Susan London

LOS ANGELES – Surgically exploring the retroperitoneum for disease may benefit some patients undergoing primary debulking of advanced ovarian cancer, a study reported at the annual meeting of the Society of Gynecologic Oncology has shown.

Investigators analyzed data from Gynecologic Oncology Group (GOG) trial 182, focusing on the 1,876 women who had stage IIIc epithelial ovarian cancer on the basis of intraperitoneal tumor size and who underwent optimal debulking.

Overall, one-third had a retroperitoneal exploration, defined in the study as removal of at least one pelvic or para-aortic lymph node.

Patients who had this procedure were 15% less likely to experience progression or death and 15% less likely to die after other factors were considered, reported lead investigator Dr. Bunja Rungruang, a gynecologic oncologist with Georgia Regents University in Augusta.

In stratified analyses, benefit was seen in the subgroup with minimal gross residual disease but not in the subgroup with microscopic residual disease.

"In this large multi-institutional trial, there is evidence that retroperitoneal exploration at the time of primary debulking surgery of patients with intraperitoneal stage IIIc epithelial ovarian cancer may provide survival benefit," she commented.

"Surgical effort and tumor biology interact to affect patient outcomes," Dr. Rungruang noted. "Retroperitoneal exploration may be a proxy for more thorough surgical effort in these patients, rather than tumor biology alone driving outcomes. Surgeon discretion is a potential factor here as well; it is conceivable that the surgeon’s impression or information about prognosis influences the retroperitoneal exploration decision, based on unmeasured indicators of patient disease burden or vitality.

"Given the small but significant survival differences and the large sample size of this study, it is possible that these survival advantages are to some degree indicative of unmeasured factors or the accuracy of the surgeon’s impression, and not completely about the act of pathologic exploration," she said.

One attendee noted that analyses have suggested that patients who do not have a retroperitoneal exploration fare even more poorly than those who have the procedure and are found to have positive lymph nodes.

"I am concerned that that is because the surgeon thought the prognosis was so bad that they didn’t bother. I don’t know whether you have a sense of whether that conclusion looked appropriate for your analysis of all the tumor burden in that patient," Dr. Rungruang said.

"For some of the patients, it seemed to be a surgeon preference that they didn’t sample the nodes because they felt that the patient was already stage IIIc and called them microscopic optimally debulked, or microscopic optimally debulked without assessing the lymph nodes. Other patients had a much larger surgery, a higher complexity of procedures, and still had a lymph node assessment on top of it. What I can tell from reading the actual operative notes is a lot of [the approach] is based on surgeon preference."

In discussing the lack of additional benefit for exploration in women with microscopic residual disease, Dr. Rungruang explained that "if you have microscopic residual disease, that seems like the best you can do for those patients. I think in the macroscopic residual patients, you see the difference because it is perhaps a proxy for just a more thorough surgical assessment in these patients. Plus, macroscopic residual disease is such a wide spectrum, you can be anywhere from one site of residual disease to miliary disease spread throughout, and that heterogeneity within that residual disease group also accounts for that difference."

Patients enrolled in GOG 182 had advanced epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer, and underwent primary debulking to optimal residual disease (less than 1 cm), followed by randomization to a variety of platinum- and paclitaxel-based adjuvant chemotherapy regimens.

The investigators restricted analyses to the subset whose disease was stage IIIc on the basis of an intraperitoneal tumor measuring at least 2 cm. Overall, 37% of this subset had a retroperitoneal exploration.

The patients undergoing this additional procedure had better median progression-free survival (18.5 vs. 16.0 months, P less than .0001) and overall survival (53.3 vs. 42.8 months, P less than .0001), reported Dr. Rungruang.

When patients were stratified, retroperitoneal exploration was beneficial in those with minimal gross residual disease in terms of both progression-free survival (16.8 vs. 15.1 months, P = .01) and overall survival (44.9 vs. 40.5 months, P = .008). But there was no such benefit in patients who had microscopic residual disease.

In a multivariate analysis, retroperitoneal exploration independently predicted better progression-free survival (hazard ratio, 0.85; P = .004) and overall survival (HR, 0.85; P = .009).

Dr. Rungruang disclosed no relevant financial conflicts.

LOS ANGELES – Surgically exploring the retroperitoneum for disease may benefit some patients undergoing primary debulking of advanced ovarian cancer, a study reported at the annual meeting of the Society of Gynecologic Oncology has shown.

Investigators analyzed data from Gynecologic Oncology Group (GOG) trial 182, focusing on the 1,876 women who had stage IIIc epithelial ovarian cancer on the basis of intraperitoneal tumor size and who underwent optimal debulking.

Overall, one-third had a retroperitoneal exploration, defined in the study as removal of at least one pelvic or para-aortic lymph node.

Patients who had this procedure were 15% less likely to experience progression or death and 15% less likely to die after other factors were considered, reported lead investigator Dr. Bunja Rungruang, a gynecologic oncologist with Georgia Regents University in Augusta.

In stratified analyses, benefit was seen in the subgroup with minimal gross residual disease but not in the subgroup with microscopic residual disease.

"In this large multi-institutional trial, there is evidence that retroperitoneal exploration at the time of primary debulking surgery of patients with intraperitoneal stage IIIc epithelial ovarian cancer may provide survival benefit," she commented.

"Surgical effort and tumor biology interact to affect patient outcomes," Dr. Rungruang noted. "Retroperitoneal exploration may be a proxy for more thorough surgical effort in these patients, rather than tumor biology alone driving outcomes. Surgeon discretion is a potential factor here as well; it is conceivable that the surgeon’s impression or information about prognosis influences the retroperitoneal exploration decision, based on unmeasured indicators of patient disease burden or vitality.

"Given the small but significant survival differences and the large sample size of this study, it is possible that these survival advantages are to some degree indicative of unmeasured factors or the accuracy of the surgeon’s impression, and not completely about the act of pathologic exploration," she said.

One attendee noted that analyses have suggested that patients who do not have a retroperitoneal exploration fare even more poorly than those who have the procedure and are found to have positive lymph nodes.

"I am concerned that that is because the surgeon thought the prognosis was so bad that they didn’t bother. I don’t know whether you have a sense of whether that conclusion looked appropriate for your analysis of all the tumor burden in that patient," Dr. Rungruang said.

"For some of the patients, it seemed to be a surgeon preference that they didn’t sample the nodes because they felt that the patient was already stage IIIc and called them microscopic optimally debulked, or microscopic optimally debulked without assessing the lymph nodes. Other patients had a much larger surgery, a higher complexity of procedures, and still had a lymph node assessment on top of it. What I can tell from reading the actual operative notes is a lot of [the approach] is based on surgeon preference."

In discussing the lack of additional benefit for exploration in women with microscopic residual disease, Dr. Rungruang explained that "if you have microscopic residual disease, that seems like the best you can do for those patients. I think in the macroscopic residual patients, you see the difference because it is perhaps a proxy for just a more thorough surgical assessment in these patients. Plus, macroscopic residual disease is such a wide spectrum, you can be anywhere from one site of residual disease to miliary disease spread throughout, and that heterogeneity within that residual disease group also accounts for that difference."

Patients enrolled in GOG 182 had advanced epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer, and underwent primary debulking to optimal residual disease (less than 1 cm), followed by randomization to a variety of platinum- and paclitaxel-based adjuvant chemotherapy regimens.

The investigators restricted analyses to the subset whose disease was stage IIIc on the basis of an intraperitoneal tumor measuring at least 2 cm. Overall, 37% of this subset had a retroperitoneal exploration.

The patients undergoing this additional procedure had better median progression-free survival (18.5 vs. 16.0 months, P less than .0001) and overall survival (53.3 vs. 42.8 months, P less than .0001), reported Dr. Rungruang.

When patients were stratified, retroperitoneal exploration was beneficial in those with minimal gross residual disease in terms of both progression-free survival (16.8 vs. 15.1 months, P = .01) and overall survival (44.9 vs. 40.5 months, P = .008). But there was no such benefit in patients who had microscopic residual disease.

In a multivariate analysis, retroperitoneal exploration independently predicted better progression-free survival (hazard ratio, 0.85; P = .004) and overall survival (HR, 0.85; P = .009).

Dr. Rungruang disclosed no relevant financial conflicts.

LOS ANGELES – Surgically exploring the retroperitoneum for disease may benefit some patients undergoing primary debulking of advanced ovarian cancer, a study reported at the annual meeting of the Society of Gynecologic Oncology has shown.

Investigators analyzed data from Gynecologic Oncology Group (GOG) trial 182, focusing on the 1,876 women who had stage IIIc epithelial ovarian cancer on the basis of intraperitoneal tumor size and who underwent optimal debulking.

Overall, one-third had a retroperitoneal exploration, defined in the study as removal of at least one pelvic or para-aortic lymph node.

Patients who had this procedure were 15% less likely to experience progression or death and 15% less likely to die after other factors were considered, reported lead investigator Dr. Bunja Rungruang, a gynecologic oncologist with Georgia Regents University in Augusta.

In stratified analyses, benefit was seen in the subgroup with minimal gross residual disease but not in the subgroup with microscopic residual disease.

"In this large multi-institutional trial, there is evidence that retroperitoneal exploration at the time of primary debulking surgery of patients with intraperitoneal stage IIIc epithelial ovarian cancer may provide survival benefit," she commented.

"Surgical effort and tumor biology interact to affect patient outcomes," Dr. Rungruang noted. "Retroperitoneal exploration may be a proxy for more thorough surgical effort in these patients, rather than tumor biology alone driving outcomes. Surgeon discretion is a potential factor here as well; it is conceivable that the surgeon’s impression or information about prognosis influences the retroperitoneal exploration decision, based on unmeasured indicators of patient disease burden or vitality.

"Given the small but significant survival differences and the large sample size of this study, it is possible that these survival advantages are to some degree indicative of unmeasured factors or the accuracy of the surgeon’s impression, and not completely about the act of pathologic exploration," she said.

One attendee noted that analyses have suggested that patients who do not have a retroperitoneal exploration fare even more poorly than those who have the procedure and are found to have positive lymph nodes.

"I am concerned that that is because the surgeon thought the prognosis was so bad that they didn’t bother. I don’t know whether you have a sense of whether that conclusion looked appropriate for your analysis of all the tumor burden in that patient," Dr. Rungruang said.

"For some of the patients, it seemed to be a surgeon preference that they didn’t sample the nodes because they felt that the patient was already stage IIIc and called them microscopic optimally debulked, or microscopic optimally debulked without assessing the lymph nodes. Other patients had a much larger surgery, a higher complexity of procedures, and still had a lymph node assessment on top of it. What I can tell from reading the actual operative notes is a lot of [the approach] is based on surgeon preference."

In discussing the lack of additional benefit for exploration in women with microscopic residual disease, Dr. Rungruang explained that "if you have microscopic residual disease, that seems like the best you can do for those patients. I think in the macroscopic residual patients, you see the difference because it is perhaps a proxy for just a more thorough surgical assessment in these patients. Plus, macroscopic residual disease is such a wide spectrum, you can be anywhere from one site of residual disease to miliary disease spread throughout, and that heterogeneity within that residual disease group also accounts for that difference."

Patients enrolled in GOG 182 had advanced epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer, and underwent primary debulking to optimal residual disease (less than 1 cm), followed by randomization to a variety of platinum- and paclitaxel-based adjuvant chemotherapy regimens.

The investigators restricted analyses to the subset whose disease was stage IIIc on the basis of an intraperitoneal tumor measuring at least 2 cm. Overall, 37% of this subset had a retroperitoneal exploration.

The patients undergoing this additional procedure had better median progression-free survival (18.5 vs. 16.0 months, P less than .0001) and overall survival (53.3 vs. 42.8 months, P less than .0001), reported Dr. Rungruang.

When patients were stratified, retroperitoneal exploration was beneficial in those with minimal gross residual disease in terms of both progression-free survival (16.8 vs. 15.1 months, P = .01) and overall survival (44.9 vs. 40.5 months, P = .008). But there was no such benefit in patients who had microscopic residual disease.

In a multivariate analysis, retroperitoneal exploration independently predicted better progression-free survival (hazard ratio, 0.85; P = .004) and overall survival (HR, 0.85; P = .009).

Dr. Rungruang disclosed no relevant financial conflicts.

SAN FRANCISCO – The risk of stillbirth in pregnancies complicated by a fetus that is small for gestational age rises after the pregnancy reaches term, supporting prompt delivery, according to a retrospective cohort study.

Investigators led by Dr. Amanda S. Trudell, an obstetrician at Washington University in St. Louis, studied more than 3,000 women with singleton gestations complicated by small for gestational age (SGA) but otherwise healthy fetuses.

Susan London/IMNG Medical Media

Analyses showed that the cumulative risk of stillbirth began to rise after gestation exceeded 37 weeks. It was significantly elevated by nearly threefold for women delivering at 39 weeks and by nearly sevenfold for those delivering at 40 or more weeks.

The number of deliveries needed to prevent a single stillbirth (number needed to treat) was 204 at 39 weeks and 60 at 40 or more weeks.

"Our data demonstrates a continuous rise in the cumulative risk of stillbirth after 37 to 38 weeks," Dr. Trudell reported when presenting the data at the Pregnancy Meeting, the annual meeting of the Society for Maternal-Fetal Medicine.

"Without a randomized controlled trial to evaluate stillbirth, and weighing the gravity of stillbirth against the morbidities of early-term delivery, given the favorable number needed to treat to prevent one stillbirth, we advocate delivery of SGA pregnancies in the 37th week and not beyond the 38th week," she said.

Session attendee Dr. Harvey Kliman of Yale University in New Haven, Conn., asked, "Do you have any data on placentas of these cases, because I think it would be important to understand why they are SGA and why they are IUFD [intrauterine fetal demise]."

Such data are not available for this study cohort, Dr. Trudell replied.

"I would just make a pitch to everybody: Don’t throw out your best defense. I do a lot of medicolegal work and will tell you, it’s important to have it," Dr. Kliman advised. "And also for these studies, we need to understand the mechanism behind this to really fix this problem."

Another attendee wondered about the definition of SGA used in the study, which was a birth weight of less than the 10th percentile.

"Have you considered using things like customized growth curves? Some people think there are better ways to truly define who is at risk and who is not at risk," he commented.

The investigators did not look at customized growth curves in this study, according to Dr. Trudell; however, they did look at a more stringent threshold for SGA, set at the 5th percentile. In that analysis, the cumulative risk of stillbirth became significantly elevated at 38 weeks, with a 2.3-fold higher risk than at 37 weeks.

"The delivery timing of SGA pregnancies weighs the competing risks of neonatal morbidity associated with early-term delivery versus the risk of stillbirth associated with expectant management," she said, giving some background to the research.

In 2010, the DIGITAT (Induction Versus Expectant Monitoring for Intrauterine Growth Restriction at Term) trial demonstrated no increase in maternal or neonatal risk with induction of SGA fetuses at 37 weeks, compared with expectant monitoring, she noted (BMJ 2010;341:c7087). "The authors concluded that either induction or expectant monitoring were acceptable management strategies for presumed growth restriction at term. Due to the rarity of stillbirth, the trial was underpowered to evaluate this outcome," Dr. Trudell said.

Starting with Washington University’s prospective perinatal database, Dr. Trudell and her colleagues identified 3,333 women with a singleton gestation of at least 37 weeks that had an SGA fetus but was not complicated by major anomalies or aneuploidy.

Overall, 0.6% of the women had a stillbirth, according to data reported at the meeting.

Life table analyses showed that the cumulative risk of stillbirth (which reflects risk through time) was 28, 41, 77, and 194 per 10,000 women at 37, 38, 39, and 40 or more weeks, respectively.

The corresponding conditional risk of stillbirth (which captures risk at just a single point in time and is conditional on survival to that point in time) was 28, 13, 36, and 120 per 10,000 women.

"The cumulative risk of stillbirth is the preferred method when attempting to answer our clinical question of delivery timing. ... Notice that the conditional risk uniformly underestimates the stillbirth risk," Dr. Trudell noted.

