Susan London

CHICAGO – Patients with end-stage renal disease have sharply elevated rates of hospitalization for pneumonia throughout the renal transplantation trajectory, researchers reported at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

The findings underscore the importance of vaccinating this group against pneumococcal and other diseases, lead investigator Lise Haubjerg Nielsen recommended in an interview. Pneumonia "is a big economic burden for society and it is a huge [source of] mortality for these patients."

In a Danish nationwide population-based cohort study among more than 90,000 individuals, those with end-stage renal disease (ESRD) had an 8- to 14-fold higher incidence of such hospitalization, depending on whether they were wait-listed, posttransplant, or post–graft failure, when compared with their counterparts in the general population.

About one-third of the posttransplant group was hospitalized for pneumonia. Male sex and older age were among the significant risk factors for pneumonia hospitalization at this stage. On the other hand, risk fell after the first year posttransplant.

The marked increase in posttransplant risk was expected, given patients’ use of immunosuppressants, according to Ms. Nielsen, who is a medical student undertaking a research year in the department of infectious diseases at Aarhus University Hospital, Skejby. However, the fact that the elevations seen before and after transplantation were even greater was surprising, she said at the meeting, which was sponsored by the American Society for Microbiology.

The increase in pretransplant risk was probably caused by patients’ uremic state, while that post–graft failure "could also be just [a reflection of] these patients being more sick than the general population," she speculated.

The investigators analyzed data from the Danish National Hospital Registry, identifying all hospitalizations since 1977 having a discharge diagnosis of pneumonia, regardless of whether the infection was community or hospital acquired.

They assessed first hospitalizations for pneumonia (excluding those caused by Pneumocystis jiroveci) occurring during 1990-2009. Patients with ESRD who were wait-listed for and/or underwent transplantation were matched by age and sex with up to 19 unaffected individuals from the general population. Analyses were based on 4,973 individuals with and 85,899 individuals without ESRD.

The incidence of first pneumonia hospitalization was 46, 32, and 63 per 1,000 person-years among wait-listed patients, renal transplant recipients, and patients who experienced graft loss, respectively.

These groups had corresponding 10-, 9, and 14-fold increases in the incidence of such hospitalization compared with the general population, according to Ms. Nielsen.

In an analysis of risk factors among the renal transplant recipients, the adjusted incidence rate of pneumonia hospitalization was significantly higher for men; patients aged 50 years or older; those who underwent 1-3 years of dialysis pretransplantation versus none; and those whose renal disease was associated with diabetes, chronic interstitial nephritis, or polycystic kidney disease as compared with glomerulonephritis. The risk of pneumonia hospitalization was significantly lower for those who were at least 1 year out from transplantation.

Ms. Nielsen reported having no conflicts of interest.

CHICAGO – Patients with end-stage renal disease have sharply elevated rates of hospitalization for pneumonia throughout the renal transplantation trajectory, researchers reported at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

The findings underscore the importance of vaccinating this group against pneumococcal and other diseases, lead investigator Lise Haubjerg Nielsen recommended in an interview. Pneumonia "is a big economic burden for society and it is a huge [source of] mortality for these patients."

In a Danish nationwide population-based cohort study among more than 90,000 individuals, those with end-stage renal disease (ESRD) had an 8- to 14-fold higher incidence of such hospitalization, depending on whether they were wait-listed, posttransplant, or post–graft failure, when compared with their counterparts in the general population.

About one-third of the posttransplant group was hospitalized for pneumonia. Male sex and older age were among the significant risk factors for pneumonia hospitalization at this stage. On the other hand, risk fell after the first year posttransplant.

The marked increase in posttransplant risk was expected, given patients’ use of immunosuppressants, according to Ms. Nielsen, who is a medical student undertaking a research year in the department of infectious diseases at Aarhus University Hospital, Skejby. However, the fact that the elevations seen before and after transplantation were even greater was surprising, she said at the meeting, which was sponsored by the American Society for Microbiology.

The increase in pretransplant risk was probably caused by patients’ uremic state, while that post–graft failure "could also be just [a reflection of] these patients being more sick than the general population," she speculated.

The investigators analyzed data from the Danish National Hospital Registry, identifying all hospitalizations since 1977 having a discharge diagnosis of pneumonia, regardless of whether the infection was community or hospital acquired.

They assessed first hospitalizations for pneumonia (excluding those caused by Pneumocystis jiroveci) occurring during 1990-2009. Patients with ESRD who were wait-listed for and/or underwent transplantation were matched by age and sex with up to 19 unaffected individuals from the general population. Analyses were based on 4,973 individuals with and 85,899 individuals without ESRD.

The incidence of first pneumonia hospitalization was 46, 32, and 63 per 1,000 person-years among wait-listed patients, renal transplant recipients, and patients who experienced graft loss, respectively.

These groups had corresponding 10-, 9, and 14-fold increases in the incidence of such hospitalization compared with the general population, according to Ms. Nielsen.

In an analysis of risk factors among the renal transplant recipients, the adjusted incidence rate of pneumonia hospitalization was significantly higher for men; patients aged 50 years or older; those who underwent 1-3 years of dialysis pretransplantation versus none; and those whose renal disease was associated with diabetes, chronic interstitial nephritis, or polycystic kidney disease as compared with glomerulonephritis. The risk of pneumonia hospitalization was significantly lower for those who were at least 1 year out from transplantation.

Ms. Nielsen reported having no conflicts of interest.

CHICAGO – Patients with end-stage renal disease have sharply elevated rates of hospitalization for pneumonia throughout the renal transplantation trajectory, researchers reported at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

The findings underscore the importance of vaccinating this group against pneumococcal and other diseases, lead investigator Lise Haubjerg Nielsen recommended in an interview. Pneumonia "is a big economic burden for society and it is a huge [source of] mortality for these patients."

In a Danish nationwide population-based cohort study among more than 90,000 individuals, those with end-stage renal disease (ESRD) had an 8- to 14-fold higher incidence of such hospitalization, depending on whether they were wait-listed, posttransplant, or post–graft failure, when compared with their counterparts in the general population.

About one-third of the posttransplant group was hospitalized for pneumonia. Male sex and older age were among the significant risk factors for pneumonia hospitalization at this stage. On the other hand, risk fell after the first year posttransplant.

The marked increase in posttransplant risk was expected, given patients’ use of immunosuppressants, according to Ms. Nielsen, who is a medical student undertaking a research year in the department of infectious diseases at Aarhus University Hospital, Skejby. However, the fact that the elevations seen before and after transplantation were even greater was surprising, she said at the meeting, which was sponsored by the American Society for Microbiology.

The increase in pretransplant risk was probably caused by patients’ uremic state, while that post–graft failure "could also be just [a reflection of] these patients being more sick than the general population," she speculated.

The investigators analyzed data from the Danish National Hospital Registry, identifying all hospitalizations since 1977 having a discharge diagnosis of pneumonia, regardless of whether the infection was community or hospital acquired.

They assessed first hospitalizations for pneumonia (excluding those caused by Pneumocystis jiroveci) occurring during 1990-2009. Patients with ESRD who were wait-listed for and/or underwent transplantation were matched by age and sex with up to 19 unaffected individuals from the general population. Analyses were based on 4,973 individuals with and 85,899 individuals without ESRD.

The incidence of first pneumonia hospitalization was 46, 32, and 63 per 1,000 person-years among wait-listed patients, renal transplant recipients, and patients who experienced graft loss, respectively.

These groups had corresponding 10-, 9, and 14-fold increases in the incidence of such hospitalization compared with the general population, according to Ms. Nielsen.

In an analysis of risk factors among the renal transplant recipients, the adjusted incidence rate of pneumonia hospitalization was significantly higher for men; patients aged 50 years or older; those who underwent 1-3 years of dialysis pretransplantation versus none; and those whose renal disease was associated with diabetes, chronic interstitial nephritis, or polycystic kidney disease as compared with glomerulonephritis. The risk of pneumonia hospitalization was significantly lower for those who were at least 1 year out from transplantation.

Ms. Nielsen reported having no conflicts of interest.

SAN FRANCISCO – Entinostat, a novel oral histone deacetylase inhibitor taken once weekly, may overcome resistance to hormonal therapy in breast cancer, the results of a randomized phase-II trial suggest.

Investigators studied 130 women with estrogen receptor–positive advanced breast cancer progressing on aromatase inhibitor (AI) therapy. Results showed that, compared with exemestane (Aromasin) plus placebo, exemestane plus entinostat reduced the risk of progression-free survival events by 27% and the risk of death by 44%. It also was well tolerated.

"The combination ... is delaying the time to disease progression, allowing patients to maintain hormonal therapy longer, and delaying the need for change of therapy and subsequent considerations of chemotherapy," principal investigator Dr. Denise A. Yardley reported at a breast cancer symposium sponsored by the American Society of Clinical Oncology.

"These results support our plans for a global, pivotal phase-III study due to begin enrollment in 2012," added Dr. Yardley, an oncologist with the Sarah Cannon Research Institute and Tennessee Oncology PLLC, both in Nashville.

In an additional finding, median progression-free survival was greatest, 8.5 months, in patients treated with the combination who had hyperacetylation of proteins in blood cells during the first cycle of treatment, suggesting that this could be a biomarker for efficacy. These data reveal "for the first time in a matched controlled trial, evidence of hyperacetylation from an HDAC [histone deacetylase] inhibitor correlating with improved outcomes," she noted.

Session chair Dr. Joyce O’Shaughnessy, an oncologist with the Baylor Sammons Cancer Center in Dallas, Texas Oncology, and US Oncology, characterized the trial’s findings as "very, very promising," saying, "I agree that it’s time for a phase III" trial. To her knowledge, this is the first randomized trial of an HDAC inhibitor in breast cancer.

A particularly impressive finding was the long progression-free survival seen in hyperacetylators, according to Dr. O’Shaughnessy. It will be important to determine whether this correlates with toxicity, as lack of toxicity might then identify patients who could benefit from dose-escalation of entinostat. "They need to really carefully look at that because you really want to optimize it for all the people in the phase-III trial," she commented.

Giving some mechanistic background to the trial, Dr. Yardley noted that HDAC inhibitors interfere with the condensation of chromatin and the silencing of genes, such as tumor suppressor genes.

Resistance to AIs occurs from upregulation and activation of growth factor signaling pathways that are not estrogen dependent. "Entinostat targets these growth factor signaling pathways, ultimately inhibiting tumor cell growth," she explained. Preclinical data also suggest that the drug resensitizes tumors to AIs.

The randomized phase-II trial, called ENCORE 301 (Entinostat Combinations Overcoming Resistance), was conducted among women in North America, the European Union, and Russia who were postmenopausal and had locally advanced or metastatic estrogen receptor–positive breast cancer that was progressing on a nonsteroidal AI (anastrozole or letrozole). Those with metastatic disease could have received up to one prior chemotherapy for metastases.

The patients were randomized in balanced fashion to double-blind treatment with exemestane plus placebo or exemestane plus entinostat. By study design, P values less than .1 were considered statistically significant.

Demographically, the patients were 62 years old on average. Eighty-five percent had experienced progression on an AI in the metastatic setting.

With a median follow-up of 18 months, entinostat was associated with longer median progression-free survival (4.28 vs. 2.27 months; hazard ratio, 0.73; P = .06), with similar findings in subgroups stratified by locally advanced vs. metastatic disease, age, and site of metastasis, Dr. Yardley reported.

In 49 patients, blood samples collected before and during the first cycle of therapy were analyzed to determine the percent change of lysines in peripheral blood mononuclear cell proteins that were acetylated. Results showed that progression-free survival was greatest, at 8.54 months, among entinostat-treated patients who had hyperacetylation, defined as an above-median percent change in lysines that were acetylated during the first cycle of treatment.

These findings "suggest that entinostat-induced hyperacetylation appeared to track with improved outcomes in these patients and suggest quite provocatively within the very first cycle of treatment that this may be a potential marker to assess the benefit from this treatment," said Dr. Yardley.

Furthermore, the association raises the "question, if you can identify early on a group that is not acetylating, whether increasing the dose may get them to be hyperacetylators and derive more benefit from the HDAC inhibitor," she said. Additionally, ongoing analyses are looking at whether hyperacetylation correlated with toxicity and could then be used as a surrogate for efficacy.

"We are going to have more correlative work planned as a part of the phase-III trial that is coming up," Dr. Yardley added.

In an analysis that was exploratory because follow-up is still short, entinostat was also associated with better overall survival (26.9 vs. 20.3 months; HR, 0.56; P = .027). Additional data with longer follow-up will be reported at the San Antonio Breast Cancer Symposium later this year.

The combination of entinostat and exemestane was well tolerated, with no unexpected safety signals. The most common grade 3/4 adverse events in the entinostat group were fatigue (13%), neutropenia (13%), nausea (5%), and vomiting (5%). The rate of discontinuation because of adverse events was 1% in the placebo group and 11% in the entinostat group.

Dr. Yardley reported that she had no relevant conflicts of interest. Syndax Pharmaceuticals, developer of entinostat, was not among Dr. O’Shaughnessy’s disclosures.

SAN FRANCISCO – Entinostat, a novel oral histone deacetylase inhibitor taken once weekly, may overcome resistance to hormonal therapy in breast cancer, the results of a randomized phase-II trial suggest.

Investigators studied 130 women with estrogen receptor–positive advanced breast cancer progressing on aromatase inhibitor (AI) therapy. Results showed that, compared with exemestane (Aromasin) plus placebo, exemestane plus entinostat reduced the risk of progression-free survival events by 27% and the risk of death by 44%. It also was well tolerated.

"The combination ... is delaying the time to disease progression, allowing patients to maintain hormonal therapy longer, and delaying the need for change of therapy and subsequent considerations of chemotherapy," principal investigator Dr. Denise A. Yardley reported at a breast cancer symposium sponsored by the American Society of Clinical Oncology.

"These results support our plans for a global, pivotal phase-III study due to begin enrollment in 2012," added Dr. Yardley, an oncologist with the Sarah Cannon Research Institute and Tennessee Oncology PLLC, both in Nashville.

In an additional finding, median progression-free survival was greatest, 8.5 months, in patients treated with the combination who had hyperacetylation of proteins in blood cells during the first cycle of treatment, suggesting that this could be a biomarker for efficacy. These data reveal "for the first time in a matched controlled trial, evidence of hyperacetylation from an HDAC [histone deacetylase] inhibitor correlating with improved outcomes," she noted.

Session chair Dr. Joyce O’Shaughnessy, an oncologist with the Baylor Sammons Cancer Center in Dallas, Texas Oncology, and US Oncology, characterized the trial’s findings as "very, very promising," saying, "I agree that it’s time for a phase III" trial. To her knowledge, this is the first randomized trial of an HDAC inhibitor in breast cancer.

A particularly impressive finding was the long progression-free survival seen in hyperacetylators, according to Dr. O’Shaughnessy. It will be important to determine whether this correlates with toxicity, as lack of toxicity might then identify patients who could benefit from dose-escalation of entinostat. "They need to really carefully look at that because you really want to optimize it for all the people in the phase-III trial," she commented.

Giving some mechanistic background to the trial, Dr. Yardley noted that HDAC inhibitors interfere with the condensation of chromatin and the silencing of genes, such as tumor suppressor genes.

Resistance to AIs occurs from upregulation and activation of growth factor signaling pathways that are not estrogen dependent. "Entinostat targets these growth factor signaling pathways, ultimately inhibiting tumor cell growth," she explained. Preclinical data also suggest that the drug resensitizes tumors to AIs.

