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Profiling Melanoma to Predict Immune Therapy Success

May is Melanoma awareness month, and our series on melanoma continues with a discussion with Dr. Douglas B. Johnson of the Vanderbilt-Ingram Cancer Center. Dr. Johnson leads Vanderbilt’s melanoma clinical and research program, overseeing clinical trials, patient care and translational research. His research interests focus on developing new immune and targeted therapies for melanoma, and in using existing treatments in the most effective ways. Specifically, he is exploring ways to profile cancers to predict which patients will benefit from immune therapies.

Combination and Targeted Therapies Allow Long-Term Survival

Real World Health Care: You published a review of therapeutic advances and treatment options in metastatic melanoma. Can you summarize the review and discuss its implications for patients with the disease?

Dr. Douglas Johnson, Vanderbilt-Ingram Cancer Center

Douglas Johnson: Treatment options for advanced melanoma have been rapidly advancing. We now have multiple options for patients with this disease, when even 5-10 years ago very few existed. Immune therapies, which unleash the immune system against the cancer, result in long-lasting responses in a large fraction of patients. The number of patients who benefit from treatment increases when two immune therapy treatments are combined, although at the cost of increased side effects. Targeted therapies, which block the effects of particular genetic mutations, have also made a big difference, particularly for patients who have mutations in the gene BRAF, which represents about half of melanoma patients. These treatments have transformed a disease which was essentially uniformly fatal to one that is often associated with long-term survival.

RWHC: Are you currently working on any new studies or trials relating to melanoma?

DJ: We have a number of combination immunotherapy trials. These types of trials are attempting to use strategies that extend the benefits of immune therapy to more patients. We are also working on developing biomarkers for immune therapy responses. In particular, we are evaluating whether the number and types of mutations in melanoma, as well as the expression of particular immune proteins, can predict which patients will respond to immune therapy. We also are studying the side effects and toxicities of immune therapy, to understand why they occur, who is affected, and develop effective prevention and treatment strategies.

Melanoma Research and Treatment 

RWHC: What do you see as the most promising treatments on the horizon for melanoma?

DJ: A number of promising immune therapy combinations are being developed. It is very difficult to say which is the most promising, but likely some combination of anti-PD-1 therapy with other immune or targeted therapy agents.

RWHC: What are the biggest challenges facing melanoma researchers?

DJ: One of the biggest challenges is predicting who will respond to current immune and/or targeted therapies so we can assign the right treatment to the right patient. Researchers also are challenged to develop the most effective combination therapies and to prevent and manage toxicities. In some ways, the development of effective therapies has made it more difficult to enroll patients in clinical trials. This is a good problem to have, but it limits the speed of developing new effective therapies.

RWHC: What are the biggest challenges facing clinicians treating patients with melanoma?

DJ: From a clinical standpoint, the challenges are similar. Despite the current advances, there is still a large subset of patients who do not respond well to treatments. We need to understand who those patients are upfront, and develop more effective treatment strategies for them.

Toxicities are also a major consideration, particularly for patients with other medical problems or who have limited functional status. It is always a difficult balancing act deciding between single agent and combination immune therapy. On one side is the potential for a somewhat higher response rate, on the other side is the significant increase in side effects (which are typically manageable). Every clinician and patient has a different threshold regarding when to offer these therapies.

Improving the Lives of Melanoma Patients

RWHC: What initially interested you in studying and treating melanoma? What continues to inspire you?

DJ: I had a friend during my medical training who developed stage III melanoma and I was struck by the lack of treatment options at the time. When I joined Vanderbilt, my mentor Dr. Jeff Sosman was doing amazing research, and I become very excited about the prospect of doing groundbreaking research that would affect patient lives. That approach continues to drive and inspire me.

Accelerating Melanoma Research

It’s Melanoma Awareness Month and this week, Real World Health Care is pleased to shine a light on The Society for Melanoma Research. We spoke with the Society’s President, Keith Flaherty, MD. In addition to his role with SMR, Dr. Flaherty serves as director of the Henri & Belinda Termeer Center for Targeted Therapy and the Richard Saltonstall Chair in Oncology at the Massachusetts General Hospital Cancer Center.

Supporting a Diverse Melanoma Research Community

Real World Health Care: Please describe the mission of the Society for Melanoma Research.

Dr. Keith Flaherty, Society for Melanoma Research

Keith Flaherty: The Society for Melanoma Research was intended to be a scientific home for the melanoma research community. When it was created in 2003, there was no organization run by and for melanoma scientists that convened regular scientific meetings to provide a venue for publication of melanoma research. Our research community is quite diverse, spanning many medical specialties and numerous scientific disciplines. Simply bridging the divide between the clinical research community and laboratory-based investigators was central to the SMR mission.

RWHC: What type of research programs do you support and how do you support them?

KF: Our primary supporting role is served by organizing and hosting an annual, international, scientific conference focused on melanoma research. We support travel to the meeting for trainees and young scientists. Plus, we maintain a web-based presence and newsletter to update our members on emerging discoveries. Additionally, we partnered with the International Federation of Pigment Cell Societies to transform a pre-existing Journal (Pigment Cell Research) into Pigment Cell and Melanoma Research in order to have a peer-reviewed journal supported by SMR with scientific leadership by melanoma researchers.

Combination Therapy Research

RWHC: Are there any studies your members are involved in that are particularly promising at this moment?

KF: As ours is the only international scientific society focused on melanoma research, our membership includes all of the clinical investigators from the major academic centers who have been conducting groundbreaking clinical trials in melanoma over the past eight years. Outcomes for patients with metastatic melanoma have been transformed by the development of molecularly targeted and immunotherapies. The most promising current trials have been investigating combinations of these two approaches at the same time. Preliminary results presented at the 2016 SMR Congress suggest that these combination approaches may further improve outcome significantly.

Multidisciplinary Collaboration

RWHC: Why are multidisciplinary collaborations so important in developing new therapies for melanoma? How is the SMR working to encourage or create such collaborations?

KF: Multidisciplinary collaborations can be defined by teams of clinical investigators, such as medical oncologists, surgical oncologists, pathologist, and radiologists. Or, they can encompass clinical and laboratory-based investigators partnering together. We have numerous examples of each kind within and across the major academic medical centers with a focus on melanoma research.

For years, the melanoma research community was characterized by empiric clinical trials in which therapies that had been successful in other cancer types were tried in melanoma, but with little scientific basis and focus on understanding whether those therapies were doing their molecular “job” or not. Since the late 2000s, the emergence of BRAF, MEK, CTLA-4 and PD-1 inhibitors has provided not only substantial benefit to patients, but it has transformed the research approach by bringing clinical and laboratory-based scientists together. Even for these FDA approved therapies, there remain questions regarding mechanisms of action and resistance which are critical to informing rational combination therapies that will be the focus of the next generation of clinical trials. This approach literally taught us how to define the limits of these partially effective therapies and will hopefully accelerate our pace of progress.