Compared with women who delivered at 37 weeks, those delivering at 38 weeks had a nonsignificant 1.5-fold higher risk of stillbirth, and those delivering at 39 weeks and at 40 or more weeks had respective significant 2.8- and 6.9-fold higher risks.

The number of deliveries needed to prevent a single stillbirth was 769, 204, and 60 at 38, 39, and 40 or more weeks, respectively.

"Although some would consider the use of birth weight as a shortcoming, we would offer it as a strength. The use of birth weight allows us to examine the direct relationship between small fetuses and stillbirth, whereas the estimated fetal weight examines the accuracy of ultrasound to predict fetal weight and is a different question altogether," Dr. Trudell maintained.

"It is only after we have tested the direct association between SGA and stillbirth, as we have in this study, that improvement in our technical ability to predict SGA by ultrasound becomes relevant."

Dr. Trudell disclosed no conflicts of interest related to the research.

obnews@frontlinemedcom.com

SAN FRANCISCO – The risk of stillbirth in pregnancies complicated by a fetus that is small for gestational age rises after the pregnancy reaches term, supporting prompt delivery, according to a retrospective cohort study.

Investigators led by Dr. Amanda S. Trudell, an obstetrician at Washington University in St. Louis, studied more than 3,000 women with singleton gestations complicated by small for gestational age (SGA) but otherwise healthy fetuses.

Susan London/IMNG Medical Media

Analyses showed that the cumulative risk of stillbirth began to rise after gestation exceeded 37 weeks. It was significantly elevated by nearly threefold for women delivering at 39 weeks and by nearly sevenfold for those delivering at 40 or more weeks.

The number of deliveries needed to prevent a single stillbirth (number needed to treat) was 204 at 39 weeks and 60 at 40 or more weeks.

"Our data demonstrates a continuous rise in the cumulative risk of stillbirth after 37 to 38 weeks," Dr. Trudell reported when presenting the data at the Pregnancy Meeting, the annual meeting of the Society for Maternal-Fetal Medicine.

"Without a randomized controlled trial to evaluate stillbirth, and weighing the gravity of stillbirth against the morbidities of early-term delivery, given the favorable number needed to treat to prevent one stillbirth, we advocate delivery of SGA pregnancies in the 37th week and not beyond the 38th week," she said.

Session attendee Dr. Harvey Kliman of Yale University in New Haven, Conn., asked, "Do you have any data on placentas of these cases, because I think it would be important to understand why they are SGA and why they are IUFD [intrauterine fetal demise]."

Such data are not available for this study cohort, Dr. Trudell replied.

"I would just make a pitch to everybody: Don’t throw out your best defense. I do a lot of medicolegal work and will tell you, it’s important to have it," Dr. Kliman advised. "And also for these studies, we need to understand the mechanism behind this to really fix this problem."

Another attendee wondered about the definition of SGA used in the study, which was a birth weight of less than the 10th percentile.

"Have you considered using things like customized growth curves? Some people think there are better ways to truly define who is at risk and who is not at risk," he commented.

The investigators did not look at customized growth curves in this study, according to Dr. Trudell; however, they did look at a more stringent threshold for SGA, set at the 5th percentile. In that analysis, the cumulative risk of stillbirth became significantly elevated at 38 weeks, with a 2.3-fold higher risk than at 37 weeks.

"The delivery timing of SGA pregnancies weighs the competing risks of neonatal morbidity associated with early-term delivery versus the risk of stillbirth associated with expectant management," she said, giving some background to the research.

In 2010, the DIGITAT (Induction Versus Expectant Monitoring for Intrauterine Growth Restriction at Term) trial demonstrated no increase in maternal or neonatal risk with induction of SGA fetuses at 37 weeks, compared with expectant monitoring, she noted (BMJ 2010;341:c7087). "The authors concluded that either induction or expectant monitoring were acceptable management strategies for presumed growth restriction at term. Due to the rarity of stillbirth, the trial was underpowered to evaluate this outcome," Dr. Trudell said.

Starting with Washington University’s prospective perinatal database, Dr. Trudell and her colleagues identified 3,333 women with a singleton gestation of at least 37 weeks that had an SGA fetus but was not complicated by major anomalies or aneuploidy.

Overall, 0.6% of the women had a stillbirth, according to data reported at the meeting.

Life table analyses showed that the cumulative risk of stillbirth (which reflects risk through time) was 28, 41, 77, and 194 per 10,000 women at 37, 38, 39, and 40 or more weeks, respectively.

The corresponding conditional risk of stillbirth (which captures risk at just a single point in time and is conditional on survival to that point in time) was 28, 13, 36, and 120 per 10,000 women.

"The cumulative risk of stillbirth is the preferred method when attempting to answer our clinical question of delivery timing. ... Notice that the conditional risk uniformly underestimates the stillbirth risk," Dr. Trudell noted.

Compared with women who delivered at 37 weeks, those delivering at 38 weeks had a nonsignificant 1.5-fold higher risk of stillbirth, and those delivering at 39 weeks and at 40 or more weeks had respective significant 2.8- and 6.9-fold higher risks.

The number of deliveries needed to prevent a single stillbirth was 769, 204, and 60 at 38, 39, and 40 or more weeks, respectively.

"Although some would consider the use of birth weight as a shortcoming, we would offer it as a strength. The use of birth weight allows us to examine the direct relationship between small fetuses and stillbirth, whereas the estimated fetal weight examines the accuracy of ultrasound to predict fetal weight and is a different question altogether," Dr. Trudell maintained.

"It is only after we have tested the direct association between SGA and stillbirth, as we have in this study, that improvement in our technical ability to predict SGA by ultrasound becomes relevant."

Dr. Trudell disclosed no conflicts of interest related to the research.

obnews@frontlinemedcom.com

SAN FRANCISCO – The risk of stillbirth in pregnancies complicated by a fetus that is small for gestational age rises after the pregnancy reaches term, supporting prompt delivery, according to a retrospective cohort study.

Investigators led by Dr. Amanda S. Trudell, an obstetrician at Washington University in St. Louis, studied more than 3,000 women with singleton gestations complicated by small for gestational age (SGA) but otherwise healthy fetuses.

Susan London/IMNG Medical Media

Analyses showed that the cumulative risk of stillbirth began to rise after gestation exceeded 37 weeks. It was significantly elevated by nearly threefold for women delivering at 39 weeks and by nearly sevenfold for those delivering at 40 or more weeks.

The number of deliveries needed to prevent a single stillbirth (number needed to treat) was 204 at 39 weeks and 60 at 40 or more weeks.

"Our data demonstrates a continuous rise in the cumulative risk of stillbirth after 37 to 38 weeks," Dr. Trudell reported when presenting the data at the Pregnancy Meeting, the annual meeting of the Society for Maternal-Fetal Medicine.

"Without a randomized controlled trial to evaluate stillbirth, and weighing the gravity of stillbirth against the morbidities of early-term delivery, given the favorable number needed to treat to prevent one stillbirth, we advocate delivery of SGA pregnancies in the 37th week and not beyond the 38th week," she said.

Session attendee Dr. Harvey Kliman of Yale University in New Haven, Conn., asked, "Do you have any data on placentas of these cases, because I think it would be important to understand why they are SGA and why they are IUFD [intrauterine fetal demise]."

Such data are not available for this study cohort, Dr. Trudell replied.

"I would just make a pitch to everybody: Don’t throw out your best defense. I do a lot of medicolegal work and will tell you, it’s important to have it," Dr. Kliman advised. "And also for these studies, we need to understand the mechanism behind this to really fix this problem."

Another attendee wondered about the definition of SGA used in the study, which was a birth weight of less than the 10th percentile.

"Have you considered using things like customized growth curves? Some people think there are better ways to truly define who is at risk and who is not at risk," he commented.

The investigators did not look at customized growth curves in this study, according to Dr. Trudell; however, they did look at a more stringent threshold for SGA, set at the 5th percentile. In that analysis, the cumulative risk of stillbirth became significantly elevated at 38 weeks, with a 2.3-fold higher risk than at 37 weeks.

"The delivery timing of SGA pregnancies weighs the competing risks of neonatal morbidity associated with early-term delivery versus the risk of stillbirth associated with expectant management," she said, giving some background to the research.

In 2010, the DIGITAT (Induction Versus Expectant Monitoring for Intrauterine Growth Restriction at Term) trial demonstrated no increase in maternal or neonatal risk with induction of SGA fetuses at 37 weeks, compared with expectant monitoring, she noted (BMJ 2010;341:c7087). "The authors concluded that either induction or expectant monitoring were acceptable management strategies for presumed growth restriction at term. Due to the rarity of stillbirth, the trial was underpowered to evaluate this outcome," Dr. Trudell said.

Starting with Washington University’s prospective perinatal database, Dr. Trudell and her colleagues identified 3,333 women with a singleton gestation of at least 37 weeks that had an SGA fetus but was not complicated by major anomalies or aneuploidy.

Overall, 0.6% of the women had a stillbirth, according to data reported at the meeting.

Life table analyses showed that the cumulative risk of stillbirth (which reflects risk through time) was 28, 41, 77, and 194 per 10,000 women at 37, 38, 39, and 40 or more weeks, respectively.

The corresponding conditional risk of stillbirth (which captures risk at just a single point in time and is conditional on survival to that point in time) was 28, 13, 36, and 120 per 10,000 women.

"The cumulative risk of stillbirth is the preferred method when attempting to answer our clinical question of delivery timing. ... Notice that the conditional risk uniformly underestimates the stillbirth risk," Dr. Trudell noted.

Compared with women who delivered at 37 weeks, those delivering at 38 weeks had a nonsignificant 1.5-fold higher risk of stillbirth, and those delivering at 39 weeks and at 40 or more weeks had respective significant 2.8- and 6.9-fold higher risks.

The number of deliveries needed to prevent a single stillbirth was 769, 204, and 60 at 38, 39, and 40 or more weeks, respectively.

"Although some would consider the use of birth weight as a shortcoming, we would offer it as a strength. The use of birth weight allows us to examine the direct relationship between small fetuses and stillbirth, whereas the estimated fetal weight examines the accuracy of ultrasound to predict fetal weight and is a different question altogether," Dr. Trudell maintained.

"It is only after we have tested the direct association between SGA and stillbirth, as we have in this study, that improvement in our technical ability to predict SGA by ultrasound becomes relevant."

Dr. Trudell disclosed no conflicts of interest related to the research.

obnews@frontlinemedcom.com

SAN FRANCISCO – Giving more than one course of antenatal corticosteroids to prevent preterm birth does not appear to benefit or harm offspring in the longer term, according to a follow-up analysis of the randomized MACS trial.

In the trial, 1,724 pregnant women at high risk for preterm birth were given either a single course of antenatal steroids or multiple courses every 14 days on a double-blind basis.

Results reported at the Pregnancy Meeting, the annual meeting of the Society for Maternal-Fetal Medicine, showed that one-fourth of the infants had died or were severely neurodevelopmentally impaired at the age of 5 years, with no significant difference between groups.

"Multiple courses of antenatal corticosteroids given every 14 days does not increase nor does it decrease the risk of death or neurodevelopmental difficulties by 5 years of age compared to a single course," commented lead author Dr. Elizabeth Asztalos of the department of pediatrics and ob.gyn. at the University of Toronto and director and scientist at the Centre for Mother, Infant and Child Research at Sunnybrook Health Sciences Centre, also in Toronto. "Because we could not identify short-term neonatal or long-term neurodevelopmental benefits, we conclude that multiple courses of antenatal steroids given every 14 days are not recommended for the woman at risk of preterm birth."

"We emphasize that continued follow-up of this cohort is needed to rule out the possibility of long-term neurobehavioral and neurosensory function [differences], as well as disabilities and metabolic and cardiovascular disease that could not be detected at this early age," she added. "Additional analyses will be conducted that will try to evaluate the interaction between multiple courses and outcomes as it relates to prolonged rupture of membranes, term versus preterm birth, and infant sex."

One attendee noted that a previous study did find a difference in developmental disability after three or four courses of antenatal steroids. "So I’m wondering whether you have a subanalysis of outcomes by number of courses," he said.

"We have not specifically done that from the neurocognitive perspective," Dr. Asztalos replied. "That is something that we will start to look at."

Another attendee commented, "It appears that the measures you looked at [at] this young age are of fairly significant impacts; yet, in human studies, there is some suggestion of behavioral abnormalities induced by steroids including anxiety and stress responses, and clearly in animal studies – particularly those done in Australia – of programming of offspring HPA [hypothalamic-pituitary-adrenal] axis that’s in a sex-specific manner. Do you plan to look at any of those factors in the future?"

"We do. We are hoping that the Canadian government will allow us to continue to follow these children [until] 12 [years of age], and we will definitely look at these measures," Dr. Asztalos replied.

Pregnant women were eligible for the MACS (Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study) trial if they were at 26-30 weeks’ gestation and were at risk for early birth and had not delivered 14 or more days after an initial course of antenatal corticosteroids.

They were assigned to receive study medication, either betamethasone or placebo, every 14 days until 33 completed weeks or delivery.

Initial trial results, previously published (Lancet 2008;372:2143-51), showed that the multicourse group did not have a lower rate of perinatal or neonatal mortality or neonatal morbidity. Birth weight and length were less, and head circumference was smaller in the multicourse group.

In addition, at the age of 18-24 months, offspring in the multicourse group did not have a lower rate of death or neurologic impairment such as cerebral palsy or cognitive delay (Pediatrics 2010;126:1045-55). They still weighed less, but appeared to be catching up.

The latest results, now at a median age of 5.2 years, showed that children in the multicourse group did not have a significantly different rate of the composite outcome of death or neurodevelopmental impairment relative to their counterparts in the single-course group (24.9% vs. 24.6%), according to data reported at the meeting.

The findings were similar for the individual components of death, neuromotor impairment (defined as nonambulatory cerebral palsy), neurosensory impairment (blindness in at least one eye, deafness, or need for visual or hearing aid), and neurocognitive impairment (abnormal attention, memory, or behavior).

At this time point, children in the two groups were statistically indistinguishable with respect to weight, height, and head circumference; systolic and diastolic blood pressure; and various measures of intelligence and specific cognitive skills, according to Dr. Asztalos.

Dr. Asztalos disclosed no conflicts of interest related to the research.

SAN FRANCISCO – Giving more than one course of antenatal corticosteroids to prevent preterm birth does not appear to benefit or harm offspring in the longer term, according to a follow-up analysis of the randomized MACS trial.

In the trial, 1,724 pregnant women at high risk for preterm birth were given either a single course of antenatal steroids or multiple courses every 14 days on a double-blind basis.

Results reported at the Pregnancy Meeting, the annual meeting of the Society for Maternal-Fetal Medicine, showed that one-fourth of the infants had died or were severely neurodevelopmentally impaired at the age of 5 years, with no significant difference between groups.

"Multiple courses of antenatal corticosteroids given every 14 days does not increase nor does it decrease the risk of death or neurodevelopmental difficulties by 5 years of age compared to a single course," commented lead author Dr. Elizabeth Asztalos of the department of pediatrics and ob.gyn. at the University of Toronto and director and scientist at the Centre for Mother, Infant and Child Research at Sunnybrook Health Sciences Centre, also in Toronto. "Because we could not identify short-term neonatal or long-term neurodevelopmental benefits, we conclude that multiple courses of antenatal steroids given every 14 days are not recommended for the woman at risk of preterm birth."

"We emphasize that continued follow-up of this cohort is needed to rule out the possibility of long-term neurobehavioral and neurosensory function [differences], as well as disabilities and metabolic and cardiovascular disease that could not be detected at this early age," she added. "Additional analyses will be conducted that will try to evaluate the interaction between multiple courses and outcomes as it relates to prolonged rupture of membranes, term versus preterm birth, and infant sex."

One attendee noted that a previous study did find a difference in developmental disability after three or four courses of antenatal steroids. "So I’m wondering whether you have a subanalysis of outcomes by number of courses," he said.

"We have not specifically done that from the neurocognitive perspective," Dr. Asztalos replied. "That is something that we will start to look at."