The randomized phase-II trial, called ENCORE 301 (Entinostat Combinations Overcoming Resistance), was conducted among women in North America, the European Union, and Russia who were postmenopausal and had locally advanced or metastatic estrogen receptor–positive breast cancer that was progressing on a nonsteroidal AI (anastrozole or letrozole). Those with metastatic disease could have received up to one prior chemotherapy for metastases.

The patients were randomized in balanced fashion to double-blind treatment with exemestane plus placebo or exemestane plus entinostat. By study design, P values less than .1 were considered statistically significant.

Demographically, the patients were 62 years old on average. Eighty-five percent had experienced progression on an AI in the metastatic setting.

With a median follow-up of 18 months, entinostat was associated with longer median progression-free survival (4.28 vs. 2.27 months; hazard ratio, 0.73; P = .06), with similar findings in subgroups stratified by locally advanced vs. metastatic disease, age, and site of metastasis, Dr. Yardley reported.

In 49 patients, blood samples collected before and during the first cycle of therapy were analyzed to determine the percent change of lysines in peripheral blood mononuclear cell proteins that were acetylated. Results showed that progression-free survival was greatest, at 8.54 months, among entinostat-treated patients who had hyperacetylation, defined as an above-median percent change in lysines that were acetylated during the first cycle of treatment.

These findings "suggest that entinostat-induced hyperacetylation appeared to track with improved outcomes in these patients and suggest quite provocatively within the very first cycle of treatment that this may be a potential marker to assess the benefit from this treatment," said Dr. Yardley.

Furthermore, the association raises the "question, if you can identify early on a group that is not acetylating, whether increasing the dose may get them to be hyperacetylators and derive more benefit from the HDAC inhibitor," she said. Additionally, ongoing analyses are looking at whether hyperacetylation correlated with toxicity and could then be used as a surrogate for efficacy.

"We are going to have more correlative work planned as a part of the phase-III trial that is coming up," Dr. Yardley added.

In an analysis that was exploratory because follow-up is still short, entinostat was also associated with better overall survival (26.9 vs. 20.3 months; HR, 0.56; P = .027). Additional data with longer follow-up will be reported at the San Antonio Breast Cancer Symposium later this year.

The combination of entinostat and exemestane was well tolerated, with no unexpected safety signals. The most common grade 3/4 adverse events in the entinostat group were fatigue (13%), neutropenia (13%), nausea (5%), and vomiting (5%). The rate of discontinuation because of adverse events was 1% in the placebo group and 11% in the entinostat group.

Dr. Yardley reported that she had no relevant conflicts of interest. Syndax Pharmaceuticals, developer of entinostat, was not among Dr. O’Shaughnessy’s disclosures.

SAN FRANCISCO – Entinostat, a novel oral histone deacetylase inhibitor taken once weekly, may overcome resistance to hormonal therapy in breast cancer, the results of a randomized phase-II trial suggest.

Investigators studied 130 women with estrogen receptor–positive advanced breast cancer progressing on aromatase inhibitor (AI) therapy. Results showed that, compared with exemestane (Aromasin) plus placebo, exemestane plus entinostat reduced the risk of progression-free survival events by 27% and the risk of death by 44%. It also was well tolerated.

"The combination ... is delaying the time to disease progression, allowing patients to maintain hormonal therapy longer, and delaying the need for change of therapy and subsequent considerations of chemotherapy," principal investigator Dr. Denise A. Yardley reported at a breast cancer symposium sponsored by the American Society of Clinical Oncology.

"These results support our plans for a global, pivotal phase-III study due to begin enrollment in 2012," added Dr. Yardley, an oncologist with the Sarah Cannon Research Institute and Tennessee Oncology PLLC, both in Nashville.

In an additional finding, median progression-free survival was greatest, 8.5 months, in patients treated with the combination who had hyperacetylation of proteins in blood cells during the first cycle of treatment, suggesting that this could be a biomarker for efficacy. These data reveal "for the first time in a matched controlled trial, evidence of hyperacetylation from an HDAC [histone deacetylase] inhibitor correlating with improved outcomes," she noted.

Session chair Dr. Joyce O’Shaughnessy, an oncologist with the Baylor Sammons Cancer Center in Dallas, Texas Oncology, and US Oncology, characterized the trial’s findings as "very, very promising," saying, "I agree that it’s time for a phase III" trial. To her knowledge, this is the first randomized trial of an HDAC inhibitor in breast cancer.

A particularly impressive finding was the long progression-free survival seen in hyperacetylators, according to Dr. O’Shaughnessy. It will be important to determine whether this correlates with toxicity, as lack of toxicity might then identify patients who could benefit from dose-escalation of entinostat. "They need to really carefully look at that because you really want to optimize it for all the people in the phase-III trial," she commented.

Giving some mechanistic background to the trial, Dr. Yardley noted that HDAC inhibitors interfere with the condensation of chromatin and the silencing of genes, such as tumor suppressor genes.

Resistance to AIs occurs from upregulation and activation of growth factor signaling pathways that are not estrogen dependent. "Entinostat targets these growth factor signaling pathways, ultimately inhibiting tumor cell growth," she explained. Preclinical data also suggest that the drug resensitizes tumors to AIs.

The randomized phase-II trial, called ENCORE 301 (Entinostat Combinations Overcoming Resistance), was conducted among women in North America, the European Union, and Russia who were postmenopausal and had locally advanced or metastatic estrogen receptor–positive breast cancer that was progressing on a nonsteroidal AI (anastrozole or letrozole). Those with metastatic disease could have received up to one prior chemotherapy for metastases.

The patients were randomized in balanced fashion to double-blind treatment with exemestane plus placebo or exemestane plus entinostat. By study design, P values less than .1 were considered statistically significant.

Demographically, the patients were 62 years old on average. Eighty-five percent had experienced progression on an AI in the metastatic setting.

With a median follow-up of 18 months, entinostat was associated with longer median progression-free survival (4.28 vs. 2.27 months; hazard ratio, 0.73; P = .06), with similar findings in subgroups stratified by locally advanced vs. metastatic disease, age, and site of metastasis, Dr. Yardley reported.

In 49 patients, blood samples collected before and during the first cycle of therapy were analyzed to determine the percent change of lysines in peripheral blood mononuclear cell proteins that were acetylated. Results showed that progression-free survival was greatest, at 8.54 months, among entinostat-treated patients who had hyperacetylation, defined as an above-median percent change in lysines that were acetylated during the first cycle of treatment.

These findings "suggest that entinostat-induced hyperacetylation appeared to track with improved outcomes in these patients and suggest quite provocatively within the very first cycle of treatment that this may be a potential marker to assess the benefit from this treatment," said Dr. Yardley.

Furthermore, the association raises the "question, if you can identify early on a group that is not acetylating, whether increasing the dose may get them to be hyperacetylators and derive more benefit from the HDAC inhibitor," she said. Additionally, ongoing analyses are looking at whether hyperacetylation correlated with toxicity and could then be used as a surrogate for efficacy.

"We are going to have more correlative work planned as a part of the phase-III trial that is coming up," Dr. Yardley added.

In an analysis that was exploratory because follow-up is still short, entinostat was also associated with better overall survival (26.9 vs. 20.3 months; HR, 0.56; P = .027). Additional data with longer follow-up will be reported at the San Antonio Breast Cancer Symposium later this year.

The combination of entinostat and exemestane was well tolerated, with no unexpected safety signals. The most common grade 3/4 adverse events in the entinostat group were fatigue (13%), neutropenia (13%), nausea (5%), and vomiting (5%). The rate of discontinuation because of adverse events was 1% in the placebo group and 11% in the entinostat group.

Dr. Yardley reported that she had no relevant conflicts of interest. Syndax Pharmaceuticals, developer of entinostat, was not among Dr. O’Shaughnessy’s disclosures.

SAN FRANCISCO – The more metabolically active a woman’s bone metastases of breast cancer are on imaging, the greater her risk of death, researchers reported at a breast cancer symposium sponsored by the American Society of Clinical Oncology.

In a retrospective cohort study of 269 women with newly diagnosed metastatic breast cancer, those whose bone metastases were "hotter" on a PET/CT – as assessed from maximum standardized uptake value (SUV-max) – had poorer overall survival.

Compared with their counterparts with values in the bottom tertile of SUV-max values, women with values in the middle and top tertiles were roughly two to three times more likely to die after other prognostic factors were taken into account.

"To our understanding, this is the first large retrospective series to correlate SUV-max at metastatic breast cancer diagnosis with overall survival," said lead author Dr. Komal Jhaveri of Memorial Sloan-Kettering Cancer Center, New York.

The risk of death also rose with increasing tertile of SUV-max in liver, lung, and lymph node metastases, but those associations were not significant. Their nonsignificance may have been due to the smaller numbers of patients having metastases in those sites, she said.

Session chair Dr. Robert R. Kuske, a radiation oncologist with Arizona Breast Cancer Specialists in Scottsdale, noted that SUV-max is a surrogate for how rapidly the tumor cells are proliferating and, hence, the tumor’s aggressiveness. "So there should be a strong correlation between this SUV on the PET and the Ki-67 [histologic proliferation index]," he said.

"This gives us another tool in our tool chest to evaluate how patients are going to do," he commented. "Now [oncologists] can look at a metastasis on PET, measure the SUV, and get a handle on what the future of that patient is going to be – is it going to be a rapid slide to death, or is it going to be a very slow, indolent progression maybe over 10 or 15 years. And they can tailor the therapy based on the aggressiveness of the disease."

The PET/CT is usually done to determine whether the patient has metastases, so this additional prognostic information "is a little something extra you get from the test."

Will these new findings be practice changing? "I’ll start looking at SUV values in my patients with newly diagnosed metastasis," said Dr. Kuske. "Yes, it will change my practice."

In the study, Dr. Jhaveri and her coinvestigators reviewed records for women with metastatic breast cancer diagnosed between 2001 and 2008 who had a PET/CT scan performed within 60 days of the detection of metastases; had at least one avid metastasis in bone, liver, lung, or lymph node; and had not received chemotherapy in the month before the scan. Prior or current hormonal therapy was permitted.

The investigators determined the SUV-max for individual metastatic sites. They compared values only within a given site because of known variation across sites such as liver and lung, Dr. Jhaveri explained.

The women had a median age of 58 years. The median time elapsed between primary breast cancer diagnosis and PET/CT was 2.3 years. A fifth each had triple-negative disease and HER2-positive disease.

The median duration of follow-up was 40 months. In a multivariate analysis that included other prognostic factors (grade, tumor phenotype, and visceral metastases), overall survival differed across tertiles of SUV-max for bone metastases (P = .006). Women with values in the middle and top tertiles were 1.87 and 2.67 times more likely to die, respectively, than their counterparts with values in the bottom tertile.

"Given the variation in SUV and the differential impact on survival by site, it is possible that SUV-max may not be the most optimal PET variable," Dr. Jhaveri commented. She proposed that an alternate variable, called total lesion glycolysis (TLG), which incorporates tumor lesion size, might perform better and be more informative.

"Ultimately, prospective studies are required to further delineate the role of PET/CT as a prognostic tool in metastatic breast cancer," she concluded.

Dr. Jhaveri and Dr. Kuske reported having no relevant conflicts of interest.

SAN FRANCISCO – The more metabolically active a woman’s bone metastases of breast cancer are on imaging, the greater her risk of death, researchers reported at a breast cancer symposium sponsored by the American Society of Clinical Oncology.

In a retrospective cohort study of 269 women with newly diagnosed metastatic breast cancer, those whose bone metastases were "hotter" on a PET/CT – as assessed from maximum standardized uptake value (SUV-max) – had poorer overall survival.

Compared with their counterparts with values in the bottom tertile of SUV-max values, women with values in the middle and top tertiles were roughly two to three times more likely to die after other prognostic factors were taken into account.

"To our understanding, this is the first large retrospective series to correlate SUV-max at metastatic breast cancer diagnosis with overall survival," said lead author Dr. Komal Jhaveri of Memorial Sloan-Kettering Cancer Center, New York.

The risk of death also rose with increasing tertile of SUV-max in liver, lung, and lymph node metastases, but those associations were not significant. Their nonsignificance may have been due to the smaller numbers of patients having metastases in those sites, she said.

Session chair Dr. Robert R. Kuske, a radiation oncologist with Arizona Breast Cancer Specialists in Scottsdale, noted that SUV-max is a surrogate for how rapidly the tumor cells are proliferating and, hence, the tumor’s aggressiveness. "So there should be a strong correlation between this SUV on the PET and the Ki-67 [histologic proliferation index]," he said.

"This gives us another tool in our tool chest to evaluate how patients are going to do," he commented. "Now [oncologists] can look at a metastasis on PET, measure the SUV, and get a handle on what the future of that patient is going to be – is it going to be a rapid slide to death, or is it going to be a very slow, indolent progression maybe over 10 or 15 years. And they can tailor the therapy based on the aggressiveness of the disease."

The PET/CT is usually done to determine whether the patient has metastases, so this additional prognostic information "is a little something extra you get from the test."

Will these new findings be practice changing? "I’ll start looking at SUV values in my patients with newly diagnosed metastasis," said Dr. Kuske. "Yes, it will change my practice."

In the study, Dr. Jhaveri and her coinvestigators reviewed records for women with metastatic breast cancer diagnosed between 2001 and 2008 who had a PET/CT scan performed within 60 days of the detection of metastases; had at least one avid metastasis in bone, liver, lung, or lymph node; and had not received chemotherapy in the month before the scan. Prior or current hormonal therapy was permitted.

The investigators determined the SUV-max for individual metastatic sites. They compared values only within a given site because of known variation across sites such as liver and lung, Dr. Jhaveri explained.

The women had a median age of 58 years. The median time elapsed between primary breast cancer diagnosis and PET/CT was 2.3 years. A fifth each had triple-negative disease and HER2-positive disease.

The median duration of follow-up was 40 months. In a multivariate analysis that included other prognostic factors (grade, tumor phenotype, and visceral metastases), overall survival differed across tertiles of SUV-max for bone metastases (P = .006). Women with values in the middle and top tertiles were 1.87 and 2.67 times more likely to die, respectively, than their counterparts with values in the bottom tertile.

"Given the variation in SUV and the differential impact on survival by site, it is possible that SUV-max may not be the most optimal PET variable," Dr. Jhaveri commented. She proposed that an alternate variable, called total lesion glycolysis (TLG), which incorporates tumor lesion size, might perform better and be more informative.

"Ultimately, prospective studies are required to further delineate the role of PET/CT as a prognostic tool in metastatic breast cancer," she concluded.

Dr. Jhaveri and Dr. Kuske reported having no relevant conflicts of interest.

SAN FRANCISCO – The more metabolically active a woman’s bone metastases of breast cancer are on imaging, the greater her risk of death, researchers reported at a breast cancer symposium sponsored by the American Society of Clinical Oncology.

In a retrospective cohort study of 269 women with newly diagnosed metastatic breast cancer, those whose bone metastases were "hotter" on a PET/CT – as assessed from maximum standardized uptake value (SUV-max) – had poorer overall survival.

Compared with their counterparts with values in the bottom tertile of SUV-max values, women with values in the middle and top tertiles were roughly two to three times more likely to die after other prognostic factors were taken into account.

