Rochester, Minnesota Lifestyle – Mayo School of Graduate Medical Education

Rochester is Minnesota’s third largest city, with a population of approximately 106,000 people. It is located about 80 miles south of Minneapolis and St. Paul (Twin Cities), the country’s 16th largest metropolitan area and the 13th most populous in the U.S., with about 3.5 million people. In the last 10 years, Rochester has twice been ranked as one of the best places to live in the U.S. by Money Magazine. Rochester combines the best aspects of an innovative and cosmopolitan city with the charm of a small town environment. Attractions, theaters, restaurants, sporting events, and entertainment are located in the heart of the city. Rochester is known as a great place to live, work and visit, welcoming about 2.75 million visitors annually, from all over the world, including about 1,600 residents and fellows in Mayo School of Graduate Medical Education http://www.mayo.edu/msgme/

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Common Causes – CJ First Candle

 

There are many causes of stillbirth. More than one of these causes may be involved a the baby’s death. Other less common causes of stillbirth include trauma (such as car accidents), post-term pregnancy (longer than 42 weeks), Rh disease and lack of oxygen during a difficult delivery. Of the deaths where a cause has been found, following are some of the more common causes:

Birth Defects

Birth defects are involved in about 15 to 20 percent of all stillbirth deaths. Nearly half of these babies have a chromosomal abnormality, such as Down Syndrome. Others have birth defects resulting from genetic or environmental causes.

Placental Problems

Placental problems cause between 10 and 20 percent of stillbirths. Placental abruption is one of the most common placental problems. The placenta separates (partially or completely) from the uterine wall before delivery, resulting in heavy bleeding that can threaten the life of the mother and the baby. Women who smoke cigarettes or use drugs during pregnancy are at increased risk for placental abruption.

Poor Fetal Growth

Poor fetal growth accounts for about 20 percent of stillborn babies. This means that the fetus is growing too slowly. Women with pre-eclampsia (high blood pressure) are at an increased risk of having a growth-restricted baby. Smoking can also increase this risk. An ultrasound can help your doctor identify poor fetal growth and more closely monitor the pregnancy.

Cord Accidents

Accidents involving the umbilical cord may contribute to a stillbirth death in about 15 percent of the cases. This can include a knot in the cord or abnormal placement of the cord into the placenta. This can deprive the baby of oxygen.

Infectious Disease

Infections in the mother, baby or placenta seem to cause anywhere from 10 to 25 percent of stillbirths. Infections may not even cause symptoms for the mother, such as a genital and urinary tract infections or certain viruses such as parvovirus B19 (Fifth Disease). If these infections go undiagnosed, they can cause serious s complications such as fetal death or preterm birth.

Chronic Health Conditions

Chronic maternal health conditions are associated with about 10 percent of stillborn babies. These include high blood pressure, diabetes and kidney disease. These conditions can also contribute to poor fetal growth or placental abruption.  Fortunately, as a result of improvements in medical care, stillbirth deaths due to maternal health conditions have greatly decreased. Last revised: October 2009

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10-Minute Easy Lower Body Workout

Use this simple routine to strengthen your legs.

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Hypothyroidism in Children

Pediatric Endocrinologist, Dr. Siobhan Pittock, of the Mayo Clinic Children’s Center, discusses the causes and medical treatment options for parents of children with hypothyroidism.

To find out more about the Mayo Clinic Children’s Center or to request an appointment visit the website at http://www.mayoclinic.org/pediatrics/?mc_id=youtube or call 855-MAYOKID; 855-629-6543.

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Talking About 13 Reasons Why & Teen Suicide: Tips for Parents

 

When the Netflix series “13 Reasons Why” premiered in March 2017, it quickly became one of the most watched—and most controversial—shows of the year. It was no surprise that the news of Season 2’s May 2018 release continued to get a lot of attention.

The drama-mystery centers on a high school student who commits suicide and leaves behind 13 audiotapes for people she blames for her action. Season 2 picks up as the community tries to deal with emotional and legal fallout from the suicide.

Raising Awareness–and Risk?

