VANCOUVER – The relationship between hospitals’ procedural volume and patient outcomes that has been observed for many cardiovascular interventions and other surgeries does not hold for endovascular mechanical thrombectomy procedures for acute ischemic stroke, according to an analysis of cases during 2008-2011 in the Nationwide Inpatient Sample.

In-hospital mortality and rates for any complications were not associated with high or low endovascular mechanical thrombectomy (EMT) volume at hospitals across the United States in the analysis of 13,502 adult patients hospitalized with a primary diagnosis of acute ischemic stroke and treated with EMT, neurology resident Dr. Abhishek Lunagariya of the University of Florida, Gainesville, reported at the annual meeting of the American Academy of Neurology.

A smaller prior study of 2,749 EMTs done in 296 hospitals in 2008 showed lower mortality in high-volume hospitals that performed 10 or more of the procedures per year (J Stroke Cerebrovasc Dis. 2013 Nov; 22[8]:1263-9).

Of the 13,502 EMTs in the study, 25% occurred at low-volume hospitals performing less than 10 per year. Low-volume hospitals had higher in-hospital mortality than did higher-volume centers performing 10 or more of the procedures per year in an unadjusted comparison (26% vs. 21%). A comparison of a combined endpoint for any complications (in-hospital mortality, intracerebral hemorrhage, and vascular complications) was also significantly in favor of high-volume hospitals (34% vs. 30%).

However, in a multivariate hierarchical model, low-volume hospitals were not associated with higher in-hospital mortality (odds ratio, 0.95; 95% confidence interval, 0.74-1.23) or rate of any complications (OR, 0.96; 95% CI, 0.76-1.21). These analyses were adjusted for age, gender, ethnicity, primary payer, median household income, hospital region/teaching status/location/bed size, Charlson Comorbidity Index, calendar year, and use of intravenous tissue plasminogen activator.

Dr. Lunagariya noted that he and his associates could not adjust the comparisons for National Institutes of Health Stroke Scale scores because they are not recorded in the National Inpatient Sample. They also could not examine what happened to patients after discharge.

Dr. Lunagariya suggested a variety of possible reasons that might help to explain the lack of an association between hospital procedure volume and outcomes after adjustment: the availability of better thrombectomy devices since the smaller 2008 study, lesser operator variability, favorable patient selection, and an increased skill set of operators working at low-volume hospitals.

One audience member noted that some endovascular interventionalists will operate at both high-volume and low-volume hospitals and could account for some of the findings. That indeed might be happening more often and needs to happen more often, Dr. Lunagariya said in an interview, in order to combat the “common belief” that it would be better to wait for a patient to undergo the procedure at a high- rather than low-volume hospital. Patients who receive initial care for stroke at a low-volume hospital but are not stable enough or do not have enough time to be transferred could benefit from EMT if an interventionalist who performs EMT drove there instead, he said.

With even newer devices now available that are thought to be easier to use, Dr. Lunagariya suggested that the similarity in outcomes at low- and higher-volume centers may not change in updated analyses of more recent EMT procedures for ischemic stroke.

The investigators received no funding for the study, and they reported having no financial disclosures.

[email protected]

VANCOUVER – The relationship between hospitals’ procedural volume and patient outcomes that has been observed for many cardiovascular interventions and other surgeries does not hold for endovascular mechanical thrombectomy procedures for acute ischemic stroke, according to an analysis of cases during 2008-2011 in the Nationwide Inpatient Sample.

In-hospital mortality and rates for any complications were not associated with high or low endovascular mechanical thrombectomy (EMT) volume at hospitals across the United States in the analysis of 13,502 adult patients hospitalized with a primary diagnosis of acute ischemic stroke and treated with EMT, neurology resident Dr. Abhishek Lunagariya of the University of Florida, Gainesville, reported at the annual meeting of the American Academy of Neurology.

A smaller prior study of 2,749 EMTs done in 296 hospitals in 2008 showed lower mortality in high-volume hospitals that performed 10 or more of the procedures per year (J Stroke Cerebrovasc Dis. 2013 Nov; 22[8]:1263-9).

Of the 13,502 EMTs in the study, 25% occurred at low-volume hospitals performing less than 10 per year. Low-volume hospitals had higher in-hospital mortality than did higher-volume centers performing 10 or more of the procedures per year in an unadjusted comparison (26% vs. 21%). A comparison of a combined endpoint for any complications (in-hospital mortality, intracerebral hemorrhage, and vascular complications) was also significantly in favor of high-volume hospitals (34% vs. 30%).

However, in a multivariate hierarchical model, low-volume hospitals were not associated with higher in-hospital mortality (odds ratio, 0.95; 95% confidence interval, 0.74-1.23) or rate of any complications (OR, 0.96; 95% CI, 0.76-1.21). These analyses were adjusted for age, gender, ethnicity, primary payer, median household income, hospital region/teaching status/location/bed size, Charlson Comorbidity Index, calendar year, and use of intravenous tissue plasminogen activator.

Dr. Lunagariya noted that he and his associates could not adjust the comparisons for National Institutes of Health Stroke Scale scores because they are not recorded in the National Inpatient Sample. They also could not examine what happened to patients after discharge.

Dr. Lunagariya suggested a variety of possible reasons that might help to explain the lack of an association between hospital procedure volume and outcomes after adjustment: the availability of better thrombectomy devices since the smaller 2008 study, lesser operator variability, favorable patient selection, and an increased skill set of operators working at low-volume hospitals.

One audience member noted that some endovascular interventionalists will operate at both high-volume and low-volume hospitals and could account for some of the findings. That indeed might be happening more often and needs to happen more often, Dr. Lunagariya said in an interview, in order to combat the “common belief” that it would be better to wait for a patient to undergo the procedure at a high- rather than low-volume hospital. Patients who receive initial care for stroke at a low-volume hospital but are not stable enough or do not have enough time to be transferred could benefit from EMT if an interventionalist who performs EMT drove there instead, he said.

With even newer devices now available that are thought to be easier to use, Dr. Lunagariya suggested that the similarity in outcomes at low- and higher-volume centers may not change in updated analyses of more recent EMT procedures for ischemic stroke.

The investigators received no funding for the study, and they reported having no financial disclosures.

[email protected]

VANCOUVER – The relationship between hospitals’ procedural volume and patient outcomes that has been observed for many cardiovascular interventions and other surgeries does not hold for endovascular mechanical thrombectomy procedures for acute ischemic stroke, according to an analysis of cases during 2008-2011 in the Nationwide Inpatient Sample.

In-hospital mortality and rates for any complications were not associated with high or low endovascular mechanical thrombectomy (EMT) volume at hospitals across the United States in the analysis of 13,502 adult patients hospitalized with a primary diagnosis of acute ischemic stroke and treated with EMT, neurology resident Dr. Abhishek Lunagariya of the University of Florida, Gainesville, reported at the annual meeting of the American Academy of Neurology.

A smaller prior study of 2,749 EMTs done in 296 hospitals in 2008 showed lower mortality in high-volume hospitals that performed 10 or more of the procedures per year (J Stroke Cerebrovasc Dis. 2013 Nov; 22[8]:1263-9).

Of the 13,502 EMTs in the study, 25% occurred at low-volume hospitals performing less than 10 per year. Low-volume hospitals had higher in-hospital mortality than did higher-volume centers performing 10 or more of the procedures per year in an unadjusted comparison (26% vs. 21%). A comparison of a combined endpoint for any complications (in-hospital mortality, intracerebral hemorrhage, and vascular complications) was also significantly in favor of high-volume hospitals (34% vs. 30%).

However, in a multivariate hierarchical model, low-volume hospitals were not associated with higher in-hospital mortality (odds ratio, 0.95; 95% confidence interval, 0.74-1.23) or rate of any complications (OR, 0.96; 95% CI, 0.76-1.21). These analyses were adjusted for age, gender, ethnicity, primary payer, median household income, hospital region/teaching status/location/bed size, Charlson Comorbidity Index, calendar year, and use of intravenous tissue plasminogen activator.

