Sharon Worcester

ATLANTA – A new scale for predicting complicated alcohol withdrawal syndrome in hospitalized medically ill patients had high sensitivity and specificity in a prospective validation study.

The Prediction of Alcohol Withdrawal Severity Scale (PAWSS) can help clinicians identify those at risk for complicated alcohol withdrawal syndrome (AWS), and either prevent or treat complicated AWS in a timely manner, Dr. José R. Maldonado of Stanford (Calif.) University said at the annual meeting of the American Psychiatric Association.

In 403 subjects hospitalized to general medicine and surgery units over a 12-month period, the PAWSS – along with the Clinical Institute Withdrawal Assessment–alcohol revised (CIWA-Ar) and clinical monitoring – was administered daily. Using a cutoff score of 4 on the 0-10 point PAWSS, the tool had sensitivity and positive predictive value of 93.1%, and specificity and negative predictive value of 99.5% for identifying complicated AWS, Dr. Maldonado said, noting that the tool also had excellent inter-rater reliability.

The findings are important because the prevalence of alcohol use disorders among hospitalized medically ill patients exceeds 40%, he said, noting that medically ill patients with AWS tend to have a significant number of complications, which makes them “not only very difficult to treat but also very high risk.”

Importantly, seizures – commonly known as “rum fits,” which occur in 5%-15% of cases – happen very early on in the course of AWS. This is a concern, because it has implications for prescribing, Dr. Maldonado said.

Another concern, and “probably the most dreadful of them all,” is delirium tremens (DTs), a severe symptom of alcohol withdrawal that occurs in about 10% of patients with AWS.

The overall mortality associated with DTs is 1% in non–medically ill patients, but in the medically ill, this figure increases to 20% because of the frequency of comorbidities, such as heart disease and diabetes in this population. Also, DTs tend to occur a few days into withdrawal, peaking on day 5, which could be problematic; a trauma patient who is intubated in the operating room, for example, still could go through withdrawal a few days later, as most medications being used in that patient are not going to prevent it, he explained.

Previously, no tool was available to predict complicated AWS to prevent seizures and DTs. Existing tools such as the CIWA and AWS scale assess AWS severity but do not predict who will withdraw, he noted, explaining that by the time the CIWA scale is positive, the patient already is in withdrawal.

One option is to treat everyone with benzodiazepines or other drugs that facilitate GABA (gamma-aminobutyric acid) transmission in patients at risk of AWS, but this unnecessarily puts 80% of patients at risk of numerous side effects, including excessive sedation, falls, respiratory depression, and medication-induced delirium.

A benzodiazepine-sparing protocol, which involved the use of alpha-2 agonists and anticonvulsants instead of benzodiazepines, was being studied at Stanford, comparing outcomes in patients treated with and without benzodiazepines.

“But before we started to use alpha-2 agonists and anticonvulsants ... we wanted to make sure that we were actually treating the population that really needs it. That was the main motivation for creating this tool,” he said. “The other thing is we wanted to make sure that we don’t scare people away from treating patients with potential alcohol withdrawal, because the consequences of withdrawal are dreadful, not only immediately but also into the future.”

Every time someone goes through withdrawal, it is more severe than before, and it lowers the threshold for DTs, he added.

An extensive literature review for anything associated with the various phases of alcohol withdrawal was performed to help develop the PAWSS, which includes 10 highly predictive questions for any patients who first indicate that they have had alcohol in the prior 30 days, or who is admitted with a positive blood alcohol level test.

A pilot study involving 70 patients yielded a sensitivity and specificity of 100% each, leading to the larger study of hospitalized patients, which was published last year in Alcohol and Alcoholism (2015 May 21. doi: 10.1093/alcalc/agv043).

A check of admission notes would have increased the ultimate sensitivity of the scale to 100%, as false answers provided on the scale were easily identified. Blood alcohol level testing also would help.

But PAWSS is meant to provide timely information, which is important in patients at risk, and another purpose for developing PAWSS was to provide an affordable tool that can be used anywhere, including rural community hospitals or clinics where other tests might not be available, Dr. Maldonado said.

Currently, he and his colleagues are evaluating whether all 10 items on the scale are needed to make a diagnosis, or whether a shorter version would be equally useful.

“The incidence of alcoholism is extremely high. It is the most common drug problem in the United States, and we know that many physicians do not feel comfortable dealing with patients who have alcohol withdrawal,” Dr. Maldonado said, adding that this tool will simplify management.

For the Stanford study, patients with a negative PAWSS (score below 4) receive no treatment specifically for AWS. If they test positive (score of 4 or more), it is assumed that they will withdraw, and the AWS scale is administered to discriminate patients who are withdrawing from those at high risk of withdrawal. Patients with a positive PAWSS and a negative AWS scale or CIWA are directed to a prophylactic treatment arm. Those with a positive PAWSS and a positive AWS scale or CIWA are directed into a treatment arm, which involves more aggressive management.

The validation study was supported by the Chase Research Fund. Dr. Maldonado reported having no disclosures.

sworcester@frontlinemedcom.com

ATLANTA – A new scale for predicting complicated alcohol withdrawal syndrome in hospitalized medically ill patients had high sensitivity and specificity in a prospective validation study.

The Prediction of Alcohol Withdrawal Severity Scale (PAWSS) can help clinicians identify those at risk for complicated alcohol withdrawal syndrome (AWS), and either prevent or treat complicated AWS in a timely manner, Dr. José R. Maldonado of Stanford (Calif.) University said at the annual meeting of the American Psychiatric Association.

In 403 subjects hospitalized to general medicine and surgery units over a 12-month period, the PAWSS – along with the Clinical Institute Withdrawal Assessment–alcohol revised (CIWA-Ar) and clinical monitoring – was administered daily. Using a cutoff score of 4 on the 0-10 point PAWSS, the tool had sensitivity and positive predictive value of 93.1%, and specificity and negative predictive value of 99.5% for identifying complicated AWS, Dr. Maldonado said, noting that the tool also had excellent inter-rater reliability.

The findings are important because the prevalence of alcohol use disorders among hospitalized medically ill patients exceeds 40%, he said, noting that medically ill patients with AWS tend to have a significant number of complications, which makes them “not only very difficult to treat but also very high risk.”

Importantly, seizures – commonly known as “rum fits,” which occur in 5%-15% of cases – happen very early on in the course of AWS. This is a concern, because it has implications for prescribing, Dr. Maldonado said.

Another concern, and “probably the most dreadful of them all,” is delirium tremens (DTs), a severe symptom of alcohol withdrawal that occurs in about 10% of patients with AWS.

The overall mortality associated with DTs is 1% in non–medically ill patients, but in the medically ill, this figure increases to 20% because of the frequency of comorbidities, such as heart disease and diabetes in this population. Also, DTs tend to occur a few days into withdrawal, peaking on day 5, which could be problematic; a trauma patient who is intubated in the operating room, for example, still could go through withdrawal a few days later, as most medications being used in that patient are not going to prevent it, he explained.

Previously, no tool was available to predict complicated AWS to prevent seizures and DTs. Existing tools such as the CIWA and AWS scale assess AWS severity but do not predict who will withdraw, he noted, explaining that by the time the CIWA scale is positive, the patient already is in withdrawal.

One option is to treat everyone with benzodiazepines or other drugs that facilitate GABA (gamma-aminobutyric acid) transmission in patients at risk of AWS, but this unnecessarily puts 80% of patients at risk of numerous side effects, including excessive sedation, falls, respiratory depression, and medication-induced delirium.

A benzodiazepine-sparing protocol, which involved the use of alpha-2 agonists and anticonvulsants instead of benzodiazepines, was being studied at Stanford, comparing outcomes in patients treated with and without benzodiazepines.

“But before we started to use alpha-2 agonists and anticonvulsants ... we wanted to make sure that we were actually treating the population that really needs it. That was the main motivation for creating this tool,” he said. “The other thing is we wanted to make sure that we don’t scare people away from treating patients with potential alcohol withdrawal, because the consequences of withdrawal are dreadful, not only immediately but also into the future.”

Every time someone goes through withdrawal, it is more severe than before, and it lowers the threshold for DTs, he added.

An extensive literature review for anything associated with the various phases of alcohol withdrawal was performed to help develop the PAWSS, which includes 10 highly predictive questions for any patients who first indicate that they have had alcohol in the prior 30 days, or who is admitted with a positive blood alcohol level test.

A pilot study involving 70 patients yielded a sensitivity and specificity of 100% each, leading to the larger study of hospitalized patients, which was published last year in Alcohol and Alcoholism (2015 May 21. doi: 10.1093/alcalc/agv043).

A check of admission notes would have increased the ultimate sensitivity of the scale to 100%, as false answers provided on the scale were easily identified. Blood alcohol level testing also would help.

But PAWSS is meant to provide timely information, which is important in patients at risk, and another purpose for developing PAWSS was to provide an affordable tool that can be used anywhere, including rural community hospitals or clinics where other tests might not be available, Dr. Maldonado said.

Currently, he and his colleagues are evaluating whether all 10 items on the scale are needed to make a diagnosis, or whether a shorter version would be equally useful.

“The incidence of alcoholism is extremely high. It is the most common drug problem in the United States, and we know that many physicians do not feel comfortable dealing with patients who have alcohol withdrawal,” Dr. Maldonado said, adding that this tool will simplify management.

For the Stanford study, patients with a negative PAWSS (score below 4) receive no treatment specifically for AWS. If they test positive (score of 4 or more), it is assumed that they will withdraw, and the AWS scale is administered to discriminate patients who are withdrawing from those at high risk of withdrawal. Patients with a positive PAWSS and a negative AWS scale or CIWA are directed to a prophylactic treatment arm. Those with a positive PAWSS and a positive AWS scale or CIWA are directed into a treatment arm, which involves more aggressive management.

The validation study was supported by the Chase Research Fund. Dr. Maldonado reported having no disclosures.

sworcester@frontlinemedcom.com

ATLANTA – A new scale for predicting complicated alcohol withdrawal syndrome in hospitalized medically ill patients had high sensitivity and specificity in a prospective validation study.

The Prediction of Alcohol Withdrawal Severity Scale (PAWSS) can help clinicians identify those at risk for complicated alcohol withdrawal syndrome (AWS), and either prevent or treat complicated AWS in a timely manner, Dr. José R. Maldonado of Stanford (Calif.) University said at the annual meeting of the American Psychiatric Association.

