In patients with clear cell renal cell carcinoma (ccRCC), radiogenomic analysis can reveal associations between specific features on CT imaging and messenger RNA-based tumor subtyping, authors of a preliminary analysis contend.

Among 177 patients with ccRCC for whom CT data and molecular subtyping information were available, well-defined vs. poorly-defined tumor margins were significantly associated with messenger RNA (mRNA) subtype m1 tumors, and a combination of margin definition and other qualitative tumor features was significantly associated with m3 subtype, reported Lan Bowen, MD, and Li Xiaojing, MD, from Huizhou (China) Central People’s Hospital.

“We demonstrated m1-subtype is positively associated with well-defined margin while m3-subtype is positively associated with ill-defined margin, renal vein invasion, and collecting-system invasion. These findings should be further investigated and validated in other cohorts,” they wrote. The report was published in Academic Radiology.

Radiogenomic analysis is a method for identifying associations between imaging features and gene expression profiles to provide information that can be used for clinical decision making.

The investigators used the technique to retrospectively explore associations between ccRCC mRNA-based subtyping and CT features.

They identified data on a total of 177 patients with ccRCC from The Cancer Genome Atlas for whom complete CT imaging, including contrast-enhanced images, and mRNA-based subtyping were available.

CT features studied included calcifications, margin definition, renal vein invasion, collecting-system invasion, multicystic tumors, nodular tumor enhancement, and intratumoral vasculature.

In univariate logistic regression analysis, well-defined tumor margins (vs. poorly-defined margins) were significant associated with m1 subtype (odd ratio [OR] 2.104, P = .041).

Similarly, a combination of well-defined tumor margins (OR 2.104, P = .013), no collecting system invasion (OR 0.421, P = .028), and renal vein invasion (OR 2.164, P = .026) were significantly associated with the m3 subtype.

They were no significant associations between CT imaging features and either the m2 or m4 subtypes, the authors found.

The authors did not report study funding sources or potential conflicts of interest.

SOURCE: Bowen L, Xiaojing L. Acad Radiol. doi: 10.1016/j.acra.2018.05.002.

In patients with clear cell renal cell carcinoma (ccRCC), radiogenomic analysis can reveal associations between specific features on CT imaging and messenger RNA-based tumor subtyping, authors of a preliminary analysis contend.

Among 177 patients with ccRCC for whom CT data and molecular subtyping information were available, well-defined vs. poorly-defined tumor margins were significantly associated with messenger RNA (mRNA) subtype m1 tumors, and a combination of margin definition and other qualitative tumor features was significantly associated with m3 subtype, reported Lan Bowen, MD, and Li Xiaojing, MD, from Huizhou (China) Central People’s Hospital.

“We demonstrated m1-subtype is positively associated with well-defined margin while m3-subtype is positively associated with ill-defined margin, renal vein invasion, and collecting-system invasion. These findings should be further investigated and validated in other cohorts,” they wrote. The report was published in Academic Radiology.

Radiogenomic analysis is a method for identifying associations between imaging features and gene expression profiles to provide information that can be used for clinical decision making.

The investigators used the technique to retrospectively explore associations between ccRCC mRNA-based subtyping and CT features.

They identified data on a total of 177 patients with ccRCC from The Cancer Genome Atlas for whom complete CT imaging, including contrast-enhanced images, and mRNA-based subtyping were available.

CT features studied included calcifications, margin definition, renal vein invasion, collecting-system invasion, multicystic tumors, nodular tumor enhancement, and intratumoral vasculature.

In univariate logistic regression analysis, well-defined tumor margins (vs. poorly-defined margins) were significant associated with m1 subtype (odd ratio [OR] 2.104, P = .041).

Similarly, a combination of well-defined tumor margins (OR 2.104, P = .013), no collecting system invasion (OR 0.421, P = .028), and renal vein invasion (OR 2.164, P = .026) were significantly associated with the m3 subtype.

They were no significant associations between CT imaging features and either the m2 or m4 subtypes, the authors found.

The authors did not report study funding sources or potential conflicts of interest.

SOURCE: Bowen L, Xiaojing L. Acad Radiol. doi: 10.1016/j.acra.2018.05.002.

In patients with clear cell renal cell carcinoma (ccRCC), radiogenomic analysis can reveal associations between specific features on CT imaging and messenger RNA-based tumor subtyping, authors of a preliminary analysis contend.

Among 177 patients with ccRCC for whom CT data and molecular subtyping information were available, well-defined vs. poorly-defined tumor margins were significantly associated with messenger RNA (mRNA) subtype m1 tumors, and a combination of margin definition and other qualitative tumor features was significantly associated with m3 subtype, reported Lan Bowen, MD, and Li Xiaojing, MD, from Huizhou (China) Central People’s Hospital.

“We demonstrated m1-subtype is positively associated with well-defined margin while m3-subtype is positively associated with ill-defined margin, renal vein invasion, and collecting-system invasion. These findings should be further investigated and validated in other cohorts,” they wrote. The report was published in Academic Radiology.

Radiogenomic analysis is a method for identifying associations between imaging features and gene expression profiles to provide information that can be used for clinical decision making.

The investigators used the technique to retrospectively explore associations between ccRCC mRNA-based subtyping and CT features.

They identified data on a total of 177 patients with ccRCC from The Cancer Genome Atlas for whom complete CT imaging, including contrast-enhanced images, and mRNA-based subtyping were available.

CT features studied included calcifications, margin definition, renal vein invasion, collecting-system invasion, multicystic tumors, nodular tumor enhancement, and intratumoral vasculature.

In univariate logistic regression analysis, well-defined tumor margins (vs. poorly-defined margins) were significant associated with m1 subtype (odd ratio [OR] 2.104, P = .041).

Similarly, a combination of well-defined tumor margins (OR 2.104, P = .013), no collecting system invasion (OR 0.421, P = .028), and renal vein invasion (OR 2.164, P = .026) were significantly associated with the m3 subtype.

They were no significant associations between CT imaging features and either the m2 or m4 subtypes, the authors found.

The authors did not report study funding sources or potential conflicts of interest.

SOURCE: Bowen L, Xiaojing L. Acad Radiol. doi: 10.1016/j.acra.2018.05.002.

When I grow up, I want to be a fireman. Not long ago, I had occasion to revisit why firefighters are such heroes to young and old. In the process, I learned quite a bit about how fires are managed and realized that a really good surgeon has much in common with a fire Incident Commander.

Gilitukha/Thinkstock

In late June 2018, a man started a fire in Southern Colorado. That small campfire became the Spring Fire, the third-largest forest fire in Colorado history, which is saying a lot. By the time the fire was mostly contained 2 weeks later, 175 square miles of land had been burned and 1,800 firefighters were involved in the disaster. More than 150 homes were destroyed. Not one person died in or as a result of this fire. Only the most grudging of critics would deny that, while the fire itself was a disaster, the response and outcome constituted a good definition of success.

This story was more than just 30 seconds on the nightly news to me because I was one of the people whose property and 32 years of precious family memories were in danger. I clung to any news of the fire. My own daughter had to evacuate our place there when smoke and flame were visible just a few miles away. I was helpless to do anything but hoped that somehow this conflagration could be stopped.

Within 48 hours, Rocky Mountain Black Team – headed by a man named Shane Greer – arrived in the area. Mr. Greer is the Incident Commander of the Black Team. Over the next 10 days he was the personification of the response to the Spring Fire. He was the main person carrying the overall responsibility for controlling the fire.

The fire is over now, but I reflect frequently on the parallels between surgery and firefighting. I identified with Mr. Greer as probably many did. He didn’t actually stop the fire, but he led the people who did. I was intrigued by this role and I did a little research in fire Incident Commanders. Here’s a list of their numerous roles and responsibilities that I gleaned from an article on the website Firehouse by editor Dennis Rubin from several years ago:
 

• The Incident Commander (IC) must be a qualified, single, central, and well-supported individual.
• The IC’s main concern is safety of lives and must be conversant in fire-safety procedures.
• The IC must have an understanding of his/her personal limitations. An IC must have firsthand experience at firefighting so that the IC is an individual well informed of the difficulties being experienced on the front line of the fire.
• The priorities of the IC are a) life safety; b) incident stabilization; and c) property conservation.
• The IC develops strategies (what to do) and tactics (how to do it) and follows action plans to achieve these goals.
• The IC develops a management structure that uses span of control (one supervisor per five subordinates) with each unit having a single boss.
• A good IC is a good delegator and calls for help early in the incident including placement of resources in staging areas.
• The IC is responsible for all communication among the team and to the media/public.
• The IC coordinates with outside agencies.

Does this sound familiar to you? Substitute surgeon for IC and you have today’s profile of a good surgeon. When executed well, everyone involved in an incident gets to be a hero and feels a part of something bigger than themselves. The IC (surgeon) gets a lot of credit, but that person also makes sure the whole team gets all the credit and thanks they deserve.

What I see happening in some situations is that we in medicine are putting the wrong ICs in charge or abdicating our positions as IC to others because being an IC is a hard, demanding, full-time job. I also see medicine violating the principles in the first bullet point above – a single, central, and well-supported individual. We get the job of IC and then payers, administrators, and outside agencies drop the support part of the ball. We also have a tendency to violate the “qualified” part of the job description. Someone who has put on the gown and gloves and borne the responsibility of operating should be the quarterback and not someone who has only observed that process.

I can’t thank enough the Black Team and all those who fought the Spring Fire. I hope we all aspire to be ICs in our surgical world. There is a great nobility in such professions as firefighting and surgery, where we jump in to help others who can’t help themselves. The Black Team showed that to me and my community in Colorado. It makes one proud of what we human beings can do when we decide to work together.

True leadership and teamwork do not fragment but instead pull resources together. Patients need that. They need to know that a qualified, single, central, and well-supported person is directing their incident. The existence of such a person fulfilling that role is key to keep the trust that the public places in us. May all our “fires” be led by a good surgeon, er, Incident Commander surgeon.

Dr. Hughes is clinical professor in the department of surgery and director of medical education at the Kansas University School of Medicine, Salina Campus, and Co-Editor of ACS Surgery News.

When I grow up, I want to be a fireman. Not long ago, I had occasion to revisit why firefighters are such heroes to young and old. In the process, I learned quite a bit about how fires are managed and realized that a really good surgeon has much in common with a fire Incident Commander.

Gilitukha/Thinkstock

In late June 2018, a man started a fire in Southern Colorado. That small campfire became the Spring Fire, the third-largest forest fire in Colorado history, which is saying a lot. By the time the fire was mostly contained 2 weeks later, 175 square miles of land had been burned and 1,800 firefighters were involved in the disaster. More than 150 homes were destroyed. Not one person died in or as a result of this fire. Only the most grudging of critics would deny that, while the fire itself was a disaster, the response and outcome constituted a good definition of success.

This story was more than just 30 seconds on the nightly news to me because I was one of the people whose property and 32 years of precious family memories were in danger. I clung to any news of the fire. My own daughter had to evacuate our place there when smoke and flame were visible just a few miles away. I was helpless to do anything but hoped that somehow this conflagration could be stopped.

Within 48 hours, Rocky Mountain Black Team – headed by a man named Shane Greer – arrived in the area. Mr. Greer is the Incident Commander of the Black Team. Over the next 10 days he was the personification of the response to the Spring Fire. He was the main person carrying the overall responsibility for controlling the fire.

