "Few data exist, however, as to the potential association."

Ms. Steffes and her colleagues studied a multiethnic cohort of 3,868 boys who were seen at 141 clinical practices in the SSCIB (Secondary Sexual Characteristics in Boys) study. In all, 277 (7%) were taking stimulant medication. Clinicians received standardized training and evaluated genital development, pubic hair growth, and testicular volume for these boys (aged 6-16 years).

There were no significant differences between medicated and nonmedicated participants. Mean onset of genital growth (Tanner stage II) in the stimulant group was 9.84 years vs. 9.85 years in the nonstimulant group. Mean onset of pubic hair (Tanner stage II) in the stimulant group was 11.49 years vs. 11.14 years, and testicular volume of 3 mL or greater was observed in the stimulant group at a median 10.11 years, compared with 9.80 years among those who were not taking stimulant medication.

"Our results suggest that there is no difference in age of pubertal onset between boys taking stimulant medication and their nonmedicated counterparts," Ms. Steffes said.

"For clinicians, our research should be used as reassurance to parents – should stimulant medication be recommended – that the use of these stimulants will not delay pubertal maturation," said Ms. Steffes, an investigator for the PROS (Pediatric Research in Office Settings) research network at the American Academy of Pediatrics.

In addition, there were no significant differences in age of pubertal onset by race or ethnicity. The study included 1,979 white, 963 black, and 926 Hispanic children. Consecutive children and adolescents who were seen for well-child visits in 2005-2010 in 41 states were recruited through practices that participated in PROS, the Academic Pediatric Association’s CORNET (Continuity Research Network), and the NMA PedsNet (National Medical Association’s Pediatric Research Network).

Participants in the stimulant cohort took the medications regularly for 3 consecutive months within the past year. Testicular volume measurements were standardized via a modified Prader orchidometer.

Rigorous clinician training, use of the orchidometer, and inclusion of a broadly-representative geographic sample of children are among the strengths of the study, Ms. Steffes said. Limitations include its cross-sectional design; she noted that a randomized sample and/or longitudinal study design might have been more rigorous. Also, stimulant use was reported from multiple sources (chart review and self- or parent-report).

A meeting attendee asked about the science behind the evidence pointing to delayed growth with stimulant medications. Ms. Steffes deferred to a study coauthor in the audience.

"There [are some] data for a number of psychoactive medications possibly altering growth hormone release," Dr. Steven A. Dowshen said. "The problem with the studies is ... there really is inconsistency in terms of effects [of stimulants] on linear growth, although those [children] who show it tend to show a slowing of linear growth. The commonly accepted end point, though, is that eventually those kids catch up.

"That brings up the possibility, certainly to an endocrinologist, that the effects on growth might be mediated by delayed puberty. So in essence, the drug might be creating a constitutional growth delay," added Dr. Dowshen, a private practice pediatric endocrinologist in Wilmington, Del. "One of the reasons we were interested in looking at the data from PROS was to [to test] that hypothesis. And that wasn’t the case."

Ms. Steffes disclosed that she received a research grant from Pfizer to fund this project.

NAPLES, FLA. – When it comes to cerebral revascularization of octogenarian patients, carotid endarterectomy may be the treatment of choice unless compelling evidence points to carotid artery angioplasty and stenting, according to Dr. Caron B. Rockman.

She and her colleagues compared in-hospital perioperative stroke and death rates between these procedures among older and younger patients in a study of 54,658 patients who underwent carotid revascularization in 2004 and 2005 in the Healthcare Cost and Utilization Project National Inpatient Sample database.

Octogenarians have been excluded from many previous trials of carotid endarterectomy (CEA), said Dr. Rockman, who is on the surgery faculty and is director of clinical research in the division of vascular surgery at New York University. However, patients aged 80 years and older accounted for 10,820 (or nearly 20%) of the patients.

"Advanced age is relevant when treatment of asymptomatic severe cerebrovascular disease is considered," Dr. Rockman said.

The prevalence of preoperative symptoms was essentially the same in the octogenarian (5.4%) and younger (5.2%) groups.

Dr. Rockman

"I am floored that 95% of octogenarians who get intervention are asymptomatic," said study discussant Dr. Samuel R. Money, chair of the department of surgery at the Mayo Clinic in Scottsdale, Ariz., at the meeting. Because the Nationwide Inpatient Sample data represent about 20% of U.S. hospital discharges, he estimated that approximately 50,000 people aged 80 years and older undergo these procedures each year in the United States. Dr. Money asked if such high utilization is justified in an era with medical management options such as statins. He estimated that these interventions cost $75 million to $1 billion annually.

"I agree with you," Dr. Rockman replied. "This is astounding."

She theorized that people who enter the ICD-9 procedural codes might incorrectly classify some patients as asymptomatic. "I hope people coding these are missing some of the symptomatology. It can be difficult to pick up [symptoms] from patient records, so I hope it’s not as alarming as it seems."

"However, I do think there is a role for endarterectomy or CAS in an elderly patient with severe disease," Dr. Rockman added.

The results of the study showed that "octogenarians had essentially equivalent rates of periprocedural stroke [1.1% in both groups], but slightly higher rates of in-hospital mortality than their younger counterparts," she said.

A meeting attendee asked why stroke outcomes were not significantly worse among octogenarians.

"I don’t know why I did not see it," said Dr. Rockman, noting that a separate meta-analysis of CAS studies found that the relative risk for periprocedural stroke in octogenarians fell above an acceptable rate of 3% in seven of eight studies (J. Am. Coll. Surg. 2009;208:1124-31). "It could be [because] this database is in-hospital only, so even if stroke occurs the day after discharge, it’s not included in this national database."

In a separate analysis of only octogenarian patients, the periprocedural stroke rate was significantly higher among those who underwent CAS than had CEA (2.2% vs. 1.1%). The rate also was consistently higher for both asymptomatic (1.9% vs. 0.9%) and symptomatic (5.2% vs. 2.3%) patients.

Because asymptomatic patients account for the largest proportion of the octogenarians, "this is arguably the most clinically important group," Dr. Rockman said.

Previous research has raised concerns about higher stroke risks associated with CAS vs. CEA in older patients (J. Vasc. Surg. 2004;40:1106-11; Catheter Cardiovasc. Interv. 2007;70:1025-33). Yet in the current study, a significantly greater percentage of asymptomatic octogenarians (10.1%) underwent CAS than did asymptomatic younger patients (5.7%).

Even though the in-hospital death rate was statistically significantly higher among octogenarians than among younger patients (1% vs. 0.6%), Dr. Rockman said that the small difference was, in her mind, "not clinically significant."

However, the story was different among symptomatic patients. The in-hospital death rate was 4.1% in the older group vs. 2.6% in younger patients. "I think this is concerning in both age categories," Dr. Rockman said. The investigators did not have access to cause-of-death information in the database.

Dr. Money asked about the causes of death in the study. "The cause of death is not in the database," Dr. Rockman responded, adding that only "in-hospital mortality" is noted.

"There are limits and good points about using a national database," Dr. Rockman said. She noted that procedures in the discharge administrative database "are really coded for the purpose of hospital reimbursement," but the large number of cases it contains may reflect "real world" practice better than do other types of studies.

Dr. Rockman said that she had no relevant disclosures.

NAPLES, FLA. – When it comes to cerebral revascularization of octogenarian patients, carotid endarterectomy may be the treatment of choice unless compelling evidence points to carotid artery angioplasty and stenting, according to Dr. Caron B. Rockman.

She and her colleagues compared in-hospital perioperative stroke and death rates between these procedures among older and younger patients in a study of 54,658 patients who underwent carotid revascularization in 2004 and 2005 in the Healthcare Cost and Utilization Project National Inpatient Sample database.

Octogenarians have been excluded from many previous trials of carotid endarterectomy (CEA), said Dr. Rockman, who is on the surgery faculty and is director of clinical research in the division of vascular surgery at New York University. However, patients aged 80 years and older accounted for 10,820 (or nearly 20%) of the patients.

"Advanced age is relevant when treatment of asymptomatic severe cerebrovascular disease is considered," Dr. Rockman said.

The prevalence of preoperative symptoms was essentially the same in the octogenarian (5.4%) and younger (5.2%) groups.

Dr. Rockman

"I am floored that 95% of octogenarians who get intervention are asymptomatic," said study discussant Dr. Samuel R. Money, chair of the department of surgery at the Mayo Clinic in Scottsdale, Ariz., at the meeting. Because the Nationwide Inpatient Sample data represent about 20% of U.S. hospital discharges, he estimated that approximately 50,000 people aged 80 years and older undergo these procedures each year in the United States. Dr. Money asked if such high utilization is justified in an era with medical management options such as statins. He estimated that these interventions cost $75 million to $1 billion annually.

"I agree with you," Dr. Rockman replied. "This is astounding."

She theorized that people who enter the ICD-9 procedural codes might incorrectly classify some patients as asymptomatic. "I hope people coding these are missing some of the symptomatology. It can be difficult to pick up [symptoms] from patient records, so I hope it’s not as alarming as it seems."

"However, I do think there is a role for endarterectomy or CAS in an elderly patient with severe disease," Dr. Rockman added.

The results of the study showed that "octogenarians had essentially equivalent rates of periprocedural stroke [1.1% in both groups], but slightly higher rates of in-hospital mortality than their younger counterparts," she said.

A meeting attendee asked why stroke outcomes were not significantly worse among octogenarians.

"I don’t know why I did not see it," said Dr. Rockman, noting that a separate meta-analysis of CAS studies found that the relative risk for periprocedural stroke in octogenarians fell above an acceptable rate of 3% in seven of eight studies (J. Am. Coll. Surg. 2009;208:1124-31). "It could be [because] this database is in-hospital only, so even if stroke occurs the day after discharge, it’s not included in this national database."

In a separate analysis of only octogenarian patients, the periprocedural stroke rate was significantly higher among those who underwent CAS than had CEA (2.2% vs. 1.1%). The rate also was consistently higher for both asymptomatic (1.9% vs. 0.9%) and symptomatic (5.2% vs. 2.3%) patients.

Because asymptomatic patients account for the largest proportion of the octogenarians, "this is arguably the most clinically important group," Dr. Rockman said.

Previous research has raised concerns about higher stroke risks associated with CAS vs. CEA in older patients (J. Vasc. Surg. 2004;40:1106-11; Catheter Cardiovasc. Interv. 2007;70:1025-33). Yet in the current study, a significantly greater percentage of asymptomatic octogenarians (10.1%) underwent CAS than did asymptomatic younger patients (5.7%).

Even though the in-hospital death rate was statistically significantly higher among octogenarians than among younger patients (1% vs. 0.6%), Dr. Rockman said that the small difference was, in her mind, "not clinically significant."

However, the story was different among symptomatic patients. The in-hospital death rate was 4.1% in the older group vs. 2.6% in younger patients. "I think this is concerning in both age categories," Dr. Rockman said. The investigators did not have access to cause-of-death information in the database.

Dr. Money asked about the causes of death in the study. "The cause of death is not in the database," Dr. Rockman responded, adding that only "in-hospital mortality" is noted.

"There are limits and good points about using a national database," Dr. Rockman said. She noted that procedures in the discharge administrative database "are really coded for the purpose of hospital reimbursement," but the large number of cases it contains may reflect "real world" practice better than do other types of studies.

Dr. Rockman said that she had no relevant disclosures.

NAPLES, FLA. – When it comes to cerebral revascularization of octogenarian patients, carotid endarterectomy may be the treatment of choice unless compelling evidence points to carotid artery angioplasty and stenting, according to Dr. Caron B. Rockman.

She and her colleagues compared in-hospital perioperative stroke and death rates between these procedures among older and younger patients in a study of 54,658 patients who underwent carotid revascularization in 2004 and 2005 in the Healthcare Cost and Utilization Project National Inpatient Sample database.

Octogenarians have been excluded from many previous trials of carotid endarterectomy (CEA), said Dr. Rockman, who is on the surgery faculty and is director of clinical research in the division of vascular surgery at New York University. However, patients aged 80 years and older accounted for 10,820 (or nearly 20%) of the patients.

"Advanced age is relevant when treatment of asymptomatic severe cerebrovascular disease is considered," Dr. Rockman said.

The prevalence of preoperative symptoms was essentially the same in the octogenarian (5.4%) and younger (5.2%) groups.

Dr. Rockman

"I am floored that 95% of octogenarians who get intervention are asymptomatic," said study discussant Dr. Samuel R. Money, chair of the department of surgery at the Mayo Clinic in Scottsdale, Ariz., at the meeting. Because the Nationwide Inpatient Sample data represent about 20% of U.S. hospital discharges, he estimated that approximately 50,000 people aged 80 years and older undergo these procedures each year in the United States. Dr. Money asked if such high utilization is justified in an era with medical management options such as statins. He estimated that these interventions cost $75 million to $1 billion annually.

"I agree with you," Dr. Rockman replied. "This is astounding."

She theorized that people who enter the ICD-9 procedural codes might incorrectly classify some patients as asymptomatic. "I hope people coding these are missing some of the symptomatology. It can be difficult to pick up [symptoms] from patient records, so I hope it’s not as alarming as it seems."

"However, I do think there is a role for endarterectomy or CAS in an elderly patient with severe disease," Dr. Rockman added.

The results of the study showed that "octogenarians had essentially equivalent rates of periprocedural stroke [1.1% in both groups], but slightly higher rates of in-hospital mortality than their younger counterparts," she said.

A meeting attendee asked why stroke outcomes were not significantly worse among octogenarians.