More Funding, More Time

RWHC: What are the biggest challenges melanoma researchers face today and how can they be overcome?

KF: Funding and time. For a decade, we have seen a decline in publicly funded research. The U.S. has always been the largest investor in biomedical research, and pairing that down has had global impact. New discoveries are made through publicly funded research before private sector research comes in to take those discoveries and reduce them to practice. This has made the melanoma research field increasingly dependent on philanthropic foundations and individuals.

Additionally, clinical researchers are constantly pulled between clinical duties and research activities. Many medical centers cannot afford to have their clinicians spending time on research. Therefore, research funding is needed to cover the portion of their time that is away from direct patient care. With the accelerated pace of technology development relevant to biomedical research and the inroads that we have made in the past eight years with regard to therapeutic approaches, there is more opportunity now than ever to accelerate the application of science to medicine for melanoma patients. But, these rate limiting factors are unquestionably slowing us down.

Industry’s Role

RWHC: What role do you think the biopharmaceutical industry should play in furthering research into new melanoma therapies?

KF: As always, advancing diagnostic and therapeutic approaches to widespread use requires risk-taking and investment by the biopharmaceutical industry.

In the cancer field overall and melanoma specifically, we have seen tighter integration between the public and private sectors that has come as a consequence of the initial successes with the now FDA-approved drugs. This has drawn in more interest from companies developing novel diagnostic technology that may allow us not only to find localized, advanced melanoma at an earlier point, but also allow us to deploy the optimal therapy for each patient in a personalized way. And, of course, the very costly process of drug development requires involvement of the biopharmaceutical industry from beginning to end.

Through close collaboration with the academic scientific community, we are able to discern very early in development whether a new therapy is accomplishing its biological task before investing massive additional resources in large-scale clinical trials to prove whether or not it has a clinical impact.

Dramatic Unmet Need

RWHC: What initially attracted you to the field of melanoma research?

KF: I was attracted to the melanoma field first and foremost by the dramatic unmet need. It is a cancer that has an awe-inspiring ability to metastasize from tiny primary tumors, making the challenge of early detection a key hurdle. And, when melanoma metastasizes, it is one of the most aggressive cancer types. Melanoma affects a far greater proportion of young adults than other more common cancers, making it one of the leading cancers with regard to aggregate years of life lost. At the time that I was entering the field, it seemed that the pace with which biologic insights into melanoma were being made was increasing. And, right at the end of my training, BRAF mutations were discovered and that drew my focus for all of the years since.

A MESSAGE FROM OUR SPONSOR:

The HealthWell Foundation, sponsor of Real World Health Care, is proud to have supported the melanoma patient community in recent years with copayment and premium assistance. We have helped more than 2,230 melanoma patients afford their treatments since approving our first Melanoma grant in 2011 — thanks to the generous support of our corporate partners. Due to high patient volume, our melanoma fund is temporarily closed until we receive additional funding. We invite corporations and individuals to help us meet this demand by contributing to our Melanoma-Medicare Access Fund, so nobody goes without essential medications because they cannot afford them.

Categories: General, Melanoma

Skin Cancer Awareness and Prevention Efforts in Focus at American Academy of Dermatology

This week, Real World Health Care continues our recognition of May’s Melanoma and Skin Cancer Awareness Month by highlighting the work of the American Academy of Dermatology. We spoke with the AAD’s new President, Henry W. Lim, MD, about the organization’s mission and some of the challenges and opportunities associated with preventing and treating melanoma and other skin diseases.

Real World Health Care: Please tell our readers about the overall mission of the American Academy of Dermatology.

Henry W. Lim, MD, American Academy of Dermatology

Henry Lim: The American Academy of Dermatology promotes leadership in dermatology and excellence in patient care through education, research and advocacy.

As the largest, most influential and representative dermatology group in the United States, and the largest such organization in the world, the AAD works to make sure its values reflect this mission. The AAD’s values include putting patients first, encouraging its members to adhere to an uncompromising code of clinical and ethical standards, fostering an interest in our members to pursue lifelong learning, encouraging collaboration and working within our communities and embracing diversity.

Public Education: Sun Safety

RWHC: How does the AAD’s mission address melanoma?

HL: It is estimated that 161,790 new cases of melanoma will be diagnosed in the U.S. in 2017.  That is a staggering number that could be reduced if people incorporated skin cancer detection and prevention behaviors into their lives.

The AAD works to increase public awareness of skin cancer and its risks through its SPOT Skin Cancer campaign, which is designed to create a world without skin cancer through public awareness, community outreach programs and services, and advocacy that promote the prevention, detection and care of skin cancer.

The first step toward a world without skin cancer is educating the public about prevention. The Academy has long communicated sun-safety messages to the public about the importance of skin cancer prevention and detection.

In addition, dermatologists have led the medical community in finding and treating skin cancer. For more than 30 years, dermatologists across the country have hosted 2.5 million free SPOTme® skin cancer screenings that have detected 28,822 suspected melanomas and 256,329 suspected skin cancer lesions.

To assist the public with learning more about skin cancer prevention and detection, the AAD offers a variety of free, online videos, downloadable handouts and skin self-exam resources, including a body mole map, as well directories to find a dermatologist and skin cancer screenings.

Melanoma & Skin Cancer Awareness

RWHC: What is the AAD doing in 2017 to recognize Skin Cancer Awareness Month?

HL: The AAD’s 2017 SPOT Skin Cancer campaign, Check Your Partner. Check Yourself, encourages the public to be aware of changes on their skin that could be signs of skin cancer. Research has shown that women are more likely to detect suspicious spots on others.  Men over the age of 50 have a higher risk of developing melanoma, than the general population, so the campaign encourages women – often the health care decision makers of a household – to check their partner’s skin regularly, check their own skin, and to visit the AAD’s SpotSkinCancer website to find a free SPOTme® screening in their area.

RWHC: Do you have additional initiatives you’d like to highlight?

HL: In addition to the activities for Skin Cancer Awareness Month in May and the SpotSkinCancer™ website, the AAD works with state dermatology societies and state legislatures to introduce and support laws and regulations that protect consumers and promote awareness about skin cancer prevention and the dangers of indoor tanning. As a result, 42 states have enacted tanning bed restrictions to potentially reduce the risk of melanoma and other forms of skin cancer.

The AAD’s Shade Structure Program awards shade structure grants to schools and non-profit organizations across the country in order to protect children and adolescents from the sun’s harmful rays.  Since its launch in 2000, the AAD’s Shade Structure Program has awarded 350 shade structure grants, which provide shade for more than 600,000 individuals each day.

The AAD also has a strategic social media presence on Facebook, Twitter, YouTube and Pinterest, designed to raise awareness about skin cancer detection and prevention.  Social media, including paid, promoted posts, reach our targeted audiences – the public, our members and the media – with links to AAD resources.  We encourage our followers to like, share and re-tweet our skin cancer awareness videos and tips.

