SGO Annual Meeting on Women's Cancer 2014

TAMPA – Paradigm changes drive radical changes in science, according to Dr. Leroy Hood, a renowned scientist and inventor who joined forces with Ohio State University to create the P4 Medicine Institute to "drive innovative approaches to disease prevention and maintenance of health and wellness by applying systems biology to medicine and care delivery."

P4 medicine (Predictive, Preventive, Personalized, Participatory) "is really the convergence of three megatrends in medicine: systems medicine on one hand, big data and its analytics on the other hand, and patient-activated social networks," Dr. Hood, president of the Institute for Systems Biology, Seattle, said at the annual meeting of the Society of Gynecologic Oncology.

As an invited presidential lecturer at the meeting, Dr. Hood described the two central features of systems medicine and how they will facilitate P4 medicine. The first feature is the idea that in the next 5-10 years, individuals will have a "virtual cloud of billions of data points."

RTEmagicC_0fq256w3_Hood_Leroy_WA.jpg.jpg

"Biological networks exist at the level of genes, the level of proteins, the level of cells, the level of organs, and obviously at the level of the individual through social networks. What is really critical is that in disease, that ‘network of networks’ becomes disease-perturbed and it alters the nature of the information it can handle. If you can capture that altered information, you gain fundamental new insights into biological mechanisms and you can design new strategies both for diagnosis and for therapy," Dr. Hood said.

What is lacking in American medicine, however, is the second feature of systems medicine: an understanding of the dynamics of how these disease-perturbed networks change with time throughout the course of the disease.

P4 medicine differs from evidence-based medicine in that it is proactive rather than reactive; it is focused on the individual and, increasingly, on wellness; it is "all about creating, for each patient, this global data cloud that gives us deep insights into the individual" and that produces predictive and actionable models of wellness and disease; and, most fundamentally, it "argues that the current clinical trial system is totally broken," Dr. Hood said.

"The idea that for a cancer diagnosis, you take 30,000 patients, give them a placebo drug, extract from the patients and put in curves their responses, and from those curves you make generalizations about how to treat the population and how well the drug has done, is wrong in every way. Each individual is different genetically and environmentally," he explained, noting that P4 medicine analyzes "the unique individual and then aggregates those into groups in accordance with what environmental opportunities you’d like to explore."

Acceptance of this new health care concept will depend upon patient-activated social networks, he said.

"I think that’s the only way we can change the incredibly conservative nature of both physicians and the health care system itself," he added.

P4 medicine is mainly about two things – quantifying wellness and demystifying disease, he said.

In contemporary health care, with regard to these two fundamental concepts, three major things have been missing: metrics for wellness, the ability to do longitudinal studies of disease, and the ability to do studies at the point of initiation. A study now underway based on the concept of P4 medicine will allow for all three.

It is a Framingham-like longitudinal study that aims to enroll 100,000 individuals who will be followed for 20-30 years. Participants will quickly be divided into two groups, including those who remain well or improve in health, and those who transition from wellness to disease.

Very soon, the study population will be large enough to see all major diseases, including cancer.

"But the really important point is that we’ll have multiple data points all the way across this longitudinal study so we can go back to the earliest origins of the divergence of wellness to disease for a particular patient, and we can look at mechanisms and new approaches to diagnostics, and hopefully change that disease trajectory very early on to a wellness trajectory," he said.

The first phase of the study, which launched in March, will enroll 1,000 individuals within a year, working up to 10,000 and ultimately to 100,000.

The plan is to collect numerous measurements, including "physical trait kinds of measurements," clinical chemistries, and special measurements of the gut microbiome and organ-specific blood protein fingerprints to monitor wellness-to-disease transitions in the brain, heart, and liver.

"And all of these data will be integrated together by analytics to create these models for each individual that are all focused on identifying and prioritizing a series of actionable traits.

In the short-term, Dr. Hood predicts that the longitudinal study will allow for creation of models for each individual to optimize wellness and minimize disease. In the intermediate term, the data from the well people will be mined for metrics of wellness. Long term, the study will generate a database that elucidates factors associated with the transition from wellness to disease, allowing alteration of the trajectory of disease for many patients.

"My own view is that in a 10- to 15-year period, the wellness industry will be independent from the health care industry, and its total market cap will far exceed that of the health care industry. What is exciting to think is that now, today, we’re just beginning to create the companies that will be the Googles and the Microsofts of the wellness industry. It really is a unique and exciting kind of opportunity," he said.

There’s no way to predict how long it will take for P4 medicine to be fully realized.

"But we are in a unique position now, for the first time, to begin looking at the dynamics of not one human disease, but many different human diseases," he said.

TAMPA – Paradigm changes drive radical changes in science, according to Dr. Leroy Hood, a renowned scientist and inventor who joined forces with Ohio State University to create the P4 Medicine Institute to "drive innovative approaches to disease prevention and maintenance of health and wellness by applying systems biology to medicine and care delivery."

P4 medicine (Predictive, Preventive, Personalized, Participatory) "is really the convergence of three megatrends in medicine: systems medicine on one hand, big data and its analytics on the other hand, and patient-activated social networks," Dr. Hood, president of the Institute for Systems Biology, Seattle, said at the annual meeting of the Society of Gynecologic Oncology.

As an invited presidential lecturer at the meeting, Dr. Hood described the two central features of systems medicine and how they will facilitate P4 medicine. The first feature is the idea that in the next 5-10 years, individuals will have a "virtual cloud of billions of data points."

RTEmagicC_0fq256w3_Hood_Leroy_WA.jpg.jpg

"Biological networks exist at the level of genes, the level of proteins, the level of cells, the level of organs, and obviously at the level of the individual through social networks. What is really critical is that in disease, that ‘network of networks’ becomes disease-perturbed and it alters the nature of the information it can handle. If you can capture that altered information, you gain fundamental new insights into biological mechanisms and you can design new strategies both for diagnosis and for therapy," Dr. Hood said.

What is lacking in American medicine, however, is the second feature of systems medicine: an understanding of the dynamics of how these disease-perturbed networks change with time throughout the course of the disease.

P4 medicine differs from evidence-based medicine in that it is proactive rather than reactive; it is focused on the individual and, increasingly, on wellness; it is "all about creating, for each patient, this global data cloud that gives us deep insights into the individual" and that produces predictive and actionable models of wellness and disease; and, most fundamentally, it "argues that the current clinical trial system is totally broken," Dr. Hood said.

"The idea that for a cancer diagnosis, you take 30,000 patients, give them a placebo drug, extract from the patients and put in curves their responses, and from those curves you make generalizations about how to treat the population and how well the drug has done, is wrong in every way. Each individual is different genetically and environmentally," he explained, noting that P4 medicine analyzes "the unique individual and then aggregates those into groups in accordance with what environmental opportunities you’d like to explore."

Acceptance of this new health care concept will depend upon patient-activated social networks, he said.

"I think that’s the only way we can change the incredibly conservative nature of both physicians and the health care system itself," he added.

P4 medicine is mainly about two things – quantifying wellness and demystifying disease, he said.

In contemporary health care, with regard to these two fundamental concepts, three major things have been missing: metrics for wellness, the ability to do longitudinal studies of disease, and the ability to do studies at the point of initiation. A study now underway based on the concept of P4 medicine will allow for all three.

It is a Framingham-like longitudinal study that aims to enroll 100,000 individuals who will be followed for 20-30 years. Participants will quickly be divided into two groups, including those who remain well or improve in health, and those who transition from wellness to disease.

Very soon, the study population will be large enough to see all major diseases, including cancer.

"But the really important point is that we’ll have multiple data points all the way across this longitudinal study so we can go back to the earliest origins of the divergence of wellness to disease for a particular patient, and we can look at mechanisms and new approaches to diagnostics, and hopefully change that disease trajectory very early on to a wellness trajectory," he said.

The first phase of the study, which launched in March, will enroll 1,000 individuals within a year, working up to 10,000 and ultimately to 100,000.

The plan is to collect numerous measurements, including "physical trait kinds of measurements," clinical chemistries, and special measurements of the gut microbiome and organ-specific blood protein fingerprints to monitor wellness-to-disease transitions in the brain, heart, and liver.

"And all of these data will be integrated together by analytics to create these models for each individual that are all focused on identifying and prioritizing a series of actionable traits.

In the short-term, Dr. Hood predicts that the longitudinal study will allow for creation of models for each individual to optimize wellness and minimize disease. In the intermediate term, the data from the well people will be mined for metrics of wellness. Long term, the study will generate a database that elucidates factors associated with the transition from wellness to disease, allowing alteration of the trajectory of disease for many patients.

"My own view is that in a 10- to 15-year period, the wellness industry will be independent from the health care industry, and its total market cap will far exceed that of the health care industry. What is exciting to think is that now, today, we’re just beginning to create the companies that will be the Googles and the Microsofts of the wellness industry. It really is a unique and exciting kind of opportunity," he said.

There’s no way to predict how long it will take for P4 medicine to be fully realized.

"But we are in a unique position now, for the first time, to begin looking at the dynamics of not one human disease, but many different human diseases," he said.

TAMPA – Paradigm changes drive radical changes in science, according to Dr. Leroy Hood, a renowned scientist and inventor who joined forces with Ohio State University to create the P4 Medicine Institute to "drive innovative approaches to disease prevention and maintenance of health and wellness by applying systems biology to medicine and care delivery."

P4 medicine (Predictive, Preventive, Personalized, Participatory) "is really the convergence of three megatrends in medicine: systems medicine on one hand, big data and its analytics on the other hand, and patient-activated social networks," Dr. Hood, president of the Institute for Systems Biology, Seattle, said at the annual meeting of the Society of Gynecologic Oncology.

As an invited presidential lecturer at the meeting, Dr. Hood described the two central features of systems medicine and how they will facilitate P4 medicine. The first feature is the idea that in the next 5-10 years, individuals will have a "virtual cloud of billions of data points."

RTEmagicC_0fq256w3_Hood_Leroy_WA.jpg.jpg

"Biological networks exist at the level of genes, the level of proteins, the level of cells, the level of organs, and obviously at the level of the individual through social networks. What is really critical is that in disease, that ‘network of networks’ becomes disease-perturbed and it alters the nature of the information it can handle. If you can capture that altered information, you gain fundamental new insights into biological mechanisms and you can design new strategies both for diagnosis and for therapy," Dr. Hood said.

What is lacking in American medicine, however, is the second feature of systems medicine: an understanding of the dynamics of how these disease-perturbed networks change with time throughout the course of the disease.

P4 medicine differs from evidence-based medicine in that it is proactive rather than reactive; it is focused on the individual and, increasingly, on wellness; it is "all about creating, for each patient, this global data cloud that gives us deep insights into the individual" and that produces predictive and actionable models of wellness and disease; and, most fundamentally, it "argues that the current clinical trial system is totally broken," Dr. Hood said.

"The idea that for a cancer diagnosis, you take 30,000 patients, give them a placebo drug, extract from the patients and put in curves their responses, and from those curves you make generalizations about how to treat the population and how well the drug has done, is wrong in every way. Each individual is different genetically and environmentally," he explained, noting that P4 medicine analyzes "the unique individual and then aggregates those into groups in accordance with what environmental opportunities you’d like to explore."

Acceptance of this new health care concept will depend upon patient-activated social networks, he said.

"I think that’s the only way we can change the incredibly conservative nature of both physicians and the health care system itself," he added.

P4 medicine is mainly about two things – quantifying wellness and demystifying disease, he said.

In contemporary health care, with regard to these two fundamental concepts, three major things have been missing: metrics for wellness, the ability to do longitudinal studies of disease, and the ability to do studies at the point of initiation. A study now underway based on the concept of P4 medicine will allow for all three.

It is a Framingham-like longitudinal study that aims to enroll 100,000 individuals who will be followed for 20-30 years. Participants will quickly be divided into two groups, including those who remain well or improve in health, and those who transition from wellness to disease.

Very soon, the study population will be large enough to see all major diseases, including cancer.

"But the really important point is that we’ll have multiple data points all the way across this longitudinal study so we can go back to the earliest origins of the divergence of wellness to disease for a particular patient, and we can look at mechanisms and new approaches to diagnostics, and hopefully change that disease trajectory very early on to a wellness trajectory," he said.

The first phase of the study, which launched in March, will enroll 1,000 individuals within a year, working up to 10,000 and ultimately to 100,000.

The plan is to collect numerous measurements, including "physical trait kinds of measurements," clinical chemistries, and special measurements of the gut microbiome and organ-specific blood protein fingerprints to monitor wellness-to-disease transitions in the brain, heart, and liver.

"And all of these data will be integrated together by analytics to create these models for each individual that are all focused on identifying and prioritizing a series of actionable traits.

In the short-term, Dr. Hood predicts that the longitudinal study will allow for creation of models for each individual to optimize wellness and minimize disease. In the intermediate term, the data from the well people will be mined for metrics of wellness. Long term, the study will generate a database that elucidates factors associated with the transition from wellness to disease, allowing alteration of the trajectory of disease for many patients.