Fans of the series say it increases much-needed awareness about teen suicide, which is currently the second leading cause of death for children and young people 10 to 24 years old. CDC Teen Suicide Stats - 2015 In addition to graphic portrayal of suicide, the show also focuses on bullying and cyberbullying, underage drinking, sexual assault, guns in the home, and other topics that can serve a tool to start discussions.

But some experts warn the show may do more harm than good. Although the series is fictional, teens can be impulsive and emotional. Watching a character decide suicide is the best option might trigger them to do the same. Researchers found a significant spike in internet searches using terms such as “how to commit suicide” and “how to kill yourself” for 19 days following the release of season 1 of “13 Reasons Why.”

Medical and mental health professionals also report teens listing their own 13 reasons why they wanted to kill themselves. Some families say they believe the show triggered their children to actually take their lives.

Critics of the show point to research that suggests exposure to a peer’s suicide can have a “contagious” effect—especially among 12- to 13-year-olds. There is specific public health recommendations for reporting on suicide in the media that this series goes against:

  • Presenting suicide as a tool for accomplishing certain ends, such as revenge or recognition.
  • Glorifying suicide or persons who commit suicide.

Who’s Watching?

The series is rated TV-MA (Mature Audience), appropriate for ages 17 and up, for its graphic violence, explicit sexual activity and crude language. But school officials and pediatricians say they’re learning of children as young as elementary-school age who are binge watching the show—sometimes without parents knowing, because it can be streamed privately on their phones, tablets, and computers. Parents are often surprised to find out their child has watched the series.

“It has come up quite a bit when I’ve been talking to my patients, especially those who’ve been depressed or anxious,” said Cora Breuner, MD, MPH, FAAP, a pediatrician and chair the American Academy of Pediatrics (AAP) Committee on Adolescence. “Quite a few of them already watched ’13 Reasons Why’—without the knowledge of their parents,” Dr. Breuner said. “It’s usually a major aha moment in my office, when the parents look at their kids and say, `Wait a minute, you watched that?'”

As a parent, it is your job to counsel your children and teens about smart and safe media use. Dr. Breuner said she also asks her patients (and their parents) how much time they spend on screens and what shows they watch.

Even if your child hasn’t watched…

Parents should be aware that their child may hear friends talking about the show at school or on social media—even if they haven’t seen it themselves. Regardless, Dr. Breuner said the series is “absolutely inappropriate” for children under age 13.

If you haven’t watched the show, look up episode summaries and be prepared talk with your child about the ways fictional shows don’t always reflect reality. Use the show as an opportunity to talk with your child about the very real situations teens face—and how your child can come to you with anything he or she may face in the future.

How to Help Teens Process the Show in a Safe & Healthy Way:

Despite concerns about ’13 Reasons Why,’ the show can serve as a powerful teaching tool with informed, adult guidance from parents, teachers, spiritual leaders, and others who work with teens.

What parents can do:

  • Co-view. The AAP media use guidelines encourage parents to co-viewing programs with their children and discuss values. This is especially important for shows such as ’13 Reasons Why’ with themes difficult to process and easy to misinterpret. Watching the show together lets parents pause and point out instances of cyberbullying, for example. Then parents can ask if their child has seen it happen at school, how he or she reacted, and what to do if it happens again. ​
    • Children in groups at a higher risk for suicidal thoughts and actions should not watch the show alone, Dr. Breuner said. This includes kids with a family history of suicide, a history of physical or sexual abuse, mood disorders, and drug and alcohol use, and/or those who identify as lesbian, gay, bisexual, transgender or questioning.
  • Discuss reality vs. fiction. Explain that the show gives an unrealistic view of the help available for teens who may feel suicidal. In particular, the lack of effective mental health care provided to lead character, Hannah Baker, is both troubling and unrealistic. Statistics show that a large majority of the time, teens with suicidal thoughts and behaviors are in the grips of treatable mental illnesses, such as depression. In the show, Hannah voices clear suicidal warning signs to her school guidance counselor. Yet, the counselor failed to connect her with other professionals and resources for help and told her simply to “move on.” Critics say this sends a dangerous message that adults can’t help.
  • Play it safe. If your teen does watch the show, make an extra effort to watch him or her a little more closely afterwards—in a mindful, nurturing way. Know the signs of depression, such as withdrawing from friends or family, eating or sleeping less or more, or losing interest in activities.
    • If you have a gun in your home, make sure it is stored unloaded and locked up separately from ammunition. Studies have found the risk of suicide is 4 to 10 times higher in homes with guns than in those without. And although Hannah Baker uses a different method to end her life, suicide by firearms is now the second leading cause of death among teens 15-19. More than 80% of guns used in teen suicide attempts were kept in the home of the victim, a relative, or a friend.
  • Provide access to help. Give your child su​​​ggestions for whom he or she can turn to in times of need—including you, as well as other trusted adults. Your pediatrician can also help. The American Academy of Pediatrics recently recommended all children over age 12 be screened for depression at their annual wellness exams. For any immediate concerns about your child, call the National Suicide Prevention Lifeline is 1-800-TALK, or text START to 741741.