"To our understanding, this is the first large retrospective series to correlate SUV-max at metastatic breast cancer diagnosis with overall survival," said lead author Dr. Komal Jhaveri of Memorial Sloan-Kettering Cancer Center, New York.

The risk of death also rose with increasing tertile of SUV-max in liver, lung, and lymph node metastases, but those associations were not significant. Their nonsignificance may have been due to the smaller numbers of patients having metastases in those sites, she said.

Session chair Dr. Robert R. Kuske, a radiation oncologist with Arizona Breast Cancer Specialists in Scottsdale, noted that SUV-max is a surrogate for how rapidly the tumor cells are proliferating and, hence, the tumor’s aggressiveness. "So there should be a strong correlation between this SUV on the PET and the Ki-67 [histologic proliferation index]," he said.

"This gives us another tool in our tool chest to evaluate how patients are going to do," he commented. "Now [oncologists] can look at a metastasis on PET, measure the SUV, and get a handle on what the future of that patient is going to be – is it going to be a rapid slide to death, or is it going to be a very slow, indolent progression maybe over 10 or 15 years. And they can tailor the therapy based on the aggressiveness of the disease."

The PET/CT is usually done to determine whether the patient has metastases, so this additional prognostic information "is a little something extra you get from the test."

Will these new findings be practice changing? "I’ll start looking at SUV values in my patients with newly diagnosed metastasis," said Dr. Kuske. "Yes, it will change my practice."

In the study, Dr. Jhaveri and her coinvestigators reviewed records for women with metastatic breast cancer diagnosed between 2001 and 2008 who had a PET/CT scan performed within 60 days of the detection of metastases; had at least one avid metastasis in bone, liver, lung, or lymph node; and had not received chemotherapy in the month before the scan. Prior or current hormonal therapy was permitted.

The investigators determined the SUV-max for individual metastatic sites. They compared values only within a given site because of known variation across sites such as liver and lung, Dr. Jhaveri explained.

The women had a median age of 58 years. The median time elapsed between primary breast cancer diagnosis and PET/CT was 2.3 years. A fifth each had triple-negative disease and HER2-positive disease.

The median duration of follow-up was 40 months. In a multivariate analysis that included other prognostic factors (grade, tumor phenotype, and visceral metastases), overall survival differed across tertiles of SUV-max for bone metastases (P = .006). Women with values in the middle and top tertiles were 1.87 and 2.67 times more likely to die, respectively, than their counterparts with values in the bottom tertile.

"Given the variation in SUV and the differential impact on survival by site, it is possible that SUV-max may not be the most optimal PET variable," Dr. Jhaveri commented. She proposed that an alternate variable, called total lesion glycolysis (TLG), which incorporates tumor lesion size, might perform better and be more informative.

"Ultimately, prospective studies are required to further delineate the role of PET/CT as a prognostic tool in metastatic breast cancer," she concluded.

Dr. Jhaveri and Dr. Kuske reported having no relevant conflicts of interest.

Young women with early breast cancer need not have a mastectomy instead of a breast-conserving therapy if the rationale is based solely on their age, investigators concluded in a pair of retrospective cohort studies being reported at the ASCO Breast Cancer Symposium.

In the studies, conducted among more than 15,000 women aged 40 years or younger having median follow-up of about 6 years, rates of locoregional recurrence, overall survival, and breast cancer–specific survival were statistically indistinguishable from those who had breast conservation and their counterparts who had mastectomy, according to data presented in a premeeting press briefing.

Collectively, the results suggest that contemporary management of breast cancer has helped to offset the poorer outcomes historically associated with younger age at diagnosis, commented Dr. Andrew D. Seidman, moderator of the press briefing and a medical oncologist at the Memorial Sloan-Kettering Cancer Center in New York.

"This is an important revisitation of the conventional wisdom that young women who have breast cancer really need to have mastectomy," he said. "There certainly are differences in the biology of the disease in young women, compared to older women."

He suggested these new findings likely reflect changing influences on breast cancer management, such as use of genetic testing to better identify women with deleterious mutations and possibly breast MRI.

"It’s reassuring to younger women that simply young age alone does not seem to mandate the need for mastectomy, and one needs to look at other variables independent of age," Dr. Seidman said. Those variables will include factors like multicentricity or multifocality, BRCA mutations, family history, and, not least, women’s concerns about recurrence and second cancers.

Additionally, research is identifying biological subtypes of breast cancer that may be useful here, he noted. For example, among women with luminal type A breast cancer, emerging data suggest that Oncotype DX recurrence score may help assess risk of local relapse.

The bottom line, he stressed, is that "if a woman is told, you need to have mastectomy because you are young, the discussion needs to go beyond that," and individualized decision making is essential.

In the first study, Dr. Julliette M. Buckley and her colleagues at Massachusetts General Hospital in Boston reviewed the medical records of 628 women aged 40 years or younger who received a diagnosis of breast cancer up to stage III between 1996 and 2008 and were treated at their institution.

The women had a median age of 37 years. Overall, 71% had breast-conserving therapy, according to Dr. Buckley.

With a median follow-up of 72 months, the women had statistically indistinguishable rates of locoregional recurrence with breast conserving–therapy vs. mastectomy. Rates of locoregional and distant recurrence were 5.6% and 12% at 5 years, respectively, and 13% and 19% at 10 years. Rates of disease-free survival and overall survival were 82.5% and 93% at 5 years, respectively, and 87% and 68.5% at 10 years.

The findings suggest "that lumpectomy is indeed a safe option for young women," concluded Dr. Buckley, a breast surgery fellow.

"We believe that awareness of the genetic risk of breast cancer, advances in the screening for breast cancer, and improvements in systemic and radiation therapy have contributed to the longer overall survival for young women with breast cancer that we have demonstrated in this study," she said. "We feel that these results ... will give young women with breast cancer some reassurance if they choose to have a lumpectomy."

In the second study, investigators led by Dr. Usama Mahmood of the University of Texas M.D. Anderson Cancer Center in Houston analyzed data from the Surveillance, Epidemiology, and End Results database for 14,764 women 20-39 years old who received a diagnosis of early breast cancer between 1990 and 2007. Overall, 45% received breast-conserving therapy. The median duration of follow-up was 5.7 years.

In multivariate analyses that adjusted for potential confounders (including year of diagnosis, age, race/ethnicity, histology, grade, one vs. multiple regions of involvement, tumor size, number of positive lymph nodes, number of examined lymph nodes, estrogen receptor status, and progesterone receptor status), women treated with breast-conserving therapy did not differ significantly from their counterparts treated with mastectomy in terms of either overall survival (hazard ratio, 0.93; P = .16) or breast cancer–specific survival (hazard ratio, 0.93; P = .26).

The findings were similar in an additional analysis of a subset of 4,644 women from the two groups who were matched for patient and tumor characteristics, according to Dr. Mahmood, a fellow in radiation oncology, who did much of her search while at the University of Maryland’s Greenebaum Cancer Center in Baltimore. In this analysis, women treated with breast-conserving therapy and their counterparts treated with mastectomy again had similar 10-year overall survival (83.5% vs. 83.6%, P = .99) and breast cancer–specific survival (85.5% vs. 85.5%, P = .88).

"We found similar survival with either breast-conserving therapy or mastectomy in the treatment of young women with early-stage breast cancer," Dr. Mahmood concluded. "This just serves as a reminder that women should be counseled appropriately regarding their treatment options and should not choose a mastectomy based on an assumption of improved survival."

Dr. Seidman, Dr. Buckley, and Dr. Mahmood reported that they had no relevant conflicts of interest.

Young women with early breast cancer need not have a mastectomy instead of a breast-conserving therapy if the rationale is based solely on their age, investigators concluded in a pair of retrospective cohort studies being reported at the ASCO Breast Cancer Symposium.

In the studies, conducted among more than 15,000 women aged 40 years or younger having median follow-up of about 6 years, rates of locoregional recurrence, overall survival, and breast cancer–specific survival were statistically indistinguishable from those who had breast conservation and their counterparts who had mastectomy, according to data presented in a premeeting press briefing.

Collectively, the results suggest that contemporary management of breast cancer has helped to offset the poorer outcomes historically associated with younger age at diagnosis, commented Dr. Andrew D. Seidman, moderator of the press briefing and a medical oncologist at the Memorial Sloan-Kettering Cancer Center in New York.

"This is an important revisitation of the conventional wisdom that young women who have breast cancer really need to have mastectomy," he said. "There certainly are differences in the biology of the disease in young women, compared to older women."

He suggested these new findings likely reflect changing influences on breast cancer management, such as use of genetic testing to better identify women with deleterious mutations and possibly breast MRI.

"It’s reassuring to younger women that simply young age alone does not seem to mandate the need for mastectomy, and one needs to look at other variables independent of age," Dr. Seidman said. Those variables will include factors like multicentricity or multifocality, BRCA mutations, family history, and, not least, women’s concerns about recurrence and second cancers.

Additionally, research is identifying biological subtypes of breast cancer that may be useful here, he noted. For example, among women with luminal type A breast cancer, emerging data suggest that Oncotype DX recurrence score may help assess risk of local relapse.

The bottom line, he stressed, is that "if a woman is told, you need to have mastectomy because you are young, the discussion needs to go beyond that," and individualized decision making is essential.

In the first study, Dr. Julliette M. Buckley and her colleagues at Massachusetts General Hospital in Boston reviewed the medical records of 628 women aged 40 years or younger who received a diagnosis of breast cancer up to stage III between 1996 and 2008 and were treated at their institution.

The women had a median age of 37 years. Overall, 71% had breast-conserving therapy, according to Dr. Buckley.

With a median follow-up of 72 months, the women had statistically indistinguishable rates of locoregional recurrence with breast conserving–therapy vs. mastectomy. Rates of locoregional and distant recurrence were 5.6% and 12% at 5 years, respectively, and 13% and 19% at 10 years. Rates of disease-free survival and overall survival were 82.5% and 93% at 5 years, respectively, and 87% and 68.5% at 10 years.

The findings suggest "that lumpectomy is indeed a safe option for young women," concluded Dr. Buckley, a breast surgery fellow.

"We believe that awareness of the genetic risk of breast cancer, advances in the screening for breast cancer, and improvements in systemic and radiation therapy have contributed to the longer overall survival for young women with breast cancer that we have demonstrated in this study," she said. "We feel that these results ... will give young women with breast cancer some reassurance if they choose to have a lumpectomy."

In the second study, investigators led by Dr. Usama Mahmood of the University of Texas M.D. Anderson Cancer Center in Houston analyzed data from the Surveillance, Epidemiology, and End Results database for 14,764 women 20-39 years old who received a diagnosis of early breast cancer between 1990 and 2007. Overall, 45% received breast-conserving therapy. The median duration of follow-up was 5.7 years.

In multivariate analyses that adjusted for potential confounders (including year of diagnosis, age, race/ethnicity, histology, grade, one vs. multiple regions of involvement, tumor size, number of positive lymph nodes, number of examined lymph nodes, estrogen receptor status, and progesterone receptor status), women treated with breast-conserving therapy did not differ significantly from their counterparts treated with mastectomy in terms of either overall survival (hazard ratio, 0.93; P = .16) or breast cancer–specific survival (hazard ratio, 0.93; P = .26).

The findings were similar in an additional analysis of a subset of 4,644 women from the two groups who were matched for patient and tumor characteristics, according to Dr. Mahmood, a fellow in radiation oncology, who did much of her search while at the University of Maryland’s Greenebaum Cancer Center in Baltimore. In this analysis, women treated with breast-conserving therapy and their counterparts treated with mastectomy again had similar 10-year overall survival (83.5% vs. 83.6%, P = .99) and breast cancer–specific survival (85.5% vs. 85.5%, P = .88).

"We found similar survival with either breast-conserving therapy or mastectomy in the treatment of young women with early-stage breast cancer," Dr. Mahmood concluded. "This just serves as a reminder that women should be counseled appropriately regarding their treatment options and should not choose a mastectomy based on an assumption of improved survival."

Dr. Seidman, Dr. Buckley, and Dr. Mahmood reported that they had no relevant conflicts of interest.

Young women with early breast cancer need not have a mastectomy instead of a breast-conserving therapy if the rationale is based solely on their age, investigators concluded in a pair of retrospective cohort studies being reported at the ASCO Breast Cancer Symposium.

In the studies, conducted among more than 15,000 women aged 40 years or younger having median follow-up of about 6 years, rates of locoregional recurrence, overall survival, and breast cancer–specific survival were statistically indistinguishable from those who had breast conservation and their counterparts who had mastectomy, according to data presented in a premeeting press briefing.

Collectively, the results suggest that contemporary management of breast cancer has helped to offset the poorer outcomes historically associated with younger age at diagnosis, commented Dr. Andrew D. Seidman, moderator of the press briefing and a medical oncologist at the Memorial Sloan-Kettering Cancer Center in New York.

"This is an important revisitation of the conventional wisdom that young women who have breast cancer really need to have mastectomy," he said. "There certainly are differences in the biology of the disease in young women, compared to older women."

He suggested these new findings likely reflect changing influences on breast cancer management, such as use of genetic testing to better identify women with deleterious mutations and possibly breast MRI.

"It’s reassuring to younger women that simply young age alone does not seem to mandate the need for mastectomy, and one needs to look at other variables independent of age," Dr. Seidman said. Those variables will include factors like multicentricity or multifocality, BRCA mutations, family history, and, not least, women’s concerns about recurrence and second cancers.

Additionally, research is identifying biological subtypes of breast cancer that may be useful here, he noted. For example, among women with luminal type A breast cancer, emerging data suggest that Oncotype DX recurrence score may help assess risk of local relapse.

The bottom line, he stressed, is that "if a woman is told, you need to have mastectomy because you are young, the discussion needs to go beyond that," and individualized decision making is essential.

In the first study, Dr. Julliette M. Buckley and her colleagues at Massachusetts General Hospital in Boston reviewed the medical records of 628 women aged 40 years or younger who received a diagnosis of breast cancer up to stage III between 1996 and 2008 and were treated at their institution.

The women had a median age of 37 years. Overall, 71% had breast-conserving therapy, according to Dr. Buckley.

With a median follow-up of 72 months, the women had statistically indistinguishable rates of locoregional recurrence with breast conserving–therapy vs. mastectomy. Rates of locoregional and distant recurrence were 5.6% and 12% at 5 years, respectively, and 13% and 19% at 10 years. Rates of disease-free survival and overall survival were 82.5% and 93% at 5 years, respectively, and 87% and 68.5% at 10 years.

The findings suggest "that lumpectomy is indeed a safe option for young women," concluded Dr. Buckley, a breast surgery fellow.

"We believe that awareness of the genetic risk of breast cancer, advances in the screening for breast cancer, and improvements in systemic and radiation therapy have contributed to the longer overall survival for young women with breast cancer that we have demonstrated in this study," she said. "We feel that these results ... will give young women with breast cancer some reassurance if they choose to have a lumpectomy."

In the second study, investigators led by Dr. Usama Mahmood of the University of Texas M.D. Anderson Cancer Center in Houston analyzed data from the Surveillance, Epidemiology, and End Results database for 14,764 women 20-39 years old who received a diagnosis of early breast cancer between 1990 and 2007. Overall, 45% received breast-conserving therapy. The median duration of follow-up was 5.7 years.

