Sharon Worcester

SAN ANTONIO – The American Medical Association is working toward numerous goals that stand to improve health care and the practice of medicine, including some that target issues of particular concern to psychiatrists, according to Dr. Jeremy A. Lazarus.

In general, the efforts aim to enhance professional satisfaction for physicians, improve outcomes for patients, and transform medical education to make sure that current medical students are prepared to practice 21st century medicine, Dr. Lazarus of the University of Colorado Denver and immediate past president of the AMA at said at the annual meeting of the American College of Psychiatrists.

During an update on the AMA’s efforts, Dr. Lazarus described several recent activities and successes, and reflected on the "tremendous partnership that the AMA has with psychiatry and the (American Psychiatric Association).""We have a long history of fighting together," he said, referring to successes such as the decade-long effort that resulted in getting the mental health parity bill passed, the joining together of more than 80 state and specialty societies to address and combat efforts – like a successful effort in New Mexico in 2002 – to give prescribing privileges to psychologists, and – recently – participation in the Joining Forces initiative to ensure that veterans with posttraumatic stress disorder, post-combat depression, or traumatic brain injury receive the care and resources they need.

Other recent AMA activities and successes outlined by Dr. Lazarus include:

• Testifying to the U.S. Senate regarding the Sunshine Act provisions of the Affordable Care Act.

Dr. Lazarus said he voiced the AMA’s support for transparency, but cautioned that physicians need to have the right to review reported information to ensure accuracy.

The AMA is committed to making sure that "the powers that be in Washington, D.C., hear physicians’ concerns loud and clear," he said.

• Working with state medical societies and associations on numerous legislative issues that affect physicians and health care.

"The AMA achieved many legislative victories in 2012-2013, including truth-in-advertising legislation, preserving existing medical liability reforms, protecting the patient-physician relationship, and also turning back and defeating many scope of practice expansions," he said.

For example, in conjunction with 10 other specialty groups, the AMA helped to overturn a Florida law that prohibited physicians from talking to patients/parents about guns in the home and gun safety, and from making any note about the conversation in patient charts.

"We feel it is imperative that lawmakers not get in the way of physician-patient communication," he said.

• Working toward Medicare reform.

Efforts toward reform have been ongoing for a decade or more, Dr. Lazarus said.

"We are close to the finish line," he noted.

Efforts to repeal the Medicare Sustainable Growth Rate formula and to move toward different systems of paying physicians continue, as scores of state and specialty societies work together to develop a system that will provide many options for payment for physicians that will reward physicians for savings in the health care system, support practice investments so that physicians can move to different forms of practicing, and tie physician payment to their own actions rather than to those of others whom they can’t control.

"We got great news on Feb. 6 – there is now joint legislation to repeal the SGR that’s advancing in both the House and the Senate," he said, noting that the impending legislation is the result of work by the AMA and other organizations working together to "keep this issue alive, to try to modify the bills as they were going through the House and the Senate, and to make sure we got to a positive outcome."

"We want the Medicare payment program to be a stable 21st-century program that can meet the growing health care needs of our senior population, and we’ve been very pleased that the committees have made many changes recommended by the AMA," he said.

The current bill under consideration – the SGR Repeal and Medicare Provider Payment Modernization Act of 2014 – includes a repeal of the SGR formula, automatic positive payment updates of 0.5% for the next 5 years, a consolidated and simpler Medicare quality reporting program, and the ability to transition to different models of care.

"We’ve now got a March 31 deadline. If nothing is done, there will be a 24% cut in Medicare payments, so stay tuned. We’re looking for things to advance ... we haven’t been any closer than we are right now, so we’re very hopeful," he said.

Those interested in participating in the effort to reform Medicare can visit the AMA’s FixMedicareNow.org website for more information, he noted.

The efforts mentioned by Dr. Lazarus are among the matters "high on the list for AMA advocacy," but are just a small part of the AMA’s activities.

"We’re also looking at the big picture in terms of the health care system in this country to try to lead a major effort on the big issues," he said.

Among the concerns are the "tremendously overburdened system," with 50 million individuals uninsured and $2.7 trillion in annual spending (18% of gross domestic product) with outcomes that are poorer than those of other developed countries – and with an estimated increase of spending up to $4.6 trillion (20% of GDP) by 2020. The fragmented delivery system, with a lack of coordination of care and an epidemic of chronic conditions that account for 75% of the spending, also are among the concerns being addressed by the AMA.

Facing these tremendously complicated and difficult situations, the AMA decided to "take our years of training on addressing major issues, and put them to work on what amounts to an AMA policy triathlon," Dr. Lazarus said, referring to the three-pronged plan of enhancing physician satisfaction, improving health outcomes, and accelerating needed changes in medical education.

"We’ve committed to finishing this race," he said, noting that it will be a long one.

Efforts to improve care delivery models include collaboration with the RAND Corp. to conduct field research at 30 diverse practice settings across the country to identify factors associated with success and satisfaction.

Results are forthcoming, but initial findings suggest that what physicians care most about is the ability to deliver high-quality care.

The plan is to create tools to help physicians choose the best model for meeting their particular needs, and to advocate both federally and locally to promote adoption of models that improve physician and patient satisfaction, he said.

The AMA will continue to work to remove regulatory barriers that get in the way of providing quality health care, level the playing field with health insurers, help facilitate relationships with hospital and other payers to ensure a physician leadership role in emerging care models, and explore solutions to improve electronic health record platforms, he added.

As for improving health outcomes, efforts include several initiatives and partnerships designed to reduce disease burden and the cost burden associated with some of the most pervasive and troubling health conditions, such as diabetes. As for medical education, the AMA has issued $1 million in grants to 11 medical schools to advance new ways of teaching – such as through more flexible and individualized learning plans – to better prepare students for practicing in the changing health care environment.

"Just imagine the possibilities if we are even partially successful with this strategic plan – if we have increased quality of care, healthier patients, lower costs, and physicians working in a sustainable health environment that they have created themselves and that they think works for them, and if we have medical students trained for 21st-century medicine," he said. "It will take a lot of work and a lot of effort and a lot of focus, but at the end, we think there will be a healthier future for our health care system ... physicians, [and] ... our country as a whole."

SAN ANTONIO – The American Medical Association is working toward numerous goals that stand to improve health care and the practice of medicine, including some that target issues of particular concern to psychiatrists, according to Dr. Jeremy A. Lazarus.

In general, the efforts aim to enhance professional satisfaction for physicians, improve outcomes for patients, and transform medical education to make sure that current medical students are prepared to practice 21st century medicine, Dr. Lazarus of the University of Colorado Denver and immediate past president of the AMA at said at the annual meeting of the American College of Psychiatrists.

During an update on the AMA’s efforts, Dr. Lazarus described several recent activities and successes, and reflected on the "tremendous partnership that the AMA has with psychiatry and the (American Psychiatric Association).""We have a long history of fighting together," he said, referring to successes such as the decade-long effort that resulted in getting the mental health parity bill passed, the joining together of more than 80 state and specialty societies to address and combat efforts – like a successful effort in New Mexico in 2002 – to give prescribing privileges to psychologists, and – recently – participation in the Joining Forces initiative to ensure that veterans with posttraumatic stress disorder, post-combat depression, or traumatic brain injury receive the care and resources they need.

Other recent AMA activities and successes outlined by Dr. Lazarus include:

• Testifying to the U.S. Senate regarding the Sunshine Act provisions of the Affordable Care Act.

Dr. Lazarus said he voiced the AMA’s support for transparency, but cautioned that physicians need to have the right to review reported information to ensure accuracy.

The AMA is committed to making sure that "the powers that be in Washington, D.C., hear physicians’ concerns loud and clear," he said.

• Working with state medical societies and associations on numerous legislative issues that affect physicians and health care.

"The AMA achieved many legislative victories in 2012-2013, including truth-in-advertising legislation, preserving existing medical liability reforms, protecting the patient-physician relationship, and also turning back and defeating many scope of practice expansions," he said.

For example, in conjunction with 10 other specialty groups, the AMA helped to overturn a Florida law that prohibited physicians from talking to patients/parents about guns in the home and gun safety, and from making any note about the conversation in patient charts.