Another attendee commented, "It appears that the measures you looked at [at] this young age are of fairly significant impacts; yet, in human studies, there is some suggestion of behavioral abnormalities induced by steroids including anxiety and stress responses, and clearly in animal studies – particularly those done in Australia – of programming of offspring HPA [hypothalamic-pituitary-adrenal] axis that’s in a sex-specific manner. Do you plan to look at any of those factors in the future?"

"We do. We are hoping that the Canadian government will allow us to continue to follow these children [until] 12 [years of age], and we will definitely look at these measures," Dr. Asztalos replied.

Pregnant women were eligible for the MACS (Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study) trial if they were at 26-30 weeks’ gestation and were at risk for early birth and had not delivered 14 or more days after an initial course of antenatal corticosteroids.

They were assigned to receive study medication, either betamethasone or placebo, every 14 days until 33 completed weeks or delivery.

Initial trial results, previously published (Lancet 2008;372:2143-51), showed that the multicourse group did not have a lower rate of perinatal or neonatal mortality or neonatal morbidity. Birth weight and length were less, and head circumference was smaller in the multicourse group.

In addition, at the age of 18-24 months, offspring in the multicourse group did not have a lower rate of death or neurologic impairment such as cerebral palsy or cognitive delay (Pediatrics 2010;126:1045-55). They still weighed less, but appeared to be catching up.

The latest results, now at a median age of 5.2 years, showed that children in the multicourse group did not have a significantly different rate of the composite outcome of death or neurodevelopmental impairment relative to their counterparts in the single-course group (24.9% vs. 24.6%), according to data reported at the meeting.

The findings were similar for the individual components of death, neuromotor impairment (defined as nonambulatory cerebral palsy), neurosensory impairment (blindness in at least one eye, deafness, or need for visual or hearing aid), and neurocognitive impairment (abnormal attention, memory, or behavior).

At this time point, children in the two groups were statistically indistinguishable with respect to weight, height, and head circumference; systolic and diastolic blood pressure; and various measures of intelligence and specific cognitive skills, according to Dr. Asztalos.

Dr. Asztalos disclosed no conflicts of interest related to the research.

SAN FRANCISCO – Giving more than one course of antenatal corticosteroids to prevent preterm birth does not appear to benefit or harm offspring in the longer term, according to a follow-up analysis of the randomized MACS trial.

In the trial, 1,724 pregnant women at high risk for preterm birth were given either a single course of antenatal steroids or multiple courses every 14 days on a double-blind basis.

Results reported at the Pregnancy Meeting, the annual meeting of the Society for Maternal-Fetal Medicine, showed that one-fourth of the infants had died or were severely neurodevelopmentally impaired at the age of 5 years, with no significant difference between groups.

"Multiple courses of antenatal corticosteroids given every 14 days does not increase nor does it decrease the risk of death or neurodevelopmental difficulties by 5 years of age compared to a single course," commented lead author Dr. Elizabeth Asztalos of the department of pediatrics and ob.gyn. at the University of Toronto and director and scientist at the Centre for Mother, Infant and Child Research at Sunnybrook Health Sciences Centre, also in Toronto. "Because we could not identify short-term neonatal or long-term neurodevelopmental benefits, we conclude that multiple courses of antenatal steroids given every 14 days are not recommended for the woman at risk of preterm birth."

"We emphasize that continued follow-up of this cohort is needed to rule out the possibility of long-term neurobehavioral and neurosensory function [differences], as well as disabilities and metabolic and cardiovascular disease that could not be detected at this early age," she added. "Additional analyses will be conducted that will try to evaluate the interaction between multiple courses and outcomes as it relates to prolonged rupture of membranes, term versus preterm birth, and infant sex."

One attendee noted that a previous study did find a difference in developmental disability after three or four courses of antenatal steroids. "So I’m wondering whether you have a subanalysis of outcomes by number of courses," he said.

"We have not specifically done that from the neurocognitive perspective," Dr. Asztalos replied. "That is something that we will start to look at."

Another attendee commented, "It appears that the measures you looked at [at] this young age are of fairly significant impacts; yet, in human studies, there is some suggestion of behavioral abnormalities induced by steroids including anxiety and stress responses, and clearly in animal studies – particularly those done in Australia – of programming of offspring HPA [hypothalamic-pituitary-adrenal] axis that’s in a sex-specific manner. Do you plan to look at any of those factors in the future?"

"We do. We are hoping that the Canadian government will allow us to continue to follow these children [until] 12 [years of age], and we will definitely look at these measures," Dr. Asztalos replied.

Pregnant women were eligible for the MACS (Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study) trial if they were at 26-30 weeks’ gestation and were at risk for early birth and had not delivered 14 or more days after an initial course of antenatal corticosteroids.

They were assigned to receive study medication, either betamethasone or placebo, every 14 days until 33 completed weeks or delivery.

Initial trial results, previously published (Lancet 2008;372:2143-51), showed that the multicourse group did not have a lower rate of perinatal or neonatal mortality or neonatal morbidity. Birth weight and length were less, and head circumference was smaller in the multicourse group.

In addition, at the age of 18-24 months, offspring in the multicourse group did not have a lower rate of death or neurologic impairment such as cerebral palsy or cognitive delay (Pediatrics 2010;126:1045-55). They still weighed less, but appeared to be catching up.

The latest results, now at a median age of 5.2 years, showed that children in the multicourse group did not have a significantly different rate of the composite outcome of death or neurodevelopmental impairment relative to their counterparts in the single-course group (24.9% vs. 24.6%), according to data reported at the meeting.

The findings were similar for the individual components of death, neuromotor impairment (defined as nonambulatory cerebral palsy), neurosensory impairment (blindness in at least one eye, deafness, or need for visual or hearing aid), and neurocognitive impairment (abnormal attention, memory, or behavior).

At this time point, children in the two groups were statistically indistinguishable with respect to weight, height, and head circumference; systolic and diastolic blood pressure; and various measures of intelligence and specific cognitive skills, according to Dr. Asztalos.

Dr. Asztalos disclosed no conflicts of interest related to the research.

SAN FRANCISCO – Prophylactic progesterone does not decrease and may even increase the rate of preterm birth in women with a twin pregnancy who have a short cervix but no symptoms of complications, a study has shown.

Among the 165 women in a randomized open-label trial conducted in France, the rate of birth before 37 weeks’ gestation did not differ significantly between those who were and were not given 17-alpha hydroxyprogesterone caproate (Makena), Dr. Philippe Deruelle reported at the annual meeting of the Society for Maternal-Fetal Medicine, on behalf of the Groupe de Recherche en Obstétrique et Gynécologie in France.

In addition, in results that he characterized as surprising, the progesterone group in fact had a higher rate of birth before 34 weeks and before 32 weeks.

"We could say that the clinical implication of our study is that 17-hydroxyprogesterone is not effective in women with an asymptomatic twin pregnancy and a short cervix for prevention of preterm delivery, and it might even be harmful," he commented. "Preterm delivery in twin pregnancies is probably due to uterine distension and contraction, with no effect of progesterone for prevention."

One session attendee said, "My issue is that you gave progesterone at 24 weeks and after. I wonder if you have a subanalysis seeing maybe if you give it earlier, you get a different effect, and if you give it later, you see more of the harm. And I thank you for reminding all of us that scope creep should not be done, and we shouldn’t use an intervention before it’s proven to work."

The investigators have not done such a subanalysis, Dr. Deruelle replied.

Another attendee questioned the relatively high dose of progesterone used – 500 mg twice weekly – and the fact that the investigators used the caproate formulation, which may have effects different from those of other formulations. "We really have to look at perhaps other progesterones. I think with caproate, specifically, we really have to be very cautious" about dosing, he said.

"We assumed with the higher doses, it might be more powerful than the dose previously published," which was ineffective, Dr. Deruelle explained.

Women from 10 university hospitals in France with twin pregnancies and a short cervix were enrolled in the trial between the 24th and 31st weeks of gestation.

They were assigned evenly to a progesterone group or a control group, with treatment continued until 36 weeks or preterm delivery.

The mean gestational age at enrollment was about 28 weeks. On average, cervical length was 15 mm in the progesterone group and 17 mm in the control group, said Dr. Deruelle of Hôpital Jeanne de Flandre, Lille, France.

Results reported at the meeting showed that the mean time between randomization and delivery – the trial’s primary outcome – did not differ significantly between the progesterone and control groups (45 vs. 52 days, P = .09).

Women in the progesterone group did not have a lower rate of birth before 37 weeks (80% vs. 77%) and in fact had higher rates of birth before 34 weeks (40% vs. 28%, P = .019) and before 32 weeks (29% vs. 12%, P = .0002), reported Dr. Deruelle.

The mean gestational age at birth was younger in the progesterone group (34 ⁶/₇ vs. 35 ³/₇ weeks, P less than .03). Rates of other adverse pregnancy outcomes were similar.

The two groups also were statistically indistinguishable with respect to most adverse neonatal outcomes as well, but neonates in the progesterone group had a lower birth weight (2,090 vs. 2,230 g, P less than .03).

Dr. Deruelle disclosed no relevant financial conflicts.

obnews@frontlinemedcom.com

SAN FRANCISCO – Prophylactic progesterone does not decrease and may even increase the rate of preterm birth in women with a twin pregnancy who have a short cervix but no symptoms of complications, a study has shown.

Among the 165 women in a randomized open-label trial conducted in France, the rate of birth before 37 weeks’ gestation did not differ significantly between those who were and were not given 17-alpha hydroxyprogesterone caproate (Makena), Dr. Philippe Deruelle reported at the annual meeting of the Society for Maternal-Fetal Medicine, on behalf of the Groupe de Recherche en Obstétrique et Gynécologie in France.

In addition, in results that he characterized as surprising, the progesterone group in fact had a higher rate of birth before 34 weeks and before 32 weeks.

"We could say that the clinical implication of our study is that 17-hydroxyprogesterone is not effective in women with an asymptomatic twin pregnancy and a short cervix for prevention of preterm delivery, and it might even be harmful," he commented. "Preterm delivery in twin pregnancies is probably due to uterine distension and contraction, with no effect of progesterone for prevention."

One session attendee said, "My issue is that you gave progesterone at 24 weeks and after. I wonder if you have a subanalysis seeing maybe if you give it earlier, you get a different effect, and if you give it later, you see more of the harm. And I thank you for reminding all of us that scope creep should not be done, and we shouldn’t use an intervention before it’s proven to work."

The investigators have not done such a subanalysis, Dr. Deruelle replied.

Another attendee questioned the relatively high dose of progesterone used – 500 mg twice weekly – and the fact that the investigators used the caproate formulation, which may have effects different from those of other formulations. "We really have to look at perhaps other progesterones. I think with caproate, specifically, we really have to be very cautious" about dosing, he said.

"We assumed with the higher doses, it might be more powerful than the dose previously published," which was ineffective, Dr. Deruelle explained.

Women from 10 university hospitals in France with twin pregnancies and a short cervix were enrolled in the trial between the 24th and 31st weeks of gestation.

They were assigned evenly to a progesterone group or a control group, with treatment continued until 36 weeks or preterm delivery.

The mean gestational age at enrollment was about 28 weeks. On average, cervical length was 15 mm in the progesterone group and 17 mm in the control group, said Dr. Deruelle of Hôpital Jeanne de Flandre, Lille, France.

Results reported at the meeting showed that the mean time between randomization and delivery – the trial’s primary outcome – did not differ significantly between the progesterone and control groups (45 vs. 52 days, P = .09).

Women in the progesterone group did not have a lower rate of birth before 37 weeks (80% vs. 77%) and in fact had higher rates of birth before 34 weeks (40% vs. 28%, P = .019) and before 32 weeks (29% vs. 12%, P = .0002), reported Dr. Deruelle.

The mean gestational age at birth was younger in the progesterone group (34 ⁶/₇ vs. 35 ³/₇ weeks, P less than .03). Rates of other adverse pregnancy outcomes were similar.

The two groups also were statistically indistinguishable with respect to most adverse neonatal outcomes as well, but neonates in the progesterone group had a lower birth weight (2,090 vs. 2,230 g, P less than .03).

Dr. Deruelle disclosed no relevant financial conflicts.

obnews@frontlinemedcom.com

SAN FRANCISCO – Prophylactic progesterone does not decrease and may even increase the rate of preterm birth in women with a twin pregnancy who have a short cervix but no symptoms of complications, a study has shown.

Among the 165 women in a randomized open-label trial conducted in France, the rate of birth before 37 weeks’ gestation did not differ significantly between those who were and were not given 17-alpha hydroxyprogesterone caproate (Makena), Dr. Philippe Deruelle reported at the annual meeting of the Society for Maternal-Fetal Medicine, on behalf of the Groupe de Recherche en Obstétrique et Gynécologie in France.

In addition, in results that he characterized as surprising, the progesterone group in fact had a higher rate of birth before 34 weeks and before 32 weeks.

"We could say that the clinical implication of our study is that 17-hydroxyprogesterone is not effective in women with an asymptomatic twin pregnancy and a short cervix for prevention of preterm delivery, and it might even be harmful," he commented. "Preterm delivery in twin pregnancies is probably due to uterine distension and contraction, with no effect of progesterone for prevention."

One session attendee said, "My issue is that you gave progesterone at 24 weeks and after. I wonder if you have a subanalysis seeing maybe if you give it earlier, you get a different effect, and if you give it later, you see more of the harm. And I thank you for reminding all of us that scope creep should not be done, and we shouldn’t use an intervention before it’s proven to work."

The investigators have not done such a subanalysis, Dr. Deruelle replied.

Another attendee questioned the relatively high dose of progesterone used – 500 mg twice weekly – and the fact that the investigators used the caproate formulation, which may have effects different from those of other formulations. "We really have to look at perhaps other progesterones. I think with caproate, specifically, we really have to be very cautious" about dosing, he said.

"We assumed with the higher doses, it might be more powerful than the dose previously published," which was ineffective, Dr. Deruelle explained.

Women from 10 university hospitals in France with twin pregnancies and a short cervix were enrolled in the trial between the 24th and 31st weeks of gestation.

They were assigned evenly to a progesterone group or a control group, with treatment continued until 36 weeks or preterm delivery.

The mean gestational age at enrollment was about 28 weeks. On average, cervical length was 15 mm in the progesterone group and 17 mm in the control group, said Dr. Deruelle of Hôpital Jeanne de Flandre, Lille, France.

Results reported at the meeting showed that the mean time between randomization and delivery – the trial’s primary outcome – did not differ significantly between the progesterone and control groups (45 vs. 52 days, P = .09).

Women in the progesterone group did not have a lower rate of birth before 37 weeks (80% vs. 77%) and in fact had higher rates of birth before 34 weeks (40% vs. 28%, P = .019) and before 32 weeks (29% vs. 12%, P = .0002), reported Dr. Deruelle.

The mean gestational age at birth was younger in the progesterone group (34 ⁶/₇ vs. 35 ³/₇ weeks, P less than .03). Rates of other adverse pregnancy outcomes were similar.

The two groups also were statistically indistinguishable with respect to most adverse neonatal outcomes as well, but neonates in the progesterone group had a lower birth weight (2,090 vs. 2,230 g, P less than .03).

Dr. Deruelle disclosed no relevant financial conflicts.

obnews@frontlinemedcom.com

LOS ANGELES – Preoperative levels of cancer antigen 125 (CA125) predict surgical and disease outcomes in women with advanced epithelial ovarian cancer who are able to undergo optimal debulking surgery, new data show, and may therefore help guide treatment decisions.

A team led by Dr. Neil S. Horowitz of Brigham and Women’s Hospital and the Dana Farber Cancer Institute in Boston assessed levels of the biomarker among nearly 1,000 women who had stage III or IV disease that was optimally debulked to less than 1 cm of residual disease and who received adjuvant paclitaxel- and platinum-containing chemotherapy.

Results showed that no cutoff value of preoperative CA125 levels clearly separated women in whom microscopic residual disease was achieved surgically from women in whom a greater volume of disease remained, he reported at the annual meeting of the Society of Gynecologic Oncology.

But the probability of achieving microscopic status decreased with increasing CA125 levels. For example, it fell from 33% in women with a level of 500 U/mL to 27% in women with a level of 1,000 U/mL.

