Susan London

AN FRANCISCO – Levels of serum markers measured in the second trimester for aneuploidy screening also may improve prediction of stillbirth, according to results of a population-based, case-control study conducted by the Stillbirth Collaborative Research Network.

Of four markers studied, inhibin A was the only one associated with the risk of stillbirth after adjustment for the other markers and risk factors known before pregnancy. But elevated levels of this marker alone had a positive likelihood ratio of just 5.44.

On the other hand, elevated levels of both inhibin A and maternal serum alpha-fetoprotein (MSAFP) had a positive likelihood ratio of 15.77.

"The combination of elevated inhibin A with elevated MSAFP improves prediction of stillbirth," Dr. George R. Saade commented at the annual meeting of the Society for Maternal-Fetal Medicine. "This association is strong and may prove useful in risk assessment."

An attendee asked how the findings could be applied clinically and whether laboratories should start flagging this combination on test results, given that it might not necessarily be flagged for Down syndrome or neural tube defects.

"That’s obviously the next step in all of this: What do we do with the result, and how do we manage these patients?" Dr. Saade acknowledged. "You cannot ignore a positive likelihood ratio of 15, but what do we do?"

Giving one possible scenario, he noted that growth restriction has been implicated in up to 40% of cases of stillbirth, so earlier delivery in pregnancies with elevation of both markers could potentially alter outcome in some cases.

But "we still don’t know," he cautioned. "What I would like to do is actually dig down deeper and develop a model, like a multiple-marker screen we do for Down syndrome, where the risk is individualized according to the patient."

For the study, births were drawn from a parent population-based, case-control study involving 59 hospitals and more than 2,500 births. Stillbirths (cases) and a representative sample of live births (controls) were evaluated with maternal interviews, medical record reviews, and analysis of biospecimens.

In the substudy, the investigators included births from the parent study in which the mother had second-trimester serum screening for aneuploidy as part of routine prenatal care and delivered after 24 weeks’ gestation.

Levels of four serum markers – inhibin A, MSAFP, HCG, and unconjugated estriol (uE3) – were analyzed alone and in selected combinations for their association with stillbirth.

In all, the substudy had 157 stillbirths and 626 live births. "This is the largest population-based study of stillbirth with an extensive evaluation of both cases and controls," noted Dr. Saade, chief of the division of maternal-fetal medicine at the University of Texas, Galveston.

In a multivariate analysis adjusted for the other markers only, women had an elevated risk of stillbirth if they had above-normal levels (defined as greater than 2.0 multiples of the median) vs. normal levels of MSAFP (odds ratio, 3.91; P = .006) and inhibin A (OR, 5.68; P less than .0001).

After additional adjustment for a prepregnancy risk score for stillbirth, which included more than a dozen sociodemographic, medical, and reproductive factors, the only marker still associated with increased risk was inhibin A (OR, 4.49; P = .001).

For predicting stillbirth, the combination of elevated MSAFP and inhibin A levels had the highest positive likelihood ratio of any of the markers individually and in combination by far (15.77).

This value "is above the cutoff of 10, traditionally considered as clinically useful," noted Dr. Saade.

In comparison, the positive likelihood ratio was 5.44 for elevated inhibin A alone and 2.58 for elevated MSAFP alone.

The combination also had high specificity (99.6%). But its sensitivity (6.0%) and negative likelihood ratio (0.94) were lower than those considered clinically useful, according to Dr. Saade.

The study’s findings were essentially the same after exclusion of births involving multiple gestations, intrapartum stillbirth, and fetal anomalies.

To expand on the findings, the investigators plan to reanalyze the data, stratifying results according to the causes of the stillbirths, he said.

Dr. Saade agreed with an attendee that it will be important to verify that the markers are, in fact, predicting stillbirth and not growth restriction instead.

"The problem is, when do you count what was the timing of the stillbirth death ... because whether it’s growth restricted or not depends on when the death occurred and whether there was even a change in the weight after the death," he said.

His team is therefore obtaining fetal measurements to better determine the timing of this event and the potential contribution of growth restriction.

Dr. Saade did not report any relevant conflicts financial disclosures.

AN FRANCISCO – Levels of serum markers measured in the second trimester for aneuploidy screening also may improve prediction of stillbirth, according to results of a population-based, case-control study conducted by the Stillbirth Collaborative Research Network.

Of four markers studied, inhibin A was the only one associated with the risk of stillbirth after adjustment for the other markers and risk factors known before pregnancy. But elevated levels of this marker alone had a positive likelihood ratio of just 5.44.

On the other hand, elevated levels of both inhibin A and maternal serum alpha-fetoprotein (MSAFP) had a positive likelihood ratio of 15.77.

"The combination of elevated inhibin A with elevated MSAFP improves prediction of stillbirth," Dr. George R. Saade commented at the annual meeting of the Society for Maternal-Fetal Medicine. "This association is strong and may prove useful in risk assessment."

An attendee asked how the findings could be applied clinically and whether laboratories should start flagging this combination on test results, given that it might not necessarily be flagged for Down syndrome or neural tube defects.

"That’s obviously the next step in all of this: What do we do with the result, and how do we manage these patients?" Dr. Saade acknowledged. "You cannot ignore a positive likelihood ratio of 15, but what do we do?"

Giving one possible scenario, he noted that growth restriction has been implicated in up to 40% of cases of stillbirth, so earlier delivery in pregnancies with elevation of both markers could potentially alter outcome in some cases.

But "we still don’t know," he cautioned. "What I would like to do is actually dig down deeper and develop a model, like a multiple-marker screen we do for Down syndrome, where the risk is individualized according to the patient."

For the study, births were drawn from a parent population-based, case-control study involving 59 hospitals and more than 2,500 births. Stillbirths (cases) and a representative sample of live births (controls) were evaluated with maternal interviews, medical record reviews, and analysis of biospecimens.

In the substudy, the investigators included births from the parent study in which the mother had second-trimester serum screening for aneuploidy as part of routine prenatal care and delivered after 24 weeks’ gestation.

Levels of four serum markers – inhibin A, MSAFP, HCG, and unconjugated estriol (uE3) – were analyzed alone and in selected combinations for their association with stillbirth.

In all, the substudy had 157 stillbirths and 626 live births. "This is the largest population-based study of stillbirth with an extensive evaluation of both cases and controls," noted Dr. Saade, chief of the division of maternal-fetal medicine at the University of Texas, Galveston.

In a multivariate analysis adjusted for the other markers only, women had an elevated risk of stillbirth if they had above-normal levels (defined as greater than 2.0 multiples of the median) vs. normal levels of MSAFP (odds ratio, 3.91; P = .006) and inhibin A (OR, 5.68; P less than .0001).

After additional adjustment for a prepregnancy risk score for stillbirth, which included more than a dozen sociodemographic, medical, and reproductive factors, the only marker still associated with increased risk was inhibin A (OR, 4.49; P = .001).

For predicting stillbirth, the combination of elevated MSAFP and inhibin A levels had the highest positive likelihood ratio of any of the markers individually and in combination by far (15.77).

This value "is above the cutoff of 10, traditionally considered as clinically useful," noted Dr. Saade.

In comparison, the positive likelihood ratio was 5.44 for elevated inhibin A alone and 2.58 for elevated MSAFP alone.

The combination also had high specificity (99.6%). But its sensitivity (6.0%) and negative likelihood ratio (0.94) were lower than those considered clinically useful, according to Dr. Saade.

The study’s findings were essentially the same after exclusion of births involving multiple gestations, intrapartum stillbirth, and fetal anomalies.

To expand on the findings, the investigators plan to reanalyze the data, stratifying results according to the causes of the stillbirths, he said.

Dr. Saade agreed with an attendee that it will be important to verify that the markers are, in fact, predicting stillbirth and not growth restriction instead.

"The problem is, when do you count what was the timing of the stillbirth death ... because whether it’s growth restricted or not depends on when the death occurred and whether there was even a change in the weight after the death," he said.

His team is therefore obtaining fetal measurements to better determine the timing of this event and the potential contribution of growth restriction.

Dr. Saade did not report any relevant conflicts financial disclosures.

AN FRANCISCO – Levels of serum markers measured in the second trimester for aneuploidy screening also may improve prediction of stillbirth, according to results of a population-based, case-control study conducted by the Stillbirth Collaborative Research Network.

Of four markers studied, inhibin A was the only one associated with the risk of stillbirth after adjustment for the other markers and risk factors known before pregnancy. But elevated levels of this marker alone had a positive likelihood ratio of just 5.44.

On the other hand, elevated levels of both inhibin A and maternal serum alpha-fetoprotein (MSAFP) had a positive likelihood ratio of 15.77.

"The combination of elevated inhibin A with elevated MSAFP improves prediction of stillbirth," Dr. George R. Saade commented at the annual meeting of the Society for Maternal-Fetal Medicine. "This association is strong and may prove useful in risk assessment."

An attendee asked how the findings could be applied clinically and whether laboratories should start flagging this combination on test results, given that it might not necessarily be flagged for Down syndrome or neural tube defects.

"That’s obviously the next step in all of this: What do we do with the result, and how do we manage these patients?" Dr. Saade acknowledged. "You cannot ignore a positive likelihood ratio of 15, but what do we do?"

Giving one possible scenario, he noted that growth restriction has been implicated in up to 40% of cases of stillbirth, so earlier delivery in pregnancies with elevation of both markers could potentially alter outcome in some cases.

But "we still don’t know," he cautioned. "What I would like to do is actually dig down deeper and develop a model, like a multiple-marker screen we do for Down syndrome, where the risk is individualized according to the patient."

For the study, births were drawn from a parent population-based, case-control study involving 59 hospitals and more than 2,500 births. Stillbirths (cases) and a representative sample of live births (controls) were evaluated with maternal interviews, medical record reviews, and analysis of biospecimens.

In the substudy, the investigators included births from the parent study in which the mother had second-trimester serum screening for aneuploidy as part of routine prenatal care and delivered after 24 weeks’ gestation.

Levels of four serum markers – inhibin A, MSAFP, HCG, and unconjugated estriol (uE3) – were analyzed alone and in selected combinations for their association with stillbirth.

In all, the substudy had 157 stillbirths and 626 live births. "This is the largest population-based study of stillbirth with an extensive evaluation of both cases and controls," noted Dr. Saade, chief of the division of maternal-fetal medicine at the University of Texas, Galveston.

In a multivariate analysis adjusted for the other markers only, women had an elevated risk of stillbirth if they had above-normal levels (defined as greater than 2.0 multiples of the median) vs. normal levels of MSAFP (odds ratio, 3.91; P = .006) and inhibin A (OR, 5.68; P less than .0001).

After additional adjustment for a prepregnancy risk score for stillbirth, which included more than a dozen sociodemographic, medical, and reproductive factors, the only marker still associated with increased risk was inhibin A (OR, 4.49; P = .001).

For predicting stillbirth, the combination of elevated MSAFP and inhibin A levels had the highest positive likelihood ratio of any of the markers individually and in combination by far (15.77).

This value "is above the cutoff of 10, traditionally considered as clinically useful," noted Dr. Saade.

In comparison, the positive likelihood ratio was 5.44 for elevated inhibin A alone and 2.58 for elevated MSAFP alone.

The combination also had high specificity (99.6%). But its sensitivity (6.0%) and negative likelihood ratio (0.94) were lower than those considered clinically useful, according to Dr. Saade.

The study’s findings were essentially the same after exclusion of births involving multiple gestations, intrapartum stillbirth, and fetal anomalies.

To expand on the findings, the investigators plan to reanalyze the data, stratifying results according to the causes of the stillbirths, he said.

Dr. Saade agreed with an attendee that it will be important to verify that the markers are, in fact, predicting stillbirth and not growth restriction instead.

"The problem is, when do you count what was the timing of the stillbirth death ... because whether it’s growth restricted or not depends on when the death occurred and whether there was even a change in the weight after the death," he said.

His team is therefore obtaining fetal measurements to better determine the timing of this event and the potential contribution of growth restriction.

Dr. Saade did not report any relevant conflicts financial disclosures.

SAN FRANCISCO - Overweight and obese pregnant women have a longer labor, especially if they have not had any previous births, according to a retrospective observational study conducted by the Consortium on Safe Labor.

Among the more than 100,000 women studied, the time required to progress from 4 cm to 10 cm of cervical dilatation increased steadily with body mass index. It was 2.9 hours (56%) longer for nulliparas and 1.4 hours (33%) longer for multiparas having the highest vs. lowest body mass index.

The duration of the second stage of labor also increased with BMI among the nulliparas, particularly if they had an epidural, according to results reported at the annual meeting of the Society for Maternal-Fetal Medicine.

"This information highlights the concept that contemporary labor practices should take into account the changing profiles of our obstetrical population, particularly increasing BMI," commented principal investigator Dr. Michelle A. Kominiarek. "Allowing for a slower progression of labor for obese gravidas prior to intervening with a cesarean has the important potential of decreasing the cesarean delivery rate."

Excess weight during pregnancy has been linked to both dysfunctional labor and cesareans, she observed. "The explanation for these findings is not known, but greater fetal size, soft tissue obstruction to labor, poor uterine contractility, more frequent inductions as a result of pregnancy complications, and caregiver biases have been proposed."

The investigators undertook the study "to describe labor patterns in a contemporary obstetrical population, one with greater inductions, greater epidurals, fewer operative deliveries, and presumably a greater maternal weight," explained Dr. Kominiarek of the University of Illinois at Chicago.

They analyzed records in an obstetric database that captured data from 12 U.S. clinical centers for the years 2002-2008. Results were based on 118,978 women who had labor at term; had a singleton, live-born infant with cephalic presentation; and had not had a previous cesarean.

The women were divided into five categories of BMI at the time of admission (less than 25.0 kg/m², 25.0-29.9, 30.0-34.9, 35.0-39.9, and 40.0 or greater).

The average BMI was 30.5 for the entire cohort, and slightly more than 7% of the women had a BMI in the highest category, Dr. Kominiarek reported.

Results showed that as BMI increased, cervical dilation proceeded more slowly, so that women in each BMI category had a distinct labor curve when dilation was plotted against time.

Among nulliparas, there were no clear inflections in these curves to indicate when labor transitioned from the latent to the active phase.

After adjustment for potential confounders (age, race, gestational age, diabetes, induction of labor, augmentation of labor, epidural use, and operative vaginal deliveries), the median time to progress from 4 to 10 cm of cervical dilatation was 5.2 hours for nulliparas in the lowest BMI category, compared with 8.1 hours for those in the highest (P less than .001).

The findings were similar in analyses that looked at each additional centimeter of cervical dilatation. The prolongation with increasing BMI was most evident early in labor, going from 3 to 4 cm and from 4 to 5 cm.

BMI was also associated with a slowing of the duration of the second stage of labor for nulliparas who had an epidural, but less so for those who did not, according to Dr. Kominiarek.

Among multiparas, the labor curves did show inflection points, with a rapid acceleration of cervical dilation indicating entry into active labor. However, the higher a woman’s BMI, the longer it took to get to that point.

The adjusted median time to progress from 4 to 10 cm of cervical dilatation was 4.3 hours for multiparas in the lowest BMI category, compared with 5.7 hours for those in the highest (P less than .001).

The findings here were also similar in analyses that looked at each additional centimeter of cervical dilation, with BMI having greatest impact on the progression from 4 to 5 cm. But the associations were mostly not significant.

Higher BMI did not slow the duration of the second stage of labor among multiparas, regardless of whether they had an epidural.

The reason for the prolongation of labor with increasing BMI is not yet clear, according to Dr. Kominiarek. But she speculated that some of the aforementioned factors, such as weight-induced alterations in physiology or comorbidities, may affect the pace of labor.

Dr. Kominiarek did not report any relevant conflicts of interest.

SAN FRANCISCO - Overweight and obese pregnant women have a longer labor, especially if they have not had any previous births, according to a retrospective observational study conducted by the Consortium on Safe Labor.

Among the more than 100,000 women studied, the time required to progress from 4 cm to 10 cm of cervical dilatation increased steadily with body mass index. It was 2.9 hours (56%) longer for nulliparas and 1.4 hours (33%) longer for multiparas having the highest vs. lowest body mass index.

The duration of the second stage of labor also increased with BMI among the nulliparas, particularly if they had an epidural, according to results reported at the annual meeting of the Society for Maternal-Fetal Medicine.