"We feel it is imperative that lawmakers not get in the way of physician-patient communication," he said.

• Working toward Medicare reform.

Efforts toward reform have been ongoing for a decade or more, Dr. Lazarus said.

"We are close to the finish line," he noted.

Efforts to repeal the Medicare Sustainable Growth Rate formula and to move toward different systems of paying physicians continue, as scores of state and specialty societies work together to develop a system that will provide many options for payment for physicians that will reward physicians for savings in the health care system, support practice investments so that physicians can move to different forms of practicing, and tie physician payment to their own actions rather than to those of others whom they can’t control.

"We got great news on Feb. 6 – there is now joint legislation to repeal the SGR that’s advancing in both the House and the Senate," he said, noting that the impending legislation is the result of work by the AMA and other organizations working together to "keep this issue alive, to try to modify the bills as they were going through the House and the Senate, and to make sure we got to a positive outcome."

"We want the Medicare payment program to be a stable 21st-century program that can meet the growing health care needs of our senior population, and we’ve been very pleased that the committees have made many changes recommended by the AMA," he said.

The current bill under consideration – the SGR Repeal and Medicare Provider Payment Modernization Act of 2014 – includes a repeal of the SGR formula, automatic positive payment updates of 0.5% for the next 5 years, a consolidated and simpler Medicare quality reporting program, and the ability to transition to different models of care.

"We’ve now got a March 31 deadline. If nothing is done, there will be a 24% cut in Medicare payments, so stay tuned. We’re looking for things to advance ... we haven’t been any closer than we are right now, so we’re very hopeful," he said.

Those interested in participating in the effort to reform Medicare can visit the AMA’s FixMedicareNow.org website for more information, he noted.

The efforts mentioned by Dr. Lazarus are among the matters "high on the list for AMA advocacy," but are just a small part of the AMA’s activities.

"We’re also looking at the big picture in terms of the health care system in this country to try to lead a major effort on the big issues," he said.

Among the concerns are the "tremendously overburdened system," with 50 million individuals uninsured and $2.7 trillion in annual spending (18% of gross domestic product) with outcomes that are poorer than those of other developed countries – and with an estimated increase of spending up to $4.6 trillion (20% of GDP) by 2020. The fragmented delivery system, with a lack of coordination of care and an epidemic of chronic conditions that account for 75% of the spending, also are among the concerns being addressed by the AMA.

Facing these tremendously complicated and difficult situations, the AMA decided to "take our years of training on addressing major issues, and put them to work on what amounts to an AMA policy triathlon," Dr. Lazarus said, referring to the three-pronged plan of enhancing physician satisfaction, improving health outcomes, and accelerating needed changes in medical education.

"We’ve committed to finishing this race," he said, noting that it will be a long one.

Efforts to improve care delivery models include collaboration with the RAND Corp. to conduct field research at 30 diverse practice settings across the country to identify factors associated with success and satisfaction.

Results are forthcoming, but initial findings suggest that what physicians care most about is the ability to deliver high-quality care.

The plan is to create tools to help physicians choose the best model for meeting their particular needs, and to advocate both federally and locally to promote adoption of models that improve physician and patient satisfaction, he said.

The AMA will continue to work to remove regulatory barriers that get in the way of providing quality health care, level the playing field with health insurers, help facilitate relationships with hospital and other payers to ensure a physician leadership role in emerging care models, and explore solutions to improve electronic health record platforms, he added.

As for improving health outcomes, efforts include several initiatives and partnerships designed to reduce disease burden and the cost burden associated with some of the most pervasive and troubling health conditions, such as diabetes. As for medical education, the AMA has issued $1 million in grants to 11 medical schools to advance new ways of teaching – such as through more flexible and individualized learning plans – to better prepare students for practicing in the changing health care environment.

"Just imagine the possibilities if we are even partially successful with this strategic plan – if we have increased quality of care, healthier patients, lower costs, and physicians working in a sustainable health environment that they have created themselves and that they think works for them, and if we have medical students trained for 21st-century medicine," he said. "It will take a lot of work and a lot of effort and a lot of focus, but at the end, we think there will be a healthier future for our health care system ... physicians, [and] ... our country as a whole."

SAN ANTONIO – The American Medical Association is working toward numerous goals that stand to improve health care and the practice of medicine, including some that target issues of particular concern to psychiatrists, according to Dr. Jeremy A. Lazarus.

In general, the efforts aim to enhance professional satisfaction for physicians, improve outcomes for patients, and transform medical education to make sure that current medical students are prepared to practice 21st century medicine, Dr. Lazarus of the University of Colorado Denver and immediate past president of the AMA at said at the annual meeting of the American College of Psychiatrists.

During an update on the AMA’s efforts, Dr. Lazarus described several recent activities and successes, and reflected on the "tremendous partnership that the AMA has with psychiatry and the (American Psychiatric Association).""We have a long history of fighting together," he said, referring to successes such as the decade-long effort that resulted in getting the mental health parity bill passed, the joining together of more than 80 state and specialty societies to address and combat efforts – like a successful effort in New Mexico in 2002 – to give prescribing privileges to psychologists, and – recently – participation in the Joining Forces initiative to ensure that veterans with posttraumatic stress disorder, post-combat depression, or traumatic brain injury receive the care and resources they need.

Other recent AMA activities and successes outlined by Dr. Lazarus include:

• Testifying to the U.S. Senate regarding the Sunshine Act provisions of the Affordable Care Act.

Dr. Lazarus said he voiced the AMA’s support for transparency, but cautioned that physicians need to have the right to review reported information to ensure accuracy.

The AMA is committed to making sure that "the powers that be in Washington, D.C., hear physicians’ concerns loud and clear," he said.

• Working with state medical societies and associations on numerous legislative issues that affect physicians and health care.

"The AMA achieved many legislative victories in 2012-2013, including truth-in-advertising legislation, preserving existing medical liability reforms, protecting the patient-physician relationship, and also turning back and defeating many scope of practice expansions," he said.

For example, in conjunction with 10 other specialty groups, the AMA helped to overturn a Florida law that prohibited physicians from talking to patients/parents about guns in the home and gun safety, and from making any note about the conversation in patient charts.

"We feel it is imperative that lawmakers not get in the way of physician-patient communication," he said.

• Working toward Medicare reform.

Efforts toward reform have been ongoing for a decade or more, Dr. Lazarus said.

"We are close to the finish line," he noted.

Efforts to repeal the Medicare Sustainable Growth Rate formula and to move toward different systems of paying physicians continue, as scores of state and specialty societies work together to develop a system that will provide many options for payment for physicians that will reward physicians for savings in the health care system, support practice investments so that physicians can move to different forms of practicing, and tie physician payment to their own actions rather than to those of others whom they can’t control.

"We got great news on Feb. 6 – there is now joint legislation to repeal the SGR that’s advancing in both the House and the Senate," he said, noting that the impending legislation is the result of work by the AMA and other organizations working together to "keep this issue alive, to try to modify the bills as they were going through the House and the Senate, and to make sure we got to a positive outcome."

"We want the Medicare payment program to be a stable 21st-century program that can meet the growing health care needs of our senior population, and we’ve been very pleased that the committees have made many changes recommended by the AMA," he said.

The current bill under consideration – the SGR Repeal and Medicare Provider Payment Modernization Act of 2014 – includes a repeal of the SGR formula, automatic positive payment updates of 0.5% for the next 5 years, a consolidated and simpler Medicare quality reporting program, and the ability to transition to different models of care.

"We’ve now got a March 31 deadline. If nothing is done, there will be a 24% cut in Medicare payments, so stay tuned. We’re looking for things to advance ... we haven’t been any closer than we are right now, so we’re very hopeful," he said.

Those interested in participating in the effort to reform Medicare can visit the AMA’s FixMedicareNow.org website for more information, he noted.

The efforts mentioned by Dr. Lazarus are among the matters "high on the list for AMA advocacy," but are just a small part of the AMA’s activities.

"We’re also looking at the big picture in terms of the health care system in this country to try to lead a major effort on the big issues," he said.