"My own view is that in a 10- to 15-year period, the wellness industry will be independent from the health care industry, and its total market cap will far exceed that of the health care industry. What is exciting to think is that now, today, we’re just beginning to create the companies that will be the Googles and the Microsofts of the wellness industry. It really is a unique and exciting kind of opportunity," he said.

There’s no way to predict how long it will take for P4 medicine to be fully realized.

"But we are in a unique position now, for the first time, to begin looking at the dynamics of not one human disease, but many different human diseases," he said.

TAMPA – Outpatient palliative care consultations are associated with decreased symptom burden in women with gynecologic malignancies, but American Society of Clinical Oncology recommendations for referral are often ignored, according to retrospective data and a review of patient records.

In one study, 78 patients seen between June 2007 and March 2013 at an outpatient symptom management clinic for follow-up within 90 days of their initial consultation completed a questionnaire at each visit, including the nine-item Edmonton Symptom Assessment System. The responses, along with information from the patients’ charts, showed significant improvements in almost all symptoms over time, Dr. Rachel Ruskin, a clinical fellow at the University of California, San Francisco, reported at the annual meeting of the Society of Gynecologic Oncology.

For example, mean pain, fatigue, anxiety, depression, nausea, drowsiness, and appetite scores decreased between 0.7 and 1.5 points from the median baseline scores (on a 10 point scale). A decline in shortness of breath score also approached significance.

No difference was seen with respect to symptom improvement between patients with and without disease, although there appeared to be a trend toward a difference in anxiety scores, Dr. Ruskin noted.

Patients who were treated with concurrent cancer-directed therapies had improvements in pain and fatigue, but to a lesser extent than did those who did not receive treatment, she said.

Among the 35 patients who attended at least two follow-up visits, the improvements in nausea and shortness of breath seen at the first visit persisted at the second, and symptoms of depression and drowsiness continued to improve at each visit. Of those 35 patients, 58% had ovarian, fallopian tube, or peritoneal cancer; 20% had uterine cancer; and 15% had cervical cancer. Most (81%) had stage III, IV, or recurrent cancer.

Mean age at study entry was 57 years, 85% of patients had disease present, and 62% were undergoing treatment. The vast majority (87%) had received chemotherapy, 30% received radiation, and 8% had undergone surgery.

In patients for whom relevant data were available, there was evidence of mild hematologic, renal, and nutritional compromise, and nearly 25% of these patients had been hospitalized within the prior month.

"Notably, in our cohort the improvement in symptoms cannot be attributed to antineoplastic therapies, since – if anything – treatment by traditional oncologic modalities was associated with less benefit in some symptoms," Dr. Ruskin said, adding that future research should focus on "which aspects of palliative care are effective and by what mechanisms," as this information would be helpful for determining best practices that can be replicated across settings and for designing prospective concurrent standard oncologic and palliative care trials.

"In the meantime, we hope that these data will encourage providers to consider referral to their outpatient palliative care colleagues," she concluded.

Findings from another study presented at the meeting suggest there is some work to do in that regard.

In that study, Dr. Carolyn Lefkowits of the University of Pittsburgh found that oncologists are falling short when it comes to following the 2012 ASCO recommendation to consider early palliative care integration for "any patient with metastatic cancer and/or high symptom burden."

Of 340 women with a gynecologic malignancy who were admitted to a gynecologic oncology service between February 2012 and August 2012, only 32% were referred to palliative care, Dr. Lefkowits said.

The patients had a median age of 62 years, and an equal number had early- and late-stage disease. Nearly 25% had recurrent disease by the end of the study period.

Multivariate logistic regression identified independent predictors of palliative care consultation, including number of admission (odds ratio, 17.4 for greater than three vs. three or fewer admissions), admission for symptom management (OR, 22.0), and death within 6 months (OR, 15.7).

Notably, only 16% of the patients died within 6 months of the last admission during the study period, and although 25% of patients overall were referred to palliative care, 54% of those who died within 6 months were referred, suggesting that most referrals are not made for patients who are early in their disease course.

Furthermore, only 53% of patients with recurrent disease – all of whom should have been considered for palliative care integration based on the ASCO recommendations – were seen for palliative care, including 59% who had received three or more lines of chemotherapy, Dr. Lefkowits said.

The findings suggest that the group of patients referred for palliative care is characterized by high symptom burden and poor prognosis. In fact, most of those referred were likely already at the point where they would be considered hospice eligible, she said.

An analysis of referrals based on each ASCO recommendation category showed that the highest referral rate was for "symptom admission" (79%), and the lowest was for recurrent disease (52%).

"So, although the predictors of consultation are in keeping, I think, with the spirit of the ASCO recommendations, we’re still not comprehensively capturing these high-risk subgroups," Dr. Lefkowits said.

She added that she hopes the findings will serve as a "conversation starter, spurring us to address questions, including which gynecologic oncology patients are most appropriate to target for consistent palliative care referral."

Other questions to consider include which systems might help improve referral rates among those patients and which patients (and at what rates) should be referred for specialized palliative care.

All of the patients in the ASCO categories should be receiving palliative care, but it remains unclear what percentage need specialized palliative care, she said

As for improving the rate of palliative care consultations, Dr. Lois M. Ramondetta of the University of Texas M.D. Anderson Cancer Center, Houston, said during a "lecturette" following the presentations by Dr. Ruskin and Dr. Lefkowits, that "branding" is important.

One study showed that 70% of Americans don’t even know what palliative care is, and many of those who do – including both patients and health care providers – equate palliative care with end-of-life care.

Simply changing the name of the palliative care clinic at M.D. Anderson to the "supportive care clinic" led to a 40% increase in consultations, she said.

Most patients and physicians reacted favorably to the concept of supportive care, she explained, noting that palliative care should be rebranded as an extra layer of support, and it should be offered throughout the treatment process.

Studies consistently show that palliative care provides multiple benefits, including decreased hospital length of stay, fewer intensive care admissions, and reduced costs and need for potentially harmful procedures. Some studies have suggested palliative care is associated with improved overall survival, she said.

A number of efforts to improve palliative care skills and to increase referral for palliative care consultations are underway through both ASCO and the SGO, including a virtual learning collaborative being developed by ASCO, efforts to incorporate palliative care education into training and recertification programs, and the revival of a palliative care task force to address these issues.

Dr. Ruskin, Dr. Lefkowits, and Dr. Ramondetta each reported having no disclosures.

tor@frontlinemedcom.com

TAMPA – Outpatient palliative care consultations are associated with decreased symptom burden in women with gynecologic malignancies, but American Society of Clinical Oncology recommendations for referral are often ignored, according to retrospective data and a review of patient records.

In one study, 78 patients seen between June 2007 and March 2013 at an outpatient symptom management clinic for follow-up within 90 days of their initial consultation completed a questionnaire at each visit, including the nine-item Edmonton Symptom Assessment System. The responses, along with information from the patients’ charts, showed significant improvements in almost all symptoms over time, Dr. Rachel Ruskin, a clinical fellow at the University of California, San Francisco, reported at the annual meeting of the Society of Gynecologic Oncology.

For example, mean pain, fatigue, anxiety, depression, nausea, drowsiness, and appetite scores decreased between 0.7 and 1.5 points from the median baseline scores (on a 10 point scale). A decline in shortness of breath score also approached significance.

No difference was seen with respect to symptom improvement between patients with and without disease, although there appeared to be a trend toward a difference in anxiety scores, Dr. Ruskin noted.

Patients who were treated with concurrent cancer-directed therapies had improvements in pain and fatigue, but to a lesser extent than did those who did not receive treatment, she said.

Among the 35 patients who attended at least two follow-up visits, the improvements in nausea and shortness of breath seen at the first visit persisted at the second, and symptoms of depression and drowsiness continued to improve at each visit. Of those 35 patients, 58% had ovarian, fallopian tube, or peritoneal cancer; 20% had uterine cancer; and 15% had cervical cancer. Most (81%) had stage III, IV, or recurrent cancer.

Mean age at study entry was 57 years, 85% of patients had disease present, and 62% were undergoing treatment. The vast majority (87%) had received chemotherapy, 30% received radiation, and 8% had undergone surgery.

In patients for whom relevant data were available, there was evidence of mild hematologic, renal, and nutritional compromise, and nearly 25% of these patients had been hospitalized within the prior month.

"Notably, in our cohort the improvement in symptoms cannot be attributed to antineoplastic therapies, since – if anything – treatment by traditional oncologic modalities was associated with less benefit in some symptoms," Dr. Ruskin said, adding that future research should focus on "which aspects of palliative care are effective and by what mechanisms," as this information would be helpful for determining best practices that can be replicated across settings and for designing prospective concurrent standard oncologic and palliative care trials.

"In the meantime, we hope that these data will encourage providers to consider referral to their outpatient palliative care colleagues," she concluded.

Findings from another study presented at the meeting suggest there is some work to do in that regard.

In that study, Dr. Carolyn Lefkowits of the University of Pittsburgh found that oncologists are falling short when it comes to following the 2012 ASCO recommendation to consider early palliative care integration for "any patient with metastatic cancer and/or high symptom burden."

Of 340 women with a gynecologic malignancy who were admitted to a gynecologic oncology service between February 2012 and August 2012, only 32% were referred to palliative care, Dr. Lefkowits said.

The patients had a median age of 62 years, and an equal number had early- and late-stage disease. Nearly 25% had recurrent disease by the end of the study period.

Multivariate logistic regression identified independent predictors of palliative care consultation, including number of admission (odds ratio, 17.4 for greater than three vs. three or fewer admissions), admission for symptom management (OR, 22.0), and death within 6 months (OR, 15.7).

Notably, only 16% of the patients died within 6 months of the last admission during the study period, and although 25% of patients overall were referred to palliative care, 54% of those who died within 6 months were referred, suggesting that most referrals are not made for patients who are early in their disease course.

Furthermore, only 53% of patients with recurrent disease – all of whom should have been considered for palliative care integration based on the ASCO recommendations – were seen for palliative care, including 59% who had received three or more lines of chemotherapy, Dr. Lefkowits said.

The findings suggest that the group of patients referred for palliative care is characterized by high symptom burden and poor prognosis. In fact, most of those referred were likely already at the point where they would be considered hospice eligible, she said.

An analysis of referrals based on each ASCO recommendation category showed that the highest referral rate was for "symptom admission" (79%), and the lowest was for recurrent disease (52%).

"So, although the predictors of consultation are in keeping, I think, with the spirit of the ASCO recommendations, we’re still not comprehensively capturing these high-risk subgroups," Dr. Lefkowits said.

She added that she hopes the findings will serve as a "conversation starter, spurring us to address questions, including which gynecologic oncology patients are most appropriate to target for consistent palliative care referral."

Other questions to consider include which systems might help improve referral rates among those patients and which patients (and at what rates) should be referred for specialized palliative care.

All of the patients in the ASCO categories should be receiving palliative care, but it remains unclear what percentage need specialized palliative care, she said

As for improving the rate of palliative care consultations, Dr. Lois M. Ramondetta of the University of Texas M.D. Anderson Cancer Center, Houston, said during a "lecturette" following the presentations by Dr. Ruskin and Dr. Lefkowits, that "branding" is important.

One study showed that 70% of Americans don’t even know what palliative care is, and many of those who do – including both patients and health care providers – equate palliative care with end-of-life care.

Simply changing the name of the palliative care clinic at M.D. Anderson to the "supportive care clinic" led to a 40% increase in consultations, she said.

Most patients and physicians reacted favorably to the concept of supportive care, she explained, noting that palliative care should be rebranded as an extra layer of support, and it should be offered throughout the treatment process.

Studies consistently show that palliative care provides multiple benefits, including decreased hospital length of stay, fewer intensive care admissions, and reduced costs and need for potentially harmful procedures. Some studies have suggested palliative care is associated with improved overall survival, she said.

A number of efforts to improve palliative care skills and to increase referral for palliative care consultations are underway through both ASCO and the SGO, including a virtual learning collaborative being developed by ASCO, efforts to incorporate palliative care education into training and recertification programs, and the revival of a palliative care task force to address these issues.

Dr. Ruskin, Dr. Lefkowits, and Dr. Ramondetta each reported having no disclosures.

tor@frontlinemedcom.com

TAMPA – Outpatient palliative care consultations are associated with decreased symptom burden in women with gynecologic malignancies, but American Society of Clinical Oncology recommendations for referral are often ignored, according to retrospective data and a review of patient records.

In one study, 78 patients seen between June 2007 and March 2013 at an outpatient symptom management clinic for follow-up within 90 days of their initial consultation completed a questionnaire at each visit, including the nine-item Edmonton Symptom Assessment System. The responses, along with information from the patients’ charts, showed significant improvements in almost all symptoms over time, Dr. Rachel Ruskin, a clinical fellow at the University of California, San Francisco, reported at the annual meeting of the Society of Gynecologic Oncology.

For example, mean pain, fatigue, anxiety, depression, nausea, drowsiness, and appetite scores decreased between 0.7 and 1.5 points from the median baseline scores (on a 10 point scale). A decline in shortness of breath score also approached significance.