"I don’t know why I did not see it," said Dr. Rockman, noting that a separate meta-analysis of CAS studies found that the relative risk for periprocedural stroke in octogenarians fell above an acceptable rate of 3% in seven of eight studies (J. Am. Coll. Surg. 2009;208:1124-31). "It could be [because] this database is in-hospital only, so even if stroke occurs the day after discharge, it’s not included in this national database."

In a separate analysis of only octogenarian patients, the periprocedural stroke rate was significantly higher among those who underwent CAS than had CEA (2.2% vs. 1.1%). The rate also was consistently higher for both asymptomatic (1.9% vs. 0.9%) and symptomatic (5.2% vs. 2.3%) patients.

Because asymptomatic patients account for the largest proportion of the octogenarians, "this is arguably the most clinically important group," Dr. Rockman said.

Previous research has raised concerns about higher stroke risks associated with CAS vs. CEA in older patients (J. Vasc. Surg. 2004;40:1106-11; Catheter Cardiovasc. Interv. 2007;70:1025-33). Yet in the current study, a significantly greater percentage of asymptomatic octogenarians (10.1%) underwent CAS than did asymptomatic younger patients (5.7%).

Even though the in-hospital death rate was statistically significantly higher among octogenarians than among younger patients (1% vs. 0.6%), Dr. Rockman said that the small difference was, in her mind, "not clinically significant."

However, the story was different among symptomatic patients. The in-hospital death rate was 4.1% in the older group vs. 2.6% in younger patients. "I think this is concerning in both age categories," Dr. Rockman said. The investigators did not have access to cause-of-death information in the database.

Dr. Money asked about the causes of death in the study. "The cause of death is not in the database," Dr. Rockman responded, adding that only "in-hospital mortality" is noted.

"There are limits and good points about using a national database," Dr. Rockman said. She noted that procedures in the discharge administrative database "are really coded for the purpose of hospital reimbursement," but the large number of cases it contains may reflect "real world" practice better than do other types of studies.

Dr. Rockman said that she had no relevant disclosures.

DENVER – When you prescribe a long-acting beta-agonist for a child with asthma, you may want to consider adding an inhaled corticosteroid as well, according to a meta-analysis conducted by Food and Drug Administration investigators.

"Overall, there was an increased risk of asthma-related hospitalizations, intubation, or death to asthmatics of all ages using long-acting beta-agonists [LABAs]," Dr. Ann W. McMahon said at the annual meeting of the Pediatric Academic Societies.

Dr. McMahon and her colleagues also found an age effect as well, with asthmatics aged 4-11 years at greater risk, compared with older patients. "Children are at increased risk, primarily of hospitalization, from asthma with LABA use compared to the overall population."

The elevated overall and age-related risks are no longer statistically significant, however, when patients are prescribed an inhaled corticosteroid (ICS) along with a LABA as part of a study protocol, Dr. McMahon said.

"Although further study is indicated, simultaneous use of inhaled corticosteroids and LABAs may mitigate this risk in children," said Dr. McMahon, deputy director of the division of pharmacovigilance, office of surveillance and epidemiology, FDA.

In a previous meta-analysis, LABA use was associated with a higher overall risk for adverse outcomes, a risk difference estimate of 2.80 for an asthma composite index of asthma-related hospitalizations, intubations, and deaths. In a 2008 meta-analysis that included 60,954 patients of all ages from 110 trials, Mark Levenson, Ph.D., one of Dr. McMahon’s FDA colleagues, found the highest risk associated with LABA therapy was among those aged 4-11 years, who had a risk difference estimate of 14.83/1,000 participants.

Dr. McMahon presented a secondary analysis of the 2008 meta-analysis in which she and her associates assessed a subset of patients assigned an ICS as part of their study regimen. Using a forest plot analysis, they compared 7,862 patients also treated with a LABA versus 7,330 who did not receive a LABA.

"What we see here is no overall risk for this subset of patients and no particular age trend either," Dr. McMahon said. The overall risk difference was 0.2/1,000 patients.

"I just want to caution that this is a smaller group of patients. So whether we can conclude this is definitive, I would say probably not," Dr. McMahon said. "But it is very intriguing that this subgroup that took assigned inhaled corticosteroids really did not have an age effect or an overall increased risk."

In contrast, when all users and nonusers of inhaled corticosteroids were combined, overall risk associated with LABA use was 6.3 additional adverse events per 1,000 patients.

Another analysis of the data looked at all patients who took some concomitant ICS therapy (those intentionally prescribed an ICS and those noted to be taking an ICS at baseline). This analysis "looks very similar, with a slight increased risk overall" of 6.1 events per 1,000 patients, Dr. McMahon said.

Age again made a difference, with a point estimate risk of 19.8/1,000 participants for those aged 4-11 years, a statistically significant higher risk compared with that of patients aged 12-17 years, 18-64 years, and 65 years and older.

"Children are at increased risk primarily of [asthma-related] hospitalization," Dr. McMahon said. Data on intubations and deaths were insufficient to calculate these outcomes among children, she added.

Dr. McMahon’s findings concur with those of other published studies. For example the Salmeterol Multicenter Asthma Research Trial (SMART) and the Serevent Nationwide Surveillance (SNS) study in the United Kingdom "both gave similar results to the extent that there was a three- to fourfold increase in risk of serious asthma outcomes such as asthma-related death and intubation" associated with LABA use (Chest 2006;129:15-26; BMJ 1993;306:1034-7). However, these trials did not include children younger than 12 years and did not include enough adolescents for investigators to be able to analyze those data separately, she added.

Three of the LABAs approved for asthma treatment in the United States are combined LABA/ICS inhalers: Advair (salmeterol, fluticasone); Dulera (formoterol, mometasone); and Symbicort (formoterol, budesonide). Other approved LABA products that do not contain an ICS are Brovana (arformoterol), Foradil (formoterol), and Serevent (salmeterol).

Dr. McMahon said she had no relevant financial disclosures.

DENVER – When you prescribe a long-acting beta-agonist for a child with asthma, you may want to consider adding an inhaled corticosteroid as well, according to a meta-analysis conducted by Food and Drug Administration investigators.

"Overall, there was an increased risk of asthma-related hospitalizations, intubation, or death to asthmatics of all ages using long-acting beta-agonists [LABAs]," Dr. Ann W. McMahon said at the annual meeting of the Pediatric Academic Societies.

Dr. McMahon and her colleagues also found an age effect as well, with asthmatics aged 4-11 years at greater risk, compared with older patients. "Children are at increased risk, primarily of hospitalization, from asthma with LABA use compared to the overall population."

The elevated overall and age-related risks are no longer statistically significant, however, when patients are prescribed an inhaled corticosteroid (ICS) along with a LABA as part of a study protocol, Dr. McMahon said.

"Although further study is indicated, simultaneous use of inhaled corticosteroids and LABAs may mitigate this risk in children," said Dr. McMahon, deputy director of the division of pharmacovigilance, office of surveillance and epidemiology, FDA.

In a previous meta-analysis, LABA use was associated with a higher overall risk for adverse outcomes, a risk difference estimate of 2.80 for an asthma composite index of asthma-related hospitalizations, intubations, and deaths. In a 2008 meta-analysis that included 60,954 patients of all ages from 110 trials, Mark Levenson, Ph.D., one of Dr. McMahon’s FDA colleagues, found the highest risk associated with LABA therapy was among those aged 4-11 years, who had a risk difference estimate of 14.83/1,000 participants.

Dr. McMahon presented a secondary analysis of the 2008 meta-analysis in which she and her associates assessed a subset of patients assigned an ICS as part of their study regimen. Using a forest plot analysis, they compared 7,862 patients also treated with a LABA versus 7,330 who did not receive a LABA.

"What we see here is no overall risk for this subset of patients and no particular age trend either," Dr. McMahon said. The overall risk difference was 0.2/1,000 patients.

"I just want to caution that this is a smaller group of patients. So whether we can conclude this is definitive, I would say probably not," Dr. McMahon said. "But it is very intriguing that this subgroup that took assigned inhaled corticosteroids really did not have an age effect or an overall increased risk."

In contrast, when all users and nonusers of inhaled corticosteroids were combined, overall risk associated with LABA use was 6.3 additional adverse events per 1,000 patients.

Another analysis of the data looked at all patients who took some concomitant ICS therapy (those intentionally prescribed an ICS and those noted to be taking an ICS at baseline). This analysis "looks very similar, with a slight increased risk overall" of 6.1 events per 1,000 patients, Dr. McMahon said.

Age again made a difference, with a point estimate risk of 19.8/1,000 participants for those aged 4-11 years, a statistically significant higher risk compared with that of patients aged 12-17 years, 18-64 years, and 65 years and older.

"Children are at increased risk primarily of [asthma-related] hospitalization," Dr. McMahon said. Data on intubations and deaths were insufficient to calculate these outcomes among children, she added.

Dr. McMahon’s findings concur with those of other published studies. For example the Salmeterol Multicenter Asthma Research Trial (SMART) and the Serevent Nationwide Surveillance (SNS) study in the United Kingdom "both gave similar results to the extent that there was a three- to fourfold increase in risk of serious asthma outcomes such as asthma-related death and intubation" associated with LABA use (Chest 2006;129:15-26; BMJ 1993;306:1034-7). However, these trials did not include children younger than 12 years and did not include enough adolescents for investigators to be able to analyze those data separately, she added.

Three of the LABAs approved for asthma treatment in the United States are combined LABA/ICS inhalers: Advair (salmeterol, fluticasone); Dulera (formoterol, mometasone); and Symbicort (formoterol, budesonide). Other approved LABA products that do not contain an ICS are Brovana (arformoterol), Foradil (formoterol), and Serevent (salmeterol).

Dr. McMahon said she had no relevant financial disclosures.

DENVER – When you prescribe a long-acting beta-agonist for a child with asthma, you may want to consider adding an inhaled corticosteroid as well, according to a meta-analysis conducted by Food and Drug Administration investigators.

"Overall, there was an increased risk of asthma-related hospitalizations, intubation, or death to asthmatics of all ages using long-acting beta-agonists [LABAs]," Dr. Ann W. McMahon said at the annual meeting of the Pediatric Academic Societies.

Dr. McMahon and her colleagues also found an age effect as well, with asthmatics aged 4-11 years at greater risk, compared with older patients. "Children are at increased risk, primarily of hospitalization, from asthma with LABA use compared to the overall population."

The elevated overall and age-related risks are no longer statistically significant, however, when patients are prescribed an inhaled corticosteroid (ICS) along with a LABA as part of a study protocol, Dr. McMahon said.

"Although further study is indicated, simultaneous use of inhaled corticosteroids and LABAs may mitigate this risk in children," said Dr. McMahon, deputy director of the division of pharmacovigilance, office of surveillance and epidemiology, FDA.

In a previous meta-analysis, LABA use was associated with a higher overall risk for adverse outcomes, a risk difference estimate of 2.80 for an asthma composite index of asthma-related hospitalizations, intubations, and deaths. In a 2008 meta-analysis that included 60,954 patients of all ages from 110 trials, Mark Levenson, Ph.D., one of Dr. McMahon’s FDA colleagues, found the highest risk associated with LABA therapy was among those aged 4-11 years, who had a risk difference estimate of 14.83/1,000 participants.

Dr. McMahon presented a secondary analysis of the 2008 meta-analysis in which she and her associates assessed a subset of patients assigned an ICS as part of their study regimen. Using a forest plot analysis, they compared 7,862 patients also treated with a LABA versus 7,330 who did not receive a LABA.

"What we see here is no overall risk for this subset of patients and no particular age trend either," Dr. McMahon said. The overall risk difference was 0.2/1,000 patients.

"I just want to caution that this is a smaller group of patients. So whether we can conclude this is definitive, I would say probably not," Dr. McMahon said. "But it is very intriguing that this subgroup that took assigned inhaled corticosteroids really did not have an age effect or an overall increased risk."

In contrast, when all users and nonusers of inhaled corticosteroids were combined, overall risk associated with LABA use was 6.3 additional adverse events per 1,000 patients.

Another analysis of the data looked at all patients who took some concomitant ICS therapy (those intentionally prescribed an ICS and those noted to be taking an ICS at baseline). This analysis "looks very similar, with a slight increased risk overall" of 6.1 events per 1,000 patients, Dr. McMahon said.

Age again made a difference, with a point estimate risk of 19.8/1,000 participants for those aged 4-11 years, a statistically significant higher risk compared with that of patients aged 12-17 years, 18-64 years, and 65 years and older.

"Children are at increased risk primarily of [asthma-related] hospitalization," Dr. McMahon said. Data on intubations and deaths were insufficient to calculate these outcomes among children, she added.

Dr. McMahon’s findings concur with those of other published studies. For example the Salmeterol Multicenter Asthma Research Trial (SMART) and the Serevent Nationwide Surveillance (SNS) study in the United Kingdom "both gave similar results to the extent that there was a three- to fourfold increase in risk of serious asthma outcomes such as asthma-related death and intubation" associated with LABA use (Chest 2006;129:15-26; BMJ 1993;306:1034-7). However, these trials did not include children younger than 12 years and did not include enough adolescents for investigators to be able to analyze those data separately, she added.

Three of the LABAs approved for asthma treatment in the United States are combined LABA/ICS inhalers: Advair (salmeterol, fluticasone); Dulera (formoterol, mometasone); and Symbicort (formoterol, budesonide). Other approved LABA products that do not contain an ICS are Brovana (arformoterol), Foradil (formoterol), and Serevent (salmeterol).

Dr. McMahon said she had no relevant financial disclosures.

