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Taking on New Challenges: 8 Questions with Gilles Salles

Source: Memorial Sloan Kettering - On Cancer
Date: 12/23/2020
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Gilles Salles recently joined Memorial Sloan Kettering as Chief of the Lymphoma Service within the Division of Hematologic Malignancies. Dr. Salles came to MSK after a long career at Claude Bernard University in Lyon, France.

In an interview conducted in early December just before the annual American Society of Hematology (ASH) meeting, where he presented updates from several studies he’s conducted, Dr. Salles spoke about his decision to join MSK, his research, and his plans for the Lymphoma Service.

Why did you decide to come to MSK?

MSK is a fantastic place in terms of clinical care, clinical research, and basic research. There are not many places in the world that have strengths in all three of these areas. There are so many opportunities here to bring talented scientists together with clinicians who can help them deliver their discoveries to patients.

I’ve been successful in my career, and I’ve been able to bring many improvements in lymphoma care to patients. I asked myself, “Should I just continue here in France and then retire in six or eight years, or should I take on a new challenge?” I decided that this kind of opportunity, to be able to interact more with basic scientists and to build upon translational research projects, doesn’t happen very often. That’s why I took the leap.

What was your relationship with MSK before you came here?

I already knew many members of the Lymphoma Service as well as people in other groups at MSK. I’ve been involved in collaborations with them over the years and have met them at conferences. They are a large part of the reason I decided to join MSK — it’s exciting to work with such talented people.

What was it like moving to a new continent in the middle of a pandemic?

It was strange. I moved to New York over the summer and started working at MSK in mid-August. I haven’t been in the same room with most of my new colleagues yet. We’ve all been meeting on Zoom.

I studied in the United States for my postdoc about 30 years ago in Boston. And I’ve been to New York and other parts of the United States many times since then, both for work and for vacations with my family. This is not the New York I was wishing to rediscover, but I’m hopeful that the pandemic will end soon.

What’s different about MSK’s Lymphoma Service?

We have the SPORE in Lymphoma [Specialized Programs of Research Excellence, a project funded by the National Cancer Institute to help move basic science findings into the clinic]. That was started by my predecessor, Anas Younes, and is now being led by Andrew Zelenetz, a leading physician in the field of B cell malignancies.  

MSK’s Lymphoma Service is quite large, with more than 20 faculty. Because there are so many of us, we can specialize not just in lymphoma but in particular types of lymphoma.

What types of lymphoma do you specialize in treating?

I was very fortunate 20 years ago to be part of the early development of the first monoclonal antibody drug for diffuse large B cell lymphoma (DLBCL), called rituximab. I’m continuing to work on developing new antibody drugs for DLBCL.

I also treat follicular lymphoma. This disease is unusual because some patients who are diagnosed with it don’t require treatment right away, only active surveillance. But it also doesn’t have a cure. Thanks to new treatments, we’ve been able to extend survival for this disease considerably, from an average of eight to ten years to an average of 15 to 20 years. But I think that with the addition of new treatments, especially different kinds of immunotherapy, we will soon be able to offer a cure for some patients.

What are some of the research collaborations you’re planning?

There are many projects I plan to pursue with people here at MSK.

I’m very excited to work with physician-scientist Santosh Vardhana, who recently started his own lab in the Human Oncology and Pathogenesis Program. He has so much knowledge about T cell biology, and we want to apply this to some of the clinical trials we are developing.

I’ve already had the opportunity to work on projects with hematopathologist Ahmet Dogan. To understand lymphoma, we have to really know what’s happening in the tumor, and pathology is the cornerstone of that.

Before I came here, I had met Sloan Kettering Institute cancer biologist Hans-Guido Wendel a few times, and I knew his work. I’ve joined his very innovative project looking at abnormal RNA translation in lymphoma to help bring his findings to the clinic.

In the past, I’ve participated in studies that looked at the ways a person’s genes influence how they respond to treatments for lymphoma. Through this work, I’ve been involved in some consortia with geneticist Vijai Joseph, who studies hereditary cancer. Now that we’re in the same place, we can find time to work more on this project.

What made you interested in pursuing science and medicine as a career — particularly cancer?

I got interested in medicine because I wanted to help people. Medicine is a profession where you bring something to others — health, one of the most precious things we have. I’m also a curious person, so that made science a natural fit.

When I finished medical school, and I had to choose where to focus, the field of oncology was attractive, in part because it was challenging. At that time, there weren’t many options for people with cancer, other than chemotherapy. We in the field were starting to learn more about the biology and immunology of the disease, and it felt like there were many opportunities to improve treatment for cancer patients.

What are you most looking forward to doing in New York once the pandemic is over?

My wife and I are both excited about getting into the jazz music scene. We sometimes hear musicians when we’re walking through Central Park, and it’s so good to hear live music.

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Remembering Jimmie Holland, a Founder of Psycho-Oncology

Source: Memorial Sloan Kettering - On Cancer
Date: 01/09/2018
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On Christmas Eve, Memorial Sloan Kettering and the wider cancer community lost a beloved and brilliant doctor, Jimmie Holland, who died of cardiovascular disease at 89. Dr. Holland was a tireless advocate for supporting the emotional and psychological needs of people with cancer. She also made huge strides in reducing the stigma surrounding the disease.

Dr. Holland was considered a founder of the field of psycho-oncology, which combines oncology and psychiatry. It is increasingly considered a vital part of comprehensive cancer care, largely thanks to her work.

In 1977, Dr. Holland joined MSK as the inaugural Chief of the Psychiatry Service, the first such service at a cancer center anywhere in the world. She was then named Chair of MSK’s Department of Psychiatry and Behavioral Sciences when it was created in 1996. The department was also the first of its kind, and Dr. Holland remained in her role there until 2003. At the time of her death, she held the Wayne E. Chapman Chair in Psychiatric Oncology.

“Jimmie’s death is a profound loss to us all,” says MSK Physician-in-Chief José Baselga. “Through her visionary work she has forever changed the landscape of cancer care.”