"This information highlights the concept that contemporary labor practices should take into account the changing profiles of our obstetrical population, particularly increasing BMI," commented principal investigator Dr. Michelle A. Kominiarek. "Allowing for a slower progression of labor for obese gravidas prior to intervening with a cesarean has the important potential of decreasing the cesarean delivery rate."

Excess weight during pregnancy has been linked to both dysfunctional labor and cesareans, she observed. "The explanation for these findings is not known, but greater fetal size, soft tissue obstruction to labor, poor uterine contractility, more frequent inductions as a result of pregnancy complications, and caregiver biases have been proposed."

The investigators undertook the study "to describe labor patterns in a contemporary obstetrical population, one with greater inductions, greater epidurals, fewer operative deliveries, and presumably a greater maternal weight," explained Dr. Kominiarek of the University of Illinois at Chicago.

They analyzed records in an obstetric database that captured data from 12 U.S. clinical centers for the years 2002-2008. Results were based on 118,978 women who had labor at term; had a singleton, live-born infant with cephalic presentation; and had not had a previous cesarean.

The women were divided into five categories of BMI at the time of admission (less than 25.0 kg/m², 25.0-29.9, 30.0-34.9, 35.0-39.9, and 40.0 or greater).

The average BMI was 30.5 for the entire cohort, and slightly more than 7% of the women had a BMI in the highest category, Dr. Kominiarek reported.

Results showed that as BMI increased, cervical dilation proceeded more slowly, so that women in each BMI category had a distinct labor curve when dilation was plotted against time.

Among nulliparas, there were no clear inflections in these curves to indicate when labor transitioned from the latent to the active phase.

After adjustment for potential confounders (age, race, gestational age, diabetes, induction of labor, augmentation of labor, epidural use, and operative vaginal deliveries), the median time to progress from 4 to 10 cm of cervical dilatation was 5.2 hours for nulliparas in the lowest BMI category, compared with 8.1 hours for those in the highest (P less than .001).

The findings were similar in analyses that looked at each additional centimeter of cervical dilatation. The prolongation with increasing BMI was most evident early in labor, going from 3 to 4 cm and from 4 to 5 cm.

BMI was also associated with a slowing of the duration of the second stage of labor for nulliparas who had an epidural, but less so for those who did not, according to Dr. Kominiarek.

Among multiparas, the labor curves did show inflection points, with a rapid acceleration of cervical dilation indicating entry into active labor. However, the higher a woman’s BMI, the longer it took to get to that point.

The adjusted median time to progress from 4 to 10 cm of cervical dilatation was 4.3 hours for multiparas in the lowest BMI category, compared with 5.7 hours for those in the highest (P less than .001).

The findings here were also similar in analyses that looked at each additional centimeter of cervical dilation, with BMI having greatest impact on the progression from 4 to 5 cm. But the associations were mostly not significant.

Higher BMI did not slow the duration of the second stage of labor among multiparas, regardless of whether they had an epidural.

The reason for the prolongation of labor with increasing BMI is not yet clear, according to Dr. Kominiarek. But she speculated that some of the aforementioned factors, such as weight-induced alterations in physiology or comorbidities, may affect the pace of labor.

Dr. Kominiarek did not report any relevant conflicts of interest.

SAN FRANCISCO - Overweight and obese pregnant women have a longer labor, especially if they have not had any previous births, according to a retrospective observational study conducted by the Consortium on Safe Labor.

Among the more than 100,000 women studied, the time required to progress from 4 cm to 10 cm of cervical dilatation increased steadily with body mass index. It was 2.9 hours (56%) longer for nulliparas and 1.4 hours (33%) longer for multiparas having the highest vs. lowest body mass index.

The duration of the second stage of labor also increased with BMI among the nulliparas, particularly if they had an epidural, according to results reported at the annual meeting of the Society for Maternal-Fetal Medicine.

"This information highlights the concept that contemporary labor practices should take into account the changing profiles of our obstetrical population, particularly increasing BMI," commented principal investigator Dr. Michelle A. Kominiarek. "Allowing for a slower progression of labor for obese gravidas prior to intervening with a cesarean has the important potential of decreasing the cesarean delivery rate."

Excess weight during pregnancy has been linked to both dysfunctional labor and cesareans, she observed. "The explanation for these findings is not known, but greater fetal size, soft tissue obstruction to labor, poor uterine contractility, more frequent inductions as a result of pregnancy complications, and caregiver biases have been proposed."

The investigators undertook the study "to describe labor patterns in a contemporary obstetrical population, one with greater inductions, greater epidurals, fewer operative deliveries, and presumably a greater maternal weight," explained Dr. Kominiarek of the University of Illinois at Chicago.

They analyzed records in an obstetric database that captured data from 12 U.S. clinical centers for the years 2002-2008. Results were based on 118,978 women who had labor at term; had a singleton, live-born infant with cephalic presentation; and had not had a previous cesarean.

The women were divided into five categories of BMI at the time of admission (less than 25.0 kg/m², 25.0-29.9, 30.0-34.9, 35.0-39.9, and 40.0 or greater).

The average BMI was 30.5 for the entire cohort, and slightly more than 7% of the women had a BMI in the highest category, Dr. Kominiarek reported.

Results showed that as BMI increased, cervical dilation proceeded more slowly, so that women in each BMI category had a distinct labor curve when dilation was plotted against time.

Among nulliparas, there were no clear inflections in these curves to indicate when labor transitioned from the latent to the active phase.

After adjustment for potential confounders (age, race, gestational age, diabetes, induction of labor, augmentation of labor, epidural use, and operative vaginal deliveries), the median time to progress from 4 to 10 cm of cervical dilatation was 5.2 hours for nulliparas in the lowest BMI category, compared with 8.1 hours for those in the highest (P less than .001).

The findings were similar in analyses that looked at each additional centimeter of cervical dilatation. The prolongation with increasing BMI was most evident early in labor, going from 3 to 4 cm and from 4 to 5 cm.

BMI was also associated with a slowing of the duration of the second stage of labor for nulliparas who had an epidural, but less so for those who did not, according to Dr. Kominiarek.

Among multiparas, the labor curves did show inflection points, with a rapid acceleration of cervical dilation indicating entry into active labor. However, the higher a woman’s BMI, the longer it took to get to that point.

The adjusted median time to progress from 4 to 10 cm of cervical dilatation was 4.3 hours for multiparas in the lowest BMI category, compared with 5.7 hours for those in the highest (P less than .001).

The findings here were also similar in analyses that looked at each additional centimeter of cervical dilation, with BMI having greatest impact on the progression from 4 to 5 cm. But the associations were mostly not significant.

Higher BMI did not slow the duration of the second stage of labor among multiparas, regardless of whether they had an epidural.

The reason for the prolongation of labor with increasing BMI is not yet clear, according to Dr. Kominiarek. But she speculated that some of the aforementioned factors, such as weight-induced alterations in physiology or comorbidities, may affect the pace of labor.

Dr. Kominiarek did not report any relevant conflicts of interest.

SAN FRANCISCO - Overweight and obese pregnant women have a longer labor, especially if they have not had any previous births, according to a retrospective observational study conducted by the Consortium on Safe Labor.

Among the more than 100,000 women studied, the time required to progress from 4 cm to 10 cm of cervical dilatation increased steadily with body mass index. It was 2.9 hours (56%) longer for nulliparas and 1.4 hours (33%) longer for multiparas having the highest vs. lowest body mass index.

The duration of the second stage of labor also increased with BMI among the nulliparas, particularly if they had an epidural, according to results reported at the annual meeting of the Society for Maternal-Fetal Medicine.

"This information highlights the concept that contemporary labor practices should take into account the changing profiles of our obstetrical population, particularly increasing BMI," commented principal investigator Dr. Michelle A. Kominiarek. "Allowing for a slower progression of labor for obese gravidas prior to intervening with a cesarean has the important potential of decreasing the cesarean delivery rate."

Excess weight during pregnancy has been linked to both dysfunctional labor and cesareans, she observed. "The explanation for these findings is not known, but greater fetal size, soft tissue obstruction to labor, poor uterine contractility, more frequent inductions as a result of pregnancy complications, and caregiver biases have been proposed."

The investigators undertook the study "to describe labor patterns in a contemporary obstetrical population, one with greater inductions, greater epidurals, fewer operative deliveries, and presumably a greater maternal weight," explained Dr. Kominiarek of the University of Illinois at Chicago.

They analyzed records in an obstetric database that captured data from 12 U.S. clinical centers for the years 2002-2008. Results were based on 118,978 women who had labor at term; had a singleton, live-born infant with cephalic presentation; and had not had a previous cesarean.

The women were divided into five categories of BMI at the time of admission (less than 25.0 kg/m², 25.0-29.9, 30.0-34.9, 35.0-39.9, and 40.0 or greater).

The average BMI was 30.5 for the entire cohort, and slightly more than 7% of the women had a BMI in the highest category, Dr. Kominiarek reported.

Results showed that as BMI increased, cervical dilation proceeded more slowly, so that women in each BMI category had a distinct labor curve when dilation was plotted against time.

Among nulliparas, there were no clear inflections in these curves to indicate when labor transitioned from the latent to the active phase.

After adjustment for potential confounders (age, race, gestational age, diabetes, induction of labor, augmentation of labor, epidural use, and operative vaginal deliveries), the median time to progress from 4 to 10 cm of cervical dilatation was 5.2 hours for nulliparas in the lowest BMI category, compared with 8.1 hours for those in the highest (P less than .001).

The findings were similar in analyses that looked at each additional centimeter of cervical dilatation. The prolongation with increasing BMI was most evident early in labor, going from 3 to 4 cm and from 4 to 5 cm.

BMI was also associated with a slowing of the duration of the second stage of labor for nulliparas who had an epidural, but less so for those who did not, according to Dr. Kominiarek.

Among multiparas, the labor curves did show inflection points, with a rapid acceleration of cervical dilation indicating entry into active labor. However, the higher a woman’s BMI, the longer it took to get to that point.

The adjusted median time to progress from 4 to 10 cm of cervical dilatation was 4.3 hours for multiparas in the lowest BMI category, compared with 5.7 hours for those in the highest (P less than .001).

The findings here were also similar in analyses that looked at each additional centimeter of cervical dilation, with BMI having greatest impact on the progression from 4 to 5 cm. But the associations were mostly not significant.

Higher BMI did not slow the duration of the second stage of labor among multiparas, regardless of whether they had an epidural.

The reason for the prolongation of labor with increasing BMI is not yet clear, according to Dr. Kominiarek. But she speculated that some of the aforementioned factors, such as weight-induced alterations in physiology or comorbidities, may affect the pace of labor.

Dr. Kominiarek did not report any relevant conflicts of interest.

SAN FRANCISCO - Overweight and obese pregnant women have a longer labor, especially if they have not had any previous births, according to a retrospective observational study conducted by the Consortium on Safe Labor.

Among the more than 100,000 women studied, the time required to progress from 4 cm to 10 cm of cervical dilatation increased steadily with body mass index. It was 2.9 hours (56%) longer for nulliparas and 1.4 hours (33%) longer for multiparas having the highest vs. lowest body mass index.

The duration of the second stage of labor also increased with BMI among the nulliparas, particularly if they had an epidural, according to results reported at the annual meeting of the Society for Maternal-Fetal Medicine.

"This information highlights the concept that contemporary labor practices should take into account the changing profiles of our obstetrical population, particularly increasing BMI," commented principal investigator Dr. Michelle A. Kominiarek. "Allowing for a slower progression of labor for obese gravidas prior to intervening with a cesarean has the important potential of decreasing the cesarean delivery rate."

Excess weight during pregnancy has been linked to both dysfunctional labor and cesareans, she observed. "The explanation for these findings is not known, but greater fetal size, soft tissue obstruction to labor, poor uterine contractility, more frequent inductions as a result of pregnancy complications, and caregiver biases have been proposed."

The investigators undertook the study "to describe labor patterns in a contemporary obstetrical population, one with greater inductions, greater epidurals, fewer operative deliveries, and presumably a greater maternal weight," explained Dr. Kominiarek of the University of Illinois at Chicago.

They analyzed records in an obstetric database that captured data from 12 U.S. clinical centers for the years 2002-2008. Results were based on 118,978 women who had labor at term; had a singleton, live-born infant with cephalic presentation; and had not had a previous cesarean.

The women were divided into five categories of BMI at the time of admission (less than 25.0 kg/m², 25.0-29.9, 30.0-34.9, 35.0-39.9, and 40.0 or greater).

The average BMI was 30.5 for the entire cohort, and slightly more than 7% of the women had a BMI in the highest category, Dr. Kominiarek reported.

Results showed that as BMI increased, cervical dilation proceeded more slowly, so that women in each BMI category had a distinct labor curve when dilation was plotted against time.

Among nulliparas, there were no clear inflections in these curves to indicate when labor transitioned from the latent to the active phase.

After adjustment for potential confounders (age, race, gestational age, diabetes, induction of labor, augmentation of labor, epidural use, and operative vaginal deliveries), the median time to progress from 4 to 10 cm of cervical dilatation was 5.2 hours for nulliparas in the lowest BMI category, compared with 8.1 hours for those in the highest (P less than .001).

The findings were similar in analyses that looked at each additional centimeter of cervical dilatation. The prolongation with increasing BMI was most evident early in labor, going from 3 to 4 cm and from 4 to 5 cm.

BMI was also associated with a slowing of the duration of the second stage of labor for nulliparas who had an epidural, but less so for those who did not, according to Dr. Kominiarek.

Among multiparas, the labor curves did show inflection points, with a rapid acceleration of cervical dilation indicating entry into active labor. However, the higher a woman’s BMI, the longer it took to get to that point.

The adjusted median time to progress from 4 to 10 cm of cervical dilatation was 4.3 hours for multiparas in the lowest BMI category, compared with 5.7 hours for those in the highest (P less than .001).

The findings here were also similar in analyses that looked at each additional centimeter of cervical dilation, with BMI having greatest impact on the progression from 4 to 5 cm. But the associations were mostly not significant.

Higher BMI did not slow the duration of the second stage of labor among multiparas, regardless of whether they had an epidural.

The reason for the prolongation of labor with increasing BMI is not yet clear, according to Dr. Kominiarek. But she speculated that some of the aforementioned factors, such as weight-induced alterations in physiology or comorbidities, may affect the pace of labor.

Dr. Kominiarek did not report any relevant conflicts of interest.

SAN FRANCISCO - Overweight and obese pregnant women have a longer labor, especially if they have not had any previous births, according to a retrospective observational study conducted by the Consortium on Safe Labor.

Among the more than 100,000 women studied, the time required to progress from 4 cm to 10 cm of cervical dilatation increased steadily with body mass index. It was 2.9 hours (56%) longer for nulliparas and 1.4 hours (33%) longer for multiparas having the highest vs. lowest body mass index.

The duration of the second stage of labor also increased with BMI among the nulliparas, particularly if they had an epidural, according to results reported at the annual meeting of the Society for Maternal-Fetal Medicine.

"This information highlights the concept that contemporary labor practices should take into account the changing profiles of our obstetrical population, particularly increasing BMI," commented principal investigator Dr. Michelle A. Kominiarek. "Allowing for a slower progression of labor for obese gravidas prior to intervening with a cesarean has the important potential of decreasing the cesarean delivery rate."

Excess weight during pregnancy has been linked to both dysfunctional labor and cesareans, she observed. "The explanation for these findings is not known, but greater fetal size, soft tissue obstruction to labor, poor uterine contractility, more frequent inductions as a result of pregnancy complications, and caregiver biases have been proposed."

The investigators undertook the study "to describe labor patterns in a contemporary obstetrical population, one with greater inductions, greater epidurals, fewer operative deliveries, and presumably a greater maternal weight," explained Dr. Kominiarek of the University of Illinois at Chicago.

They analyzed records in an obstetric database that captured data from 12 U.S. clinical centers for the years 2002-2008. Results were based on 118,978 women who had labor at term; had a singleton, live-born infant with cephalic presentation; and had not had a previous cesarean.

The women were divided into five categories of BMI at the time of admission (less than 25.0 kg/m², 25.0-29.9, 30.0-34.9, 35.0-39.9, and 40.0 or greater).

The average BMI was 30.5 for the entire cohort, and slightly more than 7% of the women had a BMI in the highest category, Dr. Kominiarek reported.

Results showed that as BMI increased, cervical dilation proceeded more slowly, so that women in each BMI category had a distinct labor curve when dilation was plotted against time.