In 403 subjects hospitalized to general medicine and surgery units over a 12-month period, the PAWSS – along with the Clinical Institute Withdrawal Assessment–alcohol revised (CIWA-Ar) and clinical monitoring – was administered daily. Using a cutoff score of 4 on the 0-10 point PAWSS, the tool had sensitivity and positive predictive value of 93.1%, and specificity and negative predictive value of 99.5% for identifying complicated AWS, Dr. Maldonado said, noting that the tool also had excellent inter-rater reliability.

The findings are important because the prevalence of alcohol use disorders among hospitalized medically ill patients exceeds 40%, he said, noting that medically ill patients with AWS tend to have a significant number of complications, which makes them “not only very difficult to treat but also very high risk.”

Importantly, seizures – commonly known as “rum fits,” which occur in 5%-15% of cases – happen very early on in the course of AWS. This is a concern, because it has implications for prescribing, Dr. Maldonado said.

Another concern, and “probably the most dreadful of them all,” is delirium tremens (DTs), a severe symptom of alcohol withdrawal that occurs in about 10% of patients with AWS.

The overall mortality associated with DTs is 1% in non–medically ill patients, but in the medically ill, this figure increases to 20% because of the frequency of comorbidities, such as heart disease and diabetes in this population. Also, DTs tend to occur a few days into withdrawal, peaking on day 5, which could be problematic; a trauma patient who is intubated in the operating room, for example, still could go through withdrawal a few days later, as most medications being used in that patient are not going to prevent it, he explained.

Previously, no tool was available to predict complicated AWS to prevent seizures and DTs. Existing tools such as the CIWA and AWS scale assess AWS severity but do not predict who will withdraw, he noted, explaining that by the time the CIWA scale is positive, the patient already is in withdrawal.

One option is to treat everyone with benzodiazepines or other drugs that facilitate GABA (gamma-aminobutyric acid) transmission in patients at risk of AWS, but this unnecessarily puts 80% of patients at risk of numerous side effects, including excessive sedation, falls, respiratory depression, and medication-induced delirium.

A benzodiazepine-sparing protocol, which involved the use of alpha-2 agonists and anticonvulsants instead of benzodiazepines, was being studied at Stanford, comparing outcomes in patients treated with and without benzodiazepines.

“But before we started to use alpha-2 agonists and anticonvulsants ... we wanted to make sure that we were actually treating the population that really needs it. That was the main motivation for creating this tool,” he said. “The other thing is we wanted to make sure that we don’t scare people away from treating patients with potential alcohol withdrawal, because the consequences of withdrawal are dreadful, not only immediately but also into the future.”

Every time someone goes through withdrawal, it is more severe than before, and it lowers the threshold for DTs, he added.

An extensive literature review for anything associated with the various phases of alcohol withdrawal was performed to help develop the PAWSS, which includes 10 highly predictive questions for any patients who first indicate that they have had alcohol in the prior 30 days, or who is admitted with a positive blood alcohol level test.

A pilot study involving 70 patients yielded a sensitivity and specificity of 100% each, leading to the larger study of hospitalized patients, which was published last year in Alcohol and Alcoholism (2015 May 21. doi: 10.1093/alcalc/agv043).

A check of admission notes would have increased the ultimate sensitivity of the scale to 100%, as false answers provided on the scale were easily identified. Blood alcohol level testing also would help.

But PAWSS is meant to provide timely information, which is important in patients at risk, and another purpose for developing PAWSS was to provide an affordable tool that can be used anywhere, including rural community hospitals or clinics where other tests might not be available, Dr. Maldonado said.

Currently, he and his colleagues are evaluating whether all 10 items on the scale are needed to make a diagnosis, or whether a shorter version would be equally useful.

“The incidence of alcoholism is extremely high. It is the most common drug problem in the United States, and we know that many physicians do not feel comfortable dealing with patients who have alcohol withdrawal,” Dr. Maldonado said, adding that this tool will simplify management.

For the Stanford study, patients with a negative PAWSS (score below 4) receive no treatment specifically for AWS. If they test positive (score of 4 or more), it is assumed that they will withdraw, and the AWS scale is administered to discriminate patients who are withdrawing from those at high risk of withdrawal. Patients with a positive PAWSS and a negative AWS scale or CIWA are directed to a prophylactic treatment arm. Those with a positive PAWSS and a positive AWS scale or CIWA are directed into a treatment arm, which involves more aggressive management.

The validation study was supported by the Chase Research Fund. Dr. Maldonado reported having no disclosures.

sworcester@frontlinemedcom.com

CHICAGO – Agents that target the HER2, BRAF, Hedgehog, or EGFR pathways show promise in nonindicated tumor types that harbor these molecular alterations, according to early findings from the MyPathway study.

Of 129 patients enrolled in the multicenter, open-label, phase IIa study, 29 had a major response, defined as tumor shrinkage of at least 30%, to such treatment. One of those patients had a complete response, and 28 had a partial response. An additional 40 patients had stable disease on treatment. Fourteen of the 29 patients progressed after a median of 6 months’ follow-up, and 15 responses were ongoing at up to 11 months, Dr. John D. Hainsworth reported at the annual meeting of the American Society of Clinical Oncology.

©Gio_tto/Thinkstock.com

No new safety signals were observed, said Dr. Hainsworth of Sarah Cannon Research Institute in Nashville, Tenn.

Treatments evaluated in MyPathway included:

• Trastuzumab + pertuzumab, which targets the HER2 pathway and is currently indicated for breast cancer.

• Vemurafenib, which targets the BRAF pathway and is currently indicated for melanoma.

• Vismodegib, which targets the Hedgehog pathway and is currently indicated for basal cell carcinoma of the skin.

• Erlotinib, which targets the EGFR pathway and is indicated for non–small-cell lung cancer.

Responses have been seen with all four of the treatments, but the best responses were seen among patients with HER2 and BRAF abnormalities.

Among 61 cancers with HER2 amplification/overexpression, trastuzumab + pertuzumab provided a benefit for colorectal, bladder, biliary, non–small-cell lung, pancreas, and head/neck cancers.

Of 20 colorectal tumors, 7 (35%) showed complete or partial response, and 3 (15%) remained stable for at least 120 days (clinical benefit rate, 50%). Complete/partial responses and stable disease, respectively, were also seen in three and two of eight bladder tumors (clinical benefit rate, 63%), in three and three of six biliary tumors (clinical benefit rate, 100%), in two and zero of seven non–small-cell lung tumors (clinical benefit rate, 29%), one and zero of six pancreas tumors (clinical benefit rate, 17%), and one and zero of three head and neck tumors (34%). One of 11 other types of tumors showed disease stability at 120 days (clinical benefit rate, 9%). The overall clinical benefit rate in the study was 43%, Dr. Hainsworth said.

Among 33 cancers with the BRAF mutation, vemurafenib showed activity for non–small-cell lung, ovary, unknown primary, colorectal, pancreas, and head/neck tumors. Of 15 non–small-cell lung tumors, 3 (20%) showed complete or partial responses and 2 (13%) remained stable for at least 120 days (clinical benefit rate, 33%). Complete/partial responses and stable disease, respectively, were also seen in one and two of four ovary tumors (clinical benefit rate, 75%), and complete or partial responses were seen in one each of three unknown primary tumors, two colorectal tumors, two pancreas tumors, and one head/neck tumor (clinical benefit rates of 33%, 50%, 50%, and 100%, respectively). No benefit was seen with tumors at other sites (total clinical benefit rate, 36%), Dr. Hainsworth said.

“Of interest in this group [of patients with BRAF mutations], seven of the eight responses were in V600E mutations, and as you know, that’s the mutation that’s been specifically correlated with high response to BRAF inhibition in melanoma where this treatment is now approved,” he said, adding that the response rate in those patients was 38%.

Based on these early results, enrollment of patients with HER2 abnormalities and colorectal, bladder, or biliary cancer, and of patients with BRAF mutations and lung cancer, will be expanded, he said.

Subjects enrolled in MyPathway have advanced cancer showing abnormalities in any of the pathways of interest. The first 129 received a mean of three prior therapies, and in the 29 who responded, 12 different types of cancer responded to the targeted treatment.

“An increasing number of targeted agents for advanced cancer are in use now based on the presence of molecular abnormalities in the cancer. … We’ve known that the same mutations that are in those cancers are found in a wide variety of other cancers, although at a lower incidence, and it’s been difficult to test how effective these same treatments are for the other cancers due to the difficulty in identifying the patient population,” he said, explaining that an increase in comprehensive genomic profiling in recent years has allowed for identification of more and more of these mutations in other cancers.

“I think we’ve shown now that this trial design is feasible, where patients are selected on the basis of molecular abnormalities in their cancers rather than on their primary tumor type or primary site, and certainly offers opportunities for patients with these molecular abnormalities,” Dr. Hainsworth concluded.

Thus far, MyPathway has enrolled more than 200 patients, and is designed to accrue up to 500, with adjustment of treatment groups based on response rates. Emerging new regimens that target these pathways, such as the MEK inhibitor cobemetinib, will also be added, as will new agents targeting additional molecular abnormalities.

The study design, using this “tumor-agnostic approach,” mirrors that of the ASCO-led TAPUR trial, according to ASCO spokesperson Dr. Sumanta Kumar Pal.

The findings of these and other precision medicine trials may ultimately shift the longstanding cancer treatment paradigm, Dr. Pal said.

MyPathway received funding from Genentech. Dr. Hainsworth reported that his institution has received research funding from Astellas Pharma, AstraZeneca, Celgene, Genentech, Johnson & Johnson, Lilly, and Novartis.

sworcester@frontlinemedcom.com

CHICAGO – Agents that target the HER2, BRAF, Hedgehog, or EGFR pathways show promise in nonindicated tumor types that harbor these molecular alterations, according to early findings from the MyPathway study.

Of 129 patients enrolled in the multicenter, open-label, phase IIa study, 29 had a major response, defined as tumor shrinkage of at least 30%, to such treatment. One of those patients had a complete response, and 28 had a partial response. An additional 40 patients had stable disease on treatment. Fourteen of the 29 patients progressed after a median of 6 months’ follow-up, and 15 responses were ongoing at up to 11 months, Dr. John D. Hainsworth reported at the annual meeting of the American Society of Clinical Oncology.

©Gio_tto/Thinkstock.com

No new safety signals were observed, said Dr. Hainsworth of Sarah Cannon Research Institute in Nashville, Tenn.

Treatments evaluated in MyPathway included:

• Trastuzumab + pertuzumab, which targets the HER2 pathway and is currently indicated for breast cancer.

• Vemurafenib, which targets the BRAF pathway and is currently indicated for melanoma.

• Vismodegib, which targets the Hedgehog pathway and is currently indicated for basal cell carcinoma of the skin.