Changing World, Changing Needs

Dr. Holland grew up in a tiny town in north Texas, the only child of a cotton farmer and his wife, neither of whom had finished high school. When she earned her medical degree from Baylor College of Medicine in the early 1950s, “cancer”was a word that most people wouldn’t say out loud. Many newspapers and magazines wouldn’t print it, and patients often were not even told of their diagnosis.

That began to change in the 1970s. Better treatments became available and people with once-fatal cancers starting living longer and even being cured. As the wife of James Holland — a leading oncologist and one of the pioneers of chemotherapy combinations — Dr. Holland had a front-row seat from which to witness the medical revolution that was taking place. While her husband and his colleagues focused on curing people of their cancer, Dr. Holland asked a question that none of them were able to answer: How do the patients feel about it?

As a psychiatrist, she had long been interested in studying how people with otherwise good mental health responded emotionally and psychologically to life-threatening illnesses. She called this focus “psychological care of the medically ill.” She began encouraging oncologists who were conducting clinical trials to include questions about patients’ quality of life in their data collection and research.

The Science of Caring

But measuring things like anxiety, depression, and fatigue was not always straightforward. Dr. Holland met this challenge by developing ways to gauge what patients were feeling that went beyond what doctors and nurses could just observe. She worked to create objective scales to evaluate aspects of people’s experience that were once considered immeasurable. This in turn could validate whether psychological treatments were working. Her research brought the emerging field of psycho-oncology into the realm of evidence-based science, which allowed it to become a recognized subspecialty.

During her years at MSK, Dr. Holland created the nation’s largest training and research program in psycho-oncology. In 1984, she produced for MSK the first-ever syllabus on psycho-oncology. In 1989, she was senior editor of the first textbook on the subject. She also shared her knowledge with the world. She co-founded the International Psycho-Oncology Society in 1984 and founded the American Psychosocial Oncology Society in 1986. She is credited with putting psychosocial and behavioral research on the agenda of the American Cancer Society in the early 1980s. She was also a founder and co-editor-in-chief of the journal Psycho-Oncology.

Dr. Holland recognized that people’s psychological distress could linger even after they were considered cured of their cancer. To address this, she advocated for the formation of a program at MSK that today is called Resources for Life After Cancer. It became a model for other similar initiatives around the world.

“Jimmie was a cancer pioneer, a remarkable woman, and a once-in-a-generation influencer,” says William Breitbart, the current Chair of Psychiatry and Behavioral Sciences and the Jimmie C. Holland Chair. “Her death is a profound loss for all of oncology.”

The Sixth Vital Sign

Dr. Holland pushed to recognize patient distress as the sixth vital sign in medicine. (The others are temperature, pulse, blood pressure, respiration, and pain.) She played a key role in the development of the National Comprehensive Cancer Network’s distress thermometer. This enables people to report their levels of anxiety and depression on a scale of zero to ten, similar to the way they rate their pain.

Other topics that were important to her included survivor guilt, diminishing the stigma of a cancer diagnosis, and evaluating ways to lessen cancer side effects like depression, anxiety, and fatigue with medication and other treatments.

In her later years, she also became particularly interested in supporting the psychosocial needs of elderly patients. As part of that effort, she founded the Vintage Readers Book Club, an offshoot of a support group she led on aging and cancer. The participants talked about classic works by writers including Cicero and Benjamin Franklin, and used their discussions as a springboard for talking about wider-ranging topics that were important to them.

“Jimmie was an inspiration on multiple levels, not least of which was her appreciation of the fact that we are more than our careers,” says psychologist and author Mindy Greenstein, who first came to know Dr. Holland when she conducted her fellowship in MSK’s Department of Psychiatry and Behavioral Sciences. The two later worked together and coauthored the book Lighter as We Go: Virtues, Character Strengths, and Aging. “While raising her own family as well as comforting patients and their family members with her Texas warmth and sound insights, she still found the time to accomplish so much in her work. Hers was a life of unique and dedicated service.”

Dr. Holland, who died at home surrounded by family, was still seeing patients up until two days before she died. She is survived by her husband; six children; nine grandchildren; and countless friends, colleagues, and collaborators.

“Jimmie was a true pioneer in the field of psycho-oncology, and her passion for her patients and her research was evident,” says MSK President and CEO Craig Thompson. “She will be dearly missed by the MSK community and by the world.”

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MSK Opens New Clinic to Monitor People with a Genetic Risk for Developing Blood Cancer

Source: Memorial Sloan Kettering - On Cancer
Date: 01/23/18
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Most cancers arise by chance and, therefore, are hard to predict. But scientists and doctors are learning more about the genetic changes that cause cancer as well as those that signal a higher risk for it. Thanks to MSK-IMPACT™, Memorial Sloan Kettering’s diagnostic test that looks for genes associated with cancer, more people who carry cancer-related genes are being identified.

To take advantage of these new opportunities, MSK has launched the Precision Interception and Prevention Initiative. This program is focused not only on catching cancer very early but also on eventually preventing it from forming in the first place. One of the program’s components is a clinic for people with an age-related condition called clonal hematopoiesis (CH). MSK’s clinic, the first of its kind, is beginning to see people with CH this month.

“This initiative unites high-impact science and clinical medicine to actively identify and help a population of people who are either at a high risk of developing cancer or who already have cancer but don’t know it,” says Luis Diaz, head of MSK’s Division of Solid Tumor Oncology, who is leading this effort.

A person with clonal hematopoiesis has an increased number of blood cells that carry some of the same mutations that are found in blood cancers. CH occurs when hematopoietic stem cells (which give rise to all types of blood cells) form cells that are genetically distinct from the rest of the blood stem cells. Sometimes these distinct cells carry cancer-associated mutations.

“This is an exciting and quickly growing field, and it’s vital for us to learn as much about it as possible,” says physician-scientist Ross Levine, who will be heading the new clinic. “By launching this effort to monitor and care for people with CH, we will be able to advance our understanding about this important area of science.”