HONOLULU – Women whose depression improved during a 1-year treatment trial for metastatic breast cancer survived a median 2 years longer than women whose depression worsened, according to a long-term follow-up study.

"Our main finding is that the course of depression over the initial year of the study can be used to predict survival up to 14 years later," Dr. David Spiegel said at the annual meeting of the American Psychiatric Association.

Therefore, screen patients with breast cancer for depression. Also, do not dismiss depressive symptoms as merely a normal component of a cancer diagnosis or treatment, he said. Another clinical implication is that psychotherapy intervention can make a significant positive difference. "There are ways of facing and living with this disease that may help patients to live longer as well as better.

"This is a tremendous opportunity for psychiatry to be a part of the mission that is now mandated at cancer centers – to help cancer patients live better with their illness," said Dr. Spiegel, director of the center on stress and health at Stanford (Calif.) University.

One-quarter of cancer patients meet the criteria for depression, Dr. Spiegel said. "The more serious your medical illness, the more likely you are to be depressed. It’s 3% of the general population, 6% of outpatients, and 12% of medical inpatients – 1 out of 9 is depressed. But we often overlook the diagnosis; we misattribute the sadness to the prognosis of the disease; the disinterest in eating to the side effects of chemotherapy; the sleep disturbance to the worry about the illness.

"All of these can be signs of depression," he said.

Therefore, more awareness of an association between depression and a cancer prognosis is warranted. "Somehow people get the idea that if you have depression, it can worsen your prognosis with heart disease. But they have a much more difficult time understanding that ... depression is just as lethal a comorbid factor with cancer," Dr. Spiegel said.

He and his associates found median survival was 53.6 months for women whose baseline scores on the Center for Epidemiologic Studies–Depression Scale (CES-D) decreased over a period of 12 months, compared with a median 25.1-month survival for women whose CES-D scores increased. This 28.5-month difference in median survival was statistically significant.

The cohort included 101 women of 125 randomized to supportive-expressive group therapy or a control group with education materials who completed the CES-D scale at baseline and at three assessment points during the year (J. Clin. Oncol. 2011;29:413-20).

Only improvement in depression ratings, not treatment vs. no treatment, was associated with longer survival in this secondary analysis of the original study (Cancer 2007;110:1130-8).

Depression was an independent, long-term predictor of mortality. The researchers controlled for all the usual prognostic variables, including estrogen receptor and progesterone receptor status, disease-free interval, and age at diagnosis.

There is other evidence that psychotherapy can significantly reduce depressive symptoms in patients with advanced cancer, said Dr. Spiegel. For example, a Cochrane database analysis showed such a benefit in patients with incurable cancer who received supportive psychotherapy, cognitive-behavioral therapy, or problem-solving psychotherapy (Cochrane Database Syst. Rev. 2008;CD005537).

Dr. Spiegel said the psychotherapy in his study reduced patients’ tendency to suppress emotion. "So this outcome is not about distress; it’s about their management of distress. This, it turned out, mediated the reduction in depression and anxiety.

"We encourage people to face their fears of dying and death. We call it ‘detoxifying dying,’ " Dr. Spiegel said. Patients learn to face death, to reorder priorities, and to communicate better with families and physicians.

More support for an association between less depression and better outcomes for cancer patients emerged from a study of 107 patients with metastatic non–small cell lung cancer (N. Engl. J. Med. 2010:363:733-42). Fewer patients who received early palliative therapy reported depressive symptoms, 16%, vs. 38% of patients assigned to standard care. In addition, the early palliative care group had a longer median survival (11.6 months vs. 8.9 months). Both differences were statistically significant.

However, there is still no consensus in the literature about psychosocial intervention and cancer survival. Seven randomized trials now show a survival benefit, and six show no difference, Dr. Spiegel said. "The results are not random; I’m glad to say that no studies show that psychotherapy kills patients."

Although further research is warranted, Dr. Spiegel said, "it is now reasonable to raise the possibility that treating depression and other psychiatric aspects of cancer may not only help people live better, but may help them live longer."

The study was sponsored by the National Institute of Mental Health, the National Cancer Institute, and the National Institute on Aging. Dr. Spiegel is an editorial advisory board member to this news organization. He reported no other relevant financial disclosures.

HONOLULU – Women whose depression improved during a 1-year treatment trial for metastatic breast cancer survived a median 2 years longer than women whose depression worsened, according to a long-term follow-up study.

"Our main finding is that the course of depression over the initial year of the study can be used to predict survival up to 14 years later," Dr. David Spiegel said at the annual meeting of the American Psychiatric Association.

Therefore, screen patients with breast cancer for depression. Also, do not dismiss depressive symptoms as merely a normal component of a cancer diagnosis or treatment, he said. Another clinical implication is that psychotherapy intervention can make a significant positive difference. "There are ways of facing and living with this disease that may help patients to live longer as well as better.

"This is a tremendous opportunity for psychiatry to be a part of the mission that is now mandated at cancer centers – to help cancer patients live better with their illness," said Dr. Spiegel, director of the center on stress and health at Stanford (Calif.) University.

One-quarter of cancer patients meet the criteria for depression, Dr. Spiegel said. "The more serious your medical illness, the more likely you are to be depressed. It’s 3% of the general population, 6% of outpatients, and 12% of medical inpatients – 1 out of 9 is depressed. But we often overlook the diagnosis; we misattribute the sadness to the prognosis of the disease; the disinterest in eating to the side effects of chemotherapy; the sleep disturbance to the worry about the illness.

"All of these can be signs of depression," he said.

Therefore, more awareness of an association between depression and a cancer prognosis is warranted. "Somehow people get the idea that if you have depression, it can worsen your prognosis with heart disease. But they have a much more difficult time understanding that ... depression is just as lethal a comorbid factor with cancer," Dr. Spiegel said.

He and his associates found median survival was 53.6 months for women whose baseline scores on the Center for Epidemiologic Studies–Depression Scale (CES-D) decreased over a period of 12 months, compared with a median 25.1-month survival for women whose CES-D scores increased. This 28.5-month difference in median survival was statistically significant.

The cohort included 101 women of 125 randomized to supportive-expressive group therapy or a control group with education materials who completed the CES-D scale at baseline and at three assessment points during the year (J. Clin. Oncol. 2011;29:413-20).

Only improvement in depression ratings, not treatment vs. no treatment, was associated with longer survival in this secondary analysis of the original study (Cancer 2007;110:1130-8).

Depression was an independent, long-term predictor of mortality. The researchers controlled for all the usual prognostic variables, including estrogen receptor and progesterone receptor status, disease-free interval, and age at diagnosis.

There is other evidence that psychotherapy can significantly reduce depressive symptoms in patients with advanced cancer, said Dr. Spiegel. For example, a Cochrane database analysis showed such a benefit in patients with incurable cancer who received supportive psychotherapy, cognitive-behavioral therapy, or problem-solving psychotherapy (Cochrane Database Syst. Rev. 2008;CD005537).

Dr. Spiegel said the psychotherapy in his study reduced patients’ tendency to suppress emotion. "So this outcome is not about distress; it’s about their management of distress. This, it turned out, mediated the reduction in depression and anxiety.

"We encourage people to face their fears of dying and death. We call it ‘detoxifying dying,’ " Dr. Spiegel said. Patients learn to face death, to reorder priorities, and to communicate better with families and physicians.

More support for an association between less depression and better outcomes for cancer patients emerged from a study of 107 patients with metastatic non–small cell lung cancer (N. Engl. J. Med. 2010:363:733-42). Fewer patients who received early palliative therapy reported depressive symptoms, 16%, vs. 38% of patients assigned to standard care. In addition, the early palliative care group had a longer median survival (11.6 months vs. 8.9 months). Both differences were statistically significant.

However, there is still no consensus in the literature about psychosocial intervention and cancer survival. Seven randomized trials now show a survival benefit, and six show no difference, Dr. Spiegel said. "The results are not random; I’m glad to say that no studies show that psychotherapy kills patients."

Although further research is warranted, Dr. Spiegel said, "it is now reasonable to raise the possibility that treating depression and other psychiatric aspects of cancer may not only help people live better, but may help them live longer."

The study was sponsored by the National Institute of Mental Health, the National Cancer Institute, and the National Institute on Aging. Dr. Spiegel is an editorial advisory board member to this news organization. He reported no other relevant financial disclosures.

HONOLULU – Women whose depression improved during a 1-year treatment trial for metastatic breast cancer survived a median 2 years longer than women whose depression worsened, according to a long-term follow-up study.

"Our main finding is that the course of depression over the initial year of the study can be used to predict survival up to 14 years later," Dr. David Spiegel said at the annual meeting of the American Psychiatric Association.

Therefore, screen patients with breast cancer for depression. Also, do not dismiss depressive symptoms as merely a normal component of a cancer diagnosis or treatment, he said. Another clinical implication is that psychotherapy intervention can make a significant positive difference. "There are ways of facing and living with this disease that may help patients to live longer as well as better.

"This is a tremendous opportunity for psychiatry to be a part of the mission that is now mandated at cancer centers – to help cancer patients live better with their illness," said Dr. Spiegel, director of the center on stress and health at Stanford (Calif.) University.

One-quarter of cancer patients meet the criteria for depression, Dr. Spiegel said. "The more serious your medical illness, the more likely you are to be depressed. It’s 3% of the general population, 6% of outpatients, and 12% of medical inpatients – 1 out of 9 is depressed. But we often overlook the diagnosis; we misattribute the sadness to the prognosis of the disease; the disinterest in eating to the side effects of chemotherapy; the sleep disturbance to the worry about the illness.

"All of these can be signs of depression," he said.

Therefore, more awareness of an association between depression and a cancer prognosis is warranted. "Somehow people get the idea that if you have depression, it can worsen your prognosis with heart disease. But they have a much more difficult time understanding that ... depression is just as lethal a comorbid factor with cancer," Dr. Spiegel said.

He and his associates found median survival was 53.6 months for women whose baseline scores on the Center for Epidemiologic Studies–Depression Scale (CES-D) decreased over a period of 12 months, compared with a median 25.1-month survival for women whose CES-D scores increased. This 28.5-month difference in median survival was statistically significant.

The cohort included 101 women of 125 randomized to supportive-expressive group therapy or a control group with education materials who completed the CES-D scale at baseline and at three assessment points during the year (J. Clin. Oncol. 2011;29:413-20).

Only improvement in depression ratings, not treatment vs. no treatment, was associated with longer survival in this secondary analysis of the original study (Cancer 2007;110:1130-8).

Depression was an independent, long-term predictor of mortality. The researchers controlled for all the usual prognostic variables, including estrogen receptor and progesterone receptor status, disease-free interval, and age at diagnosis.

There is other evidence that psychotherapy can significantly reduce depressive symptoms in patients with advanced cancer, said Dr. Spiegel. For example, a Cochrane database analysis showed such a benefit in patients with incurable cancer who received supportive psychotherapy, cognitive-behavioral therapy, or problem-solving psychotherapy (Cochrane Database Syst. Rev. 2008;CD005537).

Dr. Spiegel said the psychotherapy in his study reduced patients’ tendency to suppress emotion. "So this outcome is not about distress; it’s about their management of distress. This, it turned out, mediated the reduction in depression and anxiety.

"We encourage people to face their fears of dying and death. We call it ‘detoxifying dying,’ " Dr. Spiegel said. Patients learn to face death, to reorder priorities, and to communicate better with families and physicians.

More support for an association between less depression and better outcomes for cancer patients emerged from a study of 107 patients with metastatic non–small cell lung cancer (N. Engl. J. Med. 2010:363:733-42). Fewer patients who received early palliative therapy reported depressive symptoms, 16%, vs. 38% of patients assigned to standard care. In addition, the early palliative care group had a longer median survival (11.6 months vs. 8.9 months). Both differences were statistically significant.

However, there is still no consensus in the literature about psychosocial intervention and cancer survival. Seven randomized trials now show a survival benefit, and six show no difference, Dr. Spiegel said. "The results are not random; I’m glad to say that no studies show that psychotherapy kills patients."

Although further research is warranted, Dr. Spiegel said, "it is now reasonable to raise the possibility that treating depression and other psychiatric aspects of cancer may not only help people live better, but may help them live longer."

The study was sponsored by the National Institute of Mental Health, the National Cancer Institute, and the National Institute on Aging. Dr. Spiegel is an editorial advisory board member to this news organization. He reported no other relevant financial disclosures.

HONOLULU – Women whose depression improved during a 1-year treatment trial for metastatic breast cancer survived a median 2 years longer than women whose depression worsened, according to a long-term follow-up study.

"Our main finding is that the course of depression over the initial year of the study can be used to predict survival up to 14 years later," Dr. David Spiegel said at the annual meeting of the American Psychiatric Association.

Therefore, screen patients with breast cancer for depression. Also, do not dismiss depressive symptoms as merely a normal component of a cancer diagnosis or treatment, he said. Another clinical implication is that psychotherapy intervention can make a significant positive difference. "There are ways of facing and living with this disease that may help patients to live longer as well as better.

"This is a tremendous opportunity for psychiatry to be a part of the mission that is now mandated at cancer centers – to help cancer patients live better with their illness," said Dr. Spiegel, director of the center on stress and health at Stanford (Calif.) University.

One-quarter of cancer patients meet the criteria for depression, Dr. Spiegel said. "The more serious your medical illness, the more likely you are to be depressed. It’s 3% of the general population, 6% of outpatients, and 12% of medical inpatients – 1 out of 9 is depressed. But we often overlook the diagnosis; we misattribute the sadness to the prognosis of the disease; the disinterest in eating to the side effects of chemotherapy; the sleep disturbance to the worry about the illness.