Dr. Lunagariya noted that he and his associates could not adjust the comparisons for National Institutes of Health Stroke Scale scores because they are not recorded in the National Inpatient Sample. They also could not examine what happened to patients after discharge.

Dr. Lunagariya suggested a variety of possible reasons that might help to explain the lack of an association between hospital procedure volume and outcomes after adjustment: the availability of better thrombectomy devices since the smaller 2008 study, lesser operator variability, favorable patient selection, and an increased skill set of operators working at low-volume hospitals.

One audience member noted that some endovascular interventionalists will operate at both high-volume and low-volume hospitals and could account for some of the findings. That indeed might be happening more often and needs to happen more often, Dr. Lunagariya said in an interview, in order to combat the “common belief” that it would be better to wait for a patient to undergo the procedure at a high- rather than low-volume hospital. Patients who receive initial care for stroke at a low-volume hospital but are not stable enough or do not have enough time to be transferred could benefit from EMT if an interventionalist who performs EMT drove there instead, he said.

With even newer devices now available that are thought to be easier to use, Dr. Lunagariya suggested that the similarity in outcomes at low- and higher-volume centers may not change in updated analyses of more recent EMT procedures for ischemic stroke.

The investigators received no funding for the study, and they reported having no financial disclosures.

[email protected]

Women with mutations in the BRCA1 gene are likely to have significantly reduced ovarian reserve, according to Dr. Kelly-Anne Phillips and her associates.

After adjusting for age, the average anti-Müllerian hormone concentration for the 172 BRCA1 mutation carriers tested was about 25% less than the 216 noncarriers tested. This difference remained after adjusting for oral contraceptive pill use at time of blood draw, BMI at cohort entry, cigarette smoking ever, length of time from blood draw to analysis, or exclusion of current oral contraceptive users and women who reported they were postmenopausal. The odds ratio for mutation carriers of having an AMH concentration in the lowest quartile was 1.84.

©Christian Jasiuk/Thinkstock

Average AMH concentration in women with BRCA2 mutations did not differ from women who do not carry the mutation. The odds ratio of having an AMH concentration in the lowest quartile for BRCA2 carriers was 0.87.

“Low AMH concentrations have not been shown to affect natural fecundability in young women but are associated with reduced fecundability in older women in their 30s,” the investigators wrote. “The reduced concentrations of AMH observed in this study were equivalent, for example, to a 2-year age increase for a woman in her mid 30s. Thus it is possible that the findings of our study might not translate to clinically relevant fertility implications for younger women, but may be important for the subgroup of BRCA1 mutation carriers who wish to conceive in their late 30s or 40s when fertility is reduced even in the general population.”

Find the full study in Human Reproduction (doi: 10.1093/humrep/dew044).

[email protected]

Women with mutations in the BRCA1 gene are likely to have significantly reduced ovarian reserve, according to Dr. Kelly-Anne Phillips and her associates.

After adjusting for age, the average anti-Müllerian hormone concentration for the 172 BRCA1 mutation carriers tested was about 25% less than the 216 noncarriers tested. This difference remained after adjusting for oral contraceptive pill use at time of blood draw, BMI at cohort entry, cigarette smoking ever, length of time from blood draw to analysis, or exclusion of current oral contraceptive users and women who reported they were postmenopausal. The odds ratio for mutation carriers of having an AMH concentration in the lowest quartile was 1.84.

©Christian Jasiuk/Thinkstock

Average AMH concentration in women with BRCA2 mutations did not differ from women who do not carry the mutation. The odds ratio of having an AMH concentration in the lowest quartile for BRCA2 carriers was 0.87.

“Low AMH concentrations have not been shown to affect natural fecundability in young women but are associated with reduced fecundability in older women in their 30s,” the investigators wrote. “The reduced concentrations of AMH observed in this study were equivalent, for example, to a 2-year age increase for a woman in her mid 30s. Thus it is possible that the findings of our study might not translate to clinically relevant fertility implications for younger women, but may be important for the subgroup of BRCA1 mutation carriers who wish to conceive in their late 30s or 40s when fertility is reduced even in the general population.”

Find the full study in Human Reproduction (doi: 10.1093/humrep/dew044).

[email protected]

Women with mutations in the BRCA1 gene are likely to have significantly reduced ovarian reserve, according to Dr. Kelly-Anne Phillips and her associates.

After adjusting for age, the average anti-Müllerian hormone concentration for the 172 BRCA1 mutation carriers tested was about 25% less than the 216 noncarriers tested. This difference remained after adjusting for oral contraceptive pill use at time of blood draw, BMI at cohort entry, cigarette smoking ever, length of time from blood draw to analysis, or exclusion of current oral contraceptive users and women who reported they were postmenopausal. The odds ratio for mutation carriers of having an AMH concentration in the lowest quartile was 1.84.

©Christian Jasiuk/Thinkstock

Average AMH concentration in women with BRCA2 mutations did not differ from women who do not carry the mutation. The odds ratio of having an AMH concentration in the lowest quartile for BRCA2 carriers was 0.87.

“Low AMH concentrations have not been shown to affect natural fecundability in young women but are associated with reduced fecundability in older women in their 30s,” the investigators wrote. “The reduced concentrations of AMH observed in this study were equivalent, for example, to a 2-year age increase for a woman in her mid 30s. Thus it is possible that the findings of our study might not translate to clinically relevant fertility implications for younger women, but may be important for the subgroup of BRCA1 mutation carriers who wish to conceive in their late 30s or 40s when fertility is reduced even in the general population.”

Find the full study in Human Reproduction (doi: 10.1093/humrep/dew044).

[email protected]

Stronger teamwork among researchers, sharing data, and realignment of incentives for scientific breakthroughs, in addition to more funding, are key steps needed to advance cancer research, Vice President Joe Biden said during the annual meeting of the American Association for Cancer Research (AACR).

During a plenary speech to close the meeting, Vice President Biden praised the dedication of current cancer researchers and pledged to break down the walls that prevent them from achieving more progress in the field.

“I made a commitment that I will – as I gain this information and knowledge – I will eliminate the barriers that get in your way, get in the way of science and research and development,” he said. “I had to ... learn from all of you how we can proceed, how we can break down silos, how we can accommodate more rapidly the efforts you’re making.”

Vice President Biden, who is leading a new $1 billion initiative to eliminate cancer called “Moonshot,” outlined the top obstacles to cancer research he has garnered from recent visits with renowned cancer scientists and research leaders around the world. This includes a lack of unity among researchers, poor rewards for novel research, and limited data sharing, he said.

“The way the system now is set up, researchers are not incentivized to share their data,” Vice President Biden said, acknowledging that some medical experts are against the idea. “But every expert I’ve spoken to said you need to share these data to move this process rapidly.”

Involving patients earlier in clinical trials design is also a primary focus, he said. Patients should understand more about trials and be more open to signing up.

He noted the “incredible” research currently being conducted by various entities, such as AACR’s Project Genie, Orion Foundation, and The Parker Institute. Mr. Biden stressed however, that such efforts are too isolated.

“It raises [the] question: ‘Why is all this being done separately?’ ” Vice President Biden said. “Why is so much money being spent when if it’s aggregated, everyone acknowledges, the answers would come more quickly?”

Incentives for new research and the way in which funding is alloted must also be redesigned, he stressed. Today, it takes too long for researchers to get projects approved by the government and funding dispersed. He acknowledged the difficulty researchers face in obtaining grants and the fact that those who think “outside the box” are less likely to receive funding.

“It seems to me that we slow down our best minds by making them spend years in the lab before they can get their own grants and, when they do, they spend a third of their time writing a grant that takes months to be approved and awarded,” he said. “It’s like asking Derek Jeter to take several years off to sell bonds to build Yankee stadium.”

The Vice President did not purport to have all the answers, and asked those at the AARC meeting to provide feedback on his suggestions.

“The question I’d ask you to contemplate, because I’d like you to communicate with us, is, ‘Does it require realigning incentives; changing behaviors to take advantage of this inflection point? Does it require sharing more knowledge, treatment, and understanding? Or does that slow the process up?’ ”

He added,“I hope you all know it, but you’re one of the most valuable resources that our great country has, those of you sitting in this room. So ask your institutions, your colleagues, your mentors, your administrators: How can we move your ideas faster together in the interest of patients?”