Clonal Hematopoiesis: A Common Phenomenon Linked to Aging

Dr. Levine was part of the research team that was the first to identify the genetic basis of CH and its connection to blood cancer. They first reported that relationship in 2012. Since then, many investigators have begun to study the condition and have shown that CH is very common. Researchers have found that it is linked to an increased risk of certain blood cancers, especially myelodysplastic syndrome and acute myeloid leukemia, as well as cardiovascular disease, heart attacks, and strokes.

The most common cause of CH is aging. Studies have suggested that between 10 and 20% of people over age 70 have signs of it in their blood. Smoking also increases the risk. “CH is very common. Millions of people have it,” Dr. Levine says. “But most people don’t know they have it, and doctors don’t know what to do with it. We thought it was important to do more research on this phenomenon so that we can start figuring out who may need intensive follow-up and treatment right away and who can be observed.”

“Right now we don’t have good ways to predict who is most likely to develop a blood cancer, so any new findings that come out of this clinic have the potential to make a big difference,” says Marcel van den Brink, Head of MSK’s Division of Hematologic Oncology.

In addition, certain types of chemotherapy and radiation therapy can increase the incidence of CH. This explains why cancer survivors carry a risk for secondary leukemia. The still-rare condition is happening more often because more people with cancer are surviving longer or are cured of their disease.

A study last year from Dr. Levine, MSK researcher Michael Berger, and their colleagues found that 25% of people with any type of cancer had CH, a higher number than had previously been observed. Of that group, 4.5% had specific mutations that are known to drive the formation of leukemia.

Treating Blood Cancer Earlier

Most people with CH will never develop blood cancer, but doctors are starting to understand which individuals with CH are at the highest risk. “This is one of the reasons this clinic is so important,” says MSK hematology fellow Kelly Bolton, who will be helping to run the new program. “We hope about 100 patients with high-risk forms of CH will participate in our first year.”

The MSK investigators who designed MSK-IMPACT, including molecular pathologist Marc Ladanyi and Dr. Berger, believed it was important to look for cancer-related genes in people’s normal tissue as well as in their tumors. This would help them determine whether a person’s cancer occurred completely by chance or whether inherited factors played a role. The easiest normal tissue to obtain is blood, and the gene mutations linked to CH started to show up as part of MSK-IMPACT testing.

As MSK launches its CH clinic, people who have undergone MSK-IMPACT testing for other cancers and have been found to have high-risk forms of CH in their blood will be contacted by their surgical or medical oncologist and invited to enroll in the program. MSK patients who are treated for low blood counts and found to have CH as part of their blood work will also be seen.

“In the past, CH has been just an incidental finding. When we were worried someone had an undiagnosed blood cancer, we would refer him or her to the Leukemia Service,” Dr. Bolton explains. “Now when we discover patients with high-risk forms of CH, we will have a clinic with experts in CH to manage and coordinate their care.”

For now, those who enroll in the clinic will have the opportunity to have their blood tested on a regular basis. People who are found to have a blood cancer will be able to start treatment immediately, when the disease is much easier to control.

Looking toward Future Treatments

In the future, MSK investigators hope to launch clinical trials of treatments that could block the progression from CH to active cancer. In addition, treatment for solid tumors may be tailored to protect people who already have an increased risk of developing a second cancer. But doctors don’t yet know enough about what drives the formation of CH to make any changes to treatment now.

Recent studies suggest that people with CH are at risk for cardiovascular diseases. However, testing for CH is not currently part of screening for them. “It’s important for people with CH to follow up with their primary-care doctors and make sure they have had the appropriate screenings for cardiovascular diseases,” Dr. Bolton says. “We will encourage everyone participating in our CH clinic to do this.”

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An Unlikely Treatment for Triple-Negative Breast Cancer: Prostate Cancer Drugs

Source: Memorial Sloan Kettering - On Cancer
Date: 01/29/2018
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For many people with breast cancer, drugs that target proteins driving the cancer’s growth have made a huge difference in fighting the disease. But for those with triple-negative breast cancer — a subtype defined by what it lacks rather than by its own characteristics — there are fewer good options.

Now doctors are finding an unlikely therapy for treating some of these tumors: drugs that were originally developed to treat prostate cancer. Results from a new multicenter trial published in the Journal of Clinical Oncology (JCO) report success with this approach. Memorial Sloan Kettering is at the forefront of this research.

“There is a great unmet need for novel, active therapies for patients with triple-negative breast cancer,” says MSK Breast Medicine Service medical oncologist Tiffany A. Traina, who is leading many of these efforts and was first author of the new study. “We have many women with advanced triple-negative breast cancer looking for clinical trials because standard chemotherapy options aren’t always enough for them.”

Different Breast Cancer Subtypes, Different Treatments

The three most common proteins known to fuel breast cancer growth are the estrogen receptor, the progesterone receptor, and the HER2 receptor. Estrogen and progesterone are female hormones that help regulate the menstrual cycle, among other functions. Drugs that block estrogen, such as tamoxifen and the class of drugs called aromatase inhibitors, can slow or stop the growth of tumors with these receptors.

Breast cancers with growth driven by the HER2 receptor can be treated with drugs that block this receptor, such as trastuzumab (Herceptin®) and others.

About 15% of breast cancers, however, are defined as triple negative. This means they don’t have any of these receptors. It also means they don’t respond to drugs that target them. These cancers do respond to chemotherapy, and some studies have suggested they actually may respond better to chemotherapy than other subtypes. But chemotherapy has more side effects than these other, targeted drugs.

Triple-negative disease is more common in African Americans, younger women, and those whose cancer results from inherited mutations in the BRCA genes.

Finding an Unlikely Target for Triple-Negative Breast Cancer Treatment

It turns out that about half of triple-negative breast cancers carry another hormone receptor — the one for the male hormone androgen. In a landmark study more than ten years ago, the late MSK pathologist William Gerald was the first to report that some breast cancers could carry the androgen receptor. His research also found the androgen receptor was responsible for growth of the cancer. This opened up a possible new option for treating breast cancer with this type of hormone therapy. (Although estrogen and progesterone are considered female hormones and androgens are regarded as male ones, both types of hormones are found in people of both genders.)