The fire is over now, but I reflect frequently on the parallels between surgery and firefighting. I identified with Mr. Greer as probably many did. He didn’t actually stop the fire, but he led the people who did. I was intrigued by this role and I did a little research in fire Incident Commanders. Here’s a list of their numerous roles and responsibilities that I gleaned from an article on the website Firehouse by editor Dennis Rubin from several years ago:
 

• The Incident Commander (IC) must be a qualified, single, central, and well-supported individual.
• The IC’s main concern is safety of lives and must be conversant in fire-safety procedures.
• The IC must have an understanding of his/her personal limitations. An IC must have firsthand experience at firefighting so that the IC is an individual well informed of the difficulties being experienced on the front line of the fire.
• The priorities of the IC are a) life safety; b) incident stabilization; and c) property conservation.
• The IC develops strategies (what to do) and tactics (how to do it) and follows action plans to achieve these goals.
• The IC develops a management structure that uses span of control (one supervisor per five subordinates) with each unit having a single boss.
• A good IC is a good delegator and calls for help early in the incident including placement of resources in staging areas.
• The IC is responsible for all communication among the team and to the media/public.
• The IC coordinates with outside agencies.

Does this sound familiar to you? Substitute surgeon for IC and you have today’s profile of a good surgeon. When executed well, everyone involved in an incident gets to be a hero and feels a part of something bigger than themselves. The IC (surgeon) gets a lot of credit, but that person also makes sure the whole team gets all the credit and thanks they deserve.

What I see happening in some situations is that we in medicine are putting the wrong ICs in charge or abdicating our positions as IC to others because being an IC is a hard, demanding, full-time job. I also see medicine violating the principles in the first bullet point above – a single, central, and well-supported individual. We get the job of IC and then payers, administrators, and outside agencies drop the support part of the ball. We also have a tendency to violate the “qualified” part of the job description. Someone who has put on the gown and gloves and borne the responsibility of operating should be the quarterback and not someone who has only observed that process.

I can’t thank enough the Black Team and all those who fought the Spring Fire. I hope we all aspire to be ICs in our surgical world. There is a great nobility in such professions as firefighting and surgery, where we jump in to help others who can’t help themselves. The Black Team showed that to me and my community in Colorado. It makes one proud of what we human beings can do when we decide to work together.

True leadership and teamwork do not fragment but instead pull resources together. Patients need that. They need to know that a qualified, single, central, and well-supported person is directing their incident. The existence of such a person fulfilling that role is key to keep the trust that the public places in us. May all our “fires” be led by a good surgeon, er, Incident Commander surgeon.

Dr. Hughes is clinical professor in the department of surgery and director of medical education at the Kansas University School of Medicine, Salina Campus, and Co-Editor of ACS Surgery News.

When I grow up, I want to be a fireman. Not long ago, I had occasion to revisit why firefighters are such heroes to young and old. In the process, I learned quite a bit about how fires are managed and realized that a really good surgeon has much in common with a fire Incident Commander.

Gilitukha/Thinkstock

In late June 2018, a man started a fire in Southern Colorado. That small campfire became the Spring Fire, the third-largest forest fire in Colorado history, which is saying a lot. By the time the fire was mostly contained 2 weeks later, 175 square miles of land had been burned and 1,800 firefighters were involved in the disaster. More than 150 homes were destroyed. Not one person died in or as a result of this fire. Only the most grudging of critics would deny that, while the fire itself was a disaster, the response and outcome constituted a good definition of success.

This story was more than just 30 seconds on the nightly news to me because I was one of the people whose property and 32 years of precious family memories were in danger. I clung to any news of the fire. My own daughter had to evacuate our place there when smoke and flame were visible just a few miles away. I was helpless to do anything but hoped that somehow this conflagration could be stopped.

Within 48 hours, Rocky Mountain Black Team – headed by a man named Shane Greer – arrived in the area. Mr. Greer is the Incident Commander of the Black Team. Over the next 10 days he was the personification of the response to the Spring Fire. He was the main person carrying the overall responsibility for controlling the fire.

The fire is over now, but I reflect frequently on the parallels between surgery and firefighting. I identified with Mr. Greer as probably many did. He didn’t actually stop the fire, but he led the people who did. I was intrigued by this role and I did a little research in fire Incident Commanders. Here’s a list of their numerous roles and responsibilities that I gleaned from an article on the website Firehouse by editor Dennis Rubin from several years ago:
 

• The Incident Commander (IC) must be a qualified, single, central, and well-supported individual.
• The IC’s main concern is safety of lives and must be conversant in fire-safety procedures.
• The IC must have an understanding of his/her personal limitations. An IC must have firsthand experience at firefighting so that the IC is an individual well informed of the difficulties being experienced on the front line of the fire.
• The priorities of the IC are a) life safety; b) incident stabilization; and c) property conservation.
• The IC develops strategies (what to do) and tactics (how to do it) and follows action plans to achieve these goals.
• The IC develops a management structure that uses span of control (one supervisor per five subordinates) with each unit having a single boss.
• A good IC is a good delegator and calls for help early in the incident including placement of resources in staging areas.
• The IC is responsible for all communication among the team and to the media/public.
• The IC coordinates with outside agencies.

Does this sound familiar to you? Substitute surgeon for IC and you have today’s profile of a good surgeon. When executed well, everyone involved in an incident gets to be a hero and feels a part of something bigger than themselves. The IC (surgeon) gets a lot of credit, but that person also makes sure the whole team gets all the credit and thanks they deserve.

What I see happening in some situations is that we in medicine are putting the wrong ICs in charge or abdicating our positions as IC to others because being an IC is a hard, demanding, full-time job. I also see medicine violating the principles in the first bullet point above – a single, central, and well-supported individual. We get the job of IC and then payers, administrators, and outside agencies drop the support part of the ball. We also have a tendency to violate the “qualified” part of the job description. Someone who has put on the gown and gloves and borne the responsibility of operating should be the quarterback and not someone who has only observed that process.

I can’t thank enough the Black Team and all those who fought the Spring Fire. I hope we all aspire to be ICs in our surgical world. There is a great nobility in such professions as firefighting and surgery, where we jump in to help others who can’t help themselves. The Black Team showed that to me and my community in Colorado. It makes one proud of what we human beings can do when we decide to work together.

True leadership and teamwork do not fragment but instead pull resources together. Patients need that. They need to know that a qualified, single, central, and well-supported person is directing their incident. The existence of such a person fulfilling that role is key to keep the trust that the public places in us. May all our “fires” be led by a good surgeon, er, Incident Commander surgeon.

Dr. Hughes is clinical professor in the department of surgery and director of medical education at the Kansas University School of Medicine, Salina Campus, and Co-Editor of ACS Surgery News.

The International Relations Committee of the American College of Surgeons (ACS) sponsors three academic surgeon exchange programs to send a talented young U.S. or Canadian Fellow to the annual surgical meeting of each participating country. Afterwards, the Fellows tour several sites tailored to their specific research interests. In exchange, the College accepts fine young academic surgeon-scholars from the participating societies to attend the annual ACS Clinical Congress. This exchange is with the Royal Australasian College of Surgeons with the ACS Australia-New Zealand Chapter, the Japan Surgical Society with the ACS Japan Chapter, and the German Surgical Society with the ACS Germany Chapter.

The 2018 ANZ Exchange Fellow is Yiu Ming Ho, MB, BS, MS, FRACS, a general and colorectal surgeon University of Sydney, Australia. His recent research has been on examining personalized radiation therapy for low-risk early breast cancer. His U.S. counterpart, Mayur B. Patel, MD, MPH, FACS, is associate professor of surgery, Vanderbilt University Medical Center, TN, specializing in neurotrauma and traumatic brain injury. He attended the Annual Scientific Congress of the Royal Australasian College of Surgeons held in Sydney, Australia, in May.

The International Relations Committee of the American College of Surgeons (ACS) sponsors three academic surgeon exchange programs to send a talented young U.S. or Canadian Fellow to the annual surgical meeting of each participating country. Afterwards, the Fellows tour several sites tailored to their specific research interests. In exchange, the College accepts fine young academic surgeon-scholars from the participating societies to attend the annual ACS Clinical Congress. This exchange is with the Royal Australasian College of Surgeons with the ACS Australia-New Zealand Chapter, the Japan Surgical Society with the ACS Japan Chapter, and the German Surgical Society with the ACS Germany Chapter.

The 2018 ANZ Exchange Fellow is Yiu Ming Ho, MB, BS, MS, FRACS, a general and colorectal surgeon University of Sydney, Australia. His recent research has been on examining personalized radiation therapy for low-risk early breast cancer. His U.S. counterpart, Mayur B. Patel, MD, MPH, FACS, is associate professor of surgery, Vanderbilt University Medical Center, TN, specializing in neurotrauma and traumatic brain injury. He attended the Annual Scientific Congress of the Royal Australasian College of Surgeons held in Sydney, Australia, in May.

The International Relations Committee of the American College of Surgeons (ACS) sponsors three academic surgeon exchange programs to send a talented young U.S. or Canadian Fellow to the annual surgical meeting of each participating country. Afterwards, the Fellows tour several sites tailored to their specific research interests. In exchange, the College accepts fine young academic surgeon-scholars from the participating societies to attend the annual ACS Clinical Congress. This exchange is with the Royal Australasian College of Surgeons with the ACS Australia-New Zealand Chapter, the Japan Surgical Society with the ACS Japan Chapter, and the German Surgical Society with the ACS Germany Chapter.

The 2018 ANZ Exchange Fellow is Yiu Ming Ho, MB, BS, MS, FRACS, a general and colorectal surgeon University of Sydney, Australia. His recent research has been on examining personalized radiation therapy for low-risk early breast cancer. His U.S. counterpart, Mayur B. Patel, MD, MPH, FACS, is associate professor of surgery, Vanderbilt University Medical Center, TN, specializing in neurotrauma and traumatic brain injury. He attended the Annual Scientific Congress of the Royal Australasian College of Surgeons held in Sydney, Australia, in May.

The Commission on Cancer (CoC) of the American College of Surgeons (ACS) has granted its year-end 2017 Outstanding Achievement Award to a select group of 16 accredited cancer programs throughout the U.S. Award criteria were based on qualitative and quantitative surveys of cancer programs conducted in the second half of 2017.

The purpose of the award is to raise the bar on quality cancer care, with the ultimate goal of increasing awareness about quality care choices among cancer patients and their loved ones. In addition, the award is intended to accomplish the following:

• Recognize those cancer programs that achieve excellence in providing quality care to cancer patients

• Motivate other cancer programs to work toward improving their level of care

• Facilitate a dialogue between award recipients and health care professionals at other cancer facilities for the purpose of sharing best practices

• Encourage honorees to serve as quality-care resources to other cancer programs

The 16 award-winning cancer care programs represent approximately 7 percent of programs surveyed by the CoC July 1–December 31, 2017. “These cancer programs currently represent the best of the best when it comes to cancer care,” said Lawrence N. Shulman, MD, FACP, Chair of the CoC. “Each of these facilities is not just meeting nationally recognized standards for the delivery of quality cancer care, they are exceeding them.”

Visit the ACS website for a list of these award-winning cancer programs at facs.org/quality-programs/cancer/coc/info/outstanding/2017-part-2.

The Commission on Cancer (CoC) of the American College of Surgeons (ACS) has granted its year-end 2017 Outstanding Achievement Award to a select group of 16 accredited cancer programs throughout the U.S. Award criteria were based on qualitative and quantitative surveys of cancer programs conducted in the second half of 2017.