Keep in Mind:

It may feel uncomfortable to talk with your teen about some of the difficult issues raised in “13 Reasons Why,” but talking about tough topics with teens is every bit as important as making sure a baby’s bath water isn’t too hot.

Teen Media Quote - Dr. Cora Breuner

Remember to talk with your child’s pediatrician if you have additional questions or concerns about your child’s media use or mental health.

Additional Information & Resources:

​​​

The information contained on this Web site should not be used as a substitute for the medical care and advice of your pediatrician. There may be variations in treatment that your pediatrician may recommend based on individual facts and circumstances.

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Telomerase Targeting Drug Demonstrates Benefit in Myelofibrosis Treatment

Imetelstat, a novel drug that targets telomerase, has demonstrated potential value in treating patients with myelofibrosis, according to the results of a study published today in the New England Journal of Medicine.

“We observed that Imetelstat was active and induced morphologic and molecular remissions in some patients with myelofibrosis,” says Ayalew Tefferi, M.D., a hematologist at Mayo Clinic and lead author of the study. “We also observed that Imtelstat demonstrated selective anti-clonal activity, inhibiting the growth of cancer cells, which we had not previously documented with other drugs.”

Myelofibrosis is a chronic myeloid cancer in which bone marrow cells that produce blood cells develop and function abnormally. The result is the formation of scar tissue in the bone marrow (fibrosis), severe anemia that often requires transfusion, weakness, fatigue, and an enlarged spleen and liver. Patients with myelofibrosis harbor one of several genetic mutations in their blood stem cells, including JAK2, MPL, CALR, ASXL1 and spliceosome pathway mutations.3317325_0009[1]”Typically, myelofibrosis is characterized by marrow scarring, and, although patients may derive symptomatic relief from other treatments, such as ruxolitinib, they usually do not revert back to normal bone marrow,” Dr. Tefferi says. “Some patients treated with Imetelstat have reverted back to normal bone marrow.” Imetelstat works by inhibiting telomerase activity in tumor cells, which leads to cell death.

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What Are Boogers?

Have you ever wondered why or how boogers form? See what exactly that dried mucus in your nose is for. Learn more: http://wb.md/2dDV82J

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Youths Treated for Non-Suicidal Self Harm at Increased Risk of Suicide Within a Year

 

New research in the April 2018 Pediatrics found that youths treated for deliberate but non-suicidal self-harm, such as cutting, were more than 25 times as likely than demographically matched peers to die from suicide within the following year.

The study, “Suicide Following Deliberate Self-Harm in Adolescents and Young Adults” (published online March 19), followed 32,395 patients between ages 12 and 24 who were enrolled in Medicaid between 2001 and 2007. The risk of suicide within a year of self-harm varied considerably by age, race and other factors. It was more than four times higher for males (338.8 per 100,000) than for females (80.2 per 100,000). In addition, the risk was markedly higher for American Indians/Alaskan Natives than for non-Hispanic white patients, and for patients who patients who used more violent methods of self-harm, especially firearms.