Among the concerns are the "tremendously overburdened system," with 50 million individuals uninsured and $2.7 trillion in annual spending (18% of gross domestic product) with outcomes that are poorer than those of other developed countries – and with an estimated increase of spending up to $4.6 trillion (20% of GDP) by 2020. The fragmented delivery system, with a lack of coordination of care and an epidemic of chronic conditions that account for 75% of the spending, also are among the concerns being addressed by the AMA.

Facing these tremendously complicated and difficult situations, the AMA decided to "take our years of training on addressing major issues, and put them to work on what amounts to an AMA policy triathlon," Dr. Lazarus said, referring to the three-pronged plan of enhancing physician satisfaction, improving health outcomes, and accelerating needed changes in medical education.

"We’ve committed to finishing this race," he said, noting that it will be a long one.

Efforts to improve care delivery models include collaboration with the RAND Corp. to conduct field research at 30 diverse practice settings across the country to identify factors associated with success and satisfaction.

Results are forthcoming, but initial findings suggest that what physicians care most about is the ability to deliver high-quality care.

The plan is to create tools to help physicians choose the best model for meeting their particular needs, and to advocate both federally and locally to promote adoption of models that improve physician and patient satisfaction, he said.

The AMA will continue to work to remove regulatory barriers that get in the way of providing quality health care, level the playing field with health insurers, help facilitate relationships with hospital and other payers to ensure a physician leadership role in emerging care models, and explore solutions to improve electronic health record platforms, he added.

As for improving health outcomes, efforts include several initiatives and partnerships designed to reduce disease burden and the cost burden associated with some of the most pervasive and troubling health conditions, such as diabetes. As for medical education, the AMA has issued $1 million in grants to 11 medical schools to advance new ways of teaching – such as through more flexible and individualized learning plans – to better prepare students for practicing in the changing health care environment.

"Just imagine the possibilities if we are even partially successful with this strategic plan – if we have increased quality of care, healthier patients, lower costs, and physicians working in a sustainable health environment that they have created themselves and that they think works for them, and if we have medical students trained for 21st-century medicine," he said. "It will take a lot of work and a lot of effort and a lot of focus, but at the end, we think there will be a healthier future for our health care system ... physicians, [and] ... our country as a whole."

A novel oral antiviral agent is showing early promise as a nonvaccine treatment for measles.

Measles outbreaks have been occurring more commonly as vaccine compliance declines in some countries. This investigational drug could prove useful as a preemptive treatment in nonvaccinated individuals who are exposed to the disease.

With administration during the approximately 2-week window between infection and symptom development, the small-molecule inhibitor – which targets the viral RNA polymerase – reduced viremia by 99% in three ferrets that were infected intranasally with a lethal dose of the measles-like zoonotic canine distemper virus. All three survived, but nine control animals that received only the vehicle all died as a result of the infection, Stefanie A. Krumm of Georgia State University, Atlanta, and her colleagues reported.

Furthermore, all of the treated animals had a robust immune response and were protected against rechallenge with a lethal dose of the virus 35 days after the initial dose. In fact, none of the rechallenged animals developed signs of disease, and no virus could be isolated from peripheral blood mononuclear cells of these animals, the investigators said (Sci. Transl. Med. 2014 April 16;6:232ra52).

The drug is in the early stages of development, but if it proves safe and effective in humans, it would not be considered an alternative to vaccination, lead author Richard K. Plemper, Ph.D., said during a news conference on the findings.

"In a population with good [vaccine] coverage, such a drug could induce synergistic effects, so we could ... rapidly silence emerging measles outbreaks," noted Dr. Plemper, professor in the center for inflammation, immunity & infection at Georgia State University and in the departments of infectious diseases and pediatrics at Emory University, Atlanta, adding that the ultimate goal is global measles eradication.

The investigators plan next to test the drug in a monkey model to carefully assess for potential toxicity before moving on to human testing.

This study was funded by grants from the Agency for Science, Technology and Research, Ministry of Health, Singapore, and from the National Institutes of Health/National Institute of Allergy and Infectious Diseases. It was also supported by the German Ministry of Health and the German Centre for Infection Research. Three of the study authors, including Dr. Plemper, are inventors on a patent that includes the structure and method of use of the antiviral drug.

A novel oral antiviral agent is showing early promise as a nonvaccine treatment for measles.

Measles outbreaks have been occurring more commonly as vaccine compliance declines in some countries. This investigational drug could prove useful as a preemptive treatment in nonvaccinated individuals who are exposed to the disease.

With administration during the approximately 2-week window between infection and symptom development, the small-molecule inhibitor – which targets the viral RNA polymerase – reduced viremia by 99% in three ferrets that were infected intranasally with a lethal dose of the measles-like zoonotic canine distemper virus. All three survived, but nine control animals that received only the vehicle all died as a result of the infection, Stefanie A. Krumm of Georgia State University, Atlanta, and her colleagues reported.

Furthermore, all of the treated animals had a robust immune response and were protected against rechallenge with a lethal dose of the virus 35 days after the initial dose. In fact, none of the rechallenged animals developed signs of disease, and no virus could be isolated from peripheral blood mononuclear cells of these animals, the investigators said (Sci. Transl. Med. 2014 April 16;6:232ra52).

The drug is in the early stages of development, but if it proves safe and effective in humans, it would not be considered an alternative to vaccination, lead author Richard K. Plemper, Ph.D., said during a news conference on the findings.

"In a population with good [vaccine] coverage, such a drug could induce synergistic effects, so we could ... rapidly silence emerging measles outbreaks," noted Dr. Plemper, professor in the center for inflammation, immunity & infection at Georgia State University and in the departments of infectious diseases and pediatrics at Emory University, Atlanta, adding that the ultimate goal is global measles eradication.

The investigators plan next to test the drug in a monkey model to carefully assess for potential toxicity before moving on to human testing.

This study was funded by grants from the Agency for Science, Technology and Research, Ministry of Health, Singapore, and from the National Institutes of Health/National Institute of Allergy and Infectious Diseases. It was also supported by the German Ministry of Health and the German Centre for Infection Research. Three of the study authors, including Dr. Plemper, are inventors on a patent that includes the structure and method of use of the antiviral drug.

A novel oral antiviral agent is showing early promise as a nonvaccine treatment for measles.

Measles outbreaks have been occurring more commonly as vaccine compliance declines in some countries. This investigational drug could prove useful as a preemptive treatment in nonvaccinated individuals who are exposed to the disease.

With administration during the approximately 2-week window between infection and symptom development, the small-molecule inhibitor – which targets the viral RNA polymerase – reduced viremia by 99% in three ferrets that were infected intranasally with a lethal dose of the measles-like zoonotic canine distemper virus. All three survived, but nine control animals that received only the vehicle all died as a result of the infection, Stefanie A. Krumm of Georgia State University, Atlanta, and her colleagues reported.

Furthermore, all of the treated animals had a robust immune response and were protected against rechallenge with a lethal dose of the virus 35 days after the initial dose. In fact, none of the rechallenged animals developed signs of disease, and no virus could be isolated from peripheral blood mononuclear cells of these animals, the investigators said (Sci. Transl. Med. 2014 April 16;6:232ra52).

The drug is in the early stages of development, but if it proves safe and effective in humans, it would not be considered an alternative to vaccination, lead author Richard K. Plemper, Ph.D., said during a news conference on the findings.

"In a population with good [vaccine] coverage, such a drug could induce synergistic effects, so we could ... rapidly silence emerging measles outbreaks," noted Dr. Plemper, professor in the center for inflammation, immunity & infection at Georgia State University and in the departments of infectious diseases and pediatrics at Emory University, Atlanta, adding that the ultimate goal is global measles eradication.

The investigators plan next to test the drug in a monkey model to carefully assess for potential toxicity before moving on to human testing.

This study was funded by grants from the Agency for Science, Technology and Research, Ministry of Health, Singapore, and from the National Institutes of Health/National Institute of Allergy and Infectious Diseases. It was also supported by the German Ministry of Health and the German Centre for Infection Research. Three of the study authors, including Dr. Plemper, are inventors on a patent that includes the structure and method of use of the antiviral drug.

SAN ANTONIO – Brief cognitive-behavioral therapy is particularly helpful for the treatment of insomnia, including insomnia that occurs in association with depression or other psychiatric conditions.