Melanoma Research

RWHC: Does the AAD underwrite or otherwise support research into melanoma detection and/or treatment?

HL: While AAD is not a research funding organization, the AAD does provide annual awards for Young Investigators in Dermatology.  These awards recognize outstanding basic and clinical/translational research by young dermatology investigators and some of the projects are related to melanoma.

The purpose of the award is to acknowledge research contributions by individuals at the start of promising research careers that further the improvement of diagnosis and therapeutics in the practice and science of dermatology.

RWHC: What do you see as the biggest challenges facing researchers studying melanoma treatments and clinicians treating melanoma?

HL: The rapidly changing health care environment presents major challenges to researchers and clinicians in all aspects of dermatologic care, not just those studying and treating melanoma. 

A significant challenge is the inadequate funding for research, together with the pressure to increase clinical revenue generated by clinician researchers.  For many years, the American Academy of Dermatology Association (AADA) has been active in advocating increased research funding by NIH to dermatology research, including through our support of the 21st Century Cures Act.

The current health care system also presents barriers that impede patient access to the best possible care from a qualified physician.  To combat this, the AADA is working with all dermatology care providers and other physicians to confront these challenges.

In particular, the AAD recently launched a new specialty positioning campaign, SkinSerious, to raise awareness of the serious impact of skin disease. Our goal is also to improve access to dermatologists’ expertise and increase collaboration with our physician peers to ensure high-quality patient care. We know that when dermatologists work with other physicians as part of the health care team, everyone can benefit from improved patient outcomes and lowered health care costs.

Other concerns within the health care environment that the AADA is closely monitoring include the rise of big data and the growth of teledermatology.  We closely follow developments at the federal and state levels and, when appropriate, the AADA will take action on issues that can be influenced positively for dermatology and pursue opportunities to impact health care policy. 

Promising Melanoma Treatments

RWHC: What do you see as the most promising or breakthrough melanoma treatments on the horizon?

HL: This is an exciting era in melanoma research.  In-depth understanding of the molecular pathways of melanoma development has led to the availability of immune checkpoint inhibitors; combinations of these medications are being looked at in clinical trials.  Metabolic manipulation of the peri-tumoral environment to inhibit the growth of melanoma is being actively investigated.  Understanding of the genes responsible for melanoma resulted in the availability of gene expression profile (GEP) test that can be used to determine biologic behavior of melanoma.

Melanoma Prevention

RWHC: What are the biggest challenges facing the medical community in terms of increasing awareness of and adherence to melanoma prevention efforts among the general public?

HL: The challenges facing the medical community around melanoma prevention are two-fold.

One is the misconception that a tan is a sign of health.  Tanning is a protective physiologic response of our skin to damage caused by ultraviolet radiation.  There is no such thing as a healthy tan, yet people continue to seek the sun or use indoor tanning, thereby increasing their risk of skin cancer.  This is a particularly challenging message to get across to young women and men, who feel peer and societal pressure to be tan.

The AADA was instrumental, along with several other organizations, in having the FDA re-classify tanning lamps from the Class I to Class II medical device category, which requires more supervision and restriction in their purchase and use.  For the past several years, the AAD has released a new public service advertisement that focuses on the dangers of tanning, particularly targeting young women.  We know that melanoma is the second most common cancer in young women, and this may be due in part to their tanning habits.

The 2016/2017 public service advertisement is called “Arms,” and features two young women comparing their tans at various stages in their lives. The emotional ad concludes with the two friends clasping hands in the hospital as one of them reveals she has advanced stage melanoma.  This PSA, and our previous ones, have resonated strongly with young women, especially on social media, where they have liked and shared the video with their friends.

The second challenging misconception is that many people believe that sun exposure is the best source of vitamin D.

While our bodies need vitamin D to build and maintain strong, healthy bodies, the AAD does not recommend getting vitamin D from sun exposure or indoor tanning because of the increased risk of skin cancer.  In fact, it has been demonstrated that sun exposure that results in increased vitamin D levels is directly correlated with DNA damage.

Vitamin D from food and dietary supplements offers the same benefits — without the danger of skin cancer — as vitamin D obtained from UV light.  Vitamin D cannot be used by the body until it is processed by the liver and the kidneys. The usable form of vitamin D created by this process is the same, regardless of how it enters the body.

The AAD recommends dietary sources (foods naturally rich in vitamin D, fortified foods and beverages) and vitamin supplements as sources of vitamin D that are available year-round and can easily be incorporated into a healthy lifestyle. Good sources include fortified milk, cheeses and yogurt, fortified cereal, and oily fish like salmon and tuna. Research shows that vitamin D supplements are well tolerated, safe, and effective when taken as directed by a physician.

The fact is these myths are harmful because the consequences of this misinformation could be potentially fatal.

RWHC: What personally inspires you to build awareness of the importance of preventing melanoma?

HL: Having been in dermatology practice for 40 years, I see on a regular basis the devastating effects that melanoma has on patients and their family.  The risk of developing melanoma can be significantly decreased by sensible photoprotection, and avoidance of tanning beds.  The exciting new developments in the treatment and genetic profiling of melanoma reflect the value of investment in scientists and research projects, and I look forward to additional treatments in the future that will benefit patients.

A MESSAGE FROM OUR SPONSOR:

The HealthWell Foundation, sponsor of Real World Health Care, is proud to have supported the melanoma patient community in recent years with copayment and premium assistance. We have helped more than 2,230 melanoma patients afford their treatments since approving our first Melanoma grant in 2011 — thanks to the generous support of our corporate partners. Due to high patient volume, our melanoma fund is temporarily closed until we receive additional funding. We invite corporations and individuals to help us meet this demand by contributing to our Melanoma-Medicare Access Fund, so nobody goes without essential medications because they cannot afford them.

 

Categories: General, Melanoma

The Mechanics of Melanoma

May is Melanoma Awareness Month. This article originally appeared in the Biotech Primer WEEKLY. For more on the science behind the headlines, subscribe. 

Melanoma 101 

Emily Burke, BiotechPrimer.com

Melanoma accounts for less than one percent of skin cancer cases, yet accounts for the vast majority of skin cancer deaths (skincancer.org). If detected early enough, melanoma is almost always curable. If it is not detected early, it is likely to spread to other parts of the body, where it is more difficult to treat. It’s estimated that in 2017, there will be 87,110 new cases of melanoma in the U.S., and 9,730 melanoma-related deaths (Aim at Melanoma Foundation). Melanoma is one of the types of cancers most common in young adults, with 25 percent of new cases occurring in people under age 45. Its prevalence is growing – the number of new cases/year relative to the total population has doubled since 1973.

In this column, we’ll review the basics of melanoma, and discuss the latest new therapies recently approved and in development.