No difference was seen with respect to symptom improvement between patients with and without disease, although there appeared to be a trend toward a difference in anxiety scores, Dr. Ruskin noted.

Patients who were treated with concurrent cancer-directed therapies had improvements in pain and fatigue, but to a lesser extent than did those who did not receive treatment, she said.

Among the 35 patients who attended at least two follow-up visits, the improvements in nausea and shortness of breath seen at the first visit persisted at the second, and symptoms of depression and drowsiness continued to improve at each visit. Of those 35 patients, 58% had ovarian, fallopian tube, or peritoneal cancer; 20% had uterine cancer; and 15% had cervical cancer. Most (81%) had stage III, IV, or recurrent cancer.

Mean age at study entry was 57 years, 85% of patients had disease present, and 62% were undergoing treatment. The vast majority (87%) had received chemotherapy, 30% received radiation, and 8% had undergone surgery.

In patients for whom relevant data were available, there was evidence of mild hematologic, renal, and nutritional compromise, and nearly 25% of these patients had been hospitalized within the prior month.

"Notably, in our cohort the improvement in symptoms cannot be attributed to antineoplastic therapies, since – if anything – treatment by traditional oncologic modalities was associated with less benefit in some symptoms," Dr. Ruskin said, adding that future research should focus on "which aspects of palliative care are effective and by what mechanisms," as this information would be helpful for determining best practices that can be replicated across settings and for designing prospective concurrent standard oncologic and palliative care trials.

"In the meantime, we hope that these data will encourage providers to consider referral to their outpatient palliative care colleagues," she concluded.

Findings from another study presented at the meeting suggest there is some work to do in that regard.

In that study, Dr. Carolyn Lefkowits of the University of Pittsburgh found that oncologists are falling short when it comes to following the 2012 ASCO recommendation to consider early palliative care integration for "any patient with metastatic cancer and/or high symptom burden."

Of 340 women with a gynecologic malignancy who were admitted to a gynecologic oncology service between February 2012 and August 2012, only 32% were referred to palliative care, Dr. Lefkowits said.

The patients had a median age of 62 years, and an equal number had early- and late-stage disease. Nearly 25% had recurrent disease by the end of the study period.

Multivariate logistic regression identified independent predictors of palliative care consultation, including number of admission (odds ratio, 17.4 for greater than three vs. three or fewer admissions), admission for symptom management (OR, 22.0), and death within 6 months (OR, 15.7).

Notably, only 16% of the patients died within 6 months of the last admission during the study period, and although 25% of patients overall were referred to palliative care, 54% of those who died within 6 months were referred, suggesting that most referrals are not made for patients who are early in their disease course.

Furthermore, only 53% of patients with recurrent disease – all of whom should have been considered for palliative care integration based on the ASCO recommendations – were seen for palliative care, including 59% who had received three or more lines of chemotherapy, Dr. Lefkowits said.

The findings suggest that the group of patients referred for palliative care is characterized by high symptom burden and poor prognosis. In fact, most of those referred were likely already at the point where they would be considered hospice eligible, she said.

An analysis of referrals based on each ASCO recommendation category showed that the highest referral rate was for "symptom admission" (79%), and the lowest was for recurrent disease (52%).

"So, although the predictors of consultation are in keeping, I think, with the spirit of the ASCO recommendations, we’re still not comprehensively capturing these high-risk subgroups," Dr. Lefkowits said.

She added that she hopes the findings will serve as a "conversation starter, spurring us to address questions, including which gynecologic oncology patients are most appropriate to target for consistent palliative care referral."

Other questions to consider include which systems might help improve referral rates among those patients and which patients (and at what rates) should be referred for specialized palliative care.

All of the patients in the ASCO categories should be receiving palliative care, but it remains unclear what percentage need specialized palliative care, she said

As for improving the rate of palliative care consultations, Dr. Lois M. Ramondetta of the University of Texas M.D. Anderson Cancer Center, Houston, said during a "lecturette" following the presentations by Dr. Ruskin and Dr. Lefkowits, that "branding" is important.

One study showed that 70% of Americans don’t even know what palliative care is, and many of those who do – including both patients and health care providers – equate palliative care with end-of-life care.

Simply changing the name of the palliative care clinic at M.D. Anderson to the "supportive care clinic" led to a 40% increase in consultations, she said.

Most patients and physicians reacted favorably to the concept of supportive care, she explained, noting that palliative care should be rebranded as an extra layer of support, and it should be offered throughout the treatment process.

Studies consistently show that palliative care provides multiple benefits, including decreased hospital length of stay, fewer intensive care admissions, and reduced costs and need for potentially harmful procedures. Some studies have suggested palliative care is associated with improved overall survival, she said.

A number of efforts to improve palliative care skills and to increase referral for palliative care consultations are underway through both ASCO and the SGO, including a virtual learning collaborative being developed by ASCO, efforts to incorporate palliative care education into training and recertification programs, and the revival of a palliative care task force to address these issues.

Dr. Ruskin, Dr. Lefkowits, and Dr. Ramondetta each reported having no disclosures.

tor@frontlinemedcom.com

TAMPA – Vaginal cuff brachytherapy followed by paclitaxel and carboplatin chemotherapy was not superior to pelvic radiation therapy in randomized phase III Gynecologic Oncology Group trial 249 involving women with high-intermediate-risk, early stage endometrial cancer.

The 24-month recurrence-free survival was 82% and 84% in 301 women assigned to receive pelvic radiation therapy (PXRT) and 300 women assigned to receive vaginal cuff brachytherapy followed by paclitaxel and carboplatin chemotherapy (VCB/C) for a hazard ratio of 0.97. Survival at 24 months was 93% in the PXRT group and 92% in the VCB/C group (hazard ratio, 1.28), Dr. D. Scott McMeekin reported during a late-breaking abstract session at the annual meeting of the Society of Gynecologic Oncology.

"There was no statistically significant evidence of heterogeneity of treatment effects with respect to recurrence-free survival among stage, age, race, performance status, histology, or lymphadenectomy use in either of the groups," said Dr. McMeekin of the University of Oklahoma, Oklahoma City.

Study subjects were women with a median age of 63 years. All of the women underwent hysterectomy and had either stage I endometrioid disease with high risk based on GOG (Gynecologic Oncology Group) trial 99 study criteria, stage II disease, or stage I-II serous or clear cell tumors. Most (74%) had stage I disease, and 89% underwent lymphadenectomy. Histology was endometrioid type in 71% of patients, serous in 15%, and clear cell in 5%.

All patients participated in quality of life assessments at five time points, and tissue samples were collected for a translational research correlative, he said.

Treatment began within 12 weeks following surgery. Those in the PXRT group were treated using standard four-field or intensity-modulated radiation therapy techniques (with optional VCB for those with serous or clear cell tumors or with stage II disease), and patients in the VCB/C group received high-dose rate or low-dose rate brachytherapy followed by paclitaxel (175 mg/m² over 3 hours) and carboplatin (AUC 6) every 21 days for a total of three cycles.

Treatment was generally well tolerated, with 91% of PXRT patients and 87% of VCB/C patients completing therapy.

"That being said, acute adverse effects were more frequent and tended to be more severe in patients receiving VCB/C," Dr. McMeekin said, noting that the extent to which that affected quality of life is the subject of an analysis currently underway; those data are forthcoming.

Early-stage endometrial cancer poses a variety of clinical challenges, Dr. McMeekin said.

"Who is at risk? How is that risk defined? Which modalities reduce risk in which populations?" he said, noting that the information used on a day-to-day basis to help in decision making includes patient age and history, tumor grade, uterine characteristics, and nodal status.

Prior studies, including GOG 99 (Gyn. Oncol. 2004;92:744-51), have helped create risk models to identify patients at greater recurrence risk who might benefit most from adjuvant therapy such as pelvic radiation therapy. Risk criteria in GOG 99 were based on age and the number of risk factors, and while that study showed that pelvic radiation therapy reduced risk (and concluded that adjunctive radiation therapy in early-stage, intermediate-risk disease decreased the risk of recurrence, but should be limited to patients with high-intermediate risk), it also helped define patterns of failure, suggesting that distant sites of failure were "greater than we perhaps recognized," Dr. McMeekin said.

That, in turn, introduced the idea that a systemic therapy might improve outcomes, he added.

Chemotherapy moved to the forefront based on findings from GOG 122, which showed significant improvement in progression-free survival and overall survival with chemotherapy vs. whole abdomen radiation therapy in stage III and IV endometrial cancer, he said.

A number of uncontrolled studies have also suggested that chemotherapy may benefit other populations at increased risk, including patients with serous and clear cell stage I disease, who have a broad risk of recurrence ranging from 15% to 50% depending on disease and patient characteristics, and stage II patients, who have increased risk of loco-regional failure and progression-free survival rates comparable to those seen in high- intermediate-risk populations, he said.

The current study was initiated in light of these findings, but the investigators "could not identify subgroups for whom one therapy appeared to be more or less effective," Dr. McMeekin said.

He noted that the use of radiation therapy plus chemotherapy has been evaluated, including in two studies that demonstrated improved progression-free but not overall survival in patients with stage I-III disease.

"This is also the subject of the ongoing PORTEC-3 study, he said.

The current findings, which showed that "even in an enriched population, most patients did well," suggest that refinement is needed with respect to factors that define risk, he said, noting that selection based on clinical pathologic features and molecular profiling are underway both in the current study and another GOG study (GOG 210).

Dr. McMeekin reported having no disclosures.

TAMPA – Vaginal cuff brachytherapy followed by paclitaxel and carboplatin chemotherapy was not superior to pelvic radiation therapy in randomized phase III Gynecologic Oncology Group trial 249 involving women with high-intermediate-risk, early stage endometrial cancer.

The 24-month recurrence-free survival was 82% and 84% in 301 women assigned to receive pelvic radiation therapy (PXRT) and 300 women assigned to receive vaginal cuff brachytherapy followed by paclitaxel and carboplatin chemotherapy (VCB/C) for a hazard ratio of 0.97. Survival at 24 months was 93% in the PXRT group and 92% in the VCB/C group (hazard ratio, 1.28), Dr. D. Scott McMeekin reported during a late-breaking abstract session at the annual meeting of the Society of Gynecologic Oncology.

"There was no statistically significant evidence of heterogeneity of treatment effects with respect to recurrence-free survival among stage, age, race, performance status, histology, or lymphadenectomy use in either of the groups," said Dr. McMeekin of the University of Oklahoma, Oklahoma City.

Study subjects were women with a median age of 63 years. All of the women underwent hysterectomy and had either stage I endometrioid disease with high risk based on GOG (Gynecologic Oncology Group) trial 99 study criteria, stage II disease, or stage I-II serous or clear cell tumors. Most (74%) had stage I disease, and 89% underwent lymphadenectomy. Histology was endometrioid type in 71% of patients, serous in 15%, and clear cell in 5%.

All patients participated in quality of life assessments at five time points, and tissue samples were collected for a translational research correlative, he said.

Treatment began within 12 weeks following surgery. Those in the PXRT group were treated using standard four-field or intensity-modulated radiation therapy techniques (with optional VCB for those with serous or clear cell tumors or with stage II disease), and patients in the VCB/C group received high-dose rate or low-dose rate brachytherapy followed by paclitaxel (175 mg/m² over 3 hours) and carboplatin (AUC 6) every 21 days for a total of three cycles.

Treatment was generally well tolerated, with 91% of PXRT patients and 87% of VCB/C patients completing therapy.

"That being said, acute adverse effects were more frequent and tended to be more severe in patients receiving VCB/C," Dr. McMeekin said, noting that the extent to which that affected quality of life is the subject of an analysis currently underway; those data are forthcoming.

Early-stage endometrial cancer poses a variety of clinical challenges, Dr. McMeekin said.

"Who is at risk? How is that risk defined? Which modalities reduce risk in which populations?" he said, noting that the information used on a day-to-day basis to help in decision making includes patient age and history, tumor grade, uterine characteristics, and nodal status.

Prior studies, including GOG 99 (Gyn. Oncol. 2004;92:744-51), have helped create risk models to identify patients at greater recurrence risk who might benefit most from adjuvant therapy such as pelvic radiation therapy. Risk criteria in GOG 99 were based on age and the number of risk factors, and while that study showed that pelvic radiation therapy reduced risk (and concluded that adjunctive radiation therapy in early-stage, intermediate-risk disease decreased the risk of recurrence, but should be limited to patients with high-intermediate risk), it also helped define patterns of failure, suggesting that distant sites of failure were "greater than we perhaps recognized," Dr. McMeekin said.

That, in turn, introduced the idea that a systemic therapy might improve outcomes, he added.

Chemotherapy moved to the forefront based on findings from GOG 122, which showed significant improvement in progression-free survival and overall survival with chemotherapy vs. whole abdomen radiation therapy in stage III and IV endometrial cancer, he said.

A number of uncontrolled studies have also suggested that chemotherapy may benefit other populations at increased risk, including patients with serous and clear cell stage I disease, who have a broad risk of recurrence ranging from 15% to 50% depending on disease and patient characteristics, and stage II patients, who have increased risk of loco-regional failure and progression-free survival rates comparable to those seen in high- intermediate-risk populations, he said.