Even cognitive-behavioral therapy (CBT) sessions lasting only 8-10 minutes, when accompanied by informational handouts, can lead to improvements in insomnia, Dr. Donna M. Sudak, professor and director of the psychotherapy training program at Drexel University, Philadelphia, said during a premeeting workshop on high-yield brief CBT at the annual meeting of the American College of Psychiatrists.

"It’s really rapid," she said of the intervention and its effects on insomnia.

Dr. Sudak noted that in patients with depression, it often is assumed that "the insomnia component of depression really has to do with the depression itself," but in fact, treating the insomnia appears to also make a real difference in the depression, suggesting the two conditions are interrelated.

"CBT works really well, and it also may be important in terms of managing other conditions," she said.

In an article that synthesized the relevant empirical evidence related to the efficacy of CBT for insomnia (CBT-I) and the benzodiazepines and benzodiazepine-receptor antagonists often used for the treatment of insomnia, Dr. Sudak notes that chronic insomnia affects an estimated 6% to 10% of the population, and that the highly prevalent sleep disorder is accompanied by significant daytime impairment.

"Insomnia has significant consequences for daytime functioning and health-related quality of life. The disorder conveys serious occupational and economic burdens, including mood disturbance, sleepiness, fatigue, cognitive impairment, and high rates of absenteeism and ‘presenteeism,’ " she wrote.

She also noted that insomnia sufferers are at increased risk of compromised psychological and physical health.

In the article, which has been accepted for publication in the International Journal of Cognitive Psychotherapy, she notes that CBT-I, which typically involves six to eight individual or group sessions that employ strategies such as stimulus control, sleep restriction, relaxation, and cognitive restructuring, is recommended by the American Academy of Sleep Medicine and the National Institutes of Health based on the substantial support in the literature for its efficacy and effectiveness in treating primary insomnia. She cites, for example, a meta-analysis of randomized controlled trials that suggests that CBT-I has moderate to large effects with respect to improving sleep (Sleep and Biol. Rhythms 2011;9:24-34).

Other studies have found a high rate of treatment response and clinically significant remissions with CBT-I, she noted.

CBT-I for comorbid insomnia, psychiatric illness

CBT-I also is beneficial in patients with coexisting insomnia and psychiatric illness.

"An estimated 30% to 90% of psychiatric patients have sleep disturbances. Conversely, patients with psychiatric illness account for an estimated 40% to 50% of patients with chronic insomnia.

Furthermore, those with anxiety and depression have a fivefold increase in the likelihood of having chronic insomnia, compared with those without anxiety or depression, and numerous studies suggest that insomnia that coexists with a range of psychiatric and medical conditions benefits from the application of CBT-I.

"It is therefore worthwhile to pursue strategies for combining CBT-I and pharmacotherapy in such groups," she wrote.

However, despite the high comorbidity, insomnia is rarely independently treated with CBT-I in mood disorders, which leaves patients vulnerable to relapse of depression, as well as to morbidity associated with sleep disturbance.

"It is increasingly recognized that insomnia is often best conceptualized as a separate entity that should be managed with specific, targeted treatment rather than secondary to depression treatment," she wrote, noting that since the prevalence of comorbid insomnia increases with the severity of depression, and since insomnia increases the risk of recurrence of depression and suicide, the most important take-home lesson from the literature might well be that when patients have both major depression and insomnia, a treatment targeting both conditions is warranted.

Indeed, data increasingly suggest that CBT-I is such a treatment.

In a recent study presented at the annual meeting of the Association for Behavioral and Cognitive Therapies, 87% of 66 patients with depression whose insomnia resolved after 4 brief biweekly CBT sessions also experienced significant declines in their depression symptoms after 8 weeks of treatment – regardless of whether they were treated with an antidepressant drug or received placebo. The rate of improvement in depression symptoms in those who also experienced improvement in their insomnia was almost twice as high as in patients who did not experience improvement in their insomnia, according to the lead author, Colleen E. Carney, Ph.D., of Ryerson University, Toronto.

CBT-I in older adults

In another recent study, Nicole Lovato, Ph.D., of Flinders University, Adelaide, South Australia, and her colleagues demonstrated that 4 brief weekly CBT group-administered sessions for insomnia were effective for improving symptoms in older adults with sleep maintenance insomnia.

For that randomized controlled trial involving 118 adults with a mean age of 64 years, the investigators compared 86 CBT patients with 32 waitlist controls. At 3-month follow-up, those in the treatment group experienced significant improvements in the timing and quality of sleep, including later bedtime, earlier out-of-bed time, reduced wake after sleep onset, and improved sleep efficiency (Sleep 2014;37:117-26).

Improvements were seen on the Insomnia Severity Index, Flinders Fatigue Scale, Epworth Sleepiness Scale, Daytime Feeling and Functioning Scale, Sleep Anticipatory Anxiety Questionnaire, Dysfunctional Beliefs and Attitudes Scale, and Sleep Self-Efficacy Scale, they reported.

"These changes were supported by large effect sizes (1.14-1.54) and were significantly greater than the wait-list group both immediately following treatment and at 3-month follow-up," the investigators wrote.

The CBT intervention included bedtime restriction therapy, sleep education, and cognitive restructuring.

The group-administered treatment program used in the study, "promises to be a brief and inexpensive answer to the effective treatment of insomnia in the older population," they concluded.

Dr. Sudak’s paper also addressed CBT-I use in the elderly, who have a substantial risk of insomnia and who frequently use hypnotics for treatment of insomnia.

"Treatment with CBT-I is effective in older adults and results are more durable than medication," she said, noting that 50% of elders who receive CBT-I sustain remission for at least 2 years.

CBT-I is also effective in older adults with comorbid medical conditions; among those who are dependent on hypnotics, CBT-I helps improve subjective sleep quality and sleep onset latency. Several randomized controlled trials indicate that CBT-I "may be particularly effective in facilitating hypnotic withdrawal in older adults," she said, noting that this is important given that hypnotics are associated with falls, confusion, and constipation in this population.

She cited a study that demonstrated that the best outcomes are achieved if CBT-I is employed first, then medication added, then medication discontinued prior to the end of CBT-I (Lancet 2012;379:1129-41).

CBT-I and cost savings

Another recent study shows that in addition to improving symptoms, brief CBT-I reduces health care utilization and costs.

The medical records review of 84 outpatients with a mean age of 54 years showed that for 37 patients who completed at least three CBT session for insomnia, and 32 who completed at least three sessions and who experienced significant sleep improvement, all health care use and cost variables, with the exception of number of medications, decreased significantly or trended toward decrease after treatment.

The average decrease in CPT costs was $200 for completers and $210 for responders. No significant decreases occurred in those who did not complete therapy, Christina McCrae, Ph.D., of the University of Florida, Gainesville, and her colleagues reported in February in the Journal of Clinical Sleep Medicine.

Patients included in the study received sleep and sleep hygiene education, stimulus control therapy, sleep restriction, a 10-minute relaxation exercise, and cognitive therapy during up to 6 weekly treatment sessions led by clinical psychology graduate students and predoctoral interns.

Although the study is limited by its small sample size and non-normal data distribution, the findings underscore a need for greater dissemination of brief CBT for insomnia; as few as 3 sessions are needed for significant improvement, the therapy can be delivered by novice clinicians, and the therapy is associated with reduced costs and reduced burden of insomnia, the investigators concluded (J. Clin. Sleep Med. 2014;10:127-35).

While the cost of brief treatment, which was $460 in this study, might negate the short-term savings seen in the first 6 months after therapy, the effects of therapy are durable, so CBT for insomnia has the potential to produce substantial long-term savings, the investigator said in a press statement. They noted that this is particularly true when these results are extrapolated to the large population of insomnia patients in the U.S. health care system.

Dr. Sudak is a coauthor of the book "High-Yield Cognitive-Behavior Therapy for Brief Sessions: An Illustrated Guide" (Washington: American Psychiatric Publishing, 2010). She receives book royalties from American Psychiatric Publishing; Lippincott, Williams & Wilkins; and John Wiley & Sons. Dr. Sudak also is on an editorial board and receives honoraria from Elsevier and is a consultant for Takeda Pharmaceuticals. Dr. Lovato and Dr. McCrae reported having no disclosures.