"Although a strict CA125 value to predict microscopic residual cannot be made, these data are helpful for counseling patients regarding surgical results and outcome, and should influence decisions regarding primary debulking surgery and possibly use of other ... treatment options like neoadjuvant chemotherapy," Dr. Horowitz said. "Each surgeon and [his or her] patient have to decide for themselves what is an acceptable probability of successful surgical outcome to microscopic residual disease.

Additional study findings showed that women with higher preoperative CA125 levels and women with smaller reductions in CA125 levels between the preoperative period and the pretreatment period, before starting chemotherapy, had significantly worse progression-free and overall survival.

One session attendee asked, "What impact do you think surgical expertise has on the ability to predict the extent of cytoreduction?"

"Most trained gyn oncologists have the ability and training to take somebody to microscopic residual disease. What it takes to get to that place obviously varies from patient to patient and the disease that they have at the time that they present. Ultimately, what has to be decided between the patient and the physician is what’s going to be the best possibility for them and using CA125 as a potential guide, say, taking everything into consideration – age, where their disease is, what their CA125 is, what my comfort level is doing certain procedures being able to get them down to microscopic disease," Dr. Horowitz replied. "So I don’t think it’s a one-size-fits-all [objective] based just on the surgical expertise. Most gyn oncologists are trained adequately to be able to do this. It’s just, because you can do it, the question is, should you be doing it on everybody."

Another attendee said, "In follow-up to that, do you think that the difference in the behavior of the presurgical and the pretreatment CA125 could be confounded, the latter by surgical decisions or surgical intervention?"

"It’s potentially confounded; whether it’s surgical skill or some people would say, I don’t want to use the term honesty, but it may be a reflection of what truly is left behind versus not left behind, if it didn’t really follow the way it should. It may be a window into how accurate our predictions or our estimates of what we left behind really are," Dr. Horowitz explained. "Pretreatment CA125, it is difficult to really get a good understanding of this number because obviously the patients who start with the highest CA125 have the greatest chance to fall ... So it’s a little tricky trying to figure out what to make of that number, whereas patients who start with a lower one, although they didn’t fall with the same percentile, you still may have done just as good a job surgically."

The 998 women studied were from Gynecologic Oncology Group (GOG) trial 182. "This is the largest reported series to evaluate the ability of preoperative CA125 to predict surgical cytoreductive outcomes and survival in a population of women with optimally cytoreduced primary ovarian or peritoneal cancer," Dr. Horowitz noted.

Overall, 33% had microscopic residual disease, while the other 67% had more extensive residual disease but still measuring less than 1 cm.

The median preoperative CA125 level was 346 U/mL in the former group and 870 U/mL in the latter, reported Dr. Horowitz, who disclosed no conflicts of interest related to the research.

"Despite the difference in median preoperative CA125 values, the distributions of the preoperative CA125s in those with microscopic and less than 1 cm residual overlapped almost completely," Dr. Horowitz reported. "This suggests that there is not a preoperative CA125 beyond which one cannot achieve a complete cytoreductive surgery."

However, the higher the preoperative CA125 level, the lower the predicted probability of achieving microscopic residual disease (P less than .01). For example, the probability was 33%, 27%, and 19% for women having a level of 500, 1,000, and 2,500 U/mL, respectively.

"It is important to remember that these curves only reflect data from women who achieved optimal cytoreduction and do not include those with suboptimal primary debulking. Therefore, the estimated predictions and probabilities are likely to decrease when applied to a preoperative population of unknown surgical outcome," he said. "But if one assumes a priori that you can achieve and will achieve optimal cytoreduction, then preoperative CA125 can estimate the likelihood of obtaining either microscopic or less than 1-cm residual."

In adjusted analyses, preoperative CA125 levels and extent of residual disease jointly predicted both progression-free survival (P less than .001) and overall survival (P = .04). For example, median overall survival ranged from 82 months in women having microscopic residual disease and a CA125 level of 35 U/mL to just 39 months in their counterparts with more residual disease and a CA125 level of 1,000 U/mL.

The change from preoperative to pretreatment CA125 levels predicted both progression-free survival (P less than .0001) and overall survival (P less than .0001). For example, median overall survival ranged from 60 months in women having a reduction in levels exceeding 80% to 45 months in their counterparts having stable or increasing levels.

In addition, among the group having a greater than 80% decline in CA125 level, survival was almost twice as long among those achieving microscopic residual disease, at 82 months, as among those with greater residual disease, at 48 months, "suggesting that residual disease rather than change in CA125 is more important to survival," Dr. Horowitz said.

LOS ANGELES – Preoperative levels of cancer antigen 125 (CA125) predict surgical and disease outcomes in women with advanced epithelial ovarian cancer who are able to undergo optimal debulking surgery, new data show, and may therefore help guide treatment decisions.

A team led by Dr. Neil S. Horowitz of Brigham and Women’s Hospital and the Dana Farber Cancer Institute in Boston assessed levels of the biomarker among nearly 1,000 women who had stage III or IV disease that was optimally debulked to less than 1 cm of residual disease and who received adjuvant paclitaxel- and platinum-containing chemotherapy.

Results showed that no cutoff value of preoperative CA125 levels clearly separated women in whom microscopic residual disease was achieved surgically from women in whom a greater volume of disease remained, he reported at the annual meeting of the Society of Gynecologic Oncology.

But the probability of achieving microscopic status decreased with increasing CA125 levels. For example, it fell from 33% in women with a level of 500 U/mL to 27% in women with a level of 1,000 U/mL.

"Although a strict CA125 value to predict microscopic residual cannot be made, these data are helpful for counseling patients regarding surgical results and outcome, and should influence decisions regarding primary debulking surgery and possibly use of other ... treatment options like neoadjuvant chemotherapy," Dr. Horowitz said. "Each surgeon and [his or her] patient have to decide for themselves what is an acceptable probability of successful surgical outcome to microscopic residual disease.

Additional study findings showed that women with higher preoperative CA125 levels and women with smaller reductions in CA125 levels between the preoperative period and the pretreatment period, before starting chemotherapy, had significantly worse progression-free and overall survival.

One session attendee asked, "What impact do you think surgical expertise has on the ability to predict the extent of cytoreduction?"

"Most trained gyn oncologists have the ability and training to take somebody to microscopic residual disease. What it takes to get to that place obviously varies from patient to patient and the disease that they have at the time that they present. Ultimately, what has to be decided between the patient and the physician is what’s going to be the best possibility for them and using CA125 as a potential guide, say, taking everything into consideration – age, where their disease is, what their CA125 is, what my comfort level is doing certain procedures being able to get them down to microscopic disease," Dr. Horowitz replied. "So I don’t think it’s a one-size-fits-all [objective] based just on the surgical expertise. Most gyn oncologists are trained adequately to be able to do this. It’s just, because you can do it, the question is, should you be doing it on everybody."

Another attendee said, "In follow-up to that, do you think that the difference in the behavior of the presurgical and the pretreatment CA125 could be confounded, the latter by surgical decisions or surgical intervention?"

"It’s potentially confounded; whether it’s surgical skill or some people would say, I don’t want to use the term honesty, but it may be a reflection of what truly is left behind versus not left behind, if it didn’t really follow the way it should. It may be a window into how accurate our predictions or our estimates of what we left behind really are," Dr. Horowitz explained. "Pretreatment CA125, it is difficult to really get a good understanding of this number because obviously the patients who start with the highest CA125 have the greatest chance to fall ... So it’s a little tricky trying to figure out what to make of that number, whereas patients who start with a lower one, although they didn’t fall with the same percentile, you still may have done just as good a job surgically."

The 998 women studied were from Gynecologic Oncology Group (GOG) trial 182. "This is the largest reported series to evaluate the ability of preoperative CA125 to predict surgical cytoreductive outcomes and survival in a population of women with optimally cytoreduced primary ovarian or peritoneal cancer," Dr. Horowitz noted.

Overall, 33% had microscopic residual disease, while the other 67% had more extensive residual disease but still measuring less than 1 cm.

The median preoperative CA125 level was 346 U/mL in the former group and 870 U/mL in the latter, reported Dr. Horowitz, who disclosed no conflicts of interest related to the research.

"Despite the difference in median preoperative CA125 values, the distributions of the preoperative CA125s in those with microscopic and less than 1 cm residual overlapped almost completely," Dr. Horowitz reported. "This suggests that there is not a preoperative CA125 beyond which one cannot achieve a complete cytoreductive surgery."

However, the higher the preoperative CA125 level, the lower the predicted probability of achieving microscopic residual disease (P less than .01). For example, the probability was 33%, 27%, and 19% for women having a level of 500, 1,000, and 2,500 U/mL, respectively.

"It is important to remember that these curves only reflect data from women who achieved optimal cytoreduction and do not include those with suboptimal primary debulking. Therefore, the estimated predictions and probabilities are likely to decrease when applied to a preoperative population of unknown surgical outcome," he said. "But if one assumes a priori that you can achieve and will achieve optimal cytoreduction, then preoperative CA125 can estimate the likelihood of obtaining either microscopic or less than 1-cm residual."

In adjusted analyses, preoperative CA125 levels and extent of residual disease jointly predicted both progression-free survival (P less than .001) and overall survival (P = .04). For example, median overall survival ranged from 82 months in women having microscopic residual disease and a CA125 level of 35 U/mL to just 39 months in their counterparts with more residual disease and a CA125 level of 1,000 U/mL.

The change from preoperative to pretreatment CA125 levels predicted both progression-free survival (P less than .0001) and overall survival (P less than .0001). For example, median overall survival ranged from 60 months in women having a reduction in levels exceeding 80% to 45 months in their counterparts having stable or increasing levels.

In addition, among the group having a greater than 80% decline in CA125 level, survival was almost twice as long among those achieving microscopic residual disease, at 82 months, as among those with greater residual disease, at 48 months, "suggesting that residual disease rather than change in CA125 is more important to survival," Dr. Horowitz said.

LOS ANGELES – Preoperative levels of cancer antigen 125 (CA125) predict surgical and disease outcomes in women with advanced epithelial ovarian cancer who are able to undergo optimal debulking surgery, new data show, and may therefore help guide treatment decisions.

A team led by Dr. Neil S. Horowitz of Brigham and Women’s Hospital and the Dana Farber Cancer Institute in Boston assessed levels of the biomarker among nearly 1,000 women who had stage III or IV disease that was optimally debulked to less than 1 cm of residual disease and who received adjuvant paclitaxel- and platinum-containing chemotherapy.

Results showed that no cutoff value of preoperative CA125 levels clearly separated women in whom microscopic residual disease was achieved surgically from women in whom a greater volume of disease remained, he reported at the annual meeting of the Society of Gynecologic Oncology.

But the probability of achieving microscopic status decreased with increasing CA125 levels. For example, it fell from 33% in women with a level of 500 U/mL to 27% in women with a level of 1,000 U/mL.

"Although a strict CA125 value to predict microscopic residual cannot be made, these data are helpful for counseling patients regarding surgical results and outcome, and should influence decisions regarding primary debulking surgery and possibly use of other ... treatment options like neoadjuvant chemotherapy," Dr. Horowitz said. "Each surgeon and [his or her] patient have to decide for themselves what is an acceptable probability of successful surgical outcome to microscopic residual disease.

Additional study findings showed that women with higher preoperative CA125 levels and women with smaller reductions in CA125 levels between the preoperative period and the pretreatment period, before starting chemotherapy, had significantly worse progression-free and overall survival.

One session attendee asked, "What impact do you think surgical expertise has on the ability to predict the extent of cytoreduction?"

"Most trained gyn oncologists have the ability and training to take somebody to microscopic residual disease. What it takes to get to that place obviously varies from patient to patient and the disease that they have at the time that they present. Ultimately, what has to be decided between the patient and the physician is what’s going to be the best possibility for them and using CA125 as a potential guide, say, taking everything into consideration – age, where their disease is, what their CA125 is, what my comfort level is doing certain procedures being able to get them down to microscopic disease," Dr. Horowitz replied. "So I don’t think it’s a one-size-fits-all [objective] based just on the surgical expertise. Most gyn oncologists are trained adequately to be able to do this. It’s just, because you can do it, the question is, should you be doing it on everybody."

Another attendee said, "In follow-up to that, do you think that the difference in the behavior of the presurgical and the pretreatment CA125 could be confounded, the latter by surgical decisions or surgical intervention?"

"It’s potentially confounded; whether it’s surgical skill or some people would say, I don’t want to use the term honesty, but it may be a reflection of what truly is left behind versus not left behind, if it didn’t really follow the way it should. It may be a window into how accurate our predictions or our estimates of what we left behind really are," Dr. Horowitz explained. "Pretreatment CA125, it is difficult to really get a good understanding of this number because obviously the patients who start with the highest CA125 have the greatest chance to fall ... So it’s a little tricky trying to figure out what to make of that number, whereas patients who start with a lower one, although they didn’t fall with the same percentile, you still may have done just as good a job surgically."

The 998 women studied were from Gynecologic Oncology Group (GOG) trial 182. "This is the largest reported series to evaluate the ability of preoperative CA125 to predict surgical cytoreductive outcomes and survival in a population of women with optimally cytoreduced primary ovarian or peritoneal cancer," Dr. Horowitz noted.

Overall, 33% had microscopic residual disease, while the other 67% had more extensive residual disease but still measuring less than 1 cm.

The median preoperative CA125 level was 346 U/mL in the former group and 870 U/mL in the latter, reported Dr. Horowitz, who disclosed no conflicts of interest related to the research.

"Despite the difference in median preoperative CA125 values, the distributions of the preoperative CA125s in those with microscopic and less than 1 cm residual overlapped almost completely," Dr. Horowitz reported. "This suggests that there is not a preoperative CA125 beyond which one cannot achieve a complete cytoreductive surgery."

However, the higher the preoperative CA125 level, the lower the predicted probability of achieving microscopic residual disease (P less than .01). For example, the probability was 33%, 27%, and 19% for women having a level of 500, 1,000, and 2,500 U/mL, respectively.

"It is important to remember that these curves only reflect data from women who achieved optimal cytoreduction and do not include those with suboptimal primary debulking. Therefore, the estimated predictions and probabilities are likely to decrease when applied to a preoperative population of unknown surgical outcome," he said. "But if one assumes a priori that you can achieve and will achieve optimal cytoreduction, then preoperative CA125 can estimate the likelihood of obtaining either microscopic or less than 1-cm residual."

In adjusted analyses, preoperative CA125 levels and extent of residual disease jointly predicted both progression-free survival (P less than .001) and overall survival (P = .04). For example, median overall survival ranged from 82 months in women having microscopic residual disease and a CA125 level of 35 U/mL to just 39 months in their counterparts with more residual disease and a CA125 level of 1,000 U/mL.

The change from preoperative to pretreatment CA125 levels predicted both progression-free survival (P less than .0001) and overall survival (P less than .0001). For example, median overall survival ranged from 60 months in women having a reduction in levels exceeding 80% to 45 months in their counterparts having stable or increasing levels.

In addition, among the group having a greater than 80% decline in CA125 level, survival was almost twice as long among those achieving microscopic residual disease, at 82 months, as among those with greater residual disease, at 48 months, "suggesting that residual disease rather than change in CA125 is more important to survival," Dr. Horowitz said.

LOS ANGELES – Robotic Cyberknife radiation therapy will likely expand the treatment options for patients whose gynecologic malignancies recur, researchers reported at the annual meeting of the Society of Gynecologic Oncologists.

A total of 50 patients with recurrent gynecologic (mainly ovarian and endometrial) cancers underwent Cyberknife treatment, which allows targeting of high doses of radiation to the tumor while largely sparing adjacent healthy tissue. In this case, patients received an 8-Gy treatment on each of 3 consecutive days.

Results showed that two-thirds of the patients had a complete response, a partial response, or stable disease 6 months after treatment. Higher-severity acute adverse events were uncommon and consisted of single cases of diarrhea and hyperbilirubinemia.

"This is the first phase II clinical trial of robotic radiosurgery in the gynecologic oncology space. Robotic Cyberknife radiation therapy does definitely provide clinical benefit to your patients," commented lead author Dr. Charles Kunos, a radiation oncologist with the Case Comprehensive Cancer Center in Cleveland and the Summa Cancer Institute in Akron, Ohio.