The current study was initiated in light of these findings, but the investigators "could not identify subgroups for whom one therapy appeared to be more or less effective," Dr. McMeekin said.

He noted that the use of radiation therapy plus chemotherapy has been evaluated, including in two studies that demonstrated improved progression-free but not overall survival in patients with stage I-III disease.

"This is also the subject of the ongoing PORTEC-3 study, he said.

The current findings, which showed that "even in an enriched population, most patients did well," suggest that refinement is needed with respect to factors that define risk, he said, noting that selection based on clinical pathologic features and molecular profiling are underway both in the current study and another GOG study (GOG 210).

Dr. McMeekin reported having no disclosures.

TAMPA – Vaginal cuff brachytherapy followed by paclitaxel and carboplatin chemotherapy was not superior to pelvic radiation therapy in randomized phase III Gynecologic Oncology Group trial 249 involving women with high-intermediate-risk, early stage endometrial cancer.

The 24-month recurrence-free survival was 82% and 84% in 301 women assigned to receive pelvic radiation therapy (PXRT) and 300 women assigned to receive vaginal cuff brachytherapy followed by paclitaxel and carboplatin chemotherapy (VCB/C) for a hazard ratio of 0.97. Survival at 24 months was 93% in the PXRT group and 92% in the VCB/C group (hazard ratio, 1.28), Dr. D. Scott McMeekin reported during a late-breaking abstract session at the annual meeting of the Society of Gynecologic Oncology.

"There was no statistically significant evidence of heterogeneity of treatment effects with respect to recurrence-free survival among stage, age, race, performance status, histology, or lymphadenectomy use in either of the groups," said Dr. McMeekin of the University of Oklahoma, Oklahoma City.

Study subjects were women with a median age of 63 years. All of the women underwent hysterectomy and had either stage I endometrioid disease with high risk based on GOG (Gynecologic Oncology Group) trial 99 study criteria, stage II disease, or stage I-II serous or clear cell tumors. Most (74%) had stage I disease, and 89% underwent lymphadenectomy. Histology was endometrioid type in 71% of patients, serous in 15%, and clear cell in 5%.

All patients participated in quality of life assessments at five time points, and tissue samples were collected for a translational research correlative, he said.

Treatment began within 12 weeks following surgery. Those in the PXRT group were treated using standard four-field or intensity-modulated radiation therapy techniques (with optional VCB for those with serous or clear cell tumors or with stage II disease), and patients in the VCB/C group received high-dose rate or low-dose rate brachytherapy followed by paclitaxel (175 mg/m² over 3 hours) and carboplatin (AUC 6) every 21 days for a total of three cycles.

Treatment was generally well tolerated, with 91% of PXRT patients and 87% of VCB/C patients completing therapy.

"That being said, acute adverse effects were more frequent and tended to be more severe in patients receiving VCB/C," Dr. McMeekin said, noting that the extent to which that affected quality of life is the subject of an analysis currently underway; those data are forthcoming.

Early-stage endometrial cancer poses a variety of clinical challenges, Dr. McMeekin said.

"Who is at risk? How is that risk defined? Which modalities reduce risk in which populations?" he said, noting that the information used on a day-to-day basis to help in decision making includes patient age and history, tumor grade, uterine characteristics, and nodal status.

Prior studies, including GOG 99 (Gyn. Oncol. 2004;92:744-51), have helped create risk models to identify patients at greater recurrence risk who might benefit most from adjuvant therapy such as pelvic radiation therapy. Risk criteria in GOG 99 were based on age and the number of risk factors, and while that study showed that pelvic radiation therapy reduced risk (and concluded that adjunctive radiation therapy in early-stage, intermediate-risk disease decreased the risk of recurrence, but should be limited to patients with high-intermediate risk), it also helped define patterns of failure, suggesting that distant sites of failure were "greater than we perhaps recognized," Dr. McMeekin said.

That, in turn, introduced the idea that a systemic therapy might improve outcomes, he added.

Chemotherapy moved to the forefront based on findings from GOG 122, which showed significant improvement in progression-free survival and overall survival with chemotherapy vs. whole abdomen radiation therapy in stage III and IV endometrial cancer, he said.

A number of uncontrolled studies have also suggested that chemotherapy may benefit other populations at increased risk, including patients with serous and clear cell stage I disease, who have a broad risk of recurrence ranging from 15% to 50% depending on disease and patient characteristics, and stage II patients, who have increased risk of loco-regional failure and progression-free survival rates comparable to those seen in high- intermediate-risk populations, he said.

The current study was initiated in light of these findings, but the investigators "could not identify subgroups for whom one therapy appeared to be more or less effective," Dr. McMeekin said.

He noted that the use of radiation therapy plus chemotherapy has been evaluated, including in two studies that demonstrated improved progression-free but not overall survival in patients with stage I-III disease.

"This is also the subject of the ongoing PORTEC-3 study, he said.

The current findings, which showed that "even in an enriched population, most patients did well," suggest that refinement is needed with respect to factors that define risk, he said, noting that selection based on clinical pathologic features and molecular profiling are underway both in the current study and another GOG study (GOG 210).

Dr. McMeekin reported having no disclosures.

TAMPA – High levels of FABP4 and ADH1B gene expression in patients with high-grade serous ovarian cancer are associated with significantly increased risk of residual disease after primary debulking surgery, according to an analysis of two large-scale, publicly available genomic data sets.

The findings could aid in the development of an algorithm for triaging patients to neoadjuvant approaches versus primary debulking, said Dr. Anil K. Sood at the annual meeting of the Society of Gynecologic Oncology.

In 491 patients from The Cancer Genome Atlas (TCGA) data set, and 189 from the Tothill data set, survival was significantly greater in patients with no residual disease than in those with any degree of residual disease. In both data sets, 47 prosets representing 38 different genes – significant in both data sets at a 10% false-discovery rate – were identified.

After several sets of validation, including qualitative validation in two additional data sets, and quantitative validation using primary ovarian cancer samples from 139 individuals, FABP4 and ADH1B were found to have the highest levels of expression, with substantial enrichment of FABP4 in those with residual disease in both the TCGA and Tothill data sets, Dr. Sood of the University of Texas M.D. Anderson Cancer Center, Houston, reported.

When FABP4 and ADH1B were plotted together, it was apparent that they were coordinated. That is, "when one is up, the other tends to be up," he said.

Furthermore, the changes weren’t subtle but were bimodal, he noted.

"If we consider those individuals who have the highest quartile of these genes – the top 25% – 88% of the individuals had residual disease when either FABP4 or ADH1B was elevated," he said, adding that looking at the second gene didn’t change things much because the two genes tend to be elevated jointly.

"To look at this in another way, the odds ratio was 5.5 for residual disease with high FABP4 levels, ... so if you look at those individuals with residual disease, 30 of 35 had high FABP4 levels, compared with those with low FABP4, where 54 out of 104 had residual disease," he said.

The findings are not surprising as FABP4 was shown in a prior study to play a prominent role in promoting omental metastasis and is considered a potential target for therapeutic approaches. However, the findings are important, because gross residual disease following primary cytoreduction is the best predictor of overall survival in patients with high-grade serous ovarian carcinoma, and the accurate identification of patients who will have residual disease has remained elusive.

"Outcome predictors could be very useful in predicting who would most likely benefit from surgical care up front versus potentially doing surgery in an interval setting following neoadjuvant chemotherapy," he said, noting that most prior attempts at identifying outcome predictors have focused on identifying patients most likely to undergo optimal debulking.

Furthermore, imaging parameters and circulating markers have not been particularly reliable predictors of residual disease following surgery.

"We have learned over the last several years that the greatest differences in outcomes really tend to be for those patients who have no gross residual, compared with those left with any degree of residual," he said, noting that this information prompted the current search for molecular predictors of residual disease, which is based on the premise that underlying biology could be different in tumors that are not fully resectable.

Though limited by the possibility that gene expression levels are different in primary versus metastatic disease sites, and by varying degrees of aggressiveness in debulking approaches at different cancer centers included in the data set, the findings nonetheless suggest that patients with high tumor expression of FABP4 may be candidates for neoadjuvant chemotherapy, Dr. Sood concluded.

Dr. Sood reported having no relevant disclosures.

TAMPA – High levels of FABP4 and ADH1B gene expression in patients with high-grade serous ovarian cancer are associated with significantly increased risk of residual disease after primary debulking surgery, according to an analysis of two large-scale, publicly available genomic data sets.

The findings could aid in the development of an algorithm for triaging patients to neoadjuvant approaches versus primary debulking, said Dr. Anil K. Sood at the annual meeting of the Society of Gynecologic Oncology.

In 491 patients from The Cancer Genome Atlas (TCGA) data set, and 189 from the Tothill data set, survival was significantly greater in patients with no residual disease than in those with any degree of residual disease. In both data sets, 47 prosets representing 38 different genes – significant in both data sets at a 10% false-discovery rate – were identified.

After several sets of validation, including qualitative validation in two additional data sets, and quantitative validation using primary ovarian cancer samples from 139 individuals, FABP4 and ADH1B were found to have the highest levels of expression, with substantial enrichment of FABP4 in those with residual disease in both the TCGA and Tothill data sets, Dr. Sood of the University of Texas M.D. Anderson Cancer Center, Houston, reported.

When FABP4 and ADH1B were plotted together, it was apparent that they were coordinated. That is, "when one is up, the other tends to be up," he said.

Furthermore, the changes weren’t subtle but were bimodal, he noted.

"If we consider those individuals who have the highest quartile of these genes – the top 25% – 88% of the individuals had residual disease when either FABP4 or ADH1B was elevated," he said, adding that looking at the second gene didn’t change things much because the two genes tend to be elevated jointly.

"To look at this in another way, the odds ratio was 5.5 for residual disease with high FABP4 levels, ... so if you look at those individuals with residual disease, 30 of 35 had high FABP4 levels, compared with those with low FABP4, where 54 out of 104 had residual disease," he said.

The findings are not surprising as FABP4 was shown in a prior study to play a prominent role in promoting omental metastasis and is considered a potential target for therapeutic approaches. However, the findings are important, because gross residual disease following primary cytoreduction is the best predictor of overall survival in patients with high-grade serous ovarian carcinoma, and the accurate identification of patients who will have residual disease has remained elusive.

"Outcome predictors could be very useful in predicting who would most likely benefit from surgical care up front versus potentially doing surgery in an interval setting following neoadjuvant chemotherapy," he said, noting that most prior attempts at identifying outcome predictors have focused on identifying patients most likely to undergo optimal debulking.

Furthermore, imaging parameters and circulating markers have not been particularly reliable predictors of residual disease following surgery.

"We have learned over the last several years that the greatest differences in outcomes really tend to be for those patients who have no gross residual, compared with those left with any degree of residual," he said, noting that this information prompted the current search for molecular predictors of residual disease, which is based on the premise that underlying biology could be different in tumors that are not fully resectable.

Though limited by the possibility that gene expression levels are different in primary versus metastatic disease sites, and by varying degrees of aggressiveness in debulking approaches at different cancer centers included in the data set, the findings nonetheless suggest that patients with high tumor expression of FABP4 may be candidates for neoadjuvant chemotherapy, Dr. Sood concluded.

Dr. Sood reported having no relevant disclosures.

TAMPA – High levels of FABP4 and ADH1B gene expression in patients with high-grade serous ovarian cancer are associated with significantly increased risk of residual disease after primary debulking surgery, according to an analysis of two large-scale, publicly available genomic data sets.

The findings could aid in the development of an algorithm for triaging patients to neoadjuvant approaches versus primary debulking, said Dr. Anil K. Sood at the annual meeting of the Society of Gynecologic Oncology.

In 491 patients from The Cancer Genome Atlas (TCGA) data set, and 189 from the Tothill data set, survival was significantly greater in patients with no residual disease than in those with any degree of residual disease. In both data sets, 47 prosets representing 38 different genes – significant in both data sets at a 10% false-discovery rate – were identified.

After several sets of validation, including qualitative validation in two additional data sets, and quantitative validation using primary ovarian cancer samples from 139 individuals, FABP4 and ADH1B were found to have the highest levels of expression, with substantial enrichment of FABP4 in those with residual disease in both the TCGA and Tothill data sets, Dr. Sood of the University of Texas M.D. Anderson Cancer Center, Houston, reported.

When FABP4 and ADH1B were plotted together, it was apparent that they were coordinated. That is, "when one is up, the other tends to be up," he said.

Furthermore, the changes weren’t subtle but were bimodal, he noted.

"If we consider those individuals who have the highest quartile of these genes – the top 25% – 88% of the individuals had residual disease when either FABP4 or ADH1B was elevated," he said, adding that looking at the second gene didn’t change things much because the two genes tend to be elevated jointly.

"To look at this in another way, the odds ratio was 5.5 for residual disease with high FABP4 levels, ... so if you look at those individuals with residual disease, 30 of 35 had high FABP4 levels, compared with those with low FABP4, where 54 out of 104 had residual disease," he said.