The Vice President’s Moonshot initiative was announced during President Obama’s 2016 State of the Union Address. The effort includes a new Cancer Moonshot Task Force that will focus on federal investments, targeted incentives, private sector efforts from industry and philanthropy, patient engagement initiatives, and other mechanisms to support cancer research and enable progress in treatment and care, according to the White House. As part of the plan, the President’s fiscal 2017 budget proposes $755 million in mandatory funds for new cancer-related research activities at the National Institutes of Health and the Food and Drug Administration. The initiative also includes increased investments by the Department of Defense and the Department of Veterans Affairs in cancer research, including through funding centers of excellence focused on specific cancers and conducting longitudinal studies to determine risk factors and enhance treatment.

[email protected]

On Twitter @legal_med

Stronger teamwork among researchers, sharing data, and realignment of incentives for scientific breakthroughs, in addition to more funding, are key steps needed to advance cancer research, Vice President Joe Biden said during the annual meeting of the American Association for Cancer Research (AACR).

During a plenary speech to close the meeting, Vice President Biden praised the dedication of current cancer researchers and pledged to break down the walls that prevent them from achieving more progress in the field.

“I made a commitment that I will – as I gain this information and knowledge – I will eliminate the barriers that get in your way, get in the way of science and research and development,” he said. “I had to ... learn from all of you how we can proceed, how we can break down silos, how we can accommodate more rapidly the efforts you’re making.”

Vice President Biden, who is leading a new $1 billion initiative to eliminate cancer called “Moonshot,” outlined the top obstacles to cancer research he has garnered from recent visits with renowned cancer scientists and research leaders around the world. This includes a lack of unity among researchers, poor rewards for novel research, and limited data sharing, he said.

“The way the system now is set up, researchers are not incentivized to share their data,” Vice President Biden said, acknowledging that some medical experts are against the idea. “But every expert I’ve spoken to said you need to share these data to move this process rapidly.”

Involving patients earlier in clinical trials design is also a primary focus, he said. Patients should understand more about trials and be more open to signing up.

He noted the “incredible” research currently being conducted by various entities, such as AACR’s Project Genie, Orion Foundation, and The Parker Institute. Mr. Biden stressed however, that such efforts are too isolated.

“It raises [the] question: ‘Why is all this being done separately?’ ” Vice President Biden said. “Why is so much money being spent when if it’s aggregated, everyone acknowledges, the answers would come more quickly?”

Incentives for new research and the way in which funding is alloted must also be redesigned, he stressed. Today, it takes too long for researchers to get projects approved by the government and funding dispersed. He acknowledged the difficulty researchers face in obtaining grants and the fact that those who think “outside the box” are less likely to receive funding.

“It seems to me that we slow down our best minds by making them spend years in the lab before they can get their own grants and, when they do, they spend a third of their time writing a grant that takes months to be approved and awarded,” he said. “It’s like asking Derek Jeter to take several years off to sell bonds to build Yankee stadium.”

The Vice President did not purport to have all the answers, and asked those at the AARC meeting to provide feedback on his suggestions.

“The question I’d ask you to contemplate, because I’d like you to communicate with us, is, ‘Does it require realigning incentives; changing behaviors to take advantage of this inflection point? Does it require sharing more knowledge, treatment, and understanding? Or does that slow the process up?’ ”

He added,“I hope you all know it, but you’re one of the most valuable resources that our great country has, those of you sitting in this room. So ask your institutions, your colleagues, your mentors, your administrators: How can we move your ideas faster together in the interest of patients?”

The Vice President’s Moonshot initiative was announced during President Obama’s 2016 State of the Union Address. The effort includes a new Cancer Moonshot Task Force that will focus on federal investments, targeted incentives, private sector efforts from industry and philanthropy, patient engagement initiatives, and other mechanisms to support cancer research and enable progress in treatment and care, according to the White House. As part of the plan, the President’s fiscal 2017 budget proposes $755 million in mandatory funds for new cancer-related research activities at the National Institutes of Health and the Food and Drug Administration. The initiative also includes increased investments by the Department of Defense and the Department of Veterans Affairs in cancer research, including through funding centers of excellence focused on specific cancers and conducting longitudinal studies to determine risk factors and enhance treatment.

[email protected]

On Twitter @legal_med

Stronger teamwork among researchers, sharing data, and realignment of incentives for scientific breakthroughs, in addition to more funding, are key steps needed to advance cancer research, Vice President Joe Biden said during the annual meeting of the American Association for Cancer Research (AACR).

During a plenary speech to close the meeting, Vice President Biden praised the dedication of current cancer researchers and pledged to break down the walls that prevent them from achieving more progress in the field.

“I made a commitment that I will – as I gain this information and knowledge – I will eliminate the barriers that get in your way, get in the way of science and research and development,” he said. “I had to ... learn from all of you how we can proceed, how we can break down silos, how we can accommodate more rapidly the efforts you’re making.”

Vice President Biden, who is leading a new $1 billion initiative to eliminate cancer called “Moonshot,” outlined the top obstacles to cancer research he has garnered from recent visits with renowned cancer scientists and research leaders around the world. This includes a lack of unity among researchers, poor rewards for novel research, and limited data sharing, he said.

“The way the system now is set up, researchers are not incentivized to share their data,” Vice President Biden said, acknowledging that some medical experts are against the idea. “But every expert I’ve spoken to said you need to share these data to move this process rapidly.”

Involving patients earlier in clinical trials design is also a primary focus, he said. Patients should understand more about trials and be more open to signing up.

He noted the “incredible” research currently being conducted by various entities, such as AACR’s Project Genie, Orion Foundation, and The Parker Institute. Mr. Biden stressed however, that such efforts are too isolated.

“It raises [the] question: ‘Why is all this being done separately?’ ” Vice President Biden said. “Why is so much money being spent when if it’s aggregated, everyone acknowledges, the answers would come more quickly?”

Incentives for new research and the way in which funding is alloted must also be redesigned, he stressed. Today, it takes too long for researchers to get projects approved by the government and funding dispersed. He acknowledged the difficulty researchers face in obtaining grants and the fact that those who think “outside the box” are less likely to receive funding.

“It seems to me that we slow down our best minds by making them spend years in the lab before they can get their own grants and, when they do, they spend a third of their time writing a grant that takes months to be approved and awarded,” he said. “It’s like asking Derek Jeter to take several years off to sell bonds to build Yankee stadium.”

The Vice President did not purport to have all the answers, and asked those at the AARC meeting to provide feedback on his suggestions.

“The question I’d ask you to contemplate, because I’d like you to communicate with us, is, ‘Does it require realigning incentives; changing behaviors to take advantage of this inflection point? Does it require sharing more knowledge, treatment, and understanding? Or does that slow the process up?’ ”

He added,“I hope you all know it, but you’re one of the most valuable resources that our great country has, those of you sitting in this room. So ask your institutions, your colleagues, your mentors, your administrators: How can we move your ideas faster together in the interest of patients?”

The Vice President’s Moonshot initiative was announced during President Obama’s 2016 State of the Union Address. The effort includes a new Cancer Moonshot Task Force that will focus on federal investments, targeted incentives, private sector efforts from industry and philanthropy, patient engagement initiatives, and other mechanisms to support cancer research and enable progress in treatment and care, according to the White House. As part of the plan, the President’s fiscal 2017 budget proposes $755 million in mandatory funds for new cancer-related research activities at the National Institutes of Health and the Food and Drug Administration. The initiative also includes increased investments by the Department of Defense and the Department of Veterans Affairs in cancer research, including through funding centers of excellence focused on specific cancers and conducting longitudinal studies to determine risk factors and enhance treatment.

[email protected]

On Twitter @legal_med

MONTREAL – For individuals with stage III pancreatic cancer, neoadjuvant therapy may improve survival, compared with surgery-first treatment. “This study supports, however does not prove, the hypothesis that early and continued control of occult metastatic disease prolongs survival in surgical patients,” said Dr. Christopher Shubert.