"All of these can be signs of depression," he said.

Therefore, more awareness of an association between depression and a cancer prognosis is warranted. "Somehow people get the idea that if you have depression, it can worsen your prognosis with heart disease. But they have a much more difficult time understanding that ... depression is just as lethal a comorbid factor with cancer," Dr. Spiegel said.

He and his associates found median survival was 53.6 months for women whose baseline scores on the Center for Epidemiologic Studies–Depression Scale (CES-D) decreased over a period of 12 months, compared with a median 25.1-month survival for women whose CES-D scores increased. This 28.5-month difference in median survival was statistically significant.

The cohort included 101 women of 125 randomized to supportive-expressive group therapy or a control group with education materials who completed the CES-D scale at baseline and at three assessment points during the year (J. Clin. Oncol. 2011;29:413-20).

Only improvement in depression ratings, not treatment vs. no treatment, was associated with longer survival in this secondary analysis of the original study (Cancer 2007;110:1130-8).

Depression was an independent, long-term predictor of mortality. The researchers controlled for all the usual prognostic variables, including estrogen receptor and progesterone receptor status, disease-free interval, and age at diagnosis.

There is other evidence that psychotherapy can significantly reduce depressive symptoms in patients with advanced cancer, said Dr. Spiegel. For example, a Cochrane database analysis showed such a benefit in patients with incurable cancer who received supportive psychotherapy, cognitive-behavioral therapy, or problem-solving psychotherapy (Cochrane Database Syst. Rev. 2008;CD005537).

Dr. Spiegel said the psychotherapy in his study reduced patients’ tendency to suppress emotion. "So this outcome is not about distress; it’s about their management of distress. This, it turned out, mediated the reduction in depression and anxiety.

"We encourage people to face their fears of dying and death. We call it ‘detoxifying dying,’ " Dr. Spiegel said. Patients learn to face death, to reorder priorities, and to communicate better with families and physicians.

More support for an association between less depression and better outcomes for cancer patients emerged from a study of 107 patients with metastatic non–small cell lung cancer (N. Engl. J. Med. 2010:363:733-42). Fewer patients who received early palliative therapy reported depressive symptoms, 16%, vs. 38% of patients assigned to standard care. In addition, the early palliative care group had a longer median survival (11.6 months vs. 8.9 months). Both differences were statistically significant.

However, there is still no consensus in the literature about psychosocial intervention and cancer survival. Seven randomized trials now show a survival benefit, and six show no difference, Dr. Spiegel said. "The results are not random; I’m glad to say that no studies show that psychotherapy kills patients."

Although further research is warranted, Dr. Spiegel said, "it is now reasonable to raise the possibility that treating depression and other psychiatric aspects of cancer may not only help people live better, but may help them live longer."

The study was sponsored by the National Institute of Mental Health, the National Cancer Institute, and the National Institute on Aging. Dr. Spiegel is an editorial advisory board member to this news organization. He reported no other relevant financial disclosures.

HONOLULU – Women whose depression improved during a 1-year treatment trial for metastatic breast cancer survived a median 2 years longer than women whose depression worsened, according to a long-term follow-up study.

"Our main finding is that the course of depression over the initial year of the study can be used to predict survival up to 14 years later," Dr. David Spiegel said at the annual meeting of the American Psychiatric Association.

Therefore, screen patients with breast cancer for depression. Also, do not dismiss depressive symptoms as merely a normal component of a cancer diagnosis or treatment, he said. Another clinical implication is that psychotherapy intervention can make a significant positive difference. "There are ways of facing and living with this disease that may help patients to live longer as well as better.

"This is a tremendous opportunity for psychiatry to be a part of the mission that is now mandated at cancer centers – to help cancer patients live better with their illness," said Dr. Spiegel, director of the center on stress and health at Stanford (Calif.) University.

One-quarter of cancer patients meet the criteria for depression, Dr. Spiegel said. "The more serious your medical illness, the more likely you are to be depressed. It’s 3% of the general population, 6% of outpatients, and 12% of medical inpatients – 1 out of 9 is depressed. But we often overlook the diagnosis; we misattribute the sadness to the prognosis of the disease; the disinterest in eating to the side effects of chemotherapy; the sleep disturbance to the worry about the illness.

"All of these can be signs of depression," he said.

Therefore, more awareness of an association between depression and a cancer prognosis is warranted. "Somehow people get the idea that if you have depression, it can worsen your prognosis with heart disease. But they have a much more difficult time understanding that ... depression is just as lethal a comorbid factor with cancer," Dr. Spiegel said.

He and his associates found median survival was 53.6 months for women whose baseline scores on the Center for Epidemiologic Studies–Depression Scale (CES-D) decreased over a period of 12 months, compared with a median 25.1-month survival for women whose CES-D scores increased. This 28.5-month difference in median survival was statistically significant.

The cohort included 101 women of 125 randomized to supportive-expressive group therapy or a control group with education materials who completed the CES-D scale at baseline and at three assessment points during the year (J. Clin. Oncol. 2011;29:413-20).

Only improvement in depression ratings, not treatment vs. no treatment, was associated with longer survival in this secondary analysis of the original study (Cancer 2007;110:1130-8).

Depression was an independent, long-term predictor of mortality. The researchers controlled for all the usual prognostic variables, including estrogen receptor and progesterone receptor status, disease-free interval, and age at diagnosis.

There is other evidence that psychotherapy can significantly reduce depressive symptoms in patients with advanced cancer, said Dr. Spiegel. For example, a Cochrane database analysis showed such a benefit in patients with incurable cancer who received supportive psychotherapy, cognitive-behavioral therapy, or problem-solving psychotherapy (Cochrane Database Syst. Rev. 2008;CD005537).

Dr. Spiegel said the psychotherapy in his study reduced patients’ tendency to suppress emotion. "So this outcome is not about distress; it’s about their management of distress. This, it turned out, mediated the reduction in depression and anxiety.

"We encourage people to face their fears of dying and death. We call it ‘detoxifying dying,’ " Dr. Spiegel said. Patients learn to face death, to reorder priorities, and to communicate better with families and physicians.

More support for an association between less depression and better outcomes for cancer patients emerged from a study of 107 patients with metastatic non–small cell lung cancer (N. Engl. J. Med. 2010:363:733-42). Fewer patients who received early palliative therapy reported depressive symptoms, 16%, vs. 38% of patients assigned to standard care. In addition, the early palliative care group had a longer median survival (11.6 months vs. 8.9 months). Both differences were statistically significant.

However, there is still no consensus in the literature about psychosocial intervention and cancer survival. Seven randomized trials now show a survival benefit, and six show no difference, Dr. Spiegel said. "The results are not random; I’m glad to say that no studies show that psychotherapy kills patients."

Although further research is warranted, Dr. Spiegel said, "it is now reasonable to raise the possibility that treating depression and other psychiatric aspects of cancer may not only help people live better, but may help them live longer."

The study was sponsored by the National Institute of Mental Health, the National Cancer Institute, and the National Institute on Aging. Dr. Spiegel is an editorial advisory board member to this news organization. He reported no other relevant financial disclosures.

HONOLULU – Women whose depression improved during a 1-year treatment trial for metastatic breast cancer survived a median 2 years longer than women whose depression worsened, according to a long-term follow-up study.

"Our main finding is that the course of depression over the initial year of the study can be used to predict survival up to 14 years later," Dr. David Spiegel said at the annual meeting of the American Psychiatric Association.

Therefore, screen patients with breast cancer for depression. Also, do not dismiss depressive symptoms as merely a normal component of a cancer diagnosis or treatment, he said. Another clinical implication is that psychotherapy intervention can make a significant positive difference. "There are ways of facing and living with this disease that may help patients to live longer as well as better.

"This is a tremendous opportunity for psychiatry to be a part of the mission that is now mandated at cancer centers – to help cancer patients live better with their illness," said Dr. Spiegel, director of the center on stress and health at Stanford (Calif.) University.

One-quarter of cancer patients meet the criteria for depression, Dr. Spiegel said. "The more serious your medical illness, the more likely you are to be depressed. It’s 3% of the general population, 6% of outpatients, and 12% of medical inpatients – 1 out of 9 is depressed. But we often overlook the diagnosis; we misattribute the sadness to the prognosis of the disease; the disinterest in eating to the side effects of chemotherapy; the sleep disturbance to the worry about the illness.

"All of these can be signs of depression," he said.

Therefore, more awareness of an association between depression and a cancer prognosis is warranted. "Somehow people get the idea that if you have depression, it can worsen your prognosis with heart disease. But they have a much more difficult time understanding that ... depression is just as lethal a comorbid factor with cancer," Dr. Spiegel said.

He and his associates found median survival was 53.6 months for women whose baseline scores on the Center for Epidemiologic Studies–Depression Scale (CES-D) decreased over a period of 12 months, compared with a median 25.1-month survival for women whose CES-D scores increased. This 28.5-month difference in median survival was statistically significant.

The cohort included 101 women of 125 randomized to supportive-expressive group therapy or a control group with education materials who completed the CES-D scale at baseline and at three assessment points during the year (J. Clin. Oncol. 2011;29:413-20).

Only improvement in depression ratings, not treatment vs. no treatment, was associated with longer survival in this secondary analysis of the original study (Cancer 2007;110:1130-8).

Depression was an independent, long-term predictor of mortality. The researchers controlled for all the usual prognostic variables, including estrogen receptor and progesterone receptor status, disease-free interval, and age at diagnosis.

There is other evidence that psychotherapy can significantly reduce depressive symptoms in patients with advanced cancer, said Dr. Spiegel. For example, a Cochrane database analysis showed such a benefit in patients with incurable cancer who received supportive psychotherapy, cognitive-behavioral therapy, or problem-solving psychotherapy (Cochrane Database Syst. Rev. 2008;CD005537).

Dr. Spiegel said the psychotherapy in his study reduced patients’ tendency to suppress emotion. "So this outcome is not about distress; it’s about their management of distress. This, it turned out, mediated the reduction in depression and anxiety.

"We encourage people to face their fears of dying and death. We call it ‘detoxifying dying,’ " Dr. Spiegel said. Patients learn to face death, to reorder priorities, and to communicate better with families and physicians.

More support for an association between less depression and better outcomes for cancer patients emerged from a study of 107 patients with metastatic non–small cell lung cancer (N. Engl. J. Med. 2010:363:733-42). Fewer patients who received early palliative therapy reported depressive symptoms, 16%, vs. 38% of patients assigned to standard care. In addition, the early palliative care group had a longer median survival (11.6 months vs. 8.9 months). Both differences were statistically significant.

However, there is still no consensus in the literature about psychosocial intervention and cancer survival. Seven randomized trials now show a survival benefit, and six show no difference, Dr. Spiegel said. "The results are not random; I’m glad to say that no studies show that psychotherapy kills patients."

Although further research is warranted, Dr. Spiegel said, "it is now reasonable to raise the possibility that treating depression and other psychiatric aspects of cancer may not only help people live better, but may help them live longer."

The study was sponsored by the National Institute of Mental Health, the National Cancer Institute, and the National Institute on Aging. Dr. Spiegel is an editorial advisory board member to this news organization. He reported no other relevant financial disclosures.

HONOLULU – Women whose depression improved during a 1-year treatment trial for metastatic breast cancer survived a median 2 years longer than women whose depression worsened, according to a long-term follow-up study.

"Our main finding is that the course of depression over the initial year of the study can be used to predict survival up to 14 years later," Dr. David Spiegel said at the annual meeting of the American Psychiatric Association.

Therefore, screen patients with breast cancer for depression. Also, do not dismiss depressive symptoms as merely a normal component of a cancer diagnosis or treatment, he said. Another clinical implication is that psychotherapy intervention can make a significant positive difference. "There are ways of facing and living with this disease that may help patients to live longer as well as better.

"This is a tremendous opportunity for psychiatry to be a part of the mission that is now mandated at cancer centers – to help cancer patients live better with their illness," said Dr. Spiegel, director of the center on stress and health at Stanford (Calif.) University.

One-quarter of cancer patients meet the criteria for depression, Dr. Spiegel said. "The more serious your medical illness, the more likely you are to be depressed. It’s 3% of the general population, 6% of outpatients, and 12% of medical inpatients – 1 out of 9 is depressed. But we often overlook the diagnosis; we misattribute the sadness to the prognosis of the disease; the disinterest in eating to the side effects of chemotherapy; the sleep disturbance to the worry about the illness.

"All of these can be signs of depression," he said.

Therefore, more awareness of an association between depression and a cancer prognosis is warranted. "Somehow people get the idea that if you have depression, it can worsen your prognosis with heart disease. But they have a much more difficult time understanding that ... depression is just as lethal a comorbid factor with cancer," Dr. Spiegel said.

He and his associates found median survival was 53.6 months for women whose baseline scores on the Center for Epidemiologic Studies–Depression Scale (CES-D) decreased over a period of 12 months, compared with a median 25.1-month survival for women whose CES-D scores increased. This 28.5-month difference in median survival was statistically significant.

The cohort included 101 women of 125 randomized to supportive-expressive group therapy or a control group with education materials who completed the CES-D scale at baseline and at three assessment points during the year (J. Clin. Oncol. 2011;29:413-20).

Only improvement in depression ratings, not treatment vs. no treatment, was associated with longer survival in this secondary analysis of the original study (Cancer 2007;110:1130-8).

Depression was an independent, long-term predictor of mortality. The researchers controlled for all the usual prognostic variables, including estrogen receptor and progesterone receptor status, disease-free interval, and age at diagnosis.