The purpose of the award is to raise the bar on quality cancer care, with the ultimate goal of increasing awareness about quality care choices among cancer patients and their loved ones. In addition, the award is intended to accomplish the following:

• Recognize those cancer programs that achieve excellence in providing quality care to cancer patients

• Motivate other cancer programs to work toward improving their level of care

• Facilitate a dialogue between award recipients and health care professionals at other cancer facilities for the purpose of sharing best practices

• Encourage honorees to serve as quality-care resources to other cancer programs

The 16 award-winning cancer care programs represent approximately 7 percent of programs surveyed by the CoC July 1–December 31, 2017. “These cancer programs currently represent the best of the best when it comes to cancer care,” said Lawrence N. Shulman, MD, FACP, Chair of the CoC. “Each of these facilities is not just meeting nationally recognized standards for the delivery of quality cancer care, they are exceeding them.”

Visit the ACS website for a list of these award-winning cancer programs at facs.org/quality-programs/cancer/coc/info/outstanding/2017-part-2.

The Commission on Cancer (CoC) of the American College of Surgeons (ACS) has granted its year-end 2017 Outstanding Achievement Award to a select group of 16 accredited cancer programs throughout the U.S. Award criteria were based on qualitative and quantitative surveys of cancer programs conducted in the second half of 2017.

The purpose of the award is to raise the bar on quality cancer care, with the ultimate goal of increasing awareness about quality care choices among cancer patients and their loved ones. In addition, the award is intended to accomplish the following:

• Recognize those cancer programs that achieve excellence in providing quality care to cancer patients

• Motivate other cancer programs to work toward improving their level of care

• Facilitate a dialogue between award recipients and health care professionals at other cancer facilities for the purpose of sharing best practices

• Encourage honorees to serve as quality-care resources to other cancer programs

The 16 award-winning cancer care programs represent approximately 7 percent of programs surveyed by the CoC July 1–December 31, 2017. “These cancer programs currently represent the best of the best when it comes to cancer care,” said Lawrence N. Shulman, MD, FACP, Chair of the CoC. “Each of these facilities is not just meeting nationally recognized standards for the delivery of quality cancer care, they are exceeding them.”

Visit the ACS website for a list of these award-winning cancer programs at facs.org/quality-programs/cancer/coc/info/outstanding/2017-part-2.

The American College of Surgeons (ACS) presented the 2018 Jacobson Innovation Award to surgical oncologist Steven A. Rosenberg, MD, PhD, at a dinner held in his honor in Chicago, IL, on June 8. Dr. Rosenberg is chief of the surgery branch at the National Cancer Institute (NCI), part of the National Institutes of Health, in Bethesda, MD; and a professor of surgery at the Uniformed Services University of Health Sciences, Bethesda, and at the George Washington University School of Medicine and Health Sciences, Washington, DC.

The prestigious Jacobson Innovation Award honors living surgeons who have been innovators of a new development or technique in any field of surgery and is made possible through a gift from Julius H. Jacobson II, MD, FACS, and his wife Joan. Dr. Jacobson is a general vascular surgeon known for his pioneering work in the development of microsurgery.

Dr. Rosenberg was honored with this international surgical award for his pioneering role in the development of immunotherapy and gene therapy. When Dr. Rosenberg began his work in immunotherapy in the late 1970s, little was known about T lymphocyte function in cancer, and there was no convincing evidence that any immune reaction existed in patients against their cancers. Despite this dearth of knowledge, Dr. Rosenberg developed the first effective immunotherapies for selected patients with advanced cancer and was the first to successfully insert foreign genes into humans. His studies of cell transfer immunotherapy resulted in durable complete remissions in patients with metastatic melanoma. Additionally, his studies of the adoptive transfer of genetically modified lymphocytes resulted in the regression of metastatic cancer in patients with melanoma, sarcomas, and lymphomas.

In his current role at the NCI, Dr. Rosenberg oversees the surgery branch’s extensive clinical program, which is aimed at translating scientific advances into effective immunotherapies for cancer patients. Dr. Rosenberg’s current research is focused on defining the host immune response of patients to their cancers. These studies emphasize the ability of human lymphocytes to recognize unique cancer antigens and the identification of anti-tumor T cell receptors that can be exploited to develop new cell transfer immunotherapies for the treatment of cancer patients. Dr. Rosenberg is currently an investigator in 14 clinical trials being conducted through the NCI’s Center for Cancer Research.

Dr. Rosenberg has received numerous awards throughout his distinguished career. In 1981, he received a Meritorious Service Medal from the U.S. Public Health Service for pioneering work in the treatment of soft tissue sarcomas and osteogenic sarcoma. He received that honor again in 1986 for his excellence and leadership in research and clinical investigation relating to the cellular biology and immunology of cancer treatment. Dr. Rosenberg also twice received the Armand Hammer Cancer Prize, in 1985 and 1988, for his cancer research accomplishments. In 1991, he received the highest honor given by the American Society of Clinical Oncology, the Karnofsky Prize. He was awarded the Flance-Karl Award, the highest honor given by the American Surgical Association, in 2002. In 2005, he received the Richard V. Smalley, MD, Memorial Award, which is the highest honor given by the International Society for Biological Therapy of Cancer. Most recently, he was named the recipient of the Medal of Honor from the American Cancer Society in 2015.

Dr. Rosenberg is currently a member of the American Society of Clinical Oncology and has served on its board of directors. He also is a member of the National Academy of Medicine, the Society of University Surgeons, the American Surgical Association, the American Association for Cancer Research, and the American Association of Immunologists, among others. He has authored more than 1,100 articles in scientific literature covering various aspects of cancer research, as well as eight books. He was the editor-in-chief of the Journal of Immunotherapy from 1990 to 1995, and again from 2000 to the present.

For a list of previous Jacobson Innovation Award winners, visit the ACS website at facs.org/about-acs/ governance/acs-committees/honorscommittee/jacobson-list.

The American College of Surgeons (ACS) presented the 2018 Jacobson Innovation Award to surgical oncologist Steven A. Rosenberg, MD, PhD, at a dinner held in his honor in Chicago, IL, on June 8. Dr. Rosenberg is chief of the surgery branch at the National Cancer Institute (NCI), part of the National Institutes of Health, in Bethesda, MD; and a professor of surgery at the Uniformed Services University of Health Sciences, Bethesda, and at the George Washington University School of Medicine and Health Sciences, Washington, DC.

The prestigious Jacobson Innovation Award honors living surgeons who have been innovators of a new development or technique in any field of surgery and is made possible through a gift from Julius H. Jacobson II, MD, FACS, and his wife Joan. Dr. Jacobson is a general vascular surgeon known for his pioneering work in the development of microsurgery.

Dr. Rosenberg was honored with this international surgical award for his pioneering role in the development of immunotherapy and gene therapy. When Dr. Rosenberg began his work in immunotherapy in the late 1970s, little was known about T lymphocyte function in cancer, and there was no convincing evidence that any immune reaction existed in patients against their cancers. Despite this dearth of knowledge, Dr. Rosenberg developed the first effective immunotherapies for selected patients with advanced cancer and was the first to successfully insert foreign genes into humans. His studies of cell transfer immunotherapy resulted in durable complete remissions in patients with metastatic melanoma. Additionally, his studies of the adoptive transfer of genetically modified lymphocytes resulted in the regression of metastatic cancer in patients with melanoma, sarcomas, and lymphomas.

In his current role at the NCI, Dr. Rosenberg oversees the surgery branch’s extensive clinical program, which is aimed at translating scientific advances into effective immunotherapies for cancer patients. Dr. Rosenberg’s current research is focused on defining the host immune response of patients to their cancers. These studies emphasize the ability of human lymphocytes to recognize unique cancer antigens and the identification of anti-tumor T cell receptors that can be exploited to develop new cell transfer immunotherapies for the treatment of cancer patients. Dr. Rosenberg is currently an investigator in 14 clinical trials being conducted through the NCI’s Center for Cancer Research.

Dr. Rosenberg has received numerous awards throughout his distinguished career. In 1981, he received a Meritorious Service Medal from the U.S. Public Health Service for pioneering work in the treatment of soft tissue sarcomas and osteogenic sarcoma. He received that honor again in 1986 for his excellence and leadership in research and clinical investigation relating to the cellular biology and immunology of cancer treatment. Dr. Rosenberg also twice received the Armand Hammer Cancer Prize, in 1985 and 1988, for his cancer research accomplishments. In 1991, he received the highest honor given by the American Society of Clinical Oncology, the Karnofsky Prize. He was awarded the Flance-Karl Award, the highest honor given by the American Surgical Association, in 2002. In 2005, he received the Richard V. Smalley, MD, Memorial Award, which is the highest honor given by the International Society for Biological Therapy of Cancer. Most recently, he was named the recipient of the Medal of Honor from the American Cancer Society in 2015.

Dr. Rosenberg is currently a member of the American Society of Clinical Oncology and has served on its board of directors. He also is a member of the National Academy of Medicine, the Society of University Surgeons, the American Surgical Association, the American Association for Cancer Research, and the American Association of Immunologists, among others. He has authored more than 1,100 articles in scientific literature covering various aspects of cancer research, as well as eight books. He was the editor-in-chief of the Journal of Immunotherapy from 1990 to 1995, and again from 2000 to the present.

For a list of previous Jacobson Innovation Award winners, visit the ACS website at facs.org/about-acs/ governance/acs-committees/honorscommittee/jacobson-list.

The American College of Surgeons (ACS) presented the 2018 Jacobson Innovation Award to surgical oncologist Steven A. Rosenberg, MD, PhD, at a dinner held in his honor in Chicago, IL, on June 8. Dr. Rosenberg is chief of the surgery branch at the National Cancer Institute (NCI), part of the National Institutes of Health, in Bethesda, MD; and a professor of surgery at the Uniformed Services University of Health Sciences, Bethesda, and at the George Washington University School of Medicine and Health Sciences, Washington, DC.

The prestigious Jacobson Innovation Award honors living surgeons who have been innovators of a new development or technique in any field of surgery and is made possible through a gift from Julius H. Jacobson II, MD, FACS, and his wife Joan. Dr. Jacobson is a general vascular surgeon known for his pioneering work in the development of microsurgery.

Dr. Rosenberg was honored with this international surgical award for his pioneering role in the development of immunotherapy and gene therapy. When Dr. Rosenberg began his work in immunotherapy in the late 1970s, little was known about T lymphocyte function in cancer, and there was no convincing evidence that any immune reaction existed in patients against their cancers. Despite this dearth of knowledge, Dr. Rosenberg developed the first effective immunotherapies for selected patients with advanced cancer and was the first to successfully insert foreign genes into humans. His studies of cell transfer immunotherapy resulted in durable complete remissions in patients with metastatic melanoma. Additionally, his studies of the adoptive transfer of genetically modified lymphocytes resulted in the regression of metastatic cancer in patients with melanoma, sarcomas, and lymphomas.

In his current role at the NCI, Dr. Rosenberg oversees the surgery branch’s extensive clinical program, which is aimed at translating scientific advances into effective immunotherapies for cancer patients. Dr. Rosenberg’s current research is focused on defining the host immune response of patients to their cancers. These studies emphasize the ability of human lymphocytes to recognize unique cancer antigens and the identification of anti-tumor T cell receptors that can be exploited to develop new cell transfer immunotherapies for the treatment of cancer patients. Dr. Rosenberg is currently an investigator in 14 clinical trials being conducted through the NCI’s Center for Cancer Research.