Melanoma’s Method

Melanoma is the uncontrolled growth of the pigment-producing cells known as melanocytes, which are located in the bottom layer of the skin’s top layer (the epidermis). Like other types of cancers, melanoma arises from gene mutations in these cells that impact cell growth and division. In the case of melanoma and other skin cancers, the DNA damage is usually caused by ultraviolet (UV) radiation, resulting in a tumor that initially grows in the skin, spreading along the epidermis. If the melanoma is detected at this stage, it can often be surgically removed. If the out of control cell growth is not caught in these early stages, it penetrates deeper layers of the skin, eventually coming into contact with lymph and blood vessels which enable it to spread to other parts of the body. When the melanoma reaches this stage, it is called metastatic melanoma.

Although anyone can get melanoma, fair-skinned people are at higher risk for all types of skin cancer, since increased skin pigmentation helps to block the damaging UV rays from penetrating and damaging skin cell DNA. However, darker-skinned people can and do get skin cancer, and thus should also be vigilant about sun protection.

Atypical moles have also been linked to an increased risk of melanoma. Moles are clusters of melanocytes, and there is a slightly increased risk of melanoma arising within these clusters. Of course, most moles are harmless and do not lead to melanoma. However, any sudden changes in the color, shape, or size of a mole should be evaluated by a doctor.

Genetic Factors: p53 & BRAF 

Although most cases of all types of skin cancer are traceable to excessive sun exposure, about 10% are likely due to genetic factors. The gene most commonly mutated in familial melanoma is p53. p53 is a “tumor suppressor,” which means that it detects DNA damage in cells, and triggers either DNA repair pathways or activates cell death if the DNA damage cannot be repaired. Another gene, known as the BRAF gene, regulates cell growth and is mutated in inherited forms of melanoma. About half of all genetically-based melanomas have the BRAF mutation.

Let’s take a closer look at BRAF. BRAF codes for a protein required for the transmission of a growth signal from a cell surface receptor to the cell nucleus (growth signal transduction). Growth signaling is initiated by a growth factor binding to its receptor. This binding transmits a signal through the membrane, causing the internal portion of the receptor to interact with and activate a protein inside of the cell. This activation is then transferred to the next protein in the pathway, and so on until the signal reaches the last protein in the pathway. When this protein is activated, it enters the nucleus, where it turns on specific genes that make proteins which initiate cell division. BRAF is one of the proteins in this pathway. In BRAF-associated melanoma, the mutated BRAF is always turned on even when no growth factor is present.

Small molecule drugs that inhibit overactive BRAF have been developed and approved for the treatment of late-stage melanoma.

Immunotherapies in the Fight 

A few different checkpoint inhibitor therapies have been approved to treat metastatic melanoma. These are drugs that enable killer T-cells – immune system cells that recognize and kill threats such as cancer cells – to become fully active against a tumor cell target. These drugs target inhibitory proteins on the surface of T-cells such us CTLA-4 and PD-1. These proteins act as “off switches” for killer T-cells. By inhibiting these off switches, the killer T-cells become fully activated, and able to target and kill melanoma cells.

A second type of immunotherapy that has been approved for melanoma is an oncolytic virus therapy. An oncolytic virus is a virus that infects and kills cancer cells. The cancer cells are killed through cell lysis – as the virus multiplies inside of the cells, it causes them to burst open. This in turn releases new infectious particles that can target remaining tumor cells. In addition to direct killing of cancer cells via lysis, the presence of an actively replicating virus helps to activate the patient’s immune response to target the area.

In the Pipeline 

A new type of immunotherapy drug is in Phase 3 clinical development. The drug is a small molecule inhibitor of the enzyme IDO1. IDO1 helps regulatory T-cells to develop and become activated. Regulatory T-cells suppress the immune response, and therefore help cancer cells to escape immune surveillance. Inhibiting IDO1 should suppress the development of regulatory T-cells, bolstering the immune response against melanoma.

Implications of microRNA 

Last year, researchers at Tel Aviv University published a report describing how melanoma metastasizes. Their work suggests that melanoma cells release tiny vesicles that contain microRNA, a type of regulatory RNA produced by all cells. These micro-RNA filled vesicles induce changes in the dermis – the layer of skin just below the epidermis where the melanoma begins. The dermis contains blood vessels, and thus a pathway for metastasis. The changes in the dermis induced by the small vesicles released from the melanoma cells makes the cancer cells able to access those blood vessels. The Tel Aviv team is identifying drug candidates that may interfere with this process, preventing the metastasis that makes melanoma so deadly.

The best strategy for melanoma remains prevention and proactive monitoring – limiting sun exposure and monitoring the skin for any unusual growths or changes in moles. Increased understanding of the molecular pathways that contribute to melanoma’s development and spread will provide physicians with additional tools to fight those cases of metastatic melanoma that inevitably will continue to arise.

Categories: General, Melanoma

New Real World Health Care Series: Melanoma Research and Treatment

“Have you heard from mom and dad recently?” My sister’s question caught me off-guard.  Without realizing it, I hadn’t actually heard from my parents in a while.  She had already asked my brother the same question and he reported not hearing from them lately either.  With no imminent trips back to Michigan from our respective homes in Colorado, Maryland, and North Carolina, all three of us started calling and emailing our parents with some urgency to make sure things were well.

Krista Zodet, President, HealthWell Foundation

My mom’s email came back quickly, bringing us up to speed: “Dad went to the dermatologist about a troublesome spot on his cheek and the doctor did a full body check too.  He found a spot on the back of his thigh and did a biopsy.  Diagnosis: melanoma.  Treatment: surgery.” They removed a patch of skin from my dad’s leg – an area he couldn’t see and for the most part was covered by shorts or pants year-round.  It had been malignant and they got all of it.

That was early 2001, and my dad had just retired (talk about timing).  Because of early detection and annual check-ups since, he has been melanoma-free for 16 years.  We learned a lot about melanoma back then: It is the most dangerous form of skin cancer; and we also understand – thankfully – if it is recognized and treated early, it is almost always curable.

May is Melanoma Awareness Month

Since HealthWell opened its melanoma fund, I have learned even more about this devastating disease: Without early detection, the cancer can advance and spread to other parts of the body, where it becomes hard to treat and can be fatal. According to the Skin Cancer Foundation, melanoma kills an estimated 10,130 people in the U.S. annually.

Treatment typically begins by surgically removing the melanoma. Surgical treatments have advanced over the past decade, and most can be done in the doctor’s office or as an outpatient procedure under local anesthesia. In recent years, Mohs Micrographic Surgery has become popular as an alternative to standard surgery for certain melanomas. This procedure spares as much of the normal tissue (known as the margins) as possible while allowing the surgeon to pinpoint the cancer’s location when it is invisible to the naked eye.

When melanoma cells spread to the lymph nodes (stage III) or more distant parts of the body (stage IV), the disease is considered advanced and additional therapy usually follows surgical removal of the original skin tumor. Thanks to an array of treatment options, patients with metastatic melanoma can extend their lives by months or years. A rising number of patients go into long-term remission.