SAN ANTONIO – Brief cognitive-behavioral therapy is particularly helpful for the treatment of insomnia, including insomnia that occurs in association with depression or other psychiatric conditions.

Even cognitive-behavioral therapy (CBT) sessions lasting only 8-10 minutes, when accompanied by informational handouts, can lead to improvements in insomnia, Dr. Donna M. Sudak, professor and director of the psychotherapy training program at Drexel University, Philadelphia, said during a premeeting workshop on high-yield brief CBT at the annual meeting of the American College of Psychiatrists.

"It’s really rapid," she said of the intervention and its effects on insomnia.

Dr. Sudak noted that in patients with depression, it often is assumed that "the insomnia component of depression really has to do with the depression itself," but in fact, treating the insomnia appears to also make a real difference in the depression, suggesting the two conditions are interrelated.

"CBT works really well, and it also may be important in terms of managing other conditions," she said.

In an article that synthesized the relevant empirical evidence related to the efficacy of CBT for insomnia (CBT-I) and the benzodiazepines and benzodiazepine-receptor antagonists often used for the treatment of insomnia, Dr. Sudak notes that chronic insomnia affects an estimated 6% to 10% of the population, and that the highly prevalent sleep disorder is accompanied by significant daytime impairment.

"Insomnia has significant consequences for daytime functioning and health-related quality of life. The disorder conveys serious occupational and economic burdens, including mood disturbance, sleepiness, fatigue, cognitive impairment, and high rates of absenteeism and ‘presenteeism,’ " she wrote.

She also noted that insomnia sufferers are at increased risk of compromised psychological and physical health.

In the article, which has been accepted for publication in the International Journal of Cognitive Psychotherapy, she notes that CBT-I, which typically involves six to eight individual or group sessions that employ strategies such as stimulus control, sleep restriction, relaxation, and cognitive restructuring, is recommended by the American Academy of Sleep Medicine and the National Institutes of Health based on the substantial support in the literature for its efficacy and effectiveness in treating primary insomnia. She cites, for example, a meta-analysis of randomized controlled trials that suggests that CBT-I has moderate to large effects with respect to improving sleep (Sleep and Biol. Rhythms 2011;9:24-34).

Other studies have found a high rate of treatment response and clinically significant remissions with CBT-I, she noted.

CBT-I for comorbid insomnia, psychiatric illness

CBT-I also is beneficial in patients with coexisting insomnia and psychiatric illness.

"An estimated 30% to 90% of psychiatric patients have sleep disturbances. Conversely, patients with psychiatric illness account for an estimated 40% to 50% of patients with chronic insomnia.

Furthermore, those with anxiety and depression have a fivefold increase in the likelihood of having chronic insomnia, compared with those without anxiety or depression, and numerous studies suggest that insomnia that coexists with a range of psychiatric and medical conditions benefits from the application of CBT-I.

"It is therefore worthwhile to pursue strategies for combining CBT-I and pharmacotherapy in such groups," she wrote.

However, despite the high comorbidity, insomnia is rarely independently treated with CBT-I in mood disorders, which leaves patients vulnerable to relapse of depression, as well as to morbidity associated with sleep disturbance.

"It is increasingly recognized that insomnia is often best conceptualized as a separate entity that should be managed with specific, targeted treatment rather than secondary to depression treatment," she wrote, noting that since the prevalence of comorbid insomnia increases with the severity of depression, and since insomnia increases the risk of recurrence of depression and suicide, the most important take-home lesson from the literature might well be that when patients have both major depression and insomnia, a treatment targeting both conditions is warranted.

Indeed, data increasingly suggest that CBT-I is such a treatment.

In a recent study presented at the annual meeting of the Association for Behavioral and Cognitive Therapies, 87% of 66 patients with depression whose insomnia resolved after 4 brief biweekly CBT sessions also experienced significant declines in their depression symptoms after 8 weeks of treatment – regardless of whether they were treated with an antidepressant drug or received placebo. The rate of improvement in depression symptoms in those who also experienced improvement in their insomnia was almost twice as high as in patients who did not experience improvement in their insomnia, according to the lead author, Colleen E. Carney, Ph.D., of Ryerson University, Toronto.

CBT-I in older adults

In another recent study, Nicole Lovato, Ph.D., of Flinders University, Adelaide, South Australia, and her colleagues demonstrated that 4 brief weekly CBT group-administered sessions for insomnia were effective for improving symptoms in older adults with sleep maintenance insomnia.

For that randomized controlled trial involving 118 adults with a mean age of 64 years, the investigators compared 86 CBT patients with 32 waitlist controls. At 3-month follow-up, those in the treatment group experienced significant improvements in the timing and quality of sleep, including later bedtime, earlier out-of-bed time, reduced wake after sleep onset, and improved sleep efficiency (Sleep 2014;37:117-26).

Improvements were seen on the Insomnia Severity Index, Flinders Fatigue Scale, Epworth Sleepiness Scale, Daytime Feeling and Functioning Scale, Sleep Anticipatory Anxiety Questionnaire, Dysfunctional Beliefs and Attitudes Scale, and Sleep Self-Efficacy Scale, they reported.

"These changes were supported by large effect sizes (1.14-1.54) and were significantly greater than the wait-list group both immediately following treatment and at 3-month follow-up," the investigators wrote.

The CBT intervention included bedtime restriction therapy, sleep education, and cognitive restructuring.

The group-administered treatment program used in the study, "promises to be a brief and inexpensive answer to the effective treatment of insomnia in the older population," they concluded.

Dr. Sudak’s paper also addressed CBT-I use in the elderly, who have a substantial risk of insomnia and who frequently use hypnotics for treatment of insomnia.

"Treatment with CBT-I is effective in older adults and results are more durable than medication," she said, noting that 50% of elders who receive CBT-I sustain remission for at least 2 years.

CBT-I is also effective in older adults with comorbid medical conditions; among those who are dependent on hypnotics, CBT-I helps improve subjective sleep quality and sleep onset latency. Several randomized controlled trials indicate that CBT-I "may be particularly effective in facilitating hypnotic withdrawal in older adults," she said, noting that this is important given that hypnotics are associated with falls, confusion, and constipation in this population.

She cited a study that demonstrated that the best outcomes are achieved if CBT-I is employed first, then medication added, then medication discontinued prior to the end of CBT-I (Lancet 2012;379:1129-41).

CBT-I and cost savings

Another recent study shows that in addition to improving symptoms, brief CBT-I reduces health care utilization and costs.

The medical records review of 84 outpatients with a mean age of 54 years showed that for 37 patients who completed at least three CBT session for insomnia, and 32 who completed at least three sessions and who experienced significant sleep improvement, all health care use and cost variables, with the exception of number of medications, decreased significantly or trended toward decrease after treatment.

The average decrease in CPT costs was $200 for completers and $210 for responders. No significant decreases occurred in those who did not complete therapy, Christina McCrae, Ph.D., of the University of Florida, Gainesville, and her colleagues reported in February in the Journal of Clinical Sleep Medicine.

Patients included in the study received sleep and sleep hygiene education, stimulus control therapy, sleep restriction, a 10-minute relaxation exercise, and cognitive therapy during up to 6 weekly treatment sessions led by clinical psychology graduate students and predoctoral interns.

Although the study is limited by its small sample size and non-normal data distribution, the findings underscore a need for greater dissemination of brief CBT for insomnia; as few as 3 sessions are needed for significant improvement, the therapy can be delivered by novice clinicians, and the therapy is associated with reduced costs and reduced burden of insomnia, the investigators concluded (J. Clin. Sleep Med. 2014;10:127-35).

While the cost of brief treatment, which was $460 in this study, might negate the short-term savings seen in the first 6 months after therapy, the effects of therapy are durable, so CBT for insomnia has the potential to produce substantial long-term savings, the investigator said in a press statement. They noted that this is particularly true when these results are extrapolated to the large population of insomnia patients in the U.S. health care system.

