Real estate brokers representing medical clients have become experts in both medical office and retail lease transactions. The lesson for physicians is to borrow sophisticated mapping tools from retailers to make sure their practice thrives.
I’ve called home for over 30 years, and in that time I’ve been regularly amazed at the history, natural beauty and destination this great state keeps showing me. Most recently, I wanted to develop my wine palate and knowledge. I also needed some easy, outdoor-focused day trips. Visits and tours of some of Maryland’s highly regarded wineries aligned perfectly with these goals. I was introduced to Maryland’s winery tours via social media, and shopping sites like LivingSocial and GroupOn, and was hooked by their offers of special bundled tours. After one “special offer” purchase and several lovely weekends spent day tripping, I found a healthy and vibrant industry growing grapes, making wine and offering destination sites for tourists, wedding parties and even corporate events.
The Maryland Wineries Association has comprehensive information about our wineries, even grouping them into curated “trails,” like the Antietam Highlands, Piedmont, Carroll, and Frederick Wine Trails. I decided on the Chesapeake and Patuxent Wine Trails because those wineries are a reasonable drive from my front door. While I appreciate good wine and am very happy to call out a bad one, I’m by no means a wine snob. My expeditions started with the simple goals of learning something about a growing Maryland industry, and pick up a little general wine knowledge along the trail. Oh, and I purchased a few bottles.
First, I was drawn across the Bay Bridge to St. Michael’s Annual Wine Festival and made a visit to St. Michael’s Winery, the largest winery on the Eastern Shore. Located in the Old Mill Complex on South Talbot Street, at the southern edge of town, this business is in a small complex that also includes artists’ and floral shops. I enjoyed this winery largely because a visit to St. Michaels is always a pleasure, and their tasting room staff was ready to help. This winery, however, is not the place to bring the kids, unless you stop off at Justine’s Ice Cream Parlour (also on Talbott Street) first and at the day’s end, the retail store Simpatico’s, Italy’s Finest for a taste of almost all things Italian.
On another early spring weekend we headed off with a picnic basket and dog, and were welcomed with open arms and a dog water bowl to the rolling fields of Running Hare Vineyard, a sizeable vineyard in Prince Frederick, Carroll County. Their wines, specifically the Pinot Grigio, Sangiovese, Chardonnay, Malbec , Shiraz, and Chambourcin Dessert Wine, have won an impressive number of awards in the past five years in many national and international competitions. Their tasting room and events facilities pay homage to Tuscan farmhouse design, and there are just enough poplar trees dotting the rises that if you squint, you might mistake an out building for a Roman fortification. Maybe. Here’s a nice touch many of these wineries are adding: music, and events. Throughout the spring and summer Running Hare offers live music on the weekends, so bring the family, and a picnic, purchase some wine, and prepare to enjoy the fresh air.
Just to show off some newly acquired wine knowledge: not every winery is an estate winery, in other words, not every winery grows it’s own grapes. Some will contract independent grape growers to supply them, or will purchase bulk grapes from out of state. In a brief discussion with Kevin Atticks, executive director of the Maryland Wineries Association I learned there are six wineries that use exclusively fruit they grow themselves. “About 50 wineries have on-site vineyards, and others purchase local fruit, when available. There are over 90 varieties of grapes grown in Maryland, but about 40 varieties are grown to commercial scale,” says Attick. Black Ankle Winery in Mount Airy was the state’s first estate winery, and Knob Hall Winery near Hagerstown, and Sugarloaf Mountain Vineyards in Montgomery County are following suit. Add to that knowledge that there are now 67 licensed state wineries, up from 14 just 10 years ago, and I say, get the word out: Maryland farmers need to look into this crop. Vines can be planted close together to maximize acreage use, they need few pesticides, and this is a growing industry with a clear need. Our new motto? “Maryland, the old vine state.”
It’s tough to pick a favorite but in the running is Slack Winery, near the mouth of the Potomac River, below the Patuxent River Naval Base. Slack combines its property with the lovely 18th-Century Woodlawn Inn for an unmatched historic Maryland experience. The beautiful views of the river are virtually unchanged from the colonial time of Governor Calvert. The open farmland, and welcoming atmosphere are a breath of fresh air after a week of city traffic and deadlines. The adjacent Jubilee Farm is part of the operation, and has activities for children, dogs, and even adults looking to be not-so-adult-like for a while. They too offer weekend music, events and celebrations through the summer and into the fall. Call ahead to arrange a tour of the vineyards and farm, enjoy a flight of award winning whites or reds in the tasting room, and consider staying the night. I suggest taking a trip to Slack late fall – tastings; hot cider; Adirondack chairs and a roaring fire pit with dogs and kids around made for a truly delightful way to spend an early holiday season Saturday.