Among nulliparas, there were no clear inflections in these curves to indicate when labor transitioned from the latent to the active phase.

After adjustment for potential confounders (age, race, gestational age, diabetes, induction of labor, augmentation of labor, epidural use, and operative vaginal deliveries), the median time to progress from 4 to 10 cm of cervical dilatation was 5.2 hours for nulliparas in the lowest BMI category, compared with 8.1 hours for those in the highest (P less than .001).

The findings were similar in analyses that looked at each additional centimeter of cervical dilatation. The prolongation with increasing BMI was most evident early in labor, going from 3 to 4 cm and from 4 to 5 cm.

BMI was also associated with a slowing of the duration of the second stage of labor for nulliparas who had an epidural, but less so for those who did not, according to Dr. Kominiarek.

Among multiparas, the labor curves did show inflection points, with a rapid acceleration of cervical dilation indicating entry into active labor. However, the higher a woman’s BMI, the longer it took to get to that point.

The adjusted median time to progress from 4 to 10 cm of cervical dilatation was 4.3 hours for multiparas in the lowest BMI category, compared with 5.7 hours for those in the highest (P less than .001).

The findings here were also similar in analyses that looked at each additional centimeter of cervical dilation, with BMI having greatest impact on the progression from 4 to 5 cm. But the associations were mostly not significant.

Higher BMI did not slow the duration of the second stage of labor among multiparas, regardless of whether they had an epidural.

The reason for the prolongation of labor with increasing BMI is not yet clear, according to Dr. Kominiarek. But she speculated that some of the aforementioned factors, such as weight-induced alterations in physiology or comorbidities, may affect the pace of labor.

Dr. Kominiarek did not report any relevant conflicts of interest.

LAS VEGAS – Oncologists need to take a leadership role in crafting the practice changes that will be driven by the Patient Protection and Affordable Care Act, two key stakeholders said at the annual Community Oncology Conference.

"The silo mentality of just staying within the four walls of your practice and working harder – that will not work," said Dr. David A. Eagle, an oncologist in Mooresville, N.C., and president of the Community Oncology Alliance. "Really, there is a need for all of us to come together and find these solutions."

The act includes several cost-control measures that will affect community oncologists, including accountable care organizations, an independent payment advisory board, and bundled payments, whereby providers are given a fixed fee for an episode of care.

Implementing these measures will need to address patient heterogeneity. "As all of us who take care of cancer patients know, one patient with stage IV lung cancer can be vastly different than another patient with stage IV lung cancer," he said.

The Community Oncology Alliance was instrumental in getting on the books the National Quality Cancer Care Demonstration Project Act, which is part of the new law and rewards treatment planning, care coordination, guideline adherence, and survivorship planning. Oncologists already do many of these things daily; they will now be rewarded for demonstrating that they do them, Dr. Eagle said.

Additionally, plans are under way to take these efforts to the next step, by adding the concept of the oncology medical home, which would provide value to patients in terms of comprehensive care and to payers in terms of interventions that cut costs by avoiding hospitalization and emergency department use.

Increased measurement of performance and outcomes will become mandatory. "We are going to need to determine what is measured and set appropriate benchmarks and then demonstrate to payers and others how we are doing," Dr. Eagle said. As "accountability should be a two-way street," all parties involved in care-related activities, including payers and pharmacies, also should have their performance measured.

To address these issues going forward, Dr. Ira M. Klein, senior medical director with the health insurer Aetna in Hartford, Conn., proposed collaboration between providers and payers built on the use of mutually accepted evidence-based clinical pathways.

This collaboration would streamline care by coupling technology such as electronic health records with evidence-based medicine, would reduce hurdles such as prior authorizations, and would reward integrated care using the medical home model that, for example, averts unnecessary hospitalizations.

"The biggest issue is the wide variations in care that are going on and the use or nonuse of evidence-based guidelines, including technology. Those are things that are driving up costs." The current system mainly rewards drug therapy, hospital stays, and radiology procedures rather than guideline adherence, services that give a better holistic patient experience, and the difficult but critical tasks such as end-of-life counseling, he said.

Ideally, physicians would retain control over the guidelines, and practices would retain control over their work flow, according to Dr. Klein. And the new processes and software would be introduced gradually given that practices are already stressed by stagnant revenue and other factors.

"We want to take the costs of cancer care and move those costs into revenue streams for providers for doing the right thing in an efficient system," he said. Presently, a lot of money is spent "on oral oncolytics that get thrown down the toilet and hospital stays that happen because an oncologist is incredibly busy, just doesn’t have the ability to make the extra slot (in the schedule), or a private place to give an infusion or hydration – the things that we know we can do but we don’t do today because the system won’t let us."

"We think that we can save millions if not billions of dollars in the system, improve patient care with you, and also use this as a national social experiment to find out what health care could be by aggregating and reporting the data, doing the wonderful things in medicine that have happened in some other areas – eradicating some types of communicable diseases, reducing the mortality in pediatric leukemias and lymphomas – things that we know we can do when we all work together to share the data and move together to the same end point," Dr. Klein concluded.

Community Oncology and this news organization are owned by Elsevier.

LAS VEGAS – Oncologists need to take a leadership role in crafting the practice changes that will be driven by the Patient Protection and Affordable Care Act, two key stakeholders said at the annual Community Oncology Conference.

"The silo mentality of just staying within the four walls of your practice and working harder – that will not work," said Dr. David A. Eagle, an oncologist in Mooresville, N.C., and president of the Community Oncology Alliance. "Really, there is a need for all of us to come together and find these solutions."

The act includes several cost-control measures that will affect community oncologists, including accountable care organizations, an independent payment advisory board, and bundled payments, whereby providers are given a fixed fee for an episode of care.

Implementing these measures will need to address patient heterogeneity. "As all of us who take care of cancer patients know, one patient with stage IV lung cancer can be vastly different than another patient with stage IV lung cancer," he said.

The Community Oncology Alliance was instrumental in getting on the books the National Quality Cancer Care Demonstration Project Act, which is part of the new law and rewards treatment planning, care coordination, guideline adherence, and survivorship planning. Oncologists already do many of these things daily; they will now be rewarded for demonstrating that they do them, Dr. Eagle said.

Additionally, plans are under way to take these efforts to the next step, by adding the concept of the oncology medical home, which would provide value to patients in terms of comprehensive care and to payers in terms of interventions that cut costs by avoiding hospitalization and emergency department use.

Increased measurement of performance and outcomes will become mandatory. "We are going to need to determine what is measured and set appropriate benchmarks and then demonstrate to payers and others how we are doing," Dr. Eagle said. As "accountability should be a two-way street," all parties involved in care-related activities, including payers and pharmacies, also should have their performance measured.

To address these issues going forward, Dr. Ira M. Klein, senior medical director with the health insurer Aetna in Hartford, Conn., proposed collaboration between providers and payers built on the use of mutually accepted evidence-based clinical pathways.

This collaboration would streamline care by coupling technology such as electronic health records with evidence-based medicine, would reduce hurdles such as prior authorizations, and would reward integrated care using the medical home model that, for example, averts unnecessary hospitalizations.

"The biggest issue is the wide variations in care that are going on and the use or nonuse of evidence-based guidelines, including technology. Those are things that are driving up costs." The current system mainly rewards drug therapy, hospital stays, and radiology procedures rather than guideline adherence, services that give a better holistic patient experience, and the difficult but critical tasks such as end-of-life counseling, he said.

Ideally, physicians would retain control over the guidelines, and practices would retain control over their work flow, according to Dr. Klein. And the new processes and software would be introduced gradually given that practices are already stressed by stagnant revenue and other factors.

"We want to take the costs of cancer care and move those costs into revenue streams for providers for doing the right thing in an efficient system," he said. Presently, a lot of money is spent "on oral oncolytics that get thrown down the toilet and hospital stays that happen because an oncologist is incredibly busy, just doesn’t have the ability to make the extra slot (in the schedule), or a private place to give an infusion or hydration – the things that we know we can do but we don’t do today because the system won’t let us."

"We think that we can save millions if not billions of dollars in the system, improve patient care with you, and also use this as a national social experiment to find out what health care could be by aggregating and reporting the data, doing the wonderful things in medicine that have happened in some other areas – eradicating some types of communicable diseases, reducing the mortality in pediatric leukemias and lymphomas – things that we know we can do when we all work together to share the data and move together to the same end point," Dr. Klein concluded.

Community Oncology and this news organization are owned by Elsevier.

LAS VEGAS – Oncologists need to take a leadership role in crafting the practice changes that will be driven by the Patient Protection and Affordable Care Act, two key stakeholders said at the annual Community Oncology Conference.

"The silo mentality of just staying within the four walls of your practice and working harder – that will not work," said Dr. David A. Eagle, an oncologist in Mooresville, N.C., and president of the Community Oncology Alliance. "Really, there is a need for all of us to come together and find these solutions."

The act includes several cost-control measures that will affect community oncologists, including accountable care organizations, an independent payment advisory board, and bundled payments, whereby providers are given a fixed fee for an episode of care.

Implementing these measures will need to address patient heterogeneity. "As all of us who take care of cancer patients know, one patient with stage IV lung cancer can be vastly different than another patient with stage IV lung cancer," he said.

The Community Oncology Alliance was instrumental in getting on the books the National Quality Cancer Care Demonstration Project Act, which is part of the new law and rewards treatment planning, care coordination, guideline adherence, and survivorship planning. Oncologists already do many of these things daily; they will now be rewarded for demonstrating that they do them, Dr. Eagle said.

Additionally, plans are under way to take these efforts to the next step, by adding the concept of the oncology medical home, which would provide value to patients in terms of comprehensive care and to payers in terms of interventions that cut costs by avoiding hospitalization and emergency department use.

Increased measurement of performance and outcomes will become mandatory. "We are going to need to determine what is measured and set appropriate benchmarks and then demonstrate to payers and others how we are doing," Dr. Eagle said. As "accountability should be a two-way street," all parties involved in care-related activities, including payers and pharmacies, also should have their performance measured.

To address these issues going forward, Dr. Ira M. Klein, senior medical director with the health insurer Aetna in Hartford, Conn., proposed collaboration between providers and payers built on the use of mutually accepted evidence-based clinical pathways.

This collaboration would streamline care by coupling technology such as electronic health records with evidence-based medicine, would reduce hurdles such as prior authorizations, and would reward integrated care using the medical home model that, for example, averts unnecessary hospitalizations.

"The biggest issue is the wide variations in care that are going on and the use or nonuse of evidence-based guidelines, including technology. Those are things that are driving up costs." The current system mainly rewards drug therapy, hospital stays, and radiology procedures rather than guideline adherence, services that give a better holistic patient experience, and the difficult but critical tasks such as end-of-life counseling, he said.

Ideally, physicians would retain control over the guidelines, and practices would retain control over their work flow, according to Dr. Klein. And the new processes and software would be introduced gradually given that practices are already stressed by stagnant revenue and other factors.

"We want to take the costs of cancer care and move those costs into revenue streams for providers for doing the right thing in an efficient system," he said. Presently, a lot of money is spent "on oral oncolytics that get thrown down the toilet and hospital stays that happen because an oncologist is incredibly busy, just doesn’t have the ability to make the extra slot (in the schedule), or a private place to give an infusion or hydration – the things that we know we can do but we don’t do today because the system won’t let us."

"We think that we can save millions if not billions of dollars in the system, improve patient care with you, and also use this as a national social experiment to find out what health care could be by aggregating and reporting the data, doing the wonderful things in medicine that have happened in some other areas – eradicating some types of communicable diseases, reducing the mortality in pediatric leukemias and lymphomas – things that we know we can do when we all work together to share the data and move together to the same end point," Dr. Klein concluded.

Community Oncology and this news organization are owned by Elsevier.

LAS VEGAS – Oncologists need to take a leadership role in crafting the practice changes that will be driven by the Patient Protection and Affordable Care Act, two key stakeholders said at the annual Community Oncology Conference.

"The silo mentality of just staying within the four walls of your practice and working harder – that will not work," said Dr. David A. Eagle, an oncologist in Mooresville, N.C., and president of the Community Oncology Alliance. "Really, there is a need for all of us to come together and find these solutions."

The act includes several cost-control measures that will affect community oncologists, including accountable care organizations, an independent payment advisory board, and bundled payments, whereby providers are given a fixed fee for an episode of care.

Implementing these measures will need to address patient heterogeneity. "As all of us who take care of cancer patients know, one patient with stage IV lung cancer can be vastly different than another patient with stage IV lung cancer," he said.

The Community Oncology Alliance was instrumental in getting on the books the National Quality Cancer Care Demonstration Project Act, which is part of the new law and rewards treatment planning, care coordination, guideline adherence, and survivorship planning. Oncologists already do many of these things daily; they will now be rewarded for demonstrating that they do them, Dr. Eagle said.

Additionally, plans are under way to take these efforts to the next step, by adding the concept of the oncology medical home, which would provide value to patients in terms of comprehensive care and to payers in terms of interventions that cut costs by avoiding hospitalization and emergency department use.

Increased measurement of performance and outcomes will become mandatory. "We are going to need to determine what is measured and set appropriate benchmarks and then demonstrate to payers and others how we are doing," Dr. Eagle said. As "accountability should be a two-way street," all parties involved in care-related activities, including payers and pharmacies, also should have their performance measured.

To address these issues going forward, Dr. Ira M. Klein, senior medical director with the health insurer Aetna in Hartford, Conn., proposed collaboration between providers and payers built on the use of mutually accepted evidence-based clinical pathways.

This collaboration would streamline care by coupling technology such as electronic health records with evidence-based medicine, would reduce hurdles such as prior authorizations, and would reward integrated care using the medical home model that, for example, averts unnecessary hospitalizations.

"The biggest issue is the wide variations in care that are going on and the use or nonuse of evidence-based guidelines, including technology. Those are things that are driving up costs." The current system mainly rewards drug therapy, hospital stays, and radiology procedures rather than guideline adherence, services that give a better holistic patient experience, and the difficult but critical tasks such as end-of-life counseling, he said.

Ideally, physicians would retain control over the guidelines, and practices would retain control over their work flow, according to Dr. Klein. And the new processes and software would be introduced gradually given that practices are already stressed by stagnant revenue and other factors.

"We want to take the costs of cancer care and move those costs into revenue streams for providers for doing the right thing in an efficient system," he said. Presently, a lot of money is spent "on oral oncolytics that get thrown down the toilet and hospital stays that happen because an oncologist is incredibly busy, just doesn’t have the ability to make the extra slot (in the schedule), or a private place to give an infusion or hydration – the things that we know we can do but we don’t do today because the system won’t let us."

"We think that we can save millions if not billions of dollars in the system, improve patient care with you, and also use this as a national social experiment to find out what health care could be by aggregating and reporting the data, doing the wonderful things in medicine that have happened in some other areas – eradicating some types of communicable diseases, reducing the mortality in pediatric leukemias and lymphomas – things that we know we can do when we all work together to share the data and move together to the same end point," Dr. Klein concluded.

Community Oncology and this news organization are owned by Elsevier.

LAS VEGAS – Oncologists need to take a leadership role in crafting the practice changes that will be driven by the Patient Protection and Affordable Care Act, two key stakeholders said at the annual Community Oncology Conference.

"The silo mentality of just staying within the four walls of your practice and working harder – that will not work," said Dr. David A. Eagle, an oncologist in Mooresville, N.C., and president of the Community Oncology Alliance. "Really, there is a need for all of us to come together and find these solutions."

The act includes several cost-control measures that will affect community oncologists, including accountable care organizations, an independent payment advisory board, and bundled payments, whereby providers are given a fixed fee for an episode of care.

Implementing these measures will need to address patient heterogeneity. "As all of us who take care of cancer patients know, one patient with stage IV lung cancer can be vastly different than another patient with stage IV lung cancer," he said.

The Community Oncology Alliance was instrumental in getting on the books the National Quality Cancer Care Demonstration Project Act, which is part of the new law and rewards treatment planning, care coordination, guideline adherence, and survivorship planning. Oncologists already do many of these things daily; they will now be rewarded for demonstrating that they do them, Dr. Eagle said.

Additionally, plans are under way to take these efforts to the next step, by adding the concept of the oncology medical home, which would provide value to patients in terms of comprehensive care and to payers in terms of interventions that cut costs by avoiding hospitalization and emergency department use.

Increased measurement of performance and outcomes will become mandatory. "We are going to need to determine what is measured and set appropriate benchmarks and then demonstrate to payers and others how we are doing," Dr. Eagle said. As "accountability should be a two-way street," all parties involved in care-related activities, including payers and pharmacies, also should have their performance measured.