Dr. Sudak is a coauthor of the book "High-Yield Cognitive-Behavior Therapy for Brief Sessions: An Illustrated Guide" (Washington: American Psychiatric Publishing, 2010). She receives book royalties from American Psychiatric Publishing; Lippincott, Williams & Wilkins; and John Wiley & Sons. Dr. Sudak also is on an editorial board and receives honoraria from Elsevier and is a consultant for Takeda Pharmaceuticals. Dr. Lovato and Dr. McCrae reported having no disclosures.

SAN ANTONIO – Brief cognitive-behavioral therapy is particularly helpful for the treatment of insomnia, including insomnia that occurs in association with depression or other psychiatric conditions.

Even cognitive-behavioral therapy (CBT) sessions lasting only 8-10 minutes, when accompanied by informational handouts, can lead to improvements in insomnia, Dr. Donna M. Sudak, professor and director of the psychotherapy training program at Drexel University, Philadelphia, said during a premeeting workshop on high-yield brief CBT at the annual meeting of the American College of Psychiatrists.

"It’s really rapid," she said of the intervention and its effects on insomnia.

Dr. Sudak noted that in patients with depression, it often is assumed that "the insomnia component of depression really has to do with the depression itself," but in fact, treating the insomnia appears to also make a real difference in the depression, suggesting the two conditions are interrelated.

"CBT works really well, and it also may be important in terms of managing other conditions," she said.

In an article that synthesized the relevant empirical evidence related to the efficacy of CBT for insomnia (CBT-I) and the benzodiazepines and benzodiazepine-receptor antagonists often used for the treatment of insomnia, Dr. Sudak notes that chronic insomnia affects an estimated 6% to 10% of the population, and that the highly prevalent sleep disorder is accompanied by significant daytime impairment.

"Insomnia has significant consequences for daytime functioning and health-related quality of life. The disorder conveys serious occupational and economic burdens, including mood disturbance, sleepiness, fatigue, cognitive impairment, and high rates of absenteeism and ‘presenteeism,’ " she wrote.

She also noted that insomnia sufferers are at increased risk of compromised psychological and physical health.

In the article, which has been accepted for publication in the International Journal of Cognitive Psychotherapy, she notes that CBT-I, which typically involves six to eight individual or group sessions that employ strategies such as stimulus control, sleep restriction, relaxation, and cognitive restructuring, is recommended by the American Academy of Sleep Medicine and the National Institutes of Health based on the substantial support in the literature for its efficacy and effectiveness in treating primary insomnia. She cites, for example, a meta-analysis of randomized controlled trials that suggests that CBT-I has moderate to large effects with respect to improving sleep (Sleep and Biol. Rhythms 2011;9:24-34).

Other studies have found a high rate of treatment response and clinically significant remissions with CBT-I, she noted.

CBT-I for comorbid insomnia, psychiatric illness

CBT-I also is beneficial in patients with coexisting insomnia and psychiatric illness.

"An estimated 30% to 90% of psychiatric patients have sleep disturbances. Conversely, patients with psychiatric illness account for an estimated 40% to 50% of patients with chronic insomnia.

Furthermore, those with anxiety and depression have a fivefold increase in the likelihood of having chronic insomnia, compared with those without anxiety or depression, and numerous studies suggest that insomnia that coexists with a range of psychiatric and medical conditions benefits from the application of CBT-I.

"It is therefore worthwhile to pursue strategies for combining CBT-I and pharmacotherapy in such groups," she wrote.

However, despite the high comorbidity, insomnia is rarely independently treated with CBT-I in mood disorders, which leaves patients vulnerable to relapse of depression, as well as to morbidity associated with sleep disturbance.

"It is increasingly recognized that insomnia is often best conceptualized as a separate entity that should be managed with specific, targeted treatment rather than secondary to depression treatment," she wrote, noting that since the prevalence of comorbid insomnia increases with the severity of depression, and since insomnia increases the risk of recurrence of depression and suicide, the most important take-home lesson from the literature might well be that when patients have both major depression and insomnia, a treatment targeting both conditions is warranted.

Indeed, data increasingly suggest that CBT-I is such a treatment.

In a recent study presented at the annual meeting of the Association for Behavioral and Cognitive Therapies, 87% of 66 patients with depression whose insomnia resolved after 4 brief biweekly CBT sessions also experienced significant declines in their depression symptoms after 8 weeks of treatment – regardless of whether they were treated with an antidepressant drug or received placebo. The rate of improvement in depression symptoms in those who also experienced improvement in their insomnia was almost twice as high as in patients who did not experience improvement in their insomnia, according to the lead author, Colleen E. Carney, Ph.D., of Ryerson University, Toronto.

CBT-I in older adults

In another recent study, Nicole Lovato, Ph.D., of Flinders University, Adelaide, South Australia, and her colleagues demonstrated that 4 brief weekly CBT group-administered sessions for insomnia were effective for improving symptoms in older adults with sleep maintenance insomnia.

For that randomized controlled trial involving 118 adults with a mean age of 64 years, the investigators compared 86 CBT patients with 32 waitlist controls. At 3-month follow-up, those in the treatment group experienced significant improvements in the timing and quality of sleep, including later bedtime, earlier out-of-bed time, reduced wake after sleep onset, and improved sleep efficiency (Sleep 2014;37:117-26).

Improvements were seen on the Insomnia Severity Index, Flinders Fatigue Scale, Epworth Sleepiness Scale, Daytime Feeling and Functioning Scale, Sleep Anticipatory Anxiety Questionnaire, Dysfunctional Beliefs and Attitudes Scale, and Sleep Self-Efficacy Scale, they reported.

"These changes were supported by large effect sizes (1.14-1.54) and were significantly greater than the wait-list group both immediately following treatment and at 3-month follow-up," the investigators wrote.

The CBT intervention included bedtime restriction therapy, sleep education, and cognitive restructuring.

The group-administered treatment program used in the study, "promises to be a brief and inexpensive answer to the effective treatment of insomnia in the older population," they concluded.

Dr. Sudak’s paper also addressed CBT-I use in the elderly, who have a substantial risk of insomnia and who frequently use hypnotics for treatment of insomnia.

"Treatment with CBT-I is effective in older adults and results are more durable than medication," she said, noting that 50% of elders who receive CBT-I sustain remission for at least 2 years.

CBT-I is also effective in older adults with comorbid medical conditions; among those who are dependent on hypnotics, CBT-I helps improve subjective sleep quality and sleep onset latency. Several randomized controlled trials indicate that CBT-I "may be particularly effective in facilitating hypnotic withdrawal in older adults," she said, noting that this is important given that hypnotics are associated with falls, confusion, and constipation in this population.

She cited a study that demonstrated that the best outcomes are achieved if CBT-I is employed first, then medication added, then medication discontinued prior to the end of CBT-I (Lancet 2012;379:1129-41).

CBT-I and cost savings

Another recent study shows that in addition to improving symptoms, brief CBT-I reduces health care utilization and costs.

The medical records review of 84 outpatients with a mean age of 54 years showed that for 37 patients who completed at least three CBT session for insomnia, and 32 who completed at least three sessions and who experienced significant sleep improvement, all health care use and cost variables, with the exception of number of medications, decreased significantly or trended toward decrease after treatment.

The average decrease in CPT costs was $200 for completers and $210 for responders. No significant decreases occurred in those who did not complete therapy, Christina McCrae, Ph.D., of the University of Florida, Gainesville, and her colleagues reported in February in the Journal of Clinical Sleep Medicine.

Patients included in the study received sleep and sleep hygiene education, stimulus control therapy, sleep restriction, a 10-minute relaxation exercise, and cognitive therapy during up to 6 weekly treatment sessions led by clinical psychology graduate students and predoctoral interns.

Although the study is limited by its small sample size and non-normal data distribution, the findings underscore a need for greater dissemination of brief CBT for insomnia; as few as 3 sessions are needed for significant improvement, the therapy can be delivered by novice clinicians, and the therapy is associated with reduced costs and reduced burden of insomnia, the investigators concluded (J. Clin. Sleep Med. 2014;10:127-35).

While the cost of brief treatment, which was $460 in this study, might negate the short-term savings seen in the first 6 months after therapy, the effects of therapy are durable, so CBT for insomnia has the potential to produce substantial long-term savings, the investigator said in a press statement. They noted that this is particularly true when these results are extrapolated to the large population of insomnia patients in the U.S. health care system.