The HealthWell Foundation, sponsor of Real World Health Care, is proud to have supported the melanoma patient community in recent years with copayment and premium assistance. We have helped more than 2,230 melanoma patients afford their treatments since approving our first Melanoma grant in 2011 — thanks to the generous support of our corporate partners. Due to high patient volume, our melanoma fund is temporarily closed until we receive additional funding. We invite corporations and individuals to help us meet this demand by contributing to our Melanoma-Medicare Access Fund, so nobody goes without essential medications because they cannot afford them.

 

 

Categories: General, Melanoma

APS Calls for Pain Management Funding

Real World Health Care concludes its series on pain management with an interview with David Williams, PhD, president of the American Pain Society (APS). Dr. Williams is Professor of Anesthesiology, Medicine (Rheumatology), Psychiatry and Psychology at the University of Michigan, where he also serves as the Associate Director of the Chronic Pain and Fatigue Research Center, co-director of Research Development within the Michigan Institute for Clinical and Health Research (MICHR), and is on the senior faculty of the Neurosciences Program.

The APS is a multidisciplinary community that brings together a diverse group of scientists, clinicians and other professionals to increase the knowledge of pain and transform public policy and clinical practice to reduce pain-related suffering. APS was the first multidisciplinary professional society dedicated to pain science and the practice of evidenced-based pain care.

Research Priorities

Real World Health Care: What are the APS’s priorities in terms of pain management research?

David Williams, PhD, American Pain Society

David Williams: Pain is complex. No one view point is likely to capture such complexity.  The APS values interdisciplinary collaboration demonstrated by respect for the value of diverse views and perspectives among professionals. Our society is composed of professionals from the basic sciences who examine pain mechanisms at the level of neurons and neurotransmitters. We’re also pharmacologists exploring and developing new drugs for pain. We’re psychologists, occupational therapists, nurses, and physical therapists working to refine behavioral, psychosocial, patient-centric, and self-management approaches to pain. We are clinical and translational researchers developing and implementing multi-modal forms of treatment into real-world settings. And we’re public policy experts working to improve options for pain care at systemic levels. As a society we try to facilitate the broad-based work of our members while encouraging collaboration across disciplines.

RWHC: Can you provide an example or two of recent or current pain management research programs you are supporting or have supported? Why are those research programs so impactful?

DW: The Annual Scientific Meeting and the Society’s Journal of Pain are the two best sources to witness APS’s commitment to the dissemination of evidence supporting multidisciplinary pain care. APS also financially supports the research of many of its early career professionals in the form of the Rita Allen Foundation Award for Pain (basic science), the Future Leaders in Pain award (in part supported by the MayDay Foundation), and through contributions to the APS Pain Research Fund. This past year, the APS also partnered with Pfizer to offer a grant program focused on learning and change that will help support the implementation of aspects of the National Pain Strategy.

Research and Clinical Challenges

RWHC: What are some of the biggest challenges facing pain management researchers and how are those challenges being addressed?

DW: Funding is always a big challenge for a society focused on research. Annually, the APS meets with leadership at the National Institutes of Health (NIH) and with the inter-institute leadership of the NIH Pain Consortium. The needs of societal members are expressed, thematic research discussed, and challenges in grant review presented. There is also a need for pain to be viewed as an important national research priority. Currently many APS members have been invited to participate in the creation of the Federal Pain Research Strategy (FPRS), a document which will serve as a blue print for pain research across Federal agencies.

RWHC: What are some of the biggest pain management challenges facing clinicians, and how are those challenges being addressed?

DW: One big challenge is that as a field, we do not have great treatments for chronic pain. More research is clearly needed. An honest appraisal would suggest that we offer modest benefit for most. Complicating the problem is that relatively more beneficial approaches, such as multi-disciplinary pain care, are difficult to implement both logistically and financially. As such, it is rarely seen in practice. Currently there is research underway to study how best to implement evidence-based approaches in routine care and at a systems level. Such efforts are supported by APS and by the National Pain Strategy.

Approaches to Pain Management

RWHC: How can clinicians integrate pharmaceutical and non-pharmaceutical approaches to pain management in their practice?

DW: Optimal care would suggest integration of both pharmacological and non-pharmacological approaches to pain management. Optimal care would also include a patient-centric approach to care where the patient and provider share decision making about what medications and what non-pharmacological approaches will be utilized. Evidence exists for many medications and many non-pharmacological approaches. Matching the available approaches to the specific needs of an individual patient, however, is the clinical challenge. Informing both the patient and the provider about evidence-based approaches as well as how best to implement those options at the individual level is an area where additional research and training is needed. This important challenge was highlighted by the National Pain Strategy and has been a focus of the APS in its educational agenda.

Opioid Addiction

RWHC: How is the APS working to address the issue of opioid addiction in this country?

DW: The APS is not a practice guild. It is a Society based upon a valuation of science and evidence. As such, we let evidence guide our position rather than politics. For decades, the APS has gone on record as supporting a multi-disciplinary approach to pain management rather than a mono-therapeutic approach (e.g., a solely opioid-based approach). Opioids may or may not have relevance to the care of a given individual and should be viewed in the context of an entire integrated treatment plan designed with input from both the patient and provider. Through the promotion of evidence-based multi-modal care, APS is supporting efforts to find sources of pain relief that go beyond opioids.

Go-To Pain Information Source

RWHC: Is there anything else you would like our readers to know about the work APS is doing?

DW: The APS is the unbiased “go-to” information source regarding pain. We are sought out by governmental representatives, industry, academia, and patient advocacy groups. We support the early careers of young pain scientists and serve as a home for senior scientists, clinicians, and public policy experts interested in changing how chronic pain is managed. Our members have participated in the development of important documents such as the IOM report “Relieving Pain in America,” the “National Pain Strategy”, and the forthcoming “Federal Pain Research Strategy.”

RWHC: How did you get involved in the field of pain management? What continues to inspire you about this field?

DW: Over the years I have studied pain from the perspectives of a basic scientist, a clinical/translational researcher, and currently a clinical trialist. Our understanding of pain continues to evolve and with each finding, new questions arise.  It has been both challenging and rewarding to participate in the study of pain. It is also rewarding to see the current field of young scientists taking interest in this topic and taking fresh approaches to problems my generation was not able to solve.

 

Challenges in Pain Management for MS Patients

This week, Real World Health Care interviews Theodore R. (Ted) Brown, MD, MPH, about pain management in patients with Multiple Sclerosis (MS). Dr. Brown is director of neuro-rehabilitation at the EvergreenHealth Multiple Sclerosis Center, which cares for about 800 patients. His clinical duties include managing patients with established MS through a total wellness approach that involves drug therapy, exercise, stress management, diet and sleep. His research work focuses on developing new studies to investigate treatments for symptoms of MS and minimizing the side effects of MS drugs.