In 2013, Dr. Traina was the first to lead a multicenter study showing that this approach may be effective in treating triple-negative breast cancer. That study used another androgen-targeting drug, called bicalutamide (Casodex®).

The recent JCO study reported results from 78 women with advanced triple-negative breast cancer that expressed the androgen receptor. The purpose of the phase II trial was to evaluate the safety and efficacy of the prostate cancer drug enzalutamide (Xtandi®). All participants were treated with the drug, which is given as a pill, once a day. The investigators found that 33% of people benefited from the drug. Survival also appeared longer than expected for triple-negative breast cancer. The only serious side effect was fatigue.

Enzalutamide was co-invented by physician-scientist Charles Sawyers, Chair of MSK’s Human Oncology and Pathogenesis Program. The drug targets multiple steps in the androgen receptor signaling pathway, making it more effective in treating prostate cancer than some other androgen-blocking drugs.

“What’s so exciting is that this research started at MSK,” Dr. Traina says. “It’s a true bench-to-bedside story that begins with a discovery in the lab and has led to many trials that may offer a new, effective treatment for patients with this highest-risk subset of breast cancer.”

Further Expanding Uses of Enzalutamide

“The findings from this study support the continued development of enzalutamide for the treatment of advanced triple-negative breast cancer,” Dr. Traina adds. Another recent study that Dr. Traina participated in also found that enzalutamide can provide benefit when added to an aromatase inhibitor called exemestane (Aromasin) in people whose breast cancer carries both estrogen and androgen receptors. The findings were presented at the recent San Antonio Breast Cancer Symposium.

In addition, she and her colleagues are studying enzalutamide in early-stage triple negative breast cancer. They are also looking at several other prostate cancer drugs that block the androgen receptor, both alone and in combination with other novel targeted therapies.

Dr. Traina and MSK breast medical oncologist Ayca Gucalp are also recruiting people for a new trial that would test androgen receptor–blocking drugs specifically in men with breast cancer. About 90% of male breast cancers carry the receptors for estrogen or progesterone, and studies suggest that most of them also carry the androgen receptor.

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Chemotherapy-Immunotherapy Combination Aims to Knock Out Melanoma with a One-Two Punch

Source: Memorial Sloan Kettering - On Cancer
Date: 02/02/2018
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For some people with cancer, drugs that help the immune system recognize and attack tumor cells have been a game changer. But for most, the outcomes from these immunotherapies are not effective, and other treatments are required.

Now a collaborative group of melanoma experts is testing a novel combination therapy for certain people with that aggressive form of skin cancer. They have combined immunotherapy drugs with chemotherapy that treats only the area affected by cancer. The results of lab research, as well as the first-ever clinical trial to explore this particular approach, are being reported in the journal Cancer Immunology Research.

“Immunotherapy has had great successes, but we’re looking for ways to make it effective for more people,” says Charlotte Ariyan, a Memorial Sloan Kettering surgeon who is the lead author of the new study. “Our work in the lab is focused on developing better treatments, which we can then bring to patients as part of clinical trials.”

Using Two Treatments Together for Better Results

The approach combines the relatively new immunotherapy drug ipilimumab (Yervoy®) with a treatment that’s been around much longer, called isolated limb infusion.

Limb infusion is used as a therapy for in-transit melanoma, which means the cancer has spread throughout an arm or leg. People with this form of the disease can have dozens of small tumors, making it difficult to treat them all with surgery or radiation. The infusion treatment is given by putting a very high dose of chemotherapy directly into the affected arm or leg. A tourniquet prevents the medication from going into the rest of the body.

“Limb infusion is an interdisciplinary treatment that requires a lot of expertise,” Dr. Ariyan explains. “At MSK we have a dedicated team for limb infusion that includes an anesthesiologist, an interventional radiologist, nurses, and medical oncologists. This allows us to offer this specialized treatment to our patients in a very efficient way.”

But limb infusion often doesn’t have long-lasting results. Most of those who respond see their disease come back within a year. This is where the immunotherapy comes in.

Making Cancer Visible to Immune Cells

In research conducted in the lab, Dr. Ariyan and her colleagues, including Sloan Kettering Institute Immunology Program Chair and Director of the Ludwig Center for Cancer Immunotherapy (LCCI) Alexander Rudensky, found that when mice were given chemotherapy before ipilimumab, the responses to the immunotherapy were much better.

“The idea behind immunotherapy is that you’re trying to get the body to recognize the tumor, but a lot of times the tumor stays silent,” says Dr. Ariyan, who is also a member of LCCI. “Because chemotherapy causes some of the cancer cells to die, it leads to inflammation in the area around the tumor. This is an opportune time to give immunotherapy because the tumor is easier for the immune system to find.”

In the mice, the researchers found that combining the treatments resulted in an increase in the number of immune cells that were able to get into the tumor. This ultimately led to improved survival in the animals.

A few previous studies done in people with lung cancer have looked at combining immunotherapy with systemic chemotherapy. That’s when chemotherapy is delivered throughout the body. The results of that combination treatment have been mixed. “Because systemic chemotherapy can wipe out a person’s immune cells, it’s usually not the best approach,” she says. “However, if you can give chemotherapy in a way that the immune system is still intact, it appears to show benefits.”

Taking the Treatment Approach to People

The discoveries made in mice led to the idea to test this treatment in people. Money from Cycle for Survival — MSK’s indoor team-cycling fundraiser, which supports research on rare cancers — as well as from other foundations helped move the research into a clinical trial.

The phase II trial included 26 people who had advanced melanoma in an arm or leg. Participants were given limb infusion with chemotherapy followed by ipilimumab. After three months, 85% had their tumors shrink as a result of the treatment. Of those who responded, more than half had a complete response, meaning that their tumors disappeared. Today, 58% of them remain disease free, even after they stopped receiving ipilimumab.

Dr. Ariyan says that the team will continue to explore this approach in people with in-transit melanoma who are not responding to immunotherapy alone. In addition, they are considering it to treat other types of cancer, such as sarcoma, which frequently occurs in the muscles, bones, and connective tissues in the arms or legs and usually doesn’t respond to immunotherapy.