There is other evidence that psychotherapy can significantly reduce depressive symptoms in patients with advanced cancer, said Dr. Spiegel. For example, a Cochrane database analysis showed such a benefit in patients with incurable cancer who received supportive psychotherapy, cognitive-behavioral therapy, or problem-solving psychotherapy (Cochrane Database Syst. Rev. 2008;CD005537).

Dr. Spiegel said the psychotherapy in his study reduced patients’ tendency to suppress emotion. "So this outcome is not about distress; it’s about their management of distress. This, it turned out, mediated the reduction in depression and anxiety.

"We encourage people to face their fears of dying and death. We call it ‘detoxifying dying,’ " Dr. Spiegel said. Patients learn to face death, to reorder priorities, and to communicate better with families and physicians.

More support for an association between less depression and better outcomes for cancer patients emerged from a study of 107 patients with metastatic non–small cell lung cancer (N. Engl. J. Med. 2010:363:733-42). Fewer patients who received early palliative therapy reported depressive symptoms, 16%, vs. 38% of patients assigned to standard care. In addition, the early palliative care group had a longer median survival (11.6 months vs. 8.9 months). Both differences were statistically significant.

However, there is still no consensus in the literature about psychosocial intervention and cancer survival. Seven randomized trials now show a survival benefit, and six show no difference, Dr. Spiegel said. "The results are not random; I’m glad to say that no studies show that psychotherapy kills patients."

Although further research is warranted, Dr. Spiegel said, "it is now reasonable to raise the possibility that treating depression and other psychiatric aspects of cancer may not only help people live better, but may help them live longer."

The study was sponsored by the National Institute of Mental Health, the National Cancer Institute, and the National Institute on Aging. Dr. Spiegel is an editorial advisory board member to this news organization. He reported no other relevant financial disclosures.

HONOLULU – Women whose depression improved during a 1-year treatment trial for metastatic breast cancer survived a median 2 years longer than women whose depression worsened, according to a long-term follow-up study.

"Our main finding is that the course of depression over the initial year of the study can be used to predict survival up to 14 years later," Dr. David Spiegel said at the annual meeting of the American Psychiatric Association.

Therefore, screen patients with breast cancer for depression. Also, do not dismiss depressive symptoms as merely a normal component of a cancer diagnosis or treatment, he said. Another clinical implication is that psychotherapy intervention can make a significant positive difference. "There are ways of facing and living with this disease that may help patients to live longer as well as better.

"This is a tremendous opportunity for psychiatry to be a part of the mission that is now mandated at cancer centers – to help cancer patients live better with their illness," said Dr. Spiegel, director of the center on stress and health at Stanford (Calif.) University.

One-quarter of cancer patients meet the criteria for depression, Dr. Spiegel said. "The more serious your medical illness, the more likely you are to be depressed. It’s 3% of the general population, 6% of outpatients, and 12% of medical inpatients – 1 out of 9 is depressed. But we often overlook the diagnosis; we misattribute the sadness to the prognosis of the disease; the disinterest in eating to the side effects of chemotherapy; the sleep disturbance to the worry about the illness.

"All of these can be signs of depression," he said.

Therefore, more awareness of an association between depression and a cancer prognosis is warranted. "Somehow people get the idea that if you have depression, it can worsen your prognosis with heart disease. But they have a much more difficult time understanding that ... depression is just as lethal a comorbid factor with cancer," Dr. Spiegel said.

He and his associates found median survival was 53.6 months for women whose baseline scores on the Center for Epidemiologic Studies–Depression Scale (CES-D) decreased over a period of 12 months, compared with a median 25.1-month survival for women whose CES-D scores increased. This 28.5-month difference in median survival was statistically significant.

The cohort included 101 women of 125 randomized to supportive-expressive group therapy or a control group with education materials who completed the CES-D scale at baseline and at three assessment points during the year (J. Clin. Oncol. 2011;29:413-20).

Only improvement in depression ratings, not treatment vs. no treatment, was associated with longer survival in this secondary analysis of the original study (Cancer 2007;110:1130-8).

Depression was an independent, long-term predictor of mortality. The researchers controlled for all the usual prognostic variables, including estrogen receptor and progesterone receptor status, disease-free interval, and age at diagnosis.

There is other evidence that psychotherapy can significantly reduce depressive symptoms in patients with advanced cancer, said Dr. Spiegel. For example, a Cochrane database analysis showed such a benefit in patients with incurable cancer who received supportive psychotherapy, cognitive-behavioral therapy, or problem-solving psychotherapy (Cochrane Database Syst. Rev. 2008;CD005537).

Dr. Spiegel said the psychotherapy in his study reduced patients’ tendency to suppress emotion. "So this outcome is not about distress; it’s about their management of distress. This, it turned out, mediated the reduction in depression and anxiety.

"We encourage people to face their fears of dying and death. We call it ‘detoxifying dying,’ " Dr. Spiegel said. Patients learn to face death, to reorder priorities, and to communicate better with families and physicians.

More support for an association between less depression and better outcomes for cancer patients emerged from a study of 107 patients with metastatic non–small cell lung cancer (N. Engl. J. Med. 2010:363:733-42). Fewer patients who received early palliative therapy reported depressive symptoms, 16%, vs. 38% of patients assigned to standard care. In addition, the early palliative care group had a longer median survival (11.6 months vs. 8.9 months). Both differences were statistically significant.

However, there is still no consensus in the literature about psychosocial intervention and cancer survival. Seven randomized trials now show a survival benefit, and six show no difference, Dr. Spiegel said. "The results are not random; I’m glad to say that no studies show that psychotherapy kills patients."

Although further research is warranted, Dr. Spiegel said, "it is now reasonable to raise the possibility that treating depression and other psychiatric aspects of cancer may not only help people live better, but may help them live longer."

The study was sponsored by the National Institute of Mental Health, the National Cancer Institute, and the National Institute on Aging. Dr. Spiegel is an editorial advisory board member to this news organization. He reported no other relevant financial disclosures.

HONOLULU – Women whose depression improved during a 1-year treatment trial for metastatic breast cancer survived a median 2 years longer than women whose depression worsened, according to a long-term follow-up study.

"Our main finding is that the course of depression over the initial year of the study can be used to predict survival up to 14 years later," Dr. David Spiegel said at the annual meeting of the American Psychiatric Association.

Therefore, screen patients with breast cancer for depression. Also, do not dismiss depressive symptoms as merely a normal component of a cancer diagnosis or treatment, he said. Another clinical implication is that psychotherapy intervention can make a significant positive difference. "There are ways of facing and living with this disease that may help patients to live longer as well as better.

"This is a tremendous opportunity for psychiatry to be a part of the mission that is now mandated at cancer centers – to help cancer patients live better with their illness," said Dr. Spiegel, director of the center on stress and health at Stanford (Calif.) University.

One-quarter of cancer patients meet the criteria for depression, Dr. Spiegel said. "The more serious your medical illness, the more likely you are to be depressed. It’s 3% of the general population, 6% of outpatients, and 12% of medical inpatients – 1 out of 9 is depressed. But we often overlook the diagnosis; we misattribute the sadness to the prognosis of the disease; the disinterest in eating to the side effects of chemotherapy; the sleep disturbance to the worry about the illness.

"All of these can be signs of depression," he said.

Therefore, more awareness of an association between depression and a cancer prognosis is warranted. "Somehow people get the idea that if you have depression, it can worsen your prognosis with heart disease. But they have a much more difficult time understanding that ... depression is just as lethal a comorbid factor with cancer," Dr. Spiegel said.

He and his associates found median survival was 53.6 months for women whose baseline scores on the Center for Epidemiologic Studies–Depression Scale (CES-D) decreased over a period of 12 months, compared with a median 25.1-month survival for women whose CES-D scores increased. This 28.5-month difference in median survival was statistically significant.

The cohort included 101 women of 125 randomized to supportive-expressive group therapy or a control group with education materials who completed the CES-D scale at baseline and at three assessment points during the year (J. Clin. Oncol. 2011;29:413-20).

Only improvement in depression ratings, not treatment vs. no treatment, was associated with longer survival in this secondary analysis of the original study (Cancer 2007;110:1130-8).

Depression was an independent, long-term predictor of mortality. The researchers controlled for all the usual prognostic variables, including estrogen receptor and progesterone receptor status, disease-free interval, and age at diagnosis.

There is other evidence that psychotherapy can significantly reduce depressive symptoms in patients with advanced cancer, said Dr. Spiegel. For example, a Cochrane database analysis showed such a benefit in patients with incurable cancer who received supportive psychotherapy, cognitive-behavioral therapy, or problem-solving psychotherapy (Cochrane Database Syst. Rev. 2008;CD005537).

Dr. Spiegel said the psychotherapy in his study reduced patients’ tendency to suppress emotion. "So this outcome is not about distress; it’s about their management of distress. This, it turned out, mediated the reduction in depression and anxiety.

"We encourage people to face their fears of dying and death. We call it ‘detoxifying dying,’ " Dr. Spiegel said. Patients learn to face death, to reorder priorities, and to communicate better with families and physicians.

More support for an association between less depression and better outcomes for cancer patients emerged from a study of 107 patients with metastatic non–small cell lung cancer (N. Engl. J. Med. 2010:363:733-42). Fewer patients who received early palliative therapy reported depressive symptoms, 16%, vs. 38% of patients assigned to standard care. In addition, the early palliative care group had a longer median survival (11.6 months vs. 8.9 months). Both differences were statistically significant.

However, there is still no consensus in the literature about psychosocial intervention and cancer survival. Seven randomized trials now show a survival benefit, and six show no difference, Dr. Spiegel said. "The results are not random; I’m glad to say that no studies show that psychotherapy kills patients."

Although further research is warranted, Dr. Spiegel said, "it is now reasonable to raise the possibility that treating depression and other psychiatric aspects of cancer may not only help people live better, but may help them live longer."

The study was sponsored by the National Institute of Mental Health, the National Cancer Institute, and the National Institute on Aging. Dr. Spiegel is an editorial advisory board member to this news organization. He reported no other relevant financial disclosures.

HONOLULU – Women whose depression improved during a 1-year treatment trial for metastatic breast cancer survived a median 2 years longer than women whose depression worsened, according to a long-term follow-up study.

"Our main finding is that the course of depression over the initial year of the study can be used to predict survival up to 14 years later," Dr. David Spiegel said at the annual meeting of the American Psychiatric Association.

Therefore, screen patients with breast cancer for depression. Also, do not dismiss depressive symptoms as merely a normal component of a cancer diagnosis or treatment, he said. Another clinical implication is that psychotherapy intervention can make a significant positive difference. "There are ways of facing and living with this disease that may help patients to live longer as well as better.

"This is a tremendous opportunity for psychiatry to be a part of the mission that is now mandated at cancer centers – to help cancer patients live better with their illness," said Dr. Spiegel, director of the center on stress and health at Stanford (Calif.) University.

One-quarter of cancer patients meet the criteria for depression, Dr. Spiegel said. "The more serious your medical illness, the more likely you are to be depressed. It’s 3% of the general population, 6% of outpatients, and 12% of medical inpatients – 1 out of 9 is depressed. But we often overlook the diagnosis; we misattribute the sadness to the prognosis of the disease; the disinterest in eating to the side effects of chemotherapy; the sleep disturbance to the worry about the illness.

"All of these can be signs of depression," he said.

Therefore, more awareness of an association between depression and a cancer prognosis is warranted. "Somehow people get the idea that if you have depression, it can worsen your prognosis with heart disease. But they have a much more difficult time understanding that ... depression is just as lethal a comorbid factor with cancer," Dr. Spiegel said.

He and his associates found median survival was 53.6 months for women whose baseline scores on the Center for Epidemiologic Studies–Depression Scale (CES-D) decreased over a period of 12 months, compared with a median 25.1-month survival for women whose CES-D scores increased. This 28.5-month difference in median survival was statistically significant.

The cohort included 101 women of 125 randomized to supportive-expressive group therapy or a control group with education materials who completed the CES-D scale at baseline and at three assessment points during the year (J. Clin. Oncol. 2011;29:413-20).

Only improvement in depression ratings, not treatment vs. no treatment, was associated with longer survival in this secondary analysis of the original study (Cancer 2007;110:1130-8).

Depression was an independent, long-term predictor of mortality. The researchers controlled for all the usual prognostic variables, including estrogen receptor and progesterone receptor status, disease-free interval, and age at diagnosis.

There is other evidence that psychotherapy can significantly reduce depressive symptoms in patients with advanced cancer, said Dr. Spiegel. For example, a Cochrane database analysis showed such a benefit in patients with incurable cancer who received supportive psychotherapy, cognitive-behavioral therapy, or problem-solving psychotherapy (Cochrane Database Syst. Rev. 2008;CD005537).

Dr. Spiegel said the psychotherapy in his study reduced patients’ tendency to suppress emotion. "So this outcome is not about distress; it’s about their management of distress. This, it turned out, mediated the reduction in depression and anxiety.

"We encourage people to face their fears of dying and death. We call it ‘detoxifying dying,’ " Dr. Spiegel said. Patients learn to face death, to reorder priorities, and to communicate better with families and physicians.

More support for an association between less depression and better outcomes for cancer patients emerged from a study of 107 patients with metastatic non–small cell lung cancer (N. Engl. J. Med. 2010:363:733-42). Fewer patients who received early palliative therapy reported depressive symptoms, 16%, vs. 38% of patients assigned to standard care. In addition, the early palliative care group had a longer median survival (11.6 months vs. 8.9 months). Both differences were statistically significant.