The study also revealed differences among adolescents and young adults who were treated for the initial self-harm. Although depression and anxiety diagnoses were common in both age groups, for example, adolescents with self-harm were far more likely to have been recently diagnosed with attention deficit hyperactivity disorder (ADHD) and other disruptive behaviors, while young adults more commonly had substance use and personality disorder diagnoses.

Authors of the study said their findings underscore the importance of follow-up care for youths treated for self-harm to help ensure their safety.

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Will We Soon Reverse Diabetes and Obesity with Gene Therapy?

New research shows that gene therapy can completely reverse markers of Type 2 diabetes and obesity in rodents.  If the theory holds, small alterations to our genes could soon repair metabolic disorders such as obesity and Type 2 diabetes in humans.

The prevalence of diabetes, or the total number of existing cases, is on the rise in the United States and globally.  According to recent estimates, over 30 million U.S. adults had diabetes in 2015.

Although the number has been relatively steady in the past few years, rates of newly diagnosed cases among children and teenagers have increased sharply.  And, worldwide, the situation is even more alarming; the number of people with diabetes almost quadrupled between 1980 and 2014, according to the World Health Organization (WHO).

Now, new research brings much-needed hope of curing this metabolic disorder.  Scientists led by Fatima Bosch, a professor at the Universitat Autònoma de Barcelona (UAB) in Catalunya, Spain, have successfully reversed the disorder in rodents.  Prof. Bosch and her colleagues achieved this using gene therapy, a technique that introduces new genetic material into cells to create beneficial proteins or to offset the effects of malfunctioning genes.  The findings were published in the journal EMBO Molecular Medicine.

Using the FGF21 gene to reverse diabetes

Prof. Bosch and team designed two mouse models of obesity and type 2 diabetes. One was diet-induced, and the other one was genetically modified.  Using an adeno-associated viral vector as “transport,” the team delivered the fibroblast growth factor 21 (FGF21) gene.

This gene is responsible for encoding the FGF21 protein, which is seen as a “major metabolic regulator” that stimulates the absorption of blood sugar in adipose tissue.  By delivering this gene, the researchers stimulated the production of the protein, which caused the rodents to lose weight and lowered their insulin resistance — a major risk factor for type 2 diabetes. Additionally, the mice lost weight and the treatment reduced the fat and inflammation in their adipose tissue.

The fat content, inflammation, and fibrosis of the rodents’ livers were completely reversed, with no side effects. In turn, these improvements increased insulin sensitivity.  These beneficial effects were noted in both murine models. Also, the team found that administering FGF21 to healthy mice prevented age-related weight gain and led to healthy aging.

Gene therapy was used to alter three tissue types: liver tissue, adipose tissue, and skeletal muscle.  “This gives a great flexibility to the therapy,” explains Prof. Bosch, “since it allows [us] to select each time the most appropriate tissue, and in case some complication prevents manipulating any of the tissues, it can be applied to any of the others.”

“When a tissue produces FGF21 protein and secretes it into the bloodstream, it will be distributed throughout the body,” adds Prof. Bosch.

First reversion of obesity, insulin resistance

Study co-author and UAB researcher Claudia Jambrina explains that their findings are particularly significant given that “the prevalence of type 2 diabetes and obesity is growing at alarming rates around the world.”

The team also says that delivering FGF21 as a conventional drug would not yield the same benefits as gene therapy; firstly, the drug would have to be administered periodically for long-term benefits, and secondly, its toxicity would be high.  Using gene therapy, however, is free of side effects, and a single administration is enough to make the mice produce the protein naturally for several years.

“This is the first time that long-term reversion of obesity and insulin resistance have been achieved upon a one-time administration of a gene therapy, in an animal model that resembles obesity and type 2 diabetes in humans.”

First study author Veronica Jimenez, a UAB researcher

“The results demonstrate that it is a safe and effective therapy,” she adds. The next steps will be to “test this therapy in larger animals before moving to clinical trials with patients,” notes Prof. Bosch.  “[The] therapy described in this study,” she concludes, “constitutes the basis for the future clinical translation of FGF21 gene transfer to treat type 2 diabetes, obesity, and related comorbidities.”

Statistics and facts about type 2 diabetes

Diabetes mellitus, or diabetes, is a disease that causes high blood sugar. It occurs when there is a problem with insulin.