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Reassessing Palliative Care: MSK Emphasizes Supportive Care for All People with Cancer

Source: Memorial Sloan Kettering - On Cancer
Date: 02/15/2018
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The doctors, nurses, and other staff at Memorial Sloan Kettering are focused on all aspects of cancer care. This means that in addition to the most-advanced therapies for treating cancer, we deliver care that tends to the physical, emotional, and spiritual needs that come up during and after cancer treatment.

“We feel strongly that supportive care is compatible with the most-aggressive, state-of-the-art cancer care,” says Judith Nelson, who is Chief of the Supportive Care Service. “It’s not an either-or situation: Supportive care and cancer care go together. We emphasize the importance of the supportive services that are available from a patient’s very first appointment.”

“Supportive care is based on a person’s needs, not on their prognosis. People with all types and stages of cancer can benefit from it,” Dr. Nelson adds. “The goal of our service is to help patients live maximally and to have every day for them be the best day possible, for as many days — or weeks, years, or decades — as possible.”

A Mission of Supporting People with Cancer

Although the terms “palliative” and “supportive” can be used interchangeably, MSK wanted to emphasize the supportive part of our mission. About a year ago MSK renamed the Palliative Medicine Service in the Department of Medicine. It is now called the Supportive Care Service.

Supportive care covers a range of services for people with cancer. This includes medical care to address physical symptoms, such as pain, nausea, or fatigue. It also consists of care to help people address their emotions, such as anxiety, stress, and depression. These services can incorporate support for the spiritual distress that people may face after their diagnosis as well. And supportive care can help people with cancer ensure that their care matches their values and goals.

Members of MSK’s supportive care team train oncology doctors and nurses to notice when people need more support and to provide the care that can help them. Supportive care assessments are an ongoing part of the care that people receive at MSK, whether in the hospital or as an outpatient.

“The best way to know if patients are in distress is to ask,” Dr. Nelson says. “Moving forward, we are making sure that all of our healthcare providers are empowered to do assessments from the very beginning of treatment. Based on these assessments, patients and their families will get the help they need from their oncology team and a supportive care specialist if needed.”

A Growing, Interdisciplinary Field

Robert Sidlow leads MSK’s Division of Survivorship and Supportive Care. The group was launched about three years ago within the Department of Medicine. It bolsters and advances a number of services across MSK. These include the General Internal Medicine, Hospital Medicine, Geriatrics, Integrative Medicine, Employee Health and Wellness, Urgent Care, and Supportive Care services.

“It’s important to emphasize the interdisciplinary nature of supportive care,” Dr. Sidlow says. “In addition to members of the specialized Supportive Care Service, many MSK doctors are part of the extended supportive care team. Psycho-oncologists are tremendously helpful to patients and their families. The robust Integrative Medicine Service delivers complementary treatments, such as acupuncture and mind-body therapies. The Department of Rehabilitation Medicine is wonderfully helpful at getting people back to their regular lives as much as possible.”

MSK also has a unique supportive care fellowship program, in which doctors and nurse practitioners train side by side. “We are the standard bearer for cancer care and training across the country and around the world,” Dr. Nelson says. Applications to the training program have tripled in the past few years, and the program’s graduates have gone on to work at many leading institutions around the country.

Continuing to Improve End-of-Life Care

Despite the focus on supporting all people with cancer, end-of-life care is still a key part of supportive care services.

“We help people plan in advance so important decisions are not made in a time of crisis,” Dr. Nelson explains. “Doctors need to hear from patients and their families about what’s important to them in their lives and what their priorities are.”

Dr. Sidlow adds, “With the constant stream of new treatments available, people with cancer and their care teams now have much more prognostic uncertainty than in the past. Twenty years ago when someone had an advanced cancer, by and large everyone anticipated an inevitable downward path. But today, the course of advanced cancer can be less obvious. Often the experience of having cancer is more like congestive heart failure. People alternate between periods of relative stability and periods of greater need for supportive care.”

He says that although many people with cancer are living longer than in the past, “the burdens that they and their caregivers face — physically, emotionally, and financially — can be quite significant and worsen everyone’s quality of life. This underscores the importance of understanding patients’ values and integrating supportive care early in cancer treatment.”

MSK patients and their families who feel they may benefit from specialized supportive care services can speak to their care team.

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The Last Frontier in Cancer Care: Treating Disease When It Spreads to the Brain

Source: Memorial Sloan Kettering - On Cancer
Date: 02/16/2018
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Metastatic brain cancer gets far less attention in the media than primary brain tumors, despite being at least ten times more common. Metastatic brain cancer occurs when tumors spread from other parts of the body to the brain. It was once considered an end stage of the disease. Doctors’ main focus was making patients comfortable. But increasingly, metastatic brain cancer is being treated aggressively, with the goal of eliminating it. Memorial Sloan Kettering doctors and scientists are leading the charge to find new and innovative ways to treat this type of brain cancer.

“There used to be this feeling of therapeutic nihilism about metastatic brain cancer. Once cancer spread there, everyone assumed not much could be done,” says Adrienne Boire, a neuro-oncologist who also leads a lab in MSK’s Human Oncology and Pathogenesis Program. “Unfortunately, many doctors in the community still feel that way. But as a physician-scientist at the best cancer hospital in the country, I can’t just stand by. At MSK, we are making use of all the amazing resources we have to be able to understand and address this very complex problem.”

“Treating metastatic brain tumors is slowly turning into the last frontier in cancer care,” adds physician-scientist Viviane Tabar, Chair of MSK’s Department of Neurosurgery. “We often see people whose cancer is very well controlled in other parts of their body but who are still struggling with poorly controlled brain metastases.”

The symptoms of brain metastases and their impact can be severe. They may include headaches, nausea, weakness, seizures, and problems walking, speaking, and seeing.

An Increasing Problem in Cancer Care

“From a surgeon’s perspective, we are treating these tumors with a higher frequency than ever before, now that people have better options for medical treatment of their primary disease,” Dr. Tabar says.