The findings are not surprising as FABP4 was shown in a prior study to play a prominent role in promoting omental metastasis and is considered a potential target for therapeutic approaches. However, the findings are important, because gross residual disease following primary cytoreduction is the best predictor of overall survival in patients with high-grade serous ovarian carcinoma, and the accurate identification of patients who will have residual disease has remained elusive.

"Outcome predictors could be very useful in predicting who would most likely benefit from surgical care up front versus potentially doing surgery in an interval setting following neoadjuvant chemotherapy," he said, noting that most prior attempts at identifying outcome predictors have focused on identifying patients most likely to undergo optimal debulking.

Furthermore, imaging parameters and circulating markers have not been particularly reliable predictors of residual disease following surgery.

"We have learned over the last several years that the greatest differences in outcomes really tend to be for those patients who have no gross residual, compared with those left with any degree of residual," he said, noting that this information prompted the current search for molecular predictors of residual disease, which is based on the premise that underlying biology could be different in tumors that are not fully resectable.

Though limited by the possibility that gene expression levels are different in primary versus metastatic disease sites, and by varying degrees of aggressiveness in debulking approaches at different cancer centers included in the data set, the findings nonetheless suggest that patients with high tumor expression of FABP4 may be candidates for neoadjuvant chemotherapy, Dr. Sood concluded.

Dr. Sood reported having no relevant disclosures.

TAMPA – Malignant ascites independently predicts poor prognosis among women with newly diagnosed advanced ovarian cancer, and thus may predict the likelihood of deriving long-term benefit from bevacizumab treatment, an investigator reported at the annual meeting of the Society of Gynecologic Oncology.

Of 1,151 completely resected patients with advanced epithelial ovarian cancer who were included in the Gynecologic Oncology Group (GOG) 218 study comparing standard cytotoxic chemotherapy with and without bevacizumab, 914 (79%) had ascites, and those patients were more likely than patients without ascites to have poor performance status, high-grade serous histology, higher baseline CA 125, and suboptimal cytoreduction, Dr. James Stuart Ferriss of Temple University, Philadelphia, reported.

RTEmagicC_0nhx543z_100308.photo.jpg.jpg

However, according to a post hoc analysis of data from the randomized, placebo-controlled, double-blinded study, ascitic patients treated with concurrent and maintenance bevacizumab had significantly better overall survival (hazard ratio, 0.82) and improved progression-free survival (HR, 0.72), compared with those who did not receive bevacizumab, Dr. Ferriss said.

The presence of ascites in this study was defined prospectively as more than 50 cm³ of peritoneal fluid at the time of maximum surgical cytoreductive effort. The two treatment arms were balanced with respect to the presence of ascites and other prognostic factors, he said.

For patients without ascites, no difference was seen in progression-free survival or overall survival based on treatment arm.

This secondary analysis was undertaken because bevacizumab was shown in GOG 218 and other studies to improve progression-free survival, but not overall survival, when given with cytotoxic chemotherapy and for maintenance therapy in patients with epithelial ovarian, fallopian tube, and peritoneal cancers, but factors predictive of long-term efficacy have remained elusive.

In fact, vascular endothelial growth factor inhibition (anti-VEGF) therapy as a whole has demonstrated "mostly short-term clinical benefit," he said.

A notable exception is cediranib, which demonstrated overall survival benefit in the ICON6 trial, he noted.

Because of limitations inherent in an unplanned analysis, the findings should be considered hypothesis generating, but if confirmed, they may change the application of bevacizumab in front-line therapy, he said.

Since malignant ascites has been associated with VEGF expression, thus providing a biological rationale that targeting VEGF could have preferential benefit for patients whose cancers are producing ascites, he and his colleagues investigated the value of ascites as a predictor of efficacy for bevacizumab.

Dr. Ferriss reported having no disclosures.

TAMPA – Malignant ascites independently predicts poor prognosis among women with newly diagnosed advanced ovarian cancer, and thus may predict the likelihood of deriving long-term benefit from bevacizumab treatment, an investigator reported at the annual meeting of the Society of Gynecologic Oncology.

Of 1,151 completely resected patients with advanced epithelial ovarian cancer who were included in the Gynecologic Oncology Group (GOG) 218 study comparing standard cytotoxic chemotherapy with and without bevacizumab, 914 (79%) had ascites, and those patients were more likely than patients without ascites to have poor performance status, high-grade serous histology, higher baseline CA 125, and suboptimal cytoreduction, Dr. James Stuart Ferriss of Temple University, Philadelphia, reported.

RTEmagicC_0nhx543z_100308.photo.jpg.jpg

However, according to a post hoc analysis of data from the randomized, placebo-controlled, double-blinded study, ascitic patients treated with concurrent and maintenance bevacizumab had significantly better overall survival (hazard ratio, 0.82) and improved progression-free survival (HR, 0.72), compared with those who did not receive bevacizumab, Dr. Ferriss said.

The presence of ascites in this study was defined prospectively as more than 50 cm³ of peritoneal fluid at the time of maximum surgical cytoreductive effort. The two treatment arms were balanced with respect to the presence of ascites and other prognostic factors, he said.

For patients without ascites, no difference was seen in progression-free survival or overall survival based on treatment arm.

This secondary analysis was undertaken because bevacizumab was shown in GOG 218 and other studies to improve progression-free survival, but not overall survival, when given with cytotoxic chemotherapy and for maintenance therapy in patients with epithelial ovarian, fallopian tube, and peritoneal cancers, but factors predictive of long-term efficacy have remained elusive.

In fact, vascular endothelial growth factor inhibition (anti-VEGF) therapy as a whole has demonstrated "mostly short-term clinical benefit," he said.

A notable exception is cediranib, which demonstrated overall survival benefit in the ICON6 trial, he noted.

Because of limitations inherent in an unplanned analysis, the findings should be considered hypothesis generating, but if confirmed, they may change the application of bevacizumab in front-line therapy, he said.

Since malignant ascites has been associated with VEGF expression, thus providing a biological rationale that targeting VEGF could have preferential benefit for patients whose cancers are producing ascites, he and his colleagues investigated the value of ascites as a predictor of efficacy for bevacizumab.

Dr. Ferriss reported having no disclosures.

TAMPA – Malignant ascites independently predicts poor prognosis among women with newly diagnosed advanced ovarian cancer, and thus may predict the likelihood of deriving long-term benefit from bevacizumab treatment, an investigator reported at the annual meeting of the Society of Gynecologic Oncology.

Of 1,151 completely resected patients with advanced epithelial ovarian cancer who were included in the Gynecologic Oncology Group (GOG) 218 study comparing standard cytotoxic chemotherapy with and without bevacizumab, 914 (79%) had ascites, and those patients were more likely than patients without ascites to have poor performance status, high-grade serous histology, higher baseline CA 125, and suboptimal cytoreduction, Dr. James Stuart Ferriss of Temple University, Philadelphia, reported.

RTEmagicC_0nhx543z_100308.photo.jpg.jpg

However, according to a post hoc analysis of data from the randomized, placebo-controlled, double-blinded study, ascitic patients treated with concurrent and maintenance bevacizumab had significantly better overall survival (hazard ratio, 0.82) and improved progression-free survival (HR, 0.72), compared with those who did not receive bevacizumab, Dr. Ferriss said.

The presence of ascites in this study was defined prospectively as more than 50 cm³ of peritoneal fluid at the time of maximum surgical cytoreductive effort. The two treatment arms were balanced with respect to the presence of ascites and other prognostic factors, he said.

For patients without ascites, no difference was seen in progression-free survival or overall survival based on treatment arm.

This secondary analysis was undertaken because bevacizumab was shown in GOG 218 and other studies to improve progression-free survival, but not overall survival, when given with cytotoxic chemotherapy and for maintenance therapy in patients with epithelial ovarian, fallopian tube, and peritoneal cancers, but factors predictive of long-term efficacy have remained elusive.

In fact, vascular endothelial growth factor inhibition (anti-VEGF) therapy as a whole has demonstrated "mostly short-term clinical benefit," he said.

A notable exception is cediranib, which demonstrated overall survival benefit in the ICON6 trial, he noted.

Because of limitations inherent in an unplanned analysis, the findings should be considered hypothesis generating, but if confirmed, they may change the application of bevacizumab in front-line therapy, he said.

Since malignant ascites has been associated with VEGF expression, thus providing a biological rationale that targeting VEGF could have preferential benefit for patients whose cancers are producing ascites, he and his colleagues investigated the value of ascites as a predictor of efficacy for bevacizumab.

Dr. Ferriss reported having no disclosures.

TAMPA – Sentinel lymph nodes identified using robotic fluorescence imaging show a high degree of diagnostic accuracy in women with endometrial cancer, according to interim findings from a prospective, multicenter cohort study.

Of 106 patients with clinical stage I disease who have undergone complete surgical staging thus far in the FIRES (Fluorescence Imaging for Robotic Endometrial Cancer Sentinel Node Mapping) trial, 96 had successful sentinel lymph node (SLN) mapping, and 11 of those had positive lymph nodes, or stage 3c disease. The SLN mapping identified metastatic disease in all 11 cases, resulting in a sensitivity of 100% and a negative predictive value of 100%, Dr. Emma C. Rossi of Indiana University, Indianapolis, reported at the annual meeting of the Society of Gynecologic Oncology.

Ten patients had no SLNs identified after injection of indocyanine green (ICG) dye, and 2 of those had stage 3c disease on complete lymphadenectomy, Dr. Rossi said.

Of the patients with stage 3c disease, all had at least one known risk factor for metastases to the nodes or recurrence, she noted.

The patients had a mean age of 61 years and a mean body mass index of about 35 kg/mm². They received cervical injection of 1 mg ICG to a 1-cm depth of the cervix at 3 and 9 o’clock. To achieve this dose, a 0.5-mg/mL concentration of ICG was created and delivered at both sites.This concentration is substantially lower than that advertised for the on-label approved use of ICG (vascular injection for perfusion imaging), Dr. Rossi said.

After cervical injection, surgical access was obtained and the robot was stopped. Near infrared imaging was activated and SLN mapping performed. All patients also underwent pelvic lymphadenectomy, and 70% underwent para-aortic lymphadenectomy as well.

All lymph nodes were evaluated using hematoxylin and eosin staining, and SLNs were ultrastaged with immunohistochemistry for cytokeratin.

Most patients (87%) had endometrioid cell type with stage 1 disease, and 85% of patients had confirmed stage1 disease on final pathology.

The mean number of sentinel nodes removed was 3.8, and the mean number of total nodes removed was 22.9.

"Those were seen bilaterally in 69% of the patient population," Dr. Rossi said.

A para-aortic sentinel lymph node was described in 30% of patients, but the majority of these were downstream from the pelvic sentinel lymph node, with only two isolated para-aortic sentinel lymph nodes found.

"Interestingly, in both of these patients, there was metastatic disease in the para-aortic SLN and no disease in the pelvic nonsentinel lymph nodes," she noted.

Sentinel nodes have been thought to have potential for improving upon the accuracy of metastatic disease detection. Part of the theory is that sentinel nodes are more likely than nonsentinel nodes to contain metastatic disease, and in fact, 7 of 13 node-positive patients in the FIRES trial had metastatic disease only in the sentinel nodes, with negative nonsentinel nodes – a finding that supports this theory, Dr. Rossi said.

"Part of the reason for this ... is the concept that we apply ultrastaging techniques to the sentinel nodes," she said, noting that the 7 of 13 patients with node-positive disease had that disease detected with ultrastaging alone, and that a significant number of those patients had isolated tumor cells. The clinical significance of isolated tumor cells is unknown.

"In conclusion, the identification of nodal metastases in endometrial cancer with robotic-assisted near infrared imaging appears to have a high degree of sensitivity and negative predictive value, with no false-negative sentinel nodes detected to date in the FIRES trial," she said.

She noted, however, that the sample size is currently inadequate for making any conclusions about the comparative accuracy of sentinel nodes detected using lymphadenectomy specimens.

"It’s also really important to reiterate that lymphatic metastases can be found in patients who fail to map sentinel lymph nodes, so the absence of finding a sentinel node after injection of dye does not exclude a patient from the possibility of metastatic disease," she said.

The FIRES trial, which is sponsored by Indiana University, is ongoing and is currently recruiting at seven U.S. centers.

Dr. Rossi reported having no relevant financial disclosures.

TAMPA – Sentinel lymph nodes identified using robotic fluorescence imaging show a high degree of diagnostic accuracy in women with endometrial cancer, according to interim findings from a prospective, multicenter cohort study.

Of 106 patients with clinical stage I disease who have undergone complete surgical staging thus far in the FIRES (Fluorescence Imaging for Robotic Endometrial Cancer Sentinel Node Mapping) trial, 96 had successful sentinel lymph node (SLN) mapping, and 11 of those had positive lymph nodes, or stage 3c disease. The SLN mapping identified metastatic disease in all 11 cases, resulting in a sensitivity of 100% and a negative predictive value of 100%, Dr. Emma C. Rossi of Indiana University, Indianapolis, reported at the annual meeting of the Society of Gynecologic Oncology.