In multivariate analyses that adjusted for potential confounders (including year of diagnosis, age, race/ethnicity, histology, grade, one vs. multiple regions of involvement, tumor size, number of positive lymph nodes, number of examined lymph nodes, estrogen receptor status, and progesterone receptor status), women treated with breast-conserving therapy did not differ significantly from their counterparts treated with mastectomy in terms of either overall survival (hazard ratio, 0.93; P = .16) or breast cancer–specific survival (hazard ratio, 0.93; P = .26).

The findings were similar in an additional analysis of a subset of 4,644 women from the two groups who were matched for patient and tumor characteristics, according to Dr. Mahmood, a fellow in radiation oncology, who did much of her search while at the University of Maryland’s Greenebaum Cancer Center in Baltimore. In this analysis, women treated with breast-conserving therapy and their counterparts treated with mastectomy again had similar 10-year overall survival (83.5% vs. 83.6%, P = .99) and breast cancer–specific survival (85.5% vs. 85.5%, P = .88).

"We found similar survival with either breast-conserving therapy or mastectomy in the treatment of young women with early-stage breast cancer," Dr. Mahmood concluded. "This just serves as a reminder that women should be counseled appropriately regarding their treatment options and should not choose a mastectomy based on an assumption of improved survival."

Dr. Seidman, Dr. Buckley, and Dr. Mahmood reported that they had no relevant conflicts of interest.

A new set of nomograms based on easily assessed risk factors accurately predicts a woman’s likelihood of developing lymphedema after axillary lymph node dissection for breast cancer, researchers are reporting at a breast cancer symposium sponsored by the American Society of Clinical Oncology.

The nomograms, which enable risk assessment throughout the course of treatment using data available at the time, had accuracy exceeding 70%, according to results presented in a press briefing before the meeting.

"The accuracy is the same as mammography to detect breast cancer. ... So that’s a very good statistical tool," said lead author Dr. Jose Bevilacqua, a surgical oncologist at the Hospital Sirio-Libanês in São Paulo, Brazil.

Being able to identify high-risk patients has several potential applications, he added. They could be monitored more closely and offered interventions that might prevent or reduce the severity of lymphedema, such as use of compression sleeves. "The earlier you detect [it], the better is the outcome," Dr. Bevilacqua said.

Additionally, high-risk patients with a positive sentinel lymph node could be counseled about the risk of further surgery. Thus, "you have physicians who make closer follow-up and [have] a better discussion with the patients."

Finally, the nomograms could be applied in clinical research. "These tools might help [ongoing] or new studies to select high-risk patients in order to avoid exposing the low-risk patients to unproven therapies," he explained.

Dr. Andrew Seidman, moderator of the press briefing and a medical oncologist at the Memorial Sloan-Kettering Cancer Center in New York, commended the investigators for a study that "has real practical implications for patients."

"It allows us to identify patients who then can be appropriately triaged for early intervention and perhaps for clinical trials aimed at preventing what many consider inevitable, and that is the development of lymphedema."

The effectiveness of early interventions is controversial, according to Dr. Seidman, who did not report any relevant conflicts of interest. "There are believers and there are nonbelievers," he commented. "What I think this nomogram does is [allow] us in a scientific way to segregate out patients in terms of their risk, and by doing that, we can have more uniform cohorts for which early intervention can be studied more rigorously."

The researchers prospectively followed 1,054 women with unilateral breast cancer who underwent breast-conserving surgery or mastectomy with an axillary lymph node dissection in 2001-2002. Median follow-up was 41 months.

"As far as we know, we have established the largest prospective cohort specifically established to study the incidence and factors associated with lymphedema after axillary node dissection for breast cancer," commented Dr. Bevilacqua.

Using Data to Predict Lymphedema

The women had serial arm volume measurements starting before surgery. To facilitate this process, the researchers created a tool that is now available free online (www.armvolume.com).

They then developed and internally validated three multivariate nomograms (or statistical models) for predicting lymphedema using data available at various time points.

The first model, to be used preoperatively, incorporated age, body mass index, and number of cycles of neoadjuvant chemotherapy infusions in the ipsilateral arm.

The second model, to be used within the first 6 months after surgery, incorporated all the factors from the first plus the extent of axillary dissection, the location of radiation therapy field, and the number of cycles of adjuvant chemotherapy infusions in the ipsilateral arm.

The third model, to be used 6 months or later after surgery, incorporated all the factors from the second, plus the development of postoperative seroma and development of early edema.

Study results showed that within 5 years of axillary lymph node dissection, 30.3% of the women developed lymphedema (defined as a difference in volume of at least 200 mL between arms at 6 months or later after surgery).

All of the risk factors used in the models were significantly associated with the development of lymphedema, Dr. Bevilacqua reported.

"One of the novelties of our study is the [finding] that ipsilateral neoadjuvant chemotherapy infusion is as morbid as adjuvant chemotherapy infusion to increase the risk of lymphedema," he pointed out. "This is somewhat intuitive, but it has never been described, and the great majority of clinical oncologists are not aware of this fact."

For predicting the 5-year risk of lymphedema, the first, second, and third models had accuracy of 70.6%, 72.9%, and 73.6%, respectively. The investigators have converted the models into free, user-friendly calculators that are available online (www.lymphedemarisk.com) during the ASCO Breast Cancer Symposium (Sept. 8-10), but will be taken off line until the manuscript is published, after which they are to become available again.

Dr. Bevilacqua reported that he had no relevant conflicts of interest.

A new set of nomograms based on easily assessed risk factors accurately predicts a woman’s likelihood of developing lymphedema after axillary lymph node dissection for breast cancer, researchers are reporting at a breast cancer symposium sponsored by the American Society of Clinical Oncology.

The nomograms, which enable risk assessment throughout the course of treatment using data available at the time, had accuracy exceeding 70%, according to results presented in a press briefing before the meeting.

"The accuracy is the same as mammography to detect breast cancer. ... So that’s a very good statistical tool," said lead author Dr. Jose Bevilacqua, a surgical oncologist at the Hospital Sirio-Libanês in São Paulo, Brazil.

Being able to identify high-risk patients has several potential applications, he added. They could be monitored more closely and offered interventions that might prevent or reduce the severity of lymphedema, such as use of compression sleeves. "The earlier you detect [it], the better is the outcome," Dr. Bevilacqua said.

Additionally, high-risk patients with a positive sentinel lymph node could be counseled about the risk of further surgery. Thus, "you have physicians who make closer follow-up and [have] a better discussion with the patients."

Finally, the nomograms could be applied in clinical research. "These tools might help [ongoing] or new studies to select high-risk patients in order to avoid exposing the low-risk patients to unproven therapies," he explained.

Dr. Andrew Seidman, moderator of the press briefing and a medical oncologist at the Memorial Sloan-Kettering Cancer Center in New York, commended the investigators for a study that "has real practical implications for patients."

"It allows us to identify patients who then can be appropriately triaged for early intervention and perhaps for clinical trials aimed at preventing what many consider inevitable, and that is the development of lymphedema."

The effectiveness of early interventions is controversial, according to Dr. Seidman, who did not report any relevant conflicts of interest. "There are believers and there are nonbelievers," he commented. "What I think this nomogram does is [allow] us in a scientific way to segregate out patients in terms of their risk, and by doing that, we can have more uniform cohorts for which early intervention can be studied more rigorously."

The researchers prospectively followed 1,054 women with unilateral breast cancer who underwent breast-conserving surgery or mastectomy with an axillary lymph node dissection in 2001-2002. Median follow-up was 41 months.

"As far as we know, we have established the largest prospective cohort specifically established to study the incidence and factors associated with lymphedema after axillary node dissection for breast cancer," commented Dr. Bevilacqua.

Using Data to Predict Lymphedema

The women had serial arm volume measurements starting before surgery. To facilitate this process, the researchers created a tool that is now available free online (www.armvolume.com).

They then developed and internally validated three multivariate nomograms (or statistical models) for predicting lymphedema using data available at various time points.

The first model, to be used preoperatively, incorporated age, body mass index, and number of cycles of neoadjuvant chemotherapy infusions in the ipsilateral arm.

The second model, to be used within the first 6 months after surgery, incorporated all the factors from the first plus the extent of axillary dissection, the location of radiation therapy field, and the number of cycles of adjuvant chemotherapy infusions in the ipsilateral arm.

The third model, to be used 6 months or later after surgery, incorporated all the factors from the second, plus the development of postoperative seroma and development of early edema.

Study results showed that within 5 years of axillary lymph node dissection, 30.3% of the women developed lymphedema (defined as a difference in volume of at least 200 mL between arms at 6 months or later after surgery).

All of the risk factors used in the models were significantly associated with the development of lymphedema, Dr. Bevilacqua reported.

"One of the novelties of our study is the [finding] that ipsilateral neoadjuvant chemotherapy infusion is as morbid as adjuvant chemotherapy infusion to increase the risk of lymphedema," he pointed out. "This is somewhat intuitive, but it has never been described, and the great majority of clinical oncologists are not aware of this fact."

For predicting the 5-year risk of lymphedema, the first, second, and third models had accuracy of 70.6%, 72.9%, and 73.6%, respectively. The investigators have converted the models into free, user-friendly calculators that are available online (www.lymphedemarisk.com) during the ASCO Breast Cancer Symposium (Sept. 8-10), but will be taken off line until the manuscript is published, after which they are to become available again.

Dr. Bevilacqua reported that he had no relevant conflicts of interest.

A new set of nomograms based on easily assessed risk factors accurately predicts a woman’s likelihood of developing lymphedema after axillary lymph node dissection for breast cancer, researchers are reporting at a breast cancer symposium sponsored by the American Society of Clinical Oncology.

The nomograms, which enable risk assessment throughout the course of treatment using data available at the time, had accuracy exceeding 70%, according to results presented in a press briefing before the meeting.

"The accuracy is the same as mammography to detect breast cancer. ... So that’s a very good statistical tool," said lead author Dr. Jose Bevilacqua, a surgical oncologist at the Hospital Sirio-Libanês in São Paulo, Brazil.

Being able to identify high-risk patients has several potential applications, he added. They could be monitored more closely and offered interventions that might prevent or reduce the severity of lymphedema, such as use of compression sleeves. "The earlier you detect [it], the better is the outcome," Dr. Bevilacqua said.

Additionally, high-risk patients with a positive sentinel lymph node could be counseled about the risk of further surgery. Thus, "you have physicians who make closer follow-up and [have] a better discussion with the patients."

Finally, the nomograms could be applied in clinical research. "These tools might help [ongoing] or new studies to select high-risk patients in order to avoid exposing the low-risk patients to unproven therapies," he explained.

Dr. Andrew Seidman, moderator of the press briefing and a medical oncologist at the Memorial Sloan-Kettering Cancer Center in New York, commended the investigators for a study that "has real practical implications for patients."

"It allows us to identify patients who then can be appropriately triaged for early intervention and perhaps for clinical trials aimed at preventing what many consider inevitable, and that is the development of lymphedema."

The effectiveness of early interventions is controversial, according to Dr. Seidman, who did not report any relevant conflicts of interest. "There are believers and there are nonbelievers," he commented. "What I think this nomogram does is [allow] us in a scientific way to segregate out patients in terms of their risk, and by doing that, we can have more uniform cohorts for which early intervention can be studied more rigorously."

The researchers prospectively followed 1,054 women with unilateral breast cancer who underwent breast-conserving surgery or mastectomy with an axillary lymph node dissection in 2001-2002. Median follow-up was 41 months.

"As far as we know, we have established the largest prospective cohort specifically established to study the incidence and factors associated with lymphedema after axillary node dissection for breast cancer," commented Dr. Bevilacqua.

Using Data to Predict Lymphedema

The women had serial arm volume measurements starting before surgery. To facilitate this process, the researchers created a tool that is now available free online (www.armvolume.com).

They then developed and internally validated three multivariate nomograms (or statistical models) for predicting lymphedema using data available at various time points.

The first model, to be used preoperatively, incorporated age, body mass index, and number of cycles of neoadjuvant chemotherapy infusions in the ipsilateral arm.

The second model, to be used within the first 6 months after surgery, incorporated all the factors from the first plus the extent of axillary dissection, the location of radiation therapy field, and the number of cycles of adjuvant chemotherapy infusions in the ipsilateral arm.

The third model, to be used 6 months or later after surgery, incorporated all the factors from the second, plus the development of postoperative seroma and development of early edema.

Study results showed that within 5 years of axillary lymph node dissection, 30.3% of the women developed lymphedema (defined as a difference in volume of at least 200 mL between arms at 6 months or later after surgery).

All of the risk factors used in the models were significantly associated with the development of lymphedema, Dr. Bevilacqua reported.

"One of the novelties of our study is the [finding] that ipsilateral neoadjuvant chemotherapy infusion is as morbid as adjuvant chemotherapy infusion to increase the risk of lymphedema," he pointed out. "This is somewhat intuitive, but it has never been described, and the great majority of clinical oncologists are not aware of this fact."

For predicting the 5-year risk of lymphedema, the first, second, and third models had accuracy of 70.6%, 72.9%, and 73.6%, respectively. The investigators have converted the models into free, user-friendly calculators that are available online (www.lymphedemarisk.com) during the ASCO Breast Cancer Symposium (Sept. 8-10), but will be taken off line until the manuscript is published, after which they are to become available again.

Dr. Bevilacqua reported that he had no relevant conflicts of interest.

Many breast cancer patients would have more advanced disease at diagnosis and face harsher treatment if recently updated screening guidelines of the U.S. Preventive Services Task Force were widely adopted, suggests a retrospective cohort study of more than 5,000 women with breast cancer in Michigan.

Study results, being reported this week at a breast cancer symposium sponsored by the American Society of Clinical Oncology, show that nearly a third of the women’s cancers were detected by palpation. The guidelines do not advocate for self-exams at all and question the usefulness of clinical breast exams after age 40.

Additionally, nearly half of the cancers in women younger than 50 years were detected by mammography, while the guidelines now recommend against this practice in the 40- to 49-year age group.

Women with palpation-detected cancers had later-stage disease and were significantly more likely to undergo mastectomy and receive chemotherapy than were those with mammography-detected cancers.

"Annual screening mammograms and evaluation of palpable breast masses are important tools in breast cancer detection," second author Dr. Jamie Caughran said during a premeeting press briefing from the American Society of Clinical Oncology (ASCO).

She declined to say whether the study’s results contradict the U.S. Preventive Services Task Force (USPSTF) guidelines, as the investigators did not have adequate information on the women’s screening history.

But "we take this data to conclude that you’re better off if you can ... have your cancer detected by mammography – that you are more likely to have options and less likely to need aggressive treatment. So ... we would support the rest of the societies that continue to recommend annual screening mammography starting at age 40," she said.

Additionally, this study "highlights the still-significant number of women who present with a palpable mass that shouldn’t be overlooked by physicians even if they have a negative mammogram," pointed out Dr. Caughran, medical director of the Comprehensive Breast Center at the Lacks Cancer Center in Grand Rapids, Mich. "So it just continues to reinforce what we believe is inherently true."

Dr. Andrew Seidman, moderator of the press briefing and a medical oncologist at the Memorial Sloan-Kettering Cancer Center in New York City, commented that the appropriate age for starting screening mammography remains controversial.

"A lot of the debate and focus regarding the utility of mammography have been on overall survival and breast cancer–specific survival, and I certainly think that is the most important end point," he said, noting that the study speaks to another important end point – reduced intensity of treatment.