Duloxetine Study

Real World Health Care: In spring of 2016, you published a study on the use of duloxetine for central pain management in MS, which received the 2016 Herndon Award for best paper published in the International Journal of MS Care. Can you summarize the results and the implication of the study for MS patients?

Theodore R. Brown, MD, MPH, EvergreenHealth

Ted Brown: Pain is common in MS. Duloxetine is a serotonin-norepinephrine reuptake inhibitor that has a potential therapeutic role in treating MS-related pain. We conducted a single-center placebo-controlled, double blind trial of duloxetine involving thirty-eight MS patients. The dosing regimen was 30 mg daily for 1 week, then 60 mg daily for 5 weeks. The primary outcome measure was change in worst pain for week 6 relative to baseline recorded on a daily pain diary.

Of 38 randomized patients, 14 (78%) patients randomized to duloxetine and 19 (95%) randomized to placebo completed treatment. These participants had an average age of 55.5 years, 27% were male, and 64% had relapsing-remitting MS (RRMS). Baseline characteristics were similar. Discontinuations were due primarily to drug intolerance (nausea, headache, no serious treatment-related adverse events).

Among those who completed treatment, worst pain at 6 weeks was reduced by 29% (±20%) for duloxetine versus 12% (± 18%) for placebo (P = .016). Average daily pain at 6 weeks was reduced by 39% (±29%) on duloxetine compared to 10% (±18.8%) in the placebo group (P = .002). Change in subject global impression favored duloxetine (P = .048). There were no significant changes (week 6 vs. baseline) or between-group differences for Beck Depression Inventory or sleep quality score. This suggests that the benefits we found were due to a direct pain-relieving effect, not due to change in mood or sleep.

The implications are that duloxetine may have a role for treating central pain due to MS, that effects can be seen within 4-6 weeks, and that not all patients are able to tolerate the drug.

Research Perspective

RWHC: What are some of the biggest challenges researchers face in studying pain control in MS patients, and how can those challenges best be addressed?

TB: Studying MS pain is difficult for many reasons. Pain makes patients uncomfortable, so they need relief. This is a challenge for recruitment into a study that is placebo-controlled. There are many treatments available by prescription. So, patients may prefer to get a quick fix from a prescribed drug instead of volunteering for a study.

Funding for pain studies also is difficult, since most trials may involve drugs that may already be generic or non-drug interventions. Funding sources for such studies are scarce. The study design must be as brief as possible to limit patient discomfort, should provide some contingency for rescue treatment in case of severe pain, and must be as cost-effective as possible.

Clinical Perspective

RWHC: What are some of the biggest challenges that clinicians face in treating pain in MS patients, and how can those challenges best be addressed?

TB: We tend to assume that all pain in MS is caused by the disease itself. We may overlook non-MS factors that may be causing the pain, such as orthopedic, vascular, infectious or oncological problems. Every case requires thorough assessment, which can be difficult when patients may have several other active problems to address.

Physicians must treat the MS patient to provide pain relief and maximize quality of life. However, pain can very rarely be eliminated completely. State agencies and national organizations discourage prescription of opioid medications for nerve pain. These drugs are not all that effective and carry a host of potential side effects and problems with dose escalation and dependency. Anticonvulsant medications are usually first-line.

Non-drug treatments, such as physical activity, massage, meditation and complementary treatments should be explored. Some level of pain that is tolerable, and does not interfere with sleep and daily activities, may be the best that can be achieved in many cases.

Range of Treatments

RWHC: What are some of the most important pharmaceutical developments in treating pain in patients with MS? Is the field poised for a breakthrough?

TB: Good question. I believe that the incorporation of duloxetine in the treatment algorithm of MS pain is an important development. Some patients find medical marijuana beneficial for MS pain, yet it is very difficult to do clinical research with cannabis in the United States. This treatment is not available in all states, and where available, it is expensive and difficult to instruct patients on how to use it without taking too much or experiencing adverse effects, including cognitive dysfunction. I am not aware of any breakthroughs on the horizon. The danger is that MS pain is overlooked in the vital effort to develop drugs for neuro-protection and neural repair. Certainly, more research in MS pain is needed.

RWHC: Do you think there is a role for non-pharmaceutical pain management therapy in patients with MS?

TB: Yes, absolutely. In every case, physical exercise should be included in the pain management program. Depression is very common in MS. Treating depression and stress may help in treating the pain. We are conducting a study of laughter therapy at the moment and are hopeful that this is one of many complementary approaches that may help with pain management.

Inspiration and Dedication

RWHC: What initially attracted you to this field, and what continues to inspire you about it?

TB: Initially, I was attracted by the newness of the field. We only had a few approved drugs at that time and the MS professional community was relatively small. Now, it is the rewards of patient care that keeps me motivated. I have patients whom I have been following for more than ten years. You become friends with patients and visits can be fun and joyful. When patients have a decline in function, or health, or spirits, it is so important to stay involved as their care provider. Often just being accessible gives patients the trust and reassurance that they need to help them to cope.

 

Pain Management: Opioid Adherence in Cancer Patients

This week, Real World Health Care speaks with Salimah H. Meghani, PhD, MBE, RN, FAAN. Dr. Meghani is an associate professor and term chair in Palliative Care at the University of Pennsylvania School of Nursing. She is also associate director, NewCourtland Center for Transitions and Health. Her main research interest involves palliative care, specifically understanding and addressing sources of disparities in symptom management and outcomes among vulnerable patients.

We asked her about her study on analgesic adherence and health care utilization in outpatients with cancer pain, recently published in Patient Preference and Adherence. We also discussed the role of non-pharmacological approaches in treating cancer pain.

Opioid Adherence Patterns

Real World Health Care: Last year, you published an article: Patterns of analgesic adherence predict health care utilization among outpatients with cancer pain. Can you provide a brief summary of the article and talk about the study’s implications for cancer patients with pain management issues?

Salimah H. Meghani, University of Pennsylvania School of Nursing

Salimah Meghani: This is the first study to understand how opioid adherence patterns, over time among cancer patients, relate to health care utilization outcomes. We used objective measures of adherence (Medication Event Monitoring System – MEMS) and novel adaptive methods recently validated by the co-author, Dr. George Knafl from UNC-Chapel Hill. We found that inconsistent adherence patterns of analgesics over time was significantly associated with hospitalization over a 3-month observation period. The interaction of inconsistent adherence and strong opioids (WHO step 3 opioids) was one of the strongest predictors of health care use. It should be noted that this was a serendipitous finding. We did not plan to study adherence patterns and health care utilization. It therefore needs validation in hypothesis-driven study.

RWHC: Are you currently involved in any new research programs studying pain management in cancer patients? If yes, can you briefly describe?