Insulin is a hormone that takes sugar from foods and moves it to the body’s cells. If the body does not make enough insulin or does not use insulin well, the sugar from food stays in the blood, resulting in high blood sugar.

Diabetes is a key health concern worldwide. In the United States, the rate of new cases rose sharply from the 1990s, but it fell between 2008 and 2015, and it continues to fall, according to the Centers for Disease Control and Prevention’s (CDC) National Diabetes Report, 2017. Meanwhile, the number of adults living with diabetes continues to rise.

The most common of diabetes is type 2. According to the CDC, 90 to 95 percent of people with diabetes in the United States have type 2. Just 5 percent of people have type 1.

Key facts

Diabetes is at an all-time high in the U.S. The CDC’s Division of Diabetes Translation states that 1 percent of the population, which is about a half of a million people, had diagnosed diabetes in 1958.

In 2015, around 9.4 percent of the population in the U.S. had diabetes, including 30.2 million adults aged 18 years and over. Nearly a quarter of those with the condition do not know they have it.

Between 1990 and 2010, the number of people living with diabetes more than tripled, and the number of new cases doubled every year.

Figures suggest that the incidence is levelling off and may even be falling, but it remains unclear whether this will continue as other factors come into play, such as the aging population.

The risk of developing diabetes increases with age.

The CDC report that 4.0 percent of people aged 18 to 44 years are living with diabetes, 17 percent of those aged 45 to 64 years, and 25.2 percent of those aged over 65 years.

Causes

Type 2 diabetes is thought to result from a combination of genetic and lifestyle factors.

The exact cause is unknown, but risk factors appear to include:

  • excess body fat
  • high blood pressure or cholesterol
  • having a close family member with the condition
  • a history of gestational diabetes
  • higher age

As obesity has become more prevalent over the past few decades, so too has the rate of type 2 diabetes. In 2013, more than 1 in 3 people in the U.S. were considered to have obesity, and over 2 in 3 were either overweight or had obesity.

In 1995, obesity affected 15.3 percent of Americans, and in 2008, the figure was 25.6 percent. From 1998 to 2008, the incidence of diabetes increased by 90 percent.

Although the link between obesity and diabetes is well known, the reasons they are connected remain unclear. A report in the Journal of Clinical Endocrinology and Metabolism asks why obesity does not always lead to diabetes, given the established link between the two conditions.

The same report notes that the location of body fat appears to play a role. People with more fat in the upper body area and around the waist are more likely to get diabetes than those who carry their body fat around the hips and lower body.

Diabetes and ethnicity

Rates of diabetes vary between ethnic groups.

There may be a combination of factors, including:

  • genetics
  • health conditions
  • lifestyle
  • finances
  • environment
  • access to healthcare

The CDC’s National Diabetes Statistics Report, 2017, found that, among people aged 20 years and over, diabetes affects:

  • 7.4 percent of Non-Hispanic whites
  • 8.0 percent of Asian Americans
  • 12.1 percent of Hispanics
  • 12.7 percent of Non-Hispanic Blacks
  • 15.1 percent of American Indians and Alaska Natives

Why diabetes is serious

Diabetes can have serious health consequences.

The ADA report that more Americans die from diabetes every year than from AIDS and breast cancer combined.

According to the CDC, 79,535 deaths occur each year due to diabetes. The number of fatalities related to diabetes may be underreported.

Why and how does diabetes damage the body and cause complications?

The ADA says:

  • Adults with diabetes are significantly more likely to die from a heart attack or stroke.
  • More than a quarter of all Americans with diabetes have diabetic retinopathy, which can cause vision loss and blindness.
  • Each year, nearly 50,000 Americans begin treatment for kidney failure due to diabetes. Diabetes accounts for 44 percent of all new cases of kidney failure.
  • Each year, diabetes causes about 73,000 lower limb amputations, which accounts for 60 percent of all lower limb amputations (not including amputations due to trauma).

Costs

Because of its high prevalence and link to numerous health problems, diabetes has a significant impact on healthcare costs.