Dr. Rosenberg has received numerous awards throughout his distinguished career. In 1981, he received a Meritorious Service Medal from the U.S. Public Health Service for pioneering work in the treatment of soft tissue sarcomas and osteogenic sarcoma. He received that honor again in 1986 for his excellence and leadership in research and clinical investigation relating to the cellular biology and immunology of cancer treatment. Dr. Rosenberg also twice received the Armand Hammer Cancer Prize, in 1985 and 1988, for his cancer research accomplishments. In 1991, he received the highest honor given by the American Society of Clinical Oncology, the Karnofsky Prize. He was awarded the Flance-Karl Award, the highest honor given by the American Surgical Association, in 2002. In 2005, he received the Richard V. Smalley, MD, Memorial Award, which is the highest honor given by the International Society for Biological Therapy of Cancer. Most recently, he was named the recipient of the Medal of Honor from the American Cancer Society in 2015.

Dr. Rosenberg is currently a member of the American Society of Clinical Oncology and has served on its board of directors. He also is a member of the National Academy of Medicine, the Society of University Surgeons, the American Surgical Association, the American Association for Cancer Research, and the American Association of Immunologists, among others. He has authored more than 1,100 articles in scientific literature covering various aspects of cancer research, as well as eight books. He was the editor-in-chief of the Journal of Immunotherapy from 1990 to 1995, and again from 2000 to the present.

For a list of previous Jacobson Innovation Award winners, visit the ACS website at facs.org/about-acs/ governance/acs-committees/honorscommittee/jacobson-list.

Photo by Larry Young

Mogamulizumab is an effective treatment option for relapsed/refractory cutaneous T-cell lymphoma (CTCL), according to researchers.

In the phase 3 MAVORIC trial, mogamulizumab prolonged progression-free survival (PFS) and produced better overall response rates (ORRs) than vorinostat in patients with relapsed/refractory CTCL.

The most common adverse events (AEs) in patients treated with mogamulizumab were infusion-related reactions, diarrhea, fatigue, and drug eruptions.

Youn Kim MD, of the Stanford Cancer Institute in Palo Alto, California, and her colleagues reported these results in The Lancet Oncology.

The results supported the recent approval of mogamulizumab by the US Food and Drug Administration.

The study was sponsored by Kyowa Hakko Kirin Co., Ltd., the company developing/marketing mogamulizumab.

Treatment

For MAVORIC, researchers compared mogamulizumab and vorinostat in adults with mycosis fungoides (MF) or Sézary syndrome (SS) who had received at least 1 prior systemic therapy.

The trial included 372 patients who were randomized to receive mogamulizumab at 1.0 mg/kg (weekly for the first cycle and then every 2 weeks) or vorinostat at 400 mg daily for 28-day cycles.

Patients were treated until disease progression or unacceptable toxicity. Patients on vorinostat who progressed or experienced intolerable toxicity after 2 cycles, despite dose reduction and appropriate management of AEs, could cross over to treatment with mogamulizumab.

There were 184 patients in the mogamulizumab arm and 186 in the vorinostat arm who received treatment.

The median duration of follow-up was 17.0 months.

Most patients (n=157) ultimately discontinued mogamulizumab. Reasons included:

• Disease progression (n=76 by CTCL criteria and 22 by clinical criteria)
• AEs (n=28)
• Withdrawn consent (n=13)
• Investigator decision (n=9)
• Patient decision (n=6)
• Death (n=2)
• Noncompliance (n=1).

Most patients (n=136) in the vorinostat arm crossed over to the mogamulizumab arm, 109 due to disease progression and 27 due to treatment intolerance.

Of the 40 patients who did not cross over to mogamulizumab, reasons for stopping vorinostat included:

• Progressive disease (n=10 by CTCL criteria and 8 by clinical criteria)
• Patient decision (n=9)
• Withdrawn consent (n=5)
• AEs (n=5)
• Death (n=2)
• Lost to follow-up (n=1).

At the data cutoff, there were 27 patients assigned to mogamulizumab and 10 assigned to vorinostat who remained on treatment. There were 31 patients still on treatment who had crossed over from vorinostat to mogamulizumab.

Patient characteristics

Baseline characteristics were similar between the treatment arms.

PFS and ORR

Mogamulizumab provided a significant improvement in PFS, the study’s primary endpoint.

According to investigators, the median PFS was 7.7 months with mogamulizumab and 3.1 months with vorinostat (hazard ratio=0.53, P<0.0001).

According to independent review, the median PFS was 6.7 months and 3.8 months, respectively (hazard ratio=0.64, P<0.0007).

There was a significant improvement in ORR with mogamulizumab.

According to independent review, the global ORR was 23% (43/186) in the mogamulizumab arm and 4% (7/186) in the vorinostat arm (risk ratio=19.4, P<0.0001).

According to investigators, the global ORR was 28% (52/186) and 5% (9/186), respectively (risk ratio=23.1, P<0.0001).

For patients with MF, the investigator-assessed ORR was 21% (22/105) with mogamulizumab and 7% (7/99) with vorinostat.

For SS patients, the investigator-assessed ORR was 37% (30/81) and 2% (2/87), respectively.

Responses by disease compartment were superior with mogamulizumab as well.

The investigator-assessed blood ORR was 68% (83/122) with mogamulizumab and 19% (23/123) with vorinostat. The skin ORR was 42% (78/186) and 16% (29/186), respectively.

The lymph node ORR was 17% (21/124) and 4% (5/122), respectively. The viscera ORR was 0% in both arms.

Crossover

Among patients who crossed over from vorinostat to mogamulizumab, the ORR was 31% (41/133). In these patients, the median PFS was 8.9 months.

In the 319 patients who were assigned to mogamulizumab or crossed over to that arm, the median PFS was 8.4 months.

Safety

The most common treatment-emergent, grade 1-2 AEs, occurring in at least 20% of patients in either arm (mogamulizumab and vorinostat, respectively), were:

• Thrombocytopenia (14% vs 34%)
• Diarrhea (23% vs 57%)
• Nausea (15% vs 41%)
• Fatigue (22% vs 32%)
• Increased blood creatinine (3% vs 28%)
• Decreased appetite (7% vs 24%)
• Dysgeusia (3% vs 28%)
• Drug eruptions (20% vs 1%)
• Infusion-related reactions (32% vs 1%).

Grade 3 AEs in the mogamulizumab arm included drug eruptions (n=8), hypertension (n=8), pneumonia (n=6), fatigue (n=3), cellulitis (n=3), infusion-related reactions (n=3), sepsis (n=2), decreased appetite (n=2), AST increase (n=2), weight decrease (n=1), pyrexia (n=1), constipation (n=1), nausea (n=1), and diarrhea (n=1).

Grade 4 AEs with mogamulizumab were cellulitis (n=1) and pneumonia (n=1). Grade 5 AEs included pneumonia (n=1) and sepsis (n=1).

Photo by Larry Young

Mogamulizumab is an effective treatment option for relapsed/refractory cutaneous T-cell lymphoma (CTCL), according to researchers.

In the phase 3 MAVORIC trial, mogamulizumab prolonged progression-free survival (PFS) and produced better overall response rates (ORRs) than vorinostat in patients with relapsed/refractory CTCL.

The most common adverse events (AEs) in patients treated with mogamulizumab were infusion-related reactions, diarrhea, fatigue, and drug eruptions.

Youn Kim MD, of the Stanford Cancer Institute in Palo Alto, California, and her colleagues reported these results in The Lancet Oncology.

The results supported the recent approval of mogamulizumab by the US Food and Drug Administration.

The study was sponsored by Kyowa Hakko Kirin Co., Ltd., the company developing/marketing mogamulizumab.

Treatment

For MAVORIC, researchers compared mogamulizumab and vorinostat in adults with mycosis fungoides (MF) or Sézary syndrome (SS) who had received at least 1 prior systemic therapy.

The trial included 372 patients who were randomized to receive mogamulizumab at 1.0 mg/kg (weekly for the first cycle and then every 2 weeks) or vorinostat at 400 mg daily for 28-day cycles.

Patients were treated until disease progression or unacceptable toxicity. Patients on vorinostat who progressed or experienced intolerable toxicity after 2 cycles, despite dose reduction and appropriate management of AEs, could cross over to treatment with mogamulizumab.

There were 184 patients in the mogamulizumab arm and 186 in the vorinostat arm who received treatment.

The median duration of follow-up was 17.0 months.

Most patients (n=157) ultimately discontinued mogamulizumab. Reasons included:

• Disease progression (n=76 by CTCL criteria and 22 by clinical criteria)
• AEs (n=28)
• Withdrawn consent (n=13)
• Investigator decision (n=9)
• Patient decision (n=6)
• Death (n=2)
• Noncompliance (n=1).

Most patients (n=136) in the vorinostat arm crossed over to the mogamulizumab arm, 109 due to disease progression and 27 due to treatment intolerance.

Of the 40 patients who did not cross over to mogamulizumab, reasons for stopping vorinostat included:

• Progressive disease (n=10 by CTCL criteria and 8 by clinical criteria)
• Patient decision (n=9)
• Withdrawn consent (n=5)
• AEs (n=5)
• Death (n=2)
• Lost to follow-up (n=1).

At the data cutoff, there were 27 patients assigned to mogamulizumab and 10 assigned to vorinostat who remained on treatment. There were 31 patients still on treatment who had crossed over from vorinostat to mogamulizumab.

Patient characteristics

Baseline characteristics were similar between the treatment arms.

PFS and ORR

Mogamulizumab provided a significant improvement in PFS, the study’s primary endpoint.

According to investigators, the median PFS was 7.7 months with mogamulizumab and 3.1 months with vorinostat (hazard ratio=0.53, P<0.0001).

According to independent review, the median PFS was 6.7 months and 3.8 months, respectively (hazard ratio=0.64, P<0.0007).

There was a significant improvement in ORR with mogamulizumab.

According to independent review, the global ORR was 23% (43/186) in the mogamulizumab arm and 4% (7/186) in the vorinostat arm (risk ratio=19.4, P<0.0001).

According to investigators, the global ORR was 28% (52/186) and 5% (9/186), respectively (risk ratio=23.1, P<0.0001).

For patients with MF, the investigator-assessed ORR was 21% (22/105) with mogamulizumab and 7% (7/99) with vorinostat.

For SS patients, the investigator-assessed ORR was 37% (30/81) and 2% (2/87), respectively.

Responses by disease compartment were superior with mogamulizumab as well.

The investigator-assessed blood ORR was 68% (83/122) with mogamulizumab and 19% (23/123) with vorinostat. The skin ORR was 42% (78/186) and 16% (29/186), respectively.

The lymph node ORR was 17% (21/124) and 4% (5/122), respectively. The viscera ORR was 0% in both arms.

Crossover

Among patients who crossed over from vorinostat to mogamulizumab, the ORR was 31% (41/133). In these patients, the median PFS was 8.9 months.

In the 319 patients who were assigned to mogamulizumab or crossed over to that arm, the median PFS was 8.4 months.

Safety

The most common treatment-emergent, grade 1-2 AEs, occurring in at least 20% of patients in either arm (mogamulizumab and vorinostat, respectively), were:

• Thrombocytopenia (14% vs 34%)
• Diarrhea (23% vs 57%)
• Nausea (15% vs 41%)
• Fatigue (22% vs 32%)
• Increased blood creatinine (3% vs 28%)
• Decreased appetite (7% vs 24%)
• Dysgeusia (3% vs 28%)
• Drug eruptions (20% vs 1%)
• Infusion-related reactions (32% vs 1%).