To address these issues going forward, Dr. Ira M. Klein, senior medical director with the health insurer Aetna in Hartford, Conn., proposed collaboration between providers and payers built on the use of mutually accepted evidence-based clinical pathways.

This collaboration would streamline care by coupling technology such as electronic health records with evidence-based medicine, would reduce hurdles such as prior authorizations, and would reward integrated care using the medical home model that, for example, averts unnecessary hospitalizations.

"The biggest issue is the wide variations in care that are going on and the use or nonuse of evidence-based guidelines, including technology. Those are things that are driving up costs." The current system mainly rewards drug therapy, hospital stays, and radiology procedures rather than guideline adherence, services that give a better holistic patient experience, and the difficult but critical tasks such as end-of-life counseling, he said.

Ideally, physicians would retain control over the guidelines, and practices would retain control over their work flow, according to Dr. Klein. And the new processes and software would be introduced gradually given that practices are already stressed by stagnant revenue and other factors.

"We want to take the costs of cancer care and move those costs into revenue streams for providers for doing the right thing in an efficient system," he said. Presently, a lot of money is spent "on oral oncolytics that get thrown down the toilet and hospital stays that happen because an oncologist is incredibly busy, just doesn’t have the ability to make the extra slot (in the schedule), or a private place to give an infusion or hydration – the things that we know we can do but we don’t do today because the system won’t let us."

"We think that we can save millions if not billions of dollars in the system, improve patient care with you, and also use this as a national social experiment to find out what health care could be by aggregating and reporting the data, doing the wonderful things in medicine that have happened in some other areas – eradicating some types of communicable diseases, reducing the mortality in pediatric leukemias and lymphomas – things that we know we can do when we all work together to share the data and move together to the same end point," Dr. Klein concluded.

Community Oncology and this news organization are owned by Elsevier.

LAS VEGAS – Oncologists need to take a leadership role in crafting the practice changes that will be driven by the Patient Protection and Affordable Care Act, two key stakeholders said at the annual Community Oncology Conference.

"The silo mentality of just staying within the four walls of your practice and working harder – that will not work," said Dr. David A. Eagle, an oncologist in Mooresville, N.C., and president of the Community Oncology Alliance. "Really, there is a need for all of us to come together and find these solutions."

The act includes several cost-control measures that will affect community oncologists, including accountable care organizations, an independent payment advisory board, and bundled payments, whereby providers are given a fixed fee for an episode of care.

Implementing these measures will need to address patient heterogeneity. "As all of us who take care of cancer patients know, one patient with stage IV lung cancer can be vastly different than another patient with stage IV lung cancer," he said.

The Community Oncology Alliance was instrumental in getting on the books the National Quality Cancer Care Demonstration Project Act, which is part of the new law and rewards treatment planning, care coordination, guideline adherence, and survivorship planning. Oncologists already do many of these things daily; they will now be rewarded for demonstrating that they do them, Dr. Eagle said.

Additionally, plans are under way to take these efforts to the next step, by adding the concept of the oncology medical home, which would provide value to patients in terms of comprehensive care and to payers in terms of interventions that cut costs by avoiding hospitalization and emergency department use.

Increased measurement of performance and outcomes will become mandatory. "We are going to need to determine what is measured and set appropriate benchmarks and then demonstrate to payers and others how we are doing," Dr. Eagle said. As "accountability should be a two-way street," all parties involved in care-related activities, including payers and pharmacies, also should have their performance measured.

To address these issues going forward, Dr. Ira M. Klein, senior medical director with the health insurer Aetna in Hartford, Conn., proposed collaboration between providers and payers built on the use of mutually accepted evidence-based clinical pathways.

This collaboration would streamline care by coupling technology such as electronic health records with evidence-based medicine, would reduce hurdles such as prior authorizations, and would reward integrated care using the medical home model that, for example, averts unnecessary hospitalizations.

"The biggest issue is the wide variations in care that are going on and the use or nonuse of evidence-based guidelines, including technology. Those are things that are driving up costs." The current system mainly rewards drug therapy, hospital stays, and radiology procedures rather than guideline adherence, services that give a better holistic patient experience, and the difficult but critical tasks such as end-of-life counseling, he said.

Ideally, physicians would retain control over the guidelines, and practices would retain control over their work flow, according to Dr. Klein. And the new processes and software would be introduced gradually given that practices are already stressed by stagnant revenue and other factors.

"We want to take the costs of cancer care and move those costs into revenue streams for providers for doing the right thing in an efficient system," he said. Presently, a lot of money is spent "on oral oncolytics that get thrown down the toilet and hospital stays that happen because an oncologist is incredibly busy, just doesn’t have the ability to make the extra slot (in the schedule), or a private place to give an infusion or hydration – the things that we know we can do but we don’t do today because the system won’t let us."

"We think that we can save millions if not billions of dollars in the system, improve patient care with you, and also use this as a national social experiment to find out what health care could be by aggregating and reporting the data, doing the wonderful things in medicine that have happened in some other areas – eradicating some types of communicable diseases, reducing the mortality in pediatric leukemias and lymphomas – things that we know we can do when we all work together to share the data and move together to the same end point," Dr. Klein concluded.

Community Oncology and this news organization are owned by Elsevier.

SAN FRANCISCO – As women grow heavier, tailoring antibiotic dose to weight or body mass index may be critical for preventing surgical site infections after cesarean deliveries, a study has shown.

In the prospective cohort study reported at the annual meeting of the Society for Maternal-Fetal Medicine, all 29 women undergoing a cesarean were given the same standard fixed dose of cefazolin before their surgery. Concentrations of the antibiotic in adipose tissue collected at the start of the surgery were one-third lower in obese women and one-half lower in extremely obese women than those in their lean counterparts. Perhaps most importantly, some of the heavier women had tissue concentrations below those believed to be necessary for preventing antibiotic resistance.

"Based on the current findings, a considerable proportion of obese women undergoing cesarean delivery do not have adequate antimicrobial protection for the duration of the procedure, following current guidelines," said Dr. Leo Pevzner, an ob.gyn. at the University of California, Irvine.

The National Surgical Infection Prevention Project has endorsed tailoring antibiotic dose to weight or body mass index (BMI), but data on appropriate prophylactic doses in adults are limited, he noted. Hence, recommendations still call for an intravenous dose of 1-2 g for all adults, large or small.

"Current obesity trends, along with evolutionary changes in bacterial resistance, portend a questionable utility of existing prophylaxis regimens and have the potential to drastically increase the rates of surgical site infections if no attempts are made to address antimicrobial dosing based on patients’ weight or BMI," Dr. Pevzner commented.

The investigators enrolled in the study women with a singleton pregnancy who were scheduled for a cesarean delivery at term (greater than 37 weeks’ gestation). Any who had received antibiotics in the previous week or who had chronic hypertension or pregestational diabetes were excluded.

On the basis of their BMI, the women were classified as lean (less than 30 kg/m²), obese (30-39.9 kg/m²), or extremely obese (greater than or equal to 40 kg/m²).

All were given 2 g of cefazolin 30-60 minutes before skin incision for the cesarean surgery. The investigators collected adipose tissue at the time of skin incision (initial) and again just before closure (final), as well as myometrial tissue after delivery and blood at the end of the procedure.

The concentration of cefazolin in all samples was assessed in a blinded manner with a microbiologic plate assay performed in triplicate, using plates seeded with Streptococcus sanguis. Zones of inhibition were measured in millimeters.

The study participants were racially/ethnically diverse: 31% were white, 21% were African American, 41% were Hispanic, and 7% were Asian. They were 30 years old, on average. The mean BMI was 27, 34, and 45 kg/m² in the lean, obese, and extremely obese groups, respectively.

The mean concentration of cefazolin in adipose tissue collected at incision was 9.4 mcg/g in lean women, Dr. Pevzner reported. In comparison, it was 6.4 mcg/g, or 32% lower, in obese women (P = .009) and 4.4 mcg/g, or 53% lower, in extremely obese women (P less than .001).

Regression analysis showed that the higher the women’s BMI, the lower the concentration of the antibiotic in their initial adipose tissue sample (r = –0.67, P less than .001).

None of the lean women had an adipose concentration of cefazolin below 4 mcg/g, the theoretic breakpoint for preventing resistance, according to Dr. Pevzner.

But eight women – four obese and four extremely obese – had an initial or a final adipose concentration below this breakpoint. And three women – all extremely obese – had both initial and final adipose concentrations below this breakpoint.

The concentrations of cefazolin in the final adipose tissue, myometrial tissue, and serum also decreased with increasing BMI category, but these differences were not statistically significant, Dr. Pevzner reported.

Among the 25 women with follow-up, 2 developed surgical site infections requiring antibiotic therapy. Both were in the extremely obese group, and both had initial and final adipose cefazolin concentrations below the 4 mcg/g threshold.

The study was small, Dr. Pevzner acknowledged. "As such, there is not enough information to reach a conclusion regarding the weight or BMI above which a higher dose of antibiotics should be used," he said. Also, the impact of multiple gestations and maternal diseases, such as hypertension and diabetes, in this setting is unknown.

"Larger prospective and perhaps randomized studies are needed to confirm the current findings from a clinical standpoint and answer some of these lingering questions," he concluded.

Dr. Pevzner said he did not have any relevant financial disclosures.

SAN FRANCISCO – As women grow heavier, tailoring antibiotic dose to weight or body mass index may be critical for preventing surgical site infections after cesarean deliveries, a study has shown.

In the prospective cohort study reported at the annual meeting of the Society for Maternal-Fetal Medicine, all 29 women undergoing a cesarean were given the same standard fixed dose of cefazolin before their surgery. Concentrations of the antibiotic in adipose tissue collected at the start of the surgery were one-third lower in obese women and one-half lower in extremely obese women than those in their lean counterparts. Perhaps most importantly, some of the heavier women had tissue concentrations below those believed to be necessary for preventing antibiotic resistance.

"Based on the current findings, a considerable proportion of obese women undergoing cesarean delivery do not have adequate antimicrobial protection for the duration of the procedure, following current guidelines," said Dr. Leo Pevzner, an ob.gyn. at the University of California, Irvine.

The National Surgical Infection Prevention Project has endorsed tailoring antibiotic dose to weight or body mass index (BMI), but data on appropriate prophylactic doses in adults are limited, he noted. Hence, recommendations still call for an intravenous dose of 1-2 g for all adults, large or small.

"Current obesity trends, along with evolutionary changes in bacterial resistance, portend a questionable utility of existing prophylaxis regimens and have the potential to drastically increase the rates of surgical site infections if no attempts are made to address antimicrobial dosing based on patients’ weight or BMI," Dr. Pevzner commented.

The investigators enrolled in the study women with a singleton pregnancy who were scheduled for a cesarean delivery at term (greater than 37 weeks’ gestation). Any who had received antibiotics in the previous week or who had chronic hypertension or pregestational diabetes were excluded.

On the basis of their BMI, the women were classified as lean (less than 30 kg/m²), obese (30-39.9 kg/m²), or extremely obese (greater than or equal to 40 kg/m²).

All were given 2 g of cefazolin 30-60 minutes before skin incision for the cesarean surgery. The investigators collected adipose tissue at the time of skin incision (initial) and again just before closure (final), as well as myometrial tissue after delivery and blood at the end of the procedure.

The concentration of cefazolin in all samples was assessed in a blinded manner with a microbiologic plate assay performed in triplicate, using plates seeded with Streptococcus sanguis. Zones of inhibition were measured in millimeters.

The study participants were racially/ethnically diverse: 31% were white, 21% were African American, 41% were Hispanic, and 7% were Asian. They were 30 years old, on average. The mean BMI was 27, 34, and 45 kg/m² in the lean, obese, and extremely obese groups, respectively.

The mean concentration of cefazolin in adipose tissue collected at incision was 9.4 mcg/g in lean women, Dr. Pevzner reported. In comparison, it was 6.4 mcg/g, or 32% lower, in obese women (P = .009) and 4.4 mcg/g, or 53% lower, in extremely obese women (P less than .001).

Regression analysis showed that the higher the women’s BMI, the lower the concentration of the antibiotic in their initial adipose tissue sample (r = –0.67, P less than .001).

None of the lean women had an adipose concentration of cefazolin below 4 mcg/g, the theoretic breakpoint for preventing resistance, according to Dr. Pevzner.

But eight women – four obese and four extremely obese – had an initial or a final adipose concentration below this breakpoint. And three women – all extremely obese – had both initial and final adipose concentrations below this breakpoint.

The concentrations of cefazolin in the final adipose tissue, myometrial tissue, and serum also decreased with increasing BMI category, but these differences were not statistically significant, Dr. Pevzner reported.

Among the 25 women with follow-up, 2 developed surgical site infections requiring antibiotic therapy. Both were in the extremely obese group, and both had initial and final adipose cefazolin concentrations below the 4 mcg/g threshold.

The study was small, Dr. Pevzner acknowledged. "As such, there is not enough information to reach a conclusion regarding the weight or BMI above which a higher dose of antibiotics should be used," he said. Also, the impact of multiple gestations and maternal diseases, such as hypertension and diabetes, in this setting is unknown.

"Larger prospective and perhaps randomized studies are needed to confirm the current findings from a clinical standpoint and answer some of these lingering questions," he concluded.

Dr. Pevzner said he did not have any relevant financial disclosures.

SAN FRANCISCO – As women grow heavier, tailoring antibiotic dose to weight or body mass index may be critical for preventing surgical site infections after cesarean deliveries, a study has shown.

In the prospective cohort study reported at the annual meeting of the Society for Maternal-Fetal Medicine, all 29 women undergoing a cesarean were given the same standard fixed dose of cefazolin before their surgery. Concentrations of the antibiotic in adipose tissue collected at the start of the surgery were one-third lower in obese women and one-half lower in extremely obese women than those in their lean counterparts. Perhaps most importantly, some of the heavier women had tissue concentrations below those believed to be necessary for preventing antibiotic resistance.

"Based on the current findings, a considerable proportion of obese women undergoing cesarean delivery do not have adequate antimicrobial protection for the duration of the procedure, following current guidelines," said Dr. Leo Pevzner, an ob.gyn. at the University of California, Irvine.

The National Surgical Infection Prevention Project has endorsed tailoring antibiotic dose to weight or body mass index (BMI), but data on appropriate prophylactic doses in adults are limited, he noted. Hence, recommendations still call for an intravenous dose of 1-2 g for all adults, large or small.

"Current obesity trends, along with evolutionary changes in bacterial resistance, portend a questionable utility of existing prophylaxis regimens and have the potential to drastically increase the rates of surgical site infections if no attempts are made to address antimicrobial dosing based on patients’ weight or BMI," Dr. Pevzner commented.

The investigators enrolled in the study women with a singleton pregnancy who were scheduled for a cesarean delivery at term (greater than 37 weeks’ gestation). Any who had received antibiotics in the previous week or who had chronic hypertension or pregestational diabetes were excluded.

On the basis of their BMI, the women were classified as lean (less than 30 kg/m²), obese (30-39.9 kg/m²), or extremely obese (greater than or equal to 40 kg/m²).

All were given 2 g of cefazolin 30-60 minutes before skin incision for the cesarean surgery. The investigators collected adipose tissue at the time of skin incision (initial) and again just before closure (final), as well as myometrial tissue after delivery and blood at the end of the procedure.

The concentration of cefazolin in all samples was assessed in a blinded manner with a microbiologic plate assay performed in triplicate, using plates seeded with Streptococcus sanguis. Zones of inhibition were measured in millimeters.

The study participants were racially/ethnically diverse: 31% were white, 21% were African American, 41% were Hispanic, and 7% were Asian. They were 30 years old, on average. The mean BMI was 27, 34, and 45 kg/m² in the lean, obese, and extremely obese groups, respectively.

The mean concentration of cefazolin in adipose tissue collected at incision was 9.4 mcg/g in lean women, Dr. Pevzner reported. In comparison, it was 6.4 mcg/g, or 32% lower, in obese women (P = .009) and 4.4 mcg/g, or 53% lower, in extremely obese women (P less than .001).

Regression analysis showed that the higher the women’s BMI, the lower the concentration of the antibiotic in their initial adipose tissue sample (r = –0.67, P less than .001).

None of the lean women had an adipose concentration of cefazolin below 4 mcg/g, the theoretic breakpoint for preventing resistance, according to Dr. Pevzner.