However, there is still no consensus in the literature about psychosocial intervention and cancer survival. Seven randomized trials now show a survival benefit, and six show no difference, Dr. Spiegel said. "The results are not random; I’m glad to say that no studies show that psychotherapy kills patients."

Although further research is warranted, Dr. Spiegel said, "it is now reasonable to raise the possibility that treating depression and other psychiatric aspects of cancer may not only help people live better, but may help them live longer."

The study was sponsored by the National Institute of Mental Health, the National Cancer Institute, and the National Institute on Aging. Dr. Spiegel is an editorial advisory board member to this news organization. He reported no other relevant financial disclosures.

HONOLULU – Women whose depression improved during a 1-year treatment trial for metastatic breast cancer survived a median 2 years longer than women whose depression worsened, according to a long-term follow-up study.

"Our main finding is that the course of depression over the initial year of the study can be used to predict survival up to 14 years later," Dr. David Spiegel said at the annual meeting of the American Psychiatric Association.

Therefore, screen patients with breast cancer for depression. Also, do not dismiss depressive symptoms as merely a normal component of a cancer diagnosis or treatment, he said. Another clinical implication is that psychotherapy intervention can make a significant positive difference. "There are ways of facing and living with this disease that may help patients to live longer as well as better.

"This is a tremendous opportunity for psychiatry to be a part of the mission that is now mandated at cancer centers – to help cancer patients live better with their illness," said Dr. Spiegel, director of the center on stress and health at Stanford (Calif.) University.

One-quarter of cancer patients meet the criteria for depression, Dr. Spiegel said. "The more serious your medical illness, the more likely you are to be depressed. It’s 3% of the general population, 6% of outpatients, and 12% of medical inpatients – 1 out of 9 is depressed. But we often overlook the diagnosis; we misattribute the sadness to the prognosis of the disease; the disinterest in eating to the side effects of chemotherapy; the sleep disturbance to the worry about the illness.

"All of these can be signs of depression," he said.

Therefore, more awareness of an association between depression and a cancer prognosis is warranted. "Somehow people get the idea that if you have depression, it can worsen your prognosis with heart disease. But they have a much more difficult time understanding that ... depression is just as lethal a comorbid factor with cancer," Dr. Spiegel said.

He and his associates found median survival was 53.6 months for women whose baseline scores on the Center for Epidemiologic Studies–Depression Scale (CES-D) decreased over a period of 12 months, compared with a median 25.1-month survival for women whose CES-D scores increased. This 28.5-month difference in median survival was statistically significant.

The cohort included 101 women of 125 randomized to supportive-expressive group therapy or a control group with education materials who completed the CES-D scale at baseline and at three assessment points during the year (J. Clin. Oncol. 2011;29:413-20).

Only improvement in depression ratings, not treatment vs. no treatment, was associated with longer survival in this secondary analysis of the original study (Cancer 2007;110:1130-8).

Depression was an independent, long-term predictor of mortality. The researchers controlled for all the usual prognostic variables, including estrogen receptor and progesterone receptor status, disease-free interval, and age at diagnosis.

There is other evidence that psychotherapy can significantly reduce depressive symptoms in patients with advanced cancer, said Dr. Spiegel. For example, a Cochrane database analysis showed such a benefit in patients with incurable cancer who received supportive psychotherapy, cognitive-behavioral therapy, or problem-solving psychotherapy (Cochrane Database Syst. Rev. 2008;CD005537).

Dr. Spiegel said the psychotherapy in his study reduced patients’ tendency to suppress emotion. "So this outcome is not about distress; it’s about their management of distress. This, it turned out, mediated the reduction in depression and anxiety.

"We encourage people to face their fears of dying and death. We call it ‘detoxifying dying,’ " Dr. Spiegel said. Patients learn to face death, to reorder priorities, and to communicate better with families and physicians.

More support for an association between less depression and better outcomes for cancer patients emerged from a study of 107 patients with metastatic non–small cell lung cancer (N. Engl. J. Med. 2010:363:733-42). Fewer patients who received early palliative therapy reported depressive symptoms, 16%, vs. 38% of patients assigned to standard care. In addition, the early palliative care group had a longer median survival (11.6 months vs. 8.9 months). Both differences were statistically significant.

However, there is still no consensus in the literature about psychosocial intervention and cancer survival. Seven randomized trials now show a survival benefit, and six show no difference, Dr. Spiegel said. "The results are not random; I’m glad to say that no studies show that psychotherapy kills patients."

Although further research is warranted, Dr. Spiegel said, "it is now reasonable to raise the possibility that treating depression and other psychiatric aspects of cancer may not only help people live better, but may help them live longer."

The study was sponsored by the National Institute of Mental Health, the National Cancer Institute, and the National Institute on Aging. Dr. Spiegel is an editorial advisory board member to this news organization. He reported no other relevant financial disclosures.

HONOLULU – Women whose depression improved during a 1-year treatment trial for metastatic breast cancer survived a median 2 years longer than women whose depression worsened, according to a long-term follow-up study.

"Our main finding is that the course of depression over the initial year of the study can be used to predict survival up to 14 years later," Dr. David Spiegel said at the annual meeting of the American Psychiatric Association.

Therefore, screen patients with breast cancer for depression. Also, do not dismiss depressive symptoms as merely a normal component of a cancer diagnosis or treatment, he said. Another clinical implication is that psychotherapy intervention can make a significant positive difference. "There are ways of facing and living with this disease that may help patients to live longer as well as better.

"This is a tremendous opportunity for psychiatry to be a part of the mission that is now mandated at cancer centers – to help cancer patients live better with their illness," said Dr. Spiegel, director of the center on stress and health at Stanford (Calif.) University.

One-quarter of cancer patients meet the criteria for depression, Dr. Spiegel said. "The more serious your medical illness, the more likely you are to be depressed. It’s 3% of the general population, 6% of outpatients, and 12% of medical inpatients – 1 out of 9 is depressed. But we often overlook the diagnosis; we misattribute the sadness to the prognosis of the disease; the disinterest in eating to the side effects of chemotherapy; the sleep disturbance to the worry about the illness.

"All of these can be signs of depression," he said.

Therefore, more awareness of an association between depression and a cancer prognosis is warranted. "Somehow people get the idea that if you have depression, it can worsen your prognosis with heart disease. But they have a much more difficult time understanding that ... depression is just as lethal a comorbid factor with cancer," Dr. Spiegel said.

He and his associates found median survival was 53.6 months for women whose baseline scores on the Center for Epidemiologic Studies–Depression Scale (CES-D) decreased over a period of 12 months, compared with a median 25.1-month survival for women whose CES-D scores increased. This 28.5-month difference in median survival was statistically significant.

The cohort included 101 women of 125 randomized to supportive-expressive group therapy or a control group with education materials who completed the CES-D scale at baseline and at three assessment points during the year (J. Clin. Oncol. 2011;29:413-20).

Only improvement in depression ratings, not treatment vs. no treatment, was associated with longer survival in this secondary analysis of the original study (Cancer 2007;110:1130-8).

Depression was an independent, long-term predictor of mortality. The researchers controlled for all the usual prognostic variables, including estrogen receptor and progesterone receptor status, disease-free interval, and age at diagnosis.

There is other evidence that psychotherapy can significantly reduce depressive symptoms in patients with advanced cancer, said Dr. Spiegel. For example, a Cochrane database analysis showed such a benefit in patients with incurable cancer who received supportive psychotherapy, cognitive-behavioral therapy, or problem-solving psychotherapy (Cochrane Database Syst. Rev. 2008;CD005537).

Dr. Spiegel said the psychotherapy in his study reduced patients’ tendency to suppress emotion. "So this outcome is not about distress; it’s about their management of distress. This, it turned out, mediated the reduction in depression and anxiety.

"We encourage people to face their fears of dying and death. We call it ‘detoxifying dying,’ " Dr. Spiegel said. Patients learn to face death, to reorder priorities, and to communicate better with families and physicians.

More support for an association between less depression and better outcomes for cancer patients emerged from a study of 107 patients with metastatic non–small cell lung cancer (N. Engl. J. Med. 2010:363:733-42). Fewer patients who received early palliative therapy reported depressive symptoms, 16%, vs. 38% of patients assigned to standard care. In addition, the early palliative care group had a longer median survival (11.6 months vs. 8.9 months). Both differences were statistically significant.

However, there is still no consensus in the literature about psychosocial intervention and cancer survival. Seven randomized trials now show a survival benefit, and six show no difference, Dr. Spiegel said. "The results are not random; I’m glad to say that no studies show that psychotherapy kills patients."

Although further research is warranted, Dr. Spiegel said, "it is now reasonable to raise the possibility that treating depression and other psychiatric aspects of cancer may not only help people live better, but may help them live longer."

The study was sponsored by the National Institute of Mental Health, the National Cancer Institute, and the National Institute on Aging. Dr. Spiegel is an editorial advisory board member to this news organization. He reported no other relevant financial disclosures.

CHICAGO – Delaying adjuvant chemotherapy following curative resection of colorectal cancer worsens overall and disease-free survival, according to the findings of a meta-analysis and systematic literature review.

Using 4 weeks postoperatively as a reference, Dr. James J. Biagi and his colleagues found that each additional 4 weeks between surgery and initiation of adjuvant chemotherapy was tied to a 14% decline in overall survival. A patient medically eligible for adjuvant chemotherapy at 4 weeks but whose adjuvant chemotherapy was delayed for any reason had a 14% higher mortality risk if treatment started at 8 weeks, and an almost 30% higher risk if treatment started at 12 weeks.

A second major finding was that some benefit of adjuvant chemotherapy remained beyond 12 weeks, Dr. Biagi and his associates reported at the annual meeting of the American Society of Clinical Oncology (ASCO).

Although most protocols do not recommend adjuvant chemotherapy beyond 3 months, "it is possible that a reasonable limit may be more on the order of 4 to 5 months," Dr. Biagi and his colleagues wrote in a report (JAMA 2011;305:2335-42) released to coincide with the presentation of results at the meeting.

The findings were consistent for disease-free or cancer-specific survival as well, reported Dr. Biagi, acting head of oncology at Queen’s University Cancer Research Institute, Kingston, Ontario, and his colleagues.

Prior to the study, the optimal time from surgery to initiation of adjuvant chemotherapy had not been identified. Dr. Biagi and his coinvestigators searched MEDLINE, as well as abstracts from recent proceedings of the annual meeting of ASCO and the European Society for Medical Oncology. They found 10 relevant studies that assessed overall survival related to adjuvant chemotherapy wait times with a total 15,410 patients. Six of these studies also addressed disease-free, relapse-free, or cancer-specific survival among 12,584 patients.

The studies of overall survival yielded a combined hazard ratio of 1.14 for a relative increase in mortality for each 4 weeks of waiting time past 4 weeks. The combined hazard ratio was the same, 1.14, for the six studies with additional survival end points. In addition, three studies specifically addressed cancer-specific survival; these yielded a combined hazard ratio of 1.15.

Nine studies were population- or registry-based, and one was a secondary analysis of a randomized controlled trial. Because it is unlikely that a prospective study will be conducted to evaluate the relationship between adjuvant chemotherapy wait times and survival in this patient population, the authors wrote that "[they] believe the level of evidence from this study provides sufficient evidence of causality."

The effect of delays might be substantial, Dr. Biagi and his colleagues noted. An estimated 49,000 people are newly diagnosed with stage III colorectal cancer each year. This represents 35% of the approximately 140,000 or so new cases of colorectal cancer in the United States.

The influence of postoperative performance status on wait times was not evaluated, which is a potential limitation of the study, Dr. Biagi and his coauthors wrote. In addition, the researchers were unable to determine the effect of starting adjuvant chemotherapy in the initial weeks after resection (before 4 weeks) or what percentage of patients completed adjuvant chemotherapy. Moreover, the studies were largely from a period of fluoropyrimidine adjuvant chemotherapy prior to widespread use of oxaliplatin, so extrapolation to the current era in which oxaliplatin is often added to fluoropyrimidine is uncertain.

Dr. Biagi previously presented the results of this meta-analysis and systematic review at a meeting on gastrointestinal cancers sponsored by ASCO, and it was reported by this news organization.

Dr. Biagi had no relevant financial disclosures. A study coauthor, Dr. William J. Mackillop, disclosed that he provided expert testimony in a 2009 class action suit regarding delays in postlumpectomy radiotherapy for breast cancer and the probability of local disease control.

CHICAGO – Delaying adjuvant chemotherapy following curative resection of colorectal cancer worsens overall and disease-free survival, according to the findings of a meta-analysis and systematic literature review.

Using 4 weeks postoperatively as a reference, Dr. James J. Biagi and his colleagues found that each additional 4 weeks between surgery and initiation of adjuvant chemotherapy was tied to a 14% decline in overall survival. A patient medically eligible for adjuvant chemotherapy at 4 weeks but whose adjuvant chemotherapy was delayed for any reason had a 14% higher mortality risk if treatment started at 8 weeks, and an almost 30% higher risk if treatment started at 12 weeks.

A second major finding was that some benefit of adjuvant chemotherapy remained beyond 12 weeks, Dr. Biagi and his associates reported at the annual meeting of the American Society of Clinical Oncology (ASCO).

Although most protocols do not recommend adjuvant chemotherapy beyond 3 months, "it is possible that a reasonable limit may be more on the order of 4 to 5 months," Dr. Biagi and his colleagues wrote in a report (JAMA 2011;305:2335-42) released to coincide with the presentation of results at the meeting.