Grade 3 AEs in the mogamulizumab arm included drug eruptions (n=8), hypertension (n=8), pneumonia (n=6), fatigue (n=3), cellulitis (n=3), infusion-related reactions (n=3), sepsis (n=2), decreased appetite (n=2), AST increase (n=2), weight decrease (n=1), pyrexia (n=1), constipation (n=1), nausea (n=1), and diarrhea (n=1).

Grade 4 AEs with mogamulizumab were cellulitis (n=1) and pneumonia (n=1). Grade 5 AEs included pneumonia (n=1) and sepsis (n=1).

Photo by Larry Young

Mogamulizumab is an effective treatment option for relapsed/refractory cutaneous T-cell lymphoma (CTCL), according to researchers.

In the phase 3 MAVORIC trial, mogamulizumab prolonged progression-free survival (PFS) and produced better overall response rates (ORRs) than vorinostat in patients with relapsed/refractory CTCL.

The most common adverse events (AEs) in patients treated with mogamulizumab were infusion-related reactions, diarrhea, fatigue, and drug eruptions.

Youn Kim MD, of the Stanford Cancer Institute in Palo Alto, California, and her colleagues reported these results in The Lancet Oncology.

The results supported the recent approval of mogamulizumab by the US Food and Drug Administration.

The study was sponsored by Kyowa Hakko Kirin Co., Ltd., the company developing/marketing mogamulizumab.

Treatment

For MAVORIC, researchers compared mogamulizumab and vorinostat in adults with mycosis fungoides (MF) or Sézary syndrome (SS) who had received at least 1 prior systemic therapy.

The trial included 372 patients who were randomized to receive mogamulizumab at 1.0 mg/kg (weekly for the first cycle and then every 2 weeks) or vorinostat at 400 mg daily for 28-day cycles.

Patients were treated until disease progression or unacceptable toxicity. Patients on vorinostat who progressed or experienced intolerable toxicity after 2 cycles, despite dose reduction and appropriate management of AEs, could cross over to treatment with mogamulizumab.

There were 184 patients in the mogamulizumab arm and 186 in the vorinostat arm who received treatment.

The median duration of follow-up was 17.0 months.

Most patients (n=157) ultimately discontinued mogamulizumab. Reasons included:

• Disease progression (n=76 by CTCL criteria and 22 by clinical criteria)
• AEs (n=28)
• Withdrawn consent (n=13)
• Investigator decision (n=9)
• Patient decision (n=6)
• Death (n=2)
• Noncompliance (n=1).

Most patients (n=136) in the vorinostat arm crossed over to the mogamulizumab arm, 109 due to disease progression and 27 due to treatment intolerance.

Of the 40 patients who did not cross over to mogamulizumab, reasons for stopping vorinostat included:

• Progressive disease (n=10 by CTCL criteria and 8 by clinical criteria)
• Patient decision (n=9)
• Withdrawn consent (n=5)
• AEs (n=5)
• Death (n=2)
• Lost to follow-up (n=1).

At the data cutoff, there were 27 patients assigned to mogamulizumab and 10 assigned to vorinostat who remained on treatment. There were 31 patients still on treatment who had crossed over from vorinostat to mogamulizumab.

Patient characteristics

Baseline characteristics were similar between the treatment arms.

PFS and ORR

Mogamulizumab provided a significant improvement in PFS, the study’s primary endpoint.

According to investigators, the median PFS was 7.7 months with mogamulizumab and 3.1 months with vorinostat (hazard ratio=0.53, P<0.0001).

According to independent review, the median PFS was 6.7 months and 3.8 months, respectively (hazard ratio=0.64, P<0.0007).

There was a significant improvement in ORR with mogamulizumab.

According to independent review, the global ORR was 23% (43/186) in the mogamulizumab arm and 4% (7/186) in the vorinostat arm (risk ratio=19.4, P<0.0001).

According to investigators, the global ORR was 28% (52/186) and 5% (9/186), respectively (risk ratio=23.1, P<0.0001).

For patients with MF, the investigator-assessed ORR was 21% (22/105) with mogamulizumab and 7% (7/99) with vorinostat.

For SS patients, the investigator-assessed ORR was 37% (30/81) and 2% (2/87), respectively.

Responses by disease compartment were superior with mogamulizumab as well.

The investigator-assessed blood ORR was 68% (83/122) with mogamulizumab and 19% (23/123) with vorinostat. The skin ORR was 42% (78/186) and 16% (29/186), respectively.

The lymph node ORR was 17% (21/124) and 4% (5/122), respectively. The viscera ORR was 0% in both arms.

Crossover

Among patients who crossed over from vorinostat to mogamulizumab, the ORR was 31% (41/133). In these patients, the median PFS was 8.9 months.

In the 319 patients who were assigned to mogamulizumab or crossed over to that arm, the median PFS was 8.4 months.

Safety

The most common treatment-emergent, grade 1-2 AEs, occurring in at least 20% of patients in either arm (mogamulizumab and vorinostat, respectively), were:

• Thrombocytopenia (14% vs 34%)
• Diarrhea (23% vs 57%)
• Nausea (15% vs 41%)
• Fatigue (22% vs 32%)
• Increased blood creatinine (3% vs 28%)
• Decreased appetite (7% vs 24%)
• Dysgeusia (3% vs 28%)
• Drug eruptions (20% vs 1%)
• Infusion-related reactions (32% vs 1%).

Grade 3 AEs in the mogamulizumab arm included drug eruptions (n=8), hypertension (n=8), pneumonia (n=6), fatigue (n=3), cellulitis (n=3), infusion-related reactions (n=3), sepsis (n=2), decreased appetite (n=2), AST increase (n=2), weight decrease (n=1), pyrexia (n=1), constipation (n=1), nausea (n=1), and diarrhea (n=1).

Grade 4 AEs with mogamulizumab were cellulitis (n=1) and pneumonia (n=1). Grade 5 AEs included pneumonia (n=1) and sepsis (n=1).

Photo by Luis Alvaz

Patients undergoing autologous hematopoietic stem cell transplant (auto-HSCT) for lymphoma or myeloma have an increased risk of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), according to a retrospective study.

The study suggested these patients have 10 to 100 times the risk of AML or MDS as the general population.

The elevated risk also exceeds that of similar lymphoma and myeloma patients largely untreated with auto-HSCT.

Tomas Radivoyevitch, PhD, of the Cleveland Clinic Foundation in Ohio, and his colleagues reported these findings in Leukemia Research.

The investigators noted that exposure to DNA-damaging drugs and ionizing radiation—both used in auto-HSCT—is known to increase the risk of AML and MDS.

With this in mind, the team analyzed data on auto-HSCT recipients reported to the Center for International Blood and Marrow Transplant Research (CIBMTR).

Analyses were based on 9028 patients undergoing auto-HSCT from 1995 to 2010 for Hodgkin lymphoma (n=916), non-Hodgkin lymphoma (NHL, n=3546), or plasma cell myeloma (n=4566). Their median duration of follow-up was 90 months, 110 months, and 97 months, respectively.

Overall, 3.7% of the cohort developed AML or MDS after their transplant.

More aggressive transplant protocols increased the likelihood of this outcome. The risk of developing AML or MDS was higher for:

• Hodgkin lymphoma patients who received conditioning with total body radiation versus chemotherapy alone (hazard ratio [HR], 4.0)
• NHL patients who received conditioning with total body radiation (HR, 1.7) or with busulfan and melphalan or cyclophosphamide (HR, 1.8) versus the BEAM regimen (bischloroethylnitrosourea, etoposide, cytarabine, and melphalan)
• NHL or myeloma patients who received 3 or more lines of chemotherapy versus 1 line (HR, 1.9 for NHL and 1.8 for myeloma)
• NHL patients who underwent transplant in 2005 to 2010 versus 1995 to 1999 (HR, 2.1).

Patients reported to the Surveillance, Epidemiology and End Results database with the same lymphoma and myeloma diagnoses, few of whom underwent auto-HSCT, had risks of AML and MDS that were 5 to 10 times higher than the background level in the population.

However, the study auto-HSCT cohort had a risk of AML that was 10 to 50 times higher and a relative risk of MDS that was roughly 100 times higher than the background level.

“These increases may be related to exposure to high doses of DNA-damaging drugs given for [auto-HSCT], but this hypothesis can only be tested in a prospective study,” Dr Radivoyevitch and his coinvestigators wrote.

The reason for the greater elevation of MDS risk, compared with AML risk, is unknown.

“One possible explanation is that many cases of MDS evolve to AML, and that earlier diagnosis from increased post-transplant surveillance resulted in a deficiency of AML,” the investigators wrote. “A second is based on steeper MDS versus AML incidences versus age . . . and the possibility that transplantation recipient marrow ages (ie, marrow biological ages) are perhaps decades older than calendar ages.”

The study authors said they had no relevant conflicts of interest. The CIBMTR is supported by several US government agencies and numerous pharmaceutical companies. 

Photo by Luis Alvaz

Patients undergoing autologous hematopoietic stem cell transplant (auto-HSCT) for lymphoma or myeloma have an increased risk of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), according to a retrospective study.

The study suggested these patients have 10 to 100 times the risk of AML or MDS as the general population.

The elevated risk also exceeds that of similar lymphoma and myeloma patients largely untreated with auto-HSCT.

Tomas Radivoyevitch, PhD, of the Cleveland Clinic Foundation in Ohio, and his colleagues reported these findings in Leukemia Research.

The investigators noted that exposure to DNA-damaging drugs and ionizing radiation—both used in auto-HSCT—is known to increase the risk of AML and MDS.

With this in mind, the team analyzed data on auto-HSCT recipients reported to the Center for International Blood and Marrow Transplant Research (CIBMTR).

Analyses were based on 9028 patients undergoing auto-HSCT from 1995 to 2010 for Hodgkin lymphoma (n=916), non-Hodgkin lymphoma (NHL, n=3546), or plasma cell myeloma (n=4566). Their median duration of follow-up was 90 months, 110 months, and 97 months, respectively.

Overall, 3.7% of the cohort developed AML or MDS after their transplant.

More aggressive transplant protocols increased the likelihood of this outcome. The risk of developing AML or MDS was higher for:

• Hodgkin lymphoma patients who received conditioning with total body radiation versus chemotherapy alone (hazard ratio [HR], 4.0)
• NHL patients who received conditioning with total body radiation (HR, 1.7) or with busulfan and melphalan or cyclophosphamide (HR, 1.8) versus the BEAM regimen (bischloroethylnitrosourea, etoposide, cytarabine, and melphalan)
• NHL or myeloma patients who received 3 or more lines of chemotherapy versus 1 line (HR, 1.9 for NHL and 1.8 for myeloma)
• NHL patients who underwent transplant in 2005 to 2010 versus 1995 to 1999 (HR, 2.1).

Patients reported to the Surveillance, Epidemiology and End Results database with the same lymphoma and myeloma diagnoses, few of whom underwent auto-HSCT, had risks of AML and MDS that were 5 to 10 times higher than the background level in the population.

However, the study auto-HSCT cohort had a risk of AML that was 10 to 50 times higher and a relative risk of MDS that was roughly 100 times higher than the background level.

“These increases may be related to exposure to high doses of DNA-damaging drugs given for [auto-HSCT], but this hypothesis can only be tested in a prospective study,” Dr Radivoyevitch and his coinvestigators wrote.