There are no data to show that metastatic brain tumors are becoming more common, but there’s a general sense in the field that they are. One reason could be that better imaging techniques are more likely to detect tumors that have moved there. Another common opinion is that doctors are getting better at treating cancer in other locations so people are living longer and tumors have more time to grow in the brain.

Targeted drugs and other new therapies — such as EGFR and checkpoint inhibitors for lung cancer and HER2 inhibitors and hormone therapies for breast cancer — often are very effective at keeping cancer in check where it began. They can also work well in other organs where cancer has spread. But these therapies are less effective on tumors in the brain. This is due, in part, to what is called the blood-brain barrier. This barrier may make it harder for these drugs to reach the brain.

In addition, metastatic brain tumors usually are genetically very different from the original tumors. This is because cancer cells change as they grow and spread throughout the body.Back to top 

Identifying Variations in Tumor Biology

Because of these genetic differences, new approaches are needed to treat metastatic brain tumors. “We’re in a strange spot,” Dr. Boire says. “We know what the tumor used to be — a breast tumor, for example, or a melanoma tumor. And based on imaging, we know where it is. But we don’t know all the changes it’s gone through to get to where it is. That can be a challenge to figure out.”

To address this, MSK neurologists and pathologists are working together to develop liquid biopsies of the spinal fluid, which may contain DNA from brain tumors. This would allow them to run MSK-IMPACTTM, a test that simultaneously screens for hundreds of genes that drive tumor growth. Doctors can use it to determine the best targeted therapy for a tumor without having to obtain a tissue biopsy from the brain. “This would really be a game changer,” Dr. Boire notes.

Another tactic being studied by Dr. Boire and her colleagues, including Sloan Kettering Institute Director Joan Massagué, is finding drugs that target the microenvironment around the tumor, rather than the tumor itself. “There are many different kinds of cancer that can set up shop in the brain, which means it will be unlikely that we find one treatment that’s effective against all tumors,” she explains. “But there’s only one brain. Perhaps finding out how the brain responds to cancer holds the key to finding ways to treat brain metastasis.”

A Different Kind of Brain Tumor and Treatment

In addition to being different from the tumors in which they originated, metastatic brain cancers are also very different from primary brain cancers. Surgically, however, that may make these tumors easier to treat. “Compared with tumors like glioblastoma, brain metastases tend to look very different from the surrounding brain tissue. It is simpler to determine their boundaries when removing them,” Dr. Tabar explains. She adds that people who have surgery for brain metastases tend to recover very quickly. “Most patients can go home in only two or three days, and they usually do very well,” she says.

In some cases, brain metastases can occur in critical areas of the brain, such as those that control movement or speech. In those circumstances, Dr. Tabar doesn’t hesitate to use all of the surgical technology at her disposal. She might opt for brain mapping or keeping the patient awake during surgery. That way, she can “maximally protect their function,” she says. “Our aggressive approach to brain metastasis is motivated by the often excellent outcomes of surgery and radiation, and their positive impact on quality of life. There’s been enormous progress in systemic treatments, leading to improved survival.”

Many people with brain metastases have multiple tumors, not all of which can be removed with surgery. They are often treated with a combination of surgery and radiation. Several different types of radiation are available for people who require this treatment. These include intensity-modulated radiation therapy, which uses images from CT scans to focus high doses of radiation directly on the tumor; image-guided radiation therapy, which uses real-time imaging with a CT scan or x-rays during radiation therapy; and stereotactic radiosurgery, which can treat small tumors with a single high dose of radiation. These advanced technologies can focus the radiation beam at the specific area needing treatment while sparing the surrounding normal brain cells. Doctors at MSK avoid giving radiation to the entire brain to minimize side effects.

Radiation therapy and surgery are often combined for the same tumor, to minimize the chance it will regrow after surgery or if parts of it could not be removed. This may be the case if the tumor is in a key area of the brain or surrounding an important blood vessel. Radiation therapy may also be combined with immunotherapy.

A Multidisciplinary Team Focused on the Same Goal: The Individual

Another important contributor to MSK’s ability to treat metastatic brain cancer is our expertise in supportive services. “Our experts in rehabilitation, physical therapy, and other specialties make sure that our patients are strong enough to tolerate treatment,” Dr. Boire says. “We want to give everyone the best chance we can to have the best outcome possible after treatment is over.” This also includes experts in epilepsy, who are able to treat the seizures that are often caused by brain tumors.

“Metastatic brain cancer is a huge problem in oncology, and it doesn’t get the amount of attention it deserves,” Dr. Tabar concludes. “For that reason, here at MSK we are beginning to talk about building a formal center specifically for brain metastases. Assembling a group of experts on both the clinical side and in the lab will enable us to offer a multidisciplinary approach to a growing number of people who could benefit from an aggressive approach toward controlling brain metastasis.”

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The Latest on Genetic Testing for BRCA Mutations in Breast Cancer

Source: Memorial Sloan Kettering - On Cancer
Date: 02/21/2018
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Last month, the US Food and Drug Administration approved olaparib (Lynparza®) for people who have certain types of breast cancer that has spread and who have been previously treated with chemotherapy. Olaparib was the first drug in a class called PARP inhibitors to be approved for breast cancer.

Medical oncologist Mark Robson headed the first multicenter phase III clinical trial of this drug for breast cancer. Results from that study, which were reported at the American Society of Clinical Oncology meeting last summer, led to the drug’s approval.

Dr. Robson, who was named Chief of Memorial Sloan Kettering’s Breast Medicine Service in November 2017, was recently part of a panel discussion held at New York City’s 92nd Street Y entitled “Knowledge Is Power: Understanding and Managing BRCA-Related Cancer Risk.” We spoke with him about what this drug approval means for people with breast cancer, as well as its implications for expanding the use of genetic testing for BRCA mutations.

How do we know whether someone’s cancer is caused by a BRCA mutation?

At MSK, everyone with advanced cancer is offered the opportunity to undergo testing with MSK-IMPACT™. In addition to looking for cancer mutations in the tumor itself, this test can scan the normal tissue for cancer mutations, if the patient agrees. Because BRCA mutations are carried in the germline, meaning all the cells in the body, they show up with this test.