The findings were consistent for disease-free or cancer-specific survival as well, reported Dr. Biagi, acting head of oncology at Queen’s University Cancer Research Institute, Kingston, Ontario, and his colleagues.

Prior to the study, the optimal time from surgery to initiation of adjuvant chemotherapy had not been identified. Dr. Biagi and his coinvestigators searched MEDLINE, as well as abstracts from recent proceedings of the annual meeting of ASCO and the European Society for Medical Oncology. They found 10 relevant studies that assessed overall survival related to adjuvant chemotherapy wait times with a total 15,410 patients. Six of these studies also addressed disease-free, relapse-free, or cancer-specific survival among 12,584 patients.

The studies of overall survival yielded a combined hazard ratio of 1.14 for a relative increase in mortality for each 4 weeks of waiting time past 4 weeks. The combined hazard ratio was the same, 1.14, for the six studies with additional survival end points. In addition, three studies specifically addressed cancer-specific survival; these yielded a combined hazard ratio of 1.15.

Nine studies were population- or registry-based, and one was a secondary analysis of a randomized controlled trial. Because it is unlikely that a prospective study will be conducted to evaluate the relationship between adjuvant chemotherapy wait times and survival in this patient population, the authors wrote that "[they] believe the level of evidence from this study provides sufficient evidence of causality."

The effect of delays might be substantial, Dr. Biagi and his colleagues noted. An estimated 49,000 people are newly diagnosed with stage III colorectal cancer each year. This represents 35% of the approximately 140,000 or so new cases of colorectal cancer in the United States.

The influence of postoperative performance status on wait times was not evaluated, which is a potential limitation of the study, Dr. Biagi and his coauthors wrote. In addition, the researchers were unable to determine the effect of starting adjuvant chemotherapy in the initial weeks after resection (before 4 weeks) or what percentage of patients completed adjuvant chemotherapy. Moreover, the studies were largely from a period of fluoropyrimidine adjuvant chemotherapy prior to widespread use of oxaliplatin, so extrapolation to the current era in which oxaliplatin is often added to fluoropyrimidine is uncertain.

Dr. Biagi previously presented the results of this meta-analysis and systematic review at a meeting on gastrointestinal cancers sponsored by ASCO, and it was reported by this news organization.

Dr. Biagi had no relevant financial disclosures. A study coauthor, Dr. William J. Mackillop, disclosed that he provided expert testimony in a 2009 class action suit regarding delays in postlumpectomy radiotherapy for breast cancer and the probability of local disease control.

CHICAGO – Delaying adjuvant chemotherapy following curative resection of colorectal cancer worsens overall and disease-free survival, according to the findings of a meta-analysis and systematic literature review.

Using 4 weeks postoperatively as a reference, Dr. James J. Biagi and his colleagues found that each additional 4 weeks between surgery and initiation of adjuvant chemotherapy was tied to a 14% decline in overall survival. A patient medically eligible for adjuvant chemotherapy at 4 weeks but whose adjuvant chemotherapy was delayed for any reason had a 14% higher mortality risk if treatment started at 8 weeks, and an almost 30% higher risk if treatment started at 12 weeks.

A second major finding was that some benefit of adjuvant chemotherapy remained beyond 12 weeks, Dr. Biagi and his associates reported at the annual meeting of the American Society of Clinical Oncology (ASCO).

Although most protocols do not recommend adjuvant chemotherapy beyond 3 months, "it is possible that a reasonable limit may be more on the order of 4 to 5 months," Dr. Biagi and his colleagues wrote in a report (JAMA 2011;305:2335-42) released to coincide with the presentation of results at the meeting.

The findings were consistent for disease-free or cancer-specific survival as well, reported Dr. Biagi, acting head of oncology at Queen’s University Cancer Research Institute, Kingston, Ontario, and his colleagues.

Prior to the study, the optimal time from surgery to initiation of adjuvant chemotherapy had not been identified. Dr. Biagi and his coinvestigators searched MEDLINE, as well as abstracts from recent proceedings of the annual meeting of ASCO and the European Society for Medical Oncology. They found 10 relevant studies that assessed overall survival related to adjuvant chemotherapy wait times with a total 15,410 patients. Six of these studies also addressed disease-free, relapse-free, or cancer-specific survival among 12,584 patients.

The studies of overall survival yielded a combined hazard ratio of 1.14 for a relative increase in mortality for each 4 weeks of waiting time past 4 weeks. The combined hazard ratio was the same, 1.14, for the six studies with additional survival end points. In addition, three studies specifically addressed cancer-specific survival; these yielded a combined hazard ratio of 1.15.

Nine studies were population- or registry-based, and one was a secondary analysis of a randomized controlled trial. Because it is unlikely that a prospective study will be conducted to evaluate the relationship between adjuvant chemotherapy wait times and survival in this patient population, the authors wrote that "[they] believe the level of evidence from this study provides sufficient evidence of causality."

The effect of delays might be substantial, Dr. Biagi and his colleagues noted. An estimated 49,000 people are newly diagnosed with stage III colorectal cancer each year. This represents 35% of the approximately 140,000 or so new cases of colorectal cancer in the United States.

The influence of postoperative performance status on wait times was not evaluated, which is a potential limitation of the study, Dr. Biagi and his coauthors wrote. In addition, the researchers were unable to determine the effect of starting adjuvant chemotherapy in the initial weeks after resection (before 4 weeks) or what percentage of patients completed adjuvant chemotherapy. Moreover, the studies were largely from a period of fluoropyrimidine adjuvant chemotherapy prior to widespread use of oxaliplatin, so extrapolation to the current era in which oxaliplatin is often added to fluoropyrimidine is uncertain.

Dr. Biagi previously presented the results of this meta-analysis and systematic review at a meeting on gastrointestinal cancers sponsored by ASCO, and it was reported by this news organization.

Dr. Biagi had no relevant financial disclosures. A study coauthor, Dr. William J. Mackillop, disclosed that he provided expert testimony in a 2009 class action suit regarding delays in postlumpectomy radiotherapy for breast cancer and the probability of local disease control.

CHICAGO – Delaying adjuvant chemotherapy following curative resection of colorectal cancer worsens overall and disease-free survival, according to the findings of a meta-analysis and systematic literature review.

Using 4 weeks postoperatively as a reference, Dr. James J. Biagi and his colleagues found that each additional 4 weeks between surgery and initiation of adjuvant chemotherapy was tied to a 14% decline in overall survival. A patient medically eligible for adjuvant chemotherapy at 4 weeks but whose adjuvant chemotherapy was delayed for any reason had a 14% higher mortality risk if treatment started at 8 weeks, and an almost 30% higher risk if treatment started at 12 weeks.

A second major finding was that some benefit of adjuvant chemotherapy remained beyond 12 weeks, Dr. Biagi and his associates reported at the annual meeting of the American Society of Clinical Oncology (ASCO).

Although most protocols do not recommend adjuvant chemotherapy beyond 3 months, "it is possible that a reasonable limit may be more on the order of 4 to 5 months," Dr. Biagi and his colleagues wrote in a report (JAMA 2011;305:2335-42) released to coincide with the presentation of results at the meeting.

The findings were consistent for disease-free or cancer-specific survival as well, reported Dr. Biagi, acting head of oncology at Queen’s University Cancer Research Institute, Kingston, Ontario, and his colleagues.

Prior to the study, the optimal time from surgery to initiation of adjuvant chemotherapy had not been identified. Dr. Biagi and his coinvestigators searched MEDLINE, as well as abstracts from recent proceedings of the annual meeting of ASCO and the European Society for Medical Oncology. They found 10 relevant studies that assessed overall survival related to adjuvant chemotherapy wait times with a total 15,410 patients. Six of these studies also addressed disease-free, relapse-free, or cancer-specific survival among 12,584 patients.

The studies of overall survival yielded a combined hazard ratio of 1.14 for a relative increase in mortality for each 4 weeks of waiting time past 4 weeks. The combined hazard ratio was the same, 1.14, for the six studies with additional survival end points. In addition, three studies specifically addressed cancer-specific survival; these yielded a combined hazard ratio of 1.15.

Nine studies were population- or registry-based, and one was a secondary analysis of a randomized controlled trial. Because it is unlikely that a prospective study will be conducted to evaluate the relationship between adjuvant chemotherapy wait times and survival in this patient population, the authors wrote that "[they] believe the level of evidence from this study provides sufficient evidence of causality."

The effect of delays might be substantial, Dr. Biagi and his colleagues noted. An estimated 49,000 people are newly diagnosed with stage III colorectal cancer each year. This represents 35% of the approximately 140,000 or so new cases of colorectal cancer in the United States.

The influence of postoperative performance status on wait times was not evaluated, which is a potential limitation of the study, Dr. Biagi and his coauthors wrote. In addition, the researchers were unable to determine the effect of starting adjuvant chemotherapy in the initial weeks after resection (before 4 weeks) or what percentage of patients completed adjuvant chemotherapy. Moreover, the studies were largely from a period of fluoropyrimidine adjuvant chemotherapy prior to widespread use of oxaliplatin, so extrapolation to the current era in which oxaliplatin is often added to fluoropyrimidine is uncertain.

Dr. Biagi previously presented the results of this meta-analysis and systematic review at a meeting on gastrointestinal cancers sponsored by ASCO, and it was reported by this news organization.

Dr. Biagi had no relevant financial disclosures. A study coauthor, Dr. William J. Mackillop, disclosed that he provided expert testimony in a 2009 class action suit regarding delays in postlumpectomy radiotherapy for breast cancer and the probability of local disease control.

CHICAGO – Delaying adjuvant chemotherapy following curative resection of colorectal cancer worsens overall and disease-free survival, according to the findings of a meta-analysis and systematic literature review.

Using 4 weeks postoperatively as a reference, Dr. James J. Biagi and his colleagues found that each additional 4 weeks between surgery and initiation of adjuvant chemotherapy was tied to a 14% decline in overall survival. A patient medically eligible for adjuvant chemotherapy at 4 weeks but whose adjuvant chemotherapy was delayed for any reason had a 14% higher mortality risk if treatment started at 8 weeks, and an almost 30% higher risk if treatment started at 12 weeks.

A second major finding was that some benefit of adjuvant chemotherapy remained beyond 12 weeks, Dr. Biagi and his associates reported at the annual meeting of the American Society of Clinical Oncology (ASCO).

Although most protocols do not recommend adjuvant chemotherapy beyond 3 months, "it is possible that a reasonable limit may be more on the order of 4 to 5 months," Dr. Biagi and his colleagues wrote in a report (JAMA 2011;305:2335-42) released to coincide with the presentation of results at the meeting.

The findings were consistent for disease-free or cancer-specific survival as well, reported Dr. Biagi, acting head of oncology at Queen’s University Cancer Research Institute, Kingston, Ontario, and his colleagues.

Prior to the study, the optimal time from surgery to initiation of adjuvant chemotherapy had not been identified. Dr. Biagi and his coinvestigators searched MEDLINE, as well as abstracts from recent proceedings of the annual meeting of ASCO and the European Society for Medical Oncology. They found 10 relevant studies that assessed overall survival related to adjuvant chemotherapy wait times with a total 15,410 patients. Six of these studies also addressed disease-free, relapse-free, or cancer-specific survival among 12,584 patients.

The studies of overall survival yielded a combined hazard ratio of 1.14 for a relative increase in mortality for each 4 weeks of waiting time past 4 weeks. The combined hazard ratio was the same, 1.14, for the six studies with additional survival end points. In addition, three studies specifically addressed cancer-specific survival; these yielded a combined hazard ratio of 1.15.

Nine studies were population- or registry-based, and one was a secondary analysis of a randomized controlled trial. Because it is unlikely that a prospective study will be conducted to evaluate the relationship between adjuvant chemotherapy wait times and survival in this patient population, the authors wrote that "[they] believe the level of evidence from this study provides sufficient evidence of causality."

The effect of delays might be substantial, Dr. Biagi and his colleagues noted. An estimated 49,000 people are newly diagnosed with stage III colorectal cancer each year. This represents 35% of the approximately 140,000 or so new cases of colorectal cancer in the United States.

The influence of postoperative performance status on wait times was not evaluated, which is a potential limitation of the study, Dr. Biagi and his coauthors wrote. In addition, the researchers were unable to determine the effect of starting adjuvant chemotherapy in the initial weeks after resection (before 4 weeks) or what percentage of patients completed adjuvant chemotherapy. Moreover, the studies were largely from a period of fluoropyrimidine adjuvant chemotherapy prior to widespread use of oxaliplatin, so extrapolation to the current era in which oxaliplatin is often added to fluoropyrimidine is uncertain.

Dr. Biagi previously presented the results of this meta-analysis and systematic review at a meeting on gastrointestinal cancers sponsored by ASCO, and it was reported by this news organization.

Dr. Biagi had no relevant financial disclosures. A study coauthor, Dr. William J. Mackillop, disclosed that he provided expert testimony in a 2009 class action suit regarding delays in postlumpectomy radiotherapy for breast cancer and the probability of local disease control.

CHICAGO – Delaying adjuvant chemotherapy following curative resection of colorectal cancer worsens overall and disease-free survival, according to the findings of a meta-analysis and systematic literature review.

Using 4 weeks postoperatively as a reference, Dr. James J. Biagi and his colleagues found that each additional 4 weeks between surgery and initiation of adjuvant chemotherapy was tied to a 14% decline in overall survival. A patient medically eligible for adjuvant chemotherapy at 4 weeks but whose adjuvant chemotherapy was delayed for any reason had a 14% higher mortality risk if treatment started at 8 weeks, and an almost 30% higher risk if treatment started at 12 weeks.