But eight women – four obese and four extremely obese – had an initial or a final adipose concentration below this breakpoint. And three women – all extremely obese – had both initial and final adipose concentrations below this breakpoint.

The concentrations of cefazolin in the final adipose tissue, myometrial tissue, and serum also decreased with increasing BMI category, but these differences were not statistically significant, Dr. Pevzner reported.

Among the 25 women with follow-up, 2 developed surgical site infections requiring antibiotic therapy. Both were in the extremely obese group, and both had initial and final adipose cefazolin concentrations below the 4 mcg/g threshold.

The study was small, Dr. Pevzner acknowledged. "As such, there is not enough information to reach a conclusion regarding the weight or BMI above which a higher dose of antibiotics should be used," he said. Also, the impact of multiple gestations and maternal diseases, such as hypertension and diabetes, in this setting is unknown.

"Larger prospective and perhaps randomized studies are needed to confirm the current findings from a clinical standpoint and answer some of these lingering questions," he concluded.

Dr. Pevzner said he did not have any relevant financial disclosures.

SAN FRANCISCO – As women grow heavier, tailoring antibiotic dose to weight or body mass index may be critical for preventing surgical site infections after cesarean deliveries, a study has shown.

In the prospective cohort study reported at the annual meeting of the Society for Maternal-Fetal Medicine, all 29 women undergoing a cesarean were given the same standard fixed dose of cefazolin before their surgery. Concentrations of the antibiotic in adipose tissue collected at the start of the surgery were one-third lower in obese women and one-half lower in extremely obese women than those in their lean counterparts. Perhaps most importantly, some of the heavier women had tissue concentrations below those believed to be necessary for preventing antibiotic resistance.

"Based on the current findings, a considerable proportion of obese women undergoing cesarean delivery do not have adequate antimicrobial protection for the duration of the procedure, following current guidelines," said Dr. Leo Pevzner, an ob.gyn. at the University of California, Irvine.

The National Surgical Infection Prevention Project has endorsed tailoring antibiotic dose to weight or body mass index (BMI), but data on appropriate prophylactic doses in adults are limited, he noted. Hence, recommendations still call for an intravenous dose of 1-2 g for all adults, large or small.

"Current obesity trends, along with evolutionary changes in bacterial resistance, portend a questionable utility of existing prophylaxis regimens and have the potential to drastically increase the rates of surgical site infections if no attempts are made to address antimicrobial dosing based on patients’ weight or BMI," Dr. Pevzner commented.

The investigators enrolled in the study women with a singleton pregnancy who were scheduled for a cesarean delivery at term (greater than 37 weeks’ gestation). Any who had received antibiotics in the previous week or who had chronic hypertension or pregestational diabetes were excluded.

On the basis of their BMI, the women were classified as lean (less than 30 kg/m²), obese (30-39.9 kg/m²), or extremely obese (greater than or equal to 40 kg/m²).

All were given 2 g of cefazolin 30-60 minutes before skin incision for the cesarean surgery. The investigators collected adipose tissue at the time of skin incision (initial) and again just before closure (final), as well as myometrial tissue after delivery and blood at the end of the procedure.

The concentration of cefazolin in all samples was assessed in a blinded manner with a microbiologic plate assay performed in triplicate, using plates seeded with Streptococcus sanguis. Zones of inhibition were measured in millimeters.

The study participants were racially/ethnically diverse: 31% were white, 21% were African American, 41% were Hispanic, and 7% were Asian. They were 30 years old, on average. The mean BMI was 27, 34, and 45 kg/m² in the lean, obese, and extremely obese groups, respectively.

The mean concentration of cefazolin in adipose tissue collected at incision was 9.4 mcg/g in lean women, Dr. Pevzner reported. In comparison, it was 6.4 mcg/g, or 32% lower, in obese women (P = .009) and 4.4 mcg/g, or 53% lower, in extremely obese women (P less than .001).

Regression analysis showed that the higher the women’s BMI, the lower the concentration of the antibiotic in their initial adipose tissue sample (r = –0.67, P less than .001).

None of the lean women had an adipose concentration of cefazolin below 4 mcg/g, the theoretic breakpoint for preventing resistance, according to Dr. Pevzner.

But eight women – four obese and four extremely obese – had an initial or a final adipose concentration below this breakpoint. And three women – all extremely obese – had both initial and final adipose concentrations below this breakpoint.

The concentrations of cefazolin in the final adipose tissue, myometrial tissue, and serum also decreased with increasing BMI category, but these differences were not statistically significant, Dr. Pevzner reported.

Among the 25 women with follow-up, 2 developed surgical site infections requiring antibiotic therapy. Both were in the extremely obese group, and both had initial and final adipose cefazolin concentrations below the 4 mcg/g threshold.

The study was small, Dr. Pevzner acknowledged. "As such, there is not enough information to reach a conclusion regarding the weight or BMI above which a higher dose of antibiotics should be used," he said. Also, the impact of multiple gestations and maternal diseases, such as hypertension and diabetes, in this setting is unknown.

"Larger prospective and perhaps randomized studies are needed to confirm the current findings from a clinical standpoint and answer some of these lingering questions," he concluded.

Dr. Pevzner said he did not have any relevant financial disclosures.

SAN FRANCISCO – As women grow heavier, tailoring antibiotic dose to weight or body mass index may be critical for preventing surgical site infections after cesarean deliveries, a study has shown.

In the prospective cohort study reported at the annual meeting of the Society for Maternal-Fetal Medicine, all 29 women undergoing a cesarean were given the same standard fixed dose of cefazolin before their surgery. Concentrations of the antibiotic in adipose tissue collected at the start of the surgery were one-third lower in obese women and one-half lower in extremely obese women than those in their lean counterparts. Perhaps most importantly, some of the heavier women had tissue concentrations below those believed to be necessary for preventing antibiotic resistance.

"Based on the current findings, a considerable proportion of obese women undergoing cesarean delivery do not have adequate antimicrobial protection for the duration of the procedure, following current guidelines," said Dr. Leo Pevzner, an ob.gyn. at the University of California, Irvine.

The National Surgical Infection Prevention Project has endorsed tailoring antibiotic dose to weight or body mass index (BMI), but data on appropriate prophylactic doses in adults are limited, he noted. Hence, recommendations still call for an intravenous dose of 1-2 g for all adults, large or small.

"Current obesity trends, along with evolutionary changes in bacterial resistance, portend a questionable utility of existing prophylaxis regimens and have the potential to drastically increase the rates of surgical site infections if no attempts are made to address antimicrobial dosing based on patients’ weight or BMI," Dr. Pevzner commented.

The investigators enrolled in the study women with a singleton pregnancy who were scheduled for a cesarean delivery at term (greater than 37 weeks’ gestation). Any who had received antibiotics in the previous week or who had chronic hypertension or pregestational diabetes were excluded.

On the basis of their BMI, the women were classified as lean (less than 30 kg/m²), obese (30-39.9 kg/m²), or extremely obese (greater than or equal to 40 kg/m²).

All were given 2 g of cefazolin 30-60 minutes before skin incision for the cesarean surgery. The investigators collected adipose tissue at the time of skin incision (initial) and again just before closure (final), as well as myometrial tissue after delivery and blood at the end of the procedure.

The concentration of cefazolin in all samples was assessed in a blinded manner with a microbiologic plate assay performed in triplicate, using plates seeded with Streptococcus sanguis. Zones of inhibition were measured in millimeters.

The study participants were racially/ethnically diverse: 31% were white, 21% were African American, 41% were Hispanic, and 7% were Asian. They were 30 years old, on average. The mean BMI was 27, 34, and 45 kg/m² in the lean, obese, and extremely obese groups, respectively.

The mean concentration of cefazolin in adipose tissue collected at incision was 9.4 mcg/g in lean women, Dr. Pevzner reported. In comparison, it was 6.4 mcg/g, or 32% lower, in obese women (P = .009) and 4.4 mcg/g, or 53% lower, in extremely obese women (P less than .001).

Regression analysis showed that the higher the women’s BMI, the lower the concentration of the antibiotic in their initial adipose tissue sample (r = –0.67, P less than .001).

None of the lean women had an adipose concentration of cefazolin below 4 mcg/g, the theoretic breakpoint for preventing resistance, according to Dr. Pevzner.

But eight women – four obese and four extremely obese – had an initial or a final adipose concentration below this breakpoint. And three women – all extremely obese – had both initial and final adipose concentrations below this breakpoint.

The concentrations of cefazolin in the final adipose tissue, myometrial tissue, and serum also decreased with increasing BMI category, but these differences were not statistically significant, Dr. Pevzner reported.

Among the 25 women with follow-up, 2 developed surgical site infections requiring antibiotic therapy. Both were in the extremely obese group, and both had initial and final adipose cefazolin concentrations below the 4 mcg/g threshold.

The study was small, Dr. Pevzner acknowledged. "As such, there is not enough information to reach a conclusion regarding the weight or BMI above which a higher dose of antibiotics should be used," he said. Also, the impact of multiple gestations and maternal diseases, such as hypertension and diabetes, in this setting is unknown.

"Larger prospective and perhaps randomized studies are needed to confirm the current findings from a clinical standpoint and answer some of these lingering questions," he concluded.

Dr. Pevzner said he did not have any relevant financial disclosures.

SAN FRANCISCO – As women grow heavier, tailoring antibiotic dose to weight or body mass index may be critical for preventing surgical site infections after cesarean deliveries, a study has shown.

In the prospective cohort study reported at the annual meeting of the Society for Maternal-Fetal Medicine, all 29 women undergoing a cesarean were given the same standard fixed dose of cefazolin before their surgery. Concentrations of the antibiotic in adipose tissue collected at the start of the surgery were one-third lower in obese women and one-half lower in extremely obese women than those in their lean counterparts. Perhaps most importantly, some of the heavier women had tissue concentrations below those believed to be necessary for preventing antibiotic resistance.

"Based on the current findings, a considerable proportion of obese women undergoing cesarean delivery do not have adequate antimicrobial protection for the duration of the procedure, following current guidelines," said Dr. Leo Pevzner, an ob.gyn. at the University of California, Irvine.

The National Surgical Infection Prevention Project has endorsed tailoring antibiotic dose to weight or body mass index (BMI), but data on appropriate prophylactic doses in adults are limited, he noted. Hence, recommendations still call for an intravenous dose of 1-2 g for all adults, large or small.

"Current obesity trends, along with evolutionary changes in bacterial resistance, portend a questionable utility of existing prophylaxis regimens and have the potential to drastically increase the rates of surgical site infections if no attempts are made to address antimicrobial dosing based on patients’ weight or BMI," Dr. Pevzner commented.

The investigators enrolled in the study women with a singleton pregnancy who were scheduled for a cesarean delivery at term (greater than 37 weeks’ gestation). Any who had received antibiotics in the previous week or who had chronic hypertension or pregestational diabetes were excluded.

On the basis of their BMI, the women were classified as lean (less than 30 kg/m²), obese (30-39.9 kg/m²), or extremely obese (greater than or equal to 40 kg/m²).

All were given 2 g of cefazolin 30-60 minutes before skin incision for the cesarean surgery. The investigators collected adipose tissue at the time of skin incision (initial) and again just before closure (final), as well as myometrial tissue after delivery and blood at the end of the procedure.

The concentration of cefazolin in all samples was assessed in a blinded manner with a microbiologic plate assay performed in triplicate, using plates seeded with Streptococcus sanguis. Zones of inhibition were measured in millimeters.

The study participants were racially/ethnically diverse: 31% were white, 21% were African American, 41% were Hispanic, and 7% were Asian. They were 30 years old, on average. The mean BMI was 27, 34, and 45 kg/m² in the lean, obese, and extremely obese groups, respectively.

The mean concentration of cefazolin in adipose tissue collected at incision was 9.4 mcg/g in lean women, Dr. Pevzner reported. In comparison, it was 6.4 mcg/g, or 32% lower, in obese women (P = .009) and 4.4 mcg/g, or 53% lower, in extremely obese women (P less than .001).

Regression analysis showed that the higher the women’s BMI, the lower the concentration of the antibiotic in their initial adipose tissue sample (r = –0.67, P less than .001).

None of the lean women had an adipose concentration of cefazolin below 4 mcg/g, the theoretic breakpoint for preventing resistance, according to Dr. Pevzner.

But eight women – four obese and four extremely obese – had an initial or a final adipose concentration below this breakpoint. And three women – all extremely obese – had both initial and final adipose concentrations below this breakpoint.

The concentrations of cefazolin in the final adipose tissue, myometrial tissue, and serum also decreased with increasing BMI category, but these differences were not statistically significant, Dr. Pevzner reported.

Among the 25 women with follow-up, 2 developed surgical site infections requiring antibiotic therapy. Both were in the extremely obese group, and both had initial and final adipose cefazolin concentrations below the 4 mcg/g threshold.

The study was small, Dr. Pevzner acknowledged. "As such, there is not enough information to reach a conclusion regarding the weight or BMI above which a higher dose of antibiotics should be used," he said. Also, the impact of multiple gestations and maternal diseases, such as hypertension and diabetes, in this setting is unknown.

"Larger prospective and perhaps randomized studies are needed to confirm the current findings from a clinical standpoint and answer some of these lingering questions," he concluded.

Dr. Pevzner said he did not have any relevant financial disclosures.

SAN FRANCISCO – As women grow heavier, tailoring antibiotic dose to weight or body mass index may be critical for preventing surgical site infections after cesarean deliveries, a study has shown.

In the prospective cohort study reported at the annual meeting of the Society for Maternal-Fetal Medicine, all 29 women undergoing a cesarean were given the same standard fixed dose of cefazolin before their surgery. Concentrations of the antibiotic in adipose tissue collected at the start of the surgery were one-third lower in obese women and one-half lower in extremely obese women than those in their lean counterparts. Perhaps most importantly, some of the heavier women had tissue concentrations below those believed to be necessary for preventing antibiotic resistance.

"Based on the current findings, a considerable proportion of obese women undergoing cesarean delivery do not have adequate antimicrobial protection for the duration of the procedure, following current guidelines," said Dr. Leo Pevzner, an ob.gyn. at the University of California, Irvine.

The National Surgical Infection Prevention Project has endorsed tailoring antibiotic dose to weight or body mass index (BMI), but data on appropriate prophylactic doses in adults are limited, he noted. Hence, recommendations still call for an intravenous dose of 1-2 g for all adults, large or small.

"Current obesity trends, along with evolutionary changes in bacterial resistance, portend a questionable utility of existing prophylaxis regimens and have the potential to drastically increase the rates of surgical site infections if no attempts are made to address antimicrobial dosing based on patients’ weight or BMI," Dr. Pevzner commented.

The investigators enrolled in the study women with a singleton pregnancy who were scheduled for a cesarean delivery at term (greater than 37 weeks’ gestation). Any who had received antibiotics in the previous week or who had chronic hypertension or pregestational diabetes were excluded.

On the basis of their BMI, the women were classified as lean (less than 30 kg/m²), obese (30-39.9 kg/m²), or extremely obese (greater than or equal to 40 kg/m²).

All were given 2 g of cefazolin 30-60 minutes before skin incision for the cesarean surgery. The investigators collected adipose tissue at the time of skin incision (initial) and again just before closure (final), as well as myometrial tissue after delivery and blood at the end of the procedure.

The concentration of cefazolin in all samples was assessed in a blinded manner with a microbiologic plate assay performed in triplicate, using plates seeded with Streptococcus sanguis. Zones of inhibition were measured in millimeters.

The study participants were racially/ethnically diverse: 31% were white, 21% were African American, 41% were Hispanic, and 7% were Asian. They were 30 years old, on average. The mean BMI was 27, 34, and 45 kg/m² in the lean, obese, and extremely obese groups, respectively.

The mean concentration of cefazolin in adipose tissue collected at incision was 9.4 mcg/g in lean women, Dr. Pevzner reported. In comparison, it was 6.4 mcg/g, or 32% lower, in obese women (P = .009) and 4.4 mcg/g, or 53% lower, in extremely obese women (P less than .001).

Regression analysis showed that the higher the women’s BMI, the lower the concentration of the antibiotic in their initial adipose tissue sample (r = –0.67, P less than .001).

None of the lean women had an adipose concentration of cefazolin below 4 mcg/g, the theoretic breakpoint for preventing resistance, according to Dr. Pevzner.