The reason for the greater elevation of MDS risk, compared with AML risk, is unknown.

“One possible explanation is that many cases of MDS evolve to AML, and that earlier diagnosis from increased post-transplant surveillance resulted in a deficiency of AML,” the investigators wrote. “A second is based on steeper MDS versus AML incidences versus age . . . and the possibility that transplantation recipient marrow ages (ie, marrow biological ages) are perhaps decades older than calendar ages.”

The study authors said they had no relevant conflicts of interest. The CIBMTR is supported by several US government agencies and numerous pharmaceutical companies. 

Photo by Luis Alvaz

Patients undergoing autologous hematopoietic stem cell transplant (auto-HSCT) for lymphoma or myeloma have an increased risk of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), according to a retrospective study.

The study suggested these patients have 10 to 100 times the risk of AML or MDS as the general population.

The elevated risk also exceeds that of similar lymphoma and myeloma patients largely untreated with auto-HSCT.

Tomas Radivoyevitch, PhD, of the Cleveland Clinic Foundation in Ohio, and his colleagues reported these findings in Leukemia Research.

The investigators noted that exposure to DNA-damaging drugs and ionizing radiation—both used in auto-HSCT—is known to increase the risk of AML and MDS.

With this in mind, the team analyzed data on auto-HSCT recipients reported to the Center for International Blood and Marrow Transplant Research (CIBMTR).

Analyses were based on 9028 patients undergoing auto-HSCT from 1995 to 2010 for Hodgkin lymphoma (n=916), non-Hodgkin lymphoma (NHL, n=3546), or plasma cell myeloma (n=4566). Their median duration of follow-up was 90 months, 110 months, and 97 months, respectively.

Overall, 3.7% of the cohort developed AML or MDS after their transplant.

More aggressive transplant protocols increased the likelihood of this outcome. The risk of developing AML or MDS was higher for:

• Hodgkin lymphoma patients who received conditioning with total body radiation versus chemotherapy alone (hazard ratio [HR], 4.0)
• NHL patients who received conditioning with total body radiation (HR, 1.7) or with busulfan and melphalan or cyclophosphamide (HR, 1.8) versus the BEAM regimen (bischloroethylnitrosourea, etoposide, cytarabine, and melphalan)
• NHL or myeloma patients who received 3 or more lines of chemotherapy versus 1 line (HR, 1.9 for NHL and 1.8 for myeloma)
• NHL patients who underwent transplant in 2005 to 2010 versus 1995 to 1999 (HR, 2.1).

Patients reported to the Surveillance, Epidemiology and End Results database with the same lymphoma and myeloma diagnoses, few of whom underwent auto-HSCT, had risks of AML and MDS that were 5 to 10 times higher than the background level in the population.

However, the study auto-HSCT cohort had a risk of AML that was 10 to 50 times higher and a relative risk of MDS that was roughly 100 times higher than the background level.

“These increases may be related to exposure to high doses of DNA-damaging drugs given for [auto-HSCT], but this hypothesis can only be tested in a prospective study,” Dr Radivoyevitch and his coinvestigators wrote.

The reason for the greater elevation of MDS risk, compared with AML risk, is unknown.

“One possible explanation is that many cases of MDS evolve to AML, and that earlier diagnosis from increased post-transplant surveillance resulted in a deficiency of AML,” the investigators wrote. “A second is based on steeper MDS versus AML incidences versus age . . . and the possibility that transplantation recipient marrow ages (ie, marrow biological ages) are perhaps decades older than calendar ages.”

The study authors said they had no relevant conflicts of interest. The CIBMTR is supported by several US government agencies and numerous pharmaceutical companies. 

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of morbidity and mortality in patients with diabetes.¹ ASCVD is defined by the American College of Cardiology and the American Heart Association (ACC/AHA) as acute coronary syndrome, myocardial infarction, stable or unstable angina, coronary or other arterial revascularization, stroke, transient ischemic attack, or peripheral arterial disease presumed to be of atherosclerotic origin.² Risk factors for ASCVD include hypertension, dyslipidemia, smoking, family history of premature coronary disease, chronic kidney disease, and albuminuria.³

Hypertension, a modifiable risk factor, is prevalent in patients with diabetes. Multiple studies have shown that antihypertensive therapy in these patients reduces ASCVD events; therefore, blood pressure control is necessary.^1,3 The American Diabetes Association’s (ADA) 2018 Standards of Medical Care in Diabetes offers guidance on the assessment and treatment of hypertension in patients with diabetes—including the organization’s position statement on hypertensive treatment with comorbid diabetes.^1,3 These guidelines are relevant and useful to both primary care and specialty providers who manage these complex patients.

Screening and Diagnosis

Every clinical care visit for patients with diabetes should include a blood pressure measurement. (Evaluation for orthostatic hypotension should also be performed at the initial visit, to help guide future treatment.¹) For accuracy, blood pressure should be assessed

• By a trained individual using the appropriate size cuff
• In both arms on the initial visit
• With the patient seated, with feet on the floor and arm at heart level
• After five minutes of rest
• With two to three readings taken one to two minutes apart and results averaged.¹

If blood pressure is found to be elevated and the patient has no known history of hypertension, the elevated blood pressure should be reassessed on another visit within one month to confirm the diagnosis.¹ Patients should also monitor blood pressure at home to distinguish between white coat and masked hypertension.¹ Home blood pressures should be measured with arm cuffs that are the appropriate size. The bladder of the cuff should encircle 80% of the arm, should not cover clothing, and should be placed on the upper arm at the midpoint of the sternum.¹

The ACC/AHA’s 2017 guidelines define stage 1 hypertension as 130-139/80-89 mm Hg and stage 2 hypertension as ≥ 140/90 mm Hg.⁴ The ADA defines hypertension as a sustained blood pressure ≥ 140/90 mm Hg, noting that the definition is “based on unambiguous data that levels above this threshold are strongly associated with ­ASCVD, death, disability, and microvascular complications.”¹

BLOOD PRESSURE TARGETS

Evidence has shown that treatment of blood pressure to a goal of ≤ 140/90 mm Hg reduces cardiovascular events as well as microvascular complications.¹ For patients with diabetes, the ADA recommends treatment to a systolic blood pressure goal of < 140 mm Hg and a diastolic blood pressure goal of < 90 mm Hg, while the ACC/AHA guidelines recommend a goal of < 130/80 mm Hg.^1,4

The ADA does note that lower blood pressure targets (eg, < 130/80 mm Hg) can be appropriate for individuals at high risk for cardiovascular disease if no treatment burdens (eg, adverse effects, costs) are imposed.¹ This is important, since patients with diabetes often have multiple risk factors for ASCVD and will be considered high risk. Studies suggest lower blood pressure targets may decrease the risk for stroke and albuminuria but offer little to no effect on other ASCVD events, occurrence of heart failure, or other conditions associated with diabetes (eg, peripheral neuropathy).¹

Continue to: LIFESTYLE MANAGEMENT

LIFESTYLE MANAGEMENT

Patients with diabetes and elevated blood pressure (> 120/80 mm Hg, per the 2017 ACC/AHA guidelines) are at high risk for hypertension and its complications.^1,4 Lifestyle management—which includes weight loss, a healthy diet, increase in physical activity, and moderation in alcohol intake—is an important component of preventing or delaying a hypertension diagnosis.^1,4

Both the ADA and the ACC/AHA recommend that patients with diabetes follow the Dietary Approaches to Stop Hypertension (DASH) diet.^1,4 Guidelines include restricting sodium intake to < 2,300 mg/d, consuming 8-10 servings/d of fruits and vegetables and 2-3 servings/d of low-fat dairy products, limiting alcohol consumption to two servings/d for men and one serving/d for women, and increasing physical activity to include at least 30-45 min/d of aerobic exercise.^1,4

PHARMACOLOGIC TREATMENT

Initial treatment for patients with hypertension and diabetes depends on the severity of the hypertension and should include drug classes that have demonstrated success in reducing ASCVD events: ACE inhibitors, angiotensin receptor blockers (ARBs), thiazide-like diuretics, and dihydropyridine calcium channel blockers. The ADA offers additional guidance:

Blood pressure ≥ 140/90 mm Hg should be treated with lifestyle modifications and simultaneous initiation of a single drug, with timely titration of pharmacologic therapy to achieve blood pressure goals.

Continue to: Blood pressure ≥ 160/100 mm Hg

Blood pressure ≥ 160/100 mm Hg should be treated with lifestyle therapy and prompt initiation and timely titration of two drugs or a single-pill combination of drugs.

Multidrug therapy is generally required to achieve blood pressure targets—but ACE inhibitors and ARBs should not be used in combination due to the increased risk for adverse effects.

Firstline therapy is an ACE inhibitor or an ARB, at the maximum tolerated dose, in patients with diabetes and a urine albumin-to-creatinine ratio ≥ 30 mg/g.

Monitoring of estimated glomerular filtration rate and serum potassium levels is needed in patients treated with an ACE inhibitor, ARB, or diuretic.¹

RESISTANT HYPERTENSION

Patients with diabetes who have a blood pressure ≥ 140/90 mm Hg despite treatment that includes lifestyle management, two antihypertensives, and a diuretic, or who achieve blood pressure control with four or more medications, are considered to have resistant hypertension.^1,5 Factors such as pseudoresistance (lack of medication adherence or poor measurement technique), masked hypertension, and white coat hypertension should be ruled out in making the diagnosis of resistant hypertension. Once these have been excluded, patients should be referred for a workup of their resistant hypertension to evaluate causes of secondary hypertension. These can include endocrine issues, renal arterial disease, edema in advanced kidney disease, hormones, and drugs such as NSAIDs and decongestants.¹

Continue to: PATIENT-CENTERED CARE

When evaluating and treating a patient with diabetes, it is important to consider

• What is the patient’s overall risk for atherosclerotic cardiovascular disease?
• Does he/she have an increased risk for stroke? If so, lower blood pressure targets may be appropriate.
• Is more than one antihypertensive agent (ACE inhibitor, ARB, or diuretic) being used? If so, close monitoring of estimated glomerular filtration rate and potassium (as well as other indications of adverse effects) is important.

The treatment regimen should be a shared decision-making process between the clinician and patient and should be individualized to each patient and his/her existing comorbidities.

CONCLUSION

Clinical trials and meta-analyses support target blood pressure management to < 140/90 mm Hg in most adults with diabetes, while lower targets (< 130/80 mm Hg) may be beneficial for patients with diabetes and a high risk for cardiovascular disease.^1,5 Lifestyle management should be initiated and continued in patients with a blood pressure > 120/80 mm Hg and in those diagnosed with hypertension.¹ Medications that reduce cardiovascular events should be used in management, with ACE inhibitors or ARBs being firstline treatment in patients with albuminuria.¹

For more information on hypertensive treatment in special populations (eg, pregnant women and older adults), see the ADA’s full position statement.¹

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of morbidity and mortality in patients with diabetes.¹ ASCVD is defined by the American College of Cardiology and the American Heart Association (ACC/AHA) as acute coronary syndrome, myocardial infarction, stable or unstable angina, coronary or other arterial revascularization, stroke, transient ischemic attack, or peripheral arterial disease presumed to be of atherosclerotic origin.² Risk factors for ASCVD include hypertension, dyslipidemia, smoking, family history of premature coronary disease, chronic kidney disease, and albuminuria.³

Hypertension, a modifiable risk factor, is prevalent in patients with diabetes. Multiple studies have shown that antihypertensive therapy in these patients reduces ASCVD events; therefore, blood pressure control is necessary.^1,3 The American Diabetes Association’s (ADA) 2018 Standards of Medical Care in Diabetes offers guidance on the assessment and treatment of hypertension in patients with diabetes—including the organization’s position statement on hypertensive treatment with comorbid diabetes.^1,3 These guidelines are relevant and useful to both primary care and specialty providers who manage these complex patients.