However, the majority of women ultimately had progression in nontargeted areas of disease, and this progression was the cause of death in 40%. Therefore, the investigators have initiated a phase I trial combining Cyberknife therapy with systemic chemotherapy.

One attendee noted, "As I think we all know, many of these patients who have recurrent side-wall disease from gynecologic cancers have a loop of bowel that’s sitting immediately adjacent to the potential target. And we have always felt that you needed to adjust the dose per fraction depending on that in patients with recurrent disease who have been previously irradiated. How do you select your patients for these 8-Gy-fraction treatments?"

"Patient selection is mostly based on target volume and the number of sites that are going to be treated during the course of therapy. ... We find that the 8-Gy dose is extremely well tolerated," he noted. The team is currently performing analyses to determine maximum tissue tolerances and optimally guide patient selection.

Another attendee had a similar question, asking whether any of the lesions treated were located in a previously irradiated field.

"More than 60% of those patients had received prior radiation therapy. Almost all the cervical cancer patients in the trial, as well as the majority of those patients with endometrial cancer, had received prior radiation therapy," Dr. Kunos replied. "The prior radiation therapy is not a barrier for delivering this form of treatment at these doses. Our toxicity rates are extraordinarily low, even in the cases with the prior radiation, so with selection of the patient who has a relatively good performing health status, as well as considering the time of when the previous radiation therapy dose was delivered, I think you can adequately select patients for this type of therapy."

A third attendee posed bigger-picture questions: "Can you tell us a little bit about the cost-effectiveness of the Cyberknife therapy and, given that you have an ongoing phase I trial looking at this in dual-modality [treatment] with chemotherapy, what is the future of this therapeutic approach for gyn malignancies?"

"The NCI [National Cancer Institute] is interested in exploring the radiosurgery platform as a way of testing novel therapeutics as radiation sensitizers, but because the radiation therapy is so exquisitely tuned to the actual cancer target, there is an opportunity to study whether or not there are systemic effects of the novel drugs as well. So I think at some level, the future is relatively bright," Dr. Kunos explained.

"Regarding the cost or the expense of therapy, we are condensing 5, 6, 7 weeks of radiation therapy into 3 days on the trial, so there are considerable savings in that regard to patient travel and other, social aspects of treatment in trying to get patients back and forth for several weeks of therapy in a palliative situation," he continued. "The radiosurgery itself is expensive; that part of the cost structure will probably continue to come down in the future with the way that patients will be managed."

The cohort enrolled in the trial included 25 patients with ovarian cancer, 14 with endometrial cancer, 9 with cervical cancer, and 2 with vulvar cancer. All had received at least one chemotherapy or radiation therapy regimen previously.

The patients had up to four targets of disease to be treated. They underwent implantation of gold seeds for target tracking during treatment, and co-registered computed tomography and positron emission tomography scans were used to generate the radiation therapy plan.

The patients received a total of 24 Gy of radiation delivered in three daily doses of 8 Gy each. The median duration of follow-up was 15 months.

Study results, reported at the meeting and recently published (Front. Oncol. 2012;2:181), showed that 3 months after treatment, 50% of patients had a complete response, 46% had a partial response, and 4% had stable disease, according to Dr. Kunos.

At 6 months, the rate of clinical benefit – capturing patients with a complete response, partial response, or stable disease – was 68%.

Ultimately, 62% of patients had progression in a nontargeted disease site, and 40% died from disease progression.

"Reversible fatigue lasting up to 1 week after treatment was the most noticeable toxicity," Dr. Kunos said. In the first 30 days after treatment, the most common adverse effects were grade 2 fatigue, seen in 16% of patients, and grade 2 nausea, seen in 8%. Only 2% of patients had grade 3 diarrhea, and only 2% had grade 4 hyperbilirubinemia.

Dr. Kunos disclosed that he had no relevant conflicts of interest.

LOS ANGELES – Robotic Cyberknife radiation therapy will likely expand the treatment options for patients whose gynecologic malignancies recur, researchers reported at the annual meeting of the Society of Gynecologic Oncologists.

A total of 50 patients with recurrent gynecologic (mainly ovarian and endometrial) cancers underwent Cyberknife treatment, which allows targeting of high doses of radiation to the tumor while largely sparing adjacent healthy tissue. In this case, patients received an 8-Gy treatment on each of 3 consecutive days.

Results showed that two-thirds of the patients had a complete response, a partial response, or stable disease 6 months after treatment. Higher-severity acute adverse events were uncommon and consisted of single cases of diarrhea and hyperbilirubinemia.

"This is the first phase II clinical trial of robotic radiosurgery in the gynecologic oncology space. Robotic Cyberknife radiation therapy does definitely provide clinical benefit to your patients," commented lead author Dr. Charles Kunos, a radiation oncologist with the Case Comprehensive Cancer Center in Cleveland and the Summa Cancer Institute in Akron, Ohio.

However, the majority of women ultimately had progression in nontargeted areas of disease, and this progression was the cause of death in 40%. Therefore, the investigators have initiated a phase I trial combining Cyberknife therapy with systemic chemotherapy.

One attendee noted, "As I think we all know, many of these patients who have recurrent side-wall disease from gynecologic cancers have a loop of bowel that’s sitting immediately adjacent to the potential target. And we have always felt that you needed to adjust the dose per fraction depending on that in patients with recurrent disease who have been previously irradiated. How do you select your patients for these 8-Gy-fraction treatments?"

"Patient selection is mostly based on target volume and the number of sites that are going to be treated during the course of therapy. ... We find that the 8-Gy dose is extremely well tolerated," he noted. The team is currently performing analyses to determine maximum tissue tolerances and optimally guide patient selection.

Another attendee had a similar question, asking whether any of the lesions treated were located in a previously irradiated field.

"More than 60% of those patients had received prior radiation therapy. Almost all the cervical cancer patients in the trial, as well as the majority of those patients with endometrial cancer, had received prior radiation therapy," Dr. Kunos replied. "The prior radiation therapy is not a barrier for delivering this form of treatment at these doses. Our toxicity rates are extraordinarily low, even in the cases with the prior radiation, so with selection of the patient who has a relatively good performing health status, as well as considering the time of when the previous radiation therapy dose was delivered, I think you can adequately select patients for this type of therapy."

A third attendee posed bigger-picture questions: "Can you tell us a little bit about the cost-effectiveness of the Cyberknife therapy and, given that you have an ongoing phase I trial looking at this in dual-modality [treatment] with chemotherapy, what is the future of this therapeutic approach for gyn malignancies?"

"The NCI [National Cancer Institute] is interested in exploring the radiosurgery platform as a way of testing novel therapeutics as radiation sensitizers, but because the radiation therapy is so exquisitely tuned to the actual cancer target, there is an opportunity to study whether or not there are systemic effects of the novel drugs as well. So I think at some level, the future is relatively bright," Dr. Kunos explained.

"Regarding the cost or the expense of therapy, we are condensing 5, 6, 7 weeks of radiation therapy into 3 days on the trial, so there are considerable savings in that regard to patient travel and other, social aspects of treatment in trying to get patients back and forth for several weeks of therapy in a palliative situation," he continued. "The radiosurgery itself is expensive; that part of the cost structure will probably continue to come down in the future with the way that patients will be managed."

The cohort enrolled in the trial included 25 patients with ovarian cancer, 14 with endometrial cancer, 9 with cervical cancer, and 2 with vulvar cancer. All had received at least one chemotherapy or radiation therapy regimen previously.

The patients had up to four targets of disease to be treated. They underwent implantation of gold seeds for target tracking during treatment, and co-registered computed tomography and positron emission tomography scans were used to generate the radiation therapy plan.

The patients received a total of 24 Gy of radiation delivered in three daily doses of 8 Gy each. The median duration of follow-up was 15 months.

Study results, reported at the meeting and recently published (Front. Oncol. 2012;2:181), showed that 3 months after treatment, 50% of patients had a complete response, 46% had a partial response, and 4% had stable disease, according to Dr. Kunos.

At 6 months, the rate of clinical benefit – capturing patients with a complete response, partial response, or stable disease – was 68%.

Ultimately, 62% of patients had progression in a nontargeted disease site, and 40% died from disease progression.

"Reversible fatigue lasting up to 1 week after treatment was the most noticeable toxicity," Dr. Kunos said. In the first 30 days after treatment, the most common adverse effects were grade 2 fatigue, seen in 16% of patients, and grade 2 nausea, seen in 8%. Only 2% of patients had grade 3 diarrhea, and only 2% had grade 4 hyperbilirubinemia.

Dr. Kunos disclosed that he had no relevant conflicts of interest.

LOS ANGELES – Robotic Cyberknife radiation therapy will likely expand the treatment options for patients whose gynecologic malignancies recur, researchers reported at the annual meeting of the Society of Gynecologic Oncologists.

A total of 50 patients with recurrent gynecologic (mainly ovarian and endometrial) cancers underwent Cyberknife treatment, which allows targeting of high doses of radiation to the tumor while largely sparing adjacent healthy tissue. In this case, patients received an 8-Gy treatment on each of 3 consecutive days.

Results showed that two-thirds of the patients had a complete response, a partial response, or stable disease 6 months after treatment. Higher-severity acute adverse events were uncommon and consisted of single cases of diarrhea and hyperbilirubinemia.

"This is the first phase II clinical trial of robotic radiosurgery in the gynecologic oncology space. Robotic Cyberknife radiation therapy does definitely provide clinical benefit to your patients," commented lead author Dr. Charles Kunos, a radiation oncologist with the Case Comprehensive Cancer Center in Cleveland and the Summa Cancer Institute in Akron, Ohio.

However, the majority of women ultimately had progression in nontargeted areas of disease, and this progression was the cause of death in 40%. Therefore, the investigators have initiated a phase I trial combining Cyberknife therapy with systemic chemotherapy.

One attendee noted, "As I think we all know, many of these patients who have recurrent side-wall disease from gynecologic cancers have a loop of bowel that’s sitting immediately adjacent to the potential target. And we have always felt that you needed to adjust the dose per fraction depending on that in patients with recurrent disease who have been previously irradiated. How do you select your patients for these 8-Gy-fraction treatments?"

"Patient selection is mostly based on target volume and the number of sites that are going to be treated during the course of therapy. ... We find that the 8-Gy dose is extremely well tolerated," he noted. The team is currently performing analyses to determine maximum tissue tolerances and optimally guide patient selection.

Another attendee had a similar question, asking whether any of the lesions treated were located in a previously irradiated field.

"More than 60% of those patients had received prior radiation therapy. Almost all the cervical cancer patients in the trial, as well as the majority of those patients with endometrial cancer, had received prior radiation therapy," Dr. Kunos replied. "The prior radiation therapy is not a barrier for delivering this form of treatment at these doses. Our toxicity rates are extraordinarily low, even in the cases with the prior radiation, so with selection of the patient who has a relatively good performing health status, as well as considering the time of when the previous radiation therapy dose was delivered, I think you can adequately select patients for this type of therapy."

A third attendee posed bigger-picture questions: "Can you tell us a little bit about the cost-effectiveness of the Cyberknife therapy and, given that you have an ongoing phase I trial looking at this in dual-modality [treatment] with chemotherapy, what is the future of this therapeutic approach for gyn malignancies?"

"The NCI [National Cancer Institute] is interested in exploring the radiosurgery platform as a way of testing novel therapeutics as radiation sensitizers, but because the radiation therapy is so exquisitely tuned to the actual cancer target, there is an opportunity to study whether or not there are systemic effects of the novel drugs as well. So I think at some level, the future is relatively bright," Dr. Kunos explained.

"Regarding the cost or the expense of therapy, we are condensing 5, 6, 7 weeks of radiation therapy into 3 days on the trial, so there are considerable savings in that regard to patient travel and other, social aspects of treatment in trying to get patients back and forth for several weeks of therapy in a palliative situation," he continued. "The radiosurgery itself is expensive; that part of the cost structure will probably continue to come down in the future with the way that patients will be managed."

The cohort enrolled in the trial included 25 patients with ovarian cancer, 14 with endometrial cancer, 9 with cervical cancer, and 2 with vulvar cancer. All had received at least one chemotherapy or radiation therapy regimen previously.

The patients had up to four targets of disease to be treated. They underwent implantation of gold seeds for target tracking during treatment, and co-registered computed tomography and positron emission tomography scans were used to generate the radiation therapy plan.

The patients received a total of 24 Gy of radiation delivered in three daily doses of 8 Gy each. The median duration of follow-up was 15 months.

Study results, reported at the meeting and recently published (Front. Oncol. 2012;2:181), showed that 3 months after treatment, 50% of patients had a complete response, 46% had a partial response, and 4% had stable disease, according to Dr. Kunos.

At 6 months, the rate of clinical benefit – capturing patients with a complete response, partial response, or stable disease – was 68%.

Ultimately, 62% of patients had progression in a nontargeted disease site, and 40% died from disease progression.

"Reversible fatigue lasting up to 1 week after treatment was the most noticeable toxicity," Dr. Kunos said. In the first 30 days after treatment, the most common adverse effects were grade 2 fatigue, seen in 16% of patients, and grade 2 nausea, seen in 8%. Only 2% of patients had grade 3 diarrhea, and only 2% had grade 4 hyperbilirubinemia.

Dr. Kunos disclosed that he had no relevant conflicts of interest.

LOS ANGELES – Racial makeup based on genetic testing trumps self-reported race as a predictor of endometrial cancer outcomes, suggests the results of a study reported at the annual meeting of the Society of Gynecologic Oncology.

Researchers compared patient self reports of racial identity and the results of genotyping for markers of race in 217 women with endometrial cancer who had any-stage endometroid tumors.

The risk of cancer progression or death rose by 2% with each 1% increase in African racial genetic admixture and fell by 3% with each 1% increase in European racial genetic admixture.

"Racial genetic admixture significantly predicts the risk of recurrence and progression-free survival in endometrial cancer patients. Importantly, this risk is irrespective of self-designated race and could be used to stratify and identify patients’ recurrence risk," reported lead author Dr. Rodney P. Rocconi, a gynecologic oncologist at the Mitchell Cancer Institute and University of South Alabama in Mobile.

The results are worth examining as a key "to unraveling the etiology of this disparity, with the hopes of improving treatment outcomes and eventually eliminating this racial disparity in the future."

Dr. Rocconi acknowledged that the study included only endometroid tumors, and noted that black women typically have higher proportions of carcinosarcoma and type 2 endometrial cancers, a distinction that’s not always known preoperatively.

"In an ideal world, we would like to evaluate that (larger) population," Dr. Rocconi said. But "it came down to having enough funding to evaluate a population that is meaningful. In the future, by all means, it would be an extremely important population to look at."

African American women make up just 7% of all patients with endometrial cancer but account for 15% of deaths from the disease, he noted.

"To date, breaking down the definition of race in cancer racial disparity has largely been overlooked. Considering the majority of racial disparity research utilizes self-designated race, this in my opinion is the greatest limitation in this type of research. Self-designated race can be used as a proxy, but it is not precise in measurement of population differences. It cannot infer genetic similarity," he said.

Genetic testing "can mathematically calculate the place of origin genetically. Thus, it’s a more precise definition of race, and this methodology is important in teasing out those true factors of racial disparity. Simply put, this definition allows a continuous variable, a true percentage of African descent, as opposed to a categorical value of self-designated African American [race]," he said.

For the study, Dr. Rocconi and his coinvestigators identified women from Gynecologic Oncology Group (GOG) trial 210 who had endometroid tumors.

The team extracted DNA from tumor-free tissue samples and performed genotyping for 140 ancestry informative markers (AIMs), or single-nucleotide polymorphisms that occur in different frequencies in populations from different world geographic regions.

The 5-year rate of progression-free survival was 82% among self-reported white women and 74% among self-reported African American women, Dr. Rocconi reported.

Mean racial genetic admixture scores showed considerable racial genetic heterogeneity among both self-reported African American women (65% African, 20% European, and 15% Native American Indian) and self-reported white women (77% European, 17% Native American Indian, and 6% African).