But eight women – four obese and four extremely obese – had an initial or a final adipose concentration below this breakpoint. And three women – all extremely obese – had both initial and final adipose concentrations below this breakpoint.

The concentrations of cefazolin in the final adipose tissue, myometrial tissue, and serum also decreased with increasing BMI category, but these differences were not statistically significant, Dr. Pevzner reported.

Among the 25 women with follow-up, 2 developed surgical site infections requiring antibiotic therapy. Both were in the extremely obese group, and both had initial and final adipose cefazolin concentrations below the 4 mcg/g threshold.

The study was small, Dr. Pevzner acknowledged. "As such, there is not enough information to reach a conclusion regarding the weight or BMI above which a higher dose of antibiotics should be used," he said. Also, the impact of multiple gestations and maternal diseases, such as hypertension and diabetes, in this setting is unknown.

"Larger prospective and perhaps randomized studies are needed to confirm the current findings from a clinical standpoint and answer some of these lingering questions," he concluded.

Dr. Pevzner said he did not have any relevant financial disclosures.

SAN FRANCISCO – As women grow heavier, tailoring antibiotic dose to weight or body mass index may be critical for preventing surgical site infections after cesarean deliveries, a study has shown.

In the prospective cohort study reported at the annual meeting of the Society for Maternal-Fetal Medicine, all 29 women undergoing a cesarean were given the same standard fixed dose of cefazolin before their surgery. Concentrations of the antibiotic in adipose tissue collected at the start of the surgery were one-third lower in obese women and one-half lower in extremely obese women than those in their lean counterparts. Perhaps most importantly, some of the heavier women had tissue concentrations below those believed to be necessary for preventing antibiotic resistance.

"Based on the current findings, a considerable proportion of obese women undergoing cesarean delivery do not have adequate antimicrobial protection for the duration of the procedure, following current guidelines," said Dr. Leo Pevzner, an ob.gyn. at the University of California, Irvine.

The National Surgical Infection Prevention Project has endorsed tailoring antibiotic dose to weight or body mass index (BMI), but data on appropriate prophylactic doses in adults are limited, he noted. Hence, recommendations still call for an intravenous dose of 1-2 g for all adults, large or small.

"Current obesity trends, along with evolutionary changes in bacterial resistance, portend a questionable utility of existing prophylaxis regimens and have the potential to drastically increase the rates of surgical site infections if no attempts are made to address antimicrobial dosing based on patients’ weight or BMI," Dr. Pevzner commented.

The investigators enrolled in the study women with a singleton pregnancy who were scheduled for a cesarean delivery at term (greater than 37 weeks’ gestation). Any who had received antibiotics in the previous week or who had chronic hypertension or pregestational diabetes were excluded.

On the basis of their BMI, the women were classified as lean (less than 30 kg/m²), obese (30-39.9 kg/m²), or extremely obese (greater than or equal to 40 kg/m²).

All were given 2 g of cefazolin 30-60 minutes before skin incision for the cesarean surgery. The investigators collected adipose tissue at the time of skin incision (initial) and again just before closure (final), as well as myometrial tissue after delivery and blood at the end of the procedure.

The concentration of cefazolin in all samples was assessed in a blinded manner with a microbiologic plate assay performed in triplicate, using plates seeded with Streptococcus sanguis. Zones of inhibition were measured in millimeters.

The study participants were racially/ethnically diverse: 31% were white, 21% were African American, 41% were Hispanic, and 7% were Asian. They were 30 years old, on average. The mean BMI was 27, 34, and 45 kg/m² in the lean, obese, and extremely obese groups, respectively.

The mean concentration of cefazolin in adipose tissue collected at incision was 9.4 mcg/g in lean women, Dr. Pevzner reported. In comparison, it was 6.4 mcg/g, or 32% lower, in obese women (P = .009) and 4.4 mcg/g, or 53% lower, in extremely obese women (P less than .001).

Regression analysis showed that the higher the women’s BMI, the lower the concentration of the antibiotic in their initial adipose tissue sample (r = –0.67, P less than .001).

None of the lean women had an adipose concentration of cefazolin below 4 mcg/g, the theoretic breakpoint for preventing resistance, according to Dr. Pevzner.

But eight women – four obese and four extremely obese – had an initial or a final adipose concentration below this breakpoint. And three women – all extremely obese – had both initial and final adipose concentrations below this breakpoint.

The concentrations of cefazolin in the final adipose tissue, myometrial tissue, and serum also decreased with increasing BMI category, but these differences were not statistically significant, Dr. Pevzner reported.

Among the 25 women with follow-up, 2 developed surgical site infections requiring antibiotic therapy. Both were in the extremely obese group, and both had initial and final adipose cefazolin concentrations below the 4 mcg/g threshold.

The study was small, Dr. Pevzner acknowledged. "As such, there is not enough information to reach a conclusion regarding the weight or BMI above which a higher dose of antibiotics should be used," he said. Also, the impact of multiple gestations and maternal diseases, such as hypertension and diabetes, in this setting is unknown.

"Larger prospective and perhaps randomized studies are needed to confirm the current findings from a clinical standpoint and answer some of these lingering questions," he concluded.

Dr. Pevzner said he did not have any relevant financial disclosures.

SAN FRANCISCO – As women grow heavier, tailoring antibiotic dose to weight or body mass index may be critical for preventing surgical site infections after cesarean deliveries, a study has shown.

In the prospective cohort study reported at the annual meeting of the Society for Maternal-Fetal Medicine, all 29 women undergoing a cesarean were given the same standard fixed dose of cefazolin before their surgery. Concentrations of the antibiotic in adipose tissue collected at the start of the surgery were one-third lower in obese women and one-half lower in extremely obese women than those in their lean counterparts. Perhaps most importantly, some of the heavier women had tissue concentrations below those believed to be necessary for preventing antibiotic resistance.

"Based on the current findings, a considerable proportion of obese women undergoing cesarean delivery do not have adequate antimicrobial protection for the duration of the procedure, following current guidelines," said Dr. Leo Pevzner, an ob.gyn. at the University of California, Irvine.

The National Surgical Infection Prevention Project has endorsed tailoring antibiotic dose to weight or body mass index (BMI), but data on appropriate prophylactic doses in adults are limited, he noted. Hence, recommendations still call for an intravenous dose of 1-2 g for all adults, large or small.

"Current obesity trends, along with evolutionary changes in bacterial resistance, portend a questionable utility of existing prophylaxis regimens and have the potential to drastically increase the rates of surgical site infections if no attempts are made to address antimicrobial dosing based on patients’ weight or BMI," Dr. Pevzner commented.

The investigators enrolled in the study women with a singleton pregnancy who were scheduled for a cesarean delivery at term (greater than 37 weeks’ gestation). Any who had received antibiotics in the previous week or who had chronic hypertension or pregestational diabetes were excluded.

On the basis of their BMI, the women were classified as lean (less than 30 kg/m²), obese (30-39.9 kg/m²), or extremely obese (greater than or equal to 40 kg/m²).

All were given 2 g of cefazolin 30-60 minutes before skin incision for the cesarean surgery. The investigators collected adipose tissue at the time of skin incision (initial) and again just before closure (final), as well as myometrial tissue after delivery and blood at the end of the procedure.

The concentration of cefazolin in all samples was assessed in a blinded manner with a microbiologic plate assay performed in triplicate, using plates seeded with Streptococcus sanguis. Zones of inhibition were measured in millimeters.

The study participants were racially/ethnically diverse: 31% were white, 21% were African American, 41% were Hispanic, and 7% were Asian. They were 30 years old, on average. The mean BMI was 27, 34, and 45 kg/m² in the lean, obese, and extremely obese groups, respectively.

The mean concentration of cefazolin in adipose tissue collected at incision was 9.4 mcg/g in lean women, Dr. Pevzner reported. In comparison, it was 6.4 mcg/g, or 32% lower, in obese women (P = .009) and 4.4 mcg/g, or 53% lower, in extremely obese women (P less than .001).

Regression analysis showed that the higher the women’s BMI, the lower the concentration of the antibiotic in their initial adipose tissue sample (r = –0.67, P less than .001).

None of the lean women had an adipose concentration of cefazolin below 4 mcg/g, the theoretic breakpoint for preventing resistance, according to Dr. Pevzner.

But eight women – four obese and four extremely obese – had an initial or a final adipose concentration below this breakpoint. And three women – all extremely obese – had both initial and final adipose concentrations below this breakpoint.

The concentrations of cefazolin in the final adipose tissue, myometrial tissue, and serum also decreased with increasing BMI category, but these differences were not statistically significant, Dr. Pevzner reported.

Among the 25 women with follow-up, 2 developed surgical site infections requiring antibiotic therapy. Both were in the extremely obese group, and both had initial and final adipose cefazolin concentrations below the 4 mcg/g threshold.

The study was small, Dr. Pevzner acknowledged. "As such, there is not enough information to reach a conclusion regarding the weight or BMI above which a higher dose of antibiotics should be used," he said. Also, the impact of multiple gestations and maternal diseases, such as hypertension and diabetes, in this setting is unknown.

"Larger prospective and perhaps randomized studies are needed to confirm the current findings from a clinical standpoint and answer some of these lingering questions," he concluded.

Dr. Pevzner said he did not have any relevant financial disclosures.

SAN FRANCISCO – Advances in molecular prognosis may soon make it possible to predict the risk of recurrence of early colorectal cancer after curative resection – and thus the need for adjuvant therapy in patients who might not otherwise receive further treatment.

Five-Gene Tumor Signature

A new five-gene tumor prognostic signature has performed well in external validation testing among patients with stage I or II disease, according to Dr. Peter F. Lenehan, chief medical officer of Everist Genomics Inc., in Ann Arbor, Mich.

Dr. Lenehan and his coinvestigators validated the gene signature among 115 patients who had undergone curative resection for stage I or II colon cancer or stage I rectal cancer and did not receive adjuvant therapy. Some 40% experienced a recurrence within 3 years.

For predicting recurrence, the signature had a sensitivity of 70%, a specificity of 55%, a positive predictive value of 51%, and a negative predictive value of 73%. The overall accuracy was 61%.

Other prognostic tests can differentiate patients who will not recur, Dr. Lenehan said, but "we alone are best able to predict who is going to recur. For this population, we believe this is more clinically significant because the default position is not to treat stage I and II.

"So if we are able to detect those that actually need more aggressive follow-up or high consideration for adjuvant chemotherapy, then our test is better suited for this patient population."

Patients with a signature-predicted high risk of recurrence were more than twice as likely to have a recurrence as were their counterparts with a signature-predicted low risk (hazard ratio, 2.06; P = .02).

In contrast, the combination of criteria suggested by the National Comprehensive Cancer Network (NCCN) (T4 stage, fewer than 12 lymph nodes examined, grade of 3 or 4, lymphovascular invasion, bowel obstruction, localized perforation, or close, indeterminate, or positive margins) did not significantly predict risk.

"We are the first prognostic test in colorectal cancer to target stage I. The others target stage II and III," Dr. Lenehan added.

"The importance for us is that 10%-15% of stage I colorectal cancer patients actually recur and succumb to their disease," he said. "The standard of care for this stage is no treatment. And therefore, you have 3,000 or 4,000 patients per year which are potentially missing treatment that could potentially help them."

The signature could also be used to select only high-risk stage I patients for a clinical trial of adjuvant therapy, which would dramatically reduce the number of patients needed to determine benefit, he added.

GCC Expression in Lymph Nodes

Expression in lymph nodes of mRNA of the enzyme guanylyl cyclase C (GCC) predicts recurrence in patients with stage II colon cancer, according to Daniel J. Sargent, Ph.D., a professor of biostatistics and of oncology at the Mayo Clinic in Rochester, Minn.

"GCC is a marker that is only present in the colon, and if you find the GCC marker in the lymph nodes, it indicates that the tumor has metastasized from the colon to the lymph nodes," he explained in an interview. "So the presence of GCC in the lymph nodes should be a negative prognostic marker, and that’s indeed what we found."

The investigators retrospectively studied 241 patients who underwent resection for stage II colon cancer, did not receive adjuvant therapy, and had a minimum follow-up of 36 months. With a median follow-up of 60 months, 12% had a recurrence or cancer-related death. Some 10-41 lymph nodes (median, 15) were evaluated per patient.

The GCC assay results were expressed as a lymph node ratio (number of positive nodes divided by total number of informative nodes). In all, 35% of patients had a lymph node ratio of greater than 0.1.

These patients had more than double the risk of recurrence, compared with their counterparts who had a lower ratio (HR, 2.38; P = .02). The estimated 5-year rate of recurrence was 27% for the former and 10% for the latter.

The findings were even stronger in the subgroup of 181 patients with highly favorable clinical and pathological factors – namely, a T3 tumor, at least 12 lymph nodes examined, and negative margins – a third of whom had a lymph node ratio of greater than 0.1 (HR, 5.06; P = .003). Here, the estimated 5-year rate of recurrence was 27% with a ratio greater than 0.1 and just 4% with a lower ratio.

In a multivariate analysis among all patients that included potential confounders (age, T stage, number of lymph nodes assessed, and mismatch repair status), a GCC lymph node ratio greater than 0.1 was associated with a 2.61-fold higher risk of recurrence (P = .02).

The findings, which are considered preliminary, are being validated among an additional 500 patients, according to Dr. Sargent. "We think this is a very promising marker to be able to give patients with stage II disease an accurate prediction of what’s their likelihood of recurrence," he commented.

"We were able to define two-thirds of the population that have such a low risk for recurrence that I think it would be quite questionable whether there would be any potential reason to treat such patients," Dr. Sargent said, "whereas in the one-third of patients with high risk, they really look like stage III patients, and you might consider them as appropriate for treatment."

Tumor CDK1 Activity

Tumor activity of cyclin-dependent kinase 1 (CDK1), a key regulator of cell cycle progression, is a very strong and independent predictor of recurrence in patients with stage II colon cancer, investigators also reported.

"We believe that cell cycle profiling, the speed of the cell cycle, could be really important to predict tumor recurrence," said Dr. Masaki Shibayama of the Sysmex Corp. in Kobe, Japan, in an interview. Rapid proliferation "is one of the central hallmarks of cancer," he noted.

The investigators used the Cell Cycle Profiling (C2P) system (manufactured by Sysmex) to assess CDK1 enzymatic activity in fresh-frozen tumor samples from 254 patients from Germany and the Netherlands who underwent resection for stage II colon cancer and did not receive adjuvant therapy. With a median follow-up of 86 months, 11% developed distant metastases.

Some 40% of patients had a specific activity level of CDK1 that exceeded the cutoff of 11 and were classified as high risk, whereas 60% had a level of 11 or less and were classified as low risk. Relative to their low-risk peers, the high-risk patients were markedly more likely to develop distant metastases (HR, 6.2; P = .005) and to die from their cancer (HR, 7.6; P = .001).

These very high hazard ratios set this assay apart from other prognostic assays in stage II colon cancer, according to lead investigator Dr. Matthias Maak, a surgeon at the Technical University of Munich.

The hazard ratio for distant metastases was essentially the same after adjustment for age, sex, grade, and pathological T stage. It was still high (although no longer significant) after adjustment for tumor stroma content, possibly as a result of missing data for this parameter in about a third of cases.

"We believe this is a very nice result," Dr. Shibayama commented, and the assay may also extend to other solid tumors. "For example, we have a similar study for breast cancer, and it is also successful."

"This looks very promising," Dr. Maak concurred. "But this is, let’s say, the first test [of this assay] in colorectal carcinoma. Now we need more validation to find out if this works with another cohort, for example, or for another hospital. But we are rather positive that it will be as promising as it was in this trial."

Dr. Lenehan is an employee of Everist Genomics Inc. Dr. Sargent reported that his institution received research funding from DiagnoCure Inc. Dr. Shibayama is an employee of Sysmex Corp.; Dr. Maak did not report any conflicts of interest.

SAN FRANCISCO – Advances in molecular prognosis may soon make it possible to predict the risk of recurrence of early colorectal cancer after curative resection – and thus the need for adjuvant therapy in patients who might not otherwise receive further treatment.

Five-Gene Tumor Signature

A new five-gene tumor prognostic signature has performed well in external validation testing among patients with stage I or II disease, according to Dr. Peter F. Lenehan, chief medical officer of Everist Genomics Inc., in Ann Arbor, Mich.

Dr. Lenehan and his coinvestigators validated the gene signature among 115 patients who had undergone curative resection for stage I or II colon cancer or stage I rectal cancer and did not receive adjuvant therapy. Some 40% experienced a recurrence within 3 years.