Ten patients had no SLNs identified after injection of indocyanine green (ICG) dye, and 2 of those had stage 3c disease on complete lymphadenectomy, Dr. Rossi said.

Of the patients with stage 3c disease, all had at least one known risk factor for metastases to the nodes or recurrence, she noted.

The patients had a mean age of 61 years and a mean body mass index of about 35 kg/mm². They received cervical injection of 1 mg ICG to a 1-cm depth of the cervix at 3 and 9 o’clock. To achieve this dose, a 0.5-mg/mL concentration of ICG was created and delivered at both sites.This concentration is substantially lower than that advertised for the on-label approved use of ICG (vascular injection for perfusion imaging), Dr. Rossi said.

After cervical injection, surgical access was obtained and the robot was stopped. Near infrared imaging was activated and SLN mapping performed. All patients also underwent pelvic lymphadenectomy, and 70% underwent para-aortic lymphadenectomy as well.

All lymph nodes were evaluated using hematoxylin and eosin staining, and SLNs were ultrastaged with immunohistochemistry for cytokeratin.

Most patients (87%) had endometrioid cell type with stage 1 disease, and 85% of patients had confirmed stage1 disease on final pathology.

The mean number of sentinel nodes removed was 3.8, and the mean number of total nodes removed was 22.9.

"Those were seen bilaterally in 69% of the patient population," Dr. Rossi said.

A para-aortic sentinel lymph node was described in 30% of patients, but the majority of these were downstream from the pelvic sentinel lymph node, with only two isolated para-aortic sentinel lymph nodes found.

"Interestingly, in both of these patients, there was metastatic disease in the para-aortic SLN and no disease in the pelvic nonsentinel lymph nodes," she noted.

Sentinel nodes have been thought to have potential for improving upon the accuracy of metastatic disease detection. Part of the theory is that sentinel nodes are more likely than nonsentinel nodes to contain metastatic disease, and in fact, 7 of 13 node-positive patients in the FIRES trial had metastatic disease only in the sentinel nodes, with negative nonsentinel nodes – a finding that supports this theory, Dr. Rossi said.

"Part of the reason for this ... is the concept that we apply ultrastaging techniques to the sentinel nodes," she said, noting that the 7 of 13 patients with node-positive disease had that disease detected with ultrastaging alone, and that a significant number of those patients had isolated tumor cells. The clinical significance of isolated tumor cells is unknown.

"In conclusion, the identification of nodal metastases in endometrial cancer with robotic-assisted near infrared imaging appears to have a high degree of sensitivity and negative predictive value, with no false-negative sentinel nodes detected to date in the FIRES trial," she said.

She noted, however, that the sample size is currently inadequate for making any conclusions about the comparative accuracy of sentinel nodes detected using lymphadenectomy specimens.

"It’s also really important to reiterate that lymphatic metastases can be found in patients who fail to map sentinel lymph nodes, so the absence of finding a sentinel node after injection of dye does not exclude a patient from the possibility of metastatic disease," she said.

The FIRES trial, which is sponsored by Indiana University, is ongoing and is currently recruiting at seven U.S. centers.

Dr. Rossi reported having no relevant financial disclosures.

TAMPA – Sentinel lymph nodes identified using robotic fluorescence imaging show a high degree of diagnostic accuracy in women with endometrial cancer, according to interim findings from a prospective, multicenter cohort study.

Of 106 patients with clinical stage I disease who have undergone complete surgical staging thus far in the FIRES (Fluorescence Imaging for Robotic Endometrial Cancer Sentinel Node Mapping) trial, 96 had successful sentinel lymph node (SLN) mapping, and 11 of those had positive lymph nodes, or stage 3c disease. The SLN mapping identified metastatic disease in all 11 cases, resulting in a sensitivity of 100% and a negative predictive value of 100%, Dr. Emma C. Rossi of Indiana University, Indianapolis, reported at the annual meeting of the Society of Gynecologic Oncology.

Ten patients had no SLNs identified after injection of indocyanine green (ICG) dye, and 2 of those had stage 3c disease on complete lymphadenectomy, Dr. Rossi said.

Of the patients with stage 3c disease, all had at least one known risk factor for metastases to the nodes or recurrence, she noted.

The patients had a mean age of 61 years and a mean body mass index of about 35 kg/mm². They received cervical injection of 1 mg ICG to a 1-cm depth of the cervix at 3 and 9 o’clock. To achieve this dose, a 0.5-mg/mL concentration of ICG was created and delivered at both sites.This concentration is substantially lower than that advertised for the on-label approved use of ICG (vascular injection for perfusion imaging), Dr. Rossi said.

After cervical injection, surgical access was obtained and the robot was stopped. Near infrared imaging was activated and SLN mapping performed. All patients also underwent pelvic lymphadenectomy, and 70% underwent para-aortic lymphadenectomy as well.

All lymph nodes were evaluated using hematoxylin and eosin staining, and SLNs were ultrastaged with immunohistochemistry for cytokeratin.

Most patients (87%) had endometrioid cell type with stage 1 disease, and 85% of patients had confirmed stage1 disease on final pathology.

The mean number of sentinel nodes removed was 3.8, and the mean number of total nodes removed was 22.9.

"Those were seen bilaterally in 69% of the patient population," Dr. Rossi said.

A para-aortic sentinel lymph node was described in 30% of patients, but the majority of these were downstream from the pelvic sentinel lymph node, with only two isolated para-aortic sentinel lymph nodes found.

"Interestingly, in both of these patients, there was metastatic disease in the para-aortic SLN and no disease in the pelvic nonsentinel lymph nodes," she noted.

Sentinel nodes have been thought to have potential for improving upon the accuracy of metastatic disease detection. Part of the theory is that sentinel nodes are more likely than nonsentinel nodes to contain metastatic disease, and in fact, 7 of 13 node-positive patients in the FIRES trial had metastatic disease only in the sentinel nodes, with negative nonsentinel nodes – a finding that supports this theory, Dr. Rossi said.

"Part of the reason for this ... is the concept that we apply ultrastaging techniques to the sentinel nodes," she said, noting that the 7 of 13 patients with node-positive disease had that disease detected with ultrastaging alone, and that a significant number of those patients had isolated tumor cells. The clinical significance of isolated tumor cells is unknown.

"In conclusion, the identification of nodal metastases in endometrial cancer with robotic-assisted near infrared imaging appears to have a high degree of sensitivity and negative predictive value, with no false-negative sentinel nodes detected to date in the FIRES trial," she said.

She noted, however, that the sample size is currently inadequate for making any conclusions about the comparative accuracy of sentinel nodes detected using lymphadenectomy specimens.

"It’s also really important to reiterate that lymphatic metastases can be found in patients who fail to map sentinel lymph nodes, so the absence of finding a sentinel node after injection of dye does not exclude a patient from the possibility of metastatic disease," she said.

The FIRES trial, which is sponsored by Indiana University, is ongoing and is currently recruiting at seven U.S. centers.

Dr. Rossi reported having no relevant financial disclosures.

TAMPA – The ability to perform daily activities was not associated with the completion of chemotherapy without dose reduction or delay in elderly women with ovarian, primary peritoneal, or fallopian tube cancer.

However, reporting limited social activities was significantly associated with decreased chemotherapy tolerance, reported Dr. Vivian E. von Gruenigen at the annual meeting of the Society of Gynecologic Oncology.

In the study, 149 women with a mean age of 77 years received carboplatin and paclitaxel (regimen 1) and 59 women with a mean age of 83 years received carboplatin alone (regimen 2), either after primary surgery or as neoadjuvant therapy. Among the study participants, 82% in regimen 1 and 54% in regimen 2 completed four cycles of the chemotherapy without dose reduction or delay of more than 7 days, and 92% in regimen 1 and 75% in regimen 2 eventually completed all cycles. Treatment delays of 7 days or longer were required by 18% of women in regimen 1 and 46% of women in regimen 2.

After adjusting for chemotherapy received, age, and performance status at baseline, instrumental activities of daily living (IADL) scores were not significantly associated with the ability to complete all four cycles (P = .2); only the report of limited social activities was significantly associated with the ability to complete all four cycles (P = .034), Dr. von Gruenigen of Northeastern Ohio Universities, Rootstown, reported during a late-breaking abstract session.

Women in the study were aged 70 years or older with newly diagnosed, pathology-confirmed adenocarcinoma of the ovary, peritoneum, or fallopian tube. The treatment regimen used was decided upon by the treating physician and patient. Those in regimen 1 received carboplatin (AUC 5) and paclitaxel (135 mg/m² plus granulocyte colony-stimulating factor), every 3 weeks. Those in regimen 2 received carboplatin (AUC 5) every 3 weeks.

Geriatric assessment at baseline, before the third cycle, and after the fourth cycle included assessments of activities of daily living, quality of life, social activity, and social support. Since elderly women with primary ovarian cancer are less likely to be offered standard cancer treatments, develop higher levels of toxicity, and have lower survival rates, Dr. von Gruenigen and her colleagues aimed to determine whether the geriatric assessment was associated with the ability of elderly patients to complete platinum-based chemotherapy.

The study is the first large prospective U.S. study of elderly women with ovarian cancer, she said, noting that in addition to not being provided with appropriate care, few elderly women with ovarian cancer are included in clinical trials.

This is particularly concerning given that with the aging population, ovarian cancer rates will increase among the elderly, including among the "oldest of old."

"Chronological age does not automatically equal functional age. For healthcare professionals to apply study results to patients seen in clinical practice, we need to expand beyond measuring performance status as reported by us – the healthcare provider – and become more flexible with parameters of care," she said.

In the current study, patients in the regimen 1 and 2 groups were very different populations. In addition to being younger, having higher completion rates, and requiring fewer treatment delays, the women in the regimen 1 group were also fitter (11% vs. 37% had a performance status of 2-3), but the groups did not differ with respect to race or stage.

It is possible that physicians and patients are considering geriatric score and quality of life already when selecting treatment, Dr. von Gruenigen noted.

Regardless of therapy regimen, most patients eventually completed four cycles of chemotherapy, and quality of life improved over time – even in the very elderly.

A third "dose-dense" study arm involving weekly carboplatin and paclitaxel treatment was added in Aug. 13 after the initial two arms completed accrual. The new arm continues to accrue, and an analysis of pharmacokinetics is also ongoing.

Future study design may involve incorporating single-agent carboplatin into trials with the oldest patients.

"In summary, cautious management, appropriate treatment, and prevention of toxicity through interventions are needed in this elderly population," she said.

Dr. von Gruenigen reported having no disclosures.

TAMPA – The ability to perform daily activities was not associated with the completion of chemotherapy without dose reduction or delay in elderly women with ovarian, primary peritoneal, or fallopian tube cancer.

However, reporting limited social activities was significantly associated with decreased chemotherapy tolerance, reported Dr. Vivian E. von Gruenigen at the annual meeting of the Society of Gynecologic Oncology.

In the study, 149 women with a mean age of 77 years received carboplatin and paclitaxel (regimen 1) and 59 women with a mean age of 83 years received carboplatin alone (regimen 2), either after primary surgery or as neoadjuvant therapy. Among the study participants, 82% in regimen 1 and 54% in regimen 2 completed four cycles of the chemotherapy without dose reduction or delay of more than 7 days, and 92% in regimen 1 and 75% in regimen 2 eventually completed all cycles. Treatment delays of 7 days or longer were required by 18% of women in regimen 1 and 46% of women in regimen 2.

After adjusting for chemotherapy received, age, and performance status at baseline, instrumental activities of daily living (IADL) scores were not significantly associated with the ability to complete all four cycles (P = .2); only the report of limited social activities was significantly associated with the ability to complete all four cycles (P = .034), Dr. von Gruenigen of Northeastern Ohio Universities, Rootstown, reported during a late-breaking abstract session.

Women in the study were aged 70 years or older with newly diagnosed, pathology-confirmed adenocarcinoma of the ovary, peritoneum, or fallopian tube. The treatment regimen used was decided upon by the treating physician and patient. Those in regimen 1 received carboplatin (AUC 5) and paclitaxel (135 mg/m² plus granulocyte colony-stimulating factor), every 3 weeks. Those in regimen 2 received carboplatin (AUC 5) every 3 weeks.

Geriatric assessment at baseline, before the third cycle, and after the fourth cycle included assessments of activities of daily living, quality of life, social activity, and social support. Since elderly women with primary ovarian cancer are less likely to be offered standard cancer treatments, develop higher levels of toxicity, and have lower survival rates, Dr. von Gruenigen and her colleagues aimed to determine whether the geriatric assessment was associated with the ability of elderly patients to complete platinum-based chemotherapy.

The study is the first large prospective U.S. study of elderly women with ovarian cancer, she said, noting that in addition to not being provided with appropriate care, few elderly women with ovarian cancer are included in clinical trials.

This is particularly concerning given that with the aging population, ovarian cancer rates will increase among the elderly, including among the "oldest of old."