Dr. Shubert and his colleagues used an intention-to-treat (ITT) analysis to compare overall survival (OS) for 377 patients who were to receive neoadjuvant chemotherapy with 216 patients who received surgery first. Median OS for the neoadjuvant group was 20.7 months, compared with 13.7 months for the surgery-first group (log-rank P less than .0001).

Courtesy Dr. Lance Liotta Laboratory

This study was the first to utilize national data to look at how patients who received neoadjuvant chemotherapy for stage III pancreatic cancer fared, when compared with those treated with a surgery-first approach, Dr. Shubert, a general surgery resident at the Mayo Clinic in Rochester, Minn., said at the annual meeting of the Central Surgical Association.

Stage III pancreatic cancer (T4, any N, M0) means that the cancer has invaded the celiac trunk, or there is superior mesenteric artery involvement, he noted.

Using data from the National Cancer Database from 2002 to 2011, the investigators identified patients with clinical stage III pancreatic adenocarcinoma of the head or body of the pancreas. The ITT neoadjuvant therapy cohort included all patients whose treatment recommendations included curative-intent surgery and neoadjuvant chemotherapy, regardless of what therapies the patients received. The surgery-first cohort included those who were recommended to receive adjuvant therapy.

A total of 593 patients were identified, of whom 377 (63.5%) were in the neoadjuvant group. Of these, 104 (27.6%) were lost to presurgical attrition. The surgery-first group included 216 patients (36.3%), 30 (13.9%) of whom did not receive the intended adjuvant chemotherapy. Comparing the two ITT groups yielded an adjusted hazard ratio of 0.68 (P = .001).

A secondary aim of the study was to see which aspects of therapy, and which pathologic features, were associated with longer OS. The addition of postsurgical therapy was associated with additional survival benefit (31.6 vs. 22.6 months for no postsurgical therapy; HR, 0.60; P = .002). Node-negative and R0 status were both also significantly increased among those receiving neoadjuvant chemotherapy, and both disease characteristics were associated with increased OS, he reported.

Dr. Shubert said that study limitations included its review of a prospective database. Also, investigators could not determine the type or duration of chemotherapy; they also were unable to tell when systemic chemotherapy plus chemoradiation or just chemoradiation alone had been used. No recurrence data were available, and all cases were grouped under one procedure code, limiting information about vascular resections.

“Neoadjuvant therapy may offer survival advantages compared to a surgery-first approach,” said Dr. Shubert, and control of small occult metastases may be the mechanism behind this advantage. Still to be determined, however, are the optimal type, duration, and sequencing of neoadjuvant chemotherapy and chemoradiation, he said.

Dr. Shubert reported no relevant disclosures.

[email protected]

On Twitter @karioakes

MONTREAL – For individuals with stage III pancreatic cancer, neoadjuvant therapy may improve survival, compared with surgery-first treatment. “This study supports, however does not prove, the hypothesis that early and continued control of occult metastatic disease prolongs survival in surgical patients,” said Dr. Christopher Shubert.

Dr. Shubert and his colleagues used an intention-to-treat (ITT) analysis to compare overall survival (OS) for 377 patients who were to receive neoadjuvant chemotherapy with 216 patients who received surgery first. Median OS for the neoadjuvant group was 20.7 months, compared with 13.7 months for the surgery-first group (log-rank P less than .0001).

Courtesy Dr. Lance Liotta Laboratory

This study was the first to utilize national data to look at how patients who received neoadjuvant chemotherapy for stage III pancreatic cancer fared, when compared with those treated with a surgery-first approach, Dr. Shubert, a general surgery resident at the Mayo Clinic in Rochester, Minn., said at the annual meeting of the Central Surgical Association.

Stage III pancreatic cancer (T4, any N, M0) means that the cancer has invaded the celiac trunk, or there is superior mesenteric artery involvement, he noted.

Using data from the National Cancer Database from 2002 to 2011, the investigators identified patients with clinical stage III pancreatic adenocarcinoma of the head or body of the pancreas. The ITT neoadjuvant therapy cohort included all patients whose treatment recommendations included curative-intent surgery and neoadjuvant chemotherapy, regardless of what therapies the patients received. The surgery-first cohort included those who were recommended to receive adjuvant therapy.

A total of 593 patients were identified, of whom 377 (63.5%) were in the neoadjuvant group. Of these, 104 (27.6%) were lost to presurgical attrition. The surgery-first group included 216 patients (36.3%), 30 (13.9%) of whom did not receive the intended adjuvant chemotherapy. Comparing the two ITT groups yielded an adjusted hazard ratio of 0.68 (P = .001).

A secondary aim of the study was to see which aspects of therapy, and which pathologic features, were associated with longer OS. The addition of postsurgical therapy was associated with additional survival benefit (31.6 vs. 22.6 months for no postsurgical therapy; HR, 0.60; P = .002). Node-negative and R0 status were both also significantly increased among those receiving neoadjuvant chemotherapy, and both disease characteristics were associated with increased OS, he reported.

Dr. Shubert said that study limitations included its review of a prospective database. Also, investigators could not determine the type or duration of chemotherapy; they also were unable to tell when systemic chemotherapy plus chemoradiation or just chemoradiation alone had been used. No recurrence data were available, and all cases were grouped under one procedure code, limiting information about vascular resections.

“Neoadjuvant therapy may offer survival advantages compared to a surgery-first approach,” said Dr. Shubert, and control of small occult metastases may be the mechanism behind this advantage. Still to be determined, however, are the optimal type, duration, and sequencing of neoadjuvant chemotherapy and chemoradiation, he said.

Dr. Shubert reported no relevant disclosures.

[email protected]

On Twitter @karioakes

MONTREAL – For individuals with stage III pancreatic cancer, neoadjuvant therapy may improve survival, compared with surgery-first treatment. “This study supports, however does not prove, the hypothesis that early and continued control of occult metastatic disease prolongs survival in surgical patients,” said Dr. Christopher Shubert.

Dr. Shubert and his colleagues used an intention-to-treat (ITT) analysis to compare overall survival (OS) for 377 patients who were to receive neoadjuvant chemotherapy with 216 patients who received surgery first. Median OS for the neoadjuvant group was 20.7 months, compared with 13.7 months for the surgery-first group (log-rank P less than .0001).

Courtesy Dr. Lance Liotta Laboratory

This study was the first to utilize national data to look at how patients who received neoadjuvant chemotherapy for stage III pancreatic cancer fared, when compared with those treated with a surgery-first approach, Dr. Shubert, a general surgery resident at the Mayo Clinic in Rochester, Minn., said at the annual meeting of the Central Surgical Association.

Stage III pancreatic cancer (T4, any N, M0) means that the cancer has invaded the celiac trunk, or there is superior mesenteric artery involvement, he noted.

Using data from the National Cancer Database from 2002 to 2011, the investigators identified patients with clinical stage III pancreatic adenocarcinoma of the head or body of the pancreas. The ITT neoadjuvant therapy cohort included all patients whose treatment recommendations included curative-intent surgery and neoadjuvant chemotherapy, regardless of what therapies the patients received. The surgery-first cohort included those who were recommended to receive adjuvant therapy.

A total of 593 patients were identified, of whom 377 (63.5%) were in the neoadjuvant group. Of these, 104 (27.6%) were lost to presurgical attrition. The surgery-first group included 216 patients (36.3%), 30 (13.9%) of whom did not receive the intended adjuvant chemotherapy. Comparing the two ITT groups yielded an adjusted hazard ratio of 0.68 (P = .001).

A secondary aim of the study was to see which aspects of therapy, and which pathologic features, were associated with longer OS. The addition of postsurgical therapy was associated with additional survival benefit (31.6 vs. 22.6 months for no postsurgical therapy; HR, 0.60; P = .002). Node-negative and R0 status were both also significantly increased among those receiving neoadjuvant chemotherapy, and both disease characteristics were associated with increased OS, he reported.

Dr. Shubert said that study limitations included its review of a prospective database. Also, investigators could not determine the type or duration of chemotherapy; they also were unable to tell when systemic chemotherapy plus chemoradiation or just chemoradiation alone had been used. No recurrence data were available, and all cases were grouped under one procedure code, limiting information about vascular resections.