The productivity loss for reduced performance at work due to diabetes in 2012 was 113 million days, or $20.8 billion, according to the ADA.

Diabetes cost the U.S. $327 billion in 2017, including $237 billion in medical costs and $90 billion in reduced productivity.

However, this number does not include:

  • the millions of people who have diabetes but are undiagnosed
  • the cost of prevention programs for people with diabetes, which are not counted under standard medical costs
  • over-the-counter medications for eye and dental problems, which are more common in people with diabetes.
  • administrative costs for insurance claims
  • the cost of reduced quality of life, lost productivity of family members, and other factors that cannot be measured directly

Because diabetes affects various parts of the body, the medical costs span different areas of specialty. The ADA report that:

  • 30 percent of medical costs associated with diabetes are for circulation problems that reduce blood flow to the limbs
  • 29 percent of medical costs associated with diabetes are for kidney conditions
  • 28 percent of medical costs associated with diabetes are for nervous system conditions

Despite its complications, people can manage their diabetes with a comprehensive plan that includes lifestyle changes and proper medical care. If they control their blood sugar levels well, many people with diabetes can lead full, active lives.

Difference between types 1 and 2

In type 1 diabetes, the immune system attacks the cells in the pancreas that make insulin. As a result, the body does not produce insulin, and people with this condition must take insulin by injection or pump every day.

Type 1 diabetes usually develops in children or young adults, but it can occur at any age. There is no known way to prevent type 1 diabetes, and there is no cure.

In 2011-2012, around 17,900 children under the age of 18 years received a diagnosis of type 1 diabetes in the U.S., or around 49 children each day. Type 1 diabetes affects around 1.25 million American adults and children.

People with type 2 diabetes may still have insulin in their bodies, but not enough for proper blood sugar control. Or, the body may not be able to use the insulin it has properly. As a result, blood sugar levels can become too high.

Typically, adults are diagnosed with type 2 diabetes, but children can get it too. Certain factors increase a person’s risk of getting type 2 diabetes, including:

  • obesity
  • older age
  • a family history of diabetes
  • lack of exercise
  • problems with glucose metabolism

The annual relative increase for type 1 diabetes in 2002-2012 in the U.S. was 1.8 percent, but the annual increase for type 2 diabetes was 4.8 percent.

If diabetes or any other medical concern has you  running a little slow, join our ecosystem designed to support your well being.  Here, at HealthLynked, we are building a network that connects patients to physicians in ways never before possible for the purpose of Improving HealthCare.

Ready to get Lynked and take control of your well being?  Go to HealthLynked.com to get started, for free, today!

Adapted from:

[1]  Murrell MD, Daniel.  “Statistics and facts about type 2 diabetes.” Medical News Today. 12 June 2018

[2]  Sandoiu, Ana. “Type 2 diabetes, obesity may soon be reversed with gene therapy.”  Medical News Today, 12 July 2018

Pembrolizumab Secures FDA Approval in Stomach Cancer

 

October
12, 2017, by NCI Staff

An FDG-PET scan of a patient with gastroesophageal junction cancer.

Credit: Li M, Oxford Medical Case Reports Sept. 2014. doi: 10.1093/omcr/omu041.

The Food and Drug Administration (FDA) has granted accelerated approval to the immunotherapy drug pembrolizumab (Keytruda®) for use in some patients with advanced gastric (stomach) cancer.

The approval, announced on September 22, covers the use of pembrolizumab in patients with advanced gastric cancer or gastroesophageal junction cancer that has progressed despite two or more prior lines of treatment with standard therapies. The gastroesophageal junction is a narrow space where the esophagus meets the stomach.

To receive the drug, patients’ tumors also must express the protein PD-L1. In conjunction with the pembrolizumab approval, FDA also cleared the Dako PD-L1 IHC 22C3 pharmDx assay to measure PD-L1 expression in patients with gastric cancer.

As is often the case with accelerated approvals, FDA based its decision on promising results from an early- or mid-stage clinical trial. In this case, the approval was based on findings from a stage 2 clinical trial, called Keynote-059, in which all patients, regardless of PD-L1 status, received pembrolizumab.