Screening and Diagnosis

Every clinical care visit for patients with diabetes should include a blood pressure measurement. (Evaluation for orthostatic hypotension should also be performed at the initial visit, to help guide future treatment.¹) For accuracy, blood pressure should be assessed

• By a trained individual using the appropriate size cuff
• In both arms on the initial visit
• With the patient seated, with feet on the floor and arm at heart level
• After five minutes of rest
• With two to three readings taken one to two minutes apart and results averaged.¹

If blood pressure is found to be elevated and the patient has no known history of hypertension, the elevated blood pressure should be reassessed on another visit within one month to confirm the diagnosis.¹ Patients should also monitor blood pressure at home to distinguish between white coat and masked hypertension.¹ Home blood pressures should be measured with arm cuffs that are the appropriate size. The bladder of the cuff should encircle 80% of the arm, should not cover clothing, and should be placed on the upper arm at the midpoint of the sternum.¹

The ACC/AHA’s 2017 guidelines define stage 1 hypertension as 130-139/80-89 mm Hg and stage 2 hypertension as ≥ 140/90 mm Hg.⁴ The ADA defines hypertension as a sustained blood pressure ≥ 140/90 mm Hg, noting that the definition is “based on unambiguous data that levels above this threshold are strongly associated with ­ASCVD, death, disability, and microvascular complications.”¹

BLOOD PRESSURE TARGETS

Evidence has shown that treatment of blood pressure to a goal of ≤ 140/90 mm Hg reduces cardiovascular events as well as microvascular complications.¹ For patients with diabetes, the ADA recommends treatment to a systolic blood pressure goal of < 140 mm Hg and a diastolic blood pressure goal of < 90 mm Hg, while the ACC/AHA guidelines recommend a goal of < 130/80 mm Hg.^1,4

The ADA does note that lower blood pressure targets (eg, < 130/80 mm Hg) can be appropriate for individuals at high risk for cardiovascular disease if no treatment burdens (eg, adverse effects, costs) are imposed.¹ This is important, since patients with diabetes often have multiple risk factors for ASCVD and will be considered high risk. Studies suggest lower blood pressure targets may decrease the risk for stroke and albuminuria but offer little to no effect on other ASCVD events, occurrence of heart failure, or other conditions associated with diabetes (eg, peripheral neuropathy).¹

Continue to: LIFESTYLE MANAGEMENT

LIFESTYLE MANAGEMENT

Patients with diabetes and elevated blood pressure (> 120/80 mm Hg, per the 2017 ACC/AHA guidelines) are at high risk for hypertension and its complications.^1,4 Lifestyle management—which includes weight loss, a healthy diet, increase in physical activity, and moderation in alcohol intake—is an important component of preventing or delaying a hypertension diagnosis.^1,4

Both the ADA and the ACC/AHA recommend that patients with diabetes follow the Dietary Approaches to Stop Hypertension (DASH) diet.^1,4 Guidelines include restricting sodium intake to < 2,300 mg/d, consuming 8-10 servings/d of fruits and vegetables and 2-3 servings/d of low-fat dairy products, limiting alcohol consumption to two servings/d for men and one serving/d for women, and increasing physical activity to include at least 30-45 min/d of aerobic exercise.^1,4

PHARMACOLOGIC TREATMENT

Initial treatment for patients with hypertension and diabetes depends on the severity of the hypertension and should include drug classes that have demonstrated success in reducing ASCVD events: ACE inhibitors, angiotensin receptor blockers (ARBs), thiazide-like diuretics, and dihydropyridine calcium channel blockers. The ADA offers additional guidance:

Blood pressure ≥ 140/90 mm Hg should be treated with lifestyle modifications and simultaneous initiation of a single drug, with timely titration of pharmacologic therapy to achieve blood pressure goals.

Continue to: Blood pressure ≥ 160/100 mm Hg

Blood pressure ≥ 160/100 mm Hg should be treated with lifestyle therapy and prompt initiation and timely titration of two drugs or a single-pill combination of drugs.

Multidrug therapy is generally required to achieve blood pressure targets—but ACE inhibitors and ARBs should not be used in combination due to the increased risk for adverse effects.

Firstline therapy is an ACE inhibitor or an ARB, at the maximum tolerated dose, in patients with diabetes and a urine albumin-to-creatinine ratio ≥ 30 mg/g.

Monitoring of estimated glomerular filtration rate and serum potassium levels is needed in patients treated with an ACE inhibitor, ARB, or diuretic.¹

RESISTANT HYPERTENSION

Patients with diabetes who have a blood pressure ≥ 140/90 mm Hg despite treatment that includes lifestyle management, two antihypertensives, and a diuretic, or who achieve blood pressure control with four or more medications, are considered to have resistant hypertension.^1,5 Factors such as pseudoresistance (lack of medication adherence or poor measurement technique), masked hypertension, and white coat hypertension should be ruled out in making the diagnosis of resistant hypertension. Once these have been excluded, patients should be referred for a workup of their resistant hypertension to evaluate causes of secondary hypertension. These can include endocrine issues, renal arterial disease, edema in advanced kidney disease, hormones, and drugs such as NSAIDs and decongestants.¹

Continue to: PATIENT-CENTERED CARE

When evaluating and treating a patient with diabetes, it is important to consider

• What is the patient’s overall risk for atherosclerotic cardiovascular disease?
• Does he/she have an increased risk for stroke? If so, lower blood pressure targets may be appropriate.
• Is more than one antihypertensive agent (ACE inhibitor, ARB, or diuretic) being used? If so, close monitoring of estimated glomerular filtration rate and potassium (as well as other indications of adverse effects) is important.

The treatment regimen should be a shared decision-making process between the clinician and patient and should be individualized to each patient and his/her existing comorbidities.

CONCLUSION

Clinical trials and meta-analyses support target blood pressure management to < 140/90 mm Hg in most adults with diabetes, while lower targets (< 130/80 mm Hg) may be beneficial for patients with diabetes and a high risk for cardiovascular disease.^1,5 Lifestyle management should be initiated and continued in patients with a blood pressure > 120/80 mm Hg and in those diagnosed with hypertension.¹ Medications that reduce cardiovascular events should be used in management, with ACE inhibitors or ARBs being firstline treatment in patients with albuminuria.¹

For more information on hypertensive treatment in special populations (eg, pregnant women and older adults), see the ADA’s full position statement.¹

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of morbidity and mortality in patients with diabetes.¹ ASCVD is defined by the American College of Cardiology and the American Heart Association (ACC/AHA) as acute coronary syndrome, myocardial infarction, stable or unstable angina, coronary or other arterial revascularization, stroke, transient ischemic attack, or peripheral arterial disease presumed to be of atherosclerotic origin.² Risk factors for ASCVD include hypertension, dyslipidemia, smoking, family history of premature coronary disease, chronic kidney disease, and albuminuria.³

Hypertension, a modifiable risk factor, is prevalent in patients with diabetes. Multiple studies have shown that antihypertensive therapy in these patients reduces ASCVD events; therefore, blood pressure control is necessary.^1,3 The American Diabetes Association’s (ADA) 2018 Standards of Medical Care in Diabetes offers guidance on the assessment and treatment of hypertension in patients with diabetes—including the organization’s position statement on hypertensive treatment with comorbid diabetes.^1,3 These guidelines are relevant and useful to both primary care and specialty providers who manage these complex patients.

Screening and Diagnosis

Every clinical care visit for patients with diabetes should include a blood pressure measurement. (Evaluation for orthostatic hypotension should also be performed at the initial visit, to help guide future treatment.¹) For accuracy, blood pressure should be assessed

• By a trained individual using the appropriate size cuff
• In both arms on the initial visit
• With the patient seated, with feet on the floor and arm at heart level
• After five minutes of rest
• With two to three readings taken one to two minutes apart and results averaged.¹

If blood pressure is found to be elevated and the patient has no known history of hypertension, the elevated blood pressure should be reassessed on another visit within one month to confirm the diagnosis.¹ Patients should also monitor blood pressure at home to distinguish between white coat and masked hypertension.¹ Home blood pressures should be measured with arm cuffs that are the appropriate size. The bladder of the cuff should encircle 80% of the arm, should not cover clothing, and should be placed on the upper arm at the midpoint of the sternum.¹

The ACC/AHA’s 2017 guidelines define stage 1 hypertension as 130-139/80-89 mm Hg and stage 2 hypertension as ≥ 140/90 mm Hg.⁴ The ADA defines hypertension as a sustained blood pressure ≥ 140/90 mm Hg, noting that the definition is “based on unambiguous data that levels above this threshold are strongly associated with ­ASCVD, death, disability, and microvascular complications.”¹

BLOOD PRESSURE TARGETS

Evidence has shown that treatment of blood pressure to a goal of ≤ 140/90 mm Hg reduces cardiovascular events as well as microvascular complications.¹ For patients with diabetes, the ADA recommends treatment to a systolic blood pressure goal of < 140 mm Hg and a diastolic blood pressure goal of < 90 mm Hg, while the ACC/AHA guidelines recommend a goal of < 130/80 mm Hg.^1,4

The ADA does note that lower blood pressure targets (eg, < 130/80 mm Hg) can be appropriate for individuals at high risk for cardiovascular disease if no treatment burdens (eg, adverse effects, costs) are imposed.¹ This is important, since patients with diabetes often have multiple risk factors for ASCVD and will be considered high risk. Studies suggest lower blood pressure targets may decrease the risk for stroke and albuminuria but offer little to no effect on other ASCVD events, occurrence of heart failure, or other conditions associated with diabetes (eg, peripheral neuropathy).¹

Continue to: LIFESTYLE MANAGEMENT

LIFESTYLE MANAGEMENT

Patients with diabetes and elevated blood pressure (> 120/80 mm Hg, per the 2017 ACC/AHA guidelines) are at high risk for hypertension and its complications.^1,4 Lifestyle management—which includes weight loss, a healthy diet, increase in physical activity, and moderation in alcohol intake—is an important component of preventing or delaying a hypertension diagnosis.^1,4

Both the ADA and the ACC/AHA recommend that patients with diabetes follow the Dietary Approaches to Stop Hypertension (DASH) diet.^1,4 Guidelines include restricting sodium intake to < 2,300 mg/d, consuming 8-10 servings/d of fruits and vegetables and 2-3 servings/d of low-fat dairy products, limiting alcohol consumption to two servings/d for men and one serving/d for women, and increasing physical activity to include at least 30-45 min/d of aerobic exercise.^1,4

PHARMACOLOGIC TREATMENT

Initial treatment for patients with hypertension and diabetes depends on the severity of the hypertension and should include drug classes that have demonstrated success in reducing ASCVD events: ACE inhibitors, angiotensin receptor blockers (ARBs), thiazide-like diuretics, and dihydropyridine calcium channel blockers. The ADA offers additional guidance:

Blood pressure ≥ 140/90 mm Hg should be treated with lifestyle modifications and simultaneous initiation of a single drug, with timely titration of pharmacologic therapy to achieve blood pressure goals.