For predicting recurrence, the signature had a sensitivity of 70%, a specificity of 55%, a positive predictive value of 51%, and a negative predictive value of 73%. The overall accuracy was 61%.

Other prognostic tests can differentiate patients who will not recur, Dr. Lenehan said, but "we alone are best able to predict who is going to recur. For this population, we believe this is more clinically significant because the default position is not to treat stage I and II.

"So if we are able to detect those that actually need more aggressive follow-up or high consideration for adjuvant chemotherapy, then our test is better suited for this patient population."

Patients with a signature-predicted high risk of recurrence were more than twice as likely to have a recurrence as were their counterparts with a signature-predicted low risk (hazard ratio, 2.06; P = .02).

In contrast, the combination of criteria suggested by the National Comprehensive Cancer Network (NCCN) (T4 stage, fewer than 12 lymph nodes examined, grade of 3 or 4, lymphovascular invasion, bowel obstruction, localized perforation, or close, indeterminate, or positive margins) did not significantly predict risk.

"We are the first prognostic test in colorectal cancer to target stage I. The others target stage II and III," Dr. Lenehan added.

"The importance for us is that 10%-15% of stage I colorectal cancer patients actually recur and succumb to their disease," he said. "The standard of care for this stage is no treatment. And therefore, you have 3,000 or 4,000 patients per year which are potentially missing treatment that could potentially help them."

The signature could also be used to select only high-risk stage I patients for a clinical trial of adjuvant therapy, which would dramatically reduce the number of patients needed to determine benefit, he added.

GCC Expression in Lymph Nodes

Expression in lymph nodes of mRNA of the enzyme guanylyl cyclase C (GCC) predicts recurrence in patients with stage II colon cancer, according to Daniel J. Sargent, Ph.D., a professor of biostatistics and of oncology at the Mayo Clinic in Rochester, Minn.

"GCC is a marker that is only present in the colon, and if you find the GCC marker in the lymph nodes, it indicates that the tumor has metastasized from the colon to the lymph nodes," he explained in an interview. "So the presence of GCC in the lymph nodes should be a negative prognostic marker, and that’s indeed what we found."

The investigators retrospectively studied 241 patients who underwent resection for stage II colon cancer, did not receive adjuvant therapy, and had a minimum follow-up of 36 months. With a median follow-up of 60 months, 12% had a recurrence or cancer-related death. Some 10-41 lymph nodes (median, 15) were evaluated per patient.

The GCC assay results were expressed as a lymph node ratio (number of positive nodes divided by total number of informative nodes). In all, 35% of patients had a lymph node ratio of greater than 0.1.

These patients had more than double the risk of recurrence, compared with their counterparts who had a lower ratio (HR, 2.38; P = .02). The estimated 5-year rate of recurrence was 27% for the former and 10% for the latter.

The findings were even stronger in the subgroup of 181 patients with highly favorable clinical and pathological factors – namely, a T3 tumor, at least 12 lymph nodes examined, and negative margins – a third of whom had a lymph node ratio of greater than 0.1 (HR, 5.06; P = .003). Here, the estimated 5-year rate of recurrence was 27% with a ratio greater than 0.1 and just 4% with a lower ratio.

In a multivariate analysis among all patients that included potential confounders (age, T stage, number of lymph nodes assessed, and mismatch repair status), a GCC lymph node ratio greater than 0.1 was associated with a 2.61-fold higher risk of recurrence (P = .02).

The findings, which are considered preliminary, are being validated among an additional 500 patients, according to Dr. Sargent. "We think this is a very promising marker to be able to give patients with stage II disease an accurate prediction of what’s their likelihood of recurrence," he commented.

"We were able to define two-thirds of the population that have such a low risk for recurrence that I think it would be quite questionable whether there would be any potential reason to treat such patients," Dr. Sargent said, "whereas in the one-third of patients with high risk, they really look like stage III patients, and you might consider them as appropriate for treatment."

Tumor CDK1 Activity

Tumor activity of cyclin-dependent kinase 1 (CDK1), a key regulator of cell cycle progression, is a very strong and independent predictor of recurrence in patients with stage II colon cancer, investigators also reported.

"We believe that cell cycle profiling, the speed of the cell cycle, could be really important to predict tumor recurrence," said Dr. Masaki Shibayama of the Sysmex Corp. in Kobe, Japan, in an interview. Rapid proliferation "is one of the central hallmarks of cancer," he noted.

The investigators used the Cell Cycle Profiling (C2P) system (manufactured by Sysmex) to assess CDK1 enzymatic activity in fresh-frozen tumor samples from 254 patients from Germany and the Netherlands who underwent resection for stage II colon cancer and did not receive adjuvant therapy. With a median follow-up of 86 months, 11% developed distant metastases.

Some 40% of patients had a specific activity level of CDK1 that exceeded the cutoff of 11 and were classified as high risk, whereas 60% had a level of 11 or less and were classified as low risk. Relative to their low-risk peers, the high-risk patients were markedly more likely to develop distant metastases (HR, 6.2; P = .005) and to die from their cancer (HR, 7.6; P = .001).

These very high hazard ratios set this assay apart from other prognostic assays in stage II colon cancer, according to lead investigator Dr. Matthias Maak, a surgeon at the Technical University of Munich.

The hazard ratio for distant metastases was essentially the same after adjustment for age, sex, grade, and pathological T stage. It was still high (although no longer significant) after adjustment for tumor stroma content, possibly as a result of missing data for this parameter in about a third of cases.

"We believe this is a very nice result," Dr. Shibayama commented, and the assay may also extend to other solid tumors. "For example, we have a similar study for breast cancer, and it is also successful."

"This looks very promising," Dr. Maak concurred. "But this is, let’s say, the first test [of this assay] in colorectal carcinoma. Now we need more validation to find out if this works with another cohort, for example, or for another hospital. But we are rather positive that it will be as promising as it was in this trial."

Dr. Lenehan is an employee of Everist Genomics Inc. Dr. Sargent reported that his institution received research funding from DiagnoCure Inc. Dr. Shibayama is an employee of Sysmex Corp.; Dr. Maak did not report any conflicts of interest.

SAN FRANCISCO – Advances in molecular prognosis may soon make it possible to predict the risk of recurrence of early colorectal cancer after curative resection – and thus the need for adjuvant therapy in patients who might not otherwise receive further treatment.

Five-Gene Tumor Signature

A new five-gene tumor prognostic signature has performed well in external validation testing among patients with stage I or II disease, according to Dr. Peter F. Lenehan, chief medical officer of Everist Genomics Inc., in Ann Arbor, Mich.

Dr. Lenehan and his coinvestigators validated the gene signature among 115 patients who had undergone curative resection for stage I or II colon cancer or stage I rectal cancer and did not receive adjuvant therapy. Some 40% experienced a recurrence within 3 years.

For predicting recurrence, the signature had a sensitivity of 70%, a specificity of 55%, a positive predictive value of 51%, and a negative predictive value of 73%. The overall accuracy was 61%.

Other prognostic tests can differentiate patients who will not recur, Dr. Lenehan said, but "we alone are best able to predict who is going to recur. For this population, we believe this is more clinically significant because the default position is not to treat stage I and II.

"So if we are able to detect those that actually need more aggressive follow-up or high consideration for adjuvant chemotherapy, then our test is better suited for this patient population."

Patients with a signature-predicted high risk of recurrence were more than twice as likely to have a recurrence as were their counterparts with a signature-predicted low risk (hazard ratio, 2.06; P = .02).

In contrast, the combination of criteria suggested by the National Comprehensive Cancer Network (NCCN) (T4 stage, fewer than 12 lymph nodes examined, grade of 3 or 4, lymphovascular invasion, bowel obstruction, localized perforation, or close, indeterminate, or positive margins) did not significantly predict risk.

"We are the first prognostic test in colorectal cancer to target stage I. The others target stage II and III," Dr. Lenehan added.

"The importance for us is that 10%-15% of stage I colorectal cancer patients actually recur and succumb to their disease," he said. "The standard of care for this stage is no treatment. And therefore, you have 3,000 or 4,000 patients per year which are potentially missing treatment that could potentially help them."

The signature could also be used to select only high-risk stage I patients for a clinical trial of adjuvant therapy, which would dramatically reduce the number of patients needed to determine benefit, he added.

GCC Expression in Lymph Nodes

Expression in lymph nodes of mRNA of the enzyme guanylyl cyclase C (GCC) predicts recurrence in patients with stage II colon cancer, according to Daniel J. Sargent, Ph.D., a professor of biostatistics and of oncology at the Mayo Clinic in Rochester, Minn.

"GCC is a marker that is only present in the colon, and if you find the GCC marker in the lymph nodes, it indicates that the tumor has metastasized from the colon to the lymph nodes," he explained in an interview. "So the presence of GCC in the lymph nodes should be a negative prognostic marker, and that’s indeed what we found."

The investigators retrospectively studied 241 patients who underwent resection for stage II colon cancer, did not receive adjuvant therapy, and had a minimum follow-up of 36 months. With a median follow-up of 60 months, 12% had a recurrence or cancer-related death. Some 10-41 lymph nodes (median, 15) were evaluated per patient.

The GCC assay results were expressed as a lymph node ratio (number of positive nodes divided by total number of informative nodes). In all, 35% of patients had a lymph node ratio of greater than 0.1.

These patients had more than double the risk of recurrence, compared with their counterparts who had a lower ratio (HR, 2.38; P = .02). The estimated 5-year rate of recurrence was 27% for the former and 10% for the latter.

The findings were even stronger in the subgroup of 181 patients with highly favorable clinical and pathological factors – namely, a T3 tumor, at least 12 lymph nodes examined, and negative margins – a third of whom had a lymph node ratio of greater than 0.1 (HR, 5.06; P = .003). Here, the estimated 5-year rate of recurrence was 27% with a ratio greater than 0.1 and just 4% with a lower ratio.

In a multivariate analysis among all patients that included potential confounders (age, T stage, number of lymph nodes assessed, and mismatch repair status), a GCC lymph node ratio greater than 0.1 was associated with a 2.61-fold higher risk of recurrence (P = .02).

The findings, which are considered preliminary, are being validated among an additional 500 patients, according to Dr. Sargent. "We think this is a very promising marker to be able to give patients with stage II disease an accurate prediction of what’s their likelihood of recurrence," he commented.

"We were able to define two-thirds of the population that have such a low risk for recurrence that I think it would be quite questionable whether there would be any potential reason to treat such patients," Dr. Sargent said, "whereas in the one-third of patients with high risk, they really look like stage III patients, and you might consider them as appropriate for treatment."

Tumor CDK1 Activity

Tumor activity of cyclin-dependent kinase 1 (CDK1), a key regulator of cell cycle progression, is a very strong and independent predictor of recurrence in patients with stage II colon cancer, investigators also reported.

"We believe that cell cycle profiling, the speed of the cell cycle, could be really important to predict tumor recurrence," said Dr. Masaki Shibayama of the Sysmex Corp. in Kobe, Japan, in an interview. Rapid proliferation "is one of the central hallmarks of cancer," he noted.

The investigators used the Cell Cycle Profiling (C2P) system (manufactured by Sysmex) to assess CDK1 enzymatic activity in fresh-frozen tumor samples from 254 patients from Germany and the Netherlands who underwent resection for stage II colon cancer and did not receive adjuvant therapy. With a median follow-up of 86 months, 11% developed distant metastases.

Some 40% of patients had a specific activity level of CDK1 that exceeded the cutoff of 11 and were classified as high risk, whereas 60% had a level of 11 or less and were classified as low risk. Relative to their low-risk peers, the high-risk patients were markedly more likely to develop distant metastases (HR, 6.2; P = .005) and to die from their cancer (HR, 7.6; P = .001).

These very high hazard ratios set this assay apart from other prognostic assays in stage II colon cancer, according to lead investigator Dr. Matthias Maak, a surgeon at the Technical University of Munich.

The hazard ratio for distant metastases was essentially the same after adjustment for age, sex, grade, and pathological T stage. It was still high (although no longer significant) after adjustment for tumor stroma content, possibly as a result of missing data for this parameter in about a third of cases.

"We believe this is a very nice result," Dr. Shibayama commented, and the assay may also extend to other solid tumors. "For example, we have a similar study for breast cancer, and it is also successful."

"This looks very promising," Dr. Maak concurred. "But this is, let’s say, the first test [of this assay] in colorectal carcinoma. Now we need more validation to find out if this works with another cohort, for example, or for another hospital. But we are rather positive that it will be as promising as it was in this trial."

Dr. Lenehan is an employee of Everist Genomics Inc. Dr. Sargent reported that his institution received research funding from DiagnoCure Inc. Dr. Shibayama is an employee of Sysmex Corp.; Dr. Maak did not report any conflicts of interest.

SAN FRANCISCO – Advances in molecular prognosis may soon make it possible to predict the risk of recurrence of early colorectal cancer after curative resection – and thus the need for adjuvant therapy in patients who might not otherwise receive further treatment.

Five-Gene Tumor Signature

A new five-gene tumor prognostic signature has performed well in external validation testing among patients with stage I or II disease, according to Dr. Peter F. Lenehan, chief medical officer of Everist Genomics Inc., in Ann Arbor, Mich.

Dr. Lenehan and his coinvestigators validated the gene signature among 115 patients who had undergone curative resection for stage I or II colon cancer or stage I rectal cancer and did not receive adjuvant therapy. Some 40% experienced a recurrence within 3 years.

For predicting recurrence, the signature had a sensitivity of 70%, a specificity of 55%, a positive predictive value of 51%, and a negative predictive value of 73%. The overall accuracy was 61%.

Other prognostic tests can differentiate patients who will not recur, Dr. Lenehan said, but "we alone are best able to predict who is going to recur. For this population, we believe this is more clinically significant because the default position is not to treat stage I and II.

"So if we are able to detect those that actually need more aggressive follow-up or high consideration for adjuvant chemotherapy, then our test is better suited for this patient population."

Patients with a signature-predicted high risk of recurrence were more than twice as likely to have a recurrence as were their counterparts with a signature-predicted low risk (hazard ratio, 2.06; P = .02).

In contrast, the combination of criteria suggested by the National Comprehensive Cancer Network (NCCN) (T4 stage, fewer than 12 lymph nodes examined, grade of 3 or 4, lymphovascular invasion, bowel obstruction, localized perforation, or close, indeterminate, or positive margins) did not significantly predict risk.

"We are the first prognostic test in colorectal cancer to target stage I. The others target stage II and III," Dr. Lenehan added.

"The importance for us is that 10%-15% of stage I colorectal cancer patients actually recur and succumb to their disease," he said. "The standard of care for this stage is no treatment. And therefore, you have 3,000 or 4,000 patients per year which are potentially missing treatment that could potentially help them."

The signature could also be used to select only high-risk stage I patients for a clinical trial of adjuvant therapy, which would dramatically reduce the number of patients needed to determine benefit, he added.

GCC Expression in Lymph Nodes

Expression in lymph nodes of mRNA of the enzyme guanylyl cyclase C (GCC) predicts recurrence in patients with stage II colon cancer, according to Daniel J. Sargent, Ph.D., a professor of biostatistics and of oncology at the Mayo Clinic in Rochester, Minn.

"GCC is a marker that is only present in the colon, and if you find the GCC marker in the lymph nodes, it indicates that the tumor has metastasized from the colon to the lymph nodes," he explained in an interview. "So the presence of GCC in the lymph nodes should be a negative prognostic marker, and that’s indeed what we found."

The investigators retrospectively studied 241 patients who underwent resection for stage II colon cancer, did not receive adjuvant therapy, and had a minimum follow-up of 36 months. With a median follow-up of 60 months, 12% had a recurrence or cancer-related death. Some 10-41 lymph nodes (median, 15) were evaluated per patient.

The GCC assay results were expressed as a lymph node ratio (number of positive nodes divided by total number of informative nodes). In all, 35% of patients had a lymph node ratio of greater than 0.1.

These patients had more than double the risk of recurrence, compared with their counterparts who had a lower ratio (HR, 2.38; P = .02). The estimated 5-year rate of recurrence was 27% for the former and 10% for the latter.

The findings were even stronger in the subgroup of 181 patients with highly favorable clinical and pathological factors – namely, a T3 tumor, at least 12 lymph nodes examined, and negative margins – a third of whom had a lymph node ratio of greater than 0.1 (HR, 5.06; P = .003). Here, the estimated 5-year rate of recurrence was 27% with a ratio greater than 0.1 and just 4% with a lower ratio.