"As a medical oncologist or chemotherapist, I think this is a very important gain, independent of any potential survival benefit," he said. "Having less disfiguring surgery and the ability to deliver less chemotherapy based on the stage at diagnosis are for me a step forward."

This newest study will not quell the debate, according to Dr. Seidman. "Undoubtedly, this area will continue to remain an area of controversy for some," he said. "But certainly, women in this age group would be well served to know about this data."

In the study, Dr. Caughran and her colleagues analyzed data from a statewide breast cancer registry managed by the Michigan Breast Oncology Quality Initiative, identifying 5,628 women who received a diagnosis of stage 0 to III breast cancer between 2006 and 2009. Their average age was 59.4 years.

In the cohort overall, 65.5% of breast cancers were detected by mammography, 29.8% by palpation, and 4.7% by other means.

Fully 90% of the cancers detected by palpation were detected by the patient herself, although "it’s unclear if the patients ... were practicing regular breast self-examination or if these were incidental findings," noted Dr. Caughran.

When analyses were restricted to women younger than 50 years of age, 48.3% of breast cancers were detected by mammography, 46.1% by palpation, and 5.6% by other means.

Palpation-detected cancers were of later stages (P less than .0001) – two-thirds were stage II or higher – and were more often treated with mastectomy (45.8% vs. 27.1%, P less than .0001) and with chemotherapy (22.7% vs. 15.7%, P less than .0001).

Dr. Caughran and Dr. Seidman reported that they had no relevant conflicts of interest.

Many breast cancer patients would have more advanced disease at diagnosis and face harsher treatment if recently updated screening guidelines of the U.S. Preventive Services Task Force were widely adopted, suggests a retrospective cohort study of more than 5,000 women with breast cancer in Michigan.

Study results, being reported this week at a breast cancer symposium sponsored by the American Society of Clinical Oncology, show that nearly a third of the women’s cancers were detected by palpation. The guidelines do not advocate for self-exams at all and question the usefulness of clinical breast exams after age 40.

Additionally, nearly half of the cancers in women younger than 50 years were detected by mammography, while the guidelines now recommend against this practice in the 40- to 49-year age group.

Women with palpation-detected cancers had later-stage disease and were significantly more likely to undergo mastectomy and receive chemotherapy than were those with mammography-detected cancers.

"Annual screening mammograms and evaluation of palpable breast masses are important tools in breast cancer detection," second author Dr. Jamie Caughran said during a premeeting press briefing from the American Society of Clinical Oncology (ASCO).

She declined to say whether the study’s results contradict the U.S. Preventive Services Task Force (USPSTF) guidelines, as the investigators did not have adequate information on the women’s screening history.

But "we take this data to conclude that you’re better off if you can ... have your cancer detected by mammography – that you are more likely to have options and less likely to need aggressive treatment. So ... we would support the rest of the societies that continue to recommend annual screening mammography starting at age 40," she said.

Additionally, this study "highlights the still-significant number of women who present with a palpable mass that shouldn’t be overlooked by physicians even if they have a negative mammogram," pointed out Dr. Caughran, medical director of the Comprehensive Breast Center at the Lacks Cancer Center in Grand Rapids, Mich. "So it just continues to reinforce what we believe is inherently true."

Dr. Andrew Seidman, moderator of the press briefing and a medical oncologist at the Memorial Sloan-Kettering Cancer Center in New York City, commented that the appropriate age for starting screening mammography remains controversial.

"A lot of the debate and focus regarding the utility of mammography have been on overall survival and breast cancer–specific survival, and I certainly think that is the most important end point," he said, noting that the study speaks to another important end point – reduced intensity of treatment.

"As a medical oncologist or chemotherapist, I think this is a very important gain, independent of any potential survival benefit," he said. "Having less disfiguring surgery and the ability to deliver less chemotherapy based on the stage at diagnosis are for me a step forward."

This newest study will not quell the debate, according to Dr. Seidman. "Undoubtedly, this area will continue to remain an area of controversy for some," he said. "But certainly, women in this age group would be well served to know about this data."

In the study, Dr. Caughran and her colleagues analyzed data from a statewide breast cancer registry managed by the Michigan Breast Oncology Quality Initiative, identifying 5,628 women who received a diagnosis of stage 0 to III breast cancer between 2006 and 2009. Their average age was 59.4 years.

In the cohort overall, 65.5% of breast cancers were detected by mammography, 29.8% by palpation, and 4.7% by other means.

Fully 90% of the cancers detected by palpation were detected by the patient herself, although "it’s unclear if the patients ... were practicing regular breast self-examination or if these were incidental findings," noted Dr. Caughran.

When analyses were restricted to women younger than 50 years of age, 48.3% of breast cancers were detected by mammography, 46.1% by palpation, and 5.6% by other means.

Palpation-detected cancers were of later stages (P less than .0001) – two-thirds were stage II or higher – and were more often treated with mastectomy (45.8% vs. 27.1%, P less than .0001) and with chemotherapy (22.7% vs. 15.7%, P less than .0001).

Dr. Caughran and Dr. Seidman reported that they had no relevant conflicts of interest.

Many breast cancer patients would have more advanced disease at diagnosis and face harsher treatment if recently updated screening guidelines of the U.S. Preventive Services Task Force were widely adopted, suggests a retrospective cohort study of more than 5,000 women with breast cancer in Michigan.

Study results, being reported this week at a breast cancer symposium sponsored by the American Society of Clinical Oncology, show that nearly a third of the women’s cancers were detected by palpation. The guidelines do not advocate for self-exams at all and question the usefulness of clinical breast exams after age 40.

Additionally, nearly half of the cancers in women younger than 50 years were detected by mammography, while the guidelines now recommend against this practice in the 40- to 49-year age group.

Women with palpation-detected cancers had later-stage disease and were significantly more likely to undergo mastectomy and receive chemotherapy than were those with mammography-detected cancers.

"Annual screening mammograms and evaluation of palpable breast masses are important tools in breast cancer detection," second author Dr. Jamie Caughran said during a premeeting press briefing from the American Society of Clinical Oncology (ASCO).

She declined to say whether the study’s results contradict the U.S. Preventive Services Task Force (USPSTF) guidelines, as the investigators did not have adequate information on the women’s screening history.

But "we take this data to conclude that you’re better off if you can ... have your cancer detected by mammography – that you are more likely to have options and less likely to need aggressive treatment. So ... we would support the rest of the societies that continue to recommend annual screening mammography starting at age 40," she said.

Additionally, this study "highlights the still-significant number of women who present with a palpable mass that shouldn’t be overlooked by physicians even if they have a negative mammogram," pointed out Dr. Caughran, medical director of the Comprehensive Breast Center at the Lacks Cancer Center in Grand Rapids, Mich. "So it just continues to reinforce what we believe is inherently true."

Dr. Andrew Seidman, moderator of the press briefing and a medical oncologist at the Memorial Sloan-Kettering Cancer Center in New York City, commented that the appropriate age for starting screening mammography remains controversial.

"A lot of the debate and focus regarding the utility of mammography have been on overall survival and breast cancer–specific survival, and I certainly think that is the most important end point," he said, noting that the study speaks to another important end point – reduced intensity of treatment.

"As a medical oncologist or chemotherapist, I think this is a very important gain, independent of any potential survival benefit," he said. "Having less disfiguring surgery and the ability to deliver less chemotherapy based on the stage at diagnosis are for me a step forward."

This newest study will not quell the debate, according to Dr. Seidman. "Undoubtedly, this area will continue to remain an area of controversy for some," he said. "But certainly, women in this age group would be well served to know about this data."

In the study, Dr. Caughran and her colleagues analyzed data from a statewide breast cancer registry managed by the Michigan Breast Oncology Quality Initiative, identifying 5,628 women who received a diagnosis of stage 0 to III breast cancer between 2006 and 2009. Their average age was 59.4 years.

In the cohort overall, 65.5% of breast cancers were detected by mammography, 29.8% by palpation, and 4.7% by other means.

Fully 90% of the cancers detected by palpation were detected by the patient herself, although "it’s unclear if the patients ... were practicing regular breast self-examination or if these were incidental findings," noted Dr. Caughran.

When analyses were restricted to women younger than 50 years of age, 48.3% of breast cancers were detected by mammography, 46.1% by palpation, and 5.6% by other means.

Palpation-detected cancers were of later stages (P less than .0001) – two-thirds were stage II or higher – and were more often treated with mastectomy (45.8% vs. 27.1%, P less than .0001) and with chemotherapy (22.7% vs. 15.7%, P less than .0001).

Dr. Caughran and Dr. Seidman reported that they had no relevant conflicts of interest.

Major Finding: The positive predictive value of ultrasound-diagnosed fetal macrosomia, compared with actual macrosomia at birth, was just 37.4%.

Data Source: An observational cohort study of 235 pregnant women who had an ultrasound within 2 weeks of delivery indicating an estimated fetal weight of at least 4,500 g.

Disclosures: Dr. Wagner reported that she had no relevant financial disclosures.

VANCOUVER, B.C. – An ultrasound diagnosis of fetal macrosomia at term is inaccurate in the majority of cases, and this inaccuracy may be contributing to unnecessary cesarean deliveries, new data suggest.

In an observational cohort study of 235 pregnancies at term in which US measurements led to a diagnosis of fetal macrosomia, only about a third of the infants were actually macrosomic at birth. Additionally, these pregnancies with US-diagnosed fetal macrosomia were more than twice as likely as all pregnancies in the population to end in cesarean delivery, according to results reported at the meeting.

US-estimated fetal weight “is not very accurate, and we have to counsel patients on that, when they come to ultrasounds and they are worried that they are going to have this [enormous] monstrosity of a baby,” lead investigator Dr. Alese Wagner said in an interview. “You can tell them [that] most of the time, we are off.”

She further recommended that physicians keep this new information in mind when it comes to recommending delivery interventions for a pregnancy in which the US suggests macrosomia.

Surprisingly, the accuracy of US in assessing fetal weight is similar to that of simple clinical palpation, according to Dr. Wagner, a third-year ob.gyn. resident at the University of Calgary in Alberta.

The study used the Hadlock formula for calculating weight from US fetal measurements, “which is supposed to be one of the better formulas for macrosomic infants,” she noted. But through the years, “as the technology has gotten better – these ultrasound machines that we have now are amazing [in] what they can do – this [accuracy] hasn't gotten better,” she added, speculating that the disconnect may in part be the result of reliance on simple measurements that don't take into account tissue densities.

Additionally, US assessment late in pregnancy is inherently more difficult because the fetus is so low in the pelvis and there is less amniotic fluid. Maternal body habitus also may play a role.

Using the clinical database of a tertiary referral center for the years 2005-2009, researchers identified 235 women who had a US exam within 2 weeks of delivery that indicated the presence of fetal macrosomia (defined as an estimated fetal weight of at least 4,500 g, as calculated via the Hadlock formula). However, they found that at delivery, only 88 of these infants had an actual birth weight of at least 4,500 g, for a positive predictive value of merely 37.4%, according to results reported in a poster session. The median estimated fetal weight was 4,693 g, whereas the median birth weight was 4,368 g.

The mean percentage error of the estimated fetal weight was 8.6% overall. Viewed another way, 44% of the weights were off by more than 10%, and 7% were off by more than 20%.

There were only weak correlations between estimated fetal weight and birth weight, as well as between the individual fetal measurements used in the Hadlock formula and birth weight.

The mode of delivery was cesarean section in 66% of the pregnancies, compared with just 29% of all pregnancies in Calgary during the same period. “So it's [more than] double, the percentage who are getting C-sections, on what is [an inaccurate weight],” said Dr. Wagner.

Before the study, “there was a general feeling that we were pretty [far off] in the estimates of the fetal weights that we were getting closer to term, especially for the bigger babies,” she commented. “People … usually thought that they were overestimating them, so it was nice to actually look at … what the actual numbers were.

Physicians can tell their worried patients that most of the time, the ultrasound calculations 'are off.'

Source DR. WAGNER

Major Finding: The positive predictive value of ultrasound-diagnosed fetal macrosomia, compared with actual macrosomia at birth, was just 37.4%.

Data Source: An observational cohort study of 235 pregnant women who had an ultrasound within 2 weeks of delivery indicating an estimated fetal weight of at least 4,500 g.

Disclosures: Dr. Wagner reported that she had no relevant financial disclosures.

VANCOUVER, B.C. – An ultrasound diagnosis of fetal macrosomia at term is inaccurate in the majority of cases, and this inaccuracy may be contributing to unnecessary cesarean deliveries, new data suggest.

In an observational cohort study of 235 pregnancies at term in which US measurements led to a diagnosis of fetal macrosomia, only about a third of the infants were actually macrosomic at birth. Additionally, these pregnancies with US-diagnosed fetal macrosomia were more than twice as likely as all pregnancies in the population to end in cesarean delivery, according to results reported at the meeting.

US-estimated fetal weight “is not very accurate, and we have to counsel patients on that, when they come to ultrasounds and they are worried that they are going to have this [enormous] monstrosity of a baby,” lead investigator Dr. Alese Wagner said in an interview. “You can tell them [that] most of the time, we are off.”

She further recommended that physicians keep this new information in mind when it comes to recommending delivery interventions for a pregnancy in which the US suggests macrosomia.

Surprisingly, the accuracy of US in assessing fetal weight is similar to that of simple clinical palpation, according to Dr. Wagner, a third-year ob.gyn. resident at the University of Calgary in Alberta.

The study used the Hadlock formula for calculating weight from US fetal measurements, “which is supposed to be one of the better formulas for macrosomic infants,” she noted. But through the years, “as the technology has gotten better – these ultrasound machines that we have now are amazing [in] what they can do – this [accuracy] hasn't gotten better,” she added, speculating that the disconnect may in part be the result of reliance on simple measurements that don't take into account tissue densities.

Additionally, US assessment late in pregnancy is inherently more difficult because the fetus is so low in the pelvis and there is less amniotic fluid. Maternal body habitus also may play a role.

Using the clinical database of a tertiary referral center for the years 2005-2009, researchers identified 235 women who had a US exam within 2 weeks of delivery that indicated the presence of fetal macrosomia (defined as an estimated fetal weight of at least 4,500 g, as calculated via the Hadlock formula). However, they found that at delivery, only 88 of these infants had an actual birth weight of at least 4,500 g, for a positive predictive value of merely 37.4%, according to results reported in a poster session. The median estimated fetal weight was 4,693 g, whereas the median birth weight was 4,368 g.

The mean percentage error of the estimated fetal weight was 8.6% overall. Viewed another way, 44% of the weights were off by more than 10%, and 7% were off by more than 20%.

There were only weak correlations between estimated fetal weight and birth weight, as well as between the individual fetal measurements used in the Hadlock formula and birth weight.

The mode of delivery was cesarean section in 66% of the pregnancies, compared with just 29% of all pregnancies in Calgary during the same period. “So it's [more than] double, the percentage who are getting C-sections, on what is [an inaccurate weight],” said Dr. Wagner.

Before the study, “there was a general feeling that we were pretty [far off] in the estimates of the fetal weights that we were getting closer to term, especially for the bigger babies,” she commented. “People … usually thought that they were overestimating them, so it was nice to actually look at … what the actual numbers were.

Physicians can tell their worried patients that most of the time, the ultrasound calculations 'are off.'

Source DR. WAGNER

Major Finding: The positive predictive value of ultrasound-diagnosed fetal macrosomia, compared with actual macrosomia at birth, was just 37.4%.