A second major finding was that some benefit of adjuvant chemotherapy remained beyond 12 weeks, Dr. Biagi and his associates reported at the annual meeting of the American Society of Clinical Oncology (ASCO).

Although most protocols do not recommend adjuvant chemotherapy beyond 3 months, "it is possible that a reasonable limit may be more on the order of 4 to 5 months," Dr. Biagi and his colleagues wrote in a report (JAMA 2011;305:2335-42) released to coincide with the presentation of results at the meeting.

The findings were consistent for disease-free or cancer-specific survival as well, reported Dr. Biagi, acting head of oncology at Queen’s University Cancer Research Institute, Kingston, Ontario, and his colleagues.

Prior to the study, the optimal time from surgery to initiation of adjuvant chemotherapy had not been identified. Dr. Biagi and his coinvestigators searched MEDLINE, as well as abstracts from recent proceedings of the annual meeting of ASCO and the European Society for Medical Oncology. They found 10 relevant studies that assessed overall survival related to adjuvant chemotherapy wait times with a total 15,410 patients. Six of these studies also addressed disease-free, relapse-free, or cancer-specific survival among 12,584 patients.

The studies of overall survival yielded a combined hazard ratio of 1.14 for a relative increase in mortality for each 4 weeks of waiting time past 4 weeks. The combined hazard ratio was the same, 1.14, for the six studies with additional survival end points. In addition, three studies specifically addressed cancer-specific survival; these yielded a combined hazard ratio of 1.15.

Nine studies were population- or registry-based, and one was a secondary analysis of a randomized controlled trial. Because it is unlikely that a prospective study will be conducted to evaluate the relationship between adjuvant chemotherapy wait times and survival in this patient population, the authors wrote that "[they] believe the level of evidence from this study provides sufficient evidence of causality."

The effect of delays might be substantial, Dr. Biagi and his colleagues noted. An estimated 49,000 people are newly diagnosed with stage III colorectal cancer each year. This represents 35% of the approximately 140,000 or so new cases of colorectal cancer in the United States.

The influence of postoperative performance status on wait times was not evaluated, which is a potential limitation of the study, Dr. Biagi and his coauthors wrote. In addition, the researchers were unable to determine the effect of starting adjuvant chemotherapy in the initial weeks after resection (before 4 weeks) or what percentage of patients completed adjuvant chemotherapy. Moreover, the studies were largely from a period of fluoropyrimidine adjuvant chemotherapy prior to widespread use of oxaliplatin, so extrapolation to the current era in which oxaliplatin is often added to fluoropyrimidine is uncertain.

Dr. Biagi previously presented the results of this meta-analysis and systematic review at a meeting on gastrointestinal cancers sponsored by ASCO, and it was reported by this news organization.

Dr. Biagi had no relevant financial disclosures. A study coauthor, Dr. William J. Mackillop, disclosed that he provided expert testimony in a 2009 class action suit regarding delays in postlumpectomy radiotherapy for breast cancer and the probability of local disease control.

CHICAGO – Delaying adjuvant chemotherapy following curative resection of colorectal cancer worsens overall and disease-free survival, according to the findings of a meta-analysis and systematic literature review.

Using 4 weeks postoperatively as a reference, Dr. James J. Biagi and his colleagues found that each additional 4 weeks between surgery and initiation of adjuvant chemotherapy was tied to a 14% decline in overall survival. A patient medically eligible for adjuvant chemotherapy at 4 weeks but whose adjuvant chemotherapy was delayed for any reason had a 14% higher mortality risk if treatment started at 8 weeks, and an almost 30% higher risk if treatment started at 12 weeks.

A second major finding was that some benefit of adjuvant chemotherapy remained beyond 12 weeks, Dr. Biagi and his associates reported at the annual meeting of the American Society of Clinical Oncology (ASCO).

Although most protocols do not recommend adjuvant chemotherapy beyond 3 months, "it is possible that a reasonable limit may be more on the order of 4 to 5 months," Dr. Biagi and his colleagues wrote in a report (JAMA 2011;305:2335-42) released to coincide with the presentation of results at the meeting.

The findings were consistent for disease-free or cancer-specific survival as well, reported Dr. Biagi, acting head of oncology at Queen’s University Cancer Research Institute, Kingston, Ontario, and his colleagues.

Prior to the study, the optimal time from surgery to initiation of adjuvant chemotherapy had not been identified. Dr. Biagi and his coinvestigators searched MEDLINE, as well as abstracts from recent proceedings of the annual meeting of ASCO and the European Society for Medical Oncology. They found 10 relevant studies that assessed overall survival related to adjuvant chemotherapy wait times with a total 15,410 patients. Six of these studies also addressed disease-free, relapse-free, or cancer-specific survival among 12,584 patients.

The studies of overall survival yielded a combined hazard ratio of 1.14 for a relative increase in mortality for each 4 weeks of waiting time past 4 weeks. The combined hazard ratio was the same, 1.14, for the six studies with additional survival end points. In addition, three studies specifically addressed cancer-specific survival; these yielded a combined hazard ratio of 1.15.

Nine studies were population- or registry-based, and one was a secondary analysis of a randomized controlled trial. Because it is unlikely that a prospective study will be conducted to evaluate the relationship between adjuvant chemotherapy wait times and survival in this patient population, the authors wrote that "[they] believe the level of evidence from this study provides sufficient evidence of causality."

The effect of delays might be substantial, Dr. Biagi and his colleagues noted. An estimated 49,000 people are newly diagnosed with stage III colorectal cancer each year. This represents 35% of the approximately 140,000 or so new cases of colorectal cancer in the United States.

The influence of postoperative performance status on wait times was not evaluated, which is a potential limitation of the study, Dr. Biagi and his coauthors wrote. In addition, the researchers were unable to determine the effect of starting adjuvant chemotherapy in the initial weeks after resection (before 4 weeks) or what percentage of patients completed adjuvant chemotherapy. Moreover, the studies were largely from a period of fluoropyrimidine adjuvant chemotherapy prior to widespread use of oxaliplatin, so extrapolation to the current era in which oxaliplatin is often added to fluoropyrimidine is uncertain.

Dr. Biagi previously presented the results of this meta-analysis and systematic review at a meeting on gastrointestinal cancers sponsored by ASCO, and it was reported by this news organization.

Dr. Biagi had no relevant financial disclosures. A study coauthor, Dr. William J. Mackillop, disclosed that he provided expert testimony in a 2009 class action suit regarding delays in postlumpectomy radiotherapy for breast cancer and the probability of local disease control.

CHICAGO – Delaying adjuvant chemotherapy following curative resection of colorectal cancer worsens overall and disease-free survival, according to the findings of a meta-analysis and systematic literature review.

Using 4 weeks postoperatively as a reference, Dr. James J. Biagi and his colleagues found that each additional 4 weeks between surgery and initiation of adjuvant chemotherapy was tied to a 14% decline in overall survival. A patient medically eligible for adjuvant chemotherapy at 4 weeks but whose adjuvant chemotherapy was delayed for any reason had a 14% higher mortality risk if treatment started at 8 weeks, and an almost 30% higher risk if treatment started at 12 weeks.

A second major finding was that some benefit of adjuvant chemotherapy remained beyond 12 weeks, Dr. Biagi and his associates reported at the annual meeting of the American Society of Clinical Oncology (ASCO).

Although most protocols do not recommend adjuvant chemotherapy beyond 3 months, "it is possible that a reasonable limit may be more on the order of 4 to 5 months," Dr. Biagi and his colleagues wrote in a report (JAMA 2011;305:2335-42) released to coincide with the presentation of results at the meeting.

The findings were consistent for disease-free or cancer-specific survival as well, reported Dr. Biagi, acting head of oncology at Queen’s University Cancer Research Institute, Kingston, Ontario, and his colleagues.

Prior to the study, the optimal time from surgery to initiation of adjuvant chemotherapy had not been identified. Dr. Biagi and his coinvestigators searched MEDLINE, as well as abstracts from recent proceedings of the annual meeting of ASCO and the European Society for Medical Oncology. They found 10 relevant studies that assessed overall survival related to adjuvant chemotherapy wait times with a total 15,410 patients. Six of these studies also addressed disease-free, relapse-free, or cancer-specific survival among 12,584 patients.

The studies of overall survival yielded a combined hazard ratio of 1.14 for a relative increase in mortality for each 4 weeks of waiting time past 4 weeks. The combined hazard ratio was the same, 1.14, for the six studies with additional survival end points. In addition, three studies specifically addressed cancer-specific survival; these yielded a combined hazard ratio of 1.15.

Nine studies were population- or registry-based, and one was a secondary analysis of a randomized controlled trial. Because it is unlikely that a prospective study will be conducted to evaluate the relationship between adjuvant chemotherapy wait times and survival in this patient population, the authors wrote that "[they] believe the level of evidence from this study provides sufficient evidence of causality."

The effect of delays might be substantial, Dr. Biagi and his colleagues noted. An estimated 49,000 people are newly diagnosed with stage III colorectal cancer each year. This represents 35% of the approximately 140,000 or so new cases of colorectal cancer in the United States.

The influence of postoperative performance status on wait times was not evaluated, which is a potential limitation of the study, Dr. Biagi and his coauthors wrote. In addition, the researchers were unable to determine the effect of starting adjuvant chemotherapy in the initial weeks after resection (before 4 weeks) or what percentage of patients completed adjuvant chemotherapy. Moreover, the studies were largely from a period of fluoropyrimidine adjuvant chemotherapy prior to widespread use of oxaliplatin, so extrapolation to the current era in which oxaliplatin is often added to fluoropyrimidine is uncertain.

Dr. Biagi previously presented the results of this meta-analysis and systematic review at a meeting on gastrointestinal cancers sponsored by ASCO, and it was reported by this news organization.

Dr. Biagi had no relevant financial disclosures. A study coauthor, Dr. William J. Mackillop, disclosed that he provided expert testimony in a 2009 class action suit regarding delays in postlumpectomy radiotherapy for breast cancer and the probability of local disease control.

CHICAGO – Delaying adjuvant chemotherapy following curative resection of colorectal cancer worsens overall and disease-free survival, according to the findings of a meta-analysis and systematic literature review.

Using 4 weeks postoperatively as a reference, Dr. James J. Biagi and his colleagues found that each additional 4 weeks between surgery and initiation of adjuvant chemotherapy was tied to a 14% decline in overall survival. A patient medically eligible for adjuvant chemotherapy at 4 weeks but whose adjuvant chemotherapy was delayed for any reason had a 14% higher mortality risk if treatment started at 8 weeks, and an almost 30% higher risk if treatment started at 12 weeks.

A second major finding was that some benefit of adjuvant chemotherapy remained beyond 12 weeks, Dr. Biagi and his associates reported at the annual meeting of the American Society of Clinical Oncology (ASCO).

Although most protocols do not recommend adjuvant chemotherapy beyond 3 months, "it is possible that a reasonable limit may be more on the order of 4 to 5 months," Dr. Biagi and his colleagues wrote in a report (JAMA 2011;305:2335-42) released to coincide with the presentation of results at the meeting.

The findings were consistent for disease-free or cancer-specific survival as well, reported Dr. Biagi, acting head of oncology at Queen’s University Cancer Research Institute, Kingston, Ontario, and his colleagues.

Prior to the study, the optimal time from surgery to initiation of adjuvant chemotherapy had not been identified. Dr. Biagi and his coinvestigators searched MEDLINE, as well as abstracts from recent proceedings of the annual meeting of ASCO and the European Society for Medical Oncology. They found 10 relevant studies that assessed overall survival related to adjuvant chemotherapy wait times with a total 15,410 patients. Six of these studies also addressed disease-free, relapse-free, or cancer-specific survival among 12,584 patients.

The studies of overall survival yielded a combined hazard ratio of 1.14 for a relative increase in mortality for each 4 weeks of waiting time past 4 weeks. The combined hazard ratio was the same, 1.14, for the six studies with additional survival end points. In addition, three studies specifically addressed cancer-specific survival; these yielded a combined hazard ratio of 1.15.

Nine studies were population- or registry-based, and one was a secondary analysis of a randomized controlled trial. Because it is unlikely that a prospective study will be conducted to evaluate the relationship between adjuvant chemotherapy wait times and survival in this patient population, the authors wrote that "[they] believe the level of evidence from this study provides sufficient evidence of causality."

The effect of delays might be substantial, Dr. Biagi and his colleagues noted. An estimated 49,000 people are newly diagnosed with stage III colorectal cancer each year. This represents 35% of the approximately 140,000 or so new cases of colorectal cancer in the United States.

The influence of postoperative performance status on wait times was not evaluated, which is a potential limitation of the study, Dr. Biagi and his coauthors wrote. In addition, the researchers were unable to determine the effect of starting adjuvant chemotherapy in the initial weeks after resection (before 4 weeks) or what percentage of patients completed adjuvant chemotherapy. Moreover, the studies were largely from a period of fluoropyrimidine adjuvant chemotherapy prior to widespread use of oxaliplatin, so extrapolation to the current era in which oxaliplatin is often added to fluoropyrimidine is uncertain.

Dr. Biagi previously presented the results of this meta-analysis and systematic review at a meeting on gastrointestinal cancers sponsored by ASCO, and it was reported by this news organization.

Dr. Biagi had no relevant financial disclosures. A study coauthor, Dr. William J. Mackillop, disclosed that he provided expert testimony in a 2009 class action suit regarding delays in postlumpectomy radiotherapy for breast cancer and the probability of local disease control.