“Neoadjuvant therapy may offer survival advantages compared to a surgery-first approach,” said Dr. Shubert, and control of small occult metastases may be the mechanism behind this advantage. Still to be determined, however, are the optimal type, duration, and sequencing of neoadjuvant chemotherapy and chemoradiation, he said.

Dr. Shubert reported no relevant disclosures.

[email protected]

On Twitter @karioakes

You asked, we listened: Introducing the enhanced SHM Learning Portal!

The SHM Learning Portal, the online learning home for hospitalists with all eLearning initiatives in one place, just launched a brand-new responsive design in March 2016. Feedback gathered by the Learning Portal team in the summer and fall of 2015 was used to develop a more user-friendly design aimed at reducing the time it takes to discover and access a growing catalog of educational content.

Mobile enhancements now allow for easy access and navigation on the go. Check out the new design for yourself at www.shmlearningportal.org.

You asked, we listened: Introducing the enhanced SHM Learning Portal!

The SHM Learning Portal, the online learning home for hospitalists with all eLearning initiatives in one place, just launched a brand-new responsive design in March 2016. Feedback gathered by the Learning Portal team in the summer and fall of 2015 was used to develop a more user-friendly design aimed at reducing the time it takes to discover and access a growing catalog of educational content.

Mobile enhancements now allow for easy access and navigation on the go. Check out the new design for yourself at www.shmlearningportal.org.

You asked, we listened: Introducing the enhanced SHM Learning Portal!

The SHM Learning Portal, the online learning home for hospitalists with all eLearning initiatives in one place, just launched a brand-new responsive design in March 2016. Feedback gathered by the Learning Portal team in the summer and fall of 2015 was used to develop a more user-friendly design aimed at reducing the time it takes to discover and access a growing catalog of educational content.

Mobile enhancements now allow for easy access and navigation on the go. Check out the new design for yourself at www.shmlearningportal.org.

Engaged hospitalists drive quality care, and SHM has the tools to help you assess the level of engagement of hospitalists in your hospital medicine group. SHM offered a Hospitalist Engagement Benchmarking Service in 2015 and analyzed engagement of approximately 1,500 hospitalists. The survey can help open conversations about everything from relationships with the C-suite to sustaining teamwork.

Help ensure hospitalists are engaged in your hospital medicine group by registering now for the next cohort of the Hospitalist Engagement Benchmarking Service at www.hospitalmedicine.org/engage.

Engaged hospitalists drive quality care, and SHM has the tools to help you assess the level of engagement of hospitalists in your hospital medicine group. SHM offered a Hospitalist Engagement Benchmarking Service in 2015 and analyzed engagement of approximately 1,500 hospitalists. The survey can help open conversations about everything from relationships with the C-suite to sustaining teamwork.

Help ensure hospitalists are engaged in your hospital medicine group by registering now for the next cohort of the Hospitalist Engagement Benchmarking Service at www.hospitalmedicine.org/engage.

Engaged hospitalists drive quality care, and SHM has the tools to help you assess the level of engagement of hospitalists in your hospital medicine group. SHM offered a Hospitalist Engagement Benchmarking Service in 2015 and analyzed engagement of approximately 1,500 hospitalists. The survey can help open conversations about everything from relationships with the C-suite to sustaining teamwork.

Help ensure hospitalists are engaged in your hospital medicine group by registering now for the next cohort of the Hospitalist Engagement Benchmarking Service at www.hospitalmedicine.org/engage.

For patients with squamous cell carcinoma (SCC) of the tongue, recurrence is common and closely associated with survival, say researchers from Capital Medical University, Beijing. The researchers conducted a retrospective study of 204 patients with SCC of the tongue that aimed to identify the factors that predict relapse and prognosis.

Related: IBD and the Risk of Oral Cancer

In an earlier study, the researchers assessed the best indications for neck dissection and the prognostic factors of oral SCC. Their results showed that middle-late oral SCC is an indication for simultaneous neck dissection, even in patients whose nodes are clear. But few studies have focused on the outcomes of treatment after different surgical approaches, such as en bloc resection and discontinuous resection. En bloc dissection requires continuity between the tumor and the level I neck nodes, and the technique involves removal of the sublingual gland and the mylohyoid muscle, as well as the associated sublingual nodes.

Related: A Team Approach to Nonmelanotic Skin Cancer Procedures

Within the median follow-up of 82 months, 59 patients died (29%), 4 from non-cancer causes. Two patients in the en bloc group and 12 in the control group (discontinuous resection) had relapses. Ten of the 14 in this group had recurrences within a year of the first operation. Nine patients had salvage operations; however, only 2 experienced a successful outcome.

Surgical technique and pathological nodal (pN) status independently predicted both 5-year recurrence and disease-specific survival.

Related: Nivolumab Approved for Expanded Indication

The analysis showed a “dramatic” decrease in the 5-year disease-specific survival if the cancer recurred after the primary operation (no recurrence, 77% vs recurrence, 14%). Patients in the en bloc group “could expect an obviously lower” 5-year recurrence rate (2%, compared with 11% in the control group). They also had a better 5-year disease-specific survival (80%, versus 66%). An aggressive pN status was closely correlated with recurrence.

Source:
Feng Z, Xu QS, Qin LZ, et al. Br J Oral Maxillofac Surg. 2016;54(1):88-93.
doi: 10.1016/j.bjoms.2015.09.024

For patients with squamous cell carcinoma (SCC) of the tongue, recurrence is common and closely associated with survival, say researchers from Capital Medical University, Beijing. The researchers conducted a retrospective study of 204 patients with SCC of the tongue that aimed to identify the factors that predict relapse and prognosis.

Related: IBD and the Risk of Oral Cancer

In an earlier study, the researchers assessed the best indications for neck dissection and the prognostic factors of oral SCC. Their results showed that middle-late oral SCC is an indication for simultaneous neck dissection, even in patients whose nodes are clear. But few studies have focused on the outcomes of treatment after different surgical approaches, such as en bloc resection and discontinuous resection. En bloc dissection requires continuity between the tumor and the level I neck nodes, and the technique involves removal of the sublingual gland and the mylohyoid muscle, as well as the associated sublingual nodes.

Related: A Team Approach to Nonmelanotic Skin Cancer Procedures

Within the median follow-up of 82 months, 59 patients died (29%), 4 from non-cancer causes. Two patients in the en bloc group and 12 in the control group (discontinuous resection) had relapses. Ten of the 14 in this group had recurrences within a year of the first operation. Nine patients had salvage operations; however, only 2 experienced a successful outcome.

Surgical technique and pathological nodal (pN) status independently predicted both 5-year recurrence and disease-specific survival.

Related: Nivolumab Approved for Expanded Indication

The analysis showed a “dramatic” decrease in the 5-year disease-specific survival if the cancer recurred after the primary operation (no recurrence, 77% vs recurrence, 14%). Patients in the en bloc group “could expect an obviously lower” 5-year recurrence rate (2%, compared with 11% in the control group). They also had a better 5-year disease-specific survival (80%, versus 66%). An aggressive pN status was closely correlated with recurrence.

Source:
Feng Z, Xu QS, Qin LZ, et al. Br J Oral Maxillofac Surg. 2016;54(1):88-93.
doi: 10.1016/j.bjoms.2015.09.024

For patients with squamous cell carcinoma (SCC) of the tongue, recurrence is common and closely associated with survival, say researchers from Capital Medical University, Beijing. The researchers conducted a retrospective study of 204 patients with SCC of the tongue that aimed to identify the factors that predict relapse and prognosis.

Related: IBD and the Risk of Oral Cancer

In an earlier study, the researchers assessed the best indications for neck dissection and the prognostic factors of oral SCC. Their results showed that middle-late oral SCC is an indication for simultaneous neck dissection, even in patients whose nodes are clear. But few studies have focused on the outcomes of treatment after different surgical approaches, such as en bloc resection and discontinuous resection. En bloc dissection requires continuity between the tumor and the level I neck nodes, and the technique involves removal of the sublingual gland and the mylohyoid muscle, as well as the associated sublingual nodes.