There are many “crash courses” in Maryland wines, or as we like to call them, wine festivals, and they’re terrific opportunities to support the “buy local” movement. They really are fun events for comparing the different results from different wineries. Atticks told me, “We have seven major festivals in the fall. Our last event of the season is October 25 at the bayside Swan Harbor Farm in Havre de Grace.” The Maryland Wine website can update you on the next festival dates. Different grapes, soils, and weather systems combine to create different tastes, even from the same grape, and a wine festival can help you compare, winery to winery. The dry, rocky, steep slopes of Mount Airy, home to heralded Black Ankle, produce different results than the flat, clay and sandy soil of the Eastern Shore. I have so much more to learn, and I think I’m up to it.
For more information, visit Marylandwine.com. Next up? Discovering Maryland’s craft beer industry.
Upcoming Fall Wine Festivals
October 18 & 19
Wicomico County Autumn Wine Festival- 5561 Plantation Ln. Salisbury, MD 21801
Harvest at Swan Harbor Farm- 401 Oakington Rd. Havre de Grace, MD 21078
Cheryl is a 55-year-old woman in good health with no significant medical history, who presented with low back pain radiating to her legs that has failed six weeks of conservative treatment with physical therapy and NSAIDS. She attributed a 20-pound weight loss over two months to increased exercise and a new dietary supplement [...]
Practicing physicians should make sure to avoid licensing issues and potential disciplinary actions from the Maryland Board of Physicians by taking a few simple measures. Failure to follow these steps could result in drastic consequences for your practice.
The Board is composed of 22 members, 14 of whom are practicing licensed physicians (including at least one osteopath) appointed by the governor; one physician assistant appointed by the governor; one representative of the Department of Health and Mental Hygiene nominated by the secretary; five consumer members and one public member knowledgeable in risk management or quality assurance.
The Board’s duties range from initial licensure through regulation, declaratory rulings and education, to discipline of physicians and a vast array of allied health providers.
These basic steps will help ensure that you are on the “right” side of the Board, and not the one stricken with panic when the Board calls.
- On all applications for licensure or renewal of licensure, be scrupulously honest about everything. Double check your CME credits to be sure they are accurate. If in doubt about whether you have to disclose something, either disclose it or get legal counsel.
- Remember to keep the Board informed if you move or change your professional address or affiliation.
- Don’t miss a renewal date and end up practicing without a license. This is your non-delegable professional responsibility, so don’t rely on staff to do this task.
- Check the Board’s website and read its newsletter diligently. It may not be riveting reading, but it frequently contains information about major changes in laws or regulations relating to the practice of medicine. The website has a wealth of information, but is not terribly user-friendly, so keep exploring!
- Keep up-to-date on the Board’s and your professional associations’ guidance on matters such as pain management and controlled substances. This is an area of great concern for the Board, and one where the guidance is constantly evolving.
- Sometimes, despite your best efforts, a complaint gets filed with the Board by a patient, a patient’s family member, another physician or a hospital where you have privileges. Additionally, the Board receives copies of all malpractice claims filed with the Maryland Health Care Alternative Dispute Resolution Office. If you are notified by the Board of a complaint:
- Notify your carrier if you have coverage for Board proceedings. These proceedings can be expensive, and if you have coverage, that coverage will pay some or all of your legal expenses.
- Whether you get counsel through your insurance carrier or on your own, you should get legal advice before responding to the Board. Ideally, you will get advice from someone familiar with the Board’s procedures and processes.
- Although extensions may be granted on occasion, for good cause, do not ignore or fail to meet deadlines once they are set.
- The Board investigation can take months. During that time you likely will be required to provide copies or originals of charts and records, and be interviewed by a Board investigator. When providing charts or records, be sure to copy everything.
- After conducting its investigation, the Board will either notify you that it is satisfied and is closing the investigation, or will issue charges alleging that you have committed one or more of the offenses listed in the Board’s disciplinary statute. Md. Code Ann., Health Occ. §14-404(a).
- If you are charged, you will have an opportunity to negotiate a resolution and, failing that, have a hearing before an administrative law judge, who will make recommendations to the Board. However, the Board is the final decision-making body.
- The Board can impose sanctions ranging from a reprimand to revocation of a license, and can include a vast array of conditions such as education. It also can impose substantial fines.
You should also consider the potential collateral effects of a Board sanction when negotiating a resolution of charges. Probation, and certainly suspension of a license, can affect credentialing at hospitals and with third party payers. If you are facing Board charges and considering a consent order with anything other than a reprimand, you should ensure you are fully informed of the effects of a Board sanction on other aspects of your professional life.
Natalie McSherry is a principal at Kramon & Graham, P.A. She can be reached at email@example.com or 410.752.6030
The information in this article is provided for general informational purposes only. None of the information in the article is offered, nor should it be construed, as legal advice on any matter. You should not act or rely upon any information contained in this article without first specifically seeking professional legal advice.