In a multivariate analysis among all patients that included potential confounders (age, T stage, number of lymph nodes assessed, and mismatch repair status), a GCC lymph node ratio greater than 0.1 was associated with a 2.61-fold higher risk of recurrence (P = .02).

The findings, which are considered preliminary, are being validated among an additional 500 patients, according to Dr. Sargent. "We think this is a very promising marker to be able to give patients with stage II disease an accurate prediction of what’s their likelihood of recurrence," he commented.

"We were able to define two-thirds of the population that have such a low risk for recurrence that I think it would be quite questionable whether there would be any potential reason to treat such patients," Dr. Sargent said, "whereas in the one-third of patients with high risk, they really look like stage III patients, and you might consider them as appropriate for treatment."

Tumor CDK1 Activity

Tumor activity of cyclin-dependent kinase 1 (CDK1), a key regulator of cell cycle progression, is a very strong and independent predictor of recurrence in patients with stage II colon cancer, investigators also reported.

"We believe that cell cycle profiling, the speed of the cell cycle, could be really important to predict tumor recurrence," said Dr. Masaki Shibayama of the Sysmex Corp. in Kobe, Japan, in an interview. Rapid proliferation "is one of the central hallmarks of cancer," he noted.

The investigators used the Cell Cycle Profiling (C2P) system (manufactured by Sysmex) to assess CDK1 enzymatic activity in fresh-frozen tumor samples from 254 patients from Germany and the Netherlands who underwent resection for stage II colon cancer and did not receive adjuvant therapy. With a median follow-up of 86 months, 11% developed distant metastases.

Some 40% of patients had a specific activity level of CDK1 that exceeded the cutoff of 11 and were classified as high risk, whereas 60% had a level of 11 or less and were classified as low risk. Relative to their low-risk peers, the high-risk patients were markedly more likely to develop distant metastases (HR, 6.2; P = .005) and to die from their cancer (HR, 7.6; P = .001).

These very high hazard ratios set this assay apart from other prognostic assays in stage II colon cancer, according to lead investigator Dr. Matthias Maak, a surgeon at the Technical University of Munich.

The hazard ratio for distant metastases was essentially the same after adjustment for age, sex, grade, and pathological T stage. It was still high (although no longer significant) after adjustment for tumor stroma content, possibly as a result of missing data for this parameter in about a third of cases.

"We believe this is a very nice result," Dr. Shibayama commented, and the assay may also extend to other solid tumors. "For example, we have a similar study for breast cancer, and it is also successful."

"This looks very promising," Dr. Maak concurred. "But this is, let’s say, the first test [of this assay] in colorectal carcinoma. Now we need more validation to find out if this works with another cohort, for example, or for another hospital. But we are rather positive that it will be as promising as it was in this trial."

Dr. Lenehan is an employee of Everist Genomics Inc. Dr. Sargent reported that his institution received research funding from DiagnoCure Inc. Dr. Shibayama is an employee of Sysmex Corp.; Dr. Maak did not report any conflicts of interest.

SAN FRANCISCO – Advances in molecular prognosis may soon make it possible to predict the risk of recurrence of early colorectal cancer after curative resection – and thus the need for adjuvant therapy in patients who might not otherwise receive further treatment.

Five-Gene Tumor Signature

A new five-gene tumor prognostic signature has performed well in external validation testing among patients with stage I or II disease, according to Dr. Peter F. Lenehan, chief medical officer of Everist Genomics Inc., in Ann Arbor, Mich.

Dr. Lenehan and his coinvestigators validated the gene signature among 115 patients who had undergone curative resection for stage I or II colon cancer or stage I rectal cancer and did not receive adjuvant therapy. Some 40% experienced a recurrence within 3 years.

For predicting recurrence, the signature had a sensitivity of 70%, a specificity of 55%, a positive predictive value of 51%, and a negative predictive value of 73%. The overall accuracy was 61%.

Other prognostic tests can differentiate patients who will not recur, Dr. Lenehan said, but "we alone are best able to predict who is going to recur. For this population, we believe this is more clinically significant because the default position is not to treat stage I and II.

"So if we are able to detect those that actually need more aggressive follow-up or high consideration for adjuvant chemotherapy, then our test is better suited for this patient population."

Patients with a signature-predicted high risk of recurrence were more than twice as likely to have a recurrence as were their counterparts with a signature-predicted low risk (hazard ratio, 2.06; P = .02).

In contrast, the combination of criteria suggested by the National Comprehensive Cancer Network (NCCN) (T4 stage, fewer than 12 lymph nodes examined, grade of 3 or 4, lymphovascular invasion, bowel obstruction, localized perforation, or close, indeterminate, or positive margins) did not significantly predict risk.

"We are the first prognostic test in colorectal cancer to target stage I. The others target stage II and III," Dr. Lenehan added.

"The importance for us is that 10%-15% of stage I colorectal cancer patients actually recur and succumb to their disease," he said. "The standard of care for this stage is no treatment. And therefore, you have 3,000 or 4,000 patients per year which are potentially missing treatment that could potentially help them."

The signature could also be used to select only high-risk stage I patients for a clinical trial of adjuvant therapy, which would dramatically reduce the number of patients needed to determine benefit, he added.

GCC Expression in Lymph Nodes

Expression in lymph nodes of mRNA of the enzyme guanylyl cyclase C (GCC) predicts recurrence in patients with stage II colon cancer, according to Daniel J. Sargent, Ph.D., a professor of biostatistics and of oncology at the Mayo Clinic in Rochester, Minn.

"GCC is a marker that is only present in the colon, and if you find the GCC marker in the lymph nodes, it indicates that the tumor has metastasized from the colon to the lymph nodes," he explained in an interview. "So the presence of GCC in the lymph nodes should be a negative prognostic marker, and that’s indeed what we found."

The investigators retrospectively studied 241 patients who underwent resection for stage II colon cancer, did not receive adjuvant therapy, and had a minimum follow-up of 36 months. With a median follow-up of 60 months, 12% had a recurrence or cancer-related death. Some 10-41 lymph nodes (median, 15) were evaluated per patient.

The GCC assay results were expressed as a lymph node ratio (number of positive nodes divided by total number of informative nodes). In all, 35% of patients had a lymph node ratio of greater than 0.1.

These patients had more than double the risk of recurrence, compared with their counterparts who had a lower ratio (HR, 2.38; P = .02). The estimated 5-year rate of recurrence was 27% for the former and 10% for the latter.

The findings were even stronger in the subgroup of 181 patients with highly favorable clinical and pathological factors – namely, a T3 tumor, at least 12 lymph nodes examined, and negative margins – a third of whom had a lymph node ratio of greater than 0.1 (HR, 5.06; P = .003). Here, the estimated 5-year rate of recurrence was 27% with a ratio greater than 0.1 and just 4% with a lower ratio.

In a multivariate analysis among all patients that included potential confounders (age, T stage, number of lymph nodes assessed, and mismatch repair status), a GCC lymph node ratio greater than 0.1 was associated with a 2.61-fold higher risk of recurrence (P = .02).

The findings, which are considered preliminary, are being validated among an additional 500 patients, according to Dr. Sargent. "We think this is a very promising marker to be able to give patients with stage II disease an accurate prediction of what’s their likelihood of recurrence," he commented.

"We were able to define two-thirds of the population that have such a low risk for recurrence that I think it would be quite questionable whether there would be any potential reason to treat such patients," Dr. Sargent said, "whereas in the one-third of patients with high risk, they really look like stage III patients, and you might consider them as appropriate for treatment."

Tumor CDK1 Activity

Tumor activity of cyclin-dependent kinase 1 (CDK1), a key regulator of cell cycle progression, is a very strong and independent predictor of recurrence in patients with stage II colon cancer, investigators also reported.

"We believe that cell cycle profiling, the speed of the cell cycle, could be really important to predict tumor recurrence," said Dr. Masaki Shibayama of the Sysmex Corp. in Kobe, Japan, in an interview. Rapid proliferation "is one of the central hallmarks of cancer," he noted.

The investigators used the Cell Cycle Profiling (C2P) system (manufactured by Sysmex) to assess CDK1 enzymatic activity in fresh-frozen tumor samples from 254 patients from Germany and the Netherlands who underwent resection for stage II colon cancer and did not receive adjuvant therapy. With a median follow-up of 86 months, 11% developed distant metastases.

Some 40% of patients had a specific activity level of CDK1 that exceeded the cutoff of 11 and were classified as high risk, whereas 60% had a level of 11 or less and were classified as low risk. Relative to their low-risk peers, the high-risk patients were markedly more likely to develop distant metastases (HR, 6.2; P = .005) and to die from their cancer (HR, 7.6; P = .001).

These very high hazard ratios set this assay apart from other prognostic assays in stage II colon cancer, according to lead investigator Dr. Matthias Maak, a surgeon at the Technical University of Munich.

The hazard ratio for distant metastases was essentially the same after adjustment for age, sex, grade, and pathological T stage. It was still high (although no longer significant) after adjustment for tumor stroma content, possibly as a result of missing data for this parameter in about a third of cases.

"We believe this is a very nice result," Dr. Shibayama commented, and the assay may also extend to other solid tumors. "For example, we have a similar study for breast cancer, and it is also successful."

"This looks very promising," Dr. Maak concurred. "But this is, let’s say, the first test [of this assay] in colorectal carcinoma. Now we need more validation to find out if this works with another cohort, for example, or for another hospital. But we are rather positive that it will be as promising as it was in this trial."

Dr. Lenehan is an employee of Everist Genomics Inc. Dr. Sargent reported that his institution received research funding from DiagnoCure Inc. Dr. Shibayama is an employee of Sysmex Corp.; Dr. Maak did not report any conflicts of interest.

SAN FRANCISCO – Advances in molecular prognosis may soon make it possible to predict the risk of recurrence of early colorectal cancer after curative resection – and thus the need for adjuvant therapy in patients who might not otherwise receive further treatment.

Five-Gene Tumor Signature

A new five-gene tumor prognostic signature has performed well in external validation testing among patients with stage I or II disease, according to Dr. Peter F. Lenehan, chief medical officer of Everist Genomics Inc., in Ann Arbor, Mich.

Dr. Lenehan and his coinvestigators validated the gene signature among 115 patients who had undergone curative resection for stage I or II colon cancer or stage I rectal cancer and did not receive adjuvant therapy. Some 40% experienced a recurrence within 3 years.

For predicting recurrence, the signature had a sensitivity of 70%, a specificity of 55%, a positive predictive value of 51%, and a negative predictive value of 73%. The overall accuracy was 61%.

Other prognostic tests can differentiate patients who will not recur, Dr. Lenehan said, but "we alone are best able to predict who is going to recur. For this population, we believe this is more clinically significant because the default position is not to treat stage I and II.

"So if we are able to detect those that actually need more aggressive follow-up or high consideration for adjuvant chemotherapy, then our test is better suited for this patient population."

Patients with a signature-predicted high risk of recurrence were more than twice as likely to have a recurrence as were their counterparts with a signature-predicted low risk (hazard ratio, 2.06; P = .02).

In contrast, the combination of criteria suggested by the National Comprehensive Cancer Network (NCCN) (T4 stage, fewer than 12 lymph nodes examined, grade of 3 or 4, lymphovascular invasion, bowel obstruction, localized perforation, or close, indeterminate, or positive margins) did not significantly predict risk.

"We are the first prognostic test in colorectal cancer to target stage I. The others target stage II and III," Dr. Lenehan added.

"The importance for us is that 10%-15% of stage I colorectal cancer patients actually recur and succumb to their disease," he said. "The standard of care for this stage is no treatment. And therefore, you have 3,000 or 4,000 patients per year which are potentially missing treatment that could potentially help them."

The signature could also be used to select only high-risk stage I patients for a clinical trial of adjuvant therapy, which would dramatically reduce the number of patients needed to determine benefit, he added.

GCC Expression in Lymph Nodes

Expression in lymph nodes of mRNA of the enzyme guanylyl cyclase C (GCC) predicts recurrence in patients with stage II colon cancer, according to Daniel J. Sargent, Ph.D., a professor of biostatistics and of oncology at the Mayo Clinic in Rochester, Minn.

"GCC is a marker that is only present in the colon, and if you find the GCC marker in the lymph nodes, it indicates that the tumor has metastasized from the colon to the lymph nodes," he explained in an interview. "So the presence of GCC in the lymph nodes should be a negative prognostic marker, and that’s indeed what we found."

The investigators retrospectively studied 241 patients who underwent resection for stage II colon cancer, did not receive adjuvant therapy, and had a minimum follow-up of 36 months. With a median follow-up of 60 months, 12% had a recurrence or cancer-related death. Some 10-41 lymph nodes (median, 15) were evaluated per patient.

The GCC assay results were expressed as a lymph node ratio (number of positive nodes divided by total number of informative nodes). In all, 35% of patients had a lymph node ratio of greater than 0.1.

These patients had more than double the risk of recurrence, compared with their counterparts who had a lower ratio (HR, 2.38; P = .02). The estimated 5-year rate of recurrence was 27% for the former and 10% for the latter.

The findings were even stronger in the subgroup of 181 patients with highly favorable clinical and pathological factors – namely, a T3 tumor, at least 12 lymph nodes examined, and negative margins – a third of whom had a lymph node ratio of greater than 0.1 (HR, 5.06; P = .003). Here, the estimated 5-year rate of recurrence was 27% with a ratio greater than 0.1 and just 4% with a lower ratio.

In a multivariate analysis among all patients that included potential confounders (age, T stage, number of lymph nodes assessed, and mismatch repair status), a GCC lymph node ratio greater than 0.1 was associated with a 2.61-fold higher risk of recurrence (P = .02).

The findings, which are considered preliminary, are being validated among an additional 500 patients, according to Dr. Sargent. "We think this is a very promising marker to be able to give patients with stage II disease an accurate prediction of what’s their likelihood of recurrence," he commented.

"We were able to define two-thirds of the population that have such a low risk for recurrence that I think it would be quite questionable whether there would be any potential reason to treat such patients," Dr. Sargent said, "whereas in the one-third of patients with high risk, they really look like stage III patients, and you might consider them as appropriate for treatment."

Tumor CDK1 Activity

Tumor activity of cyclin-dependent kinase 1 (CDK1), a key regulator of cell cycle progression, is a very strong and independent predictor of recurrence in patients with stage II colon cancer, investigators also reported.

"We believe that cell cycle profiling, the speed of the cell cycle, could be really important to predict tumor recurrence," said Dr. Masaki Shibayama of the Sysmex Corp. in Kobe, Japan, in an interview. Rapid proliferation "is one of the central hallmarks of cancer," he noted.

The investigators used the Cell Cycle Profiling (C2P) system (manufactured by Sysmex) to assess CDK1 enzymatic activity in fresh-frozen tumor samples from 254 patients from Germany and the Netherlands who underwent resection for stage II colon cancer and did not receive adjuvant therapy. With a median follow-up of 86 months, 11% developed distant metastases.

Some 40% of patients had a specific activity level of CDK1 that exceeded the cutoff of 11 and were classified as high risk, whereas 60% had a level of 11 or less and were classified as low risk. Relative to their low-risk peers, the high-risk patients were markedly more likely to develop distant metastases (HR, 6.2; P = .005) and to die from their cancer (HR, 7.6; P = .001).

These very high hazard ratios set this assay apart from other prognostic assays in stage II colon cancer, according to lead investigator Dr. Matthias Maak, a surgeon at the Technical University of Munich.

The hazard ratio for distant metastases was essentially the same after adjustment for age, sex, grade, and pathological T stage. It was still high (although no longer significant) after adjustment for tumor stroma content, possibly as a result of missing data for this parameter in about a third of cases.

"We believe this is a very nice result," Dr. Shibayama commented, and the assay may also extend to other solid tumors. "For example, we have a similar study for breast cancer, and it is also successful."

"This looks very promising," Dr. Maak concurred. "But this is, let’s say, the first test [of this assay] in colorectal carcinoma. Now we need more validation to find out if this works with another cohort, for example, or for another hospital. But we are rather positive that it will be as promising as it was in this trial."

Dr. Lenehan is an employee of Everist Genomics Inc. Dr. Sargent reported that his institution received research funding from DiagnoCure Inc. Dr. Shibayama is an employee of Sysmex Corp.; Dr. Maak did not report any conflicts of interest.