In the trial, which enrolled 259 patients with advanced gastric or gastroesophageal junction cancer, approximately 12% of patients experienced at least partial tumor shrinkage following treatment. However, patients in the trial whose tumors expressed PD-L1 (i.e., were PD-L1 positive) were more likely to respond.

According to the most recent data from the trial, presented last month at the European Society for Medical Oncology (ESMO) annual meeting, 16% of PD-L1-positive patients achieved at least a partial response to the treatment, including several patients who had a complete disappearance of their tumors (complete response).

The results confirm suggestions from earlier studies that pembrolizumab “is clearly active in patients with gastric cancer,” said the lead investigator of Keynote-059, Charles Fuchs, M.D., M.P.H., director of the Yale Cancer Center.

Addressing the Biology of Stomach Cancer

Patients with advanced gastric cancer have few effective treatment options, particularly those whose cancer has stopped responding to existing therapies.

The targeted therapy trastuzumab (Herceptin®) is approved as an initial, or first-line, treatment for patients with advanced gastric cancer that overexpresses the HER2 protein. The only FDA-approved therapy for patients whose disease has stopped responding to initial treatment is ramucirumab (Cyramza®), which was shown to modestly improve how long patients lived in two large clinical trials.

Little progress has been made in finding new, more-effective therapies for stomach cancer, said Dr. Fuchs, because so few drugs have been designed to address its specific biology.

With the exception of ramucirumab, “there’s never been a drug that was explicitly developed and approved for stomach cancer,” he explained.

But a door opened with the findings from the first studies from The Cancer Genome Atlas.

Those studies revealed that tumors in a substantial portion of patients with gastric cancer express PD-L1, Dr. Fuchs explained. PD-L1 is a protein on tumor cells and other cells in the tumor microenvironment that binds to PD-1 on immune cells, an action that serves to tamp down the immune response against tumors.

That finding, Dr. Fuchs said, created an opportunity for researchers to test whether agents that target PD-L1 or, like pembrolizumab, its binding partner on immune cells, PD-1, may provide a new option for gastric cancer.

Durable Responses, Including in Some PD-L1-Negative Patients

In the KEYNOTE-059 trial, which was funded by pembrolizumab’s manufacturer, Merck, 148 patients had tumors that expressed PD-L1.

Many of the partial and complete responses seen in these patients persisted for long periods, ranging from just a few months to more than a year.

“The responses really are quite robust and far longer than you would see with any cytotoxic chemotherapy agent,” Dr. Fuchs said.

In addition, three patients whose tumors were PD-L1-negative—according to the parameters used for the trial and the approved test kit—also had complete responses.

In general, patients in the trial tolerated pembrolizumab well, Dr. Fuchs said, with most experiencing only mild side effects. Common side effects included fatigue, anemia, and dehydration. Seven patients, however, had to stop treatment because of severe side effects, and two patients died from treatment-related side effects.

More Research Needed on Biomarkers, Combinations

Drugs that target PD-L1 “will clearly have a role in advanced gastric cancer,” Eric Van Cutsem, M.D., Ph.D., head of the Division of Clinical Digestive Oncology at the University Hospitals Gasthuisberg in Belgium, said after the Keynote-059 results were presented at the ESMO meeting.

But he cautioned that further research is needed to understand how these agents can be used most effectively in patients with stomach cancer.

“The role of PD-L1 expression [as a predictive biomarker] has to be clarified,” Dr. Van Cutsem said, adding that other predictive markers also need to be identified.

A close analysis of the Keynote-059 trial data does provide some additional guidance on which patients are more likely to respond to pembrolizumab, Dr. Fuchs explained.

Patients who were PD-L1 positive and who had undergone only two prior lines of treatment were more likely to respond than patients receiving the drug as a fourth- or fifth-line treatment.

“So, you see a clearly diminishing response rate” in patients who have received more prior lines of treatment, he said.

“Regrettably, there are still many patients who don’t respond,” Dr. Fuchs continued. The data suggest that there are “two opportunities” to change that. One, he said, “is to look at [pembrolizumab] in earlier lines of therapy, and the other is to figure out what [therapy] to partner with it to augment that response.”

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