After adjustment for self-reported race, women’s risk of progression or death rose significantly with each 1% increase in African racial genetic admixture (hazard ratio, 1.02) and fell significantly with each 1% increase in European racial genetic admixture (HR, 0.97).

When women were stratified into quintiles of African racial genetic admixture, the risk of events rose steadily with quintile. Relative to their peers having 0%-2% of this racial genetic composition, women having 72%-86% were 7.7 times more likely to experience progression or death.

"For a reference, this is higher than any of the factors we take into account on a daily basis when stratifying high- or intermediate-risk endometrial cancer for recurrence," noted Dr. Rocconi, who disclosed that the study was sponsored by Amgen through a Young Investigator Award.

LOS ANGELES – Racial makeup based on genetic testing trumps self-reported race as a predictor of endometrial cancer outcomes, suggests the results of a study reported at the annual meeting of the Society of Gynecologic Oncology.

Researchers compared patient self reports of racial identity and the results of genotyping for markers of race in 217 women with endometrial cancer who had any-stage endometroid tumors.

The risk of cancer progression or death rose by 2% with each 1% increase in African racial genetic admixture and fell by 3% with each 1% increase in European racial genetic admixture.

"Racial genetic admixture significantly predicts the risk of recurrence and progression-free survival in endometrial cancer patients. Importantly, this risk is irrespective of self-designated race and could be used to stratify and identify patients’ recurrence risk," reported lead author Dr. Rodney P. Rocconi, a gynecologic oncologist at the Mitchell Cancer Institute and University of South Alabama in Mobile.

The results are worth examining as a key "to unraveling the etiology of this disparity, with the hopes of improving treatment outcomes and eventually eliminating this racial disparity in the future."

Dr. Rocconi acknowledged that the study included only endometroid tumors, and noted that black women typically have higher proportions of carcinosarcoma and type 2 endometrial cancers, a distinction that’s not always known preoperatively.

"In an ideal world, we would like to evaluate that (larger) population," Dr. Rocconi said. But "it came down to having enough funding to evaluate a population that is meaningful. In the future, by all means, it would be an extremely important population to look at."

African American women make up just 7% of all patients with endometrial cancer but account for 15% of deaths from the disease, he noted.

"To date, breaking down the definition of race in cancer racial disparity has largely been overlooked. Considering the majority of racial disparity research utilizes self-designated race, this in my opinion is the greatest limitation in this type of research. Self-designated race can be used as a proxy, but it is not precise in measurement of population differences. It cannot infer genetic similarity," he said.

Genetic testing "can mathematically calculate the place of origin genetically. Thus, it’s a more precise definition of race, and this methodology is important in teasing out those true factors of racial disparity. Simply put, this definition allows a continuous variable, a true percentage of African descent, as opposed to a categorical value of self-designated African American [race]," he said.

For the study, Dr. Rocconi and his coinvestigators identified women from Gynecologic Oncology Group (GOG) trial 210 who had endometroid tumors.

The team extracted DNA from tumor-free tissue samples and performed genotyping for 140 ancestry informative markers (AIMs), or single-nucleotide polymorphisms that occur in different frequencies in populations from different world geographic regions.

The 5-year rate of progression-free survival was 82% among self-reported white women and 74% among self-reported African American women, Dr. Rocconi reported.

Mean racial genetic admixture scores showed considerable racial genetic heterogeneity among both self-reported African American women (65% African, 20% European, and 15% Native American Indian) and self-reported white women (77% European, 17% Native American Indian, and 6% African).

After adjustment for self-reported race, women’s risk of progression or death rose significantly with each 1% increase in African racial genetic admixture (hazard ratio, 1.02) and fell significantly with each 1% increase in European racial genetic admixture (HR, 0.97).

When women were stratified into quintiles of African racial genetic admixture, the risk of events rose steadily with quintile. Relative to their peers having 0%-2% of this racial genetic composition, women having 72%-86% were 7.7 times more likely to experience progression or death.

"For a reference, this is higher than any of the factors we take into account on a daily basis when stratifying high- or intermediate-risk endometrial cancer for recurrence," noted Dr. Rocconi, who disclosed that the study was sponsored by Amgen through a Young Investigator Award.

LOS ANGELES – Racial makeup based on genetic testing trumps self-reported race as a predictor of endometrial cancer outcomes, suggests the results of a study reported at the annual meeting of the Society of Gynecologic Oncology.

Researchers compared patient self reports of racial identity and the results of genotyping for markers of race in 217 women with endometrial cancer who had any-stage endometroid tumors.

The risk of cancer progression or death rose by 2% with each 1% increase in African racial genetic admixture and fell by 3% with each 1% increase in European racial genetic admixture.

"Racial genetic admixture significantly predicts the risk of recurrence and progression-free survival in endometrial cancer patients. Importantly, this risk is irrespective of self-designated race and could be used to stratify and identify patients’ recurrence risk," reported lead author Dr. Rodney P. Rocconi, a gynecologic oncologist at the Mitchell Cancer Institute and University of South Alabama in Mobile.

The results are worth examining as a key "to unraveling the etiology of this disparity, with the hopes of improving treatment outcomes and eventually eliminating this racial disparity in the future."

Dr. Rocconi acknowledged that the study included only endometroid tumors, and noted that black women typically have higher proportions of carcinosarcoma and type 2 endometrial cancers, a distinction that’s not always known preoperatively.

"In an ideal world, we would like to evaluate that (larger) population," Dr. Rocconi said. But "it came down to having enough funding to evaluate a population that is meaningful. In the future, by all means, it would be an extremely important population to look at."

African American women make up just 7% of all patients with endometrial cancer but account for 15% of deaths from the disease, he noted.

"To date, breaking down the definition of race in cancer racial disparity has largely been overlooked. Considering the majority of racial disparity research utilizes self-designated race, this in my opinion is the greatest limitation in this type of research. Self-designated race can be used as a proxy, but it is not precise in measurement of population differences. It cannot infer genetic similarity," he said.

Genetic testing "can mathematically calculate the place of origin genetically. Thus, it’s a more precise definition of race, and this methodology is important in teasing out those true factors of racial disparity. Simply put, this definition allows a continuous variable, a true percentage of African descent, as opposed to a categorical value of self-designated African American [race]," he said.

For the study, Dr. Rocconi and his coinvestigators identified women from Gynecologic Oncology Group (GOG) trial 210 who had endometroid tumors.

The team extracted DNA from tumor-free tissue samples and performed genotyping for 140 ancestry informative markers (AIMs), or single-nucleotide polymorphisms that occur in different frequencies in populations from different world geographic regions.

The 5-year rate of progression-free survival was 82% among self-reported white women and 74% among self-reported African American women, Dr. Rocconi reported.

Mean racial genetic admixture scores showed considerable racial genetic heterogeneity among both self-reported African American women (65% African, 20% European, and 15% Native American Indian) and self-reported white women (77% European, 17% Native American Indian, and 6% African).

After adjustment for self-reported race, women’s risk of progression or death rose significantly with each 1% increase in African racial genetic admixture (hazard ratio, 1.02) and fell significantly with each 1% increase in European racial genetic admixture (HR, 0.97).

When women were stratified into quintiles of African racial genetic admixture, the risk of events rose steadily with quintile. Relative to their peers having 0%-2% of this racial genetic composition, women having 72%-86% were 7.7 times more likely to experience progression or death.

"For a reference, this is higher than any of the factors we take into account on a daily basis when stratifying high- or intermediate-risk endometrial cancer for recurrence," noted Dr. Rocconi, who disclosed that the study was sponsored by Amgen through a Young Investigator Award.

LOS ANGELES – Testing for high-risk human papillomavirus appears to be more reliable than performing liquid-based cytology for assessing a woman’s risk of developing advanced cervical neoplasia, based on the final results of the ATHENA trial.

In the prospective cohort study, both types of testing were performed in 42,209 women aged 25 years or older presenting for routine cervical cancer screening. A subset of these women had annual follow-up including repeat testing and colposcopy over 3 years.

The cumulative incidence rate of grade 3 cervical intraepithelial neoplasia (CIN3) or more advanced neoplasia was 0.33% in women having negative results for high-risk HPV, but much higher at 0.77% in women having negative liquid-based cytology results, regardless of HPV results. In addition, combining the two types of testing yielded very little gain over HPV testing alone; the rate was 0.29% in women with negative results on both tests.

"The adjusted 3-year cumulative incidence rate of CIN3 or greater in high-risk HPV-negative women is less than half that of women who have liquid based cytology that is negative," said lead author Thomas C. Wright Jr. at the annual meeting of the Society of Gynecologic Oncology. "Co-testing with both liquid-based cytology and high-risk HPV provides very little benefit over using high-risk HPV testing alone for screening."

"These results, we believe, suggest that high-risk HPV testing and genotyping is superior to liquid-based cytology for cervical cancer screening. And one of the goals of this trial is to go to the FDA and to get approval for HPV with genotyping for primary screening," added Dr. Wright, director of the division of gynecologic and obstetrical pathology at Columbia (N.Y.) University Medical Center.

"Certainly, the new American Cancer Society, ASCCP [American Society for Colposcopy and Cervical Pathology], and ASCP [American Society for Clinical Pathology] guidelines recommend co-testing, which is cytology and HPV, as a preferred screening approach for women 30 years and older," Dr. Wright noted. "I think the data that I showed today suggest that cytology adds so little that we would really do well to look at primary HPV screening. It’s going to be up to regulatory agencies though, as well as societies such as the American Cancer Society to make risk-benefit analyses. But, certainly, the data look very promising."

The 3-year cumulative incidence rate of CIN3 or worse was about 10% overall among patients having positive test results for any of the 14 high-risk types of HPV assessed. The main driver, however, was positivity for HPV 16 – women positive for this HPV type had a CIN3 or worse rate of 25%. HPV 18 was a lesser but still major contributor, associated with a rate of nearly 11%. The rate was 5% for women positive for any of the other 12 high-risk HPV types.

The data show "the disproportionate impact of HPV 16 positivity on the 3-year cumulative incidence rate among individuals who are high-risk HPV positive," Dr. Wright commented. "It is actually well over double that of women who have the 14 other types of high-risk HPV pooled, and compared to the other high-risk types, you have a fivefold increase."

The trial was the U.S. regulatory trial to obtain FDA clearance for the cobas HPV Test (manufactured by Roche Molecular Systems), which detects 14 types of HPV associated with a high risk of cervical neoplasia and cancer.

The analyses reported were based on 42,209 women aged 25 years or older on enrollment. They had a median age of 41 years, and 83% were white. At baseline, 10% had a high-risk HPV infection as assessed by the cobas test and 6% had atypical squamous cells of undetermined significance (ASCUS) or more advanced cervical neoplasia as detected by cytology.

The widely differing rates of CIN3 or worse for women who were high-risk HPV negative versus liquid-based cytology negative "are very similar to what has been seen in a number of large European studies," Dr. Wright noted.

And the temporal trends for the various high-risk HPV groups generally mirror those observed in a previous series of women seen at a Kaiser facility who had 10 years of follow-up (J. Natl. Cancer Inst. 2005;97:1072-9). "High-risk HPV-negative women remain very low [risk] in the ATHENA as well as in the Kaiser series," he pointed out.

In his post-presentation discussion, Dr. Wright was asked whether the study findings lend "a further push for school-based HPV vaccines in the United States."

"I’m not sure how my data address that," he responded. "However, I firmly believe that we should have school-based HPV vaccination in the United States. I think that most people in this room would believe that the percentage of our vaccinated cohort in the United States is much smaller than it should be; some people would use the word ‘appalling’ to refer to the rate at which we have vaccinated. And I think that societies such as the Society of Gynecologic Oncology should take the lead in trying to" improve vaccine uptake.

Dr. Wright disclosed that he is a consultant for Roche Molecular Systems, BD Diagnostics, Cepheid, and Hologic. The trial was sponsored by Roche Molecular Systems.

LOS ANGELES – Testing for high-risk human papillomavirus appears to be more reliable than performing liquid-based cytology for assessing a woman’s risk of developing advanced cervical neoplasia, based on the final results of the ATHENA trial.

In the prospective cohort study, both types of testing were performed in 42,209 women aged 25 years or older presenting for routine cervical cancer screening. A subset of these women had annual follow-up including repeat testing and colposcopy over 3 years.

The cumulative incidence rate of grade 3 cervical intraepithelial neoplasia (CIN3) or more advanced neoplasia was 0.33% in women having negative results for high-risk HPV, but much higher at 0.77% in women having negative liquid-based cytology results, regardless of HPV results. In addition, combining the two types of testing yielded very little gain over HPV testing alone; the rate was 0.29% in women with negative results on both tests.

"The adjusted 3-year cumulative incidence rate of CIN3 or greater in high-risk HPV-negative women is less than half that of women who have liquid based cytology that is negative," said lead author Thomas C. Wright Jr. at the annual meeting of the Society of Gynecologic Oncology. "Co-testing with both liquid-based cytology and high-risk HPV provides very little benefit over using high-risk HPV testing alone for screening."

"These results, we believe, suggest that high-risk HPV testing and genotyping is superior to liquid-based cytology for cervical cancer screening. And one of the goals of this trial is to go to the FDA and to get approval for HPV with genotyping for primary screening," added Dr. Wright, director of the division of gynecologic and obstetrical pathology at Columbia (N.Y.) University Medical Center.

"Certainly, the new American Cancer Society, ASCCP [American Society for Colposcopy and Cervical Pathology], and ASCP [American Society for Clinical Pathology] guidelines recommend co-testing, which is cytology and HPV, as a preferred screening approach for women 30 years and older," Dr. Wright noted. "I think the data that I showed today suggest that cytology adds so little that we would really do well to look at primary HPV screening. It’s going to be up to regulatory agencies though, as well as societies such as the American Cancer Society to make risk-benefit analyses. But, certainly, the data look very promising."

The 3-year cumulative incidence rate of CIN3 or worse was about 10% overall among patients having positive test results for any of the 14 high-risk types of HPV assessed. The main driver, however, was positivity for HPV 16 – women positive for this HPV type had a CIN3 or worse rate of 25%. HPV 18 was a lesser but still major contributor, associated with a rate of nearly 11%. The rate was 5% for women positive for any of the other 12 high-risk HPV types.

The data show "the disproportionate impact of HPV 16 positivity on the 3-year cumulative incidence rate among individuals who are high-risk HPV positive," Dr. Wright commented. "It is actually well over double that of women who have the 14 other types of high-risk HPV pooled, and compared to the other high-risk types, you have a fivefold increase."

The trial was the U.S. regulatory trial to obtain FDA clearance for the cobas HPV Test (manufactured by Roche Molecular Systems), which detects 14 types of HPV associated with a high risk of cervical neoplasia and cancer.

The analyses reported were based on 42,209 women aged 25 years or older on enrollment. They had a median age of 41 years, and 83% were white. At baseline, 10% had a high-risk HPV infection as assessed by the cobas test and 6% had atypical squamous cells of undetermined significance (ASCUS) or more advanced cervical neoplasia as detected by cytology.

The widely differing rates of CIN3 or worse for women who were high-risk HPV negative versus liquid-based cytology negative "are very similar to what has been seen in a number of large European studies," Dr. Wright noted.

And the temporal trends for the various high-risk HPV groups generally mirror those observed in a previous series of women seen at a Kaiser facility who had 10 years of follow-up (J. Natl. Cancer Inst. 2005;97:1072-9). "High-risk HPV-negative women remain very low [risk] in the ATHENA as well as in the Kaiser series," he pointed out.

In his post-presentation discussion, Dr. Wright was asked whether the study findings lend "a further push for school-based HPV vaccines in the United States."

"I’m not sure how my data address that," he responded. "However, I firmly believe that we should have school-based HPV vaccination in the United States. I think that most people in this room would believe that the percentage of our vaccinated cohort in the United States is much smaller than it should be; some people would use the word ‘appalling’ to refer to the rate at which we have vaccinated. And I think that societies such as the Society of Gynecologic Oncology should take the lead in trying to" improve vaccine uptake.