Dr. Sudak is a coauthor of the book "High-Yield Cognitive-Behavior Therapy for Brief Sessions: An Illustrated Guide" (Washington: American Psychiatric Publishing, 2010). She receives book royalties from American Psychiatric Publishing; Lippincott, Williams & Wilkins; and John Wiley & Sons. Dr. Sudak also is on an editorial board and receives honoraria from Elsevier and is a consultant for Takeda Pharmaceuticals. Dr. Lovato and Dr. McCrae reported having no disclosures.

HOLLYWOOD, FLA. – Patients with stage T1b gallbladder cancer who can tolerate surgery should undergo radical cholecystectomy, Dr. Chandrakanth Are said at the annual conference of the National Comprehensive Cancer Network.

Although there is little controversy about the need for simple cholecystectomy in patients with carcinoma in situ and those with T1a disease, or about the need for radical cholecystectomy in those with T2 disease or in those with T3 disease in whom the procedure will be curative, there has been less certainty about the treatment for T1b disease, said Dr. Are.

"Ten to 15 years ago we weren’t doing [radical cholecystectomy] in these patients, but we found out that is probably what we should be doing," he said. Multiple studies suggest that about 15% of patients with T1b disease have positive lymph nodes, compared with less than 3% of those with T1a disease, and that more than 10% of T1a and T1b patients have residual disease after simple cholecystectomy, with most of those cases attributable to T1b disease, he noted.

The problem is that patients with T1b disease, as well as patients with T2 disease, remain undertreated, said Dr. Are of the Fred & Pamela Buffett Cancer Center at the Nebraska Medical Center, Omaha.

At least two studies have demonstrated that few eligible patients undergo radical cholecystectomy. Both studies used data from the Surveillance, Epidemiology, and End Results (SEER) registry.

One showed that of 2,385 resected patients with T1-T3 M0 gallbladder cancer, only 8.6% underwent en bloc resection, and 5.3% had a lymphadenectomy (J. Am. Coll Surg. 2008;207:371-82).

Another showed that of 382 patients with T2 disease, only 14 underwent radical cholecystectomy (Am. J. Surg. 2007;194:820-5).

"If this is the fate of patients with T2, imagine where patients with T1b stand," he said, adding that more education is needed about the appropriate management of patients with Stage T1b disease, and more emphasis should be placed on referring these patients to centers of excellence.

Dr. Are cited other controversies in the treatment of gallbladder cancer as follows:

• Bile duct resection. Historically, bile duct resection has been performed at the time of cholecystectomy, but this practice has been found to increase morbidity without providing any survival benefit, Dr. Are said.

Current thinking is that bile duct resection should be performed only in patients with a positive cystic duct margin (because studies suggest that more than 40% of such cases will have common bile duct involvement), and in cases in which extensive lymph node dissection is necessary and might cause ischemia of the duct, he said.

• Extent of lymph node excision. There has been uncertainty regarding the appropriate number of lymph nodes to excise, but data suggest that survival improves with excision of five or more. In one study in which lymph node data were available for more than 2,500 patients, 68% had no lymph nodes excised, 28% had one to four excised, and 4% had more than five excised. The hazard ratios for survival were 0.55 (P less than .001) for one to four vs. no nodes, and 0.63 (P = .03) for more than five nodes vs. one to four nodes (Arch. Surg. 2011;146:734-8).

Another study of 122 patients showed improved survival among those with greater than six vs. less than six nodes excised, although the median total lymph node count was three (Ann. Surg. 2011;254:320-5).

The matter of setting a standard for the number of lymph nodes to dissect was discussed at a consensus conference in January, and guidelines are forthcoming.

Dr. Are predicted the consensus will be that three to six lymph nodes should be excised.

• Port sites metastases. Studies suggest that up to 19% of patients who undergo laparoscopic cholecystectomy will develop port site metastases, and it was thought that these sites should be resected. However, recent findings from a series of 113 patients, of whom 19% developed port site metastases, showed that while survival was significantly worse in those patients (42 months vs. 17 months in those without port site metastases), resection did not change the outcome (Ann. Surg. Oncol. 2012;19:409-17).

The current thinking is that port site metastases is a marker of underlying aggressive disease, and that resection is not warranted, Dr. Are said.

• Jaundice. A number of patients with gallbladder cancer present with jaundice, and data from countries in the West where the disease incidence is relatively low have suggested that jaundice is associated with poor prognosis and is thus a contraindication to resection. One U.S. study showed a 6-month survival among resected patients with jaundice, compared with 16 months for those with no jaundice. None of the patients with jaundice survived 2 years, compared with 21% of those without jaundice (Ann. Surg. Oncol. 2004;11:310-15).

Subsequent studies, including studies from India where the incidence is much higher, showed better survival. One, for example, demonstrated 50% survival among resected patients with jaundice; another demonstrated 23% 5-year survival.

"So the current recommendation is that the presence of jaundice is still a contraindication [to resection], but not an absolute contraindication," Dr. Are said.

It is a relative contraindication in selected patients; those with appropriate T stage who are fit enough for surgery and anesthesia should proceed to surgery, he added, noting that in those who are unresectable, it is important to think of biliary drainage.

"Unless you do that, it will be hard for them to get chemotherapy," he said.

• Extent of hepatic resection. The standard of care with respect to hepatic resection at the time of radical cholecystectomy is to resect only segments 4b and 5 of the liver. The controversy is whether more should be resected.

Data as to whether more extensive resection confers a survival benefit have been conflicting, with some studies showing a benefit with right lobectomy or extended right lobectomy, and others showing no such benefit, Dr. Are said.

The current standard of resecting 4b and 5 is adequate, except in selected cases where the intent of resecting more is to obtain negative margins, he said.

Dr. Are reported having no relevant disclosures.

HOLLYWOOD, FLA. – Patients with stage T1b gallbladder cancer who can tolerate surgery should undergo radical cholecystectomy, Dr. Chandrakanth Are said at the annual conference of the National Comprehensive Cancer Network.

Although there is little controversy about the need for simple cholecystectomy in patients with carcinoma in situ and those with T1a disease, or about the need for radical cholecystectomy in those with T2 disease or in those with T3 disease in whom the procedure will be curative, there has been less certainty about the treatment for T1b disease, said Dr. Are.

"Ten to 15 years ago we weren’t doing [radical cholecystectomy] in these patients, but we found out that is probably what we should be doing," he said. Multiple studies suggest that about 15% of patients with T1b disease have positive lymph nodes, compared with less than 3% of those with T1a disease, and that more than 10% of T1a and T1b patients have residual disease after simple cholecystectomy, with most of those cases attributable to T1b disease, he noted.

The problem is that patients with T1b disease, as well as patients with T2 disease, remain undertreated, said Dr. Are of the Fred & Pamela Buffett Cancer Center at the Nebraska Medical Center, Omaha.

At least two studies have demonstrated that few eligible patients undergo radical cholecystectomy. Both studies used data from the Surveillance, Epidemiology, and End Results (SEER) registry.

One showed that of 2,385 resected patients with T1-T3 M0 gallbladder cancer, only 8.6% underwent en bloc resection, and 5.3% had a lymphadenectomy (J. Am. Coll Surg. 2008;207:371-82).

Another showed that of 382 patients with T2 disease, only 14 underwent radical cholecystectomy (Am. J. Surg. 2007;194:820-5).

"If this is the fate of patients with T2, imagine where patients with T1b stand," he said, adding that more education is needed about the appropriate management of patients with Stage T1b disease, and more emphasis should be placed on referring these patients to centers of excellence.

Dr. Are cited other controversies in the treatment of gallbladder cancer as follows:

• Bile duct resection. Historically, bile duct resection has been performed at the time of cholecystectomy, but this practice has been found to increase morbidity without providing any survival benefit, Dr. Are said.

Current thinking is that bile duct resection should be performed only in patients with a positive cystic duct margin (because studies suggest that more than 40% of such cases will have common bile duct involvement), and in cases in which extensive lymph node dissection is necessary and might cause ischemia of the duct, he said.