When a young person is diagnosed with cancer, their list of questions, wonders and worries can seem never-ending. What are my chances of beating this? How sick will I get? Am I going to lose my hair? What about my work; how will I pay my bills? How will my family cope? This list goes on. But one question a young cancer patient doesn’t have to ask is “Will I be alone?” The answer, by the way, is no, and the reason is that the Ulman Cancer Fund for Young Adults works diligently to provide patients with resources and support as they battle their disease.
It all started in 1997, when Doug Ulman was diagnosed with cancer at the age of 19. Immediately understanding how important it is to have access to information and a network of other young adults who had similar questions and challenges, Doug and his family launched the Ulman Cancer Fund for Young Adults. Their goal was to create a community of support for patients and their loved ones as they fight cancer and embrace survivorship. Today, the organization is delivering exactly what it initially set out to do, with an abundance of events, programs, support groups and educational forums offered to help cancer patients forge new connections, create new friendships and never, ever, feel alone.
“The doctor’s job is focused on diagnosis and treatment; we fill the gap for everything else that surrounds the clinical part, so a young person with cancer feels supported and has the opportunity to connect with others who are going through the same thing,” said Brock Yetso, president and CEO of the Ulman Cancer Fund for Young Adults.
Those on a mission to “get back to living” following their diagnosis and treatment might opt to participate in the organization’s “Cancer to 5K” program, which brings a group together to train and ultimately cross a different kind of finish line, as a team. Then there are programs like “Help Others Fight,” which unites cancer survivors, their family members and the community at large to lend helping hands with everyday tasks that may suddenly seem daunting when you are fighting cancer.
“We organize groups of volunteers to come together to do yard work, prepare meals, put up holiday lights, or whatever else the person that is being treated for cancer, needs,” said Yetso. “These are passionate people who, in many cases, understand what it’s like to be going through cancer treatment, and they want to help.”
Yetso and his team are interested in making new connections with local physicians who care for cancer patients, in building awareness about the services offered by Ulman, and finding out how local patients can take advantage of them.
“We want doctors to know more about what we do, so they can refer their patients to us for support,” said Yetso. “We also want to learn more about what our local doctors’ needs are, and what their patients’ needs are, as we continue to grow and build new programs.”
Borrowing a line from Secretary of the Department of Health and Mental Hygiene (DHMH) Joshua M. Sharfstein, MD, “Maryland is a state where people are coping with their anxiety about the future of healthcare by putting in place structures that will actually work.” This issue is full of advances on both the clinical and practice management sides of patient care in Maryland. The September/October 2014 cover story features clinical trials that focus on advancing cancer treatment, including an interview with Steven Rosenberg, MD, PhD, chief of the Surgery Branch of the National Cancer Institute. He’s dedicated himself to using adoptive cell therapy to treat refractory cancers.
I had tears in my eyes when I had the honor of meeting Dr. Rosenberg, as I lost my mom to AML in 1997. With the advances that he and others have made, my mom might be alive today (see Clinical Trials Propel Cancer Breakthroughs). As could the sister I lost to breast cancer just a few years later (see Feature). When I met Dr. Rosenberg at NIH and shared my mom’s story with him, I thanked him for the countless lives his 40 years of research with fellows from around the world have saved.
When Managing Editor Linda Harder and I had the pleasure of our most recent interview with Dr. Sharfstein (see Policy), we were literally putting Maryland healthcare into action. Shortly after we exchanged greetings at the Maryland healthcare exchange, he apologized for needing to conduct the interview on the run, literally (federal health guidelines recommend 30 minutes of moderate exercise. We got that!). Along the way, we met a group of young people in full superhero costumes for Otakon 2014 (a conference celebrating animation and Japanese culture). Dr. Sharfstein tossed Linda his phone for a quick picture and then, like a healthcare superhero, he was off, leaving him at the steps of Baltimore City Hall.
We regularly write about the best methods and newest alternatives for managing a medical practice, whatever the size. In our last issue, July/August 2014, we examined whether or not Patient Centered Medical Homes and/or Accountable Care Organizations were positively impacting healthcare costs and improving care delivery (they are). In this issue, we explore alternatives. Don’t want to be employed by a hospital and fear that private practice is no long viable? We have solutions (see Healthcare IT).
For each issue and throughout the year, both Linda and I work with the Maryland Physician Advisory Board for editorial counsel, recommendation, submission and review. I’m delighted to announce that Vinay Satwah, DO, FACOI, with the Center for Vascular Medicine (CVM), has joined our board. He is board certified in internal medicine, cardiology, nuclear medicine and adult echocardiography with sub-specialty training in interventional cardiology and endovascular medicine. Welcome, Dr. Satwah!
Maryland autumns are spectacular. Read about one way to make the most of this year’s autumn that was inspired by my visits along the Chesapeake Wine Trail (see Living). As I say with every toast and close in my letter to you…
Don’t want to be employed by a health system or government agency, but fear that private practice is no longer viable? Learn new alternatives, from large single-specialty ‘mega’ groups to models focused on population health.