Related: A Team Approach to Nonmelanotic Skin Cancer Procedures

Within the median follow-up of 82 months, 59 patients died (29%), 4 from non-cancer causes. Two patients in the en bloc group and 12 in the control group (discontinuous resection) had relapses. Ten of the 14 in this group had recurrences within a year of the first operation. Nine patients had salvage operations; however, only 2 experienced a successful outcome.

Surgical technique and pathological nodal (pN) status independently predicted both 5-year recurrence and disease-specific survival.

Related: Nivolumab Approved for Expanded Indication

The analysis showed a “dramatic” decrease in the 5-year disease-specific survival if the cancer recurred after the primary operation (no recurrence, 77% vs recurrence, 14%). Patients in the en bloc group “could expect an obviously lower” 5-year recurrence rate (2%, compared with 11% in the control group). They also had a better 5-year disease-specific survival (80%, versus 66%). An aggressive pN status was closely correlated with recurrence.

Source:
Feng Z, Xu QS, Qin LZ, et al. Br J Oral Maxillofac Surg. 2016;54(1):88-93.
doi: 10.1016/j.bjoms.2015.09.024

NEW YORK (Reuters) - U.S. health insurers that provide Medicare Advantage plans to elderly and disabled Americans will receive government payments in 2017 that are 0.85 percent higher on average than in 2016, reflecting small anticipated growth in medical costs, the U.S. Department of Health and Human Services said on Monday.

Health and Human Services' final plan to raise payments is a bit lower than the 1.35 percent increase the agency had proposed in February. It said the lower figure reflects revisions to medical services cost calculations.

In addition, the agency said it planned to introduce a two-year transition period to implement reductions in payments to insurers that offer employer-sponsored prescription drug plans for retirees. After it proposed the cuts to 2017 payments in February, insurers and other lobbying groups said the agency was too aggressive.

Insurers including UnitedHealth Group Inc, Aetna Inc and Anthem Inc manage health benefits for more than 17 million Americans enrolled in Medicare Advantage plans.

The other more than 30 million people eligible for Medicare coverage are part of the government-run fee-for-service program.

Each year the government sets out how it will reimburse insurers for the healthcare services their members use. Payments vary by region, the quality rating earned by the plan, and the relative health of the members.

NEW YORK (Reuters) - U.S. health insurers that provide Medicare Advantage plans to elderly and disabled Americans will receive government payments in 2017 that are 0.85 percent higher on average than in 2016, reflecting small anticipated growth in medical costs, the U.S. Department of Health and Human Services said on Monday.

Health and Human Services' final plan to raise payments is a bit lower than the 1.35 percent increase the agency had proposed in February. It said the lower figure reflects revisions to medical services cost calculations.

In addition, the agency said it planned to introduce a two-year transition period to implement reductions in payments to insurers that offer employer-sponsored prescription drug plans for retirees. After it proposed the cuts to 2017 payments in February, insurers and other lobbying groups said the agency was too aggressive.

Insurers including UnitedHealth Group Inc, Aetna Inc and Anthem Inc manage health benefits for more than 17 million Americans enrolled in Medicare Advantage plans.

The other more than 30 million people eligible for Medicare coverage are part of the government-run fee-for-service program.

Each year the government sets out how it will reimburse insurers for the healthcare services their members use. Payments vary by region, the quality rating earned by the plan, and the relative health of the members.

NEW YORK (Reuters) - U.S. health insurers that provide Medicare Advantage plans to elderly and disabled Americans will receive government payments in 2017 that are 0.85 percent higher on average than in 2016, reflecting small anticipated growth in medical costs, the U.S. Department of Health and Human Services said on Monday.

Health and Human Services' final plan to raise payments is a bit lower than the 1.35 percent increase the agency had proposed in February. It said the lower figure reflects revisions to medical services cost calculations.

In addition, the agency said it planned to introduce a two-year transition period to implement reductions in payments to insurers that offer employer-sponsored prescription drug plans for retirees. After it proposed the cuts to 2017 payments in February, insurers and other lobbying groups said the agency was too aggressive.

Insurers including UnitedHealth Group Inc, Aetna Inc and Anthem Inc manage health benefits for more than 17 million Americans enrolled in Medicare Advantage plans.

The other more than 30 million people eligible for Medicare coverage are part of the government-run fee-for-service program.

Each year the government sets out how it will reimburse insurers for the healthcare services their members use. Payments vary by region, the quality rating earned by the plan, and the relative health of the members.

AML cells

NEW ORLEANS—A phase 4 study has revealed biomarkers that appear to predict the efficacy of treatment with histamine dihydrochloride (HDC) and interleukin-2 (IL-2) in patients with acute myeloid leukemia (AML).

Researchers found that patients who remained in complete remission after 1 cycle of HDC/IL-2 experienced a significant reduction in effector memory T cells (T_EM) and a concomitant increase in effector T cells (T_eff) during therapy.

This “T_EM to T_eff transition” was associated with favorable leukemia-free survival (LFS) and overall survival (OS), especially among patients older than 60.

Frida Ewald Sander, PhD, of University of Gothenburg in Sweden, and her colleagues presented this research at the 2016 AACR Annual Meeting (abstract CT116*).

The study was supported by The Swedish Research Council, The Swedish Cancer Society, The Swedish Society for Medical Research, Meda Pharma, and Immune Pharmaceuticals, which markets HDC as Ceplene®.

The combination of HDC and IL-2 is currently approved in more than 30 countries to prevent relapse in AML patients. In this phase 4 study (Re:MISSION), the researchers set out to assess the immunomodulatory properties of this treatment and correlate potential biomarkers with clinical outcomes.

The study included 84 non-transplanted AML patients (ages 18 to 79) in first complete remission. The patients received HDC (0.5 mg SC BID) and human recombinant IL-2 (1MIU SC BID) in 3-week cycles for 18 months. The patients were followed for at least 2 years from the start of immunotherapy to evaluate survival.

The researchers collected blood from the patients before they began HDC/IL-2 therapy and at the end of the first treatment cycle. From these samples, the team assessed the frequency of CD8+ T cells, including naïve T cells (CD45RA+CCR7+), central memory T cells (CD45RO+CCR7+), T_EM cells (CD45RO+CCR7-), and T_eff cells (CD45RA+CCR7-).

The researchers found that non-relapsing patients experienced a significant reduction in T_EM cells (P=0.001) and a significant increase in T_eff cells (P=0.007) during cycle 1. However, this effect was not observed in patients who did relapse.

Further analysis revealed that the reduction in T_EM cells was significantly associated with favorable LFS  and OS in the entire cohort (P=0.0007 and P=0.005, respectively) and among patients over 60 (P<0.0001 and P=0.002, respectively).

Likewise, the increase in T_eff cells was associated with favorable LFS and OS in the entire cohort (P=0.07 and P=0.04, respectively) and among patients over 60 (P=0.004 and P=0.0001, respectively).

The concomitant reduction of T_EM cells and induction of T_eff cells—the T_EM to T_eff transition—was associated with superior LFS and OS in the overall cohort (P=0.0002 and P=0.002, respectively) and in the over-60 population (P<0.0001 for LFS and OS).

The researchers said these predictors of outcome remained significant when they adjusted for potential confounders (age, risk group classification, number of induction courses required to achieve complete response, and number of consolidation courses).

Therefore, the team concluded that the altered distribution of cytotoxic T cells during treatment with HDC/IL-2 can prognosticate LFS and OS in AML patients, particularly those over 60.

“We believe that the new data may allow a personalized approach to selection of patients who are most likely to benefit from Ceplene/IL-2 treatment in AML—in particular, the older patient population, who have demonstrated almost 100% survival when positive for the T-cell transition biomarkers,” said Miri Ben-Ami, MD, executive vice president of oncology at Immune Pharmaceuticals.

“In addition, current research is revealing the potential synergy between immune checkpoint inhibitors and Ceplene, which could open the possibility of additional therapeutic indications for this combination.”

*Information in the abstract differs from that presented at the meeting.