Data Source: An observational cohort study of 235 pregnant women who had an ultrasound within 2 weeks of delivery indicating an estimated fetal weight of at least 4,500 g.

Disclosures: Dr. Wagner reported that she had no relevant financial disclosures.

VANCOUVER, B.C. – An ultrasound diagnosis of fetal macrosomia at term is inaccurate in the majority of cases, and this inaccuracy may be contributing to unnecessary cesarean deliveries, new data suggest.

In an observational cohort study of 235 pregnancies at term in which US measurements led to a diagnosis of fetal macrosomia, only about a third of the infants were actually macrosomic at birth. Additionally, these pregnancies with US-diagnosed fetal macrosomia were more than twice as likely as all pregnancies in the population to end in cesarean delivery, according to results reported at the meeting.

US-estimated fetal weight “is not very accurate, and we have to counsel patients on that, when they come to ultrasounds and they are worried that they are going to have this [enormous] monstrosity of a baby,” lead investigator Dr. Alese Wagner said in an interview. “You can tell them [that] most of the time, we are off.”

She further recommended that physicians keep this new information in mind when it comes to recommending delivery interventions for a pregnancy in which the US suggests macrosomia.

Surprisingly, the accuracy of US in assessing fetal weight is similar to that of simple clinical palpation, according to Dr. Wagner, a third-year ob.gyn. resident at the University of Calgary in Alberta.

The study used the Hadlock formula for calculating weight from US fetal measurements, “which is supposed to be one of the better formulas for macrosomic infants,” she noted. But through the years, “as the technology has gotten better – these ultrasound machines that we have now are amazing [in] what they can do – this [accuracy] hasn't gotten better,” she added, speculating that the disconnect may in part be the result of reliance on simple measurements that don't take into account tissue densities.

Additionally, US assessment late in pregnancy is inherently more difficult because the fetus is so low in the pelvis and there is less amniotic fluid. Maternal body habitus also may play a role.

Using the clinical database of a tertiary referral center for the years 2005-2009, researchers identified 235 women who had a US exam within 2 weeks of delivery that indicated the presence of fetal macrosomia (defined as an estimated fetal weight of at least 4,500 g, as calculated via the Hadlock formula). However, they found that at delivery, only 88 of these infants had an actual birth weight of at least 4,500 g, for a positive predictive value of merely 37.4%, according to results reported in a poster session. The median estimated fetal weight was 4,693 g, whereas the median birth weight was 4,368 g.

The mean percentage error of the estimated fetal weight was 8.6% overall. Viewed another way, 44% of the weights were off by more than 10%, and 7% were off by more than 20%.

There were only weak correlations between estimated fetal weight and birth weight, as well as between the individual fetal measurements used in the Hadlock formula and birth weight.

The mode of delivery was cesarean section in 66% of the pregnancies, compared with just 29% of all pregnancies in Calgary during the same period. “So it's [more than] double, the percentage who are getting C-sections, on what is [an inaccurate weight],” said Dr. Wagner.

Before the study, “there was a general feeling that we were pretty [far off] in the estimates of the fetal weights that we were getting closer to term, especially for the bigger babies,” she commented. “People … usually thought that they were overestimating them, so it was nice to actually look at … what the actual numbers were.

Physicians can tell their worried patients that most of the time, the ultrasound calculations 'are off.'

Source DR. WAGNER

Major Finding: The negative predictive values for preterm delivery were similarly high for ph IGFBP-1 and fetal fibronectin; the positive predictive values were poor for both.

Data Source: A prospective cohort study among 349 women with symptoms of preterm labor.

Disclosures: Dr. Cooper reported that she had no relevant financial disclosures.

VANCOUVER, B.C. – The phosphorylated insulinlike growth factor binding protein–1 test may edge out the fetal fibronectin test when it comes to predicting preterm delivery, a study has shown.

In the prospective cohort study among 349 women with symptoms of preterm labor, the two tests had similarly good negative predictive values, 0.86 and 0.88, researchers reported at the meeting. Both had poor sensitivity and positive predictive values.

However, the phosphorylated insulinlike growth factor binding protein–1 (ph IGFBP-1) test (marketed outside the United States as the Actim Partus test) costs about one-fourth as much as the fetal fibronectin test. Also, the former is a simple dipstick test that can be run at the bedside, and it differs in not being affected by recent intercourse or vaginal examinations.

The Actim Partus test is not currently available in the United States. “The timeline for its clearance and availability in the United States is … not yet known,” according to a spokeswoman for Medix Biochemica, Kauniainen, Finland.

“The Actim Partus compares favorably to fetal fibronectin for the ability to rule out preterm labor,” said lead investigator Dr. Stephanie Cooper, program director of maternal-fetal medicine at the University of Calgary (Alta.). “Given the benefit of reduced cost, efficiency, and ability to use it in a broad clinical scenario, institutions should consider using the newer test, the Partus test, until better tools are available.”

Her institution has not yet switched to the new test. “But what I will say is these results definitely make me do fetal fibronectin less,” she commented. “I don't think Partus is a good test, I don't think fibronectin is a good test. … I'm hoping that there's going to be a better test.”

Fetal fibronectin is generally regarded as the gold standard for predicting preterm delivery, according to Dr. Cooper.

However, “it is not a perfect test. In fact, maybe it's more like the bronze standard,” she commented. Its limitations include a poor positive predictive value; false-positivity in women who have recently had a vaginal exam or intercourse; cost; and, usually, the need for a laboratory for analysis.

“Ph IGFBP-1 is released by the cervix following disruption of the choriodecidual barrier, which we believe occurs with the onset of labor,” she explained. It has shown promise for overcoming some of the limitations of the fetal fibronectin test.

The researchers enrolled in the study 349 women who had symptoms of labor preterm (between 24 and 34 weeks' gestation) and no contraindications to vaginal examination.

Women were ineligible if they had ruptured membranes, had antepartum hemorrhage, were in active labor (defined as having a cervix diameter of greater than 3 cm), or had suspected chorioamnionitis.

All of the women received routine care. A swab for fetal fibronectin testing was obtained according to usual protocol; per institutional procedure at the time, the swab was kept for 2 hours and analyzed only if symptoms of labor were still equivocal.

A cervical swab was obtained for ph IGFBP-1 measurement with the Actim Partus test. Patients who were ineligible for a fetal fibronectin test because of a recent vaginal examination or intercourse still had this test. All of these swabs were analyzed by a study registered nurse who was blinded to the patient's clinical course.

The women were 29 years old, on average. The mean gestational age was 29.8 weeks. Forty-three percent were nulliparous, and 16% had previously experienced a preterm birth. Three-fourths had a cervical dilation on admission of 0-1 cm.

Swabs were processed for ph IGFBP-1 in all 349 women, but for fetal fibronectin in only 288 of them. In other words, 17% of the women did not have the latter test run either because they were ineligible because of recent vaginal examination or intercourse or because labor was no longer equivocal after the 2-hour wait.

Overall, 26% of the ph IGFBP-1 test results were positive (had a value of at least 10 mcg/L), and 8% of the fetal fibronectin test results were positive (had a value of at least 50 ng/mL).

Only 16% of the women were delivered preterm (before 37 weeks' gestation). “This just goes to show that the majority of patients who present with preterm labor actually will not deliver preterm,” Dr. Cooper commented.

The ph IGFBP-1 test and the fetal fibronectin test had similarly good negative predictive values for preterm delivery (0.86 and 0.88).

The positive predictive value was poor for both, although somewhat more so for ph IGFBP-1 (0.22 and 0.54).

The ph IGFBP-1 test and the fetal fibronectin test also both had poor sensitivity (39% and 33%), while specificity was marginally poorer for the former test (74% and 95%).

The investigators also assessed the performance of the two tests combined. “There were times when they agreed and times when they didn't agree, but it didn't seem to be that combining them together improved your predictability,” she said.

Recent data suggest that predictability may improve when a biochemical marker is combined with cervical length on ultrasound, noted Dr. Cooper.

“The problem is, we are looking for a rapid bedside test for people in rural areas who don't have resources,” she commented. “So if we start putting cervical length into the mix, then it takes away the primary objective of how do we help people who are living in rural areas that are rural enough to have to make decisions about clinical transfer.”

Major Finding: The negative predictive values for preterm delivery were similarly high for ph IGFBP-1 and fetal fibronectin; the positive predictive values were poor for both.

Data Source: A prospective cohort study among 349 women with symptoms of preterm labor.

Disclosures: Dr. Cooper reported that she had no relevant financial disclosures.

VANCOUVER, B.C. – The phosphorylated insulinlike growth factor binding protein–1 test may edge out the fetal fibronectin test when it comes to predicting preterm delivery, a study has shown.

In the prospective cohort study among 349 women with symptoms of preterm labor, the two tests had similarly good negative predictive values, 0.86 and 0.88, researchers reported at the meeting. Both had poor sensitivity and positive predictive values.

However, the phosphorylated insulinlike growth factor binding protein–1 (ph IGFBP-1) test (marketed outside the United States as the Actim Partus test) costs about one-fourth as much as the fetal fibronectin test. Also, the former is a simple dipstick test that can be run at the bedside, and it differs in not being affected by recent intercourse or vaginal examinations.

The Actim Partus test is not currently available in the United States. “The timeline for its clearance and availability in the United States is … not yet known,” according to a spokeswoman for Medix Biochemica, Kauniainen, Finland.

“The Actim Partus compares favorably to fetal fibronectin for the ability to rule out preterm labor,” said lead investigator Dr. Stephanie Cooper, program director of maternal-fetal medicine at the University of Calgary (Alta.). “Given the benefit of reduced cost, efficiency, and ability to use it in a broad clinical scenario, institutions should consider using the newer test, the Partus test, until better tools are available.”

Her institution has not yet switched to the new test. “But what I will say is these results definitely make me do fetal fibronectin less,” she commented. “I don't think Partus is a good test, I don't think fibronectin is a good test. … I'm hoping that there's going to be a better test.”

Fetal fibronectin is generally regarded as the gold standard for predicting preterm delivery, according to Dr. Cooper.

However, “it is not a perfect test. In fact, maybe it's more like the bronze standard,” she commented. Its limitations include a poor positive predictive value; false-positivity in women who have recently had a vaginal exam or intercourse; cost; and, usually, the need for a laboratory for analysis.

“Ph IGFBP-1 is released by the cervix following disruption of the choriodecidual barrier, which we believe occurs with the onset of labor,” she explained. It has shown promise for overcoming some of the limitations of the fetal fibronectin test.

The researchers enrolled in the study 349 women who had symptoms of labor preterm (between 24 and 34 weeks' gestation) and no contraindications to vaginal examination.

Women were ineligible if they had ruptured membranes, had antepartum hemorrhage, were in active labor (defined as having a cervix diameter of greater than 3 cm), or had suspected chorioamnionitis.

All of the women received routine care. A swab for fetal fibronectin testing was obtained according to usual protocol; per institutional procedure at the time, the swab was kept for 2 hours and analyzed only if symptoms of labor were still equivocal.

A cervical swab was obtained for ph IGFBP-1 measurement with the Actim Partus test. Patients who were ineligible for a fetal fibronectin test because of a recent vaginal examination or intercourse still had this test. All of these swabs were analyzed by a study registered nurse who was blinded to the patient's clinical course.

The women were 29 years old, on average. The mean gestational age was 29.8 weeks. Forty-three percent were nulliparous, and 16% had previously experienced a preterm birth. Three-fourths had a cervical dilation on admission of 0-1 cm.

Swabs were processed for ph IGFBP-1 in all 349 women, but for fetal fibronectin in only 288 of them. In other words, 17% of the women did not have the latter test run either because they were ineligible because of recent vaginal examination or intercourse or because labor was no longer equivocal after the 2-hour wait.

Overall, 26% of the ph IGFBP-1 test results were positive (had a value of at least 10 mcg/L), and 8% of the fetal fibronectin test results were positive (had a value of at least 50 ng/mL).

Only 16% of the women were delivered preterm (before 37 weeks' gestation). “This just goes to show that the majority of patients who present with preterm labor actually will not deliver preterm,” Dr. Cooper commented.

The ph IGFBP-1 test and the fetal fibronectin test had similarly good negative predictive values for preterm delivery (0.86 and 0.88).

The positive predictive value was poor for both, although somewhat more so for ph IGFBP-1 (0.22 and 0.54).

The ph IGFBP-1 test and the fetal fibronectin test also both had poor sensitivity (39% and 33%), while specificity was marginally poorer for the former test (74% and 95%).

The investigators also assessed the performance of the two tests combined. “There were times when they agreed and times when they didn't agree, but it didn't seem to be that combining them together improved your predictability,” she said.

Recent data suggest that predictability may improve when a biochemical marker is combined with cervical length on ultrasound, noted Dr. Cooper.

“The problem is, we are looking for a rapid bedside test for people in rural areas who don't have resources,” she commented. “So if we start putting cervical length into the mix, then it takes away the primary objective of how do we help people who are living in rural areas that are rural enough to have to make decisions about clinical transfer.”

Major Finding: The negative predictive values for preterm delivery were similarly high for ph IGFBP-1 and fetal fibronectin; the positive predictive values were poor for both.

Data Source: A prospective cohort study among 349 women with symptoms of preterm labor.

Disclosures: Dr. Cooper reported that she had no relevant financial disclosures.

VANCOUVER, B.C. – The phosphorylated insulinlike growth factor binding protein–1 test may edge out the fetal fibronectin test when it comes to predicting preterm delivery, a study has shown.

In the prospective cohort study among 349 women with symptoms of preterm labor, the two tests had similarly good negative predictive values, 0.86 and 0.88, researchers reported at the meeting. Both had poor sensitivity and positive predictive values.

However, the phosphorylated insulinlike growth factor binding protein–1 (ph IGFBP-1) test (marketed outside the United States as the Actim Partus test) costs about one-fourth as much as the fetal fibronectin test. Also, the former is a simple dipstick test that can be run at the bedside, and it differs in not being affected by recent intercourse or vaginal examinations.

The Actim Partus test is not currently available in the United States. “The timeline for its clearance and availability in the United States is … not yet known,” according to a spokeswoman for Medix Biochemica, Kauniainen, Finland.

“The Actim Partus compares favorably to fetal fibronectin for the ability to rule out preterm labor,” said lead investigator Dr. Stephanie Cooper, program director of maternal-fetal medicine at the University of Calgary (Alta.). “Given the benefit of reduced cost, efficiency, and ability to use it in a broad clinical scenario, institutions should consider using the newer test, the Partus test, until better tools are available.”

Her institution has not yet switched to the new test. “But what I will say is these results definitely make me do fetal fibronectin less,” she commented. “I don't think Partus is a good test, I don't think fibronectin is a good test. … I'm hoping that there's going to be a better test.”

Fetal fibronectin is generally regarded as the gold standard for predicting preterm delivery, according to Dr. Cooper.

However, “it is not a perfect test. In fact, maybe it's more like the bronze standard,” she commented. Its limitations include a poor positive predictive value; false-positivity in women who have recently had a vaginal exam or intercourse; cost; and, usually, the need for a laboratory for analysis.

“Ph IGFBP-1 is released by the cervix following disruption of the choriodecidual barrier, which we believe occurs with the onset of labor,” she explained. It has shown promise for overcoming some of the limitations of the fetal fibronectin test.

The researchers enrolled in the study 349 women who had symptoms of labor preterm (between 24 and 34 weeks' gestation) and no contraindications to vaginal examination.