"Chronological age does not automatically equal functional age. For healthcare professionals to apply study results to patients seen in clinical practice, we need to expand beyond measuring performance status as reported by us – the healthcare provider – and become more flexible with parameters of care," she said.

In the current study, patients in the regimen 1 and 2 groups were very different populations. In addition to being younger, having higher completion rates, and requiring fewer treatment delays, the women in the regimen 1 group were also fitter (11% vs. 37% had a performance status of 2-3), but the groups did not differ with respect to race or stage.

It is possible that physicians and patients are considering geriatric score and quality of life already when selecting treatment, Dr. von Gruenigen noted.

Regardless of therapy regimen, most patients eventually completed four cycles of chemotherapy, and quality of life improved over time – even in the very elderly.

A third "dose-dense" study arm involving weekly carboplatin and paclitaxel treatment was added in Aug. 13 after the initial two arms completed accrual. The new arm continues to accrue, and an analysis of pharmacokinetics is also ongoing.

Future study design may involve incorporating single-agent carboplatin into trials with the oldest patients.

"In summary, cautious management, appropriate treatment, and prevention of toxicity through interventions are needed in this elderly population," she said.

Dr. von Gruenigen reported having no disclosures.

TAMPA – The ability to perform daily activities was not associated with the completion of chemotherapy without dose reduction or delay in elderly women with ovarian, primary peritoneal, or fallopian tube cancer.

However, reporting limited social activities was significantly associated with decreased chemotherapy tolerance, reported Dr. Vivian E. von Gruenigen at the annual meeting of the Society of Gynecologic Oncology.

In the study, 149 women with a mean age of 77 years received carboplatin and paclitaxel (regimen 1) and 59 women with a mean age of 83 years received carboplatin alone (regimen 2), either after primary surgery or as neoadjuvant therapy. Among the study participants, 82% in regimen 1 and 54% in regimen 2 completed four cycles of the chemotherapy without dose reduction or delay of more than 7 days, and 92% in regimen 1 and 75% in regimen 2 eventually completed all cycles. Treatment delays of 7 days or longer were required by 18% of women in regimen 1 and 46% of women in regimen 2.

After adjusting for chemotherapy received, age, and performance status at baseline, instrumental activities of daily living (IADL) scores were not significantly associated with the ability to complete all four cycles (P = .2); only the report of limited social activities was significantly associated with the ability to complete all four cycles (P = .034), Dr. von Gruenigen of Northeastern Ohio Universities, Rootstown, reported during a late-breaking abstract session.

Women in the study were aged 70 years or older with newly diagnosed, pathology-confirmed adenocarcinoma of the ovary, peritoneum, or fallopian tube. The treatment regimen used was decided upon by the treating physician and patient. Those in regimen 1 received carboplatin (AUC 5) and paclitaxel (135 mg/m² plus granulocyte colony-stimulating factor), every 3 weeks. Those in regimen 2 received carboplatin (AUC 5) every 3 weeks.

Geriatric assessment at baseline, before the third cycle, and after the fourth cycle included assessments of activities of daily living, quality of life, social activity, and social support. Since elderly women with primary ovarian cancer are less likely to be offered standard cancer treatments, develop higher levels of toxicity, and have lower survival rates, Dr. von Gruenigen and her colleagues aimed to determine whether the geriatric assessment was associated with the ability of elderly patients to complete platinum-based chemotherapy.

The study is the first large prospective U.S. study of elderly women with ovarian cancer, she said, noting that in addition to not being provided with appropriate care, few elderly women with ovarian cancer are included in clinical trials.

This is particularly concerning given that with the aging population, ovarian cancer rates will increase among the elderly, including among the "oldest of old."

"Chronological age does not automatically equal functional age. For healthcare professionals to apply study results to patients seen in clinical practice, we need to expand beyond measuring performance status as reported by us – the healthcare provider – and become more flexible with parameters of care," she said.

In the current study, patients in the regimen 1 and 2 groups were very different populations. In addition to being younger, having higher completion rates, and requiring fewer treatment delays, the women in the regimen 1 group were also fitter (11% vs. 37% had a performance status of 2-3), but the groups did not differ with respect to race or stage.

It is possible that physicians and patients are considering geriatric score and quality of life already when selecting treatment, Dr. von Gruenigen noted.

Regardless of therapy regimen, most patients eventually completed four cycles of chemotherapy, and quality of life improved over time – even in the very elderly.

A third "dose-dense" study arm involving weekly carboplatin and paclitaxel treatment was added in Aug. 13 after the initial two arms completed accrual. The new arm continues to accrue, and an analysis of pharmacokinetics is also ongoing.

Future study design may involve incorporating single-agent carboplatin into trials with the oldest patients.

"In summary, cautious management, appropriate treatment, and prevention of toxicity through interventions are needed in this elderly population," she said.

Dr. von Gruenigen reported having no disclosures.

TAMPA – Women who undergo bariatric surgery to lose weight are about 70% less likely to develop uterine cancer than are obese women who do not undergo such surgery, according to findings from a large retrospective cohort study.

The risk reduction was even greater (81%) among those who maintained their weight loss after surgery. The findings suggest that obesity may be a modifiable risk factor for uterine cancer, reported Dr. Kristy Kay Ward of the Moores Cancer Center at the University of California, San Diego.

Of more than 7.4 million inpatient admissions among women aged 18 years or older who were registered in the University Health System Consortium dataset from Jan. 1, 2009, to June 1, 2013, 103,797 had a history of bariatric surgery, and 44,345 had a diagnosis of uterine malignancy. The overall rate of uterine malignancy was 599/100,000 patients among those without a history of bariatric surgery, and which was 2.8 times higher among obese vs. nonobese patients within this group (1,409 vs. 496 per 100,000).

The overall rate of uterine cancer among those with a history of bariatric surgery was 408/100,000, but the rate was 2.5 times higher among those with persistent obesity after surgery, compared with those who maintained weight loss after surgery (682/100,000 vs. 270/100,000), Dr. Ward said at the annual meeting of the Society of Gynecologic Oncology.

Compared with obese women without a history of bariatric surgery, the relative risk of uterine cancer was 0.29 for women with prior bariatric surgery, 0.19 for women with normal weight after surgery, and 0.48 for women who remained obese after surgery, so the overall risk reduction with surgery was 70%, the maximum risk reduction (for those with normal weight after surgery) was 81%, and the lowest reduction in risk (for those who had surgery but remained obese) was 52%, Dr. Ward said.

Though limited by the retrospective nature of the study and the fact that the data didn’t differentiate between types of bariatric surgery, the findings are notable, because about 50,000 women were diagnosed with uterine cancer in 2013, making it the most common cancer affecting female reproductive organs. Furthermore, endometrial cancer, which accounts for 95% of uterine cancers, is associated with obesity in about 50% of cases, she explained.

In fact, obese women are two- to fourfold more likely to develop endometrial cancer than are women of normal weight, she said.

The current findings suggest that "a history of bariatric surgery is associated with substantial and clinically significantly reduced risk of uterine malignancy," she said, adding: "Our previous work, in agreement with the findings of others, had indicated that the risk of uterine malignancy increases linearly with BMI [body mass index]. Along with the findings of the current study, this supports that obesity may be a modifiable risk factor related to the development of endometrial cancer."

The mechanism for the link between bariatric surgery and reduced uterine cancer risk remains unclear, but fat loss likely plays a role, as adiposity is known to increase endogenous estrogen circulation. The bariatric surgery itself may also "somehow be influencing the immune system and decreasing inflammation," thereby contributing to decreased cancer risk, Dr. Ward noted.

The findings suggest that weight reduction measures, including bariatric surgery in appropriate candidates, are vitally important in obese women, she said.

"Screening of patients, counseling patients about the dangers of obesity, and appropriate referral for bariatric surgery may have great impact on the overall health of this population," she concluded, adding that future research should examine the benefits of bariatric surgery for the reduction of cancer, including endometrial cancer.

Dr. Ward reported having no disclosures.

TAMPA – Women who undergo bariatric surgery to lose weight are about 70% less likely to develop uterine cancer than are obese women who do not undergo such surgery, according to findings from a large retrospective cohort study.

The risk reduction was even greater (81%) among those who maintained their weight loss after surgery. The findings suggest that obesity may be a modifiable risk factor for uterine cancer, reported Dr. Kristy Kay Ward of the Moores Cancer Center at the University of California, San Diego.

Of more than 7.4 million inpatient admissions among women aged 18 years or older who were registered in the University Health System Consortium dataset from Jan. 1, 2009, to June 1, 2013, 103,797 had a history of bariatric surgery, and 44,345 had a diagnosis of uterine malignancy. The overall rate of uterine malignancy was 599/100,000 patients among those without a history of bariatric surgery, and which was 2.8 times higher among obese vs. nonobese patients within this group (1,409 vs. 496 per 100,000).

The overall rate of uterine cancer among those with a history of bariatric surgery was 408/100,000, but the rate was 2.5 times higher among those with persistent obesity after surgery, compared with those who maintained weight loss after surgery (682/100,000 vs. 270/100,000), Dr. Ward said at the annual meeting of the Society of Gynecologic Oncology.

Compared with obese women without a history of bariatric surgery, the relative risk of uterine cancer was 0.29 for women with prior bariatric surgery, 0.19 for women with normal weight after surgery, and 0.48 for women who remained obese after surgery, so the overall risk reduction with surgery was 70%, the maximum risk reduction (for those with normal weight after surgery) was 81%, and the lowest reduction in risk (for those who had surgery but remained obese) was 52%, Dr. Ward said.

Though limited by the retrospective nature of the study and the fact that the data didn’t differentiate between types of bariatric surgery, the findings are notable, because about 50,000 women were diagnosed with uterine cancer in 2013, making it the most common cancer affecting female reproductive organs. Furthermore, endometrial cancer, which accounts for 95% of uterine cancers, is associated with obesity in about 50% of cases, she explained.

In fact, obese women are two- to fourfold more likely to develop endometrial cancer than are women of normal weight, she said.

The current findings suggest that "a history of bariatric surgery is associated with substantial and clinically significantly reduced risk of uterine malignancy," she said, adding: "Our previous work, in agreement with the findings of others, had indicated that the risk of uterine malignancy increases linearly with BMI [body mass index]. Along with the findings of the current study, this supports that obesity may be a modifiable risk factor related to the development of endometrial cancer."

The mechanism for the link between bariatric surgery and reduced uterine cancer risk remains unclear, but fat loss likely plays a role, as adiposity is known to increase endogenous estrogen circulation. The bariatric surgery itself may also "somehow be influencing the immune system and decreasing inflammation," thereby contributing to decreased cancer risk, Dr. Ward noted.

The findings suggest that weight reduction measures, including bariatric surgery in appropriate candidates, are vitally important in obese women, she said.

"Screening of patients, counseling patients about the dangers of obesity, and appropriate referral for bariatric surgery may have great impact on the overall health of this population," she concluded, adding that future research should examine the benefits of bariatric surgery for the reduction of cancer, including endometrial cancer.

Dr. Ward reported having no disclosures.

TAMPA – Women who undergo bariatric surgery to lose weight are about 70% less likely to develop uterine cancer than are obese women who do not undergo such surgery, according to findings from a large retrospective cohort study.

The risk reduction was even greater (81%) among those who maintained their weight loss after surgery. The findings suggest that obesity may be a modifiable risk factor for uterine cancer, reported Dr. Kristy Kay Ward of the Moores Cancer Center at the University of California, San Diego.

Of more than 7.4 million inpatient admissions among women aged 18 years or older who were registered in the University Health System Consortium dataset from Jan. 1, 2009, to June 1, 2013, 103,797 had a history of bariatric surgery, and 44,345 had a diagnosis of uterine malignancy. The overall rate of uterine malignancy was 599/100,000 patients among those without a history of bariatric surgery, and which was 2.8 times higher among obese vs. nonobese patients within this group (1,409 vs. 496 per 100,000).

The overall rate of uterine cancer among those with a history of bariatric surgery was 408/100,000, but the rate was 2.5 times higher among those with persistent obesity after surgery, compared with those who maintained weight loss after surgery (682/100,000 vs. 270/100,000), Dr. Ward said at the annual meeting of the Society of Gynecologic Oncology.

Compared with obese women without a history of bariatric surgery, the relative risk of uterine cancer was 0.29 for women with prior bariatric surgery, 0.19 for women with normal weight after surgery, and 0.48 for women who remained obese after surgery, so the overall risk reduction with surgery was 70%, the maximum risk reduction (for those with normal weight after surgery) was 81%, and the lowest reduction in risk (for those who had surgery but remained obese) was 52%, Dr. Ward said.

Though limited by the retrospective nature of the study and the fact that the data didn’t differentiate between types of bariatric surgery, the findings are notable, because about 50,000 women were diagnosed with uterine cancer in 2013, making it the most common cancer affecting female reproductive organs. Furthermore, endometrial cancer, which accounts for 95% of uterine cancers, is associated with obesity in about 50% of cases, she explained.

In fact, obese women are two- to fourfold more likely to develop endometrial cancer than are women of normal weight, she said.