There are other tests for inherited BRCA mutations that are available through a number of companies. But we don’t recommend taking these tests unless you speak with a genetic counselor.

Based on your findings, who do you think should get BRCA testing?

Now that olaparib is an approved therapy, I would recommend that anyone with advanced breast cancer get the BRCA test. It can help guide their treatment, and it may allow them to avoid getting chemotherapy for a longer period. Olaparib is taken at home as a pill, and it has relatively few side effects.

People with earlier-stage breast cancer as well as other forms of cancer that have been associated with BRCA mutations may want to consider getting tested if their personal or family history suggests they might be carrying a BRCA mutation. That is best determined through a consultation with a genetic counselor. Knowing that they have a mutation can help them plan ways to reduce their risk of developing another cancer. It also might tell them if there is a clinical trial that might help them.

These are genes that are inherited and run in families. Because of that, close relatives of people who are known to have BRCA mutations should strongly consider talking to a genetic counselor and getting tested.

Some people have suggested that because BRCA mutations are more common in people of Ashkenazi Jewish descent, the use of this test should be expanded to include this whole group. There is certainly the potential to benefit, since many people with mutations don’t have a family history that would prompt them to get tested. But there are also possible risks if people aren’t prepared to learn that they have a mutation. There are a number of studies that are trying to find the best way to get this information to people who want it. One of them is the BFOR study, which is being led by Kenneth Offit of the Clinical Genetics Service here at MSK.

How would a BRCA mutation affect my options for drug therapies?

PARP inhibitors work by blocking enzymes called poly (ADP-ribose) polymerases, or PARPs for short. Members of this family of enzymes help repair breaks in DNA. If DNA cannot be repaired, cells cannot divide and will die. An emerging strategy in cancer therapy has been to block the repair role of PARPs. Normal cells can overcome this type of attack, but certain cancer cells cannot.

In particular, mutations in the genes BRCA1 and BRCA2 are connected with the inability to repair this kind of damage. This weakness makes cancers linked to BRCA mutations good candidates for these drugs.

Besides breast cancer, what other cancers are BRCA mutations linked to?

BRCA mutations have been known to be associated with breast cancer and ovarian cancer for more than two decades. More recent studies have shown that they are also linked to many cases of advanced prostate cancer, as well as pancreatic cancer.

Olaparib was previously approved for treating BRCA-associated ovarian cancer. There are two other PARP inhibitors approved for ovarian cancer as well. Clinical trials at MSK and many other centers are looking at expanding PARP drugs to all cancers that are associated with BRCA mutations.

You have been studying BRCA for a long time. Is there anything that’s surprised you about recent developments?

It’s been an incredibly exciting and interesting time to be involved in this field. When the Human Genome Project was completed in 2003, there were all these theoretical ideas of how genetic information could be applied to human health. But none of them were very practical.

The ways that we are beginning to use genetic information now are what we always hoped we would be able to do, even though at that time we couldn’t envision the details. So I would not say that I’m surprised, even though I couldn’t have predicted exactly what we’d be doing today.

We have reached the place we’re at in this field because of investments in fundamental research. It’s been a privilege to help turn promise into reality.

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New MSK Initiative Focuses on the Early Detection and Prevention of Cancer

Source: Memorial Sloan Kettering - On Cancer
Date: 02/22/2018
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Cancer often begins to form years or even decades before symptoms appear. And for most cancers, the longer they remain undetected, the more opportunities they have to spread, ultimately making them much harder to treat.

That’s why early detection is an important focus of cancer research. Memorial Sloan Kettering recently launched the Precision Interception and Prevention (PIP) initiative to advance those developments. This institution-wide, broad-ranging effort will concentrate not only on catching cancer very early but also on preventing it from developing in the first place.

“This concept has always been incredibly appealing, but until very recently, the tools to address it were not there,” says MSK Physician-in-Chief José Baselga. “Today, with the capabilities we now have for genomic sequencing of tumors, everything is falling into place. We believe that PIP will change cancer as we know it.”

Developing a Tool Kit for Early Cancer Diagnosis

One of the most important tools that has made this effort possible is MSK-IMPACTTM, a diagnostic test that looks for genetic changes in people’s tumors. However, the test goes beyond just analyzing tumors; it also reveals mutations in people’s normal cells. Because of that, it’s uncovering both the genetic changes that drive existing tumors and the genetic changes that people are born with. Some of these inherited mutations make them more susceptible to developing future cancers.

Rates for any given cancer are low in the general population. That makes it hard to home in on markers for them. But people who have undergone MSK-IMPACT testing for existing cancers and have been found to carry inherited mutations can help in the development of better detection methods.

Family members of those people who have been found to carry cancer genes can also be tested. “Beyond the benefits for our patients, another important goal of our initiative is to identify family members who appear healthy but may harbor inherited mutations in cancer genes,” says Zsofia Stadler, an MSK medical oncologist and clinic director of the Clinical Genetics Service. “These at-risk family members can make more-intensive efforts at cancer screening and risk reduction, with the goal of early detection or even cancer prevention.”

Moreover, some of the inherited mutations could affect treatment. Doctors may use this genetic information to select targeted therapies for patients.

A Focus on Blood Cancers

Another major part of PIP is early-detection methods for blood cancers, such as leukemia and myelodysplastic syndrome. MSK-IMPACT testing has helped detect a condition called clonal hematopoiesis (CH). CH is a genetic signature found in the blood that identifies people who have an increased risk of developing certain blood cancers.

MSK has opened a CH clinic, the first of its kind. There, people with CH can be followed to learn more about how these cancers form and, eventually, to develop ways to prevent them.

“Our CH clinic is an important component of PIP, and one of the most novel aspects of the whole initiative,” says Luis Diaz, Head of MSK’s Division of Solid Tumor Oncology, who is spearheading PIP. Dr. Diaz joined MSK in April 2017 but was interested in the importance of developing early-detection and prevention methods even before coming to MSK. “My job is to make it happen,” he notes.