Women were ineligible if they had ruptured membranes, had antepartum hemorrhage, were in active labor (defined as having a cervix diameter of greater than 3 cm), or had suspected chorioamnionitis.

All of the women received routine care. A swab for fetal fibronectin testing was obtained according to usual protocol; per institutional procedure at the time, the swab was kept for 2 hours and analyzed only if symptoms of labor were still equivocal.

A cervical swab was obtained for ph IGFBP-1 measurement with the Actim Partus test. Patients who were ineligible for a fetal fibronectin test because of a recent vaginal examination or intercourse still had this test. All of these swabs were analyzed by a study registered nurse who was blinded to the patient's clinical course.

The women were 29 years old, on average. The mean gestational age was 29.8 weeks. Forty-three percent were nulliparous, and 16% had previously experienced a preterm birth. Three-fourths had a cervical dilation on admission of 0-1 cm.

Swabs were processed for ph IGFBP-1 in all 349 women, but for fetal fibronectin in only 288 of them. In other words, 17% of the women did not have the latter test run either because they were ineligible because of recent vaginal examination or intercourse or because labor was no longer equivocal after the 2-hour wait.

Overall, 26% of the ph IGFBP-1 test results were positive (had a value of at least 10 mcg/L), and 8% of the fetal fibronectin test results were positive (had a value of at least 50 ng/mL).

Only 16% of the women were delivered preterm (before 37 weeks' gestation). “This just goes to show that the majority of patients who present with preterm labor actually will not deliver preterm,” Dr. Cooper commented.

The ph IGFBP-1 test and the fetal fibronectin test had similarly good negative predictive values for preterm delivery (0.86 and 0.88).

The positive predictive value was poor for both, although somewhat more so for ph IGFBP-1 (0.22 and 0.54).

The ph IGFBP-1 test and the fetal fibronectin test also both had poor sensitivity (39% and 33%), while specificity was marginally poorer for the former test (74% and 95%).

The investigators also assessed the performance of the two tests combined. “There were times when they agreed and times when they didn't agree, but it didn't seem to be that combining them together improved your predictability,” she said.

Recent data suggest that predictability may improve when a biochemical marker is combined with cervical length on ultrasound, noted Dr. Cooper.

“The problem is, we are looking for a rapid bedside test for people in rural areas who don't have resources,” she commented. “So if we start putting cervical length into the mix, then it takes away the primary objective of how do we help people who are living in rural areas that are rural enough to have to make decisions about clinical transfer.”

Major Finding: Only 29% of women were counseled about gaining a specific amount or range of weight during pregnancy, and 12% were counseled correctly about how much to gain.

Data Source: A cross-sectional survey of 310 pregnant women with a live, singleton gestation, who visited prenatal clinics.

Disclosures: Dr. McDonald reported that she had no relevant financial disclosures.

VANCOUVER, B.C. – When it comes to counseling women about weight gain during pregnancy, there is plenty of room for improvement, new data suggest.

In a survey of more than 300 pregnant women, fewer than a third reported being counseled on the topic, researchers reported at the meeting. And even fewer, merely an eighth, were counseled correctly about how much weight to gain.

In likely related findings, three-fourths of women who were overweight or obese before conceiving planned to gain more weight than was recommended for them in guidelines.

“A lack of reported counseling has been associated in the literature with inappropriate weight gain, both excessive and inadequate,” said lead investigator Dr. Sarah McDonald, an ob.gyn at McMaster University in Hamilton, Ont. “So these findings were very concerning for us.”

She noted that most women who were approached agreed to participate in the survey and were comfortable about discussing weight. Therefore, “it appeared unlikely that the lack of reported counseling was due to patient-driven factors, apart from possibly forgetting.”

Interestingly, a staggered companion survey of the providers had dramatically different findings, showing high reported rates of counseling. “It was like I was surveying people on a different planet,” she commented. “We think we are doing very well,” yet there is an obvious discrepancy that is as yet unexplained.

Citing the obesity epidemic, Dr. McDonald endorsed repeated counseling of women about weight, both before and during pregnancy.

“Obviously, an optimal BMI [body mass index] prepregnancy is ideal, but that's not the situation where most of us come into contact with our patients; it's when they are already pregnant. Then, I think talking about optimal gestational weight gain to not compound the problems of overweight and obesity is important,” she said. “But given the size of the [obesity] epidemic, [the approach has] got to be multipronged.”

In 2009, the U.S. Institute of Medicine released new recommendations regarding gestational weight gain, tailored to prepregnancy BMI, that have been adopted by Canada and other countries.

“However, previous studies done in the era of the 1990 guidelines have shown that only about 30%-40% of pregnant women gained the appropriate amount of weight during pregnancy,” Dr. McDonald noted. “And we were curious what was going on in the era of the new guidelines.”

The investigators surveyed 310 women (94% of those approached) who made at least one visit to representative Hamilton prenatal clinics, other than for pregnancy diagnosis, and currently had a live, singleton gestation. The women's mean age was 30 years, and the median gestational age was 33.0 weeks. Fully 74% were white, and for 43%, the birth would be their first. They had a mean prepregnancy BMI of 25.1 kg/m

“Interestingly enough, 84% of the women reported that they were either comfortable or very comfortable talking about weight-related issues with their care provider, despite the fact that the mean BMI [in this study] is already in the overweight category prepregnancy,” Dr. McDonald observed.

Only 29% of the women reported that their provider counseled them to gain a specific amount or range of weight, and for just 12% overall, that amount or range was correct according to the new guidelines. Only about a quarter of women reported being told that there were risks associated with gaining too much or too little weight during pregnancy.

The median number of prenatal visits before the survey was 10 for the study population, she pointed out, and “so there were multiple opportunities for discussion about weight gain.”

“We wondered, are clinicians just too busy to be talking about weight and weight-related matters, and nutrition, and preventive-type medicine?” said Dr. McDonald. Yet nearly all of the women (97%) reported being counseled to take a vitamin.

When asked how much weight they planned to gain during pregnancy, only 12%-54% of women, depending on prepregnancy BMI category, cited an amount within the guideline-recommended range for them. In particular, in a finding that she described as “alarming,” 75% of overweight and obese women were planning to gain more weight than was recommended for them.

The proportion of women counseled about weight gain differed by the type of provider that had provided the majority of a woman's pregnancy care; it was 40% for midwives, 24% for obstetricians, 23% for general practitioners, and 28% for other providers. The proportion that was correctly counseled showed a similar pattern, but the differences were not significant.

Clinicians' survey responses were so different, 'it was like I was surveying people on a different planet.'

Source DR. McDONALD

Major Finding: Only 29% of women were counseled about gaining a specific amount or range of weight during pregnancy, and 12% were counseled correctly about how much to gain.

Data Source: A cross-sectional survey of 310 pregnant women with a live, singleton gestation, who visited prenatal clinics.

Disclosures: Dr. McDonald reported that she had no relevant financial disclosures.

VANCOUVER, B.C. – When it comes to counseling women about weight gain during pregnancy, there is plenty of room for improvement, new data suggest.

In a survey of more than 300 pregnant women, fewer than a third reported being counseled on the topic, researchers reported at the meeting. And even fewer, merely an eighth, were counseled correctly about how much weight to gain.

In likely related findings, three-fourths of women who were overweight or obese before conceiving planned to gain more weight than was recommended for them in guidelines.

“A lack of reported counseling has been associated in the literature with inappropriate weight gain, both excessive and inadequate,” said lead investigator Dr. Sarah McDonald, an ob.gyn at McMaster University in Hamilton, Ont. “So these findings were very concerning for us.”

She noted that most women who were approached agreed to participate in the survey and were comfortable about discussing weight. Therefore, “it appeared unlikely that the lack of reported counseling was due to patient-driven factors, apart from possibly forgetting.”

Interestingly, a staggered companion survey of the providers had dramatically different findings, showing high reported rates of counseling. “It was like I was surveying people on a different planet,” she commented. “We think we are doing very well,” yet there is an obvious discrepancy that is as yet unexplained.

Citing the obesity epidemic, Dr. McDonald endorsed repeated counseling of women about weight, both before and during pregnancy.

“Obviously, an optimal BMI [body mass index] prepregnancy is ideal, but that's not the situation where most of us come into contact with our patients; it's when they are already pregnant. Then, I think talking about optimal gestational weight gain to not compound the problems of overweight and obesity is important,” she said. “But given the size of the [obesity] epidemic, [the approach has] got to be multipronged.”

In 2009, the U.S. Institute of Medicine released new recommendations regarding gestational weight gain, tailored to prepregnancy BMI, that have been adopted by Canada and other countries.

“However, previous studies done in the era of the 1990 guidelines have shown that only about 30%-40% of pregnant women gained the appropriate amount of weight during pregnancy,” Dr. McDonald noted. “And we were curious what was going on in the era of the new guidelines.”

The investigators surveyed 310 women (94% of those approached) who made at least one visit to representative Hamilton prenatal clinics, other than for pregnancy diagnosis, and currently had a live, singleton gestation. The women's mean age was 30 years, and the median gestational age was 33.0 weeks. Fully 74% were white, and for 43%, the birth would be their first. They had a mean prepregnancy BMI of 25.1 kg/m

“Interestingly enough, 84% of the women reported that they were either comfortable or very comfortable talking about weight-related issues with their care provider, despite the fact that the mean BMI [in this study] is already in the overweight category prepregnancy,” Dr. McDonald observed.

Only 29% of the women reported that their provider counseled them to gain a specific amount or range of weight, and for just 12% overall, that amount or range was correct according to the new guidelines. Only about a quarter of women reported being told that there were risks associated with gaining too much or too little weight during pregnancy.

The median number of prenatal visits before the survey was 10 for the study population, she pointed out, and “so there were multiple opportunities for discussion about weight gain.”

“We wondered, are clinicians just too busy to be talking about weight and weight-related matters, and nutrition, and preventive-type medicine?” said Dr. McDonald. Yet nearly all of the women (97%) reported being counseled to take a vitamin.

When asked how much weight they planned to gain during pregnancy, only 12%-54% of women, depending on prepregnancy BMI category, cited an amount within the guideline-recommended range for them. In particular, in a finding that she described as “alarming,” 75% of overweight and obese women were planning to gain more weight than was recommended for them.

The proportion of women counseled about weight gain differed by the type of provider that had provided the majority of a woman's pregnancy care; it was 40% for midwives, 24% for obstetricians, 23% for general practitioners, and 28% for other providers. The proportion that was correctly counseled showed a similar pattern, but the differences were not significant.

Clinicians' survey responses were so different, 'it was like I was surveying people on a different planet.'

Source DR. McDONALD

Major Finding: Only 29% of women were counseled about gaining a specific amount or range of weight during pregnancy, and 12% were counseled correctly about how much to gain.

Data Source: A cross-sectional survey of 310 pregnant women with a live, singleton gestation, who visited prenatal clinics.

Disclosures: Dr. McDonald reported that she had no relevant financial disclosures.

VANCOUVER, B.C. – When it comes to counseling women about weight gain during pregnancy, there is plenty of room for improvement, new data suggest.

In a survey of more than 300 pregnant women, fewer than a third reported being counseled on the topic, researchers reported at the meeting. And even fewer, merely an eighth, were counseled correctly about how much weight to gain.

In likely related findings, three-fourths of women who were overweight or obese before conceiving planned to gain more weight than was recommended for them in guidelines.

“A lack of reported counseling has been associated in the literature with inappropriate weight gain, both excessive and inadequate,” said lead investigator Dr. Sarah McDonald, an ob.gyn at McMaster University in Hamilton, Ont. “So these findings were very concerning for us.”

She noted that most women who were approached agreed to participate in the survey and were comfortable about discussing weight. Therefore, “it appeared unlikely that the lack of reported counseling was due to patient-driven factors, apart from possibly forgetting.”

Interestingly, a staggered companion survey of the providers had dramatically different findings, showing high reported rates of counseling. “It was like I was surveying people on a different planet,” she commented. “We think we are doing very well,” yet there is an obvious discrepancy that is as yet unexplained.

Citing the obesity epidemic, Dr. McDonald endorsed repeated counseling of women about weight, both before and during pregnancy.

“Obviously, an optimal BMI [body mass index] prepregnancy is ideal, but that's not the situation where most of us come into contact with our patients; it's when they are already pregnant. Then, I think talking about optimal gestational weight gain to not compound the problems of overweight and obesity is important,” she said. “But given the size of the [obesity] epidemic, [the approach has] got to be multipronged.”

In 2009, the U.S. Institute of Medicine released new recommendations regarding gestational weight gain, tailored to prepregnancy BMI, that have been adopted by Canada and other countries.

“However, previous studies done in the era of the 1990 guidelines have shown that only about 30%-40% of pregnant women gained the appropriate amount of weight during pregnancy,” Dr. McDonald noted. “And we were curious what was going on in the era of the new guidelines.”

The investigators surveyed 310 women (94% of those approached) who made at least one visit to representative Hamilton prenatal clinics, other than for pregnancy diagnosis, and currently had a live, singleton gestation. The women's mean age was 30 years, and the median gestational age was 33.0 weeks. Fully 74% were white, and for 43%, the birth would be their first. They had a mean prepregnancy BMI of 25.1 kg/m

“Interestingly enough, 84% of the women reported that they were either comfortable or very comfortable talking about weight-related issues with their care provider, despite the fact that the mean BMI [in this study] is already in the overweight category prepregnancy,” Dr. McDonald observed.

Only 29% of the women reported that their provider counseled them to gain a specific amount or range of weight, and for just 12% overall, that amount or range was correct according to the new guidelines. Only about a quarter of women reported being told that there were risks associated with gaining too much or too little weight during pregnancy.

The median number of prenatal visits before the survey was 10 for the study population, she pointed out, and “so there were multiple opportunities for discussion about weight gain.”

“We wondered, are clinicians just too busy to be talking about weight and weight-related matters, and nutrition, and preventive-type medicine?” said Dr. McDonald. Yet nearly all of the women (97%) reported being counseled to take a vitamin.

When asked how much weight they planned to gain during pregnancy, only 12%-54% of women, depending on prepregnancy BMI category, cited an amount within the guideline-recommended range for them. In particular, in a finding that she described as “alarming,” 75% of overweight and obese women were planning to gain more weight than was recommended for them.

The proportion of women counseled about weight gain differed by the type of provider that had provided the majority of a woman's pregnancy care; it was 40% for midwives, 24% for obstetricians, 23% for general practitioners, and 28% for other providers. The proportion that was correctly counseled showed a similar pattern, but the differences were not significant.

Clinicians' survey responses were so different, 'it was like I was surveying people on a different planet.'

Source DR. McDONALD

VANCOUVER, B.C. – A clinical trial is needed to assess the risk-benefit profile of salpingectomy for ovarian cancer prevention, said Dr. Barry Rosen.

A recent, serendipitous discovery, resulting from pathology examination of tissues removed during prophylactic salpingo-oophorectomy in patients with BRCA mutations, was that serous “ovarian” cancers actually arise from the fimbriae of the fallopian tubes.

“We didn't know it when we started doing [the surgery],” Dr. Rosen explained. “We sort of all of a sudden started to identify cancers, and most of them were in the tube. … All of a sudden, there has been a shift in the understanding that serous carcinomas do come from the tube.”