A recent article in the Journal of the American Medical Association (JAMA) confirmed what many radiologists already believed and what single-institution studies had indicated – that tomosynthesis, the newer 3D approach to mammography, detects more crucial breast cancers while reducing callbacks.
The study, published on June 25, 2014, evaluated over 450,000 mammograms, nearly half of which included tomosynthesis. It found significantly greater invasive cancer detection rates for mammography plus tomosynthesis (4.1 per 1,000 screens) than for digital mammography alone (2.9 per 1,000). At the same time, recall rates dropped from 107 to 91 per 1,000 when tomosynthesis was added to a conventional mammogram.
Daina Pack, MD, chief of breast imaging at Anne Arundel Diagnostics, says, “This study was well constructed and it found a demonstrable difference. Tomosynthesis is an important step forward, though it’s not perfect. We keep trying to make mammography a better test.”
Judy Destouet, MD, FACR, who recently stepped down from her long-held position as chief of breast imaging for Advanced Radiology to work part-time, concurs. “Three-dimensional mammography is not just finding more breast cancer, it is also finding more invasive cancers which are the most clinically significant.”
Single Millimeter Slices
Breast tomosynthesis produces a three-dimensional view of the breast tissue in one-millimeter thick slices that help mammographers detect breast lesions by minimizing the superimposed tissue seen on traditional 2D mammograms.
However, the new technology imposes additional burdens on breast imagers. “Tomosynthesis provides thinner sections of the breast, allowing us to see findings that previously were obscured by overlapping breast tissue,” explains Dr. Pack. “It’s a completely different way of looking at the breast. However, it takes far more time, especially with larger breasts, since we are looking at approximately 300-400 images, instead of the traditional four images. For each traditional image obtained, that image is now reconstructed into one-millimeter slices for the entire the thickness of the breast.”
She notes that new software reduces the radiation dose. “Until recently, two set of images had to be obtained. This included the traditional 2D views and then the 3D additional images. Now, with newer software, the 2D imaging can be reconstructed from the 3D data set. This allows us to keep the radiation dose essentially the same as for a routine mammogram.
“You want to get an overall, global picture, then hone in on a microscopic area,” Dr. Pack continues. “First, we compare the 2D images with prior 2D mammograms, then we review the one-millimeter-thick images to determine if anything is hidden within the layers. It’s like seeing the individual pages of a book. Tomosynthesis has been shown to be of benefit for patients of all breast densities, but will be most helpful in those with moderate or dense breast tissue. Finding lesions in dense breasts can be like, as the saying goes, trying to find a polar bear in a snowstorm.”
Already Yielding Benefits in Practice
Dr. Destouet, a major proponent of tomosynthesis, notes that the exam has already benefited patients in their practice. “Several hundred women at Advanced Radiology have had tomosynthesis, but the out-of-pocket cost is dampening demand,” she observes. “Thanks to tomosynthesis, we’ve already detected additional cancers in the same breast that were not seen on 2D mammography, though some of the lesions were seen on sonography and MRI. We’re currently using it almost as a diagnostic tool – if we see something suspicious on a 2D exam, we bring the patient in for tomography. It would be wonderful if we could use it as a screening tool, especially on women with dense breasts.”
She continues, “Clearly, dense breasts benefit the most from 3D, which allows us to section and look at different slices in the breast. These women usually have no risk factors other than dense breast tissue – no family history or age-related factors.”
Dr. Destouet notes that tomography is not a replacement for breast MRI. “While 3D mammography may change our patient management, such as indicating that the patient should undergo mastectomy rather than lumpectomy, we still use MRI for women because it examines the vascularity, and some cancers simply don’t show up on mammography. MRI allows us to see if anything enhances.”
Comparable Patient Experience
In addition to producing exceptionally sharp images, the technology also offers an advanced ergonomic design to improve patient comfort. Appropriate for all screening and diagnostic mammography patients, it can be especially valuable for those who have dense breast tissue and/or women with a personal history of breast cancer.
“From the patient experience standpoint, there’s not much difference between a conventional mammogram and mammogram plus tomography,” Dr. Pack notes. “The screening still involves compression and we still don’t want any motion.
Tips for Ordering Tomosynthesis
Physicians may wonder how they can order tomosynthesis for their patients. “No special referral is needed,” notes Dr. Pack, “but because it’s available in a limited number of centers, be sure to ask the scheduler which office offers it, and get on the schedule for that particular machine.”
Dr. Pack also advises that physicians “inform patients that it’s critical, regardless of whether the exam is 2D or 3D, to bring in prior mammograms if they had them taken at a different facility previously. Each mammogram is almost like a fingerprint for each person – they’re very unique, and prior studies prevent us from doing unnecessary imaging of stable, benign findings.”
While tomosynthesis is FDA-approved, many insurers do not reimburse for its additional cost. Typical out-of-pocket charges for patients getting 3D mammography are $50 to $100. Dr. Destouet laments, “The American College of Radiology presented information to the government for coverage, but private insurers still consider 3D experimental. Hopefully, that will change.”