Eliminating Traces of Cancer

PIP will also be looking for better ways to detect and treat the small amounts of cancer that may be left after people have had treatment. This is called minimal residual disease.

Even after someone has had surgery, radiation, and chemotherapy to treat a tumor, some cancer cells may remain. These cells may continue to circulate in the blood or may hide out in the body. Eventually, they can start growing again and form new tumors.

An important tool for both cancer screening and ensuring that all traces of cancer are gone will be liquid biopsies. This approach seeks to detect cancer with a simple blood test. As cancer cells break down in the normal course of cell death, they shed their DNA into the bloodstream. New gene-sequencing technology has made it increasingly possible to detect cancer genes in the blood.

In the case of minimal residual disease, liquid biopsies could be able to tell that there’s still cancer in the body so doctors could offer their patients additional treatments. This way, people can make sure that when cancer is gone, it’s gone for good.

Focusing on Groups at High Risk

Perhaps the biggest risk factor for cancer, along with aging, is tobacco use. The link between tobacco and cancer has been well established for decades. There are a few methods for detecting tobacco-related cancers early, but none for preventing them.

For several years, MSK has offered low-dose CT screening for people at the highest risk of lung cancer due to smoking, but this technology can miss some cancers. In addition, CT screening has a high rate of false positives: More than 90% of findings are not cancer. And there are no established screening methods for other tobacco-related cancers, including head and neck cancers, esophageal cancer, and bladder cancer. PIP plans to address those shortcomings.

“This program will leverage what we can learn from people who are heavy smokers with the ambition of looking for novel markers for detection,” Dr. Diaz says. “We plan to screen thousands of people to look for tumor markers not only in the blood but also in the saliva and urine.”

Eventually, he adds, the program will focus on developing and testing therapies that will actually prevent smoking-related cancers.

“Everyone in the scientific community recognizes and values the merits of these preventive approaches for cancer,” Dr. Baselga concludes. “As we have already shown with the development of MSK-IMPACT, MSK has an amazing operational strength to do whatever we set our minds to doing. Across the institution, our sense of commitment and personal excellence will make us leaders in this area.”

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Single-Cell Analysis Enables Researchers to Understand the Differences within Tumors

Source: Memorial Sloan Kettering - On Cancer
Date: 02/27/2018
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Precision oncology is based on the idea that the molecular changes driving cancer can be targeted with drugs to stop a tumor from growing. But what happens if not all of the cells in a single tumor are driven by the same set of mutations? This phenomenon is called tumor heterogeneity, and it’s extremely common in cancer.

Researchers want to get around this problem with an approach called single-cell analysis. This allows them to analyze tumors with greater detail than ever before. Being able to find the genetic mutations that direct individual cells within a tumor may lead to more-effective targeted therapies. Plus, single-cell analysis can help doctors learn when some of the cells in a tumor have begun to develop new mutations that allow them to resist targeted therapies.

“Genetic heterogeneity within tumors is one of the main challenges that we face in precision oncology,” says Memorial Sloan Kettering experimental pathologist Jorge Reis-Filho. His laboratory focuses on the genes that drive the formation and growth of breast cancer. “We use single-cell genomics to understand heterogeneity within tumors and how it contributes to disease progression,” he says.

Looking for Changes in Many Cells

Single-cell analysis is being developed hand in hand with another technology known as liquid biopsy. This technique searches the blood for tumor cells or free-floating DNA that has escaped from a tumor. In many cases, liquid biopsy lets doctors and researchers see a broad range of genetic changes across an entire tumor. This can provide them with much more information than they might get from a tissue biopsy taken from a single area of a tumor.

In spelling out the DNA sequences for many, many individual cells, these studies create a huge amount of data. For that reason, computational biology and bioinformatics are an important part of this field of research. Dana Pe’er, Chair of the Sloan Kettering Institute’s Computational and Systems Biology Program, is leading this effort at MSK. She and her team are creating mathematical algorithms that allow computers to scan the large amounts of data that come from single-cell analysis, providing a filter to identify the most important findings.

These approaches are expensive and are not used as a regular part of cancer care. But researchers are looking at ways to reduce the costs. The goal is that these tools will eventually become widely available and the standard way to diagnose cancer and monitor how well treatment is working.

An Important Laboratory Tool for DCIS and Beyond

Currently, Dr. Reis-Filho and his team are using single-cell analysis to study tumor samples from surgical biopsies. In February 2017, they reported that they had developed the first method for doing single-cell sequencing from older tumor samples — even those that have been preserved and stored for years.

At the San Antonio Breast Cancer Symposium in December 2017, Dr. Reis-Filho discussed research in which he used this technique to study preserved tumor samples from a type of breast tumor called ductal carcinoma in situ (DCIS). DCIS is a very early-stage, noninvasive cancer. Women who develop it have about a 25% chance that the cancer will come back after surgery, and then it can become invasive.

The long-term goal of this work is to find genetic changes in individual cells that predict which people are more likely to have the tumor return and to define if the genetic heterogeneity itself could predict the behavior of DCIS. That way some women with DCIS could receive more-aggressive treatment right away, while others who are not at a high risk could avoid it.

“One interesting finding from our study was that intratumor heterogeneity can occur very early in the formation of a tumor, even in the DCIS stage,” says Dr. Reis-Filho, who is a member of MSK’s Human Oncology and Pathogenesis Program. “This is contrary to what was previously believed — that heterogeneity was an event that developed later in the growth of tumors.” This discovery uncovered new clues about the genetic underpinnings of this type of cancer.

The problem of intratumor heterogeneity is not limited to breast cancer. “We know more about it in types of cancer that have been more extensively studied, like breast cancer and lung cancer,” Dr. Reis-Filho adds. “But we suspect that it applies to most types of solid tumors.”

Investigators continue to advance their ability to study tumors at the level of a single cell. Through this research, they expect to find even more information about what drives tumor growth. This, in turn, will help them improve ways to diagnose cancer. Single-cell analysis may also enable the development of more-effective targeted therapies or combinations of targeted therapies to treat the most-aggressive cells within a tumor.