In the wake of this new information, the Society of Gynecologic Oncology of Canada (GOC) issued two key recommendations, according to Dr. Rosen, professor of ob.gyn. and head of gynecologic oncology at the University of Toronto.

First, the GOC recommends that physicians discuss the risk-benefit profile of salpingectomy with women who are already having a hysterectomy or seeking irreversible contraception. “We don't come out and say 'Do it,'” he noted. “But we are coming out to say that it makes sense, and you should discuss it, and in that discussion, if it makes sense, that you should go ahead and proceed to do it.”

Second, the GOC recommends that, given the lack of evidence, a national study of ovarian cancer prevention through salpingectomy be a priority of the society. “We want to collect the evidence to support this, and we want to be sure that the evidence supports it before we really jump in and say everybody should be doing this,” Dr. Rosen said.

“I don't think there's any question that salpingectomy makes sense. Serous carcinoma is the worst [ovarian] cancer, it's the most common cancer, [and] it causes more deaths than any,” he commented. “So if you can prevent this cancer, you are probably going to have the biggest impact on ovarian cancer that we have today. Bigger than screening, for sure – we know [screening] doesn't work. But bigger than any treatment and any of the fancy treatments that are coming out that are really very expensive treatments.”

Adding salpingectomy to other, planned surgeries could potentially provide preventive benefit to tens of thousands of women annually in Canada alone. For starters, roughly 47,000 Canadian women undergo hysterectomy nationally each year. Removal of the ovaries and tubes at the same time is fairly standard for those who are postmenopausal. “But it's the premenopausal women for whom you would have the benefit of taking out the tubes and leaving the ovaries so that they could continue to have their hormone function,” he noted.

And the procedure could be offered even more widely. For example, approximately 10,100 new cases of colon cancer are diagnosed annually among Canadian women, many of whom undergo pelvic surgery as a result.

There are many “other situations where urologists or general surgeons are doing surgery, so I don't think we have to limit this discussion to gynecologists,” commented Dr. Rosen. “We need to expand it to all disciplines that may operate in the pelvis, because a surgeon can take out the tubes as well as we can.”

When asked by an attendee whether it might perhaps be better to recommend simpler distal salpingectomy instead of total salpingectomy, he expressed reservations.

“While the belief is that most of these cancers arise in the fimbriated end, there are some that do arise further up the tube.” Additionally, “we have to be careful if we put in the word 'distal.' We also have to define what distal is. So it's trickier than you think.”

Dr. Rosen offered a few notes of caution from his own perspective. “Salpingectomy at open hysterectomy is different than at laparoscopic hysterectomy or tubal ligation,” he said. “It's pretty simple if you have an open case to be able to put your favorite clamp across the tube and remove it; laparascopically, [for some it may be] a little bit more difficult. … When doing the procedure, you need to treat this as a surgical procedure, and not just think, 'Oh yeah, we'll just take out the tubes,' and find yourself in some trouble with bleeding or an injury of some sort.”

Also, the medical profession must decide what level of complications is acceptable. “I don't know the answer to that, but we need to know what the complication rate is, and we do know that there will be complications,” Dr. Rosen said.

Finally, the new recommendations are currently based on a hypothesis, not on evidence. “There are other situations in our history in medicine where physicians really believed something very strongly and proceeded with limited information,” he noted, citing by way of example the use of diethylstilbestrol in the 1940s and 1950s to prevent miscarriage, and its subsequent linkage to cancer. “We need to be sure that we get the evidence. I believe that we need to evaluate this in some form of clinical trial.”

Should salpingectomy prove to be effective and adequately safe for preventing ovarian cancer, it would constitute a major turning point in a disease that still has a poor prognosis, he said.

To be sure, treatments have improved steadily over the past 25 years, prolonging life and improving its quality. “We can continue to expect improvements, but I think they are going to be gradual and they are going to be small,” he said.

Efforts to detect the cancer early through screening have thus far not panned out. Three large screening studies were initiated in 1985-2001, one each in the United Kingdom, Japan, and the United States.

Results from the last – the PLCO (Prostate, Lung, Colorectal, and Ovarian) trial, which tested screening with cancer antigen 125 (CA 125) and transvaginal ultrasound – were recently reported (JAMA 2011;305:2295-303). They showed that 20 surgeries had to be performed to detect one cancer, and the rate of major complications was 20% among patients who underwent surgery. And at the end of the day, there was no reduction in ovarian cancer mortality.

Results of the U.K. study, which is using a different, serial multimodality approach to screening, are expected in the 2014 timeframe.

Prevention efforts up to this point have been limited to birth control pills and to BRCA testing with prophylactic surgery for carriers, but this group makes up only about a tenth of all patients with ovarian cancer, he noted.

Dr. Rosen said he had no relevant financial disclosures.

'I don't think there's any question that salpingectomy makes sense.'

Source DR. ROSEN

VANCOUVER, B.C. – A clinical trial is needed to assess the risk-benefit profile of salpingectomy for ovarian cancer prevention, said Dr. Barry Rosen.

A recent, serendipitous discovery, resulting from pathology examination of tissues removed during prophylactic salpingo-oophorectomy in patients with BRCA mutations, was that serous “ovarian” cancers actually arise from the fimbriae of the fallopian tubes.

“We didn't know it when we started doing [the surgery],” Dr. Rosen explained. “We sort of all of a sudden started to identify cancers, and most of them were in the tube. … All of a sudden, there has been a shift in the understanding that serous carcinomas do come from the tube.”

In the wake of this new information, the Society of Gynecologic Oncology of Canada (GOC) issued two key recommendations, according to Dr. Rosen, professor of ob.gyn. and head of gynecologic oncology at the University of Toronto.

First, the GOC recommends that physicians discuss the risk-benefit profile of salpingectomy with women who are already having a hysterectomy or seeking irreversible contraception. “We don't come out and say 'Do it,'” he noted. “But we are coming out to say that it makes sense, and you should discuss it, and in that discussion, if it makes sense, that you should go ahead and proceed to do it.”

Second, the GOC recommends that, given the lack of evidence, a national study of ovarian cancer prevention through salpingectomy be a priority of the society. “We want to collect the evidence to support this, and we want to be sure that the evidence supports it before we really jump in and say everybody should be doing this,” Dr. Rosen said.

“I don't think there's any question that salpingectomy makes sense. Serous carcinoma is the worst [ovarian] cancer, it's the most common cancer, [and] it causes more deaths than any,” he commented. “So if you can prevent this cancer, you are probably going to have the biggest impact on ovarian cancer that we have today. Bigger than screening, for sure – we know [screening] doesn't work. But bigger than any treatment and any of the fancy treatments that are coming out that are really very expensive treatments.”

Adding salpingectomy to other, planned surgeries could potentially provide preventive benefit to tens of thousands of women annually in Canada alone. For starters, roughly 47,000 Canadian women undergo hysterectomy nationally each year. Removal of the ovaries and tubes at the same time is fairly standard for those who are postmenopausal. “But it's the premenopausal women for whom you would have the benefit of taking out the tubes and leaving the ovaries so that they could continue to have their hormone function,” he noted.

And the procedure could be offered even more widely. For example, approximately 10,100 new cases of colon cancer are diagnosed annually among Canadian women, many of whom undergo pelvic surgery as a result.

There are many “other situations where urologists or general surgeons are doing surgery, so I don't think we have to limit this discussion to gynecologists,” commented Dr. Rosen. “We need to expand it to all disciplines that may operate in the pelvis, because a surgeon can take out the tubes as well as we can.”

When asked by an attendee whether it might perhaps be better to recommend simpler distal salpingectomy instead of total salpingectomy, he expressed reservations.

“While the belief is that most of these cancers arise in the fimbriated end, there are some that do arise further up the tube.” Additionally, “we have to be careful if we put in the word 'distal.' We also have to define what distal is. So it's trickier than you think.”

Dr. Rosen offered a few notes of caution from his own perspective. “Salpingectomy at open hysterectomy is different than at laparoscopic hysterectomy or tubal ligation,” he said. “It's pretty simple if you have an open case to be able to put your favorite clamp across the tube and remove it; laparascopically, [for some it may be] a little bit more difficult. … When doing the procedure, you need to treat this as a surgical procedure, and not just think, 'Oh yeah, we'll just take out the tubes,' and find yourself in some trouble with bleeding or an injury of some sort.”

Also, the medical profession must decide what level of complications is acceptable. “I don't know the answer to that, but we need to know what the complication rate is, and we do know that there will be complications,” Dr. Rosen said.

Finally, the new recommendations are currently based on a hypothesis, not on evidence. “There are other situations in our history in medicine where physicians really believed something very strongly and proceeded with limited information,” he noted, citing by way of example the use of diethylstilbestrol in the 1940s and 1950s to prevent miscarriage, and its subsequent linkage to cancer. “We need to be sure that we get the evidence. I believe that we need to evaluate this in some form of clinical trial.”

Should salpingectomy prove to be effective and adequately safe for preventing ovarian cancer, it would constitute a major turning point in a disease that still has a poor prognosis, he said.

To be sure, treatments have improved steadily over the past 25 years, prolonging life and improving its quality. “We can continue to expect improvements, but I think they are going to be gradual and they are going to be small,” he said.

Efforts to detect the cancer early through screening have thus far not panned out. Three large screening studies were initiated in 1985-2001, one each in the United Kingdom, Japan, and the United States.

Results from the last – the PLCO (Prostate, Lung, Colorectal, and Ovarian) trial, which tested screening with cancer antigen 125 (CA 125) and transvaginal ultrasound – were recently reported (JAMA 2011;305:2295-303). They showed that 20 surgeries had to be performed to detect one cancer, and the rate of major complications was 20% among patients who underwent surgery. And at the end of the day, there was no reduction in ovarian cancer mortality.

Results of the U.K. study, which is using a different, serial multimodality approach to screening, are expected in the 2014 timeframe.

Prevention efforts up to this point have been limited to birth control pills and to BRCA testing with prophylactic surgery for carriers, but this group makes up only about a tenth of all patients with ovarian cancer, he noted.

Dr. Rosen said he had no relevant financial disclosures.

'I don't think there's any question that salpingectomy makes sense.'

Source DR. ROSEN

VANCOUVER, B.C. – A clinical trial is needed to assess the risk-benefit profile of salpingectomy for ovarian cancer prevention, said Dr. Barry Rosen.

A recent, serendipitous discovery, resulting from pathology examination of tissues removed during prophylactic salpingo-oophorectomy in patients with BRCA mutations, was that serous “ovarian” cancers actually arise from the fimbriae of the fallopian tubes.

“We didn't know it when we started doing [the surgery],” Dr. Rosen explained. “We sort of all of a sudden started to identify cancers, and most of them were in the tube. … All of a sudden, there has been a shift in the understanding that serous carcinomas do come from the tube.”

In the wake of this new information, the Society of Gynecologic Oncology of Canada (GOC) issued two key recommendations, according to Dr. Rosen, professor of ob.gyn. and head of gynecologic oncology at the University of Toronto.

First, the GOC recommends that physicians discuss the risk-benefit profile of salpingectomy with women who are already having a hysterectomy or seeking irreversible contraception. “We don't come out and say 'Do it,'” he noted. “But we are coming out to say that it makes sense, and you should discuss it, and in that discussion, if it makes sense, that you should go ahead and proceed to do it.”

Second, the GOC recommends that, given the lack of evidence, a national study of ovarian cancer prevention through salpingectomy be a priority of the society. “We want to collect the evidence to support this, and we want to be sure that the evidence supports it before we really jump in and say everybody should be doing this,” Dr. Rosen said.

“I don't think there's any question that salpingectomy makes sense. Serous carcinoma is the worst [ovarian] cancer, it's the most common cancer, [and] it causes more deaths than any,” he commented. “So if you can prevent this cancer, you are probably going to have the biggest impact on ovarian cancer that we have today. Bigger than screening, for sure – we know [screening] doesn't work. But bigger than any treatment and any of the fancy treatments that are coming out that are really very expensive treatments.”

Adding salpingectomy to other, planned surgeries could potentially provide preventive benefit to tens of thousands of women annually in Canada alone. For starters, roughly 47,000 Canadian women undergo hysterectomy nationally each year. Removal of the ovaries and tubes at the same time is fairly standard for those who are postmenopausal. “But it's the premenopausal women for whom you would have the benefit of taking out the tubes and leaving the ovaries so that they could continue to have their hormone function,” he noted.

And the procedure could be offered even more widely. For example, approximately 10,100 new cases of colon cancer are diagnosed annually among Canadian women, many of whom undergo pelvic surgery as a result.

There are many “other situations where urologists or general surgeons are doing surgery, so I don't think we have to limit this discussion to gynecologists,” commented Dr. Rosen. “We need to expand it to all disciplines that may operate in the pelvis, because a surgeon can take out the tubes as well as we can.”

When asked by an attendee whether it might perhaps be better to recommend simpler distal salpingectomy instead of total salpingectomy, he expressed reservations.

“While the belief is that most of these cancers arise in the fimbriated end, there are some that do arise further up the tube.” Additionally, “we have to be careful if we put in the word 'distal.' We also have to define what distal is. So it's trickier than you think.”

Dr. Rosen offered a few notes of caution from his own perspective. “Salpingectomy at open hysterectomy is different than at laparoscopic hysterectomy or tubal ligation,” he said. “It's pretty simple if you have an open case to be able to put your favorite clamp across the tube and remove it; laparascopically, [for some it may be] a little bit more difficult. … When doing the procedure, you need to treat this as a surgical procedure, and not just think, 'Oh yeah, we'll just take out the tubes,' and find yourself in some trouble with bleeding or an injury of some sort.”

Also, the medical profession must decide what level of complications is acceptable. “I don't know the answer to that, but we need to know what the complication rate is, and we do know that there will be complications,” Dr. Rosen said.

Finally, the new recommendations are currently based on a hypothesis, not on evidence. “There are other situations in our history in medicine where physicians really believed something very strongly and proceeded with limited information,” he noted, citing by way of example the use of diethylstilbestrol in the 1940s and 1950s to prevent miscarriage, and its subsequent linkage to cancer. “We need to be sure that we get the evidence. I believe that we need to evaluate this in some form of clinical trial.”

Should salpingectomy prove to be effective and adequately safe for preventing ovarian cancer, it would constitute a major turning point in a disease that still has a poor prognosis, he said.

To be sure, treatments have improved steadily over the past 25 years, prolonging life and improving its quality. “We can continue to expect improvements, but I think they are going to be gradual and they are going to be small,” he said.

Efforts to detect the cancer early through screening have thus far not panned out. Three large screening studies were initiated in 1985-2001, one each in the United Kingdom, Japan, and the United States.

Results from the last – the PLCO (Prostate, Lung, Colorectal, and Ovarian) trial, which tested screening with cancer antigen 125 (CA 125) and transvaginal ultrasound – were recently reported (JAMA 2011;305:2295-303). They showed that 20 surgeries had to be performed to detect one cancer, and the rate of major complications was 20% among patients who underwent surgery. And at the end of the day, there was no reduction in ovarian cancer mortality.

Results of the U.K. study, which is using a different, serial multimodality approach to screening, are expected in the 2014 timeframe.

Prevention efforts up to this point have been limited to birth control pills and to BRCA testing with prophylactic surgery for carriers, but this group makes up only about a tenth of all patients with ovarian cancer, he noted.

Dr. Rosen said he had no relevant financial disclosures.

'I don't think there's any question that salpingectomy makes sense.'

Source DR. ROSEN