Daina Pack, MD, Chief of breast imaging at Anne Arundel Diagnostics
Judy Destouet, MD, FACR, breast imaging specialist and former chief of breast imaging at Advanced Radiology
DHMH Secretary Joshua Sharfstein, MD
Shortly after Dr. Sharfstein announced that he would be leaving his current position as secretary of the Department of Health and Mental Hygiene (DHMH) to accept a position with Johns Hopkins Bloomberg School of Public Health beginning January 2015, Maryland Physician sat down with him to reflect on his challenges and accomplishments and learn where his next position will take him. Maryland Physician first interviewed Dr. Sharfstein in its July/August 2012 issue.
Q: At the end of this year, you’ll leave public office to become the associate dean for Public Health Practice and Training at Johns Hopkins’ Bloomberg School of Public Health. You’ll also hold a faculty position in the department of Health Policy & Management. What will be your role at Hopkins?
For half of my time, I’ll supervise the preventive medicine residency program and student training in public health practice. For the other half, I will be on the faculty of the department of Health Policy & Management. I’ll be a link between school and public health in Maryland, and will help to train future leaders in public health.
Q: You’ve served as Baltimore City’s health commissioner, as deputy commissioner of the FDA, as the top minority staffer on the House Government Reform Committee, and now as DHMH secretary. As city health commissioner, you expanded treatment for addicts and vaccinated healthcare workers against influenza. Looking back on your many years of public service, what have been your greatest challenges and successes?
It is very satisfying to show that it is possible to tackle stubborn challenges. Many people think that substance use disorders, infant mortality, access to healthcare, or even a particular IT problem, whatever it is, can’t ever be fixed. That demoralizes people and keeps them from trying to improve things. Half the battle is overcoming that mindset. The challenge is to show people that there’s something they can do and that problems are amenable to intervention.
When I started as city health commissioner, the idea that there would be drug treatment available on demand was like a pipe dream for the city, but now it largely exists. People thought that infant mortality in the city was very difficult to improve, and they couldn’t imagine we’d make significant progress, but we’ve seen it.
I’ve been involved in everything from getting unsafe caffeinated alcoholic beverages and cough-and-cold medications for infants off the market to restructuring hospital payment in Maryland. It’s been an incredible privilege to serve in these positions. I’ve been lucky to have such support from the political leaders in the city and the state, and they played a critical role in getting people to think that things can get better.
Q: When Maryland Physician interviewed John Colmers, he noted that in Maryland we all have the same idea that government is good and we have the same mindset.
In Maryland, there’s an expectation that our job as public officials is to solve problems. To that extent, people sometimes get upset that problems aren’t solved quickly enough. I don’t think that’s a bad thing. There are places in the country where they don’t consider problems to be solvable. We’ve seen a lot of collaboration with the private sector over the past few years, private-public health coalitions across the state, and the Chesapeake Regional Information System for our Patients (CRISP) is a great example of that.
We just published a white paper called “A Prescription for Innovation: Maryland’s Data-Driven Approach to Containing Costs and Advancing Health” – August 2014, which describes some of the recent accomplishments.
It’s beyond just government. Maryland is a state where people are coping with their anxiety about the future of healthcare by putting in place structures that will actually work. Everyone is anxious that there’s not enough money for healthcare, but here we have a structure – through the waiver – the ability for the state to control its own destiny. Doctors and hospitals are looking for ways to share the savings. It doesn’t guarantee it will be successful, but there’s so much effort to get that moving in the right direction, and people elsewhere just feel that they’re being tossed on the seas of change.
Q: There are some metrics from CMS that show things are moving in a positive direction nationally, though with some questions about whether that’s due to healthcare reform or other economic factors.
Nationally, particularly with respect to costs, there is some uncertainty. Here in Maryland, by contrast, people are focused. The budgets are set. Hospitals are collaborating more, doctors are engaged, and long-term care facilities and community health providers are looking to collaborate. It’s an incredible moment.
Q: What would you advise Maryland physicians to do moving forward?
I would advise them to become involved in the dialogue about what’s happening in Maryland.
Med Chi is working closely with the Health Services Cost Review Commission (HSCRC) to support a request to CMS to permit different types of sharing between doctors and hospitals under certain circumstances. But this is just the tip of the iceberg of physician involvement in the change underway.
For example, the PCMH model is very exciting, and we’re looking to strengthen it.
Q: The Maryland health exchange, Maryland Health Connection, is being rebuilt using the software of the Connecticut exchange. There’s been some controversy surrounding both states’ site construction. Your comments?
The Connecticut exchange has been doing very well. Consumers really love the system. The exchange opens up November 15 – it will be a different open enrollment season this year than last.
It’s been an incredible recovery story. Obviously, things did not go the way we wanted last year, but you can look at it as, when we faced that kind of challenge, what happened. It was an incredible effort by all to exceed our enrollment goals despite the IT problems. We were able to aggressively pivot to a much better system. Maryland’s Secretary of the Department of Information Technology Isabel FitzGerald and her staff have done a great job, and the Connecticut team has also been very helpful.