• Erlotinib, which targets the EGFR pathway and is indicated for non–small-cell lung cancer.

Responses have been seen with all four of the treatments, but the best responses were seen among patients with HER2 and BRAF abnormalities.

Among 61 cancers with HER2 amplification/overexpression, trastuzumab + pertuzumab provided a benefit for colorectal, bladder, biliary, non–small-cell lung, pancreas, and head/neck cancers.

Of 20 colorectal tumors, 7 (35%) showed complete or partial response, and 3 (15%) remained stable for at least 120 days (clinical benefit rate, 50%). Complete/partial responses and stable disease, respectively, were also seen in three and two of eight bladder tumors (clinical benefit rate, 63%), in three and three of six biliary tumors (clinical benefit rate, 100%), in two and zero of seven non–small-cell lung tumors (clinical benefit rate, 29%), one and zero of six pancreas tumors (clinical benefit rate, 17%), and one and zero of three head and neck tumors (34%). One of 11 other types of tumors showed disease stability at 120 days (clinical benefit rate, 9%). The overall clinical benefit rate in the study was 43%, Dr. Hainsworth said.

Among 33 cancers with the BRAF mutation, vemurafenib showed activity for non–small-cell lung, ovary, unknown primary, colorectal, pancreas, and head/neck tumors. Of 15 non–small-cell lung tumors, 3 (20%) showed complete or partial responses and 2 (13%) remained stable for at least 120 days (clinical benefit rate, 33%). Complete/partial responses and stable disease, respectively, were also seen in one and two of four ovary tumors (clinical benefit rate, 75%), and complete or partial responses were seen in one each of three unknown primary tumors, two colorectal tumors, two pancreas tumors, and one head/neck tumor (clinical benefit rates of 33%, 50%, 50%, and 100%, respectively). No benefit was seen with tumors at other sites (total clinical benefit rate, 36%), Dr. Hainsworth said.

“Of interest in this group [of patients with BRAF mutations], seven of the eight responses were in V600E mutations, and as you know, that’s the mutation that’s been specifically correlated with high response to BRAF inhibition in melanoma where this treatment is now approved,” he said, adding that the response rate in those patients was 38%.

Based on these early results, enrollment of patients with HER2 abnormalities and colorectal, bladder, or biliary cancer, and of patients with BRAF mutations and lung cancer, will be expanded, he said.

Subjects enrolled in MyPathway have advanced cancer showing abnormalities in any of the pathways of interest. The first 129 received a mean of three prior therapies, and in the 29 who responded, 12 different types of cancer responded to the targeted treatment.

“An increasing number of targeted agents for advanced cancer are in use now based on the presence of molecular abnormalities in the cancer. … We’ve known that the same mutations that are in those cancers are found in a wide variety of other cancers, although at a lower incidence, and it’s been difficult to test how effective these same treatments are for the other cancers due to the difficulty in identifying the patient population,” he said, explaining that an increase in comprehensive genomic profiling in recent years has allowed for identification of more and more of these mutations in other cancers.

“I think we’ve shown now that this trial design is feasible, where patients are selected on the basis of molecular abnormalities in their cancers rather than on their primary tumor type or primary site, and certainly offers opportunities for patients with these molecular abnormalities,” Dr. Hainsworth concluded.

Thus far, MyPathway has enrolled more than 200 patients, and is designed to accrue up to 500, with adjustment of treatment groups based on response rates. Emerging new regimens that target these pathways, such as the MEK inhibitor cobemetinib, will also be added, as will new agents targeting additional molecular abnormalities.

The study design, using this “tumor-agnostic approach,” mirrors that of the ASCO-led TAPUR trial, according to ASCO spokesperson Dr. Sumanta Kumar Pal.

The findings of these and other precision medicine trials may ultimately shift the longstanding cancer treatment paradigm, Dr. Pal said.

MyPathway received funding from Genentech. Dr. Hainsworth reported that his institution has received research funding from Astellas Pharma, AstraZeneca, Celgene, Genentech, Johnson & Johnson, Lilly, and Novartis.

sworcester@frontlinemedcom.com

CHICAGO – Agents that target the HER2, BRAF, Hedgehog, or EGFR pathways show promise in nonindicated tumor types that harbor these molecular alterations, according to early findings from the MyPathway study.

Of 129 patients enrolled in the multicenter, open-label, phase IIa study, 29 had a major response, defined as tumor shrinkage of at least 30%, to such treatment. One of those patients had a complete response, and 28 had a partial response. An additional 40 patients had stable disease on treatment. Fourteen of the 29 patients progressed after a median of 6 months’ follow-up, and 15 responses were ongoing at up to 11 months, Dr. John D. Hainsworth reported at the annual meeting of the American Society of Clinical Oncology.

©Gio_tto/Thinkstock.com

No new safety signals were observed, said Dr. Hainsworth of Sarah Cannon Research Institute in Nashville, Tenn.

Treatments evaluated in MyPathway included:

• Trastuzumab + pertuzumab, which targets the HER2 pathway and is currently indicated for breast cancer.

• Vemurafenib, which targets the BRAF pathway and is currently indicated for melanoma.

• Vismodegib, which targets the Hedgehog pathway and is currently indicated for basal cell carcinoma of the skin.

• Erlotinib, which targets the EGFR pathway and is indicated for non–small-cell lung cancer.

Responses have been seen with all four of the treatments, but the best responses were seen among patients with HER2 and BRAF abnormalities.

Among 61 cancers with HER2 amplification/overexpression, trastuzumab + pertuzumab provided a benefit for colorectal, bladder, biliary, non–small-cell lung, pancreas, and head/neck cancers.

Of 20 colorectal tumors, 7 (35%) showed complete or partial response, and 3 (15%) remained stable for at least 120 days (clinical benefit rate, 50%). Complete/partial responses and stable disease, respectively, were also seen in three and two of eight bladder tumors (clinical benefit rate, 63%), in three and three of six biliary tumors (clinical benefit rate, 100%), in two and zero of seven non–small-cell lung tumors (clinical benefit rate, 29%), one and zero of six pancreas tumors (clinical benefit rate, 17%), and one and zero of three head and neck tumors (34%). One of 11 other types of tumors showed disease stability at 120 days (clinical benefit rate, 9%). The overall clinical benefit rate in the study was 43%, Dr. Hainsworth said.

Among 33 cancers with the BRAF mutation, vemurafenib showed activity for non–small-cell lung, ovary, unknown primary, colorectal, pancreas, and head/neck tumors. Of 15 non–small-cell lung tumors, 3 (20%) showed complete or partial responses and 2 (13%) remained stable for at least 120 days (clinical benefit rate, 33%). Complete/partial responses and stable disease, respectively, were also seen in one and two of four ovary tumors (clinical benefit rate, 75%), and complete or partial responses were seen in one each of three unknown primary tumors, two colorectal tumors, two pancreas tumors, and one head/neck tumor (clinical benefit rates of 33%, 50%, 50%, and 100%, respectively). No benefit was seen with tumors at other sites (total clinical benefit rate, 36%), Dr. Hainsworth said.

“Of interest in this group [of patients with BRAF mutations], seven of the eight responses were in V600E mutations, and as you know, that’s the mutation that’s been specifically correlated with high response to BRAF inhibition in melanoma where this treatment is now approved,” he said, adding that the response rate in those patients was 38%.

Based on these early results, enrollment of patients with HER2 abnormalities and colorectal, bladder, or biliary cancer, and of patients with BRAF mutations and lung cancer, will be expanded, he said.

Subjects enrolled in MyPathway have advanced cancer showing abnormalities in any of the pathways of interest. The first 129 received a mean of three prior therapies, and in the 29 who responded, 12 different types of cancer responded to the targeted treatment.

“An increasing number of targeted agents for advanced cancer are in use now based on the presence of molecular abnormalities in the cancer. … We’ve known that the same mutations that are in those cancers are found in a wide variety of other cancers, although at a lower incidence, and it’s been difficult to test how effective these same treatments are for the other cancers due to the difficulty in identifying the patient population,” he said, explaining that an increase in comprehensive genomic profiling in recent years has allowed for identification of more and more of these mutations in other cancers.

“I think we’ve shown now that this trial design is feasible, where patients are selected on the basis of molecular abnormalities in their cancers rather than on their primary tumor type or primary site, and certainly offers opportunities for patients with these molecular abnormalities,” Dr. Hainsworth concluded.

Thus far, MyPathway has enrolled more than 200 patients, and is designed to accrue up to 500, with adjustment of treatment groups based on response rates. Emerging new regimens that target these pathways, such as the MEK inhibitor cobemetinib, will also be added, as will new agents targeting additional molecular abnormalities.

The study design, using this “tumor-agnostic approach,” mirrors that of the ASCO-led TAPUR trial, according to ASCO spokesperson Dr. Sumanta Kumar Pal.

The findings of these and other precision medicine trials may ultimately shift the longstanding cancer treatment paradigm, Dr. Pal said.

MyPathway received funding from Genentech. Dr. Hainsworth reported that his institution has received research funding from Astellas Pharma, AstraZeneca, Celgene, Genentech, Johnson & Johnson, Lilly, and Novartis.

sworcester@frontlinemedcom.com

CHICAGO – Liquid biopsy, the testing of the blood for circulating tumor DNA (ctDNA), identified cancer mutations useful as biomarkers in 85% of all advanced cancer cases in the largest-ever genomic analysis performed using such technology.

In nearly half of those (49%), the biomarkers were associated with an approved targeted drug, Philip C. Mack, Ph.D., reported at the annual meeting of the American Society of Clinical Oncology.

The patterns of genetic changes detected in the 17,628 blood specimens analyzed for the study using a highly sensitive next-generation sequencing technique closely mirrored those identified using traditional tumor biopsies, suggesting that liquid biopsy provides a non-invasive alternative to tissue biopsy in certain cases, Dr. Mack, professor and director of molecular pharmacology at the University of California, Davis Comprehensive Cancer Center, said during a press briefing at the meeting.

Overall, taking into account FDA-approved drugs and eligibility for clinical trials, the ctDNA testing revealed a possible treatment option for 63.6% of the 15,191 patients who provided samples.

Further, the commercially available liquid biopsy assay used in the study (Guardant360) identified the presence of resistance alterations that could guide new therapy in patients with tumors that acquire resistance to an effective treatment, he said, noting that these resistance mutations are not typically present at the time of initial tissue-biopsy.