AML cells

NEW ORLEANS—A phase 4 study has revealed biomarkers that appear to predict the efficacy of treatment with histamine dihydrochloride (HDC) and interleukin-2 (IL-2) in patients with acute myeloid leukemia (AML).

Researchers found that patients who remained in complete remission after 1 cycle of HDC/IL-2 experienced a significant reduction in effector memory T cells (T_EM) and a concomitant increase in effector T cells (T_eff) during therapy.

This “T_EM to T_eff transition” was associated with favorable leukemia-free survival (LFS) and overall survival (OS), especially among patients older than 60.

Frida Ewald Sander, PhD, of University of Gothenburg in Sweden, and her colleagues presented this research at the 2016 AACR Annual Meeting (abstract CT116*).

The study was supported by The Swedish Research Council, The Swedish Cancer Society, The Swedish Society for Medical Research, Meda Pharma, and Immune Pharmaceuticals, which markets HDC as Ceplene®.

The combination of HDC and IL-2 is currently approved in more than 30 countries to prevent relapse in AML patients. In this phase 4 study (Re:MISSION), the researchers set out to assess the immunomodulatory properties of this treatment and correlate potential biomarkers with clinical outcomes.

The study included 84 non-transplanted AML patients (ages 18 to 79) in first complete remission. The patients received HDC (0.5 mg SC BID) and human recombinant IL-2 (1MIU SC BID) in 3-week cycles for 18 months. The patients were followed for at least 2 years from the start of immunotherapy to evaluate survival.

The researchers collected blood from the patients before they began HDC/IL-2 therapy and at the end of the first treatment cycle. From these samples, the team assessed the frequency of CD8+ T cells, including naïve T cells (CD45RA+CCR7+), central memory T cells (CD45RO+CCR7+), T_EM cells (CD45RO+CCR7-), and T_eff cells (CD45RA+CCR7-).

The researchers found that non-relapsing patients experienced a significant reduction in T_EM cells (P=0.001) and a significant increase in T_eff cells (P=0.007) during cycle 1. However, this effect was not observed in patients who did relapse.

Further analysis revealed that the reduction in T_EM cells was significantly associated with favorable LFS  and OS in the entire cohort (P=0.0007 and P=0.005, respectively) and among patients over 60 (P<0.0001 and P=0.002, respectively).

Likewise, the increase in T_eff cells was associated with favorable LFS and OS in the entire cohort (P=0.07 and P=0.04, respectively) and among patients over 60 (P=0.004 and P=0.0001, respectively).

The concomitant reduction of T_EM cells and induction of T_eff cells—the T_EM to T_eff transition—was associated with superior LFS and OS in the overall cohort (P=0.0002 and P=0.002, respectively) and in the over-60 population (P<0.0001 for LFS and OS).

The researchers said these predictors of outcome remained significant when they adjusted for potential confounders (age, risk group classification, number of induction courses required to achieve complete response, and number of consolidation courses).

Therefore, the team concluded that the altered distribution of cytotoxic T cells during treatment with HDC/IL-2 can prognosticate LFS and OS in AML patients, particularly those over 60.

“We believe that the new data may allow a personalized approach to selection of patients who are most likely to benefit from Ceplene/IL-2 treatment in AML—in particular, the older patient population, who have demonstrated almost 100% survival when positive for the T-cell transition biomarkers,” said Miri Ben-Ami, MD, executive vice president of oncology at Immune Pharmaceuticals.

“In addition, current research is revealing the potential synergy between immune checkpoint inhibitors and Ceplene, which could open the possibility of additional therapeutic indications for this combination.”

*Information in the abstract differs from that presented at the meeting.

AML cells

NEW ORLEANS—A phase 4 study has revealed biomarkers that appear to predict the efficacy of treatment with histamine dihydrochloride (HDC) and interleukin-2 (IL-2) in patients with acute myeloid leukemia (AML).

Researchers found that patients who remained in complete remission after 1 cycle of HDC/IL-2 experienced a significant reduction in effector memory T cells (T_EM) and a concomitant increase in effector T cells (T_eff) during therapy.

This “T_EM to T_eff transition” was associated with favorable leukemia-free survival (LFS) and overall survival (OS), especially among patients older than 60.

Frida Ewald Sander, PhD, of University of Gothenburg in Sweden, and her colleagues presented this research at the 2016 AACR Annual Meeting (abstract CT116*).

The study was supported by The Swedish Research Council, The Swedish Cancer Society, The Swedish Society for Medical Research, Meda Pharma, and Immune Pharmaceuticals, which markets HDC as Ceplene®.

The combination of HDC and IL-2 is currently approved in more than 30 countries to prevent relapse in AML patients. In this phase 4 study (Re:MISSION), the researchers set out to assess the immunomodulatory properties of this treatment and correlate potential biomarkers with clinical outcomes.

The study included 84 non-transplanted AML patients (ages 18 to 79) in first complete remission. The patients received HDC (0.5 mg SC BID) and human recombinant IL-2 (1MIU SC BID) in 3-week cycles for 18 months. The patients were followed for at least 2 years from the start of immunotherapy to evaluate survival.

The researchers collected blood from the patients before they began HDC/IL-2 therapy and at the end of the first treatment cycle. From these samples, the team assessed the frequency of CD8+ T cells, including naïve T cells (CD45RA+CCR7+), central memory T cells (CD45RO+CCR7+), T_EM cells (CD45RO+CCR7-), and T_eff cells (CD45RA+CCR7-).

The researchers found that non-relapsing patients experienced a significant reduction in T_EM cells (P=0.001) and a significant increase in T_eff cells (P=0.007) during cycle 1. However, this effect was not observed in patients who did relapse.

Further analysis revealed that the reduction in T_EM cells was significantly associated with favorable LFS  and OS in the entire cohort (P=0.0007 and P=0.005, respectively) and among patients over 60 (P<0.0001 and P=0.002, respectively).

Likewise, the increase in T_eff cells was associated with favorable LFS and OS in the entire cohort (P=0.07 and P=0.04, respectively) and among patients over 60 (P=0.004 and P=0.0001, respectively).

The concomitant reduction of T_EM cells and induction of T_eff cells—the T_EM to T_eff transition—was associated with superior LFS and OS in the overall cohort (P=0.0002 and P=0.002, respectively) and in the over-60 population (P<0.0001 for LFS and OS).

The researchers said these predictors of outcome remained significant when they adjusted for potential confounders (age, risk group classification, number of induction courses required to achieve complete response, and number of consolidation courses).

Therefore, the team concluded that the altered distribution of cytotoxic T cells during treatment with HDC/IL-2 can prognosticate LFS and OS in AML patients, particularly those over 60.

“We believe that the new data may allow a personalized approach to selection of patients who are most likely to benefit from Ceplene/IL-2 treatment in AML—in particular, the older patient population, who have demonstrated almost 100% survival when positive for the T-cell transition biomarkers,” said Miri Ben-Ami, MD, executive vice president of oncology at Immune Pharmaceuticals.

“In addition, current research is revealing the potential synergy between immune checkpoint inhibitors and Ceplene, which could open the possibility of additional therapeutic indications for this combination.”

*Information in the abstract differs from that presented at the meeting.

Brian Sorrentino, MD

Photo courtesy of St. Jude

Children’s Research Hospital

Lentiviral gene therapy with reduced-intensity conditioning can provide long-term benefits for older patients with X-linked severe combined immunodeficiency (SCID-X1), according to a small study.

All 5 patients who received this therapy exhibited selective expansion of gene-marked B, T, and natural killer (NK) cells.

In 2 of the older patients, the treatment restored normal immune function, an effect that lasted 2 and 3 years, respectively.

“This study demonstrates that lentivirus gene therapy, when combined with busulfan conditioning, can rebuild the immune system and lead to broad immunity in young adults with this devastating disorder,” said Brian Sorrentino, MD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.

Dr Sorrentino and his colleagues described this research in Science Translational Medicine.

The researchers explained that SCID-X1 is a profound deficiency of T, B, and NK cell immunity caused by mutations in IL2RG encoding the common chain (γc) of several interleukin receptors. And gammaretroviral gene therapy given without conditioning can restore T-cell immunity in young children with SCID-X1 but fails in older patients.