Q: Why did you select Connecticut’s exchange system and not the federal health exchange?
We picked the Connecticut system because it is simple and elegant, and it has a proven track record. The federal system doesn’t fulfill our requirements on the Medicaid side, and it was much more expensive, and to some extent risky, because of our very old Medicaid system.
It was very difficult to go through the signup last fall, but I can’t say enough about how people rolled up their sleeves and did an enormous amount manually to help people get health insurance. There were people who said we should give up, but we pushed through.
Now we’re poised to see a much improved website this year.
Q: Would more time have helped prevent some of the rollout issues?
I think the fundamental issue was the technology. Once we were committed to the use of a platform that really could not handle the job, we were in trouble.
Q: What do you expect the impact of the new Medicare waiver to be on physician practice in the state?
I think it will bring the healthcare system together. Under the old system, hospitals succeeded if they did their job, but now hospitals will only succeed if the healthcare system does its job. That pushes the hospitals to engage with physicians.
I think that the HSCRC has helped every hospital move to global payments in year one – achieving our five-year goal in one year. The hospitals were very interested in moving out of fee-for-service, so that’s created an urgency for collaboration, which we’re seeing in all sorts of different ways. I know there are physicians who are nervous, but many are very excited about it. The ones who are more engaged are more excited. I urge physicians to get more engaged in the process.
LINDA HARDER | PHOTOGRAPHY TRACEY BROWN
While a vast array of mutations make it impossible to find one treatment approach that suits all cancers, thanks to clinical trials, researchers’ painstaking efforts are improving our understanding and use of the genome and immune system for more customized therapies.
Adoptive Cell Therapy: New Hope for Refractory Cancer
Celebrating his 40th year as chief of the Surgery Branch of the National Cancer Institute, Steven Rosenberg, MD, PhD, has not slowed in his relentless search to harness patients’ own immune systems to destroy cancer. He notes, “Immunotherapy is a new type of therapy for cancer, providing a new tool to cure the nearly 50% of those with cancer who aren’t cured through radiation, chemotherapy and surgery. This is significant, as more than half a million Americans died last year from cancer.”
Various approaches to immunotherapy have been explored in the past decades. The Identification of Interleukin-2 (IL-2), a T-cell growth factor, in 1976, allowed researchers to grow T lymphocytes in vitro for the first time. In 1985, Dr. Rosenberg and colleagues reported in the New England Journal of Medicine the first effective immunotherapy for the treatment of human cancer using high-dose IL-2 T remission in patients with metastatic melanoma. They achieved cancer regression in 15% of patients, including about 7% with durable regressions lasting over 20 years.
Adoptive Cell Therapy (ACT)
Many of the earlier limitations of immunotherapy have been addressed by developing an approach called adoptive cell therapy (ACT). This technique involves extracting autologous lymphocytes with anti-tumor properties from the stroma of resected tumors, growing them in vitro, and then infusing them back into the host. The first successful cell transfers from a tumor were reported in the New England Journal of Medicine in 1998. Even with ACT, however, early studies found that tumor reduction was transient in most patients. Subsequent research found that giving patients a non-myeloablative lymphodepleting regimen before the ACT dramatically improved results.
“What we learned since the early days of ACT is that the body has its own mechanism to reject or regulate the response to lymphocytes, so ‘wiping out’ the immune system using chemotherapy and radiation prior to reintroducing them into the body is key to improving outcomes,” Dr. Rosenberg explains. “We live in this balance of positive and negative physiological influences in the body, which has its own mechanisms to regulate itself.”
As a result of such advances in technique, clinical trials reported in 2011 found 40% of patients with metastatic melanoma had complete responses to ACT, and, according to Dr. Rosenberg, all of these patients are still ongoing responders today.
Expanding the Approach to Solid Cancers
“ACT is a more targeted approach that is producing clinically meaningful results,” Dr. Rosenberg notes. “Today, for the first time, immunotherapy can cure metastatic melanoma and lymphomas, and many other cancer types are under study. To target many common solid cancers it appears that we will have to target the unique mutations present in each individual cancer. The problem is that most mutations are not recognized and attacked by the immune system.”
Dr. Rosenberg and his colleagues set out to find additional ways to apply ACT to solid tumors. He recalls, “Two-thousand-six was the first time we could take normal lymphocytes and genetically engineer them to fight cancer.”
In 2012, his team performed the first successful extraction of tumor-infiltrating T cells from a patient with advanced cholangiocarcinoma that had metastasized to her lungs. The patient initially was treated with the standard approach to ACT, and her tumors shrank.
However, her initial tumor regression proved short-lived. Rosenberg and his colleagues then extracted T cells from the woman’s tumor that specifically recognized her own cancer mutations, and infused more than 120 billion of these T cells back into the patient. This time, her tumors shrank quickly and remained in remission so she could resume her normal activities.