Of the patients included in the study, 37% had lung cancer, 14% had breast cancer, 10% had colorectal cancer, and 39% had other cancers. A comparison of genomic changes in ctDNA in 398 patients with available tumor tissue genetic test results showed that when ctDNA was positive for key abnormalities associated with tumor growth, the same mutations were reported in tissue 94% to 100% of the time.

©Zffoto/Thinkstock

Most of the ctDNA alterations were found at very low levels – with half occurring at a frequency below 0.4% of the total DNA in circulation; even at such low levels, the accuracy of the liquid biopsy assay remained high, Dr. Mack noted.

The ctDNA findings also compared well with those from publicly available population-scale sequencing projects, most notably the Cancer Genome Atlas, he said.

Alterations observed at ctDNA fractions as low as 0.06% responded to treatment, which highlights the importance of assay sensitivity.

Interest in comprehensive tumor genetic profiling to guide patients toward appropriate targeted therapies based on the molecular makeup of their tumors has been increasing, and the current findings underscore its potential value. Advantages of plasma testing include ease of use in any clinic setting, avoidance of biopsy-related complications, ability to monitor changes in disease over time, potential identification of mutations in metastatic lesions not observed in the original tumor biopsy (as genetic changes driving tumor growth often differ in different parts of the tumor), and the opportunity to identify treatment-induced resistance mechanisms, Dr. Mack said.

Additionally, liquid biopsy could be particularly helpful in cases involving tumors for which a traditional biopsy is difficult to obtain.

In fact, the clinical utility of liquid biopsy was evident among 362 lung cancer cases in the study. Tissue was insufficient for traditional biopsy in 63% of the cases, and ctDNA testing identified key genetic mutations at frequencies consistent with their prevalence in the published literature. Thus, ctDNA provided these patients with their only source of an actionable target, Dr. Mack noted.

As for whether liquid biopsy could or should replace tissue biopsy, he explained that it should be viewed more as an additional tool.

“I think there is always going to be a role for tissue-based biopsy,” he said, explaining that a tissue biopsy allows the pathologist to assess the morphological features of the cancer to diagnose it and determine what the tumor type is and where it originated. “That will always be required.”

Leftover tissue should be used for mutational testing, and this is the gold standard. It is in cases when the tissue is of insufficient quality or quantity to allow a broader array of testing that liquid biopsy can provide a complementary source of information, he said.

Further, while it would be ideal to have biopsies of any progressing lesion in a patient who initially had a great response to treatment, that is not feasible, he said.

“So probably, the biggest role for plasma analysis will be occurring down the road as patients are progressing on therapies, as their tumors are evolving, as a way to monitor progression of those cancers,” he said.

Dr. Sumanta Kumar Pal, an ASCO spokesperson and a panel member at the press briefing, noted that “the data that Dr. Mack reported provides key insights into the feasibility of the so-called liquid biopsy.”

“We’re increasingly using genomic data from day-to-day in our clinics to guide therapies,” he said, reiterating that tests such as this provide a useful alternative to tissue-based testing, particularly for the many patients in clinics who have tumors that are challenging to access, such as tumors on bone or near the brain.

“The authors have demonstrated not only the feasibility of the test in detecting alterations, but that the results are often potentially actionable as well ... As oncologists obtain this assay, it’s important to keep in mind trials such as the ASCO-led TAPUR study. TAPUR can potentially link patients with selected genomic alterations to relevant therapies that would otherwise be challenging to access,” he said.

Dr. Pal also noted that there are several other blood-based genomic tests emerging, and it will be important to “rigorously define which of these platforms deliver optimal results.”

Going forward, Dr. Mack and his colleagues will be working to increase the sensitivity of the Gaurdant360 assay to detect mutations at extremely low ctDNA level, as some tumors – glioblastomas, for example – diminish the ability to detect ctDNA. Improved sensitivity could also enable the use of the assay in earlier-stage cancers, he said.

This study was supported by funding from Guardant Health.

sworcester@frontlinemedcom.com

CHICAGO – Liquid biopsy, the testing of the blood for circulating tumor DNA (ctDNA), identified cancer mutations useful as biomarkers in 85% of all advanced cancer cases in the largest-ever genomic analysis performed using such technology.

In nearly half of those (49%), the biomarkers were associated with an approved targeted drug, Philip C. Mack, Ph.D., reported at the annual meeting of the American Society of Clinical Oncology.

The patterns of genetic changes detected in the 17,628 blood specimens analyzed for the study using a highly sensitive next-generation sequencing technique closely mirrored those identified using traditional tumor biopsies, suggesting that liquid biopsy provides a non-invasive alternative to tissue biopsy in certain cases, Dr. Mack, professor and director of molecular pharmacology at the University of California, Davis Comprehensive Cancer Center, said during a press briefing at the meeting.

Overall, taking into account FDA-approved drugs and eligibility for clinical trials, the ctDNA testing revealed a possible treatment option for 63.6% of the 15,191 patients who provided samples.

Further, the commercially available liquid biopsy assay used in the study (Guardant360) identified the presence of resistance alterations that could guide new therapy in patients with tumors that acquire resistance to an effective treatment, he said, noting that these resistance mutations are not typically present at the time of initial tissue-biopsy.

Of the patients included in the study, 37% had lung cancer, 14% had breast cancer, 10% had colorectal cancer, and 39% had other cancers. A comparison of genomic changes in ctDNA in 398 patients with available tumor tissue genetic test results showed that when ctDNA was positive for key abnormalities associated with tumor growth, the same mutations were reported in tissue 94% to 100% of the time.

©Zffoto/Thinkstock

Most of the ctDNA alterations were found at very low levels – with half occurring at a frequency below 0.4% of the total DNA in circulation; even at such low levels, the accuracy of the liquid biopsy assay remained high, Dr. Mack noted.

The ctDNA findings also compared well with those from publicly available population-scale sequencing projects, most notably the Cancer Genome Atlas, he said.

Alterations observed at ctDNA fractions as low as 0.06% responded to treatment, which highlights the importance of assay sensitivity.

Interest in comprehensive tumor genetic profiling to guide patients toward appropriate targeted therapies based on the molecular makeup of their tumors has been increasing, and the current findings underscore its potential value. Advantages of plasma testing include ease of use in any clinic setting, avoidance of biopsy-related complications, ability to monitor changes in disease over time, potential identification of mutations in metastatic lesions not observed in the original tumor biopsy (as genetic changes driving tumor growth often differ in different parts of the tumor), and the opportunity to identify treatment-induced resistance mechanisms, Dr. Mack said.

Additionally, liquid biopsy could be particularly helpful in cases involving tumors for which a traditional biopsy is difficult to obtain.

In fact, the clinical utility of liquid biopsy was evident among 362 lung cancer cases in the study. Tissue was insufficient for traditional biopsy in 63% of the cases, and ctDNA testing identified key genetic mutations at frequencies consistent with their prevalence in the published literature. Thus, ctDNA provided these patients with their only source of an actionable target, Dr. Mack noted.

As for whether liquid biopsy could or should replace tissue biopsy, he explained that it should be viewed more as an additional tool.

“I think there is always going to be a role for tissue-based biopsy,” he said, explaining that a tissue biopsy allows the pathologist to assess the morphological features of the cancer to diagnose it and determine what the tumor type is and where it originated. “That will always be required.”

Leftover tissue should be used for mutational testing, and this is the gold standard. It is in cases when the tissue is of insufficient quality or quantity to allow a broader array of testing that liquid biopsy can provide a complementary source of information, he said.

Further, while it would be ideal to have biopsies of any progressing lesion in a patient who initially had a great response to treatment, that is not feasible, he said.

“So probably, the biggest role for plasma analysis will be occurring down the road as patients are progressing on therapies, as their tumors are evolving, as a way to monitor progression of those cancers,” he said.

Dr. Sumanta Kumar Pal, an ASCO spokesperson and a panel member at the press briefing, noted that “the data that Dr. Mack reported provides key insights into the feasibility of the so-called liquid biopsy.”

“We’re increasingly using genomic data from day-to-day in our clinics to guide therapies,” he said, reiterating that tests such as this provide a useful alternative to tissue-based testing, particularly for the many patients in clinics who have tumors that are challenging to access, such as tumors on bone or near the brain.

“The authors have demonstrated not only the feasibility of the test in detecting alterations, but that the results are often potentially actionable as well ... As oncologists obtain this assay, it’s important to keep in mind trials such as the ASCO-led TAPUR study. TAPUR can potentially link patients with selected genomic alterations to relevant therapies that would otherwise be challenging to access,” he said.

Dr. Pal also noted that there are several other blood-based genomic tests emerging, and it will be important to “rigorously define which of these platforms deliver optimal results.”

Going forward, Dr. Mack and his colleagues will be working to increase the sensitivity of the Gaurdant360 assay to detect mutations at extremely low ctDNA level, as some tumors – glioblastomas, for example – diminish the ability to detect ctDNA. Improved sensitivity could also enable the use of the assay in earlier-stage cancers, he said.

This study was supported by funding from Guardant Health.

sworcester@frontlinemedcom.com

CHICAGO – Liquid biopsy, the testing of the blood for circulating tumor DNA (ctDNA), identified cancer mutations useful as biomarkers in 85% of all advanced cancer cases in the largest-ever genomic analysis performed using such technology.

In nearly half of those (49%), the biomarkers were associated with an approved targeted drug, Philip C. Mack, Ph.D., reported at the annual meeting of the American Society of Clinical Oncology.

The patterns of genetic changes detected in the 17,628 blood specimens analyzed for the study using a highly sensitive next-generation sequencing technique closely mirrored those identified using traditional tumor biopsies, suggesting that liquid biopsy provides a non-invasive alternative to tissue biopsy in certain cases, Dr. Mack, professor and director of molecular pharmacology at the University of California, Davis Comprehensive Cancer Center, said during a press briefing at the meeting.

Overall, taking into account FDA-approved drugs and eligibility for clinical trials, the ctDNA testing revealed a possible treatment option for 63.6% of the 15,191 patients who provided samples.

Further, the commercially available liquid biopsy assay used in the study (Guardant360) identified the presence of resistance alterations that could guide new therapy in patients with tumors that acquire resistance to an effective treatment, he said, noting that these resistance mutations are not typically present at the time of initial tissue-biopsy.

Of the patients included in the study, 37% had lung cancer, 14% had breast cancer, 10% had colorectal cancer, and 39% had other cancers. A comparison of genomic changes in ctDNA in 398 patients with available tumor tissue genetic test results showed that when ctDNA was positive for key abnormalities associated with tumor growth, the same mutations were reported in tissue 94% to 100% of the time.