Dr. Wright disclosed that he is a consultant for Roche Molecular Systems, BD Diagnostics, Cepheid, and Hologic. The trial was sponsored by Roche Molecular Systems.

LOS ANGELES – Testing for high-risk human papillomavirus appears to be more reliable than performing liquid-based cytology for assessing a woman’s risk of developing advanced cervical neoplasia, based on the final results of the ATHENA trial.

In the prospective cohort study, both types of testing were performed in 42,209 women aged 25 years or older presenting for routine cervical cancer screening. A subset of these women had annual follow-up including repeat testing and colposcopy over 3 years.

The cumulative incidence rate of grade 3 cervical intraepithelial neoplasia (CIN3) or more advanced neoplasia was 0.33% in women having negative results for high-risk HPV, but much higher at 0.77% in women having negative liquid-based cytology results, regardless of HPV results. In addition, combining the two types of testing yielded very little gain over HPV testing alone; the rate was 0.29% in women with negative results on both tests.

"The adjusted 3-year cumulative incidence rate of CIN3 or greater in high-risk HPV-negative women is less than half that of women who have liquid based cytology that is negative," said lead author Thomas C. Wright Jr. at the annual meeting of the Society of Gynecologic Oncology. "Co-testing with both liquid-based cytology and high-risk HPV provides very little benefit over using high-risk HPV testing alone for screening."

"These results, we believe, suggest that high-risk HPV testing and genotyping is superior to liquid-based cytology for cervical cancer screening. And one of the goals of this trial is to go to the FDA and to get approval for HPV with genotyping for primary screening," added Dr. Wright, director of the division of gynecologic and obstetrical pathology at Columbia (N.Y.) University Medical Center.

"Certainly, the new American Cancer Society, ASCCP [American Society for Colposcopy and Cervical Pathology], and ASCP [American Society for Clinical Pathology] guidelines recommend co-testing, which is cytology and HPV, as a preferred screening approach for women 30 years and older," Dr. Wright noted. "I think the data that I showed today suggest that cytology adds so little that we would really do well to look at primary HPV screening. It’s going to be up to regulatory agencies though, as well as societies such as the American Cancer Society to make risk-benefit analyses. But, certainly, the data look very promising."

The 3-year cumulative incidence rate of CIN3 or worse was about 10% overall among patients having positive test results for any of the 14 high-risk types of HPV assessed. The main driver, however, was positivity for HPV 16 – women positive for this HPV type had a CIN3 or worse rate of 25%. HPV 18 was a lesser but still major contributor, associated with a rate of nearly 11%. The rate was 5% for women positive for any of the other 12 high-risk HPV types.

The data show "the disproportionate impact of HPV 16 positivity on the 3-year cumulative incidence rate among individuals who are high-risk HPV positive," Dr. Wright commented. "It is actually well over double that of women who have the 14 other types of high-risk HPV pooled, and compared to the other high-risk types, you have a fivefold increase."

The trial was the U.S. regulatory trial to obtain FDA clearance for the cobas HPV Test (manufactured by Roche Molecular Systems), which detects 14 types of HPV associated with a high risk of cervical neoplasia and cancer.

The analyses reported were based on 42,209 women aged 25 years or older on enrollment. They had a median age of 41 years, and 83% were white. At baseline, 10% had a high-risk HPV infection as assessed by the cobas test and 6% had atypical squamous cells of undetermined significance (ASCUS) or more advanced cervical neoplasia as detected by cytology.

The widely differing rates of CIN3 or worse for women who were high-risk HPV negative versus liquid-based cytology negative "are very similar to what has been seen in a number of large European studies," Dr. Wright noted.

And the temporal trends for the various high-risk HPV groups generally mirror those observed in a previous series of women seen at a Kaiser facility who had 10 years of follow-up (J. Natl. Cancer Inst. 2005;97:1072-9). "High-risk HPV-negative women remain very low [risk] in the ATHENA as well as in the Kaiser series," he pointed out.

In his post-presentation discussion, Dr. Wright was asked whether the study findings lend "a further push for school-based HPV vaccines in the United States."

"I’m not sure how my data address that," he responded. "However, I firmly believe that we should have school-based HPV vaccination in the United States. I think that most people in this room would believe that the percentage of our vaccinated cohort in the United States is much smaller than it should be; some people would use the word ‘appalling’ to refer to the rate at which we have vaccinated. And I think that societies such as the Society of Gynecologic Oncology should take the lead in trying to" improve vaccine uptake.

Dr. Wright disclosed that he is a consultant for Roche Molecular Systems, BD Diagnostics, Cepheid, and Hologic. The trial was sponsored by Roche Molecular Systems.

SAN FRANCISCO – Primary care providers should ask women if they have experienced placental abruption during pregnancy as this complication sharply increases the risk of cardiovascular mortality, finds a population-based cohort study of 47,918 women delivering in Israel.

Placental abruption was rare, seen in just 1.3% of the women, presenting author Dr. Eyal Sheiner reported at the annual meeting of the Society for Maternal-Fetal Medicine.

Susan London/IMNG Medical Media

However, with a median follow-up of about 15 years, these women had a significant near quintupling of the risk of cardiovascular death when compared with their peers who had not experienced that pregnancy complication.

Main results showed that after adjustment for potential confounders, women who had experienced placental abruption had sharply higher odds of cardiovascular death during follow-up (odds ratio, 4.8; P = .01), reported Dr. Sheiner.

Abruption did not significantly increase the adjusted odds of simple cardiovascular events or complex cardiovascular events, although there were trends in that direction.

"We all know that we can’t ignore pregnancy and say, ‘Okay, this patient had abruption, but she’s healthy,’ " he said in an interview. "Pregnancy is part of the lifetime of the patient, and if you want to reduce the [cardiovascular] risk, you have to ask about the complications during pregnancy."

"It’s very easy – it’s not that I am telling them to do something invasive. But I’m telling family practitioners to ask about pregnancy complications. It’s just a single question, and it’s part of the risk assessment," he added.

Dr. Sheiner hastened to point out that absolute rates of cardiovascular death among the women studied were low: 0.3% in the group with and 0.1% in the group without placental abruption.

"My aim is not to stress patients," he said, but rather to convey the importance of asking specifically about this complication.

The 2011 guidelines of the American Heart Association mention the importance of asking about other pregnancy complications during cardiovascular risk assessment, according to Dr. Sheiner, professor of obstetrics and gynecology and director of the maternity department at Soroka University Medical Center in Beer-Sheva, Israel.

"In their report, they recommend that all women should be asked about pregnancy-induced hypertension and diabetes. So we were thinking about other complications that might be risk factors for subsequent complications," he explained.

Specifically, "we wanted to see if placental abruption might serve as a trigger for long-term cardiovascular events because placental abruption has a vascular etiology, and we know that pregnancy might be considered as a stress test for things to happen."

Study analyses were based on women delivering between 1988 and 1999 at a single institution – the lone, tertiary-care hospital serving Israel’s Negev region – which permitted good long-term follow-up, he pointed out. The investigators assessed cardiovascular outcomes through 2010.

The study’s findings were reported during a poster session at the meeting.

Dr. Sheiner disclosed no relevant conflicts of interest.

SAN FRANCISCO – Primary care providers should ask women if they have experienced placental abruption during pregnancy as this complication sharply increases the risk of cardiovascular mortality, finds a population-based cohort study of 47,918 women delivering in Israel.

Placental abruption was rare, seen in just 1.3% of the women, presenting author Dr. Eyal Sheiner reported at the annual meeting of the Society for Maternal-Fetal Medicine.

Susan London/IMNG Medical Media

However, with a median follow-up of about 15 years, these women had a significant near quintupling of the risk of cardiovascular death when compared with their peers who had not experienced that pregnancy complication.

Main results showed that after adjustment for potential confounders, women who had experienced placental abruption had sharply higher odds of cardiovascular death during follow-up (odds ratio, 4.8; P = .01), reported Dr. Sheiner.

Abruption did not significantly increase the adjusted odds of simple cardiovascular events or complex cardiovascular events, although there were trends in that direction.

"We all know that we can’t ignore pregnancy and say, ‘Okay, this patient had abruption, but she’s healthy,’ " he said in an interview. "Pregnancy is part of the lifetime of the patient, and if you want to reduce the [cardiovascular] risk, you have to ask about the complications during pregnancy."

"It’s very easy – it’s not that I am telling them to do something invasive. But I’m telling family practitioners to ask about pregnancy complications. It’s just a single question, and it’s part of the risk assessment," he added.

Dr. Sheiner hastened to point out that absolute rates of cardiovascular death among the women studied were low: 0.3% in the group with and 0.1% in the group without placental abruption.

"My aim is not to stress patients," he said, but rather to convey the importance of asking specifically about this complication.

The 2011 guidelines of the American Heart Association mention the importance of asking about other pregnancy complications during cardiovascular risk assessment, according to Dr. Sheiner, professor of obstetrics and gynecology and director of the maternity department at Soroka University Medical Center in Beer-Sheva, Israel.

"In their report, they recommend that all women should be asked about pregnancy-induced hypertension and diabetes. So we were thinking about other complications that might be risk factors for subsequent complications," he explained.

Specifically, "we wanted to see if placental abruption might serve as a trigger for long-term cardiovascular events because placental abruption has a vascular etiology, and we know that pregnancy might be considered as a stress test for things to happen."

Study analyses were based on women delivering between 1988 and 1999 at a single institution – the lone, tertiary-care hospital serving Israel’s Negev region – which permitted good long-term follow-up, he pointed out. The investigators assessed cardiovascular outcomes through 2010.

The study’s findings were reported during a poster session at the meeting.

Dr. Sheiner disclosed no relevant conflicts of interest.

SAN FRANCISCO – Primary care providers should ask women if they have experienced placental abruption during pregnancy as this complication sharply increases the risk of cardiovascular mortality, finds a population-based cohort study of 47,918 women delivering in Israel.

Placental abruption was rare, seen in just 1.3% of the women, presenting author Dr. Eyal Sheiner reported at the annual meeting of the Society for Maternal-Fetal Medicine.

Susan London/IMNG Medical Media

However, with a median follow-up of about 15 years, these women had a significant near quintupling of the risk of cardiovascular death when compared with their peers who had not experienced that pregnancy complication.

Main results showed that after adjustment for potential confounders, women who had experienced placental abruption had sharply higher odds of cardiovascular death during follow-up (odds ratio, 4.8; P = .01), reported Dr. Sheiner.

Abruption did not significantly increase the adjusted odds of simple cardiovascular events or complex cardiovascular events, although there were trends in that direction.

"We all know that we can’t ignore pregnancy and say, ‘Okay, this patient had abruption, but she’s healthy,’ " he said in an interview. "Pregnancy is part of the lifetime of the patient, and if you want to reduce the [cardiovascular] risk, you have to ask about the complications during pregnancy."

"It’s very easy – it’s not that I am telling them to do something invasive. But I’m telling family practitioners to ask about pregnancy complications. It’s just a single question, and it’s part of the risk assessment," he added.

Dr. Sheiner hastened to point out that absolute rates of cardiovascular death among the women studied were low: 0.3% in the group with and 0.1% in the group without placental abruption.

"My aim is not to stress patients," he said, but rather to convey the importance of asking specifically about this complication.

The 2011 guidelines of the American Heart Association mention the importance of asking about other pregnancy complications during cardiovascular risk assessment, according to Dr. Sheiner, professor of obstetrics and gynecology and director of the maternity department at Soroka University Medical Center in Beer-Sheva, Israel.

"In their report, they recommend that all women should be asked about pregnancy-induced hypertension and diabetes. So we were thinking about other complications that might be risk factors for subsequent complications," he explained.

Specifically, "we wanted to see if placental abruption might serve as a trigger for long-term cardiovascular events because placental abruption has a vascular etiology, and we know that pregnancy might be considered as a stress test for things to happen."

Study analyses were based on women delivering between 1988 and 1999 at a single institution – the lone, tertiary-care hospital serving Israel’s Negev region – which permitted good long-term follow-up, he pointed out. The investigators assessed cardiovascular outcomes through 2010.

The study’s findings were reported during a poster session at the meeting.

Dr. Sheiner disclosed no relevant conflicts of interest.

SAN FRANCISCO – Compared with the traditional, on-call approach to coverage of labor and delivery units, the laborist model of continuous, uninterrupted coverage yields better obstetric outcomes and is cost-effective, according to a trio of studies reported at the Pregnancy Meeting, the annual meeting of the Society for Maternal-Fetal Medicine.

Improved maternal and birth outcomes

In a cohort study, Dr. Sindhu K. Srinivas, an obstetrician-gynecologist at the University of Pennsylvania in Philadelphia, and her team assessed changes in pregnancy outcomes over a 13-year period, comparing 8 hospitals that reported implementing a laborist approach with 16 matched hospitals that reported sticking to the traditional approach.

Adjusted analyses based on nearly 550,000 patients showed that women delivering in the laborist hospitals were less likely to have labor induction (odds ratio, 0.85) and preterm birth (OR, 0.83), with similar benefit for medically indicated birth and spontaneous preterm birth.

There were no significant differences in cesarean delivery, chorioamnionitis, intensive care unit admission, or prolonged length of stay, or in a variety of neonatal outcomes, such as birth asphyxia and death.

"Our study demonstrates that implementation of laborists is a promising obstetric care delivery model, but additional studies are needed to evaluate the impact of this model in different care settings and the mechanisms by which these outcomes are improved," Dr. Srinivas commented. "If we can understand the mechanisms of these outcome improvements, these lessons may be transferrable and may assist us in achieving optimal maternal and neonatal outcomes, even in settings without laborists."

Session attendee Dr. Manuel Porto, professor and chairman of obstetrics and gynecology at the University of California, Irvine, wondered about the uniformity of the laborist approach across hospitals. "Some hospitals will call themselves a laborist hospital when they have nocturn-ists, weekend-ists, and any other variation, when we are thinking of 24-hour-a-day, 7-day-a-week dedicated services," he commented. "That might have had a great impact on your results."

There are likely two levels of effects, Dr. Srinivas replied. "One is related to the laborist who is the provider and their skill set ... and the other has to do with a model of care where you take people who might have even already worked at your institution, add a couple of people who are laborists, or hospitalists, or nocturnists, or whatever, and actually combine that and create a model of care that’s 24-hour coverage," she explained. "It’s very hard to disentangle those things. So we are now doing some qualitative interviewing of the hospitals...to better answer that question."

In another cohort study, a team led by Dr. Yvonne W. Cheng of the University of California, San Francisco, retrospectively assessed obstetric outcomes of uncomplicated singleton term live births in hospitals having at least 1,200 births a year, using birth certificates linked to hospital discharge and death data.

They compared outcomes between 274,109 deliveries at hospitals using on-call, as-needed labor and delivery coverage and 465,913 deliveries at hospitals using 24-hour coverage, with type of coverage reported by staff.

Results showed that 24-hour coverage was associated with lower adjusted odds of cesarean delivery (odds ratio, 0.87), with the same reduction seen for nulliparas and for multiparas in terms of primary cesarean. The rate of cesarean delivery among women having labor induction did not differ significantly.

Continuous coverage was also associated with higher adjusted odds of a trial of labor after cesarean (TOLAC) (OR, 2.21) but, among women having such a trial, no difference in rates of vaginal birth after cesarean (VBAC).

The odds of neonatal asphyxia and neonatal death were statistically indistinguishable between the two groups.

Dr. Cheng acknowledged that it is unclear whether the observed changes were due to the laborist model or to other factors, or some combination.

"Even though we attempted to control for patient characteristics, could there exist inherent differences between the two groups of women which we could not measure? Or could the on-call physicians make medical decisions that differ from those of around-the-clock physicians given a similar clinical scenario? Alternatively, could the hospitals that implement around-the-clock coverage have different values and culture regarding labor management?" she proposed.

"Certainly more studies are needed to address these crucial questions," she concluded.

Cost-effective for many hospitals

In a third study, Allison Allen, a medical student at Oregon Health & Science University in Portland, and colleagues used a decision analytic model to assess the cost-effectiveness of the laborist approach, looking at time-to-delivery outcomes after introducing the emergent scenarios of umbilical cord prolapse and major abruption.