“The most important part of immunotherapy is picking the appropriate target,” states Dr. Rosenberg. “TIL can recognize the mutations that are unique to that cancer and that are creating uncontrolled growth. Targeting the unique mutation for this woman created a blueprint for treating cancers of many types. It was complex – we had to perform complete exomic sequencing, finding every mutation in the DNA that codes for proteins. Then we had to determine which mutations are recognized by the immune system and guide the system to attack those. It’s now a complicated technology that we are working hard to simplify.”
This year’s American Society of Clinical Oncology meeting included a small Phase II study that showed that two of nine patients with refractory metastatic cervical cancer were able to achieve complete remission after a single treatment with HPV-targeted T cells harvested from their tumors and re-infused.
This approach is not without hazards. As the T cells multiply in the body, patients can experience an acute toxicity phase that can cause severe reactions and even death.
“Adoptive cell transfer therapy is ready for prime time today,” exclaims Dr. Rosenberg. “Four companies – Kite Pharma, Lion Biotechnologies, Novartis and Celgene, are working on getting therapies ready for FDA approval.” However, commercial availability of ACT likely will not occur until 2016 or later.
He acknowledges, “Addressing a specific mutation is a whole other level of complexity. Since 90% of people die from solid cancers, we have more work to do. It’s not an approach usually taken by big pharma, as we essentially have to create a new drug for every patient.”
Ivana Gojo, MD, associate professor of oncology in the Hematologic Malignancies and Bone Marrow Transplantation Program at Johns Hopkins Medicine, directs the leukemia drug development program. She is chiefly focused on finding new approaches to treating acute leukemias, which fall into two major groups – acute myeloid leukemia (AML), more prevalent in adults, and acute lymphocytic leukemia (ALL), more common in children.
“The median age of patients is with AML is 67 years,” Dr. Gojo states. “For 40 years, the standard therapy entailing cytarabine and anthracyline has achieved a 30 to 40% long-term survival rate in those under age 60, but less than 10% in older patients.” Relapse
Tied to Leukemia Clones
Today, newer laboratory techniques, including whole genome sequencing, have identified novel and recurring mutations in AML. Researchers now know that some of these mutations may occur early on (‘driver’ mutations) or later (‘passenger’ mutations), the knowledge of which helps them develop targeted therapies uniquely designed for patients with individual mutation.
These studies also demonstrated that leukemia relapse, the major problem in AML therapy, occurs because initial leukemia clones were not eradicated with chemotherapy. Dr. Gojo explains, “These clones evolve over time, which is why it’s much harder to put relapsed AML in remission. Our goal is to eradicate leukemia at the time of initial therapy to avoid relapse. Thus, it is important to monitor and treat minimal residual disease.”
Minimal Residual Disease (MRD)
Newer tests can assess the level of residual disease after induction chemotherapy, to help determine whether or not the patient should be treated more aggressively. Dr. Gojo notes, “Previously, we used only prognostic markers such as karyotype and molecular mutations at diagnosis, but having MRD is also associated with relapse. At Hopkins, we have developed flow cytometry assay to detect leukemia stem cells using specific markers, and have a clinical study where we use this test to decide whether or not patients with favorable or intermediate prognosis AML should go to transplant in first remission.”
Novel Targeted Therapies Clinical trials are testing targeted therapies for several mutations, including IDH 1/2 and MLL. Dr. Gojo says, “Hopkins has been at the forefront of developing inhibitors targeting FLT3 mutation, which can be found in some 30% of leukemias. After treatment with FLT3 inhibitors, some patients can be cured using allogeneic stem cell transplant. We’re also exploring the use of sorafenib, an FLT3 inhibitor, after transplant to improve outcomes.”
Ongoing AML Trials
Current AML clinical studies fall into roughly five categories:
- Kinase inhibitors such as FLT3 inhibitors.
- Modulation of the immune system to detect and control leukemia cells. Trials are testing anti-CTLA4 antibody, approved in melanoma, and pomalidomide, to remove suppressive T cells after induction chemotherapy in newly diagnosed AML patients and enhance the immune system’s anti-leukemia activity.
- DNA repair. Because AML cells have difficulty repairing DNA damage, trials are testing different agents (PARP and CHk1 inhibitors) that affect cell cycle and DNA damage response, to improve the effectiveness of chemotherapy.
- Novel agents targeting leukemia stem cells, such as hedgehog (Hh) inhibitors and antibodies. Aberrant Hh functioning is believed to cause cell proliferation and tumors.
- Less intensive chemotherapies, used to treat elderly patients who cannot tolerate aggressive therapy.
Extending Bone Marrow Transplants
Notes Dr. Gojo, “We also have developed less intensive strategies, such as nonmyeloablative transplant, that allows us to transplant patients up to age 75 without a problem. And we are one of the leaders in haploidentical transplants, which allow us to easily use half-matched related donors – father, mother, siblings, children – for transplant, so that these days almost everyone can have a suitable donor.”