©Zffoto/Thinkstock

Most of the ctDNA alterations were found at very low levels – with half occurring at a frequency below 0.4% of the total DNA in circulation; even at such low levels, the accuracy of the liquid biopsy assay remained high, Dr. Mack noted.

The ctDNA findings also compared well with those from publicly available population-scale sequencing projects, most notably the Cancer Genome Atlas, he said.

Alterations observed at ctDNA fractions as low as 0.06% responded to treatment, which highlights the importance of assay sensitivity.

Interest in comprehensive tumor genetic profiling to guide patients toward appropriate targeted therapies based on the molecular makeup of their tumors has been increasing, and the current findings underscore its potential value. Advantages of plasma testing include ease of use in any clinic setting, avoidance of biopsy-related complications, ability to monitor changes in disease over time, potential identification of mutations in metastatic lesions not observed in the original tumor biopsy (as genetic changes driving tumor growth often differ in different parts of the tumor), and the opportunity to identify treatment-induced resistance mechanisms, Dr. Mack said.

Additionally, liquid biopsy could be particularly helpful in cases involving tumors for which a traditional biopsy is difficult to obtain.

In fact, the clinical utility of liquid biopsy was evident among 362 lung cancer cases in the study. Tissue was insufficient for traditional biopsy in 63% of the cases, and ctDNA testing identified key genetic mutations at frequencies consistent with their prevalence in the published literature. Thus, ctDNA provided these patients with their only source of an actionable target, Dr. Mack noted.

As for whether liquid biopsy could or should replace tissue biopsy, he explained that it should be viewed more as an additional tool.

“I think there is always going to be a role for tissue-based biopsy,” he said, explaining that a tissue biopsy allows the pathologist to assess the morphological features of the cancer to diagnose it and determine what the tumor type is and where it originated. “That will always be required.”

Leftover tissue should be used for mutational testing, and this is the gold standard. It is in cases when the tissue is of insufficient quality or quantity to allow a broader array of testing that liquid biopsy can provide a complementary source of information, he said.

Further, while it would be ideal to have biopsies of any progressing lesion in a patient who initially had a great response to treatment, that is not feasible, he said.

“So probably, the biggest role for plasma analysis will be occurring down the road as patients are progressing on therapies, as their tumors are evolving, as a way to monitor progression of those cancers,” he said.

Dr. Sumanta Kumar Pal, an ASCO spokesperson and a panel member at the press briefing, noted that “the data that Dr. Mack reported provides key insights into the feasibility of the so-called liquid biopsy.”

“We’re increasingly using genomic data from day-to-day in our clinics to guide therapies,” he said, reiterating that tests such as this provide a useful alternative to tissue-based testing, particularly for the many patients in clinics who have tumors that are challenging to access, such as tumors on bone or near the brain.

“The authors have demonstrated not only the feasibility of the test in detecting alterations, but that the results are often potentially actionable as well ... As oncologists obtain this assay, it’s important to keep in mind trials such as the ASCO-led TAPUR study. TAPUR can potentially link patients with selected genomic alterations to relevant therapies that would otherwise be challenging to access,” he said.

Dr. Pal also noted that there are several other blood-based genomic tests emerging, and it will be important to “rigorously define which of these platforms deliver optimal results.”

Going forward, Dr. Mack and his colleagues will be working to increase the sensitivity of the Gaurdant360 assay to detect mutations at extremely low ctDNA level, as some tumors – glioblastomas, for example – diminish the ability to detect ctDNA. Improved sensitivity could also enable the use of the assay in earlier-stage cancers, he said.

This study was supported by funding from Guardant Health.

sworcester@frontlinemedcom.com

ATLANTA – Vagal activity predicts survival in patients with metastatic or recurrent breast cancer, a study showed.

The findings are intriguing, given that vagal activity is modifiable, according to Dr. David Spiegel, Willson Professor of Psychiatry and Behavioral Sciences and director of the center on stress and health at Stanford (Calif.) University.

The study, conducted by Dr. Spiegel and his colleagues, is one of several that together are beginning to elucidate the connections among sleep, stress, and vagal tone, and the effects these factors have on cancer outcomes. For example, in one earlier study of metastatic breast cancer patients, the group demonstrated that good sleep efficiency predicted longer survival (Sleep. 2014 May 1;37[5]:837-42).

“There’s something about sleep that we think has an effect on disease progression,” Dr. Spiegel said at the annual meeting of the American Psychiatric Association.

In another study, the team showed that breast cancer patients who slept better at night had better vagal tone the following morning.

“We all kind of know that a problem that has been keeping you from getting to sleep or worrying you a lot the night before suddenly seems more soluble in the morning after you’ve had a good night’s sleep. You’re better able to self-soothe in the morning,” he said, noting the importance of this evidence that “sleep improves vagal tone.”

Heart rate variability is a good measure of vagal tone, vagal activity, and the ability to self-soothe, he explained, noting that heart rate variability also predicts longer survival with cardiac disease; it seems to reduce the risk of fatal arrhythmias, and also predicts recovery from myocardial infarction.

Others have suggested that it might have an effect on cancer, and there seems to be a link between vagal activity and inflammatory processes, Dr. Spiegel said.

“There is reason to think that poor heart rate variability might be associated with cancer progression as well, and that’s what we wanted to study in a group of metastatic cancer patients,” he said.

Dr. Spiegel and his colleagues measured high-frequency heart rate variability (HF-HRV), which appears to be the best measure of parasympathetic tone, has been associated with longer survival in humans and animals, and is related to immune system functioning.

“We hypothesized that higher heart rate variability would predict longer survival in patients with MRBC [metastatic or recurrent breast cancer],” he said.

In 87 patients with metastases to bone, skin, or viscera who underwent a variety of stress measures, including a 5-minute resting baseline electrocardiogram, 43 had higher HF-HRV, and 44 had lower HF-HRV. Higher baseline HF-HRV did, indeed, predict significantly longer survival (hazard ratio, 0.75).

“The main hypothesis was confirmed – that patients with better vagal tone, higher high-frequency heart rate variability had significantly longer survival over the ensuing 7 years, compared with the patients who had poorer heart rate variability, poorer vagal tone,” he said (Psychosom Med. 2015;77[4]:346-55).

Visceral metastasis status and baseline heart rate both were related to HF-HRV and survival, and the combination of HF-HRV and heart rate further improved survival prediction (HR, 0.64), he noted.

“This is basically coactivation of higher parasympathetic and lower sympathetic activity related to longer survival,” he explained.

Reconstructive surgery, the presence of visceral metastases, and sleep efficiency each were found to be associated with heart rate variability; thus several analyses were conducted “to try to disentangle these relationships and determine what the major variables were that predicted survival,” Dr. Spiegel said.

“It turns out that heart rate variability and visceral metastases were significantly related, and heart rate variability did not predict survival,” he said, explaining that those with visceral metastases (and therefore, cancer with a much poorer prognosis) died sooner, but heart rate variability didn’t make much of a difference. “Where we saw the heart rate variability effect was among those with better prognosis.”

A combination measure of high heart rate variability (“a pretty pure measure of vagal activity, not sympathetic activity”) and low heart rate (“more driven by the sympathetic adrenal-medullary system”) is an even stronger predictor of overall survival, he said.

This suggests that autonomic nervous system variables play a strong role in predicting overall cancer survival, Dr. Spiegel said, noting that depression was not a confounder.

“This is important, because we have, in other studies, found that depression is associated with lower heart rate variability, as you might expect,” he said. In fact, depression has been found to predict shorter survival in cancer patients over a period of 10 years. In an earlier study, cancer patients with worsening depression in the first year died sooner than those with depression that improved during the first year (J Clin Oncol. 2011;29[4]:413-20).

“The median survival difference was about 2 years, so this is not a trivial difference in overall survival,” he said, stressing that the finding is based on more chronic and severe depression.

Other studies have demonstrated relationships between circadian rhythm disruption and cancer survival. In one such study involving patients with metastatic colorectal cancer, circadian rhythm/rest activity cycle (more activity during the day, more rest at night) was associated with better quality of life and predicted survival.

“This has been shown now in several cancers, and it’s clear that a combination of higher activity and better sleep predict longer survival with different kinds of cancers,” Dr. Spiegel said, explaining that a hallmark of a healthy hypothalamic-pituitary-adrenal axis is good diurnal variation of cortisol with high levels in the morning and declining levels throughout the day.

Women with metastatic breast cancer and poorer survival tended to have flat or increasing levels of cortisol throughout the day, he said, adding that the same was true in a study of patients with lung cancer, and that there is evidence that those among them with flatter, more abnormal cortisol patterns throughout the day also have shorter survival.

Animal studies suggest that cortisol might directly suppress the activity of tumor suppressor genes, he explained, noting that there is also increasing evidence of autonomic dysregulation effects on inflammatory processes associated with tumor growth.

“Some basic research on this in animal models shows that if you block adrenergic arousal, you can block the growth of blood vessels from tumors. This has led some people to look at the use of antiadrenergic drugs like the beta-blocker propranolol, and it turned out – to everyone’s surprise – that breast cancer patients who happened to be on beta-blockers for hypertension actually lived longer than those who didn’t,” he said.

This adds to the growing evidence that dysregulation in the sympathetic and parasympathetic systems have effects on survival, he said.

A look at another factor related to sleep disruption – bedtime misalignment – showed that patients who adhere to their preferred sleep pattern, and who are therefore sleeping better, had a difference in disease-free interval; those whose bedtime was misaligned had a shorter time between diagnosis and disease recurrence (Chronobiol Int. 2014 Mar 31[2]214-21).

“Disease-free interval is a very strong predictor of ultimate overall survival, so there seems to be another relationship here between circadian disruption and disease progression in breast cancer,” Dr. Spiegel said.

Taken together, these findings demonstrate a strong association between vagal activity and survival in patients with metastatic or recurrent breast cancer, extending the known predictive window of HF-HRV beyond palliative care to cancer, Dr. Spiegel said.

“Vagal activity can be altered through behavioral, pharmacological, and surgical interventions and thus may be a promising target for increasing survival in patients with metastatic cancer,” he said.

Dr. Spiegel’s studies were funded by the National Cancer Institute and the National Institute on Aging.

sworcester@frontlinemedcom.com

ATLANTA – Vagal activity predicts survival in patients with metastatic or recurrent breast cancer, a study showed.

The findings are intriguing, given that vagal activity is modifiable, according to Dr. David Spiegel, Willson Professor of Psychiatry and Behavioral Sciences and director of the center on stress and health at Stanford (Calif.) University.