SM: Yes, I am studying outcomes of opioid adherence and adherence patterns among cancer outpatients. This is an important topic as few recent U.S. based studies exist on the topic despite all the recent guideline contentions (e.g., CDC guidelines for managing chronic pain including chronic cancer pain and ASCO response) and national policy debates on opioids.

How Patients Manage Cancer Pain

RWHC: What do you think are the biggest challenges facing researchers studying pain management in cancer patients? How can those challenges be addressed?

SM: One of the biggest challenges is that we know very little about how patients manage their cancer pain. We know that opioids are widely prescribed, but we also know that there is poor adherence to prescribed opioids. Other treatments such as acupuncture are not consistently covered by health insurance or lack data on clinical effectiveness. There is a need to understand how patients are managing their cancer pain and what health care systems can do better to address the great burden on unrelieved cancer pain. Future work should also include improving access to effective non-opioid treatments for cancer patients. My previous research has also documented racial and ethnic disparities in cancer pain treatment for African Americans, which requires continued attention.

Safe Opioid Use

RWHC: What do you think are the biggest challenges facing clinicians treating pain in cancer patients? How can those challenges be addressed?

SM: There is a lot of confusion among clinicians about the role of opioids and the safe and rational use of opioids among cancer patients. Unfortunately, there is little empirical evidence base about the outcomes of opioid treatment among cancer patients. A look at the recent CDC guidelines on managing chronic pain would indicate that cancer patients frequently, if not invariably, have been excluded from the studies of the outcomes of chronic opioid therapy. More empirical evidence is needed to help clinicians develop comfort in opioid prescriptions.

Non-Opioid Treatments

RWHC: What do you think is the role of non-pharmaceutical pain management therapies for cancer patients? How can clinicians integrate both pharmaceutical and non-pharma therapies for cancer patients?

SM: I think access to non-pharmacological treatments is the biggest problem. While the NCCN guidelines for cancer pain identify a number of non-pharmacological modalities, they are not readily accessible to cancer patients. I have argued this in a recent letter to JAMA Oncology about the CDC opioid guideline that recommends that non-opioid treatments should be the first line therapy for chronic pain. This paradigm assumes easy and consistent access to non-opioid treatments. Also, access to effective non-pharmacological treatments are very different among poor, minorities, those with limited literacy.

Global Disparities

RWHC: What initially attracted you to this field? What continues to inspire you about it?

SM: My original research interest was global disparities in opioid availability for cancer pain management and the role of the International Narcotics Control Board. After migrating to the United States, I became familiar with racial and ethnic disparities in pain care and the toll it has for patients and families. This work continues to inspire me.

Multiple Sclerosis: Overcoming Pain

Real World Health Care continues our series on pain management by speaking with Dawn Ehde, PhD, Department of Rehabilitation Medicine, University of Washington School of Medicine. Dr. Ehde serves as a clinical psychologist and professor at UW. She conducts research evaluating the efficacy of various behavioral, exercise, and pharmacological interventions for chronic pain, depression, and/or fatigue in adults with multiple sclerosis (MS) and other acquired neurological conditions.

Dr. Ehde discusses some of her recent clinical and research work on cognitive-behavioral interventions for MS-related pain.

Living with MS and Pain

Real World Health Care: In 2015, you published an article: Utilization and Patients’ Perceptions of the Effectiveness of Pain Treatments in Multiple Sclerosis. Can you summarize the key results of your study and the implications for patients with MS?

Dawn Ehde, PhD, University of Washington School of Medicine

Dawn Ehde: We conducted this survey to learn more about pain management from the perspective of people living with MS and pain. We found that people with MS and pain try a lot of different treatments to manage pain, but few treatments provide adequate pain relief.

Nonprescription medications such as nonsteroidal anti-inflammatories and physical modalities such as massage were some of the most common methods used. Many use more than one treatment to manage pain. Some of the treatments that individuals rated as most helpful, such as hypnosis, were infrequently used. In fact, we found that very few people surveyed had tried or accessed behavioral pain treatments such as training in mindfulness meditation, cognitive behavioral self-management, or self-hypnosis. This was the case even though there is good evidence that these types of treatments are beneficial to many people with chronic pain, including MS, and have few or no negative side effects. This study highlighted for me the need to improve access to these types of non-pharmacological pain management.

Integrated Care Approach

RWHC: Are you currently involved in any other research relating to pain management in MS patients?

DE: We have several studies in various stages that address pain management in MS. We recently published a study that found that an eight-session telephone-delivered self-management intervention was effective in reducing pain (both its severity and its interference with activities) and fatigue. It also was effective in improving mood, quality of life, and resilience. The benefits were maintained at 6- and 12-month follow ups. Patient satisfaction with the treatment was high as well.

The study I am most excited about is the MS Care study, which is a comparative effectiveness trial that evaluated the benefits of an integrated care approach to pain and depression management in the clinic called “collaborative care.” The MS version, called “MS Care,” aims to improve the quality of pain care in the clinic by adding an MS Care manager to coordinate care, deliver brief behavioral treatments, initiate or adjust other medical treatments, and ensure patients do not slip through the cracks. We also offer patients the choice of getting their care management by phone or in person. Seventy-five percent chose the phone. We found that patients with chronic pain and/or depression randomly assigned to MS Care had significantly improved pain and depression symptoms, including less severe pain, less interference, less disability, and less fatigue. Additional details on the results are available at http://www.uwmscare.org/background.

Opportunities in MS Pain Research

RWHC: What are some of the biggest challenges facing researchers who are studying pain management in MS patients? How can those challenges be overcome?

DE: I actually see a lot of opportunities as an MS pain researcher. The MS community is interested in improving pain management and supporting research in this area. For example, the National MS Society has named pain as one of its research priorities. We also often find people with MS are willing participants in our research, both as participants as well as stakeholders who guide us in our research. For example, we used stakeholders to guide our MS Care study. At times, we have had to work hard to convince potential funders that pain is an issue that warrants funding and study, but that has improved in the time that I’ve been doing research. We have come a long way since I first started in this area, when pain was not always recognized as an important problem deserving attention in MS.

Challenges for MS Clinicians

RWHC: What are some of the biggest challenges facing clinicians who are treating MS patients with pain management problems?

DE: MS presents many different symptoms to manage, and thus both patients and clinicians have a lot to discuss and manage in the typical clinic appointment. One challenge is that pain management is often only one of several issues being addressed. As such, it may be difficult to fully manage a complex issue like chronic pain. I think these challenges may be overcome by rethinking how we approach and deliver pain care. We need to look at harnessing technology — including telehealth technologies — to improve care. We also need to empower patients and the MS community to recognize that pain management is something that requires active self-management and multimodal strategies.

Pain Management Therapies

RWHC: What do you see as the most promising pharmaceutical therapies for treating pain in MS patients? What are the caveats that must be understood by clinicians when prescribing such therapies?