She concludes on a hopeful note. “A key message is that physicians should pursue treatment options for patients with AML. Much has changed, and there is far more we can do to treat these patients today than in the past.”
Radiation Oncology Clinical Trials
Enrolling in a clinical trial once entailed numerous trips to a major medical center. Today, many community hospitals offer the same clinical trials as academic institutions. Illustrating that point is Randi Cohen, MD, MS, associate director of clinical research, Community Practice Program, University of Maryland Baltimore Washington Medical Center (BWMC).
She notes, “We’ve been selective about which trials go to the community. It’s a long process to get each center to have a protocol, which varies depending on their Internal Review Board (IRB) process. We have many breast and prostate cancer trials in the BWMC community because that’s what is common. And since most radiation therapy is provided daily Monday through Friday, we want to make it as convenient for patients as possible, and coordinate their radiation therapy visits with care from their other providers.”
She adds, “Clinical trials can be overwhelming for patients because there’s so much complex information, coupled with anxiety. I try to talk about appropriate treatment options first, and then provide verbal and written information on the trial as appropriate.”
Dr. Cohen noted that Dr. Hongchao Pan’s retrospective study of 80,000 women, presented at this year’s American Society of Clinical Oncology meeting, found that obese women under age 50 with estrogen receptor-positive breast cancer have a 34% greater risk of death than those who were not obese. Overweight women were also at higher risk than those of normal weight. However, the risk in menopausal women did not increase with increased weight.
“The message for physicians is that this is one more reason to encourage their patients to be proactive about diet and exercise. However, Phase III randomized trials are the gold standard,” Dr. Cohen reminds clinicians.
Metastatic Breast Cancer Trial
Dr. Cohen is the University of Maryland institutional principal investigator for E2108, a randomized Phase III Trial of the Value of Early Local Therapy for the Intact Primary Tumor in Patients With Metastatic Breast Cancer. The goal of this prospective, randomized trial of 368 women is to determine if early, localized therapy to the breast can improve quality of life and/or prolong survival for patients with Stage IV breast cancer.
One group will receive the current standard of care, consisting of chemotherapy, hormone therapy or other medications. The second group will receive the standard treatment plus surgery (either lumpectomy or mastectomy) and possibly also radiation therapy to the breast.
Dr. Cohen explains, “Some clinicians think that primary breast tumor treatment is not important once the cancer has metastasized, but others think treatment of the breast will improve patient outcomes. All patients in this study will get systemic chemotherapy or hormone therapy up front, then those who do well will be randomly assigned to one of the groups.
“Good retrospective data suggests there is benefit to treating the breast in select women with metastatic breast cancer,” she continues, “and my guess is that for women with minimal comorbidities who can perform their normal activities, treating the primary cancer site will help them. But women have to deal with so much emotional duress and costs that we don’t want to add to their burden unnecessarily.”
Prostate Cancer Clinical Trials
Dr. Cohen is also involved in two randomized Phase III clinical trials for prostate cancer. The first is RTOG 0815, a Phase III Prospective Randomized Trial of Dose-Escalated Radiotherapy with or without Short-Term Androgen Deprivation Therapy for Patients with Intermediate-Risk Prostate Cancer. The goal of this trial is to determine if those with intermediate risk, clinically localized prostate adenocarcinoma (Gleason Score of 7 and/or PSA between 10 and 20) benefit from adding six months of androgen deprivation therapy (ADT) to their radiation therapy regimen.
The second prostate trial, RTOG 0924, evaluates whether ADT combined with whole-pelvic radiation therapy improves survival in patients with unfavorable intermediate-risk or favorable high-risk prostate cancer better than ADT plus radiation therapy to only the prostate and seminal vesicles.
“Thanks to clinical trials, there have been significant improvements in radiation therapy techniques, delivery and planning in the past 10 years,” Dr. Cohen reflects. “There have also been many technological advances in radiation oncology, allowing us to be more precise with radiation treatments. Today, for example, we can do a 4D CT scan of the lung to account for breathing and movement of the tumor. That allows us to more precisely administer radiation and reduce dose to normal surrounding tissue. And in the prostate, we can use Calypso™ 4D Localization System, which is like having GPS for this organ. It helps us track prostate motion in real time, which equals smaller margins and lower doses to neighboring organs. Clinical trials have helped us optimize radiation dose levels and hone our therapeutic approaches.”
Steven Rosenberg, MD, PhD, chief, Surgery Branch, National Cancer Institute
Ivana Gojo, MD, director, Leukemia Drug Development Program, Sidney Kimmel Comprehensive Cancer Center, and associate professor of Oncology in the Hematologic Malignancies and Bone Marrow Transplantation Program, Johns Hopkins Hospital
Randi Cohen, MD, MS, assistant professor, University of Maryland and associate director of Clinical Research, Community Practice Program, University of Maryland Baltimore Washington Medical Center