The study, conducted by Dr. Spiegel and his colleagues, is one of several that together are beginning to elucidate the connections among sleep, stress, and vagal tone, and the effects these factors have on cancer outcomes. For example, in one earlier study of metastatic breast cancer patients, the group demonstrated that good sleep efficiency predicted longer survival (Sleep. 2014 May 1;37[5]:837-42).

“There’s something about sleep that we think has an effect on disease progression,” Dr. Spiegel said at the annual meeting of the American Psychiatric Association.

In another study, the team showed that breast cancer patients who slept better at night had better vagal tone the following morning.

“We all kind of know that a problem that has been keeping you from getting to sleep or worrying you a lot the night before suddenly seems more soluble in the morning after you’ve had a good night’s sleep. You’re better able to self-soothe in the morning,” he said, noting the importance of this evidence that “sleep improves vagal tone.”

Heart rate variability is a good measure of vagal tone, vagal activity, and the ability to self-soothe, he explained, noting that heart rate variability also predicts longer survival with cardiac disease; it seems to reduce the risk of fatal arrhythmias, and also predicts recovery from myocardial infarction.

Others have suggested that it might have an effect on cancer, and there seems to be a link between vagal activity and inflammatory processes, Dr. Spiegel said.

“There is reason to think that poor heart rate variability might be associated with cancer progression as well, and that’s what we wanted to study in a group of metastatic cancer patients,” he said.

Dr. Spiegel and his colleagues measured high-frequency heart rate variability (HF-HRV), which appears to be the best measure of parasympathetic tone, has been associated with longer survival in humans and animals, and is related to immune system functioning.

“We hypothesized that higher heart rate variability would predict longer survival in patients with MRBC [metastatic or recurrent breast cancer],” he said.

In 87 patients with metastases to bone, skin, or viscera who underwent a variety of stress measures, including a 5-minute resting baseline electrocardiogram, 43 had higher HF-HRV, and 44 had lower HF-HRV. Higher baseline HF-HRV did, indeed, predict significantly longer survival (hazard ratio, 0.75).

“The main hypothesis was confirmed – that patients with better vagal tone, higher high-frequency heart rate variability had significantly longer survival over the ensuing 7 years, compared with the patients who had poorer heart rate variability, poorer vagal tone,” he said (Psychosom Med. 2015;77[4]:346-55).

Visceral metastasis status and baseline heart rate both were related to HF-HRV and survival, and the combination of HF-HRV and heart rate further improved survival prediction (HR, 0.64), he noted.

“This is basically coactivation of higher parasympathetic and lower sympathetic activity related to longer survival,” he explained.

Reconstructive surgery, the presence of visceral metastases, and sleep efficiency each were found to be associated with heart rate variability; thus several analyses were conducted “to try to disentangle these relationships and determine what the major variables were that predicted survival,” Dr. Spiegel said.

“It turns out that heart rate variability and visceral metastases were significantly related, and heart rate variability did not predict survival,” he said, explaining that those with visceral metastases (and therefore, cancer with a much poorer prognosis) died sooner, but heart rate variability didn’t make much of a difference. “Where we saw the heart rate variability effect was among those with better prognosis.”

A combination measure of high heart rate variability (“a pretty pure measure of vagal activity, not sympathetic activity”) and low heart rate (“more driven by the sympathetic adrenal-medullary system”) is an even stronger predictor of overall survival, he said.

This suggests that autonomic nervous system variables play a strong role in predicting overall cancer survival, Dr. Spiegel said, noting that depression was not a confounder.

“This is important, because we have, in other studies, found that depression is associated with lower heart rate variability, as you might expect,” he said. In fact, depression has been found to predict shorter survival in cancer patients over a period of 10 years. In an earlier study, cancer patients with worsening depression in the first year died sooner than those with depression that improved during the first year (J Clin Oncol. 2011;29[4]:413-20).

“The median survival difference was about 2 years, so this is not a trivial difference in overall survival,” he said, stressing that the finding is based on more chronic and severe depression.

Other studies have demonstrated relationships between circadian rhythm disruption and cancer survival. In one such study involving patients with metastatic colorectal cancer, circadian rhythm/rest activity cycle (more activity during the day, more rest at night) was associated with better quality of life and predicted survival.

“This has been shown now in several cancers, and it’s clear that a combination of higher activity and better sleep predict longer survival with different kinds of cancers,” Dr. Spiegel said, explaining that a hallmark of a healthy hypothalamic-pituitary-adrenal axis is good diurnal variation of cortisol with high levels in the morning and declining levels throughout the day.

Women with metastatic breast cancer and poorer survival tended to have flat or increasing levels of cortisol throughout the day, he said, adding that the same was true in a study of patients with lung cancer, and that there is evidence that those among them with flatter, more abnormal cortisol patterns throughout the day also have shorter survival.

Animal studies suggest that cortisol might directly suppress the activity of tumor suppressor genes, he explained, noting that there is also increasing evidence of autonomic dysregulation effects on inflammatory processes associated with tumor growth.

“Some basic research on this in animal models shows that if you block adrenergic arousal, you can block the growth of blood vessels from tumors. This has led some people to look at the use of antiadrenergic drugs like the beta-blocker propranolol, and it turned out – to everyone’s surprise – that breast cancer patients who happened to be on beta-blockers for hypertension actually lived longer than those who didn’t,” he said.

This adds to the growing evidence that dysregulation in the sympathetic and parasympathetic systems have effects on survival, he said.

A look at another factor related to sleep disruption – bedtime misalignment – showed that patients who adhere to their preferred sleep pattern, and who are therefore sleeping better, had a difference in disease-free interval; those whose bedtime was misaligned had a shorter time between diagnosis and disease recurrence (Chronobiol Int. 2014 Mar 31[2]214-21).

“Disease-free interval is a very strong predictor of ultimate overall survival, so there seems to be another relationship here between circadian disruption and disease progression in breast cancer,” Dr. Spiegel said.

Taken together, these findings demonstrate a strong association between vagal activity and survival in patients with metastatic or recurrent breast cancer, extending the known predictive window of HF-HRV beyond palliative care to cancer, Dr. Spiegel said.

“Vagal activity can be altered through behavioral, pharmacological, and surgical interventions and thus may be a promising target for increasing survival in patients with metastatic cancer,” he said.

Dr. Spiegel’s studies were funded by the National Cancer Institute and the National Institute on Aging.

sworcester@frontlinemedcom.com

ATLANTA – Vagal activity predicts survival in patients with metastatic or recurrent breast cancer, a study showed.

The findings are intriguing, given that vagal activity is modifiable, according to Dr. David Spiegel, Willson Professor of Psychiatry and Behavioral Sciences and director of the center on stress and health at Stanford (Calif.) University.

The study, conducted by Dr. Spiegel and his colleagues, is one of several that together are beginning to elucidate the connections among sleep, stress, and vagal tone, and the effects these factors have on cancer outcomes. For example, in one earlier study of metastatic breast cancer patients, the group demonstrated that good sleep efficiency predicted longer survival (Sleep. 2014 May 1;37[5]:837-42).

“There’s something about sleep that we think has an effect on disease progression,” Dr. Spiegel said at the annual meeting of the American Psychiatric Association.

In another study, the team showed that breast cancer patients who slept better at night had better vagal tone the following morning.

“We all kind of know that a problem that has been keeping you from getting to sleep or worrying you a lot the night before suddenly seems more soluble in the morning after you’ve had a good night’s sleep. You’re better able to self-soothe in the morning,” he said, noting the importance of this evidence that “sleep improves vagal tone.”

Heart rate variability is a good measure of vagal tone, vagal activity, and the ability to self-soothe, he explained, noting that heart rate variability also predicts longer survival with cardiac disease; it seems to reduce the risk of fatal arrhythmias, and also predicts recovery from myocardial infarction.

Others have suggested that it might have an effect on cancer, and there seems to be a link between vagal activity and inflammatory processes, Dr. Spiegel said.

“There is reason to think that poor heart rate variability might be associated with cancer progression as well, and that’s what we wanted to study in a group of metastatic cancer patients,” he said.

Dr. Spiegel and his colleagues measured high-frequency heart rate variability (HF-HRV), which appears to be the best measure of parasympathetic tone, has been associated with longer survival in humans and animals, and is related to immune system functioning.

“We hypothesized that higher heart rate variability would predict longer survival in patients with MRBC [metastatic or recurrent breast cancer],” he said.

In 87 patients with metastases to bone, skin, or viscera who underwent a variety of stress measures, including a 5-minute resting baseline electrocardiogram, 43 had higher HF-HRV, and 44 had lower HF-HRV. Higher baseline HF-HRV did, indeed, predict significantly longer survival (hazard ratio, 0.75).

“The main hypothesis was confirmed – that patients with better vagal tone, higher high-frequency heart rate variability had significantly longer survival over the ensuing 7 years, compared with the patients who had poorer heart rate variability, poorer vagal tone,” he said (Psychosom Med. 2015;77[4]:346-55).

Visceral metastasis status and baseline heart rate both were related to HF-HRV and survival, and the combination of HF-HRV and heart rate further improved survival prediction (HR, 0.64), he noted.

“This is basically coactivation of higher parasympathetic and lower sympathetic activity related to longer survival,” he explained.

Reconstructive surgery, the presence of visceral metastases, and sleep efficiency each were found to be associated with heart rate variability; thus several analyses were conducted “to try to disentangle these relationships and determine what the major variables were that predicted survival,” Dr. Spiegel said.

“It turns out that heart rate variability and visceral metastases were significantly related, and heart rate variability did not predict survival,” he said, explaining that those with visceral metastases (and therefore, cancer with a much poorer prognosis) died sooner, but heart rate variability didn’t make much of a difference. “Where we saw the heart rate variability effect was among those with better prognosis.”

A combination measure of high heart rate variability (“a pretty pure measure of vagal activity, not sympathetic activity”) and low heart rate (“more driven by the sympathetic adrenal-medullary system”) is an even stronger predictor of overall survival, he said.

This suggests that autonomic nervous system variables play a strong role in predicting overall cancer survival, Dr. Spiegel said, noting that depression was not a confounder.

“This is important, because we have, in other studies, found that depression is associated with lower heart rate variability, as you might expect,” he said. In fact, depression has been found to predict shorter survival in cancer patients over a period of 10 years. In an earlier study, cancer patients with worsening depression in the first year died sooner than those with depression that improved during the first year (J Clin Oncol. 2011;29[4]:413-20).

“The median survival difference was about 2 years, so this is not a trivial difference in overall survival,” he said, stressing that the finding is based on more chronic and severe depression.