Continue to: Blood pressure ≥ 160/100 mm Hg

Blood pressure ≥ 160/100 mm Hg should be treated with lifestyle therapy and prompt initiation and timely titration of two drugs or a single-pill combination of drugs.

Multidrug therapy is generally required to achieve blood pressure targets—but ACE inhibitors and ARBs should not be used in combination due to the increased risk for adverse effects.

Firstline therapy is an ACE inhibitor or an ARB, at the maximum tolerated dose, in patients with diabetes and a urine albumin-to-creatinine ratio ≥ 30 mg/g.

Monitoring of estimated glomerular filtration rate and serum potassium levels is needed in patients treated with an ACE inhibitor, ARB, or diuretic.¹

RESISTANT HYPERTENSION

Patients with diabetes who have a blood pressure ≥ 140/90 mm Hg despite treatment that includes lifestyle management, two antihypertensives, and a diuretic, or who achieve blood pressure control with four or more medications, are considered to have resistant hypertension.^1,5 Factors such as pseudoresistance (lack of medication adherence or poor measurement technique), masked hypertension, and white coat hypertension should be ruled out in making the diagnosis of resistant hypertension. Once these have been excluded, patients should be referred for a workup of their resistant hypertension to evaluate causes of secondary hypertension. These can include endocrine issues, renal arterial disease, edema in advanced kidney disease, hormones, and drugs such as NSAIDs and decongestants.¹

Continue to: PATIENT-CENTERED CARE

When evaluating and treating a patient with diabetes, it is important to consider

• What is the patient’s overall risk for atherosclerotic cardiovascular disease?
• Does he/she have an increased risk for stroke? If so, lower blood pressure targets may be appropriate.
• Is more than one antihypertensive agent (ACE inhibitor, ARB, or diuretic) being used? If so, close monitoring of estimated glomerular filtration rate and potassium (as well as other indications of adverse effects) is important.

The treatment regimen should be a shared decision-making process between the clinician and patient and should be individualized to each patient and his/her existing comorbidities.

CONCLUSION

Clinical trials and meta-analyses support target blood pressure management to < 140/90 mm Hg in most adults with diabetes, while lower targets (< 130/80 mm Hg) may be beneficial for patients with diabetes and a high risk for cardiovascular disease.^1,5 Lifestyle management should be initiated and continued in patients with a blood pressure > 120/80 mm Hg and in those diagnosed with hypertension.¹ Medications that reduce cardiovascular events should be used in management, with ACE inhibitors or ARBs being firstline treatment in patients with albuminuria.¹

For more information on hypertensive treatment in special populations (eg, pregnant women and older adults), see the ADA’s full position statement.¹

In the July 26, 2018, issue of the New England Journal of Medicine, Ira L. Leeds, MD, David T. Efron, MD, FACS, and Lisa S. Lehmann, MD, raise the important issue of how to proceed when a patient has an indication for surgery and wants the surgery, but the patient has modifiable risk factors that make the likelihood of surgical complications high.¹ Specifically, the authors describe a 45-year-old woman with morbid obesity and chronic opioid dependency who presented with a large incisional hernia. The patient suffers from debilitating pain and nausea that has been attributed to her hernia. She is homebound and is seeking a third opinion on repair of the hernia. She has smoked for 30 years and continues to do so after prior unsuccessful attempts to quit. She has been turned down previously by two surgeons who reportedly felt she was too high risk. Application of an all-procedure risk calculator has shown a 38% higher than average risk of a complication with an expected length of stay 80% longer than average.

Reference

1. Leeds IL et al. Surgical gatekeeping – modifiable risk factors and ethical decision making. N Engl J Med. 2018 Jul 26. doi:10.1056/NEJMms1802079.

Dr. Angelos is the Linda Kohler Anderson Professor of Surgery and Surgical Ethics, chief of endocrine surgery, and associate director of the MacLean Center for Clinical Medical Ethics at the University of Chicago.

In the July 26, 2018, issue of the New England Journal of Medicine, Ira L. Leeds, MD, David T. Efron, MD, FACS, and Lisa S. Lehmann, MD, raise the important issue of how to proceed when a patient has an indication for surgery and wants the surgery, but the patient has modifiable risk factors that make the likelihood of surgical complications high.¹ Specifically, the authors describe a 45-year-old woman with morbid obesity and chronic opioid dependency who presented with a large incisional hernia. The patient suffers from debilitating pain and nausea that has been attributed to her hernia. She is homebound and is seeking a third opinion on repair of the hernia. She has smoked for 30 years and continues to do so after prior unsuccessful attempts to quit. She has been turned down previously by two surgeons who reportedly felt she was too high risk. Application of an all-procedure risk calculator has shown a 38% higher than average risk of a complication with an expected length of stay 80% longer than average.

Reference

1. Leeds IL et al. Surgical gatekeeping – modifiable risk factors and ethical decision making. N Engl J Med. 2018 Jul 26. doi:10.1056/NEJMms1802079.

Dr. Angelos is the Linda Kohler Anderson Professor of Surgery and Surgical Ethics, chief of endocrine surgery, and associate director of the MacLean Center for Clinical Medical Ethics at the University of Chicago.

In the July 26, 2018, issue of the New England Journal of Medicine, Ira L. Leeds, MD, David T. Efron, MD, FACS, and Lisa S. Lehmann, MD, raise the important issue of how to proceed when a patient has an indication for surgery and wants the surgery, but the patient has modifiable risk factors that make the likelihood of surgical complications high.¹ Specifically, the authors describe a 45-year-old woman with morbid obesity and chronic opioid dependency who presented with a large incisional hernia. The patient suffers from debilitating pain and nausea that has been attributed to her hernia. She is homebound and is seeking a third opinion on repair of the hernia. She has smoked for 30 years and continues to do so after prior unsuccessful attempts to quit. She has been turned down previously by two surgeons who reportedly felt she was too high risk. Application of an all-procedure risk calculator has shown a 38% higher than average risk of a complication with an expected length of stay 80% longer than average.

Reference

1. Leeds IL et al. Surgical gatekeeping – modifiable risk factors and ethical decision making. N Engl J Med. 2018 Jul 26. doi:10.1056/NEJMms1802079.

Dr. Angelos is the Linda Kohler Anderson Professor of Surgery and Surgical Ethics, chief of endocrine surgery, and associate director of the MacLean Center for Clinical Medical Ethics at the University of Chicago.

Attend the Annual American College of Surgeons Accredited Educational Institutes (ACS-AEI) Postgraduate Course, Novice to Expert: Let’s Get It Done, September 14–15 at the Mayo Clinic Multidisciplinary Simulation Center, Rochester, MN, to learn new techniques in simulation education that will meet the needs of all levels of learners, from novice to expert. Succinct presentations and hands-on activities at the simulation center will expose attendees to useful ideas, initiatives, and best practices that can be incorporated at their respective centers. The deadline to register for the course is August 31.

Sessions on Friday, September 14, will take place at the host hotel, the DoubleTree by Hilton Rochester—Mayo Clinic Area, and will feature simulation presentations that address learners at the Novice, Advanced Beginner, Competent, Proficient, and Expert levels. The day will end with a special cocktail reception and dinner at the historic Mayo Foundation House, where you will enjoy networking and making connections with fellow attendees for more relevant research and educational efforts. Saturday, September 15, will begin with a tour of the simulation center, followed by interactive activities that showcase Mayo’s strengths, including the Surgical X-Games, low-fidelity models, assessment, Maintenance of Certification for anesthesiology, and more. View the complete course agenda at facs.org/~/media/files/education/aei/pg_course_agenda_2018.ashx.

Registrants are offered a special booking rate at the DoubleTree by Hilton Rochester—Mayo Clinic Area. Reservations may be made by booking online at bit.ly/2mviB8Q or by calling 507-281-8000 and mentioning the American College of Surgeons September 2018 Meeting. Hotel reservations must be made by August 22 to qualify for the group rate.

Visit the postgraduate course web page at facs.org/education/accreditation/aei/pgcourse for more details and to register. Contact Cathy Sormalis at [email protected] with questions.
 

Attend the Annual American College of Surgeons Accredited Educational Institutes (ACS-AEI) Postgraduate Course, Novice to Expert: Let’s Get It Done, September 14–15 at the Mayo Clinic Multidisciplinary Simulation Center, Rochester, MN, to learn new techniques in simulation education that will meet the needs of all levels of learners, from novice to expert. Succinct presentations and hands-on activities at the simulation center will expose attendees to useful ideas, initiatives, and best practices that can be incorporated at their respective centers. The deadline to register for the course is August 31.

Sessions on Friday, September 14, will take place at the host hotel, the DoubleTree by Hilton Rochester—Mayo Clinic Area, and will feature simulation presentations that address learners at the Novice, Advanced Beginner, Competent, Proficient, and Expert levels. The day will end with a special cocktail reception and dinner at the historic Mayo Foundation House, where you will enjoy networking and making connections with fellow attendees for more relevant research and educational efforts. Saturday, September 15, will begin with a tour of the simulation center, followed by interactive activities that showcase Mayo’s strengths, including the Surgical X-Games, low-fidelity models, assessment, Maintenance of Certification for anesthesiology, and more. View the complete course agenda at facs.org/~/media/files/education/aei/pg_course_agenda_2018.ashx.

Registrants are offered a special booking rate at the DoubleTree by Hilton Rochester—Mayo Clinic Area. Reservations may be made by booking online at bit.ly/2mviB8Q or by calling 507-281-8000 and mentioning the American College of Surgeons September 2018 Meeting. Hotel reservations must be made by August 22 to qualify for the group rate.

Visit the postgraduate course web page at facs.org/education/accreditation/aei/pgcourse for more details and to register. Contact Cathy Sormalis at [email protected] with questions.
 

Attend the Annual American College of Surgeons Accredited Educational Institutes (ACS-AEI) Postgraduate Course, Novice to Expert: Let’s Get It Done, September 14–15 at the Mayo Clinic Multidisciplinary Simulation Center, Rochester, MN, to learn new techniques in simulation education that will meet the needs of all levels of learners, from novice to expert. Succinct presentations and hands-on activities at the simulation center will expose attendees to useful ideas, initiatives, and best practices that can be incorporated at their respective centers. The deadline to register for the course is August 31.

Sessions on Friday, September 14, will take place at the host hotel, the DoubleTree by Hilton Rochester—Mayo Clinic Area, and will feature simulation presentations that address learners at the Novice, Advanced Beginner, Competent, Proficient, and Expert levels. The day will end with a special cocktail reception and dinner at the historic Mayo Foundation House, where you will enjoy networking and making connections with fellow attendees for more relevant research and educational efforts. Saturday, September 15, will begin with a tour of the simulation center, followed by interactive activities that showcase Mayo’s strengths, including the Surgical X-Games, low-fidelity models, assessment, Maintenance of Certification for anesthesiology, and more. View the complete course agenda at facs.org/~/media/files/education/aei/pg_course_agenda_2018.ashx.

Registrants are offered a special booking rate at the DoubleTree by Hilton Rochester—Mayo Clinic Area. Reservations may be made by booking online at bit.ly/2mviB8Q or by calling 507-281-8000 and mentioning the American College of Surgeons September 2018 Meeting. Hotel reservations must be made by August 22 to qualify for the group rate.

Visit the postgraduate course web page at facs.org/education/accreditation/aei/pgcourse for more details and to register. Contact Cathy Sormalis at [email protected] with questions.