The current findings suggest that "a history of bariatric surgery is associated with substantial and clinically significantly reduced risk of uterine malignancy," she said, adding: "Our previous work, in agreement with the findings of others, had indicated that the risk of uterine malignancy increases linearly with BMI [body mass index]. Along with the findings of the current study, this supports that obesity may be a modifiable risk factor related to the development of endometrial cancer."

The mechanism for the link between bariatric surgery and reduced uterine cancer risk remains unclear, but fat loss likely plays a role, as adiposity is known to increase endogenous estrogen circulation. The bariatric surgery itself may also "somehow be influencing the immune system and decreasing inflammation," thereby contributing to decreased cancer risk, Dr. Ward noted.

The findings suggest that weight reduction measures, including bariatric surgery in appropriate candidates, are vitally important in obese women, she said.

"Screening of patients, counseling patients about the dangers of obesity, and appropriate referral for bariatric surgery may have great impact on the overall health of this population," she concluded, adding that future research should examine the benefits of bariatric surgery for the reduction of cancer, including endometrial cancer.

Dr. Ward reported having no disclosures.

TAMPA – Women with BRCA1 mutations who undergo risk-reducing salpingo-oophorectomy may remain at risk for rare types of aggressive uterine cancer, according to preliminary findings from a prospective cohort study.

Of 525 women with BRCA1 or BRCA2 gene mutations who underwent risk-reducing salpingo-oophorectomy (RRSO) without hysterectomy and who were followed for a median of 5.8 years, 4 developed a high-risk uterine corpus cancer, including 2 who developed serous disease, 1 who developed carcinosarcoma, and 1 who developed leiomyosarcoma. All occurred in the 296 women in the study who had BRCA1 mutations, for a 2.1% 10-year risk of uterine cancer following RRSO in those women, Dr. Catherine Shu reported during a late-breaking abstract session at the annual meeting of the Society of Gynecologic Oncology.

RTEmagicC_kb5grhcj_100096.photo.jpg.jpg

The expected number of these types of high-risk cancer in this population, based on age- and race-based Surveillance, Epidemiology, and End Results (SEER) data adjusted for prevalence of hysterectomy, was 0.28, for a highly significant ratio of observed to expected cancers (O/E) of 14.48 (P less than .001), said Dr. Shu, chief fellow in medical oncology at Memorial Sloan Kettering Cancer Center, New York.

One of the cases occurred among the 169 women in the study with no prior breast cancer (O/E, 16.7; P =.06), and three occurred among 356 with prior breast cancer (O/E, 14.01; P =.001). When stratified based on tamoxifen exposure, high-risk uterine cancer was observed in 2 of 131woman with exposure (O/E, 21.68; P =.004), and in 2 of 394 with no exposure (O/E, 10.87; P =.015), Dr. Shu said.

The women included in the study represented 79% of all women at Memorial Sloan Kettering Cancer Center who underwent genetic testing followed by risk-reducing surgery without hysterectomy from June 1, 1995, to Dec. 31, 2011. They had a mean age of 46.1 years.

The "time at risk" for participants began after both receipt of genetic testing results and RRSO, and the participants were followed annually by questionnaires and medical records review. Censoring events were hysterectomy, uterine cancer diagnosis, last follow-up, or death, Dr. Shu noted.

Importantly, no increased risk was seen for more common types of uterine cancer, including endometrioid, mucinous, adenocarcinoma, and not otherwise specified cancers.

Those who developed high-risk cancer were treated with chemotherapy and/or radiation, and all four were living at the time of Dr. Shu’s presentation, although one had metastatic disease.

Although this study is one of the largest prospective studies to date to look at the likelihood of high-risk uterine cancer among BRCA-positive patients who undergo RRSO without hysterectomy, it has a number of limitations, such as possible misclassification of rare uterine cancer subtypes in the SEER database and possible confounding by tamoxifen exposure. The findings require confirmation and should thus be considered preliminary, Dr. Shu said.

Indeed, it would be premature at this point to recommend routine hysterectomy along with RRSO women with BRCA1 mutations; the decision regarding hysterectomy at the time of RRSO may depend on the patient’s age, prior cancer history, and other risk factors, senior author Noah D. Kauff of Memorial Sloan Kettering Cancer Center, said in a press statement.

Currently, based on the fact that women with a BRCA1 mutation have a 39%-46% chance of developing ovarian cancer and 50%-85% chance of developing breast cancer, the National Comprehensive Cancer Network recommends RRSO between ages 35 years and 40 years, after childbearing is complete.

Hysterectomy at the time of RRSO is not recommended because of risks associated with the procedure, including bleeding and infection risks, as well the potential for long-term problems with bladder, bowel, and sexual function, and also because uterine cancers that develop after RRSO have been thought to generally be low risk, according to the press statement.

The current findings suggest this may not be the case,

Pending confirmation of the findings, women with BRCA1 gene mutations who are considering risk-reducing surgery should be advised that "this report suggests they may be at risk for rare types of aggressive uterine cancer," and the potential advantages and disadvantages of concomitant hysterectomy should be discussed, Dr. Kauff said.

Dr. Shu and Dr. Kauff reported having no disclosures.

TAMPA – Women with BRCA1 mutations who undergo risk-reducing salpingo-oophorectomy may remain at risk for rare types of aggressive uterine cancer, according to preliminary findings from a prospective cohort study.

Of 525 women with BRCA1 or BRCA2 gene mutations who underwent risk-reducing salpingo-oophorectomy (RRSO) without hysterectomy and who were followed for a median of 5.8 years, 4 developed a high-risk uterine corpus cancer, including 2 who developed serous disease, 1 who developed carcinosarcoma, and 1 who developed leiomyosarcoma. All occurred in the 296 women in the study who had BRCA1 mutations, for a 2.1% 10-year risk of uterine cancer following RRSO in those women, Dr. Catherine Shu reported during a late-breaking abstract session at the annual meeting of the Society of Gynecologic Oncology.

RTEmagicC_kb5grhcj_100096.photo.jpg.jpg

The expected number of these types of high-risk cancer in this population, based on age- and race-based Surveillance, Epidemiology, and End Results (SEER) data adjusted for prevalence of hysterectomy, was 0.28, for a highly significant ratio of observed to expected cancers (O/E) of 14.48 (P less than .001), said Dr. Shu, chief fellow in medical oncology at Memorial Sloan Kettering Cancer Center, New York.

One of the cases occurred among the 169 women in the study with no prior breast cancer (O/E, 16.7; P =.06), and three occurred among 356 with prior breast cancer (O/E, 14.01; P =.001). When stratified based on tamoxifen exposure, high-risk uterine cancer was observed in 2 of 131woman with exposure (O/E, 21.68; P =.004), and in 2 of 394 with no exposure (O/E, 10.87; P =.015), Dr. Shu said.

The women included in the study represented 79% of all women at Memorial Sloan Kettering Cancer Center who underwent genetic testing followed by risk-reducing surgery without hysterectomy from June 1, 1995, to Dec. 31, 2011. They had a mean age of 46.1 years.

The "time at risk" for participants began after both receipt of genetic testing results and RRSO, and the participants were followed annually by questionnaires and medical records review. Censoring events were hysterectomy, uterine cancer diagnosis, last follow-up, or death, Dr. Shu noted.

Importantly, no increased risk was seen for more common types of uterine cancer, including endometrioid, mucinous, adenocarcinoma, and not otherwise specified cancers.

Those who developed high-risk cancer were treated with chemotherapy and/or radiation, and all four were living at the time of Dr. Shu’s presentation, although one had metastatic disease.

Although this study is one of the largest prospective studies to date to look at the likelihood of high-risk uterine cancer among BRCA-positive patients who undergo RRSO without hysterectomy, it has a number of limitations, such as possible misclassification of rare uterine cancer subtypes in the SEER database and possible confounding by tamoxifen exposure. The findings require confirmation and should thus be considered preliminary, Dr. Shu said.

Indeed, it would be premature at this point to recommend routine hysterectomy along with RRSO women with BRCA1 mutations; the decision regarding hysterectomy at the time of RRSO may depend on the patient’s age, prior cancer history, and other risk factors, senior author Noah D. Kauff of Memorial Sloan Kettering Cancer Center, said in a press statement.

Currently, based on the fact that women with a BRCA1 mutation have a 39%-46% chance of developing ovarian cancer and 50%-85% chance of developing breast cancer, the National Comprehensive Cancer Network recommends RRSO between ages 35 years and 40 years, after childbearing is complete.

Hysterectomy at the time of RRSO is not recommended because of risks associated with the procedure, including bleeding and infection risks, as well the potential for long-term problems with bladder, bowel, and sexual function, and also because uterine cancers that develop after RRSO have been thought to generally be low risk, according to the press statement.

The current findings suggest this may not be the case,

Pending confirmation of the findings, women with BRCA1 gene mutations who are considering risk-reducing surgery should be advised that "this report suggests they may be at risk for rare types of aggressive uterine cancer," and the potential advantages and disadvantages of concomitant hysterectomy should be discussed, Dr. Kauff said.

Dr. Shu and Dr. Kauff reported having no disclosures.

TAMPA – Women with BRCA1 mutations who undergo risk-reducing salpingo-oophorectomy may remain at risk for rare types of aggressive uterine cancer, according to preliminary findings from a prospective cohort study.

Of 525 women with BRCA1 or BRCA2 gene mutations who underwent risk-reducing salpingo-oophorectomy (RRSO) without hysterectomy and who were followed for a median of 5.8 years, 4 developed a high-risk uterine corpus cancer, including 2 who developed serous disease, 1 who developed carcinosarcoma, and 1 who developed leiomyosarcoma. All occurred in the 296 women in the study who had BRCA1 mutations, for a 2.1% 10-year risk of uterine cancer following RRSO in those women, Dr. Catherine Shu reported during a late-breaking abstract session at the annual meeting of the Society of Gynecologic Oncology.

RTEmagicC_kb5grhcj_100096.photo.jpg.jpg

The expected number of these types of high-risk cancer in this population, based on age- and race-based Surveillance, Epidemiology, and End Results (SEER) data adjusted for prevalence of hysterectomy, was 0.28, for a highly significant ratio of observed to expected cancers (O/E) of 14.48 (P less than .001), said Dr. Shu, chief fellow in medical oncology at Memorial Sloan Kettering Cancer Center, New York.

One of the cases occurred among the 169 women in the study with no prior breast cancer (O/E, 16.7; P =.06), and three occurred among 356 with prior breast cancer (O/E, 14.01; P =.001). When stratified based on tamoxifen exposure, high-risk uterine cancer was observed in 2 of 131woman with exposure (O/E, 21.68; P =.004), and in 2 of 394 with no exposure (O/E, 10.87; P =.015), Dr. Shu said.

The women included in the study represented 79% of all women at Memorial Sloan Kettering Cancer Center who underwent genetic testing followed by risk-reducing surgery without hysterectomy from June 1, 1995, to Dec. 31, 2011. They had a mean age of 46.1 years.

The "time at risk" for participants began after both receipt of genetic testing results and RRSO, and the participants were followed annually by questionnaires and medical records review. Censoring events were hysterectomy, uterine cancer diagnosis, last follow-up, or death, Dr. Shu noted.

Importantly, no increased risk was seen for more common types of uterine cancer, including endometrioid, mucinous, adenocarcinoma, and not otherwise specified cancers.

Those who developed high-risk cancer were treated with chemotherapy and/or radiation, and all four were living at the time of Dr. Shu’s presentation, although one had metastatic disease.

Although this study is one of the largest prospective studies to date to look at the likelihood of high-risk uterine cancer among BRCA-positive patients who undergo RRSO without hysterectomy, it has a number of limitations, such as possible misclassification of rare uterine cancer subtypes in the SEER database and possible confounding by tamoxifen exposure. The findings require confirmation and should thus be considered preliminary, Dr. Shu said.

Indeed, it would be premature at this point to recommend routine hysterectomy along with RRSO women with BRCA1 mutations; the decision regarding hysterectomy at the time of RRSO may depend on the patient’s age, prior cancer history, and other risk factors, senior author Noah D. Kauff of Memorial Sloan Kettering Cancer Center, said in a press statement.

Currently, based on the fact that women with a BRCA1 mutation have a 39%-46% chance of developing ovarian cancer and 50%-85% chance of developing breast cancer, the National Comprehensive Cancer Network recommends RRSO between ages 35 years and 40 years, after childbearing is complete.

Hysterectomy at the time of RRSO is not recommended because of risks associated with the procedure, including bleeding and infection risks, as well the potential for long-term problems with bladder, bowel, and sexual function, and also because uterine cancers that develop after RRSO have been thought to generally be low risk, according to the press statement.

The current findings suggest this may not be the case,

Pending confirmation of the findings, women with BRCA1 gene mutations who are considering risk-reducing surgery should be advised that "this report suggests they may be at risk for rare types of aggressive uterine cancer," and the potential advantages and disadvantages of concomitant hysterectomy should be discussed, Dr. Kauff said.

Dr. Shu and Dr. Kauff reported having no disclosures.