Other studies have demonstrated relationships between circadian rhythm disruption and cancer survival. In one such study involving patients with metastatic colorectal cancer, circadian rhythm/rest activity cycle (more activity during the day, more rest at night) was associated with better quality of life and predicted survival.

“This has been shown now in several cancers, and it’s clear that a combination of higher activity and better sleep predict longer survival with different kinds of cancers,” Dr. Spiegel said, explaining that a hallmark of a healthy hypothalamic-pituitary-adrenal axis is good diurnal variation of cortisol with high levels in the morning and declining levels throughout the day.

Women with metastatic breast cancer and poorer survival tended to have flat or increasing levels of cortisol throughout the day, he said, adding that the same was true in a study of patients with lung cancer, and that there is evidence that those among them with flatter, more abnormal cortisol patterns throughout the day also have shorter survival.

Animal studies suggest that cortisol might directly suppress the activity of tumor suppressor genes, he explained, noting that there is also increasing evidence of autonomic dysregulation effects on inflammatory processes associated with tumor growth.

“Some basic research on this in animal models shows that if you block adrenergic arousal, you can block the growth of blood vessels from tumors. This has led some people to look at the use of antiadrenergic drugs like the beta-blocker propranolol, and it turned out – to everyone’s surprise – that breast cancer patients who happened to be on beta-blockers for hypertension actually lived longer than those who didn’t,” he said.

This adds to the growing evidence that dysregulation in the sympathetic and parasympathetic systems have effects on survival, he said.

A look at another factor related to sleep disruption – bedtime misalignment – showed that patients who adhere to their preferred sleep pattern, and who are therefore sleeping better, had a difference in disease-free interval; those whose bedtime was misaligned had a shorter time between diagnosis and disease recurrence (Chronobiol Int. 2014 Mar 31[2]214-21).

“Disease-free interval is a very strong predictor of ultimate overall survival, so there seems to be another relationship here between circadian disruption and disease progression in breast cancer,” Dr. Spiegel said.

Taken together, these findings demonstrate a strong association between vagal activity and survival in patients with metastatic or recurrent breast cancer, extending the known predictive window of HF-HRV beyond palliative care to cancer, Dr. Spiegel said.

“Vagal activity can be altered through behavioral, pharmacological, and surgical interventions and thus may be a promising target for increasing survival in patients with metastatic cancer,” he said.

Dr. Spiegel’s studies were funded by the National Cancer Institute and the National Institute on Aging.

sworcester@frontlinemedcom.com

CHICAGO – Elective ventral hernia repair improves hernia-related quality of life for low- to moderate-risk patients, according to findings from a prospective patient-centered study.

The findings suggest that the risks and benefits of a conservative operative strategy should be reassessed, and that patient-centered outcomes should be considered, Dr. Julie Holihan reported at the annual meeting of the American Surgical Association.

Of 152 patients with a ventral hernia from a single hernia clinic, 97 were managed non-operatively, and 55 were managed operatively. In a propensity-matched cohort of 90 patients with similar demographics, baseline comorbidities, and quality of life scores, only operatively managed patients had improved quality of life scores at 6 months (improvement from 34.7 to 56.9 vs. from 35.6 to 36.6), according to Dr. Holihan of the University of Texas, Houston.

Further, satisfaction scores increased significantly more in the operative than in the non-operative group at follow-up (from a median score of 2 at baseline in both groups to scores of 9 and 3, respectively), and pain scores decreased significantly more in the operative group than in the non-operative group (from a baseline score of 5 down to 3 in the operative group, with no change [score of 6] in the non-operative group).

Two surgical site infections and one hernia recurrence occurred in the operative group.

Notably, the predicted risk of surgery in the cohort was much greater than the observed risk.

“We may be overestimating surgical risk in these patients,” she said.

Based on a multivariable analysis in the overall cohort, non-operative management was strongly associated with lower quality of life score (coefficient, -26.5), Dr. Holihan said.

Nonoperative management of ventral hernias is often recommended for patients, particularly in those with increased risk of surgical complications due to factors such as obesity, poorly controlled diabetes, smoking, or significant comorbidities like coronary artery disease, but this approach to management has not been well studied with respect to patient-centered outcomes such as quality of life and function, she explained.

Traditional outcomes that have been studied, including infection and hernia recurrence, may not be the outcomes that are most important to patients, she added.

For the current study, patients with ventral hernias were prospectively enrolled between June 2014 and June 2015. Non-operative management was recommended for smokers, those with a body mass index greater than 33 kg/m², and those with poorly controlled diabetes. Measured outcomes included surgical site infection, hernia recurrence, and quality of life using a validated quality of life measure.

This is the first prospective study comparing management strategies in ventral hernia patients with comorbidities, Dr. Holihan said.

She concluded that “the elective repair of ventral hernia, compared with non-operative management, improves patient-centered outcomes in similar-risk patients.”

“Furthermore, the low occurrence of complications suggests that we may be overestimating surgical risk and that we may be too conservative in our patient selection for elective ventral hernia repair. It may be time to reevaluate patient selection criteria in order to better incorporate patient-centered outcomes,” she said.

In response to a question about managing patients with higher risk and/or higher BMI, Dr. Holihan’s coauthor, Dr. Mike K. Liang, also of the University of Texas, Houston, noted that the findings of the study provide estimates for potential future randomized trials. He also noted that the moderate-risk patients at the center often undergo “prehabilitation,” or a preoperative exercise and diet program designed to help optimize outcomes. Currently, patients with BMI of 30-40 kg/m² are randomized to preoperative rehabilitation vs. current care.

“BMI is a very important decision making factor. We were not able to pick a standardized point [with respect to BMI] for when to operate vs. non-operate. Because of that, we used BMI as a factor in developing our propensity score,” he said, explaining that this is why the propensity-matched groups had similar BMI, while the non-operative group in the overall cohort had substantially higher BMI.

A randomized trial on prehabilitation may be able to provide some insight into the effects of rapid changes in weight and how they affect outcomes in order to make the best choices regarding surgery.

“We do hypothesize that significant weight loss prior to surgery may improve outcomes, and may make the abdominal wall more compliant and enable us to tackle more challenging hernias. We also hypothesize that patients who have a sudden increase in weight after having their ventral hernia repaired may end up having worse outcomes. Hopefully in the next year we will be able to shed more light on these very important questions.”

The authors reported having no disclosures.

The complete manuscript of this presentation is anticipated to be published in the Annals of Surgery pending editorial review.

sworcester@frontlinemedcom.com

CHICAGO – Elective ventral hernia repair improves hernia-related quality of life for low- to moderate-risk patients, according to findings from a prospective patient-centered study.

The findings suggest that the risks and benefits of a conservative operative strategy should be reassessed, and that patient-centered outcomes should be considered, Dr. Julie Holihan reported at the annual meeting of the American Surgical Association.

Of 152 patients with a ventral hernia from a single hernia clinic, 97 were managed non-operatively, and 55 were managed operatively. In a propensity-matched cohort of 90 patients with similar demographics, baseline comorbidities, and quality of life scores, only operatively managed patients had improved quality of life scores at 6 months (improvement from 34.7 to 56.9 vs. from 35.6 to 36.6), according to Dr. Holihan of the University of Texas, Houston.

Further, satisfaction scores increased significantly more in the operative than in the non-operative group at follow-up (from a median score of 2 at baseline in both groups to scores of 9 and 3, respectively), and pain scores decreased significantly more in the operative group than in the non-operative group (from a baseline score of 5 down to 3 in the operative group, with no change [score of 6] in the non-operative group).

Two surgical site infections and one hernia recurrence occurred in the operative group.

Notably, the predicted risk of surgery in the cohort was much greater than the observed risk.

“We may be overestimating surgical risk in these patients,” she said.

Based on a multivariable analysis in the overall cohort, non-operative management was strongly associated with lower quality of life score (coefficient, -26.5), Dr. Holihan said.

Nonoperative management of ventral hernias is often recommended for patients, particularly in those with increased risk of surgical complications due to factors such as obesity, poorly controlled diabetes, smoking, or significant comorbidities like coronary artery disease, but this approach to management has not been well studied with respect to patient-centered outcomes such as quality of life and function, she explained.

Traditional outcomes that have been studied, including infection and hernia recurrence, may not be the outcomes that are most important to patients, she added.

For the current study, patients with ventral hernias were prospectively enrolled between June 2014 and June 2015. Non-operative management was recommended for smokers, those with a body mass index greater than 33 kg/m², and those with poorly controlled diabetes. Measured outcomes included surgical site infection, hernia recurrence, and quality of life using a validated quality of life measure.

This is the first prospective study comparing management strategies in ventral hernia patients with comorbidities, Dr. Holihan said.

She concluded that “the elective repair of ventral hernia, compared with non-operative management, improves patient-centered outcomes in similar-risk patients.”

“Furthermore, the low occurrence of complications suggests that we may be overestimating surgical risk and that we may be too conservative in our patient selection for elective ventral hernia repair. It may be time to reevaluate patient selection criteria in order to better incorporate patient-centered outcomes,” she said.

In response to a question about managing patients with higher risk and/or higher BMI, Dr. Holihan’s coauthor, Dr. Mike K. Liang, also of the University of Texas, Houston, noted that the findings of the study provide estimates for potential future randomized trials. He also noted that the moderate-risk patients at the center often undergo “prehabilitation,” or a preoperative exercise and diet program designed to help optimize outcomes. Currently, patients with BMI of 30-40 kg/m² are randomized to preoperative rehabilitation vs. current care.

“BMI is a very important decision making factor. We were not able to pick a standardized point [with respect to BMI] for when to operate vs. non-operate. Because of that, we used BMI as a factor in developing our propensity score,” he said, explaining that this is why the propensity-matched groups had similar BMI, while the non-operative group in the overall cohort had substantially higher BMI.

A randomized trial on prehabilitation may be able to provide some insight into the effects of rapid changes in weight and how they affect outcomes in order to make the best choices regarding surgery.

“We do hypothesize that significant weight loss prior to surgery may improve outcomes, and may make the abdominal wall more compliant and enable us to tackle more challenging hernias. We also hypothesize that patients who have a sudden increase in weight after having their ventral hernia repaired may end up having worse outcomes. Hopefully in the next year we will be able to shed more light on these very important questions.”

The authors reported having no disclosures.

The complete manuscript of this presentation is anticipated to be published in the Annals of Surgery pending editorial review.

sworcester@frontlinemedcom.com

CHICAGO – Elective ventral hernia repair improves hernia-related quality of life for low- to moderate-risk patients, according to findings from a prospective patient-centered study.

The findings suggest that the risks and benefits of a conservative operative strategy should be reassessed, and that patient-centered outcomes should be considered, Dr. Julie Holihan reported at the annual meeting of the American Surgical Association.