They used a hypothetical cohort of pregnant patients receiving care at hospitals that did and did not employ laborists; in base case analyses, the hospitals had 1,000 deliveries per year.

The investigators assessed a variety of costs, including the costs of delivery, of neonatal intensive care unit (NICU) care, and of caring for a child with cerebral palsy over their lifetime.

Results showed that when applied to 100,000 patients, compared with not employing laborists, employing laborists was associated with 38 fewer intrapartum stillbirths (an 83% reduction), 25 fewer cases of major neurodevelopmental injury (a 17% reduction), and 15 fewer cases of neonatal death (a 13% reduction) per year.

Employing laborists was also cost-effective, at a cost of $45,508 per quality-adjusted life-year (QALY) gained. In fact, that value is "well under our willingness-to-pay threshold of $100,000 per QALY," Ms. Allen noted.

However, employing laborists "never became the dominant model, meaning better outcomes at lower cost," she added. "Even in hospitals with up to 10,000 deliveries per year, the employment of a laborist was still not cost-saving to that hospital. This is in part due to the fact that there is an increased probability of physicians being available in hospitals without a laborist."

Sensitivity analyses showed that the model remained cost-effective down to a hospital volume of 424 deliveries per year.

"Our decision analytic model found that employment of laborists was cost-effective and produced better outcomes for moms and babies. ... Given these results, we believe that more research and discussion are necessary, not only on delineating time-to-delivery outcomes, but also on how to make 24-hour coverage of labor and delivery more feasible in small and midsized hospitals," Ms. Allen commented.

"As laborists may not generate the revenue to cover their salary, particularly in smaller hospitals, this raises an interesting dilemma: The costs of laborists must be taken on by the hospital, while the costs saved by the employment of this strategy are largely societal, being the costs of caring for neonates with major neurodevelopmental injury," she added. "However, our model did not take into account the decreased cost of litigation related to bad outcomes in hospitals without a laborist."

Attendee Dr. Michael Berman, of the Beth Israel Medical Center in New York, said, "I don’t think you should discount the importance of the litigation. Many hospitalist and laborist programs are being funded – just like patient safety programs – with funds from captive insurance companies. And it has definitely been shown to lower malpractice premiums. But on the other side of the coin, having better outcomes, even one baby a year, can really pay for a laborist program. ... I think it’s something we should all keep in mind."

And Dr. Jennifer Bailit, of the Case Western Reserve University School of Medicine in Cleveland, noted that some of the costs assessed in the study would not be ones seen by the hospital. "I just want to caution hospitals not to look at that data to say that it’s not going to be cost-effective for them to get a laborist model, because there is more to the story," she asserted.

Dr. Srinivas, Dr. Cheng, and Ms. Allen disclosed no relevant conflicts of interest.

SAN FRANCISCO – Compared with the traditional, on-call approach to coverage of labor and delivery units, the laborist model of continuous, uninterrupted coverage yields better obstetric outcomes and is cost-effective, according to a trio of studies reported at the Pregnancy Meeting, the annual meeting of the Society for Maternal-Fetal Medicine.

Improved maternal and birth outcomes

In a cohort study, Dr. Sindhu K. Srinivas, an obstetrician-gynecologist at the University of Pennsylvania in Philadelphia, and her team assessed changes in pregnancy outcomes over a 13-year period, comparing 8 hospitals that reported implementing a laborist approach with 16 matched hospitals that reported sticking to the traditional approach.

Adjusted analyses based on nearly 550,000 patients showed that women delivering in the laborist hospitals were less likely to have labor induction (odds ratio, 0.85) and preterm birth (OR, 0.83), with similar benefit for medically indicated birth and spontaneous preterm birth.

There were no significant differences in cesarean delivery, chorioamnionitis, intensive care unit admission, or prolonged length of stay, or in a variety of neonatal outcomes, such as birth asphyxia and death.

"Our study demonstrates that implementation of laborists is a promising obstetric care delivery model, but additional studies are needed to evaluate the impact of this model in different care settings and the mechanisms by which these outcomes are improved," Dr. Srinivas commented. "If we can understand the mechanisms of these outcome improvements, these lessons may be transferrable and may assist us in achieving optimal maternal and neonatal outcomes, even in settings without laborists."

Session attendee Dr. Manuel Porto, professor and chairman of obstetrics and gynecology at the University of California, Irvine, wondered about the uniformity of the laborist approach across hospitals. "Some hospitals will call themselves a laborist hospital when they have nocturn-ists, weekend-ists, and any other variation, when we are thinking of 24-hour-a-day, 7-day-a-week dedicated services," he commented. "That might have had a great impact on your results."

There are likely two levels of effects, Dr. Srinivas replied. "One is related to the laborist who is the provider and their skill set ... and the other has to do with a model of care where you take people who might have even already worked at your institution, add a couple of people who are laborists, or hospitalists, or nocturnists, or whatever, and actually combine that and create a model of care that’s 24-hour coverage," she explained. "It’s very hard to disentangle those things. So we are now doing some qualitative interviewing of the hospitals...to better answer that question."

In another cohort study, a team led by Dr. Yvonne W. Cheng of the University of California, San Francisco, retrospectively assessed obstetric outcomes of uncomplicated singleton term live births in hospitals having at least 1,200 births a year, using birth certificates linked to hospital discharge and death data.

They compared outcomes between 274,109 deliveries at hospitals using on-call, as-needed labor and delivery coverage and 465,913 deliveries at hospitals using 24-hour coverage, with type of coverage reported by staff.

Results showed that 24-hour coverage was associated with lower adjusted odds of cesarean delivery (odds ratio, 0.87), with the same reduction seen for nulliparas and for multiparas in terms of primary cesarean. The rate of cesarean delivery among women having labor induction did not differ significantly.

Continuous coverage was also associated with higher adjusted odds of a trial of labor after cesarean (TOLAC) (OR, 2.21) but, among women having such a trial, no difference in rates of vaginal birth after cesarean (VBAC).

The odds of neonatal asphyxia and neonatal death were statistically indistinguishable between the two groups.

Dr. Cheng acknowledged that it is unclear whether the observed changes were due to the laborist model or to other factors, or some combination.

"Even though we attempted to control for patient characteristics, could there exist inherent differences between the two groups of women which we could not measure? Or could the on-call physicians make medical decisions that differ from those of around-the-clock physicians given a similar clinical scenario? Alternatively, could the hospitals that implement around-the-clock coverage have different values and culture regarding labor management?" she proposed.

"Certainly more studies are needed to address these crucial questions," she concluded.

Cost-effective for many hospitals

In a third study, Allison Allen, a medical student at Oregon Health & Science University in Portland, and colleagues used a decision analytic model to assess the cost-effectiveness of the laborist approach, looking at time-to-delivery outcomes after introducing the emergent scenarios of umbilical cord prolapse and major abruption.

They used a hypothetical cohort of pregnant patients receiving care at hospitals that did and did not employ laborists; in base case analyses, the hospitals had 1,000 deliveries per year.

The investigators assessed a variety of costs, including the costs of delivery, of neonatal intensive care unit (NICU) care, and of caring for a child with cerebral palsy over their lifetime.

Results showed that when applied to 100,000 patients, compared with not employing laborists, employing laborists was associated with 38 fewer intrapartum stillbirths (an 83% reduction), 25 fewer cases of major neurodevelopmental injury (a 17% reduction), and 15 fewer cases of neonatal death (a 13% reduction) per year.

Employing laborists was also cost-effective, at a cost of $45,508 per quality-adjusted life-year (QALY) gained. In fact, that value is "well under our willingness-to-pay threshold of $100,000 per QALY," Ms. Allen noted.

However, employing laborists "never became the dominant model, meaning better outcomes at lower cost," she added. "Even in hospitals with up to 10,000 deliveries per year, the employment of a laborist was still not cost-saving to that hospital. This is in part due to the fact that there is an increased probability of physicians being available in hospitals without a laborist."

Sensitivity analyses showed that the model remained cost-effective down to a hospital volume of 424 deliveries per year.

"Our decision analytic model found that employment of laborists was cost-effective and produced better outcomes for moms and babies. ... Given these results, we believe that more research and discussion are necessary, not only on delineating time-to-delivery outcomes, but also on how to make 24-hour coverage of labor and delivery more feasible in small and midsized hospitals," Ms. Allen commented.

"As laborists may not generate the revenue to cover their salary, particularly in smaller hospitals, this raises an interesting dilemma: The costs of laborists must be taken on by the hospital, while the costs saved by the employment of this strategy are largely societal, being the costs of caring for neonates with major neurodevelopmental injury," she added. "However, our model did not take into account the decreased cost of litigation related to bad outcomes in hospitals without a laborist."

Attendee Dr. Michael Berman, of the Beth Israel Medical Center in New York, said, "I don’t think you should discount the importance of the litigation. Many hospitalist and laborist programs are being funded – just like patient safety programs – with funds from captive insurance companies. And it has definitely been shown to lower malpractice premiums. But on the other side of the coin, having better outcomes, even one baby a year, can really pay for a laborist program. ... I think it’s something we should all keep in mind."

And Dr. Jennifer Bailit, of the Case Western Reserve University School of Medicine in Cleveland, noted that some of the costs assessed in the study would not be ones seen by the hospital. "I just want to caution hospitals not to look at that data to say that it’s not going to be cost-effective for them to get a laborist model, because there is more to the story," she asserted.

Dr. Srinivas, Dr. Cheng, and Ms. Allen disclosed no relevant conflicts of interest.

SAN FRANCISCO – Compared with the traditional, on-call approach to coverage of labor and delivery units, the laborist model of continuous, uninterrupted coverage yields better obstetric outcomes and is cost-effective, according to a trio of studies reported at the Pregnancy Meeting, the annual meeting of the Society for Maternal-Fetal Medicine.

Improved maternal and birth outcomes

In a cohort study, Dr. Sindhu K. Srinivas, an obstetrician-gynecologist at the University of Pennsylvania in Philadelphia, and her team assessed changes in pregnancy outcomes over a 13-year period, comparing 8 hospitals that reported implementing a laborist approach with 16 matched hospitals that reported sticking to the traditional approach.

Adjusted analyses based on nearly 550,000 patients showed that women delivering in the laborist hospitals were less likely to have labor induction (odds ratio, 0.85) and preterm birth (OR, 0.83), with similar benefit for medically indicated birth and spontaneous preterm birth.

There were no significant differences in cesarean delivery, chorioamnionitis, intensive care unit admission, or prolonged length of stay, or in a variety of neonatal outcomes, such as birth asphyxia and death.

"Our study demonstrates that implementation of laborists is a promising obstetric care delivery model, but additional studies are needed to evaluate the impact of this model in different care settings and the mechanisms by which these outcomes are improved," Dr. Srinivas commented. "If we can understand the mechanisms of these outcome improvements, these lessons may be transferrable and may assist us in achieving optimal maternal and neonatal outcomes, even in settings without laborists."

Session attendee Dr. Manuel Porto, professor and chairman of obstetrics and gynecology at the University of California, Irvine, wondered about the uniformity of the laborist approach across hospitals. "Some hospitals will call themselves a laborist hospital when they have nocturn-ists, weekend-ists, and any other variation, when we are thinking of 24-hour-a-day, 7-day-a-week dedicated services," he commented. "That might have had a great impact on your results."

There are likely two levels of effects, Dr. Srinivas replied. "One is related to the laborist who is the provider and their skill set ... and the other has to do with a model of care where you take people who might have even already worked at your institution, add a couple of people who are laborists, or hospitalists, or nocturnists, or whatever, and actually combine that and create a model of care that’s 24-hour coverage," she explained. "It’s very hard to disentangle those things. So we are now doing some qualitative interviewing of the hospitals...to better answer that question."

In another cohort study, a team led by Dr. Yvonne W. Cheng of the University of California, San Francisco, retrospectively assessed obstetric outcomes of uncomplicated singleton term live births in hospitals having at least 1,200 births a year, using birth certificates linked to hospital discharge and death data.

They compared outcomes between 274,109 deliveries at hospitals using on-call, as-needed labor and delivery coverage and 465,913 deliveries at hospitals using 24-hour coverage, with type of coverage reported by staff.

Results showed that 24-hour coverage was associated with lower adjusted odds of cesarean delivery (odds ratio, 0.87), with the same reduction seen for nulliparas and for multiparas in terms of primary cesarean. The rate of cesarean delivery among women having labor induction did not differ significantly.

Continuous coverage was also associated with higher adjusted odds of a trial of labor after cesarean (TOLAC) (OR, 2.21) but, among women having such a trial, no difference in rates of vaginal birth after cesarean (VBAC).

The odds of neonatal asphyxia and neonatal death were statistically indistinguishable between the two groups.

Dr. Cheng acknowledged that it is unclear whether the observed changes were due to the laborist model or to other factors, or some combination.

"Even though we attempted to control for patient characteristics, could there exist inherent differences between the two groups of women which we could not measure? Or could the on-call physicians make medical decisions that differ from those of around-the-clock physicians given a similar clinical scenario? Alternatively, could the hospitals that implement around-the-clock coverage have different values and culture regarding labor management?" she proposed.

"Certainly more studies are needed to address these crucial questions," she concluded.

Cost-effective for many hospitals

In a third study, Allison Allen, a medical student at Oregon Health & Science University in Portland, and colleagues used a decision analytic model to assess the cost-effectiveness of the laborist approach, looking at time-to-delivery outcomes after introducing the emergent scenarios of umbilical cord prolapse and major abruption.

They used a hypothetical cohort of pregnant patients receiving care at hospitals that did and did not employ laborists; in base case analyses, the hospitals had 1,000 deliveries per year.

The investigators assessed a variety of costs, including the costs of delivery, of neonatal intensive care unit (NICU) care, and of caring for a child with cerebral palsy over their lifetime.

Results showed that when applied to 100,000 patients, compared with not employing laborists, employing laborists was associated with 38 fewer intrapartum stillbirths (an 83% reduction), 25 fewer cases of major neurodevelopmental injury (a 17% reduction), and 15 fewer cases of neonatal death (a 13% reduction) per year.

Employing laborists was also cost-effective, at a cost of $45,508 per quality-adjusted life-year (QALY) gained. In fact, that value is "well under our willingness-to-pay threshold of $100,000 per QALY," Ms. Allen noted.

However, employing laborists "never became the dominant model, meaning better outcomes at lower cost," she added. "Even in hospitals with up to 10,000 deliveries per year, the employment of a laborist was still not cost-saving to that hospital. This is in part due to the fact that there is an increased probability of physicians being available in hospitals without a laborist."

Sensitivity analyses showed that the model remained cost-effective down to a hospital volume of 424 deliveries per year.

"Our decision analytic model found that employment of laborists was cost-effective and produced better outcomes for moms and babies. ... Given these results, we believe that more research and discussion are necessary, not only on delineating time-to-delivery outcomes, but also on how to make 24-hour coverage of labor and delivery more feasible in small and midsized hospitals," Ms. Allen commented.

"As laborists may not generate the revenue to cover their salary, particularly in smaller hospitals, this raises an interesting dilemma: The costs of laborists must be taken on by the hospital, while the costs saved by the employment of this strategy are largely societal, being the costs of caring for neonates with major neurodevelopmental injury," she added. "However, our model did not take into account the decreased cost of litigation related to bad outcomes in hospitals without a laborist."

Attendee Dr. Michael Berman, of the Beth Israel Medical Center in New York, said, "I don’t think you should discount the importance of the litigation. Many hospitalist and laborist programs are being funded – just like patient safety programs – with funds from captive insurance companies. And it has definitely been shown to lower malpractice premiums. But on the other side of the coin, having better outcomes, even one baby a year, can really pay for a laborist program. ... I think it’s something we should all keep in mind."

And Dr. Jennifer Bailit, of the Case Western Reserve University School of Medicine in Cleveland, noted that some of the costs assessed in the study would not be ones seen by the hospital. "I just want to caution hospitals not to look at that data to say that it’s not going to be cost-effective for them to get a laborist model, because there is more to the story," she asserted.

Dr. Srinivas, Dr. Cheng, and Ms. Allen disclosed no relevant conflicts of interest.