DE: As a psychologist, I’m less able to speak to promising pharmaceutical therapies on the horizon. However, I think there are promising practices for how we deliver pain care, including medications and other rehabilitation interventions. We did manage medications in our MS Care study, and our goal within that was to promote the appropriate and effective use of pain medications and other medications that can benefit pain management, such as some of the antidepressants which have analgesic benefits. We know from our research that too often, patients get started on a treatment, perhaps at a “low dose,” and for whatever reason, they don’t have adequate follow up to adjust, intensify, or change treatment plan. In the MS Care study, we closely and quickly followed patients’ pain and adjusted treatments to optimize their benefits or switched treatments if needed. We also know that physical activity — whether it is physical therapy or encouraging physical activity — benefits people with MS and likely helps with pain management.

RWHC: Do you see a role for non-pharmaceutical pain management therapies in treating pain in patients with MS?

DE: Certainly. This is where I’ve spent most of my energy, not only because I am a psychologist, but also because many people with MS want to use non-pharmacological therapies and strategies. The people with MS I know and our stakeholders are eager to advance our understanding and use of non-pharmacological treatments such as mindfulness meditation, relaxation, and cognitive behavioral coping skills.

Partnering with Patients

RWHC: What initially got you interested in this field? What continues to inspire you?

DE: I have had family and friends with MS, and thus was drawn to learning more about MS. I started out conducting chronic pain research in people where chronic pain such as headaches was the primary problem. When I started working with patients with MS clinically, I was struck by how little we knew about MS pain management and how people with MS pain were not accessing care we knew was helpful in other pain populations.

I’ve been inspired and continue to be inspired by the people with MS whom we’ve partnered with to conduct our research. Our best research has resulted from partnering with people living with MS. They’ve also taught me a lot about resiliency. Although MS can present many challenges like pain, many people with MS and pain live full, meaningful and happy lives.

I also have been fortunate to have training grants from the National MS Society, which have allowed me to train postdoctoral fellows in MS and rehabilitation research. They represent the next generation of clinical researchers in pain and symptom management in MS.

Pain Management for Cancer Survivors

This week, Real World Health Care continues our series on Pain Management by speaking with Judith A. Paice, PhD, RN, who is the lead author for the American Society of Clinical Oncology’s guideline, Management of Chronic Pain in Survivors of Adult Cancer. Dr. Paice is Research Professor of Medicine, Hematology/Oncology, at Northwestern University’s Feinberg School of Medicine and a full member of the Robert H. Lurie Comprehensive Cancer Center. Dr. Paice’s clinical work focuses on the management of cancer-related pain, and her research focuses on the study of chemotherapy-induced peripheral neuropathy. We spoke about the ASCO guideline and the need for clinicians to balance pharmaceutical and non-pharmaceutical approaches to pain management.

Real World Health Care: Why did ASCO issue a guideline for the management of pain in survivors of adult cancer?

Judith A. Paice, Feinberg School of Medicine, Northwestern University

Judith Paice: The oncology field has evolved tremendously in recent years. Not only are people living longer with cancer, but they’re being cured of their disease thanks to some fantastic treatments. These treatments provide good clinical responses, but they can also cause significant toxicity, some of which may lead to chronic pain syndromes. The goal of the guideline was to alert oncologists to the presence of these long-term, persistent pain syndromes. A secondary goal was to provide support for chronic pain syndrome treatment.

Clinician Guidance

RWHC: What are the most important take-aways for clinicians?

JP: First are ASCO’s recommendations for screening and assessment. Second are recommended treatment options, both pharmacological and, equally important, non-pharmacological treatments. The guideline also provides insights and risk mitigation strategies for clinicians around the long-term use of opioids.

Today’s oncologists are faced with a very different pain management phenomenon than they were 20 years ago, when opioids were primarily used at end of life. Opioids are now being used for patients with a much longer survival trajectory — 20 to 30 years or more. As clinicians, we need to ask if such long-term use of opioids is appropriate and safe. How do we go about determining that? The guideline helps oncologists with those types of assessments and decision making.

RWHC: What do you feel are the biggest challenges facing oncologists in managing chronic pain in cancer patients, and how is ASCO helping clinicians manage those challenges?

JP: Our society is facing a serious public health problem in the opioid abuse and misuse epidemic. As a result of this problem, we’ve seen regulations at both the state and federal level that are having a chilling effect on the availability of opioids, even for those in desperate need of these medications. ASCO has a position paper on protecting access to treatment for cancer-related pain that I encourage all clinicians to read. ASCO also advocates for better third-party reimbursement for physical therapy, occupational therapy, cognitive behavioral therapy and mental health counseling. These are crucial therapies for patients facing the “new normal” of cancer survivorship, yet most third party payers provide little or no support for these treatments. As clinicians, we need to help our patients maintain function and cope with the fact that their lives are going to be very different. For patients, it’s more than surviving cancer. It’s about finding their own inner strength in survivorship.

New Pain Management Treatments

RWHC: Where do the biggest opportunities lie for new pharmaceutical pain management treatments?

JP: Several new findings in the laboratory may lead to novel agents that do not produce opioid related adverse effects. This is promising, assuming the findings can be translated into a clinical setting. There have also been numerous compounds that proved effective in animal models of pain, but when moved into the clinical setting, they either had adverse effects that weren’t seen in animals, or they didn’t have the efficacy they presented in the lab. It is very difficult to develop a model of cancer pain in animals.

Unfortunately, there haven’t been many completely new drugs. Most of the agents approved recently are slight variations of existing compounds or an update in the delivery method: a spray instead of a tablet, for example. The industry has been more focused recently on abuse-deterrent compounds. This is a somewhat controversial area because while such formulations prevent people from crushing, snorting or injecting the drugs, they don’t keep people from taking more than what is prescribed.

Non-Pharmacologic Therapies

RWHC: What should the role be for non-pharmaceutical pain management therapies in treating cancer patients?

JP: For quite a long time, there was a tendency in medicine to rely only on pharmaceutical therapies. This made sense when patients did not have long-term survival prospects and when managing pain meant helping the patient get from their bed to a chair. Today, cancer patients are living longer. They want to get back to work and function safely without the risk of falls and other complications.

We’ve seen good data around the usefulness of physical therapy, occupational therapy and cognitive behavioral therapy for many chronic pain situations, including cancer-related pain. These non-pharmacologic therapies must go hand-in-hand with pharmaceutical therapies.

Part of the challenge with non-pharmacologic therapies is limited reimbursement. The other big challenge is getting buy-in from patients. Most of us want a quick fix. Redefining expectations can be difficult. Physical and occupational therapy can be demanding, and access to specialists who understand the special needs of those surviving cancer are in short supply. Also, there remains a stigma attached to seeing a mental health counselor. It’s important for cancer patients to know that they aren’t “weak” if they need support to help them cope with the physical and emotional challenges of being a cancer survivor. Our field needs to do a better job educating our patients about the importance of including non-pharmacologic therapies as part of our pain management repertoire.