• Extent of lymph node excision. There has been uncertainty regarding the appropriate number of lymph nodes to excise, but data suggest that survival improves with excision of five or more. In one study in which lymph node data were available for more than 2,500 patients, 68% had no lymph nodes excised, 28% had one to four excised, and 4% had more than five excised. The hazard ratios for survival were 0.55 (P less than .001) for one to four vs. no nodes, and 0.63 (P = .03) for more than five nodes vs. one to four nodes (Arch. Surg. 2011;146:734-8).

Another study of 122 patients showed improved survival among those with greater than six vs. less than six nodes excised, although the median total lymph node count was three (Ann. Surg. 2011;254:320-5).

The matter of setting a standard for the number of lymph nodes to dissect was discussed at a consensus conference in January, and guidelines are forthcoming.

Dr. Are predicted the consensus will be that three to six lymph nodes should be excised.

• Port sites metastases. Studies suggest that up to 19% of patients who undergo laparoscopic cholecystectomy will develop port site metastases, and it was thought that these sites should be resected. However, recent findings from a series of 113 patients, of whom 19% developed port site metastases, showed that while survival was significantly worse in those patients (42 months vs. 17 months in those without port site metastases), resection did not change the outcome (Ann. Surg. Oncol. 2012;19:409-17).

The current thinking is that port site metastases is a marker of underlying aggressive disease, and that resection is not warranted, Dr. Are said.

• Jaundice. A number of patients with gallbladder cancer present with jaundice, and data from countries in the West where the disease incidence is relatively low have suggested that jaundice is associated with poor prognosis and is thus a contraindication to resection. One U.S. study showed a 6-month survival among resected patients with jaundice, compared with 16 months for those with no jaundice. None of the patients with jaundice survived 2 years, compared with 21% of those without jaundice (Ann. Surg. Oncol. 2004;11:310-15).

Subsequent studies, including studies from India where the incidence is much higher, showed better survival. One, for example, demonstrated 50% survival among resected patients with jaundice; another demonstrated 23% 5-year survival.

"So the current recommendation is that the presence of jaundice is still a contraindication [to resection], but not an absolute contraindication," Dr. Are said.

It is a relative contraindication in selected patients; those with appropriate T stage who are fit enough for surgery and anesthesia should proceed to surgery, he added, noting that in those who are unresectable, it is important to think of biliary drainage.

"Unless you do that, it will be hard for them to get chemotherapy," he said.

• Extent of hepatic resection. The standard of care with respect to hepatic resection at the time of radical cholecystectomy is to resect only segments 4b and 5 of the liver. The controversy is whether more should be resected.

Data as to whether more extensive resection confers a survival benefit have been conflicting, with some studies showing a benefit with right lobectomy or extended right lobectomy, and others showing no such benefit, Dr. Are said.

The current standard of resecting 4b and 5 is adequate, except in selected cases where the intent of resecting more is to obtain negative margins, he said.

Dr. Are reported having no relevant disclosures.

HOLLYWOOD, FLA. – Patients with stage T1b gallbladder cancer who can tolerate surgery should undergo radical cholecystectomy, Dr. Chandrakanth Are said at the annual conference of the National Comprehensive Cancer Network.

Although there is little controversy about the need for simple cholecystectomy in patients with carcinoma in situ and those with T1a disease, or about the need for radical cholecystectomy in those with T2 disease or in those with T3 disease in whom the procedure will be curative, there has been less certainty about the treatment for T1b disease, said Dr. Are.

"Ten to 15 years ago we weren’t doing [radical cholecystectomy] in these patients, but we found out that is probably what we should be doing," he said. Multiple studies suggest that about 15% of patients with T1b disease have positive lymph nodes, compared with less than 3% of those with T1a disease, and that more than 10% of T1a and T1b patients have residual disease after simple cholecystectomy, with most of those cases attributable to T1b disease, he noted.

The problem is that patients with T1b disease, as well as patients with T2 disease, remain undertreated, said Dr. Are of the Fred & Pamela Buffett Cancer Center at the Nebraska Medical Center, Omaha.

At least two studies have demonstrated that few eligible patients undergo radical cholecystectomy. Both studies used data from the Surveillance, Epidemiology, and End Results (SEER) registry.

One showed that of 2,385 resected patients with T1-T3 M0 gallbladder cancer, only 8.6% underwent en bloc resection, and 5.3% had a lymphadenectomy (J. Am. Coll Surg. 2008;207:371-82).

Another showed that of 382 patients with T2 disease, only 14 underwent radical cholecystectomy (Am. J. Surg. 2007;194:820-5).

"If this is the fate of patients with T2, imagine where patients with T1b stand," he said, adding that more education is needed about the appropriate management of patients with Stage T1b disease, and more emphasis should be placed on referring these patients to centers of excellence.

Dr. Are cited other controversies in the treatment of gallbladder cancer as follows:

• Bile duct resection. Historically, bile duct resection has been performed at the time of cholecystectomy, but this practice has been found to increase morbidity without providing any survival benefit, Dr. Are said.

Current thinking is that bile duct resection should be performed only in patients with a positive cystic duct margin (because studies suggest that more than 40% of such cases will have common bile duct involvement), and in cases in which extensive lymph node dissection is necessary and might cause ischemia of the duct, he said.

• Extent of lymph node excision. There has been uncertainty regarding the appropriate number of lymph nodes to excise, but data suggest that survival improves with excision of five or more. In one study in which lymph node data were available for more than 2,500 patients, 68% had no lymph nodes excised, 28% had one to four excised, and 4% had more than five excised. The hazard ratios for survival were 0.55 (P less than .001) for one to four vs. no nodes, and 0.63 (P = .03) for more than five nodes vs. one to four nodes (Arch. Surg. 2011;146:734-8).

Another study of 122 patients showed improved survival among those with greater than six vs. less than six nodes excised, although the median total lymph node count was three (Ann. Surg. 2011;254:320-5).

The matter of setting a standard for the number of lymph nodes to dissect was discussed at a consensus conference in January, and guidelines are forthcoming.

Dr. Are predicted the consensus will be that three to six lymph nodes should be excised.

• Port sites metastases. Studies suggest that up to 19% of patients who undergo laparoscopic cholecystectomy will develop port site metastases, and it was thought that these sites should be resected. However, recent findings from a series of 113 patients, of whom 19% developed port site metastases, showed that while survival was significantly worse in those patients (42 months vs. 17 months in those without port site metastases), resection did not change the outcome (Ann. Surg. Oncol. 2012;19:409-17).

The current thinking is that port site metastases is a marker of underlying aggressive disease, and that resection is not warranted, Dr. Are said.

• Jaundice. A number of patients with gallbladder cancer present with jaundice, and data from countries in the West where the disease incidence is relatively low have suggested that jaundice is associated with poor prognosis and is thus a contraindication to resection. One U.S. study showed a 6-month survival among resected patients with jaundice, compared with 16 months for those with no jaundice. None of the patients with jaundice survived 2 years, compared with 21% of those without jaundice (Ann. Surg. Oncol. 2004;11:310-15).

Subsequent studies, including studies from India where the incidence is much higher, showed better survival. One, for example, demonstrated 50% survival among resected patients with jaundice; another demonstrated 23% 5-year survival.

"So the current recommendation is that the presence of jaundice is still a contraindication [to resection], but not an absolute contraindication," Dr. Are said.

It is a relative contraindication in selected patients; those with appropriate T stage who are fit enough for surgery and anesthesia should proceed to surgery, he added, noting that in those who are unresectable, it is important to think of biliary drainage.

"Unless you do that, it will be hard for them to get chemotherapy," he said.

• Extent of hepatic resection. The standard of care with respect to hepatic resection at the time of radical cholecystectomy is to resect only segments 4b and 5 of the liver. The controversy is whether more should be resected.

Data as to whether more extensive resection confers a survival benefit have been conflicting, with some studies showing a benefit with right lobectomy or extended right lobectomy, and others showing no such benefit, Dr. Are said.

The current standard of resecting 4b and 5 is adequate, except in selected cases where the intent of resecting more is to obtain negative margins, he said.

Dr. Are reported having no relevant disclosures.

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.

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.

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.

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.