Of 152 patients with a ventral hernia from a single hernia clinic, 97 were managed non-operatively, and 55 were managed operatively. In a propensity-matched cohort of 90 patients with similar demographics, baseline comorbidities, and quality of life scores, only operatively managed patients had improved quality of life scores at 6 months (improvement from 34.7 to 56.9 vs. from 35.6 to 36.6), according to Dr. Holihan of the University of Texas, Houston.

Further, satisfaction scores increased significantly more in the operative than in the non-operative group at follow-up (from a median score of 2 at baseline in both groups to scores of 9 and 3, respectively), and pain scores decreased significantly more in the operative group than in the non-operative group (from a baseline score of 5 down to 3 in the operative group, with no change [score of 6] in the non-operative group).

Two surgical site infections and one hernia recurrence occurred in the operative group.

Notably, the predicted risk of surgery in the cohort was much greater than the observed risk.

“We may be overestimating surgical risk in these patients,” she said.

Based on a multivariable analysis in the overall cohort, non-operative management was strongly associated with lower quality of life score (coefficient, -26.5), Dr. Holihan said.

Nonoperative management of ventral hernias is often recommended for patients, particularly in those with increased risk of surgical complications due to factors such as obesity, poorly controlled diabetes, smoking, or significant comorbidities like coronary artery disease, but this approach to management has not been well studied with respect to patient-centered outcomes such as quality of life and function, she explained.

Traditional outcomes that have been studied, including infection and hernia recurrence, may not be the outcomes that are most important to patients, she added.

For the current study, patients with ventral hernias were prospectively enrolled between June 2014 and June 2015. Non-operative management was recommended for smokers, those with a body mass index greater than 33 kg/m², and those with poorly controlled diabetes. Measured outcomes included surgical site infection, hernia recurrence, and quality of life using a validated quality of life measure.

This is the first prospective study comparing management strategies in ventral hernia patients with comorbidities, Dr. Holihan said.

She concluded that “the elective repair of ventral hernia, compared with non-operative management, improves patient-centered outcomes in similar-risk patients.”

“Furthermore, the low occurrence of complications suggests that we may be overestimating surgical risk and that we may be too conservative in our patient selection for elective ventral hernia repair. It may be time to reevaluate patient selection criteria in order to better incorporate patient-centered outcomes,” she said.

In response to a question about managing patients with higher risk and/or higher BMI, Dr. Holihan’s coauthor, Dr. Mike K. Liang, also of the University of Texas, Houston, noted that the findings of the study provide estimates for potential future randomized trials. He also noted that the moderate-risk patients at the center often undergo “prehabilitation,” or a preoperative exercise and diet program designed to help optimize outcomes. Currently, patients with BMI of 30-40 kg/m² are randomized to preoperative rehabilitation vs. current care.

“BMI is a very important decision making factor. We were not able to pick a standardized point [with respect to BMI] for when to operate vs. non-operate. Because of that, we used BMI as a factor in developing our propensity score,” he said, explaining that this is why the propensity-matched groups had similar BMI, while the non-operative group in the overall cohort had substantially higher BMI.

A randomized trial on prehabilitation may be able to provide some insight into the effects of rapid changes in weight and how they affect outcomes in order to make the best choices regarding surgery.

“We do hypothesize that significant weight loss prior to surgery may improve outcomes, and may make the abdominal wall more compliant and enable us to tackle more challenging hernias. We also hypothesize that patients who have a sudden increase in weight after having their ventral hernia repaired may end up having worse outcomes. Hopefully in the next year we will be able to shed more light on these very important questions.”

The authors reported having no disclosures.

The complete manuscript of this presentation is anticipated to be published in the Annals of Surgery pending editorial review.

sworcester@frontlinemedcom.com

ATLANTA – A new smartphone application aimed at providing psychoeducation to patients with bipolar disorder was well received and showed promise for improving outcomes in a feasibility study, according to Dr. Eduard Vieta.

Early results of the study showed that adherence was quite high, with retention at 76% among 49 patients with bipolar disorder who tested the SIMPle app (Self Monitoring and Psychoeducation in Bipolar Patients with a Smartphone Application), Dr. Vieta said at the annual meeting of the American Psychiatric Association.

The app, currently available for free for Android and iPhones, is an interactive educational program that includes weekly and daily tests, with alerts for patients to take medications or see their doctor.

The patients in the study were representative of generally stable bipolar disorder patients in a real-world setting, as the app ideally would be used by those who are “in near remission or at least not acutely ill,” said Dr. Vieta of the University of Barcelona.

“People like the app and did follow the daily and weekly tests, which is a good sign,” he said, noting that satisfaction was high, and good correlation between test scores and mood changes suggested that the app is reliable for monitoring mood changes.

There were 10 suicide alerts during the study that were quickly addressed because messages were received immediately, he said.

The latest version of the app includes simpler navigation, rewards for fulfilling the daily and weekly testing, and medication reminders.

Dr. Vieta and his colleagues at the University of Barcelona previously have demonstrated the value of psychoeducation among patients with bipolar disorder. They developed a successful psychoeducation program in the late 1990s, which led to a trial published in 2003 and development of a training manual in 2006 that has been translated into numerous languages.

The program and trial showed that adding psychoeducation to medication in patients with bipolar disorder improves outcomes in terms of relapse and hospitalizations: the rate of relapses in the study was reduced by nearly 80%, Dr. Vieta said.

Providing such education, however, which has become a standard of care, is limited by the need for personnel training and by staffing and financial resource constraints.

“We wanted something nonstigmatizing but also linked to the clinical care team. … Clearly, we would like to make this intervention more widely available without compromising quality,” Dr. Vieta said, describing the impetus for the SIMPle app.

A phase II, randomized controlled study of the app is now underway, he said, adding that “this is really quite exciting. … There is huge potential for things we can do with this app.”

Dr. Vieta is a consultant or adviser for several pharmaceutical companies. He also has received research grants, honoraria, or consulting fees from numerous entities.

sworcester@frontlinemedcom.com

ATLANTA – A new smartphone application aimed at providing psychoeducation to patients with bipolar disorder was well received and showed promise for improving outcomes in a feasibility study, according to Dr. Eduard Vieta.

Early results of the study showed that adherence was quite high, with retention at 76% among 49 patients with bipolar disorder who tested the SIMPle app (Self Monitoring and Psychoeducation in Bipolar Patients with a Smartphone Application), Dr. Vieta said at the annual meeting of the American Psychiatric Association.

The app, currently available for free for Android and iPhones, is an interactive educational program that includes weekly and daily tests, with alerts for patients to take medications or see their doctor.

The patients in the study were representative of generally stable bipolar disorder patients in a real-world setting, as the app ideally would be used by those who are “in near remission or at least not acutely ill,” said Dr. Vieta of the University of Barcelona.

“People like the app and did follow the daily and weekly tests, which is a good sign,” he said, noting that satisfaction was high, and good correlation between test scores and mood changes suggested that the app is reliable for monitoring mood changes.

There were 10 suicide alerts during the study that were quickly addressed because messages were received immediately, he said.

The latest version of the app includes simpler navigation, rewards for fulfilling the daily and weekly testing, and medication reminders.

Dr. Vieta and his colleagues at the University of Barcelona previously have demonstrated the value of psychoeducation among patients with bipolar disorder. They developed a successful psychoeducation program in the late 1990s, which led to a trial published in 2003 and development of a training manual in 2006 that has been translated into numerous languages.

The program and trial showed that adding psychoeducation to medication in patients with bipolar disorder improves outcomes in terms of relapse and hospitalizations: the rate of relapses in the study was reduced by nearly 80%, Dr. Vieta said.

Providing such education, however, which has become a standard of care, is limited by the need for personnel training and by staffing and financial resource constraints.

“We wanted something nonstigmatizing but also linked to the clinical care team. … Clearly, we would like to make this intervention more widely available without compromising quality,” Dr. Vieta said, describing the impetus for the SIMPle app.

A phase II, randomized controlled study of the app is now underway, he said, adding that “this is really quite exciting. … There is huge potential for things we can do with this app.”

Dr. Vieta is a consultant or adviser for several pharmaceutical companies. He also has received research grants, honoraria, or consulting fees from numerous entities.

sworcester@frontlinemedcom.com

ATLANTA – A new smartphone application aimed at providing psychoeducation to patients with bipolar disorder was well received and showed promise for improving outcomes in a feasibility study, according to Dr. Eduard Vieta.

Early results of the study showed that adherence was quite high, with retention at 76% among 49 patients with bipolar disorder who tested the SIMPle app (Self Monitoring and Psychoeducation in Bipolar Patients with a Smartphone Application), Dr. Vieta said at the annual meeting of the American Psychiatric Association.

The app, currently available for free for Android and iPhones, is an interactive educational program that includes weekly and daily tests, with alerts for patients to take medications or see their doctor.

The patients in the study were representative of generally stable bipolar disorder patients in a real-world setting, as the app ideally would be used by those who are “in near remission or at least not acutely ill,” said Dr. Vieta of the University of Barcelona.

“People like the app and did follow the daily and weekly tests, which is a good sign,” he said, noting that satisfaction was high, and good correlation between test scores and mood changes suggested that the app is reliable for monitoring mood changes.

There were 10 suicide alerts during the study that were quickly addressed because messages were received immediately, he said.

The latest version of the app includes simpler navigation, rewards for fulfilling the daily and weekly testing, and medication reminders.

Dr. Vieta and his colleagues at the University of Barcelona previously have demonstrated the value of psychoeducation among patients with bipolar disorder. They developed a successful psychoeducation program in the late 1990s, which led to a trial published in 2003 and development of a training manual in 2006 that has been translated into numerous languages.

The program and trial showed that adding psychoeducation to medication in patients with bipolar disorder improves outcomes in terms of relapse and hospitalizations: the rate of relapses in the study was reduced by nearly 80%, Dr. Vieta said.

Providing such education, however, which has become a standard of care, is limited by the need for personnel training and by staffing and financial resource constraints.

“We wanted something nonstigmatizing but also linked to the clinical care team. … Clearly, we would like to make this intervention more widely available without compromising quality,” Dr. Vieta said, describing the impetus for the SIMPle app.

A phase II, randomized controlled study of the app is now underway, he said, adding that “this is really quite exciting. … There is huge potential for things we can do with this app.”

Dr. Vieta is a consultant or adviser for several pharmaceutical companies. He also has received research grants, honoraria, or consulting fees from numerous entities.

sworcester@frontlinemedcom.com