With this in mind, the team developed a lentiviral vector γc transduced autologous hematopoietic stem cell (HSC) gene therapy and tested it with nonmyeloablative busulfan conditioning in 5 SCID-X1 patients.

The patients were 7 to 23 years old. They all had chronic viral infections and other health problems related to SCID-X1, despite having received 1 or more haploidentical HSC transplants.

More than 2 years after undergoing gene therapy, the first 2 patients (ages 22 and 23) were producing a greater percentage of T, B, and NK cells with the corrected gene. The therapy had also restored antibody production in response to vaccination.

Furthermore, the patients’ health improved as their chronic viral infections resolved, and they put on weight as their protein absorption improved. One patient’s disfiguring warts were eased, and both patients ended life-long immune globulin therapy.

However, one of these patients died from pre-existing lung damage more than 2 years after receiving gene therapy.

Like the 2 older patients, the 3 younger patients (ages 7, 10, and 15) began producing a greater percentage of T, B, and NK cells with the corrected gene after therapy. But the younger patients have only been followed for several months.

The researchers said the safety results in this study were reassuring. There were no adverse events associated with the gene therapy and no indication of possible precancer cell proliferation.

As expected, patients experienced busulfan-related neutropenia and thrombocytopenia but recovered without any intervention. And 3 patients developed febrile neutropenia that responded to empiric antimicrobial therapy.

“While additional clinical experience and follow-up is needed, these promising results suggest gene therapy should be considered as an early treatment for patients in order to minimize or prevent the life-threatening organ damage that occurs when bone marrow transplant therapy fails to provide a sufficient immune response,” Dr Sorrentino said.

To that end, St. Jude has opened a gene therapy trial using the same lentiviral vector and busulfan conditioning for newly identified infants with SCID-X1 who lack a genetically matched sibling HSC donor.

“Based on the safety and health benefits for older patients reported in this study, we hope this novel gene therapy will help improve immune functioning and transform the lives of younger patients with this devastating disease,” Dr Sorrentino said.

Brian Sorrentino, MD

Photo courtesy of St. Jude

Children’s Research Hospital

Lentiviral gene therapy with reduced-intensity conditioning can provide long-term benefits for older patients with X-linked severe combined immunodeficiency (SCID-X1), according to a small study.

All 5 patients who received this therapy exhibited selective expansion of gene-marked B, T, and natural killer (NK) cells.

In 2 of the older patients, the treatment restored normal immune function, an effect that lasted 2 and 3 years, respectively.

“This study demonstrates that lentivirus gene therapy, when combined with busulfan conditioning, can rebuild the immune system and lead to broad immunity in young adults with this devastating disorder,” said Brian Sorrentino, MD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.

Dr Sorrentino and his colleagues described this research in Science Translational Medicine.

The researchers explained that SCID-X1 is a profound deficiency of T, B, and NK cell immunity caused by mutations in IL2RG encoding the common chain (γc) of several interleukin receptors. And gammaretroviral gene therapy given without conditioning can restore T-cell immunity in young children with SCID-X1 but fails in older patients.

With this in mind, the team developed a lentiviral vector γc transduced autologous hematopoietic stem cell (HSC) gene therapy and tested it with nonmyeloablative busulfan conditioning in 5 SCID-X1 patients.

The patients were 7 to 23 years old. They all had chronic viral infections and other health problems related to SCID-X1, despite having received 1 or more haploidentical HSC transplants.

More than 2 years after undergoing gene therapy, the first 2 patients (ages 22 and 23) were producing a greater percentage of T, B, and NK cells with the corrected gene. The therapy had also restored antibody production in response to vaccination.

Furthermore, the patients’ health improved as their chronic viral infections resolved, and they put on weight as their protein absorption improved. One patient’s disfiguring warts were eased, and both patients ended life-long immune globulin therapy.

However, one of these patients died from pre-existing lung damage more than 2 years after receiving gene therapy.

Like the 2 older patients, the 3 younger patients (ages 7, 10, and 15) began producing a greater percentage of T, B, and NK cells with the corrected gene after therapy. But the younger patients have only been followed for several months.

The researchers said the safety results in this study were reassuring. There were no adverse events associated with the gene therapy and no indication of possible precancer cell proliferation.

As expected, patients experienced busulfan-related neutropenia and thrombocytopenia but recovered without any intervention. And 3 patients developed febrile neutropenia that responded to empiric antimicrobial therapy.

“While additional clinical experience and follow-up is needed, these promising results suggest gene therapy should be considered as an early treatment for patients in order to minimize or prevent the life-threatening organ damage that occurs when bone marrow transplant therapy fails to provide a sufficient immune response,” Dr Sorrentino said.

To that end, St. Jude has opened a gene therapy trial using the same lentiviral vector and busulfan conditioning for newly identified infants with SCID-X1 who lack a genetically matched sibling HSC donor.

“Based on the safety and health benefits for older patients reported in this study, we hope this novel gene therapy will help improve immune functioning and transform the lives of younger patients with this devastating disease,” Dr Sorrentino said.

Brian Sorrentino, MD

Photo courtesy of St. Jude

Children’s Research Hospital

Lentiviral gene therapy with reduced-intensity conditioning can provide long-term benefits for older patients with X-linked severe combined immunodeficiency (SCID-X1), according to a small study.

All 5 patients who received this therapy exhibited selective expansion of gene-marked B, T, and natural killer (NK) cells.

In 2 of the older patients, the treatment restored normal immune function, an effect that lasted 2 and 3 years, respectively.

“This study demonstrates that lentivirus gene therapy, when combined with busulfan conditioning, can rebuild the immune system and lead to broad immunity in young adults with this devastating disorder,” said Brian Sorrentino, MD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.

Dr Sorrentino and his colleagues described this research in Science Translational Medicine.

The researchers explained that SCID-X1 is a profound deficiency of T, B, and NK cell immunity caused by mutations in IL2RG encoding the common chain (γc) of several interleukin receptors. And gammaretroviral gene therapy given without conditioning can restore T-cell immunity in young children with SCID-X1 but fails in older patients.

With this in mind, the team developed a lentiviral vector γc transduced autologous hematopoietic stem cell (HSC) gene therapy and tested it with nonmyeloablative busulfan conditioning in 5 SCID-X1 patients.

The patients were 7 to 23 years old. They all had chronic viral infections and other health problems related to SCID-X1, despite having received 1 or more haploidentical HSC transplants.

More than 2 years after undergoing gene therapy, the first 2 patients (ages 22 and 23) were producing a greater percentage of T, B, and NK cells with the corrected gene. The therapy had also restored antibody production in response to vaccination.

Furthermore, the patients’ health improved as their chronic viral infections resolved, and they put on weight as their protein absorption improved. One patient’s disfiguring warts were eased, and both patients ended life-long immune globulin therapy.

However, one of these patients died from pre-existing lung damage more than 2 years after receiving gene therapy.

Like the 2 older patients, the 3 younger patients (ages 7, 10, and 15) began producing a greater percentage of T, B, and NK cells with the corrected gene after therapy. But the younger patients have only been followed for several months.

The researchers said the safety results in this study were reassuring. There were no adverse events associated with the gene therapy and no indication of possible precancer cell proliferation.

As expected, patients experienced busulfan-related neutropenia and thrombocytopenia but recovered without any intervention. And 3 patients developed febrile neutropenia that responded to empiric antimicrobial therapy.

“While additional clinical experience and follow-up is needed, these promising results suggest gene therapy should be considered as an early treatment for patients in order to minimize or prevent the life-threatening organ damage that occurs when bone marrow transplant therapy fails to provide a sufficient immune response,” Dr Sorrentino said.

To that end, St. Jude has opened a gene therapy trial using the same lentiviral vector and busulfan conditioning for newly identified infants with SCID-X1 who lack a genetically matched sibling HSC donor.

“Based on the safety and health benefits for older patients reported in this study, we hope this novel gene therapy will help improve immune functioning and transform the lives of younger patients with this devastating disease,